Binder 1

CARTILAGINOUS TUMORS
A varie ty of neoplasms occurring withi n the

soft tissues and bone are characterized by
the production of a chondroid or Ch OI1-
dromyxoid matrix. Their cl inical behavior
vari es considerably, with some being entirely
benign (enchondroma) while others dem-
onstrate an aggressive course (mesenchymal
chondrosarcoma, dediffe rentiated chondro-
sarcoma) . The presence of signifi cant quan-
ti ties of chondroid or myxoid-chondroid ma-
trix ge nerally all ows cytologic categori zation
of these lesions as cartilage-producing neo-
plasms, but subcategorization and at times
even separation into benign and malignant
entiti es is chall enging on both histologic ex-
aminati on and cytologic study. Study of ra-
di ographs greatly facili tates the histologic
and cytologic diagnosis of carti laginous neo-
plasms of bone. The cytologic separati on of
chondroma from grade I chondrosarcoma
without radiographic correlati on is impossi-
ble. Even when radiologic-cytologic corre-
lation is undertaken, defi nitive diagnosis of
these neoplasms may require histologic eval-
uation. Howeve r, many other carti laginous
tumors (chondroblastoma, osteochondroma)
have di stinct cli nical and radiographi c fea-
tures all owing definitive cytologic diagnosis
in the maj ority of cases.
168
CHONDROMA
Enchondromas are beni gn cartilaginous
neoplasms occurri ng within bone. Many in-
volve the small tubul ar bones of the hands
and feet, but lesions are also found within
the femur and humerus. [n the latter sites,
separation from low-grade chondrosarcoma
is the major diagnosti c concern. These neo-
plasms occur with equal frequency in rnen
and women. The peak age of occurrence is
the second decade of life, but examples are
found in all decades. While the maj or ity of
neoplasms are asymptomati c, occasional
ones are associated "vith pain or pathologic
fracture.
RADIOLOGIG F INDINGS
Plain fil m examination demonstrates a well-
ci rcumscri bed, expansil e osteolytic lesion
usually situated in a medull ary locati on.
Punctate calcifications or a popcorn ap-
pearance are frequent findings.
H ISTOLOGI G F INDINGS
These neoplasm are characterized by lobules
of hyali ne cartilage with low to at most mod-
CARTILAGINOUS TUMORS 169
erate cellul arity (Fig. J I - I ). The lobul es of
cartilage are well circumscr ibed and sepa-
ra ted from the marrow cavity by thin shell s
of woven or lamell ar bone. Fingers of carti-
lage or small cartil aginous nodul es do not
extend between host bone trabeculae, but
rather exhi bit a well-defined pushing mar-
gin. Hence, no per meative pattern of growth
is seen. I
The cartil age cell s are relatively uniform
in size. Small , rounded nucl ei are sur-
rounded by moderate amounts of eosino-
phili c and occasionally vacuolated cytopl asm
(Fig. J 1-2) . Mitoti c fi gures are absent, but
rare chondrocytes may be doubl e-nucleated .
More than an occasional double-nucleated
chrondrocyte should raise suspicion about
the presence of a well-differentiated chron-
drosarcoma.
2
The presence of a signi.fi cant
spindl e cell component also favors the diag-
nosis of low-grade chondrosarcoma.
Histologically, cell ul ari ty varies among ex-
amples of enchondroma and demonsu'ates
some correlati on ,,,ith anatomic site, patient
age, and the presence or absence of the syn-
drome of mul tiple chondromas (Oilier 's dis-
ease) . In general, enchondromas arising in
the short tubular bones of the hands and feet
have greater cellul arity than those occurring
in the large tubular bones incl uding the fe-
Figure 11-1. Histologic sections from enchon-
dromas d iscl ose a lobulated neopl asm containing
abundant chondroid stroma in whi ch are dis-
persed a variabl e number of lacunar spaces con-
taining single chondrocytes. The chondrocytes
ge nerally have small , bland oval nucl ei and a pale
or cl ear cytoplasm. Mi totic fi gures are not see n,
and binucl eated chondrocytes are very rarely
found (H&E, X25) .

-
Figure 11-2. On examination, en-
chondromas de monstrate a somewhat nodular
distribution of lacuna r spaces and chondrocytes.
The individual chondrocytes have a pale or cl ear
cytoplasm a nd bland nucl ei with smooth nucl ear
membranes. The chromatin can be dark but is
eve nly d istributed. Because bin ucleated forms oc-
cur rarely in e ncho ndromas, their presence
should raise the possibi li ty of a grade I chon-
d rosarcoma (H&E, X100).
mur, tibia, and humerus. Greater cellulari ty
is seen in enchondromas arising in children
than in those from individuals who are skele-
tally mature. Finally, the enchondromas of
a ll ier 's disease have greater cellulari ty than
traditional solitary enchondromas.
3
In additi on to the characteristic intra-
medull ary enchondroma, chondromas can
occur in other locations and with modifi ed
growth patterns, resulti ng in enchondroma
protuberans
4
and peri osteal chondromas.
5
With small modifi cations, the histopathology
of these neopl asms is identical to that seen
in classic enchondroma. The cl inical and ra-
diogra phi c features characteristically sepa-
rate these lesions from cl assic enchondroma.
CvrOLOGIG FINDINGS
Smears contain a modest number of carti-
laginous fragments characterized by sharp
edges. The cartil aginous matrix appears
firm, without signi fi cant myxoid degenera-
tion (Fig. 11-3) . Scattered within the carti-
laginous matri x are lacunar spaces u.sually
containing a singl e small , rounded cell. On
Romanowsky staining, the cytology of these
celis is obscured by the thi ckness and strong
staini ng characteristics of the carti laginous
matrix. When seen, the cells have modest
170 CYTOPATHOLOGY OF BONE AND SOFT TISSUE TUMORS
,
Figure 11-3. Mate ri al aspirated from chondromas
is generall y of low cellul arity and is composed of
a ngul atcd o r fl owing fragmc nls of chondroid ma-
tri x in which arc distributed a small number of
lacunar spaces each containi ng a single chon-
d rocyte (Papanicolaoll , X50) .
amounts of cytoplasm containing cl ear cyto-
plasmic vacuoles. The nuclei arc small and
wi th a condensed chromatin pattern
(Fi g. J 1-4). Binucl eated cells and mitotic fig-
ures are not seen.
6
Tn general , cell ularity is
low but variable, at times overl apping that
seen in well-di fferentiated chondrosarco-
mas.
7
Because of the variable thi ckness of the
cartil aginous fragments, precise evaluation of
cellul ari ty is difficult. Assessment of cellular-
ity and nuclear detai l is most easily
plished on or hematoxylin and
eosin preparations.
Figure 11-4. Thc chondrocytes incomplc tely fill
the lacunar spaces and on Papanicolaou staining
have a moderately abundant pale cytoplasm.
Their nucl ei are bland and hype rchromatic, with
smooth nuclear membranes. The nuclei often li e
eccentri cally within the cytoplasm (Papani colaou,
XIOO) .
PROBLEMS IN DIAGNOSIS
Cytol ogic separation of chondroma from
grade I chondrosarcoma is impossible on
morphologic examination alone. The pur-
pose of needle aspiration in cases of sus-
pected chondroma or chondrosarcoma is to
prove the presence of a cartilaginous neo-
plasm. Radiographic analysis is then re-
quired to distinguish chondroma from
chondrosarcoma.
s
Solitary central cartil age
tumors of the small bones of the hands and
feet are almost invariably benign. Cartil age
tumors of the ribs, sternum, and pelvis are
inFrequently benign, especiall y when they
exceed 4 cm.
9
INFANTILE CARTILAGINOUS
HAMARTOMA OF THE RIB
Infantil e cartilaginous hamartoma of the rib
is a rare benign condition occurring in the
first decade of life. 10, II Pati ents often present
with severe respiratory symptoms and a pal-
pable chest mass.
HISTOLOGIG Fi NDI NGS
Histologic sections disclose primitive mes-
enchymal elements associated with solid ar-
eas composed ofprechondrocytes and chon-
drocytes and a variably mature cartilaginous
matri x. Areas of ossification are present.
1O
Admixed with the cartilaginous elements are
rnultinucleated osteoclast-li ke giant cells, fi -
broblasts, and fat cells. 10 Cystic zones simlu-
ati ng aneurysmal bone cyst are often present.
CYTOLOGIC FINDINGS
The smears are highly cellular, wi th a pre-
dominance of primi tive chondroblasLS rep-
rese nted by small round cell s with vacuo-
lated cytoplasm.
12
These cell s have vesicular
to dense nucl ei often surrounded by a per-
inuclear halo. The cells are arranged singl y
or in sheets, syncytia, or pseudorose ttes.
Minimal focal chondroid differentiation is
seen in the stroma. These elements are ad-
mi xed with fibrobl asts, osteoclast-li ke giant
cell s, endotl1eli al cells, and fragments of cal-
cifi ed tissue. Cellul ar anaplasia and mi totic
fi gures are not seen.
12
CI-IONDROMYXOID FIBROMA
Chondromyxoid fibromas are benign tu-
mors with a predi lecti on ror the metaphyseal
region of long tubular bones. T hese are rel-
atively rare neoplasms accounti ng for less
than 1 % of all bone tumors.
13
-
15
The neo-
plasm has a predil ection for men, preferen-
tiall y affecting indi viduals in the second and
third decades of life. The long bones of the
lower extremity are the favored sites of oc-
currence. Approximately one-third of cases
occur immediately around the knee.
1
3-15
Other sites of origin include the small bones
of the feet and the ilium. Most patients pre-
sent with pain, but local swelli ng may be the
presenting complaint.
RADIOGRN' HI C FI NDI NGS
These neopl asms present as oval, eccentric
metaphyseal lesions oriented parallel to the
long axis of the bone.
14
,15 Centered on the
metaphys is, they may extend into the epi-
physeal and diaphyseal regions. The margi ns
of the tumor are sharply defin ed, with scle-
rotic and scall oped borders that usually dis-
playa totall y lyti c appea rance.
H rSTOLOGIC FINDINGS
On low-power microscopic examination,
chondromyxoid fibromas display a pseudo-
lobulated architecture with extensive myxo-
matous and chondroid areas (Fig. 11-5). At
the periphery of tl1ese lobul es is a hypercel-
lular zone composed of mononucl ear cells
in which are scattered a small number of
multinucleated osteoclast-li ke giant cells. In
the central myxoid chondroid portions of
the lobul es clumped spindle or stellate cell s
are found , with increasing density toward
the periphery (Fig. 11-6). Whil e the major-
ity of the cell s have a bl and morphology, oc-
casional pleomorphi c and hyperchromatic
cells are seen within the myxoid-chondroid
stroma. Occasional large, bizarre, multinu-
cleated cell s may be found wit hin the lob-
ules. Despite the presence of nuclear pleo-
morphism, mitotic figures are rare or absent.
The maj ority of nucl ei \vithin both the cen-
tral and peripheral portions of the lobul es
have a bland appearance, ''lith a fine chro-
matin pattern and small , indistinct nucleoli .
Figure 11-5. Histologic sect ions of chondromyx-
aid fibromas have a distinctive lobular configu-
ration. There are exte nsive myxomatous and
chondroid a reas often showing a condensation of
stromal cell toward the periphery (H&E, X25).
CYTOLOGIC F INDrNGS
Smears have been reported to be of moder-
ate
l6
to high celiul ari ty.17 Smears demon-
strate an adrni xture of ovoid chondroid cells,
stell ate myxoid cell s, and spindle-shaped cells
within a fibrill ar chondroid background!7
(Fig. 11-7) . The chondroid cell s li e both
singly and trapped within the chondroid ma-
trix. Ovoid or stell ate cell s dominate the cy-
tologic picture (Fig. 11-8) . 'II'hile the major-
ity of these cells have a bland chromatin
pattern, they can vary significantly in size,
with some di splaying considerable nuclear
atypia. The maj ori ty of the cell s are mononu-
cl ear, but a signifi cant subpopulation of bi-
and mul tinucleated cells is present.
, ... , ,' .. '
,: ..
! . ' . .' ....
,., ... " .... '
,
I."
Figure 11-6. Highe r-powe r exami nation reveals
that the central m)'xoid-chondroid portions of
the lobules contai n spindle-shaped o r stell ate
cells with bland nucl ear reamres (H&E, XlOO).
Figure 11-7. Material aspirated from chondro-
myxoid fibromas contains amorphous clumps of
metach romali c myxoid-chondroid stroma. Di s-
tributed within this matrix material are round,
ovoid, or slightly stellate cells with bl and nucl ear
features (Diff-Quik, X50).
The nuclei of the mononuclear cells di s-
playa smudged, condensed chromatin (Fig.
11-9). The cytoplasm of the ovoid and stel-
late cell s is generally abundant and foamy. A
characteristi c finding of this neoplasm is a
mixture of ovoid to round chondrocyte-like
cells, stell ate cells, and spindle cells within a
myxoid-chondroid stroma. The majority of
the above cells have a smudgy nuclear chro-
matin without significant irregulariti es or in-
dentations of the nuclear membrane. Mi-
totic figures are absent.

-

'8

..

..
,

Figure 11-8. In the maj ority of exampl es of chon-
dromyxoid fibroma, the smears contain a signifi-
cant percentage of cells lying as dissociated cel-
lular elements. These cell s are stellate, round, or
plump spindl e in shape. The nucl ei vary in size
but usuall y do not show a significant degree of
anaplasia (Diff-Quik, X 100).
Figure 11-9. In many cases, the nucl ei of the
mononuclear cell s obtained by as pirati on [rom
chondromyxoid fi bromas show a smudged, con-
densed chromatin. The associated cytoplasm has
a stell ate, polygonal, or spindl e shape (H&E,
XI OO).
Whe n large tissue fragments are obtained,
lobules of chondromyxoid material are
characteri stic. These lobul es are rel atively
hypocellular and contain the admixture of
the cells described above. Multinucleated
gi ant cells frequen tl y surround these lob-
ules.
l s
Cell block preparations demonsu'ate
this lobular architecture to best advantage.
In cell bl ock pre parations the nucl ei have a
finely granul a r chromatin wi th occasional
nucl eoli. Nuclear groves are no t visualized
within the mononuclear cells.
18
The mul ti-
nucl eated giant cell s frequently demon-
strate nucl ear grooving. In the myxoid-
cartilaginous lobul es true lacunar spaces are
not observed.
P ROBLEMS I N DIAGNOSIS
Cytologic differential diagnosis of chrondo-
myxoid fibroma includes chondrosarcoma,
enchondroma, and chondroblastoma. Cyto-
logic material obtained from well-differenti-
ated (grade I chondrosarcomas and enchon-
dromas) cartilaginous neoplasms usually
contains fragments of de nse-appearing hya-
line cartilage (Fig. 11-3) . The matrix found
within chondromyxoid fibromas is predomi-
nantly myxoid and metachromatic on Ro-
manowsky-stained material. True hyaline car-
til age is absent in these neoplasms. True
lacunar spaces frequently containing chon-
drocytes are present in examples of e nchon-
droma and grade r chondrosarcoma but are
not seen in examples of chondromyxoid
fibroma.
A myxoid-chondroid matrix characterizes
both grade II and grade III chondrosarco-
mas a nd cho ndromyxoid fibroma. While nu-
clear pleomorphi sm is present in most ex-
amples of chondromyxoid fibroma, the cells
have a smudgy nuclear appeara nce not char-
acteristic of high-grade cho ndrosarcoma,
and most chondromyxoid fibromas have a
lower overall smear cell ularity than is char-
acteristic of high-grade chondrosarcoma. In
additi on, multinucleated giant cell s charac-
te ri ze chondromyxoid fibroma but are in-
frequent in grade II and grade III cho n-
drosarcomas. The radiographi c appearance
and age distribution of chondrosarcomas
and chondromyxoid fibromas differ signifi-
cantly. Chondromyxoid fibromas are well-
circumscribed lesions occurring in the sec-
ond and third decades oflife, whil e grade II
a nd grade III chondrosarcomas a re destruc-
tive lesions with irregular borders occurring
in a n older age gro up. Chondromyxoid fi-
broma must be di stinguished from chon-
droblastoma. In general, chondroblastomas
are characteri zed by a nearly uniform pop-
ulati on of ro unded mononucl ear cell s that
frequently contain nuclei showing signifi-
cant grooving. The cell components of cho n-
dromyxoid fibroma are more pol ymorphous,
containing ovoid, stellate, a nd spindl e cell s.
Multinucleated giant cells are found in both
neoplasms and hence are not helpful in di s-
between them. Aspirates from
chondromyxoid fibromas usually contain
greater quantities of chondromyxoid matrix
than do smear preparations from chondro-
blastomas. In addition to the cytologic fea-
tures, the epiphyseal location of chondro-
blastomas helps distinguish them from the
metaphyseal-centered chondromyxoid fibro-
mas. Recent studies have demonstrated a
chromosomal abnormality (inv (6) (p25q 13)
pericentromeric inversion) that is a useful
marker for chondromyxoid fibroma.
19
OSTEOCHONDROMA
Os toe chondroma or osteocartilaginous ex-
ostosis is a hamartomatous anomaly occur-
ring as a solitary lesion or as a component
of multipl e heredita ry exostoses. Solitary os-
teochond romas are not true neoplasms but
represent aberrant epiphyseal development
characterized by bone growth at right angles
to the long axis of the host bone.
20
,21 Os-
teochondromas are the most common be-
nign tumor of bone, representing 10% of all
bone tumors. There is a male predomi-
na nce, a nd most neoplasms occur in the ap-
pendicular skeleton, usuall y on the surface
of the metaphyseal portion of a major long
tubular bo ne. However, these lesions have
been reported at most sites containing
physeal cartil age. Osteochondromas within
the cranial facial bo nes are essentially non-
existent.
Gene rally, these hamartomatous growths
a re characteri zed by a mushroom sha pe
in which the "cap" is composed of hyaline
cartilage. They present clinically as hard
swellings but in rare cases present as pain
following fi'acture. Occasionally, ne urovas-
cular compromise may be the prese nting
symptom.
RADIOGRAPHIC F INDINGS
Radiographically, osteochondromas form a
pedunculated lesion growing on the surface
of a bone. The tumo r arises from the meta-
physeal cortex as a sl1100thl y contoured bony
stalk continuous with the adj ace nt cortex
and unde rl ying spo ngiosa. The lo ng axis of
the stalk generally points away from the clos-
est joint. The stalk e nds in a lobul ated car-
tilaginous cap that may contain calcifica-
tions.
22
In flat bones, osteochondromas may pre-
sent with a broad base and a sessile appear-
ance. The thi ckness of til e cartilaginous
cap is a good indi cation of the probability
of cho ndrosarcomatous degeneration, and
numerous imaging techniques have been
studied for the evaluation of thickness of the
cartilaginous cap. 23-25 In general, a cartil agi-
nous cap thi ckness of2 em or more raises sig-
nifi cant concern about tile presence of cho n-
drosarcoma.
HISTOLOGIC F INDINGS
The bony stalk is composed of mature COf-
tical and medullary bone with a fatty bone
marrow. The stalk blends imperceptibly with
the cortex of the host bone. The stalk jOins
a n overlying hyaline cartilage cap. At the
junction, mi croscopic features of normal en-
Figure 11-10. Hi stologic secti ons of osteochon-
dromas d isplay a mixture of cartil aginous and os-
seous e leme nts recapi tul ating a growth plate mor-
phology (1-I &E, X2S).
dochondral ossification are present (Fig.
11_10).20 The cartilage cap is composed of
moderately cellular hyaline cartilage pe-
ripherally cove red by a thin, fibrous pe ri-
chondrium. The indi vidual chondrocytes
within lacunar spaces appear mature, al-
though foci of increased cellula rity and oc-
casional atypi cal chondrocytes may be pres-
ent (Fig. ll- ll ) .
CYTOLOGI C F EATURES
Aspirates of osteochondromas usually sam-
pl e the cartil aginous cap and are character-
ized by fragme nts of mature hyaline car tilage
(Fig. 11- 12) . The fragments have sharp bor-
,
".
Figure 11-11. The cartil aginous cap may be hy-
with a well-for med hyaline cartilagi-
nous matrix. Lacunar spaces are pl entiful , and
binucleated chondrocytes are occasionally fo und
(1-I &E, XSO) .
Figure 11- 12. Cytologic specimens obtai ned by
aspiration from osteochondromas are dominated
by cartilaginous matrix. This matrix oh en has an
amorphous appearance and in H&E-stained
preparations has a bluish-red color. 'Whi le cellu-
larity vari es, in general it is low, with a modest
number of chondrocytes distributed individually
within lacunar spaces (H&, X80).
ders and appear heavy-bodi ed, with lacunar
spaces. Cellularity is variabl e but does not ex-
ceed that seen in enchondromas. Individual
chondrocytes are best seen in smears stained
by the Papanicolaou technique or H&E. Cell
block preparations are helpful in delineat-
ing th e appearance of individual chondro-
cytes as well as the relative cellul ari ty of the
lesion.
The presence of significant myxoid change,
nuclear enlargement, or atypia suggests chon-
drosarcomatous degeneration.
P ROBLEMS IN D IAGNOSIS
Separation of benign, uncomplicated osteo-
chondromas from osteochondromas har-
boring malignant dege neration and paro-
steal osteosarcomas may be diffi cult. Whil e
paras teal osteosarcomas can resembl e osteo-
chondromas radiographi cally, these lesions
do not contain a cap composed of mature
hyaline cartilage. 'Al hen parosteal osteosar-
comas contain a cartilage cap, it is composed
of cytologically malignant cells. The carti-
lage in osteochondromas usually appears
mature, without mali gnant features.
Separation of benign osteochondroma
from osteochondromas with malignant ded-
ifferentiation is generally achi evable by rec-
ogni zing the greater nuclear atypia and
myxoid-chondroid matrix characteristic of
grade II and grade III chondrosarcomas.
When the chondrosar comatous degenera-
tion is represented by a grade I chondro-
sarcoma, cytologic separation of benign
osteochondroma from grade I chondrosar-
coma is impossible. The presence of a carti-
laginous cap larger than 2 cm and the ab-
sence of cytologic features of malignancy
should result in open bi opsy to excl ude the
presence of a chondrosarcoma.
SYNOVIAL CHONDROMATOSIS
Synovial chondromatosis is a meta,Blastic
process rather than a true neopl asm. -6-28 It
involves the articular or tendon sheath syn-
ovial membranes and presents as multipl e
nodul es of cartilage that may show focal os-
sifi cation. Whil e the nodul es form in and are
initially attached to the synovium, they may
become detached and fl oat freely withi n the
joint cavity. Synovial chondromalosis typi-
cally involves the synovium in a diffuse fash-
ion and is most frequently seen within the
maj or weight-bearing j oints, parti cul arly the
knee, hip, a nd elbow, in that orde r of fre
quency.26-28 The age range of occurrence is
broad, but the peak incidence is in the fifth
decade of life. There is a male predomi-
nance of approximately 2:1.
RADIOGRAPHIC FINDI NGS
In the majority of cases, suffi cient calcifica-
tion has occurred for the nodul es to be vi-
suali zed by plain radi ographs. In typi cal
cases, the lesion presents as mul tipl e arti cu-
lar or periarticular nodul es with stippl ed or
ring-like calcifications.
H ISTOLOGIC FEATURES
Synovectomy specimens yield multi ple well-
circumscribed nodul es of hyaline cartil age,
frequently showing myxoid change (Fig.
11-13) . Within the cartilaginous nodul es,
the chondrocytes form loose clusters. Cellu-
lari ty is generally greater than in normal ar-
ti cular cartil age. The chondrocyte nucl ei
have an open chromatin pattern with small
nucleoli , but occasional cells may demon-
strate significant nuclear enl argemen t and
hyperchromasia. Binucl eated chondrocytes
are not infrequent. The nucl ear atypia and
Figure 11- 13. Synovial chondromatosis is charac-
terized histologically by mul ti pl e nodul es of ma-
ture or maturing hyaline cartilage. Thi s cartilage
may be mildly hypercellul ar but does not exceed
the cel lularity achi evabl e in chondromas (H&E,
X20).
binucleation may suggest a grade 1 to II
chondrosarcoma, but in the clini cal context
of multipl e synovial nodul es, a diagnosis of
synovial chondromatosis is appropri ate.
CYTOLOGIC F INDINGS
Cytologic smears and cell block preparations
reveal well-demarcated fragments of hyaline
cartilage demonsu'ating focal calcifi cation
(Fig. 11- 14) .'9 A few mesenchymal cells, ra re
chondrocytes, and scanty myxoid matri x are
Figure 11-14. Aspi rated material from examples
of synovia I chondromalOsis yields occasional frag-
ments of carti laginous matri x. This material,
when stained by H&, has a bluish-red color and
an amorphous appearance. Withi n it are scat-
tered a small number of single chondrocytes usu-
ally lying within lacuna r spaces (H&E, X80).
176 CYrOPATHOLOGY OF BONE AND SOFT TISSUE TUMORS
seen in smear preparations.
3o
The cellular
component is bland, wi th only small nucle-
oli. The cytoplasm of the chondrocytes is of-
ten vacuolated. Binucleated cell s are occa-
sionall y present.
30
The chondrocytes may
show mild nucl ear e nlargement and hyper-
chromasia, but true anaplasia is absent. The
cha nges are best seen on cell block prepa-
rations. Occasional fragme nts of myxoid car-
tilage with less well circumscribed borders
are also found in aspirated material.
Cytologicall y, aspirates from synovial chon-
dromatosis may rese mble grade 1 or grade 11
chondrosarcoma. Whil e the mild degrees of
nuclear e nlargeme nt and hype rchromasia
may overlap those seen in low-grade chon-
drosarcoma, the radiographic demonstra-
tion of multiple nodul es within the joint
space should establish the correct diagnosis.
CHONDROBLASTOMA
Chondroblastoma is a be nign neoplasm in
which a proliferation of immature carti lage-
producing cells is associated with focal car-
tilaginous matrix deposition.
31
,3? Chondrob-
lastoma is a relatively rare neoplasm,
representing less than 1% of bone tumors.
This neoplasm occurs in skeletall y immature
individuals, with most patie nts having open
epiphyseal plates. As such, the peak inci-
dence is in the second decade of life, al-
though a numbe r of cases occur in older
individuals. The mal e/femal e ratio is ap-
proximately 1.4:1. The majority of chon-
droblastomas occur within the epiphyses of
the major long bones. Common sites of oc-
currence are the distal femur, proximal tibia,
and proximal humerus, in that order. Chon-
droblastomas can also occur in the flat bones
with the acetabulum of the pelvis and iliac
crest being favo red sites.
The most freque nt presenting symptom is
pain, which can be oflong duration. Because
of the proximity of these lesions to large
joints, the pati e nt may locali ze the sympto-
matology to the joint rather than to the in-
volved bone.
RADIOGRAPHIC FINDINGS
On plain films, cho ndroblastomas are char-
acterized by sharply demarcated epiphyseal
lesio ns with a rim of scleroti c bone.
31
,3? The
les ions are relatively small in size and round
or oval in shape. Typi cally, chondroblas-
lOmas are centrall y located within the epi-
physis. In most cases, the cortex and bone
e nd plate are unaffected by the lesio n, but
in larger lesions the bone contour can be
di storted.
Histologically, chondroblastomas are char-
acterized by a cellular proliferation of round
to slightly oval cells with centrally placed,
round to slightly ovoid nuclei (Fig. 11-15).'2
The nuclei frequentl y display a longitudinal
groove (Fig. 11-16). Whil e the majori ty of
the cells comprising chondroblastomas are
mononcul ear, scattered osteoclast-li ke giant
cells are a frequent finding. In addition to
the cellular component, variable amounts of
chondroid matrix a re deposited as strands
or large sheets (Fig. 11-15) . On H&E stain-
ing, these sheets of chondroid matrix may
have a pink color and resemble osteoid. A
characteristic feature of chondroblastoma is
the presence of li near ossifications forming
a fi ligree ("chickenwire") patte rn. Calcifica-
tions and chondroid deposition may be ex-
te nsive, but mature hyaline cartil age is usu-
ally absent. The above features represent the
classic patte rn. Several microscopic varia nts
exist. Some chondr.oblastomas may contain
a significant spindle cell compone nt that
Figure 11-15. Histologic seclions of chondro-
bias lomas reveal a proliferation of relalively
round cells growing within a densely pink matrix.
The cells have relatively scanty cytoplasm and
round nuclei. The matrix (pink chondroid)
ten lraps these cells. A small number of
nucleated giant cells is a common
component of these neoplasms (H&E, X 100),
Figure 11- 16. Smears from aspirated material
tained from chondroblastomas show a mixture of
small round to ovoid mononucl ear stromal cells
associated \vith large multinucleated osteoclastic
giant celIs (Diff-Quik, XI 00) .
focally dominates the lesion, causing a
semblance to giant cell tumor of bone o r
solid aneurysmal bone cyst. True a neurysmal
bo ne cysts may a ri se within chondroblas-
tomas. When this happens, blood-filled cys-
tic spaces and tissue septae obscure the ba-
sic architecture of the chondroblastoma.
CYTOLOGIC F INDINGS
Smears are of moderate to high cell ular-
ity,33-39 with a mixture of mononuclear cells
and mul tinucl eated giant cell s.
3o
The cells
lie both singly and in aggregates (Fig.
11-16) . The aggregates have a lobular ap-
pearance and vary widely in size and cell u-
,
Figure 11-17. The mononuclear stromal cells
characterislic of chondroblastoma have a round
morphology, with modest to scanty cytoplasm sur-
rounding round nuclei, These nucl ei are rela-
tively large and have a granular, relatively evenly
distributed chromatin (H&E, X100).
Figure 11-18. High-power examination reveals
the chondrobl asts to have an open chromatin pat-
tern with small but distinct nucleoli. Many cells
have nuclear grooves or indentations. Such
grooves are characterisli c of chondroblasts and
are helpful in separating lhese cell s from those
of giant cell tumor of bone (H&E, X500).
larity.39 They are composed of mononuclear
cells surrounding multinucleated giant
cel1.
29
The mononucl ear cells are round to
oval and frequently lie in loose em-
bedded in abundant myxoid matrix. , 9 The
nuclei of the mo nonucl ear cell s are round,
ovoid, or reniform and are situated periph-
erally within the cytoplasm (Fig. 11-17) . The
chromatin of these cells is finely granular,
and small nucleoli are freque ntly present
(Fig. 11-18) . 33.34 On high-powe r examina-
tion, the nucl ear membrane is irregular and
may show a longitudinal groove or deep con-
volution (Fig. 11-19). Some cells contain in-
Figure 11- 19. High-power examination of the nu-
cl ear membrane of a cell from a chondroblas-
toma demonstrates it to be irregular, with a lon-
gitudinal groove or a deep convolution (H&E,
X500).
tranuclear cytoplasmic pseudoincl usions.
33
The cytoplasm has been variably reported as
vacuol ated or dense, 33-35 and some reports
describing Romanovsky staining have de-
picted a central dense area around the nu-
cleus and a more delicate ope n appearance
toward the periphery. The cytoplasm of the
mono nucl ear cell s has sharp edges. On Pa-
panicolaou stai ning, the cytoplasm occa-
sio nally contains brown granular pigment.
33
Smears from chondroblastomas exhibit two
types of multinucleated giant cells. The first
is a relatively large cell containing many nu-
cl ei identi cal to those seen in osteoclast-like
giant cells of giant cell tumors of bone. In
the second, small er form of giant cell , the
nucl ei resembl e those found in mononu-
clear cells. These nucl ei have irregular mem-
branes a nd distinct nucl eoli. Some of these
nucl ei have a reniform shape with longitu-
dinal grooves.
33
Cho ndroid matrix is usually
demonstrabl e in cell block preparatio ns, but
its presence is vari ably reported in smear
preparations. When found, the chondroid
matrix is pink to purple on Romanovsky
staining a nd green to brown with the Pa-
panicolaou technique.
34
The mononuclear
cells are freque ntly found grouped around
chondroid fragments. Mitotic figures are
ra rely fo und and are connned to the mono-
nuclea r cell population.
CHONDROSARCOMA
CONVENTIONAL INTRAMEDULLARY
C HONDROSARCOMAS
Chondrosarcomas are malignant neoplasms
that form an exclusively chondroid matrix.
Secondary e ndochondri al ossification is a
common finding, but direct production of
osteoid by neoplastic cell s excludes the le-
sion as a chondrosarcoma. Chondrosarco-
mas are the second most common primary
sarcoma of bone, comprising 20%-30% of
all primary skeletal sarcomas.
"While chondrosarcomas have been re-
ported at all ages, the majority occur in the
seventh to ninth decades oflife. Unlike most
bone neoplasms, there is an equal incide nce
in men and women.
Chondrosarcoma has a predil ection for
the large bones of the axial skeleton, with
nearly half of all cho ndrosarcomas occur-
ring within the pelvis or ribs. The ilium is
the single most frequently involved bone,
foll owed by the femur and humerus. Chon-
drosarcomas do occ ur at acral locations, but
the majority of cartil aginous lesions occur-
ring in the small bones of the distal ex-
tremities are benign.
The presenting symptom is most com-
monl y pain unassociated with trauma. Pain
occurs at rest and is frequently most severe
at night. Historically, the duratio n of the
pain is generally several months to years.
The majority of chondrosarcomas present as
areas of radiolucency demonstrating vari-
able degrees of mineralization .
41
,42 The ma-
jority of lesions appear as radiolucent zones
containing moderate numbers of punctate
calcifi cations. In the typi cal case, expansion
of the corti cal contour occurs and is associ-
ated with irregulariti es of the inner cortical
margin. In hi gh-grade cho ndrosarcomas a
permeative growth pattern with destr uction
of bone is characteristic.
HISTOLOGIC FINDINGS
Chondrosarcomas a re characterized by the
production of a uniformly cartil aginous ma-
trix that may show focal endocho ndrial os-
sifi cation. Unlike other sarcomas of bone,
there appears to be a close correlation be-
tween the prognosis and the hi stopathologic
grade.
43
-45 A three-tier system is most com-
monly used to grade chondrosarcomas. Ir-
respective of grade, all cho ndrosarcomas are
characterized by a permeative pattern of
growth in which fingers or nodul es of neo-
plastic cartil age infil trate between host bone.
This infiltrative process is associated with
bony destruction (Fig. ll-20). In addition
to this permeative pattern, chondrosarco-
mas di splay greater cellularity, increased cell
and nuclear size, a prominence of nucleoli ,
and increased levels of nuclear pleomor-
phism in comparison to enchondromas.
More double-nucleated cho ndrocytes are
seen in chondrosarcomas than in enchon-
dromas. The presence of neoplastic spindle
cell elements also favors the diagnosis of
cho ndrosarcoma.
Grade I Chondrosarcoma
Grade I chondrosarcomas are composed
predominantly of hyaline cartilage display-
Figure 11-20. Chondrosarcomas are character-
ized by sheets of cellular cani laginous matrix
growing into and between host bone in a de-
structive fashion (chondrosarcoma permeation
pattern) (H&E, X20).
jng a cellularity somewhat greater than that
characteristic of e nchondroma (Fig. 11-21) .
The chondrocyte nuclei tend to be plump,
with an open chromatin structure. The neo-
plastic cartilage demonstrates an infiltrative
growth pattern with erosion, engulfme nt,
and destruction of adjacent bone. Some
grade I chondrosarcomas contain a minor
spindle cell element, which is helpful in es-
tablishing the diagnosis of chondrosarcoma.
The extent of nuclear enlargement, cellu-
la ri ty, and nucl ear atypia in grade I chon-
drosarcomas frequently does not vary sub-
sLantially from that seen in e nchondromas.
Hence, considerable experie nce is required
Figure 11-21. Grade J chondrosarcomas are char-
acterized by relatively low cellulari ty. The indi-
vidual chondrocytes have mildly enlarged nucl ei
showing nucl ear hyperchromasia. Bipucleated
chondrocytes are a characteri stic finding but are
not pathognomonic of grade I chondrosarcoma
(H&E, XIOO).
Figure 11-22. The chondrosarcoma permeation
pattern shown here helps separate chondrosar-
coma from enchondroma. The chondrosarcoma
permeation pattern is characteri zed by sheets of
neoplastic ti ss ue growing be tween and destroyi ng
host bone (H&E, X25).
to separate low-grade chondrosarcoma from
enchondroma usi ng these features. The doc-
ume ntation of a pe rmeative growth pattern
more reliably separates chondrosarcoma
from enchondroma (Fig. ll-22).'
Gr a de II Chondrosarcoma
Grade II chondrosarcomas are characterized
by an extensive cartilaginous matrix com-
posed of both hyaline and myxoid cartil age
(Fig. 11-23) . In general , the extent of myx-
oid mau'ix present correlates with increasing
grade in chondrosa rcomas. Cellulari ty is
demonstrably increased in these neoplasms.
The cartilage cells a re plump, with defini-
..
. .
'. ..
, :.
:' .- ~
. .
.. , ~
. .. -
,
. .
,
. '.
..... .. .'
.' ..... .
." . ", ...
,'. . ....
Figure 11-23. Grade II chondrosarcomas show in-
creased cellulari ty and nuclear atypia over [hal
characteri stic of grade I chondrosarcomas. The
nuclei are also more irregular in shape, and bill-
ucl eated chondrocytes are more frequent (H&E,
X25).
-

#
-

"
p

'"

.,
..

Figure 11-24. Grade II chondrosarcomas are
characterized by cells with larger, plumper nuclei
that frequently have nuclear membrane irregu-
larities. While mitotic figures are not seen, binu-
cleated chondrocytes are frequent (H&E, XIOO) .
tively enlarged nuclei containing prominent
nucleoli. The chromatin pattern is open.
Both binucleated and multinucleated chon-
drocytes are present (Fig. 11- 24). The pres-
ence of a significant myxoid component is
helpful in separating grade II from grade I
chondrosarcomas.
Grade III Ch ondrosarcoma
Grade III chondrosarcomas are hi ghly cel-
lular neoplasms displaying prominent nu-
clear atypia and scattered mitotic figures
(Fig. 11-25). In general, the majority of the
Figure 11-25. Grade III chondrosarcomas are
highly cellular, with a reduced amount of chon-
droid matrix. The neoplastic cells are large, with
significant nuclear atypia, hyperchromasia, and
nuclear membrane irregularities. Occasionally
mitotic figures are seen, some of which may be
atypi cal (H&E, X80).
matrix is myxoid rather than hyaline carti-
lage in high-grade chondrosarcoma .
CYTOLOGIC FINDINGS
Grade I Chondrosarcoma
Grade I chondrosarcomas are characterized
by smears oflow cellul arity and thick, dense,
well-circumscribed aggregates of hyaline car-
tilaginous matrix (Fig. 11-26). Within these
hya1ine cartilage fragments, lacunar spaces
containing one or two chondrocytes are
identified (Fig. 11-27). The cellularity of
these cartilaginous tissue fragments is higher
than that seen in most enchondromas. In-
dividual chondrocyte nuclei are enlarged,
with a coarse open chromatin pattern and
one or two prominent nucleoli
46
(Fig.
11-27). While binucleated tumor cells are
seen, mitotic figures are absent. The neo-
plastic chondrocytes are relatively large, with
well-defined cytoplasm that may appear
foamy or vacuolated.
6
.46
Grade II Chondrosarcoma
Grade II chondrosarcomas are characterized
by smears of low to moderate cellul arity with
a significant component of myxoid carti-
laginous matrix in the background.
4
6--49 The
Figure 11-26. Aspirates of material obtained from
grade I chondrosarcomas are dominated by a
chondroid matrix in which are dispersed a mod-
erate number of chondrocytes. The definitive
separation of grade I chondrosarcoma from en-
chondroma is impossible by cytologic examina-
tion alone. Grade I chondrosarcoma is favored by
the identification of more than an occasional bin-
ucleated chondrocyte, spindle cell elements, and
nuclear hyperchromasia or irregularity (Papani-
colaou, X50).
Figure 11-27. Binucleated chondrocytes are a rel-
atively common finding in grade I chondrosar-
comas when abundant material is obtained at as-
piration (H&E, XIOO).
individual cells are found singly, in small
sheets, and in loose aggregates, as well as
within the lacunar spaces of the cartilagi-
nous matrix (Fig. 11-29). Overall cellularity
is higher than in grade I chondrosarcoma
(Figs. 11-28 and 11-29). The cytoplasm of
the individual cells is generally extensive and
con tains smal l vacuoles and/or small gran-
ules (Romanovsky stain) (Fig. 11-30). The
nuclei are large, with a coarse chromatin
pattern and one or more distinct nucle-
oli.6.46--49 Binucleated and multinucleated
chondrocytes are common features.
7
,47 The
majority of cells have a rounded shape, but
occasionally the cytoplasmic vacuoles are suf-
Figure 11-28. In aspirates from grade II chon-
drosarcomas, overall cell ularity is significantly
higher than in either grade 1 chondrosarcoma or
e nchondroma. Also, the cartilaginous matrix ap-
pears more myxoid and may obscure the nucl ear
features (Diff-Quik, X100).
Figure 11-29. Carti lagi nous fragments obtained
from grade II chondrosarcomas are relatively hy-
percellular, with prominent lobul es oflacunae oc-
cupied by one or two chondrocytes. This lobu-
lated appearance is more prominent in grade II
chondrosarcomas than in either grade I or III
chondrosarcomas (H&E, X50).
ficiently large to displace the nucleus to the
periphery and give the cell a signet-ring ap-
pearance.
Grade III Chondrosarcoma
High-grade chondrosarcomas (grade III)
yield smears of moderate to high cellularity
with extensive deposits of myxoid-chondroid
matrix (Fig. 1I-31) 6.46 Few or no fragments
of hyaline carti lage are found.
6
The basic cell
type is round to oval, with a well-defined cy-
toplasm that may be vacuolated'" Cellular
pleomorphism may be present, with en-
larged, hyperchromatic nucl ei containing a
Figure 11-30. The cytoplasm of the indivi dual
chondrocyte is usually extensive and contains
small vacuoles and/or small granul es seen in air-
dried materials (DiffQuik, X200).
Figure 11-31. Grade III chondrosarcomas yield
smears of high to moderate cellularity in which
are di stributed extensive amounts of loose myx-
oi d-chondroid substance (Oiff-Quik, X50) .
coarse chromatin pattern and prominent
nucl eoli (Fi g. 11-32). A small but signifi cant
spindl e cell element is often present in high-
grade chondrosarcomas. Mitotic figures qre
rarely found in these sarcomas.
DIAGNOSTIC CRITERIA
We ll-Differentiated (Grade I)
Chondrosar coma
Smears are of low cellularity.
There are fragments of hyaline cartilage
with lacunar spaces containing neopl astic
chondrocytes.
Figure 11-32. The individual cells of grade III
chondrosarcomas show signifi cant nuclear plco-.
morphism characterized by enlarged, hyperchro-
malic nuclei with a coarse chromatin pattern and
prominent nucleoli (H&E, X200).
Neoplastic chondrocytes are round to
oval, with moderate to abundant cytolasm.
Binucleated chondrocytes are occasion-
ally present.
Neoplastic cell nuclei are enl arged, with
a moderately to coarsely granular chromatin
and one or two distinct nucleoli.
The cytoplasm may be vacuolated and
occasionally contains a single large vacuol e
di splacing the nucleus to the periphery of
the cell.
Mitotic figures are not present.
Littl e or no myxoid-chondroid matrix is
present.
Grade II Chondrosarcoma
Smears are of low to moderate cellu-
lari ty.
Hyaline and myxoid-chondroid matrix
are frequently abundant.
Neoplastic cell s lie singly in small clus-
te rs, within lacunar spaces, and in small
sheets.
Cell nuclei are enlarged, with a coarsely
granul ar chromatin and one or two en-
larged, distinct nucleoli.
Binucleated chondrocytes are prese nt.
Individual cells have moderate to abun-
dant amounts of cytoplasm frequently con-
taining multiple vacuoles.
Occasional neoplastic chondrocytes con-
tain a single large vacuole displacing the nu-
cleus to the periphery, resulting in a signet-
ring appearance.
Mitoti c figures are not observed.
Myxoid-chondroid matrix is more abun-
dant than true hyaline carti lage.
Grade III Chondrosaroma
Smears are highly cellular, with abun-
dan t myxoid-chondroid stroma.
Cells are enlarged, with large, atypi cal
hyperchromatic nuclei.
The chromatin pattern is coarse, with
one or more large, distinct nucl eoli.
Mitotic fi gures may be present.
Binucl eated chondrocytes are present.
Chondrocytes li e both singly and in
clusters, with occasional malignant chon-
drocytes being present in poorly formed la-
cunar spaces.
Individual neoplastic cells have moder-
ate to abundant, frequently vacuolated cyto-
plasm.
Occasional cell s have single large vac-
uol es displacing the nucl eus to the peri ph-
ery, giving a Signet-ring appeara nce.
Diagnostic problems ari se at both ends of
the spectrum of differentiation. Distinction
of chondrosarcoma from chordoma may
also be diffi cul t, as is the distinction of some
high-grade pelvic chondrosarcomas from
signet-ring cell adenocarcinomas.
Cytologi c differences between grade I
chondrosarcomas and enchondromas may
be subtle, making a purely morphologic sep-
aration of these two neoplasms impossible.
In general , chondrosarcomas have greater
smear cellularity and increased nuclear
atypia than are seen in enchondromas. How-
ever, the overlap between cellular forms of
enchondroma and grade I chondrosarcoma
is extensive, making definitive cytologic sep-
aration impossi bl e. [n these cases, fine-
needle aspiration (FNA) is valuable by prov-
ing the chondroid nature of the neoplasm.
Definitive diagnosis reli es on clinical and ra-
diologic features.
37
Grade I or grade II chondrosarcomas
showi ng extensive myxoid degeneration can
be mistaken for chondromyxoid fibroma.
5o
An absence of stellate cell s should rule out
chondromyxoid fibroma.
5o
Radiologic cor-
relation is also useful.
Hi gh-grade chondrosarcomas must be dis-
tinguished from signet-ring cell adenocarci-
nomas, chordomas, and some pleomorphic
myxoid sarcomas. In general, the abundant
myxoid-chondroid substance, the vacuo-
lated nature of tile cytoplasm, and the oc-
casional lacunar spaces within matrix allow
distinction of grade rn chondrosarcomas
from most other pl eomorphi c sarcomas. Pa-
tien t age and location of the neoplasm also
help distinguis h hi gh-grade chondrosarco-
mas from chondroblastic osteosarcomas.
The latter neopl asms occur in a younger age
group.
Grade III chondrosarcomas can have a
subpopulation of cell s with a signet-ring cell
morphology. In these cases, the differential
diagnosis includes signet-ring cell adenocar-
cinoma and chordoma. The presence of
chondroid stromal fragments Witll lacunar
spaces supports the diagnosis of chondro-
sar coma. Immunohi stochemistry can be ex-
tremely helpful since chondrosarcomas
display S-100 positivily but are cytokeratin
negative. Adenocarcinomas are frequentl y
carci noembryonic antigen and cytokeratin
positive, all owing distinction of these two neo-
plasms. Morphologically, chordomas contain
a small granul ar cell component along with
large, multivacuolated physaliphorolls cells.
These are morphologically distinct from the
signet-ring cell s seen in chondrosarcomas. In
addition, chordomas express both cytoker-
atin and S-100 protein, allowing distinction of
chordomas from chondrosarcomas by im-
munohistochemi cal analysis.
5 1
CHONDROSARCOMA VARIANTS
Mesenchymal Chondrosarcoma
Mesenchymal chondrosarcoma is a rare ma-
lignant tumor of bone composed of tightly
packed ovoid to spindle-shaped primitive
mesenchymal cells surrounding foci of car-
tilage. In addition to the differences in hi s-
tomorphology, thi s entity displays distinct
clinical and radiographi c features.
Mesenchymal chondrosarcoma represents
less than 2% of all chondrosarcomas
52
,53 and
most commonly affects young adults and
teenagers. The incidence in males and fe-
mal es is approximately equal, and the most
frequent sites of involvement are the maxi ll a
and mandible. Less frequently, this sarcoma
is seen in the vertebrae, ribs, pelvis, or
humerus. The lower extremi ties are rarely
involved. Approximately one-tllird of mes-
enchymal chondrosarcomas are extraskeletal.
Most patients present with pain and
swelling of the affected area.
Radiographi call y, mesenchymal chondrosar-
comas demonstrate a radiolucent appear-
ance with varying degrees of matrix calcifi-
cation. Stippled calcifi cati ons are frequentl y
present but may form larger opacities. The
lesion is often eccentrically located within
the bone and usually shows a destructive or
permeative pattern, but occasional examples
have been sharply demarcated, with a de-
finitive sclerotic margin. A soft tissue mass is
a frequent finding.
HISTOLOGIC FI NDINGS
Mesenchymal chondrosarcomas are charac-
terized by solid areas of primi tive round,
ovoid, or sli ghtly spindl e-shaped mesenchy-
mal cell s (Fig. 11-33). These primitive mes-
enchymal cell s grow in sheets or may exhibit
a hemangioperi cytoma-like pattern. In the
latter instance, multiple vascular spaces with
a staghorn appearance are characteristic. In-
terspersed among this small cell element are
islands of cartilage (Fig. 11_34).52,53 The
distributi on and amount of cartilaginous
matrix are vari able. Thi s matrix may dem-
onstrate foci of coarse calcification, endo-
chondri al ossifi cation, or even bone forma-
ti on with a recapitulation of marrow spaces.
The cartil aginous areas contain cells that
react with antisera directed against S-100
protein.
Separation of these lesions from conven-
ti onal chondrosarcoma is important since
mesenchymal chondrosarcoma appears to
be a more aggressive neoplasm, with a 50%
mortali ty within two years of diagnosis.
52
.
53
CYrOLOCIC FINDINGS
Aspirated material from mesenchymal chon-
drosarcoma is reported to be gelatinous and
blood-tinged.
54
Prepared smears are cellular
and occasionall y contain necrotic debris with
acute infl ammatory infiltrates.
54
The individ-
ual tumor cells li e in a myxoid background
that has a purple-red color and a waxy COI1-
Figure 11-33. Histologically, mesenchymal chon-
d rosarcomas are characterized by a prominent
hemangiopericytoma-like vascular pattern, a pre-
dominance of small stromal cell s, and scaltered
nodules ofchondoid matrix (H&E, XIO).
Figure 11-34. In some areas there is an intimate
association between the small cell proliferation
resembling Ewing's sarcoma and nodul es of
chondroid matrix (H&E, X50).
sistency. Two distinct cell populati ons are
present. One is composed of small , primitive.
undifferentiated cells (Fig. 11-35). The other
shows cartilaginous differentiation with mod-
erate to abundant cytoplasm (Fig. 11-36).
The cytoplasm of these latter cells occasion-
ally shows vacuoli zation. Small cells li e singly
and in loose aggregates. The nuelei of the
small cell population are round to oval and
are surrounded by moderate amounts of
granular cytoplasm with distinct cytoplasmi c
outlines. The nuclei are generally centrally
placed and are occasionally e1efted. The chro-
matin pattern is coarsely granular, with
Figure 11-35. Fine-needle aspirates from mes-
e nchymal chondrosarcomas are characterized by
small round 0 1- ovoid cells with hyperch romatic
nucl ei. Cytoplasm is generally scanty. The back-
ground may contain small streamers of a fil a-
mentous myxoid-chondroid matrix (Diff-Qui k,
X100).
Figure 11-36. Infrequently, aspirates from mes-
enchymal chondrosarcoma contain large tissue
fragments composed of chondroid matrix in
whi ch and around which are dispersed smaH
round or ovoid cells with hypel-chromatic nuclei
(Diff-Quik, X80).
prominent chromocenters and small , eosino-
philic nucleoli .
The cells resembling more mature chon-
drocytes have larger nuclei and are more
frequently embedded in the myxoid matrix.
These cells have greater nucl ear atypia, and
the nuclei are more often eccentrically lo-
cated within the cell. The chromatin pattern
is coarse, and multiple irregular, large nu-
cleoli are frequently seen. Binucleated and
multinucl eated giant cells are frequent com-
ponents of the smears. In most cases, the
small primitive cellul ar component pre-
dominates.
DIAGNOSTIC FEATURES
Smears are cellular, with a rich myxoid-
chondroid background matrix.
There are two cell populations: a small ,
primitive-appearing cell population and a
cell population showing chondrocytic dif-
ferentiation.
Focal necrosis and acute inflammation
are seen.
The chondrocyte-like cell population
has moderate to abundant cytoplasm fre-
quently containing vacuoles.
This cell populati on is generally char-
acterized by eccentri c nucl ei with coarsely
granular chromatin and distinct nucleoli.
The small cell population has scan ty to
modest amounts of cytoplasm
the cells, with prominent chromocenters but
small nucleoli.
Mesenchymal chondrosarcomas must be dif-
ferentiated from small round cell malignan-
cies and in traosseous hemangiopericytoma.
Mesenchymal chondrosarcomas can gener-
ally be separated from Ewing's sarcoma by
the presence of abundant myxoid-chondroid
matrix in the background of smears obtained
from mesenchymal chondrosarcomas as well
as the subpopulation of clearly chondrocytic
cells. These cell s have greater amounts of cy-
toplasm than those seen in true small round
cell malignancies (Ewing's sarcoma). The cy-
toplasm of these chondrocytic cells is fre-
quently vacuolated, anotll er helpful distin-
guishing feature.
Mesenchymal chondrosarcoma can usu-
ally be separated from hemangiopericytoma
on cytologic evaluation by documentation of
the myxoid-chondroid matrix and by the
popul ation of cells with moderate to abun-
dant vacuolated cytoplasm.
Dedifferentiated Chondrosarcoma
Occasionally, low-grade chondrosarcomas
will transform into hi gh-grade sarcomas
li ttl e or no cartilaginous differenti-
ation.
5
,56 These frequently display the hi s-
tologic appearance of malignant fibrous his-
tiocytoma or osteosarcoma.
57
To qualify as
this histopathologic enti ty, the neoplasm
must have two components: a high-grade sar-
coma and a low-grade cartilaginous neo-
plasm. Dedifferentiated chondrosarcomas
represent approximately 10% of all chon-
drosarcomas and have an anatomic distri-
bution similar to that of conventional chon-
drosarcoma. The majority of patients are
over 50 years of age.
RADIOGRAPHIC FINDINCS
Radiographs typically exhibit a bimodal pat-
tern conforming to the mixed histology. In
most cases, the radiograph demonstrates an
area of punctate opacities surrounded by in-
tensely lytiC areas invading and destroying
the surrounding bone in a permeative
growth pattern. Complete cortical destruc-
ti on and lysis are frequent and are usuall y
associ ated with a soft ti ssue mass. At times,
the hi gh-grade component can dominate or
compl etely efface the underlying low-grade
cartil aginous neoplasm.
HISTOLOGIC FINDINGS
Hi stologically, these neoplasms are charac-
teri zed by two components. The first is a low-
grade chondrosarcoma, with features similar
to those described in the section on con-
venti onal chondrosarcoma. The second is a
hi gh-grade sarcoma that may or may not
have heterol ogous elements including ma-
li gnant fibrous hi sti ocytoma, osteosarcoma,
or rhabdomyosarcoma. The transition be-
tween the high-grade and low-grade areas is
generall y abrupt (Fi g. 11-37).
CvrOLOGIC FINDINGS
Smears from the reported case are moder-
ately to abundantly cellular and are com-
posed of pl eomorphic spindle-shaped cells
58
The pl eomorphi c cell s have a spindle-shaped
or elongated cytoplasm. Nuclei are generally
markedly hype rchromatic and irregular in
shape. Nucl eoli are prominent, often multi-
ple and irregular. Multinucleated anaplasti c
tumor giant cell s are a frequent finding.
There is littl e or no myxoid-chondroid ma-
trix in the background. Because of sampling,
Figure 11- 37. Dedifferenti ated chondrosarcomas
are characteri zed by a nonspecific proliferation
of a naplastic spindl e cells growing in a fibrosar-
coma or maligna nt fibrous histiocytoma-like pat-
tern. Admi xed with these are residual areas of
charaCleristic chondrosarcoma with chondroid
matri x ( H&E, X 10).
the pl eomorphi c cell component Ill ay be
the onl y population present in aspiration
smears. vVhen seve ral areas are aspirated,
smears characteristic of a well-differenti ated
chrondrosarcoma may be obtained.
Clear Cell Chondrosarcoma
Clear cell chondrosarcomas are low-grade
malignant cartilaginous tumors composed
of cells with abundant cytoplasmi c glyco-
ge n.
S9
,60 These chondrosarcomas are rare,
representing less than 5% of all chondro-
sarcomas.Most have been reported to occur
within the third and fourth decades of li fe,
and a distinct male predilection has been
documented.
59
60
Of the reported cases, the
maj ority have occurred in the upper femur
and upper tibia.
RADI OGRAPHIC FINDI NGS
The typi cal clear cell chondrosarcoma in-
volves the epiphyseal ends of long tubular
bones, often involving the articular ca rtilage.
T hi s neoplasm produces a lytic defect sirni-
Jar to that seen in chondroblastoma.
59
The
destructive lesion can be either radiolucent
or heavily mineralized and is generally
Sharply demarcated. Some cases demon-
strate scl erotic margins. Aneurys mal bone
cyst formati on may occur, resulting in a
"bl owout" appearance.
MI CROSCOPI C FrNDI NGS
Clear cell chondrosarcomas are composed
of round to oval cells with abundant clear
cytopl asm embedded in a watery cartilagi-
nous matrix (Fi g. 11_38) .59,60 Cell mem-
brane boundaries are distinct. The nucl ei
<I re most often centrally located and have
prominent nucl eoli. Foci of coarse calcifi ca-
ti on are often present, and some areas of
the tumor are heavi ly calcifi ed. Under low-
power examination, the lesi on has an over-
all lobulated architecture and a grossly well-
demarcated border.
CvrOLOGIC FrNDI NGS
Cytologic prepar ations from clear cell chon-
drosarcomas demonstra te moderate to hi gh
cellularity. The majority of cells are round to
Figure 11-38. Clear cell chondrosa rcomas are
composed of round to oval cells with abundant
cl ear cytoplasm e mbedded in a watery cartilagi-
nous matri x (H&E, X50) .
ovoid, with modera te to abundant amounts
of clear, frequently vacuolated cYLOplasm
(Fig. 11-39) . The cytoplasm may have two
areas of differential staining: an inner,
slightly granul ar, more densely staining zone
and an outer cl ear or heavi ly vacuolated
zone. The nucl ei are enl arged, with moder-
ately to coarsely granular chromatin and
large, distinct nucl eoli. There is a significant
component of binucl eated cells. The back-
ground has a watery myxoid appearance best
seen in air-dri ed, Romanowsky-s tained spec-
imens. In additi on to the clear cell popula-
tion, a minor component of multinucleated
osteoclast-like giant cells is present.
Figure 11-39. Cytologic preparations obtained by
aspi ration from clear cell chondrosarcomas con-
tain individual and loosely cohesive clusters of
polygonal cells wit h moderate to abundant
amounts of cl ear or fi ne ly vacuolated cytoplasm
(H&E, X250).
DIAGNOSTIC F EATURES
Smears are moderately cellul ar, with a
rich, wa tery myxoid background.
Neopl astic cell s have modera te to abun-
dant amounts of cytoplasm with a watery,
clear appearance on Papani colaou or H&E
staining.
On H&E and Papani colaou staining the
cytoplasm often has two zones: an outer cl ear
zone and an inner granular zone.
A component of cell s is binucleated.
Nucl ei are enl arged, \vith moderately to
coarsely granular chromatin and di stinct,
large nucl eoli.
Multinucl eated osteocl ast-like giant cells
are present.
CHORDOMA
Chordoma is a slow-growing destructive nee-
pl asm closely simul ating embryonal noto-
chordal ti ssue. Chordoma shares with noto-
chordal ti ssue coexpression of S-100 protein
and epitheli al markers.
6 1
Whi le occasional
cases have been reported in the thoracic and
lumbar vertebral bodies, the majority of
chordomas occur wi thin the sacrococcygeal
region and at the base of the skull. The over-
whe lming maj ority of chordomas occur in
pati ents over age 50. For sacrococcygeal
and skull base chordomas there is
a nearl y equal distributi on between the
sexes.
62
The of chordomas present
with pain, generall y of long standing. Chor-
domas arising within the sacrococcygeal re-
gion may lead to rectal obstruction, whil e
those occurring in the spheno-occipi tal re-
gion may produce symptoms secondary to
compression and destructi on of the opti c
nerves or pituitary gland.
RADI OGRAPHI C F INDI NGS
Pl ain film examinati on of chordomas reveals
a lyti c destructive lesion that may contain
scattered opaciti es. Sacrococcygeal tumors
result in extensive bony destruction and ex-
pansion of the bone contour, frequently with
a large soft ti ssue mass. These neoplasms
may expand both anteri orly and posteriorly
within the sacrum. Sphene-occipital neo-
plasms show extensive bony involvement,
with destruction of the cli vus or sella turcica.
HISTOLOGIC FINDINGS
Histologic sections of chordomas reveal
cords and nests of polygonal cells growing
in a myxoid matrix (Fig. 11_40)63-65 The
cellularity varies considerably within and
among cases. Some areas are highly cellul ar,
whereas others are composed predomi-
nantly of a myxoid matrix. The component
cells can be divided into two populations.
One is characterized by vacuolated cyto-
plasm; the other is small er, with granular
cytoplasm.
The most characteristic cell has relatively
abundant vacuolated cytoplasm (Fig. 11-41)
surrounding a round or oval nucleus with a
prominent nucleolus. The vacuoles may be
single or multipl e and frequently displace
the nucl eus to the periphery, giving a signet-
ring appearance (Fig. 11-41). The charac-
teristic cell is the so-call ed physaliphorous or
basket cell , which contains numerous large
vacuoles surrounded by thin cytoplasmic
strands. At times the vacuoles may be so ex,:,
tensive as to give the cell a clear appearance
on H&E or Papanicolaou staining. The sec-
ond cell component, present in lesser num-
bers, consists of small oval or polygonal cells
with moderate amounts of granular cyto-
plasm. The nuclei tend to be small er than
those seen in the vacuolated cells, but they
may have a simil ar appearance with distinct
nucleoli. At times these cell s may dominate
the neoplasm, giving it the appearance of a
"pink cell " chordoma.
Figure 11-40. Chordomas are composed of cords
and nes ts of polygonal cells g r O \ \ ~ n g in an abun-
dant myxoid matrix. These cells may contain mul-
tiple large vacuoles showi ng the classic physali-
phorous appearance (H&E, X25).
Figure 11-41. The neoplasm is composed of avo
cell types. The fi rst is a large ovoid multivacuo-
lated physaliphorous cell , and the second is a
small er stromal cell with moderate amounts of
granular pink cytoplasm (H&E, X100).
CYTOLOGIC F INDINGS
Smears of cytologic material obtained from
chordomas by FNA are most frequently dom-
inated by a myxoid matrix.
6
6-75 This matrix
substance stains mauve to magenta in air-
dried, Romanowsky-stained preparations.
The matrix has a mucoid appearance with-
out evidence of lacunae, and often has a
more opaque fibrillar appearance than that
seen in other predominantly myxoid neo-
pl asms.
74
The matrix frequently surrounds
and engulfs single cells as well as cl usters of
cells (Fig. 11-42). The cells li e singly, in lob-
Figure 11-42. Aspirates from chordomas contain
abundant watery metachromatic stroma in which
are e mbedded large, bubbly physaliphorous cells
and smaller oval stromal cells with a granular cy-
toplasm. Many of the large physaliphorous cells
contain a metachromatic inclusion within their
cytoplasm (Diff-Quik, X100).
CARTILAGINOUS TUMORS
189
Figure 11-43. With hematoxylin and eosin stain-
ing the physaliphorous cells have the "basket" or
multivacuolated appearance characteristic of this
neoplasm. The nuclei are enlarged but generally
not anaplastic. Mitotic fi gu res are infrequently
seen (H&E, XIOO) .
ulated clusters, or in vaguely trabecul ar
cords?4 The majority of cells are large, wi th
vacuolated cytoplasm (Fig. 11-43). The nu-
,. clei are round to oval , with a bland chro-
matin pattern and small but distinct nucle-
oli. A component of these vacuolated cells is
large, with numerous vacoules separated by
thin cytoplasmic strands giving a classic bas-
ket or physaliphorous cell appearance (Fig.
11-44). Other cells have a signet-ring cell ap-
pearance. The vac uoles in air-dried prepa-
rations contain purple material (Fig. 11- 45).
A second population of cells is character-
istically present, consisting of small oval or
polygonal cells with modest amounts of
Figure 11-44. High-power view of a physaliphor-
ous cell demonstrating its large, multivacuolated
cytoplasmic appearance. The nucleus is pushed
to one side and is relatively bland (H&E, X 500).
Figure 11-45. A significant minority of phys-
aliphorous cells contain densely metachromatic
inclusions within their vacuoles when stained with
a Romanowsky preparation (DifT-Quik, X200) .
granular cytoplasm. The nuclei are oval and
have a finely granul ar chromatin pattern. At
ti mes this small cell fg0pulation dominates
the cytologic picture. 9
DlAGNOSTIC FEATURES
There is an abundant myxoid mucoid
background matrix.
Large cells with abundant multiply vac-
uolated cytoplasm are present.
There is a large number of cell s with a
signet-ring appearance.
There is a second population of small
round or ovoid cells with modest amounts
of granular cytoplasm.
Nuclei within both the vacuolated and
granular cells have a bland, finely granular
chromatin. The vacuolated cells may display
moderate anisonucleosis.
Nucleoli, when present, are generally
small.
Neoplastic cells stain for both 5-100 pro-
tein and cytokeratin.
PROBLEMS IN DlAGNOSIS
Chordomas must be distinguished from
myxoid chondrosarcomas and metastatic
adenocarcinomas (of the colon). Consider-
able morphologic overlap exists between
myxoid chondrosarcomas and chordomas.
In general, some areas of a myxoid chon-
drosarcoma display cartilaginous fragments
with lacunar spaces. In addition, myxoid
chondrosarcomas lack large cells with mul-
190
CYrOPATHOLOCY OF BONE AND SOFT TISSUE TUMORS
tipl e large vacuol es (physaliphorous cells)
characteristic of chordoma. Both neoplasms
may contain cells with fine vacuol es, but
large vacuoles displacing and deforming
the nucleus are more characteristic of chor-
doma. Immunohistochemical findings are of
help. Chordomas are positive for 5-100 pro-
tein and cytokeratin, whi le chondrosarco-
mas are positive only for S-100 protein.
Separation of mucinous adenocarcinomas
from chordomas may also be difficult. Signet-
ring cell carcinomas arising in the colon or
stomach may show considerable morpho-
logic overlap with chordoma. Signet-ring
cell s are seen in both chordomas and mucin-
prod ucing ade nocarcinomas. Large multiple
vacuoles characteristic of physali phorous
cell s are found only in chordomas. [mmuno-
histochemistry is helpful since chordomas
are positive for both 5-100 protein and cy-
tokeratin, whil e carcinomas usuall y a re ker-
atin positive but S-100 protein negative.
MYXOID CHONDROSARCOMA
Skeletal myxoid chondrosarcoma is a histo-
logic variant of chondrosarcoma that is char-
acterized both histologically and cytologi-
cally by a dominant myxoid matrix (95%)
and minimal hyaline carti lage.
76
EXLraskele-
tal myxoid chondrosarcomas appear to be
distinct neoplasms with a characteristic (9,
22) (q22. q12) reciprocal translocation.'6
The cytologic appearance of exuask!' letal
myxoid cho ndrosarcoma is described
7/
,78 in
Chapter 10.
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63. Brondi LA, Podrecca S, Catoldo L Chordoma: study
of 245 cases verified at the Instituto Nazionale dei
Tumori de Milano. Rev Paul Med 1980; 95:71-73.
64. Dahlin DC, MacCarty CS. Chordoma: a study of
fifty-nine cases. Cancer 1952; 5:1170-11 78.
65. Forsyth rA, Cascilla TL, Shaw EG, Schei thauer BW,
O' Fallon JR, Dozier J C, I)icpgras DC. In tracranial
chordomas: a cl inicopathologic and prognostic
study of 5 1 cases. J Neurosurg 1993; 78:74 '1 -747.
66. Nuhawan VS, Rajwanshi A, Das A, J ayaram N,
Gupta SK. Fine-needle aspirati on cyL01ob'Y of sar-
cococcygeal chordoma. Diagn Cytopalhol 1989; 5:
404-407.
67. Carvalho C, Coelho LH. Chordoma of rhinophar-
ynx: report of a case. Acta Cytol 1974; J 8:425-428.
68. Finley JL, Sil verman J F, Dubbs OJ , West RL, Dick-
e ns A, Feldman PS, Fiable \<\1. Chordoma: diagno-
sis by fi ne-needle aspi ration biopsy wi th hi sLOlogic.
immunocytochemical and ultrastructural confir-
mation. Diagn Cyt&jJalhoL 1986; 2:330-337.
69. Thompson SI(. Callery RT. Cytologic diagnosis of
a chordoma without physaliferous cells. Diagn Cy-
lO/JathoI1988; 4: 144-147.
70. Rone R, Ramzy I, Duncan D. Anaplasti c sacrococ-
cygeal chordoma: fin e-needle aspi ration cytologic
fi ndi ngs and embryologic considerations. Acta Cy-
101 1986; 30; 183- 188.
71. Elli olt EC, McKin ney S, Banks I-I , Ful ks RM. Aspi-
ration cytology of metastatic chordoma. Acta Cylol
1983; 27;658-662.
72. O' Dowd GJ , Sch umann GB. Aspi ra ti on cytolob'Y
,
and cytohistochemistry of coccygeal chordoma: a
' ~ case report and review of the li terature. Acta Cylol
1983; 27;] 78-] 83.
73. Hazarika 0 , Kumar RV, Muniyappa GO, Mukheljee
D, Rao CR, Nanlsimhamurthy NK, Shenoy AM,
Nanjundappa N. Diagnosis of d ival chordoma by
fi ne needle aspiration of an oropharyngeal mass: a
case report. Acta Cyto1 1995; 39:507-5 10.
74. Wakely PEJr. Myomatous soft tissue t umors: corre-
lation of cytopathology and hisLOpathology. Ann Di-
agn Pat/lOl1999; 3:227-242.
75. Walaas L, Kindblom LG. Fine--needle aspi rati on bi-
opsy in the preoperative di agnosis of chordoma: a
study of 17 cases with application of electron mi-
croscopic. histochemical and immunocytoche mical
examination. Hum Pathol l 99 l ; 22:22-28.
76. Rubi n BP, Fletcher JA. Skeletal and extraskeletal
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77. Niemann TH, Bottles K, Cohen MB. Exu<lskeletal
myxoid chondrosarcoma: fi ne-needle aspi ration
biopsy findings. Diagn Cytopathol 1994 ; 11 :303-366.
78. Tsang S, Nguyen GK. Aspi nl lion biopsy cytology of
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and its cytologic diffe re ntial diagnosis. Acu, Cytol
1985; 29;566-569.
12
OSTEOID-PRODUCING LESIONS
A vari ety of reactive processes and neo-
plasms are characteri zed and defined by
their ability to directly produce osteoid.
Their biologi c behavi or vari es markedly,
from the reparati ve bone-forming response
of osteobl asts in exube rant fracture callus to
high-grade malignancies represented by in-
termedull ary osteosarcoma. Di agnosis of
these entiti es is a chall enge both histologi-
cally and cytologically. The value of cl ose
clini cal, radiographic, and microscopi c cor-
relati on in the di agnosis of bone tumors can-
not be overemphasized. The advan tages of
radiograph revi ew by the surgical patholo-
gist before histologic di agnosis has been
demonstrated, I,2 as has the value of review
of the cl ini cal history and radiograph pri or
to the cytologiC interpretation of bone Ie-
sions.
3
Review is parti cularly important for
osteOid-producing tumors.
Whil e many osteiod-producing lesions are
amenable to diagnosis by fine-needle aspira-
tion (FNA), some lesions are structurally un-
suitabl e for cytologic diagnosis. Exceedingly
dense bone-forming neoplasms (osteoma, os-
teoid osteoma, and some osteoblastomas)
are impenetrabl e with the needles generally
used for aspirati on cytol ogy and hence can-
not be sampl ed by thi s technique. Predomi-
nantly cystic or blood-fill ed lesions (aneurys-
193
mal bone cyst, tel angiectatic osteosarcoma)
may yield little lesional tissue in a back-
ground ri ch in red blood cells, again pre-
cluding cytologic di agnosis. Fortunately, the
majority of these bone tumors can be iden-
tifi ed as unsui table for FNA by radiographic
analysis. Finally, small neoplasms surrounded
by a thi ck intact cortex may also frustrate at-
tempts at cytologiC di agnosis due to the in-
abili ty of the aspirationist to penetrate the
cortex and enter the tumor.
FRACTURE CALLUS
Injury to bone initi ates a generally orderly
sequence of evenLS culminating in the
reestablishment of morphologically normal
mature bone. The course of the typi cal frac-
ture callus is characteri zed by a gradual tran-
sition from a hypercellular, richly vascular
proliferation of pri mitive mesenchymal cell s
to mature lamellar bone resembling the
original structure. Secondary changes due
to repeated trauma, refracture, infecti on , or
metabolic abnormalities may significantly
disrupt thi s orderly progression and resul t in
atypical and exuberant fracture callus that
can be confused both histologically and
cytologically with neoplasms, particularly os-
194
CYTOPATHOLOGY OF BONE AND SOFT TISSUE TUMORS
teosarcoma. Cases of exuberant fraclUre cal-
lus may be radiographi cally atypical, result-
ing in bi opsy. at which time they can both be
mistaken pathologically and cytologically for
osteosarcoma. Di stinction of these reparative
proliferations from osteosarcoma depends
on recognizi ng the stage of the lesion and
the basic reparati ve nanlre of the process.
Fractures related to obvious and signifi-
cant trauma are generally easily diagnosed
both cl inicall y and radiographi call y. Stress
fractures are cl ini cally less obvious and may
be misinterpre ted as a "bone tumor, " Stress
fractures may occur at a vari ety of sites in
otherwi se healthy individuals. The more
common si tes of occurrence include the cer-
vicodorsal spinus process, calcaneus, lmyer
lumbar spine, rib, tibia or fibula Uoggers),
second or third metatarsal , and ulna.
Radiographicall y, stress fractures most
commonly appear as a hairline crack with a
blastic intramedull ary response presenting
as a symmetric rectangular split running
from one cortical surface to the other. Fre-
quently, concentri c nuffy new periosteal
bone formation is seen on both sides of the
hairline crack within corti cal bone.
HISTOLOGIG FEATURES
Immediately after iruury, extensive hemor-
rhage, fibrin deposition, and vari able amounts
of necrosis occur between the bony fragments.
As healing begins, there is a proliferation of
immature mesenchymal cell s that have a stel-
late or spi ndle shape. These are accompani ed
by small capillary segments that colonize the
area between the bone fragments. These cells
are associated with a myxomatous fibl;n-ri ch
matrix.
4
At this point, the reparative myofi-
broblasts are cytologically atypical , with a high
nucl ear/cytoplasmi c ratio, an open nuclear
chromatin pattern, and frequently prominent
nucl eoli. Mitotic activity is brisk. This repara-
tive tissue infiltrates the surrounding bony
fragments and soft tissue, giving an invasive
appearance to the callus. As the fl'dculre ma-
tures (l week to to days), primative osteoid
and chondroid are produced, which subse-
quently develop into a primitive fonn of wo-
ven bone.
4
As the callus matures, additional
woven bone is fonned and osteoblasts become
prominent as they rim tlle sU'eamers of repar-
ative osteoid. In fracture callus, the pedphery
is more mature tllan the center of the lesion.
As time passes (three Lo four weeks), tJ,e os-
~ e o i d and woven bone streamers thi cken, WiUl
the mesenchymal tissue between bone U"3-
beculae becoming less cellular and tlle surface
osteoblasts fl attening against the bone trabec-
ul ae. By the fifth to seventh week, lamellar
bone begins to be deposited over the woven
bone scaffolding, and marrow fat reappears.4
CYTOLOGIC FI NDI NGS
The cytologic appearance of fraq ure callus
depends on its stage of development and the
presence or absence of secondary factors in-
cluding infection, refracture, and improper
fi xation. In the first two wee ks after fracture,
smears obtained from the callus are domi-
nated by red blood cell s, histiocytes, slender
fibroblasts, and plump stell ate cells associ-
ated with fragments of myxoid stroma (Fig.
12-1) .5 The individual mesenchymal cells
can have enlarged, irregular nucl ei and may
possess prominent nucl eoli. Multinucl eated
giant cells and capillary segments are fre-
quentl y present within the smears. As the
fracture matures, oval or plasmacytoid os-
teo blasts come to dominate the morphology
of the smear (Fig. 12-2), along wi th a back-
ground rich in red blood cells. With further
maturation (six to eight weeks), fragments
of osteoid and bone can be found within the
Figure 12-1. Mate ri al aspirated from fracllIres is
characteri zed by a bl oody background in whi ch
are di spersed a modest number of osteoblasts.
These cell s have a pl as macytoid configuration
wilh a granular cytoplasm and eccenlri c nucleus.
The nucl eus has a smoolh nuclear membrane
a nd displays modest hyperchromasia. Reactive fi-
brobl asts are also seen , and fat may be present in
the background (Diff-Quik, X50).
OSTEOID-PRODUCING LESIONS 195
Figure 12-2. The osteoblasts characteristic of a
fracture demonstrate a n overall plasmacytoid ap-
pearance. They are relatively plentiful in mid-
phase fraclUres (Oitf-Quik, X200).
smears. The osteoblasts are frequently en-
larged and plump, with eccentric nucl ei.
These nuclei are round to oval, with di stinct
nucl eoli and smooth, nuclear contours.
~ Whil e enl arged, the nucl ei of the reactive os-
teoblasts do not show the degrees of atypia
seen in high-grade intermedullary osteosar-
comas. However, the morphology of these
reactive osteoblasts overlaps that seen in
some low-grade intermedullary and paro-
steal osteosarcomas. Because of this overl ap,
careful clinical-radiologic-pathologic corre-
lation is necessary for the accurate separa-
tion of fracture callus from low-grade osteo-
sarcoma.
KEy DIAGNOSTI C F EATURES
Early-stage (up to two weeks) smears are
dominated by red blood cell s with scattered
histi ocytes, stellate mesenchymal ceil s, and
slender fibroblasts. Fragments of myxoid
stroma are often present at this stage.
Stomal cell s have enlarged nucl ei with
distinct nucl eoli , but nucl ear anapl asia is
lacking.
Fracture calluses offour to eight ,veeks'
duration reveal plump, often plasmacytoid
osteoblaslS with eccentric large nucl ei con-
taining single distinct nucl eoli.
While nuclei are hyperchromatic and en-
larged, they have smooth contours and lack
the degree of atypia seen in osteosarcomas.
Fragmen ts of osteoid and crushed bone
may be present in later stages of fracture
callus.
Fracture callus must be distinguished Crom
osteosarcoma and osteoblastoma. In gen-
eral , fl"3cture call us can be separated from
hi gh-grade intermec1ullary osteosarcoma by
recogni zing the general bland appearance
of the spindle and stell ate cell s within earl y
fracture callus. The nucl ear membranes
prese nt in the mesenchymal cells of fracture
callus usually have a smooth contour, whil e
those of hi gh-grade osteosarcomas are gen-
erally irregular. In addition , the nucleoli
see n in high-grade osteosarcomas are often
3 to 4 fLm in size, but those in the repara-
tive callus are smaller. While mitoti c activity
may be marked in a fracture callus, the mi-
totic fi gures are mirror image in form. Non-
mirror-image mitoti c fi gures are a strong in-
di cator of osteosarcoma. In all cases of bone
lesions potenti ally representing exuberan t
fracture callus or osteosarcoma, careful clin-
ical, cytologic, and radiographic-cytologic
correl ation is mandatory. If agreement be-
tween these diagnostic modaliti es and the
clinical hi story is not present, open biopsy is
mandatory.
OSTEOID OSTEOMA
Osteoid osteoma is a relativel y common le-
sion of bone in young men, but because of
its densely osteoblastic nature, it rarely un-
dergoes successful FNA cytology. I am un-
aware of any reports describing the cytologi c
findings in thi s neopl asm. [n additi on, I have
been unsuccessful in aspirating any osteoid
osteomas.
OSTEOBLASTOMA
Osteoblastoma is a beni gn lytic lesion of
bone predominantl y affecting men in the
second decade of lifeY-9 These neoplasms
most commonly occur in the dorsal ele-
ments of the vertebra but are found else-
where, including the humerus, ribs, and
skull. Their radiographi c and histologic ap-
pearance is similar to that of osteoid os-
teoma, but the nidus in the former is larger,
generall y exceeding 1.5 cm in diameter. The
zone of sclerosis within osteoblastomas is
quite variable in size and may not be visibl e.
Osteoblastomas may expand the bone con-
tour, wi th secondary thinning of the cor-
tex.6-9 In some cases, there is cortical de-
struction with periosteal new bone formation
mimicking a malignancy.7
While the majority of osteoblastomas fol-
Iow a beni gn course, occasional examples
with a more aggressive be havior midway be-
tween that of benign osteoblastoma and os-
teosarcoma have been reported.
1O
In gen-
eral, aggressive osteoblastomas are larger
than their benign counterparts, usually ex-
ceeding 4 cm.
tO
Histologically, aggressive os-
teoblastomas contain epi thelioid osteoblasts
rimming the osteoid trabeculae, a feature
not seen in their beni gn counterparts.
Osteoblastomas demonstrate a variably
lytic blastic radiographic appearance that
commonly expands the involved bone in a
fusiform fashion. The area of bony expan-
sion is often surrounded by a thin rim of be-
nign scl erotic bone. In the majori ty of cases,
osteoblastomas produce a round or oval
well-demarcated lytic defect with a variably
sized zone of reactive bone sclerosis. In half
of the cases, patchy or cloud-like radiopaci-
ties are present.
HISTOLOGIC FINDINGS
Histologic examination of nidus tissue re-
veals an interlacing network of bone trabec-
ulae relatively evenly distributed in a loose,
immature fibrovascular stroma. 6--9 Small cap-
illary vessels are quite prominent and form
a signifi cant portion of the stromal tissue be-
tween the irregular bone trabeculae (Fig.
12-3). Plump osteoblasts border the trabec-
ulae, whi ch form an interlacing network.
Multinucl eated osteoclast-like giant cells are
often present. While the osteoblasts are fre-
quently numerous, they do not form solid
sheets. Mitotic fi gures are plentiful, but no
atypical forms are present. If a signifi cant
cartilaginous component is identifi ed, os-
teosarcoma is a more likely diagnosis than
osteoblastoma.
CYTOLOGIC FINDINGS
Smears are moderately cellular, 'With abun-
dant blood in the background.
lI
In our ex-
perience, the predominant cell type is a plas-
macytoid cell with nucl ei that appear to
protrude from one side of the cell, a feature
Figure 12-3. Histologic sections of osteoblas-
LOmas are characteri zed by an interlacing netvwrk
of woven bone trabeculae between whi ch li es a
loose, immature, richly vascular stroma (H&.E,
X50) . Osteoblastic rimming of the bone lrabec-
ulae is frequent.
characteristic of osteoblasts.1
2
The nucl ei are
round to oval, with one to three distinct nu-
cleoli. The chromatin pattern is relatively
fine, and the nuclear membranes are
smooth. In addition to these osteoblasts, the
smears contain a component of cohesive
spindle cells showing no Significant nuclear
atypia, as well as multinucl eated giant cells
containing up to 20 nuclei. II The osteoblast-
like cells occasionally line the surface of
short fragments of pinkish fibrillar matrix
(Romanowsky-stained material). Mitotic fi g-
ures are exceptionally rare or absent. There
appear to be no cytologic features separat-
ing aggressive osteoblastoma from benign
osteoblastoma.
DIAGNOSTIC C RITERIA
Smears are moderately cellular, with a
bloody background.
There is a large number of plasmacytoid
cells with eccentric nuclei that appear to pro-
trude from the cell.
Osteoclastic giant cells with up to 20 nu-
clei per cell are visible.
Spindle cell aggregates occur in which
the cells show no significant nuclear atypia.
Fragmen ts of pink osteoid surrounded
by osteoblast-like cells are seen.
Mitotic figures are rare to absent in
smear preparations.
OSTEOSARCOMA
Current concepts regarding osteosarcoma
have evolved over the last several years and
have resul ted in an increasingly complex cat-
egori zation, with intramedullary, surface, and
intracorlical forms being described. The first
two categories contain several subtypes wi th
variable histomorphologic appearances and
clinical behaviors. Accurate diagnosis and
subcategori zation are becoming increasingly
important for the selection of appropriate
therapy.I S-15
Osteosarcomas show two patterns of inci-
dence. The larger peak occurs in the second
decade of life, and the second small er peak
occurs from the mid-fifth decade on. Sites of
prevalence for conventional intramedullary
osteosarcoma include gnathic bones, upper
portion of the humerus, ileum, proximal
and distal femur, and proximal tibia. Over-
all , osteosarcoma accounts for approxi-
mately 20% of all primary sarcomas of bone.
As with most neopl asms of bone, there is a
male predominance.
The majority of osteosarcomas occur in the
following sites in order of frequency: femur,
proximal tibia, proximal humerus, pelvis,
proximal femur, and mid-shaft of femur. Ap-
proximately ninety percent of osteosarcomas
are centered within the metaphysis, and an
additi onal 9% occur within the diaphysis.
RADIOLOGIC FINDINGS IN HIGH-GRADE
I NTERMEDULlARY OSTEOSARCOMA
Some 90% of osteosarcomas are centered in
the metaphysis but may demonstrate exten-
sion into the diaphysis. The radiographi c ap-
pearance varies immensely, with tumors
ranging from entirely lytic to densely scle-
rotic. Variable degrees of minerali zati on
produce cloudy opacities varying in shape,
density, size, and distribution within the
neoplasm. Osteosarcomas exhibit a destruc-
tive growth pattern with irregular ill-defi ned
borders. In the maj ority of instances the
cortex is invaded and frequently destroyed.
The outer surface of the cortex overlying
the neoplasm generall y demonstrates a pe-
riosteal reaction in which new periosteal
bone is laid down, producing the traditional
Codman's triangle and/ or a characteristic
"sunburst" pattern in whi ch perpendicular
or radiati ng calcified stri ations are found. At
times, thin layers of new calcifi ed bone are
laid down parallel to the cortex, giving a lyp-
ical "oni on skin" appearance. Pathologic
fracture may be superimposed, compli cating
the radiographi c appearance of this lesion.
Several subtypes of osteosarcoma have
characteri stic radiographic patterns distinct
from that of traditional hi gh-grade intra-
medullary osteosarcoma. Prominent among
these are the radiographi c appearances seen
in telangiectatic osteosarcoma, parosteal os-
teosarcoma, and periosteal osteosarcoma.
Telangi ectatic osteosarcomas are charac-
teri zed radiographically by a predominantly
lytic lesion that may be associated with focal
or complete cortical destruction. Because
these sarcomas produce relatively Ii ttle
bone matrix, they appear as an osteolytic le-
sion with a permeative destructive growth
pattern. Telangiectatic osteosarcomas fre-
quently expand the contour of the bone,
with associated cortical disruption but mini-
mal or no periosteal new bone formation. If
periosteal new bone formation is present, it
often appears as a multi layered process
(onion skin pattern).
Parosteal osteosarcomas have a very typi-
cal anatomic distribution, with more than
80% being located in the poslerior aspect of
the knee, specifi cally the distal posterior por-
tion of the femoral shaft. Th is location is fol-
lowed in frequency by a posteri or tibial site
of origin. Parosteal osteosarcomas are found
on the surface of the bone and are attached
over a broad-based cortex. Osteosarcoma
may arise in a mushroom-like fashion in the
underlying cortex and appears radiographi-
cally as a densely mineralized, lobulated tu-
mor. Mineralization is frequently irregular,
with randomly scattered opacities. Infre-
quently, parosteal osteosarcomas encircl e
the bone of origin. Because this sarcoma
originates on the surface of the periosteum.
new periosteal reactive bone formati on
does not occur. As these sarcomas enlarge.
medullary involvement occurs but may be
difficult to document on plain radiographs.
Periosteal osteosarcomas are relatively un-
common, occurring almost exclusively along
the long tubular bones of the lower ex-
tremity. Unlike classic intramedullary os-
teosarcoma and parosteal osteosarcoma, the
tibia is the most frequent si te of origin.
Radiographi cal ly, periosteal osteosarco-
mas are predominantly radi olucent tumors
arising from the surface of a long bone. The
periosteum is ge nerally elevated by the neo-
plasm's expansion and a prominent pe-
riosteal new bone reaction is seen, with both
perpendicular striae and Cod man 's triangles
being present on pl ain ftIms. Patchy areas of
mineralization are frequentl y demonstrable
radiographically within these neoplasms,
and the outer layer of cortical bone beneath
the neoplasm shows irregular erosions. The
medullary cavity is generall y spared until late
in the progression of the disease.
HISTOLOGIC FINDINGS
According to current nosologic concepts, in-
tramedullary osteosarcoma is divided into
conventi onal, telangiectatic, and central law-
grade forms.
16
Conventional osteosarcomas
are subdivided histomorphologically into os-
teoblastic, chondrobl astic, fibrobl astic, giant
cell rich, small cell, epitheli oid, malignant fi-
brous histiocytoma-like, and osteoblastoma-
like subtypes.' 6 More than one subtype may
be found within a single neopl asm. Osteo-
sarcomas are composed of an extracell ular
matri x (osteoid and chondroid) and a cel-
lular component in which there is direct os-
teoid production by the neoplasti c cells. The
type and amount of matrix produced, and
the relati onship between the matrix and sar-
coma cell s, determine the subtype of con-
ventional intramedullary osteosarcoma pres-
ent. Hence, extensive production of osteoid
correlates with the osteoblastic subtype, while
extensive chondroid is seen in the chon-
droblastic subtype of conventional osteosar-
coma. A predominantly spindle cell sarcoma
showing collagen production but little os-
teoid production by neopl astic cells defines
the fibroblastic type of osteosarcoma.
Osteoblastic osteosarcomas are character-
ized by a fine lace-like network of tumoral
osteoid. This osteoid runs in streamers,
forms sheets and interlacing trabecul ae be-
tween whi ch the neoplastic cells are distrib-
uted (Fig. 12-4). The related scl erosing
form of osteosarcoma shows streamers of os-
teoid or immature woven bone infiltrating
between remnants of normal and cancell ous
bone. At times, deposition of osteoid or wo-
ven bone may be massive, resulting in tightly
entrapped neoplasti c osteoblasts with the
Figure 12-4. Osteoblastic osteosarcomas are char-
acterized by a fine lace-li ke network of tumoral
osteoid. This osteoid runs in streamers or forms
sheets, and neoplastic atypical osteoblasts are dis-
tributed bet\veen and within the osteoid material
(H&E, X50).
morphologic appearance of small , dark cell s
containing regul ar bland-looki ng nuclei.
This so-call ed normali zation ofnucl ei
l7
may
result in misinterpretation of the cells as be-
ni gn. In general, the di agnosis of osteosar-
coma can be based on the infiltrating pat-
tern of the proliferation, along with the
presence of a component of cells showing
signifi cant atypia and enlargement (Fig.
12-5) . In general , osteosarcomas display a
Figure 12- 5. The mali gnant cells characteristic of
osteosarcoma show signifi cant nuclear enlarge-
ment and atypia. They are frequemly hyperchro-
matic and may show a vesicular chromati n pat-
tern with prominent nucleoli. Mitotic fi gures
including atypical forms are frequent. Streamers
of osteoid directl y produced by the malignant
cell s are characteristic of osteosarcoma (H&E,
X50).
greater range of vari abili ty in nuclear size
and shape than is seen in reactive and repar-
ative conditions. Mitotic activity with atypi-
cal forms are not infrequent. In osteobl astic
and sclerosing osteosarcomas, tumor bone
may merge directly with preexisting nontu-
mor bone and may even grow along such re-
sidual nonneoplastic bone for considerable
distances. Polari zation is helpful in separat-
ing this immature woven neopl astiC bone
from residual nonneoplasti c lamellar bone.
Chondroblastic osteosarcomas exhibit
such extensive chondroid production that
superfici al examinati on gives the impression
of chondrosarcoma. This cartilaginous dif-
ferentiati on can represent all stages of car-
tilaginous matrix formation, ranging from
immature myxoid cartilage to mature hya-
line cartilage. Calcifi cation of the matri x is
frequent, resulting in a deep blue granul ar
appearance. The diagnosis of osteosarcoma
is establi shed by the identifi cation of at least
focal direct osteoi d production by the neo-
plasti c cells. Layers of cartil age and bone for-
mation are often intermingled, and areas of
transition bet,,,een the two matrix forms may
be present.
Fibrobl astic osteosarcomas are dominated
by a spindl e cell component generally re-
sembling high-grade fibrosarcoma. Tumor
osteoid must be present to support the di-
agnosis of osteosarcoma (Fig. 12-6) but may
be very scanty in amount. In such cases, only
inconspicuous small foci of homogeneous
Figure 12-6. Fibrosarcoma-like osteosarcomas are
dominated by spindle cells running in bundles
and fascicles simulating fibrosarcoma. Only small
amounts of osteoid are presenl but, when identi-
fi ed, confi rm the nature of the neoplasm (H&E,
X50).
eosinophilic material are present to charac-
terize the lesion as an osteosarcoma. At
times, foci of osteoid are not identified in bi-
opsy specimens. When such neoplasms are
found in the appropriate clini cal and radio-
graphi c settings, they should be classified as
osteosarcoma.
Small cell osteosarcoma is a microscopic
variant with clinical and prognostic features
of osteosarcoma but mi croscopically resem-
bling Ewing's sarcoma. The dominant mi-
croscopi c pattern is that of a proliferation of
undifferentiated small round cells possess-
ing minimal amounts of cytoplasm.
1S
,19 Bone
and osteoid formation are minimal bUl
are usuall y identifi able after a meticulous
search. The precise relationship between
small cell osteosarcoma, conventional os-
teosarcomas, and Ewing's sarcoma is not en-
tirely cl ear. While small cell osteosarcomas
display immunoreactivity for osteonestin, os-
teocalcin, and alkali ne phosphatase, 18 they
also react with antibodies recogni zing the
glycoprotein MIC-2, characteristic of Ewing's
sarcoma, and primitive neural ectodermal
tumor. IS
Some osteosarcomas display marked cellu-
lar anaplasia with a mixture of spin die-shaped
and polygonal cells forming short, irregular
fascicles and storiform patterns. Large pleo-
morphic, multinucleated neoplastic cells ex-
hibiting phagocytosis, debris and engulfed
eosi nophilic bodies are found. These malig-
nant fibrous histiocytoma (MFH)-like osteo-
sarcomas generally occur in the elderly, and
this histologiC pattern may correlate ,,'lith a
particularly aggressive course.
20
Occasional osteosarcomas have promi-
nent bland-appeari ng multinucleated osteo-
clast-type giant cells. These cell s may domi-
nate the morphologic appearance and result
in the misinterpretation of the lesion as a
giant cell tumor (Fi g. 12-7). These osteo-
cl ast-type giant cells are probably a benign
reactive component, and careful morpho-
logic study will di sclose traditional spindl e
cell-shaped and atypical osteoblast-like cells
associated \'lith the osteoid matrix produc-
ti on characteristic of osteosarcoma. The
identification of these neoplastic cells asso-
ci ated \'lith matrix production establi shes
the diagnosis of osteosarcoma.
Several variants of osteosarcoma have been
described, including telangiectatic osteosar-
comas, surface osteosarcomas (parosteal and
Figure 12- 7. Giant cell rich osteosarcomas COI1-
tain a prominent population of osteoclast-like
giant cells or anaplastic giant cells. The presence
of osteoid and malignant osteoblasts confirms the
diagnosis or osteosarcoma (H&E, X50).
peri osteal), and central low-grade osteosar-
comas. Telangiectati c, parosteal, and per-
iosteal osteosarcomas have characteri stic ra-
di ographi c appearances and histologic
morphologies. The radiographic appearance
of cen tral low-grade osteosarcoma is crucial
to its correct identifi cation.
Telangiectati c osteosarcomas have a sponge-
like or mu' ticrstic appearance on low-power
examination.
2
,22 Sponge-li ke spaces are sub-
divided by septae superficially resembling
those seen in aneurysmal bone cysts (Fig.
12-8). On higher-power examination, the sep-
tae disclose a \"'Iiable number of highly
Figure 12-8. Telangiectatic osteosarcomas are
characterized by large blood-filled spaces sur-
rounded by septae of cellular tissue contai ning
streame rs of osteoid. In many cases, the cell ula r
compo nent is relatively bland, but there is always
a population of anaplastic osteoblasts confirming
the diagnosis of sarcoma (H&E, XIO).
anaplasti c polygonal cells admixed with
streamers of osteoid and spindl e cells with
lesser degrees of nuclear atypia (Fig. 12-9).
Large aggregates of red blood cells are pres-
ent in the spaces between the septae. In gen-
eral, anaplastic cells are easily found withi n the
septae of telangiectatic osteosarcomas, but oc-
casionally such pleomorphic cells are infre-
quent, making di stinction from aneurysmal
bone cyst difficult. The maj ori ty of telang-
iectatic osteosarcomas are composed of septae
in which the neoplastic cells show a high de-
gree of nuclear atypia, a high mitotic rate, and
a large number of mitotic figures with an atyp-
ical fOnTI. Many examples contain multinucle-
ated anaplastic giant cells containing multiple
bizarre nuclei. Osteoid production is generally
scant but demonstrable after a careful search.
On occasion, free-floating atypical neoplastic
cells are found wi thin the areas ofhemorrhage.
Parosteal osteosarcomas are associated
with characteristic radiographic findings and
sites of origi n. These neoplasms have a low-
grade appearance in which streamers of os-
teoid and woven bone are separated by a
low-grade spindl e cell fibroblastic prolifera-
tion.
23
,24 The cellular component has a de-
ceptively benign appearance and, when com-
bined with the streamers of well-developed
trabecular bone, may be mi staken for frac-
ture callus or a benign subper iosteal reac-
ti on. While spindle cells \vi th mild nuclear
atypia are the predominant cell type, occa-
sional foci of neoplastic cartilage are found.
This carti lage shows an abnormal patte rn of
ossification and generally contains atypi cal
Figure 12- 9. This higher-power photomicro-
graph of a telangiecta ti c osteosarcoma confi rms
the presence of both tumoral osteoid and cells
showing signifi cant nuclear atypia (H&E, X ( 00).
Figure 12- 10. Parosteal osteosarcomas are low-
grade lesions forming well-developed streamers
or trabeculae of bone surrounded by a low-grade
fibrosarcoma-like stroma (H&E, X 10).
chondrocytes. Diagnosis is achi eved by rec-
ognizing the grade I fibrosarcomatous ap-
pearance of the spindl e elements, along \vith
the exuberant production of osteoid and wo-
ven bone (Fig. 12-10).
Periosteal osteosarcomas are surface os-
teosarcomas with a predominant chondro-
blastic appearance both cytologically and
histologically.25-27 Areas of carti laginous dif-
ferentiation are separated by bands of prim-
itive sarcomatous cells showing clear nuclear
anaplasia and a hi gh mitotic rate. The areas
of cartilaginous production resemble those
seen in grade II or III chondrosarcoma.
Central or intramedullary low-grade os-
teosarcomas are relatively rare neoplasms
\vith low-grade fibroblasti c and osseous com-
ponents proliferating within the medullary
compartment of bone.
28
Osteoid and woven
bone dominate the mau'ix portion of these
lesions, and the proliferating cellular com-
ponent resembles either grade I fibrosarcoma
or the spindle cell population seen in fi-
brous dysplasia. At times the resemblance to
fibrous dysplasia can be striking, with reca-
pitulation of the "Chinese character" appear-
ance in the woven bone. The fibroblast-like
spindle cells are generally plump, \vith en-
larged nuclei containing prominent nucleoli,
but their uniform appearance beli es their sar-
comatous nature. Nuclear atypia is minimal
and mitoses are generally infrequent, with
atypical forms being very rare or absent. Ma-
trix production in these neoplasms varies
from mature, slender woven bone u-abeculae
to irregular bony spicules or solid areas of
bone. True lamellar architecture is not char-
acteristic of bone formed by the neoplastic
component of these sarcomas. Separation of
these low-grade intelmedullary osteosarco-
mas from fracture callus and fibrous dyspla-
sia is difficult. Correlation with l-adiographs is
imperative in establishing the correct diag-
nosis. Despite a close resemblance between
low-grade intermedullary osteosarcoma, fi-
brous dysplasia, and fracture callus, these sar-
comas shmv greater coarseness of the bone
matrix trabeculae than is seen in fibrous dys-
plasia, and in general , greater degrees of nu-
clear atypia and mitotic activity are seen in
the sarcomas than in fibrous dysplasia. Dif-
ferentiati on from fracture callus is best
achieved by correlation with imaging studies.
CYTOLOGIC FINDINGS
Cytologic Features Common
to Conventio n al Osteosarcoma
and Its Variants
Cytologically, osteosarcomas present a di-
verse morphologic picture tied together by
the presence of anaplastic cells producing
osteoid (Fig. 12-11). These anaplastic cells
can take the form of spindle cells, pleomor-
phic multi- or mononucleated giant cells,
and polygonal cells, often with a plasmacy-
toid shape.
29
,30 The polygonal cells are most
characteristic of osteosarcoma and fre-
quently surround fragments of osteoid rna-
Figure 12-11. Cytologic preparations obtained
from osteosarcomas are characterized by the pres-
ence of anaplastic cells producing osteoid. The
osteoid has a heavy appearance and is often sur-
rounded by the stromal cells. Occasional stromal
cells are engulfed by the osteoid matrix (Oiff-
Quik, X50).
trix. Plasmacytoid cell s represent malignant
osteoblasts (Fig. 12-12), and have blue to
mauve cytoplasm on Romanowsky-stained
preparations, and may contain vacuoles and
purpl e-red small granui es.
29
,30 These vac-
uoles and granules may be related to the pri-
mary matrix vesicles identified in the 05-
teoblasts seen hi stologically in both fracture
callus and osteosarcomas.
To faci litate cytologic diagnosis, V\rhite et
al.
31
have subclassified the FNA cytomor-
phologic appearance of osteosarcomas into
five categories. While these cytomorphologic
categori es may overlap with the histologic
appearances described above, there is no
one-Lo-one correspondence bet\veen cyto-
morphologi c appearances and the histologic
category. The cytomorphologic groups or-
gani zed by White et al.
31
are (1 ) pleomor-
phi c (MFH-li ke), (2) epithelioid, (3) chron-
droblastic, (4) small cell , and (5) mi xed.
In the experi ence of White et al. ,31 the
pleomorphi c pattern is the most commonly
obse rved cytomorphologi c type, compri sing
half of all aspirates. Cells closely resembl e
those derived from MFHs in whi ch the cell
population is composed of various propor-
tions of mali gnant spindl e cells and large,
pl eomorphic, multinucl eated neopl astic cells
(Fig. 12-13). Both cell types exhibit clear-cut
mal ignant features including a high nucl ear!
cytoplasmi c rati o, signifi cant enlargement in
nuclear size, irregular nucl ear membranes,
a coarse chromati n pattern with Significant
Figure 12-12. Malignant osteoblasts have a plas-
macyLOid appearance with e nlarged, hyperchro-
mati c nuclei. The nuclei often have sli ght mem-
brane irregulariti es. The cytoplasm may contain
small deep purpl e granules or cl ear vacuoles
(Di fT-QlIik, x200).

Figure 12-13. Hi gh-grade osteosarcomas resem-
ble MFHs with anaplastic multinucleated giant
cells (1-1 &, X200). The presence of osteoid con-
fi rms the osteosarcomatous nature of the prolif-
era tion.
chrornatin clumping, and prominent, irreg-
ular nucleoli. The nucleoli can be single or
multipl e. In addition. the rnultinucleated
neopl asti c cells are generally bizarre, with
huge nuclei surrounded by abundant dense
cytopl asm. A vari able number of osteoclast-
like giant cells with a benign appearance are
present in the majori ty of cases (Fig. l 2-14) .
This cytomorphologic pattern is found in
several histologi c types of osteosarcoma but
is present in all telangiectatic osteosarcomas.
The epithel ioid pattern is dominated by
plump, rounded cells corresponding to the
classic malignant osteoblast (Fig. 12-15).
The cells are characterized by eccentri c nu-
clei surrounded by variable amounts of cy-
toplasm. The cytoplasm frequently contains

Figure 12- 14. Giant cell ri ch osteosarcomas are
characterized by a promine nt populati on of
bland-appearing osteoclast-like giant cell s (Diff-
QlIik, X200) .
Figure 12- 15. The epithelioid pattern of os-
teosarcoma is dominated by plump rounded cells
corresponding to the classic malignant osteoblast
(H&E, X200) .
vacuol es and, at times, small red granules
characteristic of malignant osteoblasts. The
nucl ei are round to oval, but occasi onal ir-
regularities of the nucl ear membrane are
present. Some nuclei contain a single large
central nucleolus.
Aspirates demonstrating the chondroblas-
ti c cytomorphologic pattern are character-
ized by an abundant gelatinous chondroid
matrix within the background. On Papani-
colaou-stained preparations this matrix has
a finel y granular blue-green appearance with
scattered clear bubbles. On Romanowsky
staining, the matrix has a granular to feath-
ery magenta appearance, again wilh clear
bubbl es. The cells associated with the chon-
droblasti c pattern vary in appearance, rang-
ing from malignant spindl e cells to more
rounded osteoblast-like cells similar to those
seen in the epithelioid pattern. Occasional
malignant multinucleated giant cells and be-
nign-appearing osteoclast-like giant cells are
found within the chondroid matri x.
The small cell pattern of osteosarcoma is
characterized by cell ular smears dominated
by a rather uniform population of cells
whose size is approximately three to four
times that of a mature lymphocyte (Fig.
12-16). The cytoplasm is scanty in these
cells, and the associated nucl ei have a finely
dispersed chromatin simil ar to that seen in
Ewing's sarcoma. The cells lay both singly
and in cohesive fragments. Litt1e or no os-
teoid is demonstrable.
The mixed pattern can contain any com-
bination of the above cyLOmorphol ogic pat-
terns. While the presence of an osteoid-like
matrix is variabl e, onl y 16 of 45 positive as-
pirates contained osteoid in the series of
White et al.
31
The osteoid-like matri x has
a dense, homogeneous appearance ,"vith a
blue-green color on Papani colaou staining
and magenta in Romanowsky preparations
(Fig. 12-16). The osteoid matrix has a
denser appearance than chondroid matrix
and is generall y seen in small er fragments
than is characteri stic of chondroid. Defini-
tive separation of osteoid matrix from dense
coll agen can not always be achi eved. The cy-
tologic identification of osteoid-like matrix
requires careful correlation with radio-
graphs. When imaging studi es reveal a ma-
trix-forming lesion. t11e presence of dense,
homogeneous mature matrix fragments can
be interpreted as osteoid. These fragments
can appear as thin trabaculae, ovoid frag-
ments, or irregular aggregates. Osteoblast-
like cells are often seen rimming such ma-
trix aggregates.
In addition to the five cytomorphologic
patterns described by White et al.,31 I would
add a sixth pattern in whi ch benign-appear-
ing osteoclast-like giant cell s predominate.
These cells may be so prominent that the le-
sion is initially mistaken for a benign giant
cell tumor of bone or a solid aneurysmal
bone cyst. The bl and-appearing osteoclast-
like giant cell s are large, with abundant pale
cytoplasm surrounding up to 50 nuclei (Fig.
Figure 12-16. The small cell pattern of osteosar-
coma is cha ractel-ized by cellular smears domi-
nated by a ralher uniform population of cells ap-
proximately three to four times the size of mature
lymphocytes (Difl"-Quik, XIOO). Osteoid strea m-
ers are a frequent finding, at least rocally wi thin
these smears.
Figure 12-17. The neoplastic stromal cells pres-
ent in giant cell rich osteosarcomas may be spin-
dle-shaped or ovoid but have clearly malignant
features (H&E, X 100).
12-14). The nuclei are ovoid, with an even
chromatin pattern and occasional small, dis-
tinct nucleoli. The mononuclear stromal
cells may have a spindle shape or may re-
semble the neoplastic osteoblasts described
in the epithelioid pattern (Fig. 12-17). Sep-
aration from giant cell tumor of bone is
achieved by recognizing the greater degree
of nuclear atypia and enlargement present
within the osteosarcoma's mononuclear cell
component (Fig. 12-17). In general, the nu-
clei within the mononuclear stromal cells of
giant cell tumor of bone are identical in ap-
pearance to the nuclei within the giant cells.
The mononuclear cell nuclei of giant cell-
rich osteosarcomas are larger and more atyp-
ical than the nuclei of bland giant cells.
Morphologic Appearance of
Specific Histologic Subtypes
of Osteosarcoma
The morphologic subtypes of osteosarcoma
are often associated with relatively charac-
teristic smear patterns. However, overlap of
these cytologic patterns among the histo-
logic types of osteosarcoma can be consid-
erable. The highest correlation between
cytomorphology and histologic category oc-
curs in small cell osteosarcomas and chon-
droblastic osteosarcomas. Parosteal osteosar-
comas and central low-grade osteosarcomas
are characterized by a cell population show-
ing little nuclear atypia. These osteosarco-
mas are dominated by bland spindle cells
with a minor component of oval "osteoblast-
like" cells similar to those seen in the epi-
thelioid cytomorphologic group.
CONVENTIONAL
< INTRAMEDULLARY
OSTEOSARCOMA, NOT
OTHERWISE SPECIFIED
Conventional intramedullary osteosarcomas
of no specific type are characterized by the
pleomorphic, epithelioid, or mixed cyto-
morphologic patterns. Most cases show a
predominance of the pleomorphic cell type
and contain small amounts of osteoid-like
matrix.
32
Frequently, these matrix fragments
are rimmed by cells with an epithelioid cy-
tomorphology (Fig. 12-18). Mitotic figures
including atypical forms are not infrequent.
'When osteoid-like matrix is not present or is
seen in only tiny amounts, separation of
these osteosarcomas from other high-grade
sarcomas involving bone (MFH) may be im-
possible, and correlation with radiographs to
demonstrate matrix formation is critical to
establish the diagnosis of osteosarcoma.
CHONDROBLASTIC
OSTEOSARCOMA
This histologic subtype of osteosarcoma is
uniformly associated wi th the chondroblas-
tic cytomorphologic group. In these cases,
the background is dominated by a myxoid-
chondroid matrix (Fig. 12-19). Fragments
of hyaline cartilage with well-formed lacunar
spaces are present in these smears.33 Fre-
Figure 12-18. The production of neoplastic os-
teoid is the feature diagnostic for osteosarcoma.
This stroma has a dense appearance, is frequently
seen as thin streamers, and may be surrounded
or lined by osteoblasts. Also, occasional atypical
osteoblasts are trapped \vithin this matrix. (Diff-
Quik, XIOO)
Figure 12-19. Chondroblastic osteosarcomas
yield smears dominated by a myxoid-chondroid
matrix. This matrix is identical to that seen in
high-grade chondrosarcomas; hence, separation
of chondroblastic osteosarcomas from chon-
drosarcomas is frequently impossible by cytologic
evaluation (Diff-Quik, X 160).
quently, the appearance is identical to that
of a grade II-III chondrosarcoma, and os-
teoid matrix is not cytologically identifiable.
In these cases, cytologic separation from
chondrosarcoma is impossible, and the di-
agnosis rests on correlation with radio-
graphic and clinical features.
TELANGIECTATIC
OSTEOSARCOMA
Telangiectatic osteosarcomas have a charac-
teristic radiographic appearance that is cru-
cial to their cytologic diagnosis. Aspiration
yields bloody smears. The numerous red
blood cells frequently obscure the underly-
ing malignant nature of the process. In our
experience, approximately half of all telang-
iectatic osteosarcomas undergoing FNA
yield excessively bloody smears, precluding
definitive diagnosis. In the experience of
White et al.,3} nearly all aspirates positive for
malignancy derived from telangiectatic os-
teosarcoma demonstrate the pleomorphic
cytomorphologic pattern (Fig. 12-20). Oc-
casional examples have a mixed appear-
ance, with the pleomorphic pattern pre-
dominating.
SMALL CELL OSTEOSARCOMA
In our experience, small cell osteosaromas
are dominated by the small cell cytomor-
Figure 12-20. Smears obtained from telang-
iectatic osteosarcomas are characterized by an ex-
tensively bloody background in which are dis-
tributed a small number of tissue fragments
containing atypical plasmacytoid cells. These cell
clusters may be dominated by relatively bland
stromal elements similar to those seen in aneurys-
mal bone cysts, but in all diagnosable cases at least
rare anaplastic polygonal or plasmacytoid cells
are found (H&E, X 100).
phologic pattern, with smears containing a
mixture of individual small round cells and
cohesive clusters of similar cells. These cells
are three to four times the size of a mature
lymphocyte (Fig. 12-16) and have a minimal
amount of cytoplasm. The nuclei are similar
in appearance to those of Ewing's sarcoma,
with a very fine dispersed chromatin. The
cell clusters are larger and more cohesive
than similar clusters observed in Ewing's sar-
coma. In contrast to Ewing's sarcoma, some
of the cells have an oval or spindle shape,
with greater variability in nuclear shape and
size. At present there appear to be no im-
munohistochemical techniques clearly sepa-
rating small cell osteosarcoma from Ewing's
sarcoma.
GIANT CELL RICH
OSTEOSARCOMA
These osteosarcomas are characterized by a
prominent population of bland-appearing
osteoclast-like giant cells (Fig. 12-14). These
giant cells have multiple nuclei, frequently
more than 50, and moderate to abundant cy-
toplasm. The nuclei found within the mult-
inucleate giant cells are oval or coffee bean
shaped, with no nuclear anaplasia or pleo-
morphism. The diagnostic feature separat-
ing this osteosarcoma from giant cell tumor
of bone is the signifi cant nuclear atypia
(anaplasia) within the mononuclear stromal
cell component of the sarcoma. At least a
component of the spindle or osteoblast-like
cells display signifi cant nucl ear atypia be-
yond that see n in giant cell tumo r of bone.
The mononuclear cells found in giant cell
tumor of bone possess nuclei ide nti cal to
those seen in the osteocl ast-like giant cells,
but the nuclei in the mononuclear stromal
cells of a gia nt cell ri ch osteosarcoma show
conside rabl y greater degrees of nucl ear
atypia. Reactive osteoid can be found in
giant cell tumors; he nce the finding of small
amounts of osteoid does not distinguish
giant cell rich osteosarcoma from giant
cell tUlll o r of bone. However, signifi cant
amounts of osteoid-l ike matrix favors the di-
agnosis of giant cell ri ch osteosarcoma.
PERIOSTEAL OSTEOSARCOMA
These OSLeosarcomas invariably display the
chondroblasti c cYLOmorphologic pattern with
abundant chondroid matrix (Fig. 12-19).
Specifi c di agnosis is based on close correla-
tion of radiographs, clinical findings, and
cytomorphology.
PAROSTEAL OSTEOSARCOMA
These well-diffe re ntiated neoplasms are
generally cytomorphologicall y inseparable
from fracture callus and active osteoblastic
proliferations. Diagnosis depe nds o n careful
correlation of radiographs, clinical features,
a nd cytomorphologic findings. Aspirates
from parosteal osteosarcomas contai n a
small to modest number of spindl e cell s
showing low degrees of nucl ear atypia. In
general, mitotic fi gures are not found. The
predominant cell is a slender fibroblast-like
cell with a bacillary-shaped nucl eus. Nuclear
membrane irregul ari ties a re minimal , and
the chromatin pattern is fine to minimally
coarse. Small but di stinct nucl eoli are often
fo und on Papan icolaou staining. Mitotic fi g-
ures a re rare, a nd atypi cal forms are essen-
tiall y absent. Small fragments a nd clusters of
osteoid matrix may be present and, when
seen, are frequently surrounded by enlarged
ovoid osteoblast-like cells.
CENTRAL LOW-GRADE
-l OSTEOSARCOMA
Like parosteal osteosarcomas, these lesions
a re generally not identifiable as malignant by
purely cytomorphologi c analysis. Careful cor-
relation with radiographic and clini cal find-
ings is ma ndatory for their diagnosis. Often,
open biopsy is required for their identifica-
tio n. As with parosteal osteosarcomas, smears
are of low cellularity and the dominant cel-
lul ar component is a bland-appearing spin-
dle cell showing slight nucl ear e nlargement
and hyperchromasia. Small fragments of
osteoid may be present but are frequently
absent.
KEy DIAGNOSTIC FIGURES
Conventio nal Intramedullaary
Osteosarcoma
There is a pl eomorphi c spindl e and oval
cell population.
There is a subpopulation of atypi cal
plasmacytoid cell s resembing osteobl asts.
These cell s may have cytoplasmic vacuoles
a nd intracytoplasmic small red granules (on
Romanowsky staining).
Anaplasti c multinucleated neoplastic
gia nt cells are present.
T he re is a prominent number of mi totic
figures, some of whi ch are atypi cal.
Clumps a nd streamers of pink (RD-
manowsky stain) matrix representing os-
teoid are found.
Neoplastic cells stain strongly for alka-
line phosphatase.
Radiographic findings are consistent
with osteosarcoma.
Small Cell Osteosarcoma
There is a population of small round
cells with scanty cytoplasm a nd ro und nucl ei
containing fine dark chromatin.
Some variation in nucl ear size and
shape is seen.
Most cell s li e singly, but some cell clus-
ters are present.
Lymphoglandular bodies are absent.
Ch o ndro bl astic Osteosarcoma
The re is an abundant myxoid-chondroid
background.
A mixture of atypical spindle a nd oval
cells is found.
Atypical neoplastic giant cells are seen.
Radiographic and cl inical findings are
consistent with osteosarcoma.
Telangiectatic Osteosarcoma
The smear background is bloody.
There is a scanty cellul ar compone nt of
anaplastic spindl e-sha ped and polygonal
cells.
Rare fragme nts of pink dense matrix
(osteoid) are seen on Romanowsky staining.
The radiographic findings are consis-
tent with tela ngiectatic osteosarcoma.
Paraosteal a nd Cen t ra l Low-Grade
Osteosarcomas
Low-grade spindl e cell elements are
found.
Streamers of dense pink matrix (os-
teoid) are seen on Romanowsky staining.
Occasional atypical oval to round cell s
(neoplastic ostobl asts) a re present.
The radiograph ic findings are consis-
tent with osteosarcoma.
Periosteal Osteosarcomas
(Features as seen in chondroblasti c os-
teosarcomas)
Cytologic diagnosis requires close correla-
tio n benveen the radiographs and the cyto-
logic picture. Many difficulties in cytologic
diagnosis are resolved by discussing the ra-
diographs with a radiologist who is expert in
the diagnosis of musculoskeletal lesions. Par-
ticular areas of difficulty in cytologic diag-
nosis of osteosarcoma incl ude (1) diagnosis
of low-grade osteosarcomas (parosteal os-
teosarcoma and central well-differentiated
osteosarcoma), (2) the diagnosis of chron-
droblastic osteosarcoma, (3) separation of
conventional intramedull ary osteosarcoma
from o ther hi gh-grade sarcomas, (MFM)
when no osteoid matrix is identifi ed in the
smears, a nd (4) diagnosis of telangiectatic
osteosarcoma.
The distinction of well-diffe rentiated os-
teosarcoma (parosteal osteosarcoma a nd
central well-differentiated osteosarcoma)
from fracture callus, periosteal reactive le-
sions, and fibrous dysplasia can be extremely
difficult. In general, well-differentiated os-
teosarcomas have greater degrees of nuclear
atypia than are found in fibrous dysplasia or
most maturing fracture calluses. These well-
differentiated osteosarcomas usually have a
large r population of atypical spindle cell s
than are seen with benign lesions. None-
theless, many well-diffe rentiated osteosarco-
mas elude cytologic di agnosis and require
open biopsy. In the appropri ate clinical set-
ting and with characteristic radiographs,
parosteal osteosarcomas can be diagnosed
by FNA if the spindl e cell population ex-
hibi ts suffi cient nucl ear atypia and frag-
me n ts of osteoid are presen t.
Cho ndroblastic osteosar comas cannot be
separated from chondrosarcomas by purely
cytologic eval uati on. Radiographic diffe r-
e nces between chrondroblastic osteosarcoma
and chondrosarcoma may allow differentia-
tion of chrondroblasti c osteosarcoma from
chondrosarcoma.
Because conve ntional osteosarcomas are
high-grade sarcomas composed of anaplas-
tic spindl e and polygonal cell s, they may be
cytologicall y inseparabl e from other high-
grade sa rcomas, particularly MFH, when
fragments of osteoid canno t be identified.
Separation of these osteosarcomas from
MFH requires the demonstration of frag-
ments of osteoid or the presence of atypical
osteoblast-like cells characteri zed by a plas-
macytoid or oval shape with an eccentric nu-
cleus. The cytoplasm of these cell s frequently
has small vacuoles and / or red cytoplasmic
granules that are seen on Romanowsky-
stained preparations. The presence of these
cell s, coupled with osteoid or a radiograph
showing defi ni tive matrix formation, all ows
distinction of high-grade intramedullary os-
teosarcoma from MFH and othe r pleomor-
phic sarcomas.
Because telangiectatic osteosarcomas are
blood rich, needle aspiration smears are
characteristicall y blOOdy. Frequently, th e
bloody component is so extensive as to ex-
clude a neoplastic cellul ar element. In these
cases, cytologic diagnosis cannot be made.
Careful search of the smears, particularly
within areas of clotted blood, may reveal di-
agnosti c pleomorphic spindl e and polygonal
cell s alo ng with tiny fragments of osteoid.
When such tissue fragments are present
along with the appropriate radiographi c
findings, a diagnosis of telangiectatic osteo-
sarcoma can be made.
OTHER LESIONS
Rarely, foci of osteomyelitis are not recog-
ni zed on radiologic and clinical grounds and
undergo FNA. Culture of aspirated material
is the most valuabl e component of the pro-
cedure when an infectious lesion is ex-
pected. In acute bacterial osteomyeliti s, the
smears are dominated by large numbers of
neutrophils and smaller numbers of histi o-
cytes, lymphocytes, and plasma cells
3
Fre-
quently the aspirate is grossly purulent, im-
mediately suggesting the need for culture of
the aspirated material. Gram stains or other
bacterial/fungal stains are helpful in con-
firming the presence of bacteria.
34
Bacterial
infections may secondarily involve primary
sarcomas of bone.
35
The radiographic appearance of osteo-
myelitis depends on the phase of the disease.
In the acute phase of bacterial osteomyeli tis,
radiologic changes are usually absent. As the
process becomes more established, signifi-
can t bone destruction occurs and areas of
reactive new bone formation are seen. As the
process enters the subacute phase, areas of
lysis become ragged and often eccentric in
locati on. Bone death occurs, resulting in a
sequestrum. With further evolution, the pe-
riosteum is lifted from the cortex and new
reactive bone is laid down, resulting in an
involucrum. The surrounding soft tissues
show changes due to edema. In the chronic
phase, the involucrum and sequestrum are
well formed. The bone demonstrates lytic
and blastic zones that are poorly marginated.
Differentiation from Ewing's sarcoma,
phoma, and other hi gh-grade malignancies
may be difficult when the clinical history and
findings are not present.
The cytologic features of chronic osteo-
myelitis are less definitive, but examples
of fungal osteomyelitis have been confirmed
by cytologic study with the aid of special
stains.
30
,36 In these cases, alcian blue-periodi c
acid-Schiff stains along with methenamine
silver stains are helpful in demonstrati ng the
responsible organisms. In cases of granulo-
matous osteomyelitis, epithelioid histiocytes
along with Langerhans-type giant cells are fre-
quently seen in aspirate preparations. The
finding of such cellular elements is highly sus-
picious for tuberculosis, but culture confir-
mation is suggested.
OSTEOCHONDROMA
This lesion is an exostosis having a mush-
room shape in which the cortex of the nor-
mal bone merges with the stalk of the os-
teochondroma in a smooth, continuous
fashion. The osteochondroma's stalk is com-
posed of well-formed cortical and med ullary
bone with a marfOW cavity. A cartilaginous
cap of vari abl e thickness covers the head of
the lesion. The thi ckness of the cortical cap,
along with histiologic features, aids in sepa-
rating benign osteochondromas from those
showing sarcomatous degeneration of the
cartilaginous cap. Needle aspirates obtained
from osteochondromas generally are char-
acterized by tissue arising in the cartilagi-
nous cap or marrow elements. Because the
cytologic features are dominated by the car-
ti laginous cap material, this lesion is di s-
cussed more fully under cartil aginous le-
sions. Suffice it to say that the distinction of
benign osteochrondroma from grade I
chondrosarcoma may be impossibl e, and
tologic evaluation is required. Please see
Chapter 11 for further discussion.
FIBROUS DYSPLASIA
Fibrous dysplasia may occur in either a
mono-osteal or a polyosteal form. This de-
velopmental disorder primarily affects chil-
dren and young adults and occurs equally in
males and females. Most mono-{)sti c lesions
are asymptomatic, while the polyostic form
presents as multiple pathologic fractures of
the long bones in children
3
? Any bone may
be involved by fibrous dysplasia, but the
form most frequentl y involves
the femur, ribs, and cranial facial bones.
37
,38
The polyostic form most frequently involves
the femur, tibia, humerus, pelvic bones, ribs,
and bones of the hands and feet.
Radiographically, fibrous dysplasia ap-
pears as a medullary lesion with a ground
glass appearance. The radiographi c density
depends on the rel ative proportions of bone
and fibrous elements, with a predominance
of fibrous tissue be more radiolucent. In gen-
eral, lesions of the craniofacial bones display
greater radiodensity than lesions occurring
elsewhere. In the majority of cases, the bone
contour is expanded by a lesion with a
ground glass appearance, and may cause sig-
nifi cant cortical thinning and osteal scallop-
ing. In the long tubular bones the preferred
site is the diaphysis, but metaphyseal in-
volvement has also been reported. Signs of
punctate or ring-like calcifications can be
found, but in the majority of cases fibrous
dysplasia appears radiographi cally well cir-
cumscribed, associated ,vith a relatively wide
rim of sclerotic bone (rind). In weight-bear-
ing bones considerable deformity of the
bones occurs, resulting in changes such as
the shepherd's crook deformity characteris-
tic in the proximal femur.
HISTOPATHOLOGY
Fibrous dysplasia is characteri zed by a pro-
liferation of small spindle cells composed of
oval nuclei surrounded by a scanty to mod-
est amount of cytoplasm with indisti nct
toplasmic borders. Overall cellularity can be
quite variable, with the highest cellularity ob-
served in lesions from young patients. In
general, the cells proliferate in a disorgan-
ized fashion surrounding C- and V-shaped
fragments of woven bone (Fig. 12-21).
These trabeculae of immature bone and
teoid vary considerably in size and shape.
Figure 12-21. Fibrous dysplasia is characterized
histologicall y by a proliferation of small , bland
cells containing oval nuclei and
woven bone. The woven bone lies in and
Y-shaped formations and appears to arise directly
from the fibrous tissue without intervening osteo-
blasts (H&E. XIO) .
Figure 12-22. Woven bone trabeculae in a
nese character" configuration is characteristic of
fibrous dysplasia. Note that there is no
blastic rimming, and the woven bone appears to
arise directly from the fibroblastic stroma (H&E,
X50).
The immature bone appears to arise directly
from the connective tissue stroma wi thout
intervening recognizable osteoblasts (Fig.
12-22). Osteoblasti c rimming is not a fea-
ture of fibrous dysplasia. Osteoid seams may
surround the trabeculae of woven bone.
CYrOLOGIC FEATURES
Aspirates of these lesions yield smears of
low to moderate cellulari ty. The individual
spindle-shaped cells are short or oval (Fig.
12-23). The nuclei are bland and oval to
Figure 12-23. Aspirated material from examples
of fibrous dysplasia is relatively nonspecific and is
characterized by small , bland spindle cells with
scanty amounts of wispy cytoplasm. The
ual cells have ovoid nuclei with smooth nuclear
membranes and even, dense chromatin
Quik, Xl00).
Figure 12-24. The stromal cell s aspira ted from
examples of fibrous dysplasia have an eve n chro-
matin pattern, a smooth nuclear membrane, and
scanty, wispy cytoplasm often with a bipolar ap-
pearance. The background may contain a few red
blood cells and small , punctate blue-purple de-
posits (Dilt' Quik, X200).
spindl e-shaped, without prominent nucleoli
(Fig. 12-24). A fine granular chromatin pat-
tern is prese nt. Mitoti c activity is not demo n-
strable in cytologic smears. Occasional frag-
ments of bone or osteoid with a n irregular
three-dime nsional shape are found. Rarely,
multinucl eated giant cell s are present within
smears. The cytologi c features are insuffi-
cie nt to substanti ate a diagnosis of fibrous
dysplasia purely o n cytologic grounds. At
times the radiographic findings are so char-
acteristi c of fibrous dysplasia that the rela-
tivel y nonspecific cytologic findings are suf-
ficient to confi rm the d iagnosis.
OSSIFYING
FIBROMYXOID TUMOR
Ossifying fibromyxoid tumors are ra re soft
ti ssue lesions that usuall y present as small ,
painless nodules within the subcutaneous tis-
sues.
39
The re has been a mal e predomi-
nance in reported cases, and almost all have
occurred in adullS. The clinical behavior has
varied, with most tumors following a be nign
course; however, up to a third have recurred
locally.
Histologically, this neoplasm is composed
of a uniform round or polygonal cell popu-
lation arranged in cord-li ke or nest-like col-
lections that lie in a predominantly myxoid
background. While the majority of the back-
ground has a myxoid, sli ghtl y hyaline a p-
j:>earance, othe r areas are ri chly collagenous,
and foci of metaplastic bone are present in
most cases. Bone most freque ntly is found in
a narrow zone near the pe riphery of the neo-
plasm, where it forms irregular branch ing
spi cules or trabeculae between tumor lobul es.
CYTOLOGI G F INDINGS
Smears from these lesions are rnoderately
cellular, with t issue fragme nts composed of
fine fibrillary ground substance.
4o
The cell s
are moderate in si ze and mildly pleomor-
phic. Most form small groups, occasionally
with a rosette-li ke appearance. Single ceil s,
when present, have ill-prese rved cytopl asm,
with many bare nuclei being scattered in the
background. The nuclei are round to oval in
sha pe and eccentrically located within the
cytoplasm. The chromatin clumping patte rn
is fine, and nucleoli are indisti nct. Mitoti c
fi gures are not ide ntified.
4o
The cells fre-
quently surround fragments of the fibrill ary
matrix. Bone is not identified in the smears.
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13
GIANT CELL-CONTAINING LESIONS
A variety of neoplastic and reparative lesions
of bone are characterized by osteoclast-like
multinucleated giant cells. The giant cells
form variable portions of the total cellulari ty
in these lesions and, whil e rarely dominating
the cell population numerically, they are a
prominent and defining morphologic fea-
ture of this set of lesions. The giant cells are
frequently a reactive component and are not
necessarily neoplastic themselves. As would
be expected from a diagnostic category de-
fined by a single morphologic feature, these
lesions have widely varying behaviors. Some
(giant cell reparative granuloma. brown tu-
mor of hyperparathyroidism) are reactive
proliferations associated with metabolic dis-
turbances or injury; others are true neo-
plasms with intermediate (conventional
giant cell tumor ) or fully malignant (giant
cell-rich osteosarcoma) behavior. The le-
sions are best separated on the basis of the
mononuclear cell component, although
some differences in giant cell morphology
exist. Careful analysis of the mononuclear
cell component, along with clinicopatho-
logic correlation, is mandatory for the accu-
rate diagnosis of these lesions.
212
ANEURYSMAL BONE CYST
Aneurysmal bone cyst is a term coined by Jaffe
and Lichtenstein
1
,2 to describe a lesion
occurring within bone and possessing a ra-
diographic appearance characterized by
"blowout" distention of the cortical bony
contour. The gross appearance at surgery is
that of a spongy or multiloculated blood-
filled cyst. Aneurysmal bone cysts occur in
two forms. Primary aneurysmal bone cysts
arise de novo, unassociated with a preexist-
ing neoplasm, while secondary cysts are mor-
phologically identical structures superim-
posed on a preexisting lesion. Primary
aneurysmal bone cysts appear to be locally
destructive, with a significant recurrence
rate, but are otherwise benign. The behav-
ior of secondary aneurysmal bone cysts is de-
termined by the prognosis of the underlying
lesion.
A distinct maj ori ty (80%) of aneurysmal
bone cysts occur in individuals whose epi-
physes have not yet closed (skeletally imma-
ture) and who are under 20 years of age,s4
The male/female ratio is equal. Any bone
may be affected, including long tubular
GIANT CELL-CONTAINING LESIONS 213
bones and flat bones.3-5 Wi thin the long tu-
bular bones the metaphyseal areas are fa-
vored sites of occurrence. The majority of
aneurysmal bone cysts present with pain
and/ or swelling of variable duration.
Aneurysmal bone cysts have a dramatic and
distinctive radiographic appearance in
whi ch there is extensive ballooning of the
bone contour resul ting in distention of the
periosteum and a thin shell of residual sub-
periosteal bone. The lesion is lytic and may
have a radiogTaphi c "soap bubble" appear-
ance representing the multiloculation typi-
cal of these lesions. Thi s blowout appear-
ance is characteristic of aneurysmal bone
cysts. The lesion is typically metaphyseal and
eccentri c. Aneurysmal bone cysts are capa-
ble of crossing joints and within the verte-
bral column may involve several adj acent
bones, sometimes with extension into asso-
ciated ribs.
HISTOLOGIC FINDINGS
Histologi c sections of curettings from
aneurysmal bone cysts reveal tissue septae
surrounding collapsed or distended, blood-
filled spaces (Fig. 13-1). The septae are com-
posed of fibrous tissue with loose capillary
channels, scattered multinucleated giant
cells, and streamers of osteoid and woven
bone oriented along the long axis of the sep-
Figure 13-1. Aneurysmal bone cysts are charac-
terized by fibro-osseous septae surrounding
blood-filled spaces. The septae vary in thickness,
as do the sizes of the blood-filled channels (H&E,
X20).
Figure 13-2. The septae of aneurysmal bone cysts
are composed of fibrous tissue with loose capil-
lary channels, scattered multinucl eated giant
cell s, and streamers of osteoid or woven bone ori-
ented along the long axis ofseptae (H&E, X50).
tae (Fig 13-2). Solid areas resembling gran-
ulation tissue or storiform swi rls are a fre-
quent finding.
Secondary aneurysmal bone cysts have a
microscopic appearance identical to that of
primary aneurysmal bone cysts. However, they
also contain residual foci of the primary le-
sion (giant cell reparative granuloma, giant
cell tumor, chondroblastoma, osteosarcoma).
CYTOLOGIC FINDINCS
In our experience, aspirates obtained from
aneurysmal bone cysts are composed pre-
dominantly of blood, with very rare reactive-
appearing spindle cells and osteoclast-like
giant cells (Fig. 13-3). The spindle cell com-
ponent is bipolar, with wispy cytoplasm and
an oval- to spindl e-shaped nucleus.
6
The nu-
cleus has finely granular chromatin and a
smal l, indistinct nucleolus. Rarely, fragments
of septae are found (Fig. 13-4).
Cytologic preparations made from im-
prints of septal tissue from aneurysmal bone
cysts contain fusiform and rounded cells in
a blood-rich background. Neither by exam-
ination of aspirati on smears nor by imprint
preparations can aneurysmal bone cysts be
specifi cally diagnosed. Fine needle aspira-
tion (FNA) may be helpful in establishing
the blood-rich nature of the lesion and the
absence of obviously malignant elements.
These findings aid in confirmation of the ra-
diologic impression of aneurysmal bone cyst.
214 CYTOPATHOLOGY OF BONE AND SOFT TISSUE TUMO RS
Figure 13-3. Smears pre pared from f i n e ~ n e e d l e
aspirales of ane urysmal bone CYS LS are extremely
hypocellular and consist predominantly of blood.
Within the bl oody background are scattered fi-
broblasts, rare oSlcoblasts, and occasional osteo-
c1 a') Li c giant cells (Diff-Quik, X50).
SOLID ANEURYSMAL
BONE CYST
Occasionally, predominantly soli d lesions
occur at sites characteristi c of aneurysmal
bone cysts and have a morphologi c appear-
ance similar to that of solid areas of typical
aneurysmal bone cysts. These lesi ons are re-
ferred to as solid aneurysmal bone cysts.
7
-
9
They
contain some aneurysmally dilated sinu-
soids, but the predominant component is a
solid fibrovascular tissue containing signifi-
cant fibromyxoid areas with variable degrees
of calcificati on and ossification (Fig. 13-5).
The dominant fibroblastic cell component is
Figure 13-4. OccasionaUy, small fragments of in-
tact septae are present, demonstrating the fibro-
osseous nature of the lesion. These fragments
contain bland spindle celi s, small osteoblasts, and
fragments of osteoid streamers (H&E, X100).
Figure 13--5. Solid aneurysmal bone cysts are com-
posed predominantly of a solid growth of fibro-
vascular ti ss ue containi ng significant fibromyxoid
areas with variable degrees of calcification and os-
sification (H&E, x25).
arranged in whorls or in a storiform pattern ,
often with a hi gh mitotic index. Nucl ear
pleomorphism is absent. Osteoclast-like giant
cell s are scattered around areas of hemor-
rhage and are frequently prominent. The
woven bone and osteoid may be extensive
and at times lack osteoblasti c rimming.
The cytologic appearance of these lesions
has not been described.
HYPERPARATHYROIDISM AND
OSTEITIS FIBROSA CYSTICA
Hyperparathyroi dism may result in excessive
osteoclastic bone reabsorption with diffuse
deminerali zation of the skeleton. Reabsorp-
tion may be parti cularly active in some ar-
eas, resulting in cystic lesions mimi cking a
primary bone tumor on radiographs. Bone
lesions are symptomatic in only 10%-25% of
cases, with severe bone di sease being even
rarer.
Tn most cases of hyperparathyroidism, skele-
tal changes are subtle and require hi gh-qual-
ity radiographic imaging or digitali zed radi-
ography of the bones. The earliest changes
are seen in the hands
lO
Classically, hyper-
parathyroidism presents radiographi cally as
subperiosteal bone reabsorption, which is
most conspicuous on the radial aspect of the
phal anges.
1
(
GlANT CELL-CONTAiNING LESIONS 215
At sites of seve re involvement, osteitis fi-
brosa cystica occurs. In this conditi on, ec-
centric corti cal osteolysis and bubbly lytic le-
sions are seen.
HI STOLOGIC FINDINGS
Hi stologic secti ons show normal bone tra-
beculae undergoing reabsorption and re-
placement by loose fibrous tissue containing
large numbers of osteoclast-like giant cells.
Frequently, the giant cells cluster around
zones of hemorrhage or hemosi derin depo-
sition. At the periphery, active osteoclastic
bone reabsorpti on is prominent.
ll
Foci of
bone formation similar to those seen in giant
cell reparative granuloma may be found.
CYTOLOGIC FINDINGS
Multinucleated osteoclast-like y-iant cells
dominate the cytologic picture. 2,13 These
cells have regular ovoid nuclei. A second
population of mononucl ear stromal cells
with a spindle shape is present.
J2
The nuclei
of the stromal cell s are sli ghtly larger, with a
more open chromatin pattern than that of
the nuclei found \.vithin the osteoclast-l ike
giant cells. The background is bloody, and
granular basophili c calcium debris is often
present, l3
PROBLEMS IN D IAGNOSIS
The cytologi c findings in brown tumor ofhy-
perparathyroidism overl ap those of aneurys-
mal bone cyst, giant cell reparative granu-
loma, and true giant cell tumor of bone.
Clini cal and radiographi c findings are help-
ful in separating these lesions. In general,
the giant cells of conventional giant cell tu-
mor have a larger number of nucl ei than are
seen in the other lesions, but overlap be-
tween these entities in the number of nuclei
per giant cell is substantial. Separation of
these lesions strongly depends on clinical-
radiographic-cytologic correlation.
GIANT CELL REPARATIVE
GRANULOMA
Giant cell reparative granuloma is a rare re-
active lesion preferentially affecting the
craniofacial bones.
14
, 15 Similar lesions are
know to occur within the small bones of the
hands.
16
This entity may be an abnormal
reaction to intraosseous hemorrhage or
trauma. Its relationship to aneurysmal bone
cyst, particularly the solid variant, is unclear.
RADIOGRPHIC FINDINGS
\l\lithin the craniofacial bones, giant cell
reparative granul oma is associated with
round or oval areas of osteolys is, occasion-
ally showing fine trabeculati on. The oste-
olytic areas have distinct borders with mini-
mal reactive scl erosis. The cortex of the
craniofacial bones generally remains intact,
with a periosteal reaction being observed.
In long tubular bones, giant cell repara-
tive granuloma is associated with an exten-
sive metaphyseal or diaphyseal lytic defect.
While the contour of the bone is eccentri-
cally expanded and the cortex is thinned,
the cortex genera lly remains intact.
HISTOLOGIC FiNDINGS
Giant cell reparative granulomas are charac-
terized histologically by a coll agenous stroma
with enmeshed spindle-shaped fibrobl asts.
The cellularity is variable but often high. In-
terspersed \'1rithin the fibroblastic tissue is a
variable number of multinucl eated osteo-
clast-like giant cells. The distribution of these
cells is irregular, the cells often aggregating
in areas of hemorrhage or hemosiderin dep-
osition. Occasional trabecul ae of reactive wo-
ven bone lined by os teo blasts are present.
CYTOLOGIC FiNDINGS
Smears of giant cell reparative granul oma
are moderately cellular, with large, cohesive
tissue fragments. 17 T he tissue fragments are
composed of two cell types. The first is a mul-
tinucleated osteoclast-li ke giant cell that is
closely admixed with the mononuclear cell
component. The second is a mononuclear
cell that forms the bulk of the tissue frag-
ments. Exfoliation of cells from the edges of
these fragments is a prominent finding re-
sulting in scattered single spindle-shaped
cells surrounding the tissue clusters. The
spindle cells have ovoid nuclei with a finely
granular chromatin and inconspicuous nu-
cleoli. Cytoplasm is of moderate amount and
is associated \\rith indistinct cell borders. The
216 CYTOPATHOLOGY OF BONE AND SOY[ TISSUE TUMORS
cell clusters frequently have a syncytial ap-
pearance.
The multinucleated giant cell s most fre-
quently congregate at the edges of the tissue
fragments. Occasional isolated multinucl e-
ated giant cell s are seen. These giant cell s
contain 5 to 40 or more nuclei that overlap:
The cytoplasm of the giant cells is abundant
and dense. Mitoti c fi gures are not seen in
the smeared material. Hemosideri n-laden
macrophages and inflammatory cell s are
present in small numbers.
Giant cell reparative granul oma, solid
aneurysmal bone cyst, and the brown tumor
of hyperparathyroidi sm cannot be separated
solely on cytologic analysis. Fine-needle as-
piration is of value by demonstrating the
bland spindle cell morphology and multi-
nucl eated osteoclast-like giant cell s that
characterize these lesions. The clin ical and
imaging findings usuall y all ow separati on of
these entiti es. In most cases, precise clini cal
separation is relatively unimportant once hy-
perparathyroidism has been excluded.
The cytologic pictures of giant cell repar-
ative granuloma and conventional giant cell
tumor show substantial overlap, frequently
making it impossible to separate them by
purely cytomorphologic study.
CONVENTIONAL GIANT CELL
TUMOR OF BONE
Conventi onal giant cell tumors of bone
(GCTB) are locally aggressive and a
tendency toward local recurrence. !7- 9 Oc-
casional reports of metastati c but otherwise
conventional GCTB exist.
2o
,2! Giant cell tu-
mors of bone represent approximately 5%
of all primary bone neoplasms
19
They dis-
playa distinct predil ection for women, with
a female/ male ratio of approximately 1. 5: l.
The maj ority of patients affected by GCTB
are skeletally mature and are over 18 years
of age. The peak incidence occurs in the
third decade. but the age ra nge is broad.
The majority of GCTBs occ ur within the
long bones, with the distal femur, proximal
tibia, distal radius, humerus
being the favored sites.! Wlthm the long
bones. the maj ority of GCTBs occur within
th\' epiphyses.
Giant cell tumors of bone usually present as
eccentric osteolytic lesions wi th li ttle or
incomplete surrounding sclerosis.
17
,22 The
bony contour is not infrequently expanded,
and a multilocul ated appearance is common.
The neoplasm is centered in the epiphysis
and extends to the subarti cul ar cOftex.
HISTOLOGIC FINDINGS
Whi le GCTBs most frequentl y appear as uni-
formly highly cell ular neoplasms. they may
show degenerative and senescent changes
that compli cate the histologic appearance.
Such changes incl ude fibrosis, xanthoma-
tous infiltrates, and the development of an
aneurysmal bone cyst.
Conventional GCTBs are composed of
sheets of mononuclear cell s with rather uni-
formly distributed multinucl eated osteoclast-
like giant cells (Fig. 13-6) . The mononucl ear
cell s are ovoid or spindle-shaped. with mod-
est amounts of eosinophilic cytoplasm. Oc-
casional cells are binucleated. Whi le mi totic
activity is usually slight. it may at times be
prominent. Nucl ear atypia and pleomor-
phism are generally absent, but on the rare
occasions when atypi a is present, it is degen-
erative.
Figure 13-6. Conventional CCTBS are charac-
teri zed by a rather monotonous proliferation of
mononuclear stromal cells admi xed wi th a promi-
nent component of multinucl eated osteoclasl-
li ke giant cells (H&E. X25).
GlANT CELL-CONTAlNING LESIONS 217
Figure 13-7. The nuclei of the mononuclear cells
and multinucleated giant cells are identical in ap-
pearance in GCTS. Characteristically, the multi-
nucl eated giant cell s seen in GCTB have 40 or
more nuclei. In addi tion, the mononuclear cell
component tends to have a spindle shape (H&E,
X50).
The mul tinucl eated giant cell s are dif-
fusely distributed th roughout the neopl asm
and characteristically contain 40 or more
nucl ei (Fig. 13-7). The nuclei are morpho-
logi cally identical to those seen in the mono-
nucl ear cell component. The nuclei are
round to oval, with small , distinct nucl eoli.
The cytoplasm is generally granular and
eosinophilic in appearance but may be vac-
uolated (Fig. 13-8). Recurrent GCTBs fre-
quently show senescent or regenerative
changes, with broad bands of fibrous tissue
Figure 13-8. On high-power examination, the nu-
clei of the mononuclear stromal cells and giant
cells appear identical. The mononuclear cells ap-
pear as plump spindle-shaped cells rather than
the round cells seen in chondroblastoma (H&E,
X200).
replicating the storiform pattern of benign
fibrous histiocytoma.
23
Reactive bone formation occurs in a sig-
nificant number of GCTBs and is usually lo-
cated at the periphery of the neoplasm.
24
CYTOLOGIC FINDINGS
Smears are mOderately to abundantly cell u-
lar, with numerous ti ssue fragments lying in
a blood-stained background.
25
,26 On low-
power examination the bimorphic cell pop-
ul ation is evident, with mononuclear cells
and multinucl eated osteoclast-like giant cell s
being present (Fig. 13-9). The mononucl ear
cells frequently form cohesive tissue frag-
ments to whi ch variable numbers of multi-
nucleated osteoclast-like giant cells are at-
tached. This clustering and attachment of
multinucleated giant cells frequently result
in the so-call ed checkerboard pattern.
26
In
other microscopic fields, the mononuclear
cells and multinucl eated osteoclast-like giant
cells are dissociated.
26
The mononucl ear cell component has
an ovoid to spindle-shaped morphol ogy
with small to moderate amounts of cyto-
plasm.
25
-
27
When the cells li e in clusters. the
cytoplasm has a syncytial appearance.
26
The
mononuclear cells have round, ovoid, or
elongated nuclei that often are eccentri cally
positioned (Fig. 13-10). Occasionally these
mononuclear cells have vacuolated cyto-
Figure 13-9. Low-power examination of cytologic
smears from conventional GCTBs shows a bi-
morphic cell population with mononuclear cells
and multinucl eated osteoclast-like giant cells.
This pattern often produces a checkerboard ap-
pearance (Diff-Qui k. X50).
Figure 13-10. Cytologic mate ri al obtained from
GCTBs shows the mononuclear cells to have
round, ovoid, or elongated nuclei , often eccen-
tricall y positioned within the cell (H&E, X 100) .
plasm. Scattered mononuclear cells demon-
strate mitotic figures.
26
27
The nuclei of the osteoclast-like giant cell s
arc either the same size as or sli ghtly large r
than the nucl ei of the mononucl ear cell
component (Fig. 13_11)25-27 The number
of nucl ei lvilhin the multinucleated giant
cell s vari es considerably, from 3-4 to more
than 50 (Fig. 13-11 ) .26,27 The numeri cal re-
lationship bct\veen osteocl ast-li ke g'iant cells
and mononucl ear cell s vari es among speci-
mens, but in the maj ori ty of cases osteoclast-
like giant cells are a prominent component
of the smears. Tn additi on to the multinu-
cleated giant cells, binucl eated stromal cells
are not infrequent.
Figure 13-11. Tn cytologic preparations, the
osteoclast-l ike giant cells characteristi c of GCTS
con tain nuclei simi lar to those seen in the mono-
nucl ear cell componenL. The number of nuclei
within the multinucleated giant cells vari es con-
siderably but is often 50 or more (1-1 &, X 100) .
The reported cytomorphology of metasta-
t ic ben ign GcrB is variabl e.
28
,29 [n one re-
pon, the appearance was entirely benign
and did not signi fi cantly differ from the fea-
tures of primary conventional GCTB.28 In
another report, the metastati c deposit ap-
peared to demonstrate less cohesion be-
tween the multinucl eated giant cell s and the
mononuclear cell tissue fragments. In addi-
tion, the deposit demonstrated an increased
number of mitotic fi gures in the mononu-
cl ear cell s.
29
D IAGNOSTI C FEATURES
Smears are moderately to abundantly
cellular, with a bloody background.
Scattered ti ssue fragments ,,,ith periph-
erally adherent mul tinucleated osteoclast-
like giant cells give a checkerboard appear-
ance.
There are mononuclear cells with an
ovoid to spindle shape containing modest
amounts of cytoplasm.
Mononuclear cells in clusters frequently
give the cytoplasm a syncytial appearance.
The mononuclear cell nuclei are ap-
proximately the same size as or sli ghtly
smaller than the nucl ei of the osteoclast-like
gian t cell s.
The monon uclear cell nucl ei have a
condensed chromatin with small but fre-
quentl y di sti nct nucl eoli.
Mitoti c fi gures may be seen in the
mononucl ear cell component.
The mul tinucleated giant cells contain
a variabl e number of nucl ei but often 40 or
more nuclei per giant cell .
The cytoplasm of the multinucl eated
giant cells may contain vacuoles or may have
a granular eosinophilic appearance.
A subpopulation of mononuclear cells
and multinucl eated osteoclastic giant cells
may li e indi vidually in the baCkground.
PROBLEMS I N DIAGNOSIS
Giant cell tumors of bone must be disti n-
guished from nonossifying fibromas, chon-
droblastomas, chondromyxoid fibromas, giant
cell-ri ch osteosarcomas, the brown mmor of
hyperparathyroidism, and some aneUll'smal
bone cysts.
Nonossifying fibromas generally contain
fewer multinucleated giant cell s than is char-
GlANT CELL-CONTAINING LESIONS 219
acteristic of GCTB. In addition, sign ifi cant
radi ographic diffe rences are present and are
extremely helpful in separating these le-
sIons.
Chondroblastoma is an important entity
in the differential di agnosis of conven ti onal
GCTB, as both are epiphyseal lesions. In con-
trast to conve nti onal GCfB, chondroblas-
tomas more frequently involve the skeletally
immature, usuall y occurring in pati ents un-
der 18 yea rs of age. Giant cell tumors of bone
occur in skeletall y mature indi viduals, who
are usually over 18. Cytologically, chondro-
blastomas are characteri zed by a mono-
nucl eated cell populati on that is predomi-
nantly round to ovoid in morphology. The
nucl ei of chondroblastomas freque ntly con-
tain nucl ear clefts or folds, whi ch also aid in
their distinction from GeTB. The cells
found in GCTBs have a more ovoid to spin-
dl e shape in the mononucleated population.
Chondroblastomas are character ized by a
metach romatic (chondromyxoid) stromal
component in the background, whil e that of
conventi onal GerB is bloody and lacks a
stromal component.
Smears obtained from chondrornyxoid fi -
bromas contain abundant chondromyxoid
materi al and a populati on of spindle-shaped
to stell ate cells. The latter cell s all ow di s-
tinction from smears obtained from GeTS.
Smears of material aspi rated from the
brown tumor of hyperparathyroidi sm may
be indistinguishable from those obtained
from Gers. Clini cal and laboratory findi ngs
often all ow distinction of these two lesions.
Distinction of giant cell-ri ch osteosar-
coma from conventional GcrB is achieved
by analysis of the mononucleated cell com-
ponent. While mi totic figures may be pres-
ent in both lesions, the mononucleated cell s
of GCTB lack the atypia characteristic of os-
teosarcoma. In addition, most examples of
osteosarcoma reveal some osteoid, a feature
usuall y absent in smears obtained from
GCTB. In addition, the characteri stic chec-
kerboard morphology of GerB is not seen
in smears obtained from giant cell-rich os-
teosarcoma. Radiographic findings also ar e
important in separating GCTS rrom os-
teosarcoma.
Separation of aneUll'smal bone cyst from
GeTS may be impossibl e since some sec-
ondary aneurysmal bone cysts arise in a back-.
ground of conventi onal GCTB. In most
cases, howeve r, aspirates obtai ned from
aneurysmal bone cysts are extremely bloody,
with few tissue fragments. The presence of
tissue fragments and adherent multinucl e-
ated giant cell s giving a checkerboard pat-
tern excludes the diagnosis of pure aneurys-
mal bone cyst and indicates the presence of
GerB. In these ci rcumstances, a secondary
aneurysmal bone cyst component cannot be
excl uded, but radiographi c studi es will usu-
ally clarify the situati on.
CHONDROBLASTOMA
While chondroblastomas are characteri zed
by a compone nt of chondroid matrix on hi s-
tologic examination, some exampl es ana-
lyzed cytologically disclose little or no chon-
droid matri x. These smears are dominated
by a mixed population of small round
mal cell s and osteoclast-like giant cell s. Be-
ca use of their size and striking morphologic
features, the osteocl astic-l ike giant cells tend
to be a promine nt portion of the smear mor-
phology. The clini cal, radiographic, and hi s-
tologic findings of chondroblastoma are de-
scribed in Chapter 11. In the sections bel ow,
the cytologic findings of chondrobl astoma
will be discussed and compared with those
of other giant cell-predominant lesions.
O 'TOLOGI C FINDINGS
Smears made from aspirates of chondrob-
lastomas are rnoderately to markedly cell u-
lar, containing both single cells and cell ag-
gregates. 30-33 Numeri call y, the smears are
dominated by monol1ucl eated cell s that are
relatively uniform in size and round or
polygonal in shape (Fig. 11_17) .31-33 The
mononucleated cells contain nuclei with li t-
tle or no pl eomorphism and are character-
ized by deli cate nuclear membranes and an
evenl y di stributed chromati n. Reniform or
grooved nucl ei are a frequent finding (Fig.
11_19)30-34 Nucleoli have bee n described as
small or inconspicuous. Rarely, binucl eated
forms are present. Mitotic fi gures are rare to
absent. Some nucl ei demonstrate distinct in-
tranuclear cytoplasmic pseucloincl usions.
The second cell population is comprised
of osteoclast-type giant cell s with multipl e
uniform nucl ei exhibiting a bland
ance (Fig. 13-12) 30-33
Figure 13- 12. Cytologic smears from chondro-
blastomas are dominated by mononucl ear cell s
that are relatively uniform in size and have a
round or polygonal shape. A prominent compo-
nent of osteoclast-type giant cell s is present.
These cells have mul tiple uniform nuclei with a
bland nuclear appearance (OiA-:'Quik, X50).
Within the cell aggregates, occasional
smears demonstrate thin "chicke n-wire" cal- '
cifi cati ons surrounding individual cells.
34
Whi1e visibl e on Papa ni colaou stai ning, this
calcificatio n is most easily seen in hema-
toxylin and eosin (H&E) preparations."
DIAGNOSTI C FEATURES
Smears a rc mode rately to highly cellu-
lar, composed of both mononucleated cells
and osteoclast-like giant cells.
The maj o rity of cells li e singly, but some
form loose aggregates.
The mononucleated cells are round or,
less commonly, pOlygonal in shape a nd pos-
sess round nucl ei.
The nucl ei of the mononudeated cells
have thin, delicate me mbranes and a fine
chromatin.
A subpopulation of the mononucl eated
cell s has reniform nuclei with nucl ear
grooves or folds.
Rarely, the mononucl eated cells have in-
tranucl ear cytoplasmic pseudoinclusions.
The osteoclast-like giant cells have
bland nucl ei, which can fall into one of two
patterns:
Large multinucleated giant cell s with
many unifo rm nucl ei and inconspi cli ous
nucleoli.
Relatively small multi nucleated gia nt
cells with oval, irregul ar nuclei and promi-
nent nucl eoli simil ar to those seen in the
1nono nuclealeci cells.
Mitotic fi gures are rare but may be
present.
The majority of smears have chondroid
matrix; occasionally, chicke n-wire calcifi ca-
tions a re visible in cell clusters.
Chicken-wire calcifications are best seen
in cell block mate ri al or in smeared material
stained with H&E.
Chondroblastoma must be distinguished
from o ther giant cell- rich neoplasms and
from those containing a signifi cant amount
of chondroid matrix. The differe ntial diag-
nosis of chondroid matrix-containing lesions
is discussed in Chapter 11. The main diffe r-
e nti al di agnosis for giant cell-ri ch chondro-
blastomas includes conventi onal GCTB,
ane urysmal bone cyst, nonossifying fibroma,
and osteoclast-ri ch osteosarcoma. Fanning et
al. 35 regard the presence of typical-appearing
rounded, well-defined chondroblasts as the
single most useful feature in establishing the
di agnosis of chondroblastoma. Others con-
side r the presence of a chondroid matrix to
be a distinctive feature.
3o
In our experience, the distinction be-
tween GCTB and chondroblastoma is the
most challenging differential diagnosis.
Both are epiphyseal lesions and have a lytic
appearance on radiographs. Both yield mod-
erately to highl y cellular smears composed
of a mixture of mononucleated cells and os-
teoclast-like giant cells. Distinctio n betwee n
these tumors is achieved by examination of
the mononucl eated cell component. In
cho ndroblastoma this component is charac-
te ri zed by round to polygonal cells with
round or reniform nucl ei. The nuclei often
contain a nucl ear fold or groove and occa-
sionally contain a n intranucl ear cytoplasmi c
pse udoinclusion. Conventi onal GeTB is
characteri zed by cells with a mo re spindled
shape, a nd the nucl ei do not contain grooves
or pseudoinclusio ns. The presence of chon-
droid matrix in significant amounts also
helps exclude GGTB. In occasio nal exam-
pl es, the aggregated cell s in chondroblas-
toma are associated with chicken-wire calci-
fication,34 a feature not seen in conventional
GCTB.
Nonossifying fibromas can be separated
GIANT CELL-CONTAINING LESJ ONS 221
from chondroblasto mas o n the basis of nu-
clear features. The nuclei of nonossifying fi-
bromas have a spindl e shape a nd lack the
round contour or reniform appearance of
the cell s typitying chondroblaslOma. They
also lack the nuclear grooving and cytoplas-
mic pseudoinclusions seen in some exam-
pl es of cho ndroblastoma. Again, the cho n-
droid matri x seen in a signifi cant numbe r of
cho ndroblastomas is absent in non ossifying
fibroma. Nonossifying fibromas freque ntly
contain a population of foam cells, a cell
type not characte ri stic of cho ndroblastoma.
Osteoclast-ri ch osteosarcomas contain
mo no nuclear cells with greater degrees of
nucl ear atypia and pl eomorphism than are
found in chondroblastomas. Also, the nuclei
found within the sarcoma cells lack the nu-
clear grooves and cytoplasmic pseudoinclu-
sions cha racte risti c of many chond roblas-
tomas.
NONOSSIFYING FIBROMA AND
FIBROUS CORTICAL DEFECT
Nonossifying fibroma and fibrous cortical
defect are two similar, if not histologically
identical lesions separated by size a nd evo-
luti onary seque nce. Both are fibrohi stiocytic
processes occurring in the growing portions
of long tubular bones of skeletally immature
individuals.
36
,3? These lesio ns frequently
show involution with skeletal maturity a nd
he nce probably represent developmental
defects related to incomplete ossifi cation.
Up to 30% of children and adol escents have
radiographi c evidence of fibrous cortical de-
fect in a long tubular bone.
38
,39
These lesions occur in the skeletally im-
mature a nd he nce a re restricted to the first
and second decades oflife. The distal
proximal tibia, and distal tibia are the most
freque nt sites of occurrence. The maj ority of
lesions are e ntirely asymptomati c, with only
occasional larger lesio ns resulting in path o-
logic fracture. Multifocal exampl es have
been re ported in whi ch several symrnetric
metaphyseal sites within the bones of
the lower extremity are involved. 0
RADIOGRAPHI C F INDI NGS
Nonossifying fibromas are characterized by
eccentric cortically based lytic lesio ns with
distinct sclerotic margins.
36
,:m The scl e rotic
margin often has a scall oped appea rance.
The overlying cortex is usually mildly ex-
panded and intact but dramaticall y thinned .
No matrix calcifi cation is found within the
area of osteOlysis. The di stance between the
lesion and the growth plate increases with
age, a nd when followed, the lesio n appears
to migrate toward the centra l dia physis of
the lo ng bo ne.
Nonossifying fibromas are characteri zed by
a highly cell ul ar fibroblasti c proliferati o n
having a storiform or constell atio n-like swirl
patte rn (Fig. 13-13) . Within the spindl e cell
proliferation are scattered multinucleated
giant cells that ofte n appear indi stinct, merg-
ing with the surrounding mononucl ear cell
population. Foci of xanthomatous change
and hemoside rin-laden macrophages are
gene rally present. Areas of cystic change and
hemorrhage similar to those seen in a neurys-
mal bone cysts are not uncommon. The
giant cells te nd to congregate around a reas
of hemorrhage. Areas of necrosis and fibro-
sis characte ri ze these lesions, and occasional
mitoti c figures are an expected compone nt.
Atypical mi totic figures, on the other ha nd,
are absent. Reactive new bone deposition
surrounds a nd compresses the majori ty of
no n ossifying fibromas and fibrous cortical
defects.
Figure 13- 13. Histologi c sections of nonossifying
fibroma are characte rized by a hi ghly cellul ar fi-
broblastic prolirerati on growing in a storiform or
constellation-like swi rl pattern (H&E, X25). In
no nossifyi ng fibromas, the multinucleated gi ant
cells often blend with the surrounding mononu-
clear component.
..

Figure 13- 14. CyLOlogic preparations obtained
from nonossifying fibromas are of mode rate cel-
lularity and contain a mi xture of both mul tin u-
cl eated osteoclast-type giant cells and bland spin-
dle cells. Thus, they are difficull to separate [rom
convcntial GGIB on purely cytologic analys is.
The mononuclear cell compone nt is spind ly in
shape and has bl and nuclear featu res (Diff-Quik,
X50).
CYTOLOGIG FI NDINGS
Cytologic preparations obtained from 11 0 11-
ossify ing fibromas demonstrate an admix-
ture of ovoid and fusiform mononucl ear
stromal cell s and occasional osteocl ast-like
giant cell s (Fig. 13- 14) : 11 These mononu-
cl eated cells have elongated nuclei (Fig.
13-15). Most smears contain a second pop-
ulation of polygonal or rounded phagocytic
Figure 13-15. The mononuclear compone m in
nonossirying fib roma has nucl ei with a morc spin-
dled appeara nce than the nuclei present within
the giant cells (I-I&E, x200). This difference in
nucl ear con figuration between the a vo cell types,
while sli gh t, is helprul in separating nonossifYing
fibromas from GCTBs. Rad iograph ic correlation
is helpful.
cel)s of apparent hi Sliocytic li neage. These
cells have round or oval nucl ei. Osteoclasts
are present in most cases and may be abun-
dant. Variable numbers of li pid-laden foa m
cells are present. The proporti on of mul ti-
nucleated giant cell s and phagocytic Ii pid-
laden or pigment-lade n hi sti ocytes depends
on their di stri buti on within the lesion. Oc-
casionall y, osteoblasts with typi cal pl asmacy-
toid morphology are present but are not a
signifi cant component in most srnears .
KEy FEATURES
Smears are moderately cell ul ar, con-
taining spindl e-shaped cells, round or polyg-
onal phagocytic cell s, and multinucl eated
osteocl asti c giant cell s.
Spi ndle-shaped stromal cells have elon-
gated fusiform nucl ei.
I-li stiocytes/ phagocyti c cell s have round
or oval nucl ei.
Osteocl ast-like gia nt cell s contain rnul-
tipl e bland-appearing ovoid nuclei.
Lipid-laden macrophages and hemo-
siderin-laden macrophages are frequently
present.
Nucl ear anaplasia is absent.
P ROBLEMS I N D IAGNOSIS
Nonossifying fi broma must be di stingui shed
from other giant cell -containing lesions,
most notably CCfB, chondroblastoma, and
giant cell- rich osteosarcoma. In many cases,
nonossifying fibroma cl osely resembles con-
ventional GcrB by cytologic examination.
In these cases, cl inical and radiogra phic dif-
ferences all ow separation.
Nonossifying fibroma is separated cyto-
logically from chondroblastoma by di ffer-
ences in the nucl ear morphology of the
mononucleated stromal cell component.
In chondroblastoma these mononucJeated
cell s have round nucl ei, occasionally con-
taining intranuclear cytoplasmic pseudoin-
elusions. Cases of chondroblastoma may also
contain cells with reniform nuclei and
prominent nuelear grooves. These nucl ear
features do not characteri ze the cells of
nonossifying fi broma. The nuclei of the
mononucleated cell s seen in non ossifying fi -
broma are spindle-shaped, and lack intra-
nuclear cytoplasmic pseudoinelusions and
nuclear folds.
CIANT CELL-CONTAINING LESIONS 223
Nuclear atypia and mitotic activity are sig-
ni fica ntly greater in osteoclast-rich osteosar-
coma than in non ossifying fi broma. The
higher degree of nuclear atypi a in the sar-
coma all ows easy separation of these lesions.
In addi ti on. radiograph ic and cl ini cal find-
ings are signifi cantly d iffe rent.
Aneurysrnal bone cysts and nonossi fying
fibroma may have considerable overl ap cy-
tologically. and ane urysmal bone cyst may
compl icate sorne nonossifying fi bromas. In
most cases, nonossifying fibromas are con-
siderably more cellul ar than aneurysmal
bone cysts, all owing distinction between
them. In addi tion. radiographic features al-
low separation of uncompli cated nonossify-
ing fibroma/ metaphyseal corti cal defect
from aneurysmal bone cyst.
PIGMENTED
VILLONODULAR SYNOVITIS
Pi gmented vill onodul ar synoviti s and giant
cell tumor of tendon sheath are two related
entities occurring in or near the j oints.
pi gmented vi ll onodul ar synovitis may
Invade bone, it is primaril y a lesion of the
peri- and in tra-ar ticular soft tissues and is dis-
cussed in Chapter 4.
OSTEOCLAST-RICH
OSTEOSARCOMA
A subset of osteosarcoma contains a promi-
nent number of osteoclast-li ke giant cells.
These giant cell s have a ben ign appearance
overl apping that seen in the benign neo-
plasms and reactive condi tions described in
this chapter. Separation of these osteoclast-
rich osteosarcomas from oth er giant cell-
ri ch lesions is based on exami nation of the
mononucl eated cell component. In osteo-
clast-ri ch osteosarcoma the mononucleated
cells displ ay nucl ear atypi a to a degree not
seen in the other lesions. Osteoclast-rich os-
teosarcomas are discussed in greater depth
in Chapter 12.
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1950; 11 :3--13.
2. Lichtenstein L. Aneurysmal bone cyst: observations
on fifty cases. j /3one joint Swg 1957; 39A:873-882.
3. Dabska M, Buraczcwski J Aneurysmal bone cyst
pathology, clinical course and radiographic ap-
pearances. Cancer 1969; 23:371-389.
4. Martinez V, Sissons HA. Aneurysmal bone cyst: a re-
view of 123 cases including primary lesi ons and
those secondary to other bone pathOlOgy. uti/err
1988; 6 L2291-2304.
5. Till man BP, Dahlin DC, Li pscomb PR, Stewart J R.
Aneurysmal bone cyst: an analysis of ninety-five
cases. MaJo Clin J>lVr 1968; 43:478-495.
6. Sanerkin NC, .I effree GM. G)1tology oj Bone TUlllollrs .
A ColOllr Alias willE Texi. Philadelphia: J B. lippi n-
cott Co., 19S0, p. 146.
7. Karabcla-Boliropoliiou V, Liapi-Avgcri C, Paxinos
0 , Antoniou D. Solid variant of aneurysmal bone
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distal fe moral metaphyses. Virchows Arch 1994; 25:
531-535.
8. Sanerkin NG, MOll MG, Roylance J. An unus ual in-
traosseous lesion wi th fi broblastic, osteoclastic, os-
teoblastic, aneurysmal and fibromyxoid el ements:
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51 :2227-2286.
9. Bertoni F, Bacchini P, Capanna R, Ruggieri P, Bi-
agin i R, A, Bcttell i G, Picci P, Campanacci
M. Solid va ri ant of aneurysmal bone cyst. Cancer
1993; 7L729-734.
10. Meema HE, Meema S, Oreopoulous DC. Periosteal
resoq>lion of fi nger phalanges: radial versus ulnar
surfaces . .1 um Assac Radiol 1978; 29:
1[. J affe HL. Hyperparathyroidism (Rcckli ngh<l usen's
disease of bone). Arch Palhol l933; 16:63--1 12.
12. K..'ls hkari S, Kelly TR, Belhem D, Pepe RG. Osteitis
fi brosa cystica (brown tumor) ohhe spine with cord
comp"cssion: report of a case wi th needle aspira-
tion biopsy Diagl/. GylolJalllOll990; 6:349-
353.
13. Gupta RK, Voss OM, McHutchison ACR, Halfield
PJ. Osteitis fibrosa cyst.ica (brown tumor) in a pa-
tient with renal t ransplantation. Report of" a case
with aspi ration cytodiagnOSiS. Aela Gyiol 1992; 36:
555-558.
14. jaffe HL. Ciant cell reparative granuloma, t rau-
matic bone cyst and fibrous (fi bro-osseous) dyspla-
sia of the jaw bones. Oml Su.rg 1953; 6: 159- 175.
15. Chuong R, Kaba n LB, Kozakcwich H, Perez-Atayde
A. CcnU<l.1 giant cell lesions of the jaws: a cli nico-
pathologic study. j Oml MaxilloJac Swg 1986; 44:
708-713.
16. Caskey PM, ,.volf MD, Fechner RE. Multicentric
giant cell repal<l.tive granuloma of the small bones
of t he hand: case report and review of t he lite ra-
LUre. Clin Or/hojJ 1985; 193: 199-205.
17. Frassica Fj , Sanjay BK, Unni KK, McLeod RA, Silll
FH. Bcnign giant celllUmor. OrlholJetiics 1993; 16:
1179- 11 83.
18. Dahlin DC. Caldwell Lecture. Cialll cell tuomr of
bone: highlights of 407 cases. AjR 1985; L 44:955--960.
19. Sch.yowicz F, C'<l.Il<HO DB, McDonald OJ, Sun-
daram M. Cl inical and radiological features ofatyp-
ical giant cell tumors of bone. Hr.l Ratliol 1991 ;
64,877-889.
20. Mirra .J M, Uli ch T, Magidson .1 . Ka iser L, Eckanlt J ,
Cold R. A case of probable benign pulmonary
melaslases or implants arisi ng fmlll a giant cell tu-
mor of bone. Clin Ort/wl) 1982; l 62:245-254.
21. Vanel 0 , Contesso C, Rebibo C, Zafrani B, M"lssolot
J. Ben ign gianl ceillumors of bone with pulmo nary
metastases and favorable prognosis. Slleil'tal HadiQl
1983; 10;22 1-226.
22. Sung I-JW, Kuo DJ', Sh u WP, Chai VB, Li n ce, Li
SM. Giant cell tUlllor of bones: analysis of two hun-
dred and eighty cases in Chinese patienlS. } Bone
joint Surg (Am) 1982; 64:755-761.
23. Mirra.l M. Bone TII-mors. Clinical, Radiologic an.d Patho-
logic Corte/alions. Philadelphia: Lea and Fcbiger,
j 989, PI' 942-992.
24. ShulTstall RM, Gregory JE. QSlcoid fonnalion in
giant cell wmor of bone. Am} Pa(hol 1953; 29:
11 23- 113 1.
25. Sncigc N, Ayala AC, Carrasco CI-I , Murray J, Ray-
mond AK. Giant cell lUlllor of bone: a cyLO\ogic
study of 24 cases. Dialf'l C)'to/Jalhol 1985; 2: 1 I I-I 17.
26. Vertani A, FlI1c ini ti r ~ Boschi R, Mari no G, Zeppa
P, Troncone G, Palombini L. Fine needle aspiration
biopsy diagnosis of giant-cell t umor of bonc. An ex-
perie nce with nine cases. Acta C)'lolI990; 34:863-
867.
27. Sanerki n NG, Jeffree GM. C),folofJ), of BOlle 1hmoun.
A Cowur Atlas with 'lext. Philadel phia: J. B. Lippin-
cott Co., 1980, pp 9 1- 100.
28. Szyfelbei n WM, Schiller AL Cytologic diagnosis of
giant cell tumor of bone metasta ti c to lung. A case
repo rt. Acta C),lol I 979; 23:460-464.
29. Ri os-Marti n 11, Otal-Salavcrri C, Vazquez-Ramirez
I:), Gonzalez-Campora R, Davidson HG. Fine '
needle aspiration diagnosis of nggress ive giant cell
tumor of bone. A case repo rt. Acta C)'lol 1995; 39:
550-554.
30. Po har-Mali nse k Z. Us-Kr<lsovec M, La movec J.
Chondroblasloma in fin e needle aspi ra tes. Acta C),-
lof 1992; 36:367-370.
31. Kil patrick SE, Pi ke EJ , Geisi nger KR, Ward WC.
ChondroblaslOma of bone: use of fi ne-needle aspi-
ratio n biopsy and pote ntial diagnostic pitfalls. Di-
_ agn C)'fo/mllwl I997; 16:65-71.
32. Ascoli Y, Facciolo F. Muda AO, Manelli M, Nardi F.
Chondroblastoma of the rib presenting as an in-
trathoracic mass. Report of a case with fine needle
aspi ratio n biopsy, immunocytochemisu), and elec-
tron microscopy. Acta C),tol I992; 36:423-429.
33. Hazaika D, Kumar RV, Rao CR, Mukherjee C. Pat-
tabhiramman V, Shekar Me. Fine needl e aspiration
cytology of cho ndroblastoma and chondromyxoid
fibroma. A repon of two cases. Acta C)'Lol 1994;
38;592-596.
34. Bommer KK, Ramzy I, Mody D. Fine-needle aspi-
ration biopsy in the diagnosis and management of
bone lesions. Cancer C)11()pathol I997; 81: 148-156.
35. Fanning CV, Sneige NS, Carrasco CH, Ayala AG,
Murray J A, Raymond AK. Fine needle aspiration cy-
tology of cho ndroblastoma of bonc. Ca.ncer 1990;
65;184 7- 1863.
36. Jaffe I-IL, Lichtenstein L. Non-osteogenic fibroma
of bonc. Am) PalhoL 1942; 28:205-221.
37. Selby S. Metaphyseal cortical defeccs in the tabular
bones of growing children. J Bone )oint SUlg 1961;
43;395-400.
38. Ponseti IV, Friedman B. Evolution of metaphyseal
fib rous defects.) BOlleJoi1l1 Swg 1949; 31:582.
39. ColTey J. On fi brous defects in cortical wall s ofgro\\!-
ing tubulal- bones: theil' radiologic appearance,
structure, prevalence, natura l course and di agnos-
tic significance. AdTJ Pedialr 1955; 7: 13-5 1.
40. Moser RP J r, Sweet DE, Haseman DB, Madewell
JE. Multiple skeleJ...'l1 fi broxanthoma:;: radiologic-
pathologic corrcl<ltion of 72 cases. SlIelefal Ra(liol
1987; 16;353-359.
4 1. Sanerkin NG, J effrec eM. C)'lology ojBone Tumours.
A Colour Atlas with Tex/. Philadelphia: J. B. Lippin-
cott Co., 1980, pp. 85-90.
SMALL CELL NEOPLASMS OF BONE
EWING'S SARCOMA
First described by J ames Ewing in the early
1 920s, 1 Ewing's sarcoma is the prototypical
non hematopoietic small round cell malig-
nancy of bone_ Ewing's sarcoma is a member
of a group of lesions characteri zed by speci fi c
cytogenetic and molecul ar abnormali ties.
Other members of thi s group include pe-
ripheral neuroectodermal tumor, Askin's nl-
mor, mesenchymal chondrosarcoma, and
some small cell osteosarcomas.
2
Until the elu-
cidation of the characteristic 11 ;22 translo-
cation tll ;22) (q24;qI 2)), the diagnosis of
Ewi ng's sarcoma was in many cases one of ex-
clusion. The reciprocal translocation be-
tween chromosomes 11 and 22 is found in
approximately 90% of Ewing's sarcomas,3-5
along with abnormal fusion products of the
EWS and FU-I genes.",7 These cytoge neti c
and molecular changes all ow specifi c char-
acterization of many small round cell tumors
as members of thi s family of neoplasms. Ew-
ing's sarcoma is the prototype for thi s tumor
group. with other members showing differ-
entiation to neural [primitive neuroecto-
determal tumor (PNET) 1,. chrondroblastic
(mesenchymal chondrosarcoma), osseous
(some small cell osteosarcomas) and neural
tumors with myogenic differentiation (ecto-
225
mesenchymoma). Other representatives of
this seri es include Askin's tumor and small
cell desmoplastic tumor of the peritoneum.
Classic Ewing's sarcoma is a small round
cell malignancy of bone occurring in skele-
tall y immature indi viduals, with a peak oc-
currence between 5 and 25 years of age_
B
There is a male predominance. The cl ini cal
presentation includes pai n, a mass, and at
times systemic ill ness incl uding fever.
RADIOGRAPHI C F INDINCS
Imaging studies of classic Ewing's sarcomas
de monstrate an ill-defi ned, permeative, de-
structi ve in tramedullary lesion. Most exam-
ples ar e centered within the diaphysis of
long tubular bones, most commonly the
humerus, femur, tibia, or fibula. The de-
structive diaphyseal lesion is freque ntly ac-
compani ed by a prominent "onion skin" pe-
riosteal reaction . In other cases, Ewi ng's
sarcoma produces a concave (saucerization)
defect in the bone surface. A large soft tis-
sue mass may accompany the bony lesion.
H ISTOLOGIC FiNDI NCS
Ewing's sarcoma is characterized by a sheet-
like proliferation of small , round. undiffer-
Figure 14-1. The predominant architcCLu re pat-
tern seen in Ewing's sarcoma is one of large sheets
of sma ll round cell s with li llIe inte rvening stroma
(I-I&E, X25).
entiated mese nchymal cell s (Fig. 14_1 )9-lJ
The individual cell s have scanty. indi sti nct cy-
topl asm and round, centrally located nucl ei
(Fig. 14-2). T he nucl ear chromatin has a
fin ely granular a ppearance, a nd one to three
small nucl eoli are usuall y present. A bipha-
sic cell patte rn is freque ntly present, com-
posed of dark a nd li ght cells. The ligh t cells
have a relatively o pe n chro matin pattern,
whil e the dark cell s displ ay a de nse chro-
matin .
The predominant architectural pattern is
one of large sheets of cell s with relatively lit-
tl e intervening stroma (Fig. ]4-1). Less com-
mo n patterns include the lobular or alveolaT
pattern a nd the filigree or checherboard pat-
Figure 14-2. The individual cells have scanty, in-
distinct cYLOplasm and round, centrally located
nucl ei. The nucl ea r chroma tin is finel y gran ular,
an d one to three small nucleoli are often present
(H&E, X 100).
tern. Varia ble amounts of necrosis and hem-
orr;:hage are prese nt and are characteristic of
Ewi ng's sarcoma even before treatmenl with
che molherapeutic protocols. RaJ'ely, Homer-
vVirght rosettes have been reported in Ew-
ing's sarcoma, not a surprising occurre nce
given the relati onshi p between Ewing's sar-
coma and PNET. With the developme nt of
antibodies to the MIC-2 gene product, im-
munoh isLOchemisty has assumed significant
importance in the d iagnosis of Ewing's sar-
corna.
12
,1 3 Unfortunately, a vari e ty. of lym-
phoblasti c T-cell lymphomas, some rhabdo-
myosarcomas, and Wilms' tumors also react
with this a ntibody.
Ne ural markers are variably presen t within
Ewing's sarcoma, with ne uron specific e no-
lase, Le u-7, a nd synaptophysin being positi ve
in a number of cases. 14- 16
CYTOLOGIG F I NDI NGS
Fine needle aspi ratio n (FNA) has been
shown to be a useful method for the diag-
nosis o f Ewing's sarcoma, achieving a diag-
nostic accuracy of over 80%.17 Smears o rEw-
ing's sa rcoma obtained by aspi raLi on are
highl y cellular, with the compo ne nt cell s
a rranged in variabl y sized clusters, as well as
lying indi viduall y within the background
(Fig. 14--3).18-25 The background may be
bloody or composed of cytoplasmic debris
forming a n irregular lace-like pattern. The
cells a ppear uniform in shape and size a nd
possess ro und nucl ei (Fig. 14-4). 19-23 Ex-
aminati on of most smears d iscloses two cell
Figure 14-3. Smears from Ewing's sarcoma a re
hi ghly cellular. The cells are arranged in variably
as well as lying singly (Diff-Quik,
X50).
SMALL CELL NEOPLASMS OF BONE 227
Figure 14-4. In cytologic preparations, the cells
of Ewing's sarcoma fo rm two cell populati ons,
each of which is relatively uniform in size a nd
shape. They possess round nuclei with very scanty
cyloplasm (I-I &E, x200).
types based on the nucl ear chromatin pat-
tern. As with histologic specimens, ligh t a nd
dark cell s are present; the nucl ear chro-
matin pattern appears as either conde nsed
,(dark) (Fig. 14--5) or fine and open (li ght)
(Fig. 14--6). The nucl ei are round, with o ne
to three small , indistinct nucl eoli . Scanty cy-
toplasm is presen t and forms a thin rim
around the nucle us (Fig. 14-7). The cell bor-
ders appear well defi ned, and occasional
cells have large, "punched-out" clear spaces
wi thin the cytoplasm.
19
These clear spaces
usually li e within the perinucl ea r regio n, but
in occasional cells with elongated cytoplas-
mic processes these spaces may be mo re pe-
Figure 14-5. Two cell types arc frequentl y d is-
cernible in cytologic preparations, the so-call ed
li gh t and dark cell s. These 1:\\'0' types are disLin-
guished by their ch romatin pattern. whi ch may
appear eiLher condensed (dark) or fine and open
(li ght) (Ditl'QlIik, X100).
Figure 14-6. The maj ol-ity of cells in thi s fi gure
are li ghl cell s (1-1 &10, x200) .
ripheral vvithin the cytoplasm. Ofte n fine
reticula r cytoplasmic 'visps are seen con-
necting the neoplastic cell s, giving the back-
ground a cha racte ri stic fibri llary appear-
a nce.
23
Nuclear molding is generally not a promi-
ne nt feature in smears. Rose tte-like struc-
tures have been reported with va riable fre-
que ncy.19,26 The prese nce of glycogen has
also been variable.
23
,26
Tn a sign ifi cant number of smears, a large
percentage of the neoplastic cell s have a de-
generate appearance. In these cell s the cy-
toplasm has been stripped away, leaving
bare, often deformed nucl ei. In othe r cases,
a signifi cant number of pyknotic degene rat-
ing cells are present, compli cating the mo r-
phologic picture. Logistic regression analy-
Figure 14-7. Cytologic preparation showing a
mixtUl-e of li gh( and dark cells. Both cell types
have relatively sca nty cytopl as m witholll apparent
cytoplasmic processes or features of d iffe rentia-
lion (Diff-QlIik, X200).
sis has shown cytoplasmic vacuoli zation and
scanty cytoplasm to be most helpful in dis-
tinguishing E\ving's sarcoma from other
small round cell malignancies.
27
Examples ofa large cell vari ant of Ewing's
sarcoma have been reported.
28
In these
cases, the neoplastic cells have a round to
oval nucleus that varies in size but generally
is t\vo to three times the size of a red blood
cel1.
28
The nuclear membrane is reported to
be prominent and the chromatin coarse.
One or two nucleoli are present. The cyto-
plasm in the reported cases has been ho-
mogeneous, with sharp borders'
s
Most sig-
nificantly, approximately one-third of the
cells have noticeably larger amounts of cy-
toplasm than the others.
DIAGNOSTIC CRJTERIA
Smears are cellular, composed of neo-
plasti c cells with a relatively uniform size and
a round shape.
There is a bimodal population of light
and dark cells in some smear s.
Light cells have a fine open chromatin,
whil e dark cells have a condensed chro-
matin.
The background may be extremely
bloody or may have a proteinaceous lace-like
pattern or a fibrillary appearance.
Glycogen and rosette-like suuctures are
variably present.
Cell nuclei are round, with one or two
small nucleoli.
Cytoplasm is scanty and appears most
frequently as a thin rim surrounding the nu-
cleus. In some examples, eccentric wisps of
cytoplasm are apparent.
Ewing's sarcoma must be separated from
other round cell malignancies. Distinction
from lymphoma and metastatic neuroblas-
toma is cl ini cally most important. Ewing's
sarcoma can generally be separated from
lymphomas by the presence of lymphoglan-
dular bodies in the background of lym-
phomas. These cytoplasmic fragments char-
acterize lymphoid proliferations but have
been reported occasionally in other small
round cell malignancies. When doubt exists,
performance of immunohistochemisty on
cell block or cytospin preparations can be
extremely helpful. Benign and malignant
lymphoid proliferations wi ll react wi th com-
mon leukocyte antigen (CD45) , whil e Ew-
ing's sarcoma will react with antibodies di-
rected against 0 13, the MIC-2 oncogene
protein product. Unfortunately, some lym-
phomas also react with this antiserum, and
performance of immunohistochemistry for
lymphoid markers is important for definitive
separation.
29
Several authors have demon-
strated the utility of MIC-2 immunocyto-
chemistry in the diagnosis of Ewing's sarco-
mas.
30
Sl
Reverse transcriptase polymerase
chain reaction has also been shown to be
useful in the diagnosis of Ewing's sarcoma
by FNA."
Distinction of Ewing's sarcoma from met-
astatic neuroblastoma can be extremely dif-
ficult. Whi le the presence of a large number
of rosettes or the presence of several neural
markers by hi stochemical analysis strongly
favors the diagnosis of neuroblastoma, Ew-
ing's sarcoma occasionally demonstrates pos-
itivity for neural markers as well as rare
rosettes. Correlation with clinical and blood
chemistry fmdings vanilmandeli c acid (VMA)
is extremely helpful in excl uding or estab-
lishing the diagnosis of metastatic neuro-
blastoma. Extraskeletal Ewing's sarcoma
with a cytomorphology identical to that of
the osseous neoplasm has been described
cytologically.33
NON-HODGKIN'S LYMPHOMA
Primary non-Hodgkin's lymphoma of bone
is a relatively rare disease, representing less
than 1 % of all non-Hodgkin's lymphomas.
To be considered within this category, a
non-Hodgkin's lymphoma must present pri-
marily within the bone and produce a tu-
mor mass.
34
,35 Most patien ts are over 40
years of age, and there is a slight male Ere-
dominance in the majority of series. 4-S6
Nearly half of all cases occur in either the
femur or pelvis; the humerus and vetebrae
are the next most frequent sites. Multi fo-
cality is a common finding, with 10%-40%
of patients having several foci of involve-
ment. Pain is the most common single symp-
tom, but pathologic fracture may be the pre-
senting complaint.
Figure 14-8. The majority of primary lymphomas
of bone are of the diffuse large cel l type. These
neoplasms are characLerized by a diffuse popula-
tion of rou nd neoplastic cell s whose nuclei con-
tain promi nent nucleoli (H&, XI OO).
RADIOGRAPHI C FINDINGS
The maj ority of non-Hodgkin's lymphomas
have a lytic appearance on plain films, of-
ten associated with a permeative, "moth-
eaten
n
pattern of growth. The cortex is of-
ten lysed, with extension of the process into
the surrounding soft tissues. Periosteal new
bone, often with a "onion ski n" appearance,
is a frequent finding. In long tubular bones,
the diaphysis is the favored site of involve-
ment, but the process may extend into
the metaphysis and epiphysis. Rarely, non-
Hodgkin's lymphomas may be associated
with bone sclerosis and have an osteoblastic-
appearance.
While the accepted classifications of non-
Hodgkin's lymphoma do not adequately pre-
dict the behavior of primary non-Hodgkin's
lymphomas of bone, these classification sys-
tems are utilized for consistency in classify-
ing primary lymphomas of bone. The ma-
jority of primary lymphomas occurring
within bone are diffuse large cell lymphomas
(Fig. 14-8) 3 7-39 In these cases, a diffuse pro-
liferation of round neoplastic cells extends
through the bone marrow spaces and Haver-
sian channels, destroying the surrounding
bone. ] n some areas, dense fibrosis and fi-
brous cords are associated with t he round
cell infiltrate. The fibrous tissue may com-
press the lymphoid elements to such a de-
gree that they take on a spindle shape. Nu-
clear crush artifact may be extensive.
As with lymphomas at otller sites, im-
munohistochemical staining for lymphoid
markers can be extremely helpful in diag-
nosis. Similarly, flow cytometry can elucidate
the lymphocyte lineage of these neoplasms.
CYTOLOGIC FINDINGS
Smears obtained from primary lymphomas
of bone have varied in cellularity from mod-
erate to hi ghly cellular.
4
0-42 This variation is
related in part to the degree of fibrosis and
sclerosis within th e lesion. 'I1 The cell popu-
lation has been variousl y described as poly-
morphous
41
or monomorphous.
4o
In either
case. a prominent population of monoto-
nous-appearing large lymphoid cells is pres-
ent (Fig. 14-9)40,41 The cells usually li e
si ngly but can form clumps and tissue frag-
ments. Tissue fragments are most commonly
associated with sclerotic lymphomas. In well-
smeared specimens. the tissue clumps are
seen to be composed of collagen fibers with
enmeshed atypical lymphoid cells. The atyp-
ical lymphoid clemen ts arc two to th ree
ti mes the size of a small mature lymphocyte
(Fig. 14-10)40 High-power examinati on re-
veals tll e majority of cell s to contai n spheri-
cal nuclei with a regular contour and
Figure 14-9. Cytologic preparations from primary
lymphomas or bone contain a monomOl'phous
population of large lymphoid cells showing nu-
clear enlargement, hyperchromasia, and atypia
(Diff-Quik, XI OO). The background is often dirty
and contains the characteristic Iymphoglandular
bodies.
Figure 14- 10. In cytologic preparations, the atyp-
ical lymphoid elements are two LO three times the
size of a small , maLUre lymphocyte. The back-
ground has a proteinaceous appearance with scat-
Lered Iymphoglaodular bodies (Diff-Quik, X200).
coarsely granul ar chromatin. Areas of inter-
chromatin clearing are present, and occa-
sional nucl eoli or chromocenters are found.
In other cases, the nucl ei di splay irregul ar'
contours with folds in the nucl ear mem-
branes, givi ng the appearance of cleaved nu-
c1e i.
4o
,4 ! Crush artifact may be extensive.
41
The background can contain moderate
amounts of bl ood with a large number of
Iymphoglandular bodies. In other cases, the
baCkground contains abundant necrotic de-
bris. When necrosis is extensive, numerous
atypical naked nuclei are present.
Because many of these malignant lym-
phomas are of B-cell li neage, immunoper-
oxidase is helpful and will demonstrate stain-
ing of the neoplasti c cells with leukocyte
common anti gen (CD45) and pan B-cell
markers (CD20). Immunoperoxidase stain-
ing is most accurate when performed on cy-
tospin materi al or cell block preparations.
Simil ar data can be obtained by flow
cytometry.
DIAGNOSTIC CRITERIA
There is a relatively monomorphous
populati on of large, atypical round cells.
Individual cells have a modest to scanty
amount of cytoplasm surrounding the nu-
cl eus as a thin rim. Occasional plasmacytoid
forms are seen.
Nucl ear patterns are variable:
The nuclei may be round. with a
smooth nucl ear contour.
Alternatively, the nuclei may have an
irregular nuclear membrane, giving the
appearance of nuclear clefting.
Nuclei have one to several chromocen-
ters or nucleoli .
The majority of cells lie singly, but in
scl eroti c forms of lymphoma, tissue frag-
ments with collagen fibers and enmeshed
lymphoid cell s are found.
The background contains numerous
lymphoglandular bodies.
Some smears show extensive ncrosis.
Occasional smears have a polymorphous
appearance with a background populati on of
small to medium-sized lymphocytes and a
monotonous population of larger, atypical
lymphoid cells.
Immunoperoxi dase studi es demon-
strate positi vity for common leukocyte anti-
gen (CD45) and, in B-celllymphomas, mon-
oclonality for kappa or lambda light chains,
as well as CD20 positivity.
Primary lymphomas of bone must be distin-
guished from Ewing's sarcoma, metastati c
neuroblastoma, and PNET. In general, lym-
phomas can be separated from the other
neoplasms in this differential diagnosis by
the demonstration of positive staining for
common leukocyte antigen (CD45) . Mor-
phologically, the presence of numerous
lymphoglandular bodies in the background
supports the diagnosis of lymphoma. Occa-
sionally, lymphoglandular bodies can be
found in Ewing's sarcoma and neuroblas-
toma, but not in the numbers characteri stic
of lymphoma. In the maj ori ty of cases, the
cell population found in lymphoma is more
monotonous than the bimorphic popul ation
characteri stic of Ewing's sarcoma. Immuno-
peroxidase staining for 0 13 can be helpful ,
but a number of lymphomas are known to
react with antibodies directed against 013.
29
Myeloma can generally be separated from
classic non-Hodgkin' s lymphomas by the
plasmacytoid appearance seen in the major-
ity of myelomas, as well as by the character-
isti c anti gen profi les demonstrabl e by im-
munohi stochemistry.
In an adult. metastatic oat cell carci noma
to bone must be considered in the differen-
tial diagnosis of small round cell mali gnan-
cies. Unlike lymphoma, small cell undiffer-
entiated carcinoma demonstrates positive
staining with antibodies directed against cy-
tokeratin and frequently with an tibodies
directed against neuron-speci fi c enol ase.
Small cell undifferentiated carcinomas do
not react with antibodies directed against
common leukocyte antigen.
MYELOMA
Myeloma is a plasma cell dyscrasia that may
take one of several forms. including multi-
ple myeloma, soli tary myeloma, and ex-
tramedullary myeloma (plasmacytoma). Ex-
tramedullary myeloma ge nerally affects the
upper respiratory tract and is outside the
scope of this monograph. The majori ty of
patients suffering from myeloma exhibit
multifocal involvement by a monoclonal
neoplastic proliferation of plasma cells. This
generally involves the bone marrow but can
also occur at extraskeletal sites. Because of
r their characteri sti c multifocality, these le-
sions are not confused with other primary
neoplasms of bone and hence wi ll not be dis-
cussed in tllis chapter.
Solitary myeloma is a rare locali zed pro-
li feration of neopl asti c plasma cells. This
clonal proli feration produces a soli tary de-
structive bone lesion generall y discovered
during radiologic skeletal survey but is some-
times associated with pathologic fracture. In
addition to differences in focali ty, solitary
myeloma is distinguished from multipl e
myeloma by the absence of a demonsu-able
M component in the serum. SOli tary myeloma
most often occurs lvithin the vertebral bod-
ies (50% of cases), but examples have also
been reported in the pelvis, femur, and
humerus.
43
,44 Nearly three-quarters of soli-
tary myelomas prop-ress to multifocal di s-
seminated disease.
4
:>
RADIOGRAPHIC FINDI NGS
The majority of soli tary myelomas of bone
occur within the vertebral bodies, where
they produce a sharply demarcated lyti c
lesion often described as "punched-out. "
These lesions may erode the overlying cor-
tex and in small er tubular bones may expand
the cortical contour. Pathologic fracture or
collapse of a vertebral body is a frequent pre-
senting symptom.
HISTOLOGIC FINDI NGS
Soli tary myeloma consists of a single focal
proliferation of small round to ovoid cells re-
sembling normal or atypical plasma cells.
The cells often have a sheet-like growth pat-
tern (Fig. 14-11). These cell s have eccentri c
nucl ei with a prominent nucleolus. The
chromatin pattern frequently exhibi ts a
characteristic "spoke wheel" confi guration.
The associated cytoplasm is dense and
slightly blue-red. The degree of atypia ex-
hibited by the plasma cell s is variable, and at
times anaplastic ovoid cells are present that
still exhibi t features charac teristic of a
plasma cell . Binucl eated forms are not in-
frequent. and mi totic activity is often brisk.
Anaplastic giant plasma cells with bi zarre nu-
clear features are present in some cases. The
atypia and immaturityofthe plasma celljOp-
ulation are of prognosti c signifi cance.
4
Pl asma cell proli fe rations generally ex-
press the plasma cell-associated antigen
(PCA or CD38), whi ch may aid in their dis-
tincti on from other hematopoietic lesions.
In exampl es of highly anaplastic myeloma,
expression of the plasma cell-associated
anti ge n all ows distinction from other ana-
plasti c mali gnancies.
CYTOLOGIC FINDINGS
Smears obtained from the lytic lesions of
both soli tary and multi ple myeloma are sim-
ilar. The smears are generally highly cell ul ar
Figure 14-11. Hi stologic specimens from exam-
ples of myeloma or solitary plasmacytoma are
characlerized by a sheet-like growth of plasmacy-
toid cells. These cell s may closely resembl e n OI"-
mal plasma cell s or show significant degrees of
atypia (H&E, X 100).
Figure 14-12. Smears obt.."1ined from exampl es of
soli tary or multipl e myeloma are generall y highly
cellular a nd composed of round to ovoid cell s
with eccentric nuclei, giving them a d istinctive
pl asmacytoid appearance (Diff-Qui k, X80) .
a nd a re composed of ro und to ovoid cell s
with eccentric nuclei (Fig. 14-12). The nu-
cl ei vary in degree of atypi a but are usually
round in shape, with a spoke wheel chro-
matin pattern (Fig. 14-13) and a promine nt
nucl eolus. The nucl ei are usually eccentri-
cally located. The cytoplasm is mode rate to
abundant in amount and contains a pale
Goigi zone in a pe rinucl ear locati on. Methyl
green- pyronine demonstrates prominent
pyroninophili a but is usually unnecessary for
the diagnosis. Binucl eated and even trinu-
cl eated neopl astic cells are not infreque nt.
Occasional multinucleated anaplasti c giant
Figure 14--13. High-power view of these malig-
na nt plasma cells demonstrates varying degrees
of atypia , but t he nuclei are usually round and
frequently di splay the classic spoke-wheel chro-
matin pattern (Di ff-Qui k, X200) .
cell fo rms are seen in anaplastic soli tary
myelomas. The degree of cellul ar atypia can
be extensive, but in most cases a component
of easily recogni zed plasmacytoid cell s is
present. In more anaplasti c exampl es, the
clumped chromatin cartwheel pattern is of-
ten abse nt, making recogniti on of the cell
type more difficult. In such cases, applica-
tion of methyl-green-pyronine o r CD68 is
helpful.
47
DIAGNOSTIC C RITERIA
Smears a re highly cell ular, composed of
single noncohesive round to ovoid cells.
Individual cell s have an ovoid (pl asma-
cytoid) shape with eccentri c nucl ei.
The cytoplasm frequently contains a
prominent cl eared Golgi zone in a paranu-
cl ear location.
In well-diffe rentiated forms the nuclei
have the classic cartwheel chromati n pattern.
Nucl eoli are freque ntly promine nt.
Mi totic activity is generally bri sk.
Binucleated and trinucl eated pl asma
cell forms are not infreque nt.
In anaplastic forms of solitary myeloma,
nucl ear atpyia can be signifi cant a nd cyto-
pl asm is more variabl e in amount.
In anaplastic myelo mas the characteris-
tic cartwheel chromatin patte rn is ofte n
absent.
Immunohistochemical staining fo r CD68
or staining with methyl green- pyronine is
often helpful in diagnosis.
P ROBLEMS IN D IAGNOSIS
The maj ority of soli tary plasmacytomas of
bone are easily diagnosed by recogniti on of
the plasmacytoid features of the individual
cells. In anaplastic plasmacytoma (solitary
myeloma), distinction from otl1er small round
cell malignancies, especially lymphomas and
poorly differentiated carci nomas, can be dif-
fi cult. Immunohistochemical staining for
CD68 is helpful in these cases. In most poorly
differentiated or anapl astic solitary myelomas
of bone, some better-diffe renti ated pl asma
cell forms will be present, aiding in the di ag-
nosis. A careful search for these more typical
forms wi.ll usually allow distinction from other
round cell malignancies.
EOSINOPHILIC GRANULOMA
(LANGERHANS' HISTIOCYTOSIS)
Langerhans' cell histiocytosis (granul omato-
sis) can presen t in a multifocal or soli tary
form. Cases with solitary bone involvemen t
are the most frequen t variety and are usually
referred to as eosinophilic granuloma. Such
cases involve young ad ults, and while any
bone may be involved, the crani al vault,jaw,
humerus, ribs, and femur are the most
commo n sites of occurrence.
48
These lesions
are characterized roentgenographi cally by
lytic lesions most frequently situated within
the metaphysis of a long bone.
Histologically, these lesions are character-
ized by an admixture of eosinophils, multi-
nucleated giant cells, neutrophils, xanthoma-
tous histiocytes, and areas of fibrosis (Fig.
14-14) . While eosinophils are a promi nent
component of the prolife ration, the charac-
teristic cell is the so-called Langerhans' cell ,
which has a specific morphology (Fig. 14-15)
and immunohi stochemi cal profile.
49
These
cells have lobulated nuclei, often with a lon-
gitudinal groove. The cytoplasm is eosino-
philic and on ultrami croscopic analysis con-
tains characteristic Birbeck's granul es.
CYTOLOGIC FINDINGS
The cytologic findings from smear and cell
block preparations of Langerhans' cell his-
Figure 14--14. Histologic sections from exampl es
of eosinophilic granuloma reveal a polymorphous
population composed of an admixture of eosino-
phils, multinucleated giant cells, neutrophils, xan-
thomatous histiocytes, and Langerhans'-type cells
(H&E, X50).
Figure 14--15. The characteristic Langerhans' cell
has a lobulated nucl eus with a promi nent longi-
tudinal groove. The cytoplasm is eosinophilic
(H&E, XIOO) .
tiocytosis (eosinophilic granuloma) have
been well described.
5
0--
55
In the maj ori ty of
cases, the smears are dominated by a popu-
lation of round to ovoid histiocytes contain-
ing large, pale nuclei and eosinophils (Fig.
14-16) . The nucl ei are frequently kidney-
shaped and display a distinct irregul ar or
folded nuclear outline (Fig. 14-16) . The
chromatin patte rn is bland, and nucl eoli are
generally small and frequently multipl e. Nu-
cl ear membrane features are best seen wi th
Papanicolaou staining. The cytoplasm is
present in abundant amounts and is pale,
with well-defined borders. The cytoplasm is
Figure 14--16. Smear preparations from examples
of Langerhans' cell histiocytosis have a variable
appearance, but in most cases the smears are
dominated by a population of round to ovoid his-
tiocytes containing large, pale nuclei. A second
of eosinophils is frequently promi-
( nt (H&,,"\X200).
frequently vacuolaLcd or foamy and may con-
ta in phagocytized debris. Occasional mul ti-
nucleated giant cell s of simil ar morphology
are seen in most smears. A modest number
of eosinophils are commonl y present but in
some smears may be quite sparse.
Whil e th e cytologic pi cture is quite char-
acte ri stic, occasionally ancillary tests will be
necessary to confirm the diagnosis. Immuno-
histochemi stry is helpful since the histi ocytes
stain for the markers 8-100 protein and
CDl A. Electron mi croscopy can also be per-
formed to demonstrate the characteri sti c
Birbeck's granul es.
D IAGNOSTIC FEATURES
Smears are cellul ar, containing a mi x-
ture of eosinophil s and large histiocytes.
Hi stiocytes have characteristi c large nu-
cl ei with irregul ar or folded nucl ear mem-
bra nes.
Histi ocyte nuclei are pale and kidney-.
shaped.
Hi sti ocytes contain abundant pale, fj-e-
quently foamy or vacuolated cytoplasm, of-
ten with phagocyti zed debris.
Multinucl eated giant cells are frequentl y
prese nt.
Eosinophil s are present in vari able
number, at times abundant and in others
scan ty.
The immunohi stochemi cal findings on
- .1 00 protei n and COl A staining are char-
acteri stic.
Ultramicroscopi c examinati on reveals
Birbeck's granul es.
PROBLEMS IN D IAGNOSIS
Aspi rates from eOSinophilic gra nuloma can
be confused with chroni c osteomyelitis and,
in some cases, with metastatic melanoma or
carcinoma. Se paration from osteomyelitis is
achi eved by recogni zing that the mi xture of
inflarnmatory cells is predominantly eosino-
phil s and histiocytes. The histi ocytes also
have characteri stic features of prominent
nuclear folds and nucl ear membrane irreg-
ul ari ties. The nuclei lvithin the histi ocytes of
La ngerhans' hi stiocytosis tend to be larger
and paler than the nucl ei commonly found
in infl ammatory processes. Exampl es of os-
teomyeliti s usuall y con lain a wider ran ge of
innammatory cell types, incl uding lympho-
cytes, plasma cells, and neutrophil s.
The large, ovoid Langerhans' cell s may be
confused with some examples of melanoma.
In both cases the cell s are large and oval or
polygonal, with abundant cytopl asm. Dis-
lincti on is usuall y achi eved by recognizing
lhe greater degree of nuclear atypi a in mel-
anomas. Many metastatic melanomas are
amelanoti c, but a careful search for melanin
pigment is warranted to establi sh the pres-
ence of melanoma. Milotic fi gures are much
more common in exampl es of melanoma
and help separate these two lesions. In spec-
imens stained by hematoxylin and eosin
(H&E) or Papani colaou techniques, the nu-
clear fo lds characteri sti c of Langerhans' cell
hi sti ocytosis aid in its distinction from mela-
noma. BOlh melanoma and the cells of
Langerhans' cell histi ocytosis are positi ve for
S-100 protein , but CDIA is posilive only in
Langerhans' cell histi ocytosis.
Some poorl y differenti ated carcinomas
may have a single cell morphology with large
polygonal cell s containing abundant cyto-
plasm. Di stinction from Langerhans' cell
hi stiocytosis is generally ach ieved by finding
eosinophil s in the latter, as well as immuno-
histochemi cal staining for S-100 protein and
CD1A, both of whi ch are positive in Langer-
hans' cell s. Cytokeratin is usually positive in
the carcinomas.
SMALL CELL OSTEOSARCOMA
A small nurnber of osteosarcomas have a pre-
dominantl y small cell morphology and yet
produce small amounts of neoplastic os-
leoid. Separation of these lesions from Ew-
ing's sarcoma and metastatic neurobl astoma
may be di ffic ult. Some lesions traditionall y
di agnosed as small cell osteosarcoma are in
fact Ewing's sarcoma, as demonstra ted by the
presence of the MIC-2 oncoge ne protein
product. Further di scussion of these lesions
ca n be found in the secti on describing Ew-
ing's sarcoma and in Chapter 12.
ACUTE AND CHRONIC
OSTEOMYELITIS
Examples of osteomyelitis are infrequently
aspirated. Smears contain a mixture of acute
and/ or chronic inflammatory cell s. While
smears may suggest the d iagnosis, culture of
aspirated material is more defi ni tive and re-
liable. Cytologic descriptions of specifi c le-
sions have been publi shed.
5
6-58
MELANOTIC
NEUROECTODERMAL
TUMOR OF INFANCY
Melanoti c neuroectodermal tumor of in-
fancy is a rare beni gn neoplasm most often
occurring in the maxill a or epididymi s.
59
Other si tes can also be involved, including
the cranium.
60
These neoplasms are be-
li eved to arise from neural crest remnants.
They may be confused with mali gnant slll all
round cell neopl asms.
HISTOLOGIG f iNDI NGS
These neoplasms are characteri zed by two
popul ati ons of cell s: a small basophil ic cell re-
sembling a neuroblast and a larger epi theli-
oid cell with eosinophili c cytopl asm and a
vesicular The lattc r cell s often con-
tain melanin pi gment. Thcy are arranged in
an alveolar or pse udoglandul ar pattern sur-
rounded by a dense fi broti c stroma. 'Within
the glandul ar spaces, the small cell compo-
nent is distributed in loosely cohesive clusters.
Both cell types stain for neuron specifi c eno-
lase (NSE) and synaptophysin but not for
-1 00 protein. The larger cells react with an-
tibodies against cytokeratin and HMB 45.
CYfOLOGIC f iNDINGS
Smears are hi ghly cellul ar and contain large
fragments composed of ti ghtly packed, uni-
form small cells.
60
-
62
The edges of these ti s-
sue fragments are irregul ar, individual
cell s "dropping ofT' the edges. T he nuclei of
the tumor cell s are smooth , without irregu-
larity or molding. The chromatin is finel y
granul ar.
6
0-
62
T he background is cl ean. Oc-
casional larger pigment-containing cells are
seen in some cases.
G2
T he small cells are neu-
ron specifi c enolase positive, whil e the larger
cell s stain wit h HMB 45
62
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37. Dosoretz DE, Raymond AK, MUI"phy CF, Ooppke
KP, Schi ll er AL, Wang CC, Suit HO. Primary lym-
phoma of bone: the relatio nship of morphologic
diversity to cl inical behavior. Cancer 1982; 50: 1009-
1014.
38. Falini B, Bi nazzi R, Pil eri S, Mori A, Benoni F,
Canino S, Fagioli M, Minelli 0, Ciani C, Pellicioli
P. L'u ge cell lymphoma of bone: a repon of three
cases of B-cell o rigi n. HistopalllOlogy 1988; 12:177-
180.
39. Radas Z, Ki ewicz T, Hansmann ML. Prio.lary hi gh
grade malignant lymphomas of bone. Virchmvs Arch
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40. Ascoli V, Facciolo F, Nardi F. Cytodiagnosis of a pri -
mary non-Hodgki n's lymphoma of bone. Diagn Cy-
lopathol l 994; 11:1 68-173.
4 1. Htwe WM, Lucas DR, Bedross ian CWM, Ryan JR.
Fine-needle aspirate of primary lymphoma of bone.
Diagn CytopalllOl 1996; 15:421-426.
42. Orucevic A, Reddy VB, Selvaggi SM, Green L, Spitz
OJ , Gattuso P. Fine needle aspiration of extranodal
and extramedullary hematopoietic malignancies.
Diagn C)'lopalhol 2000; 23:318-321.
43. Meisj M, Butl er ll , Osborne BM, Ordo nez NG. Soli-
tary plasmacytomas of bone and extramedull ary
plasmacytomas: a clinicopathol ogic and immuno-
hi stochemical study. Cancel" 1987; 59:1475-1485.
44. vVoodruff RK, ~ ...Ial pas j S, \"Ihite FE. Solitary plas-
macytoma. II . Solitary plasmacytoma of bone. ClIn-
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45. Wiltshaw E. The natural hi story of extramedullal),
plasmacytomas and its relatio n to solitary myelo mas
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46. Greipp PR, Raymond NM, Kyle RA, O' Fallon WM.
Multipl e myeloma: significance of plasmablas tic
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65:305-3 10.
47. Sanerkin NG, Jeffree GM. Cytology o/Bone Tumours.
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cott Co., 1980, PI'. 11 8- 120.
48. Makley JT, Carter JR. Eosinophil ic granuloma of
bone. Clin Orthop 198[; 204:37-44.
49. Nezelof C, Basset F, Rousseau MF. Hislocytosis X.
Histogenetic arguments for a Langerhans' cell ori-
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50. Franzen S, Stenkuist B. Cytologic diagnosiS of eosin-
ophilic granuloma-reticuloendotheli osis. Acta Palhol
Microbiol Scand 1968; 72:385--390.
5 1. Katz RL, Silva EG, de Santos L, LukemanjM. Di-
agnosis of eosi nophil ic gran uloma of bone by cy-
tology, histology and electron microscopy of tran-
scutaneous bone aspi ration biopsy. } BoneJoint S1Irg
1980; 60: 1284-1290.
52. Musy .J P, Ruf L, Erne.up I, Baltissen-Bielecka l. Cy
topathologic diagnosis of an eosinophili c granu-
loma of bone by needle aspiration biopsy. Acta Cy-
101 1989; 33:683-685.
53. Van Heerde P, ;\ilaanen Egler R. The cytology of
Langerhans' cell histiocytosis (histiocytosis X). Cy-
lopathowgy 1991 ; 2:1 49- 158.
54. Elsheikh T, Silverman j F, Wakely PE .J r, Holbrook
CT, j ushi W . Fine needle aspiration cytology of
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lo ma) of bone in children, Diaf51l Cytopat/101 199 1;
7:261-266.
55, Shabb N, Fanning CV, Carrasco CH, Guo SQ, Katz
RL, Ayal a AG, Raymond AK, Cangir A. DiagnOSiS of
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agn Cylopatlwl 1993; 9:3-12.
56. Schnadig Vj , Quadri SF, Boyvat F, Borucki M. My-
cobaclenU1n kanasii osteomyeli tis presen ting as a
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57. Fl euria U, Chateau PS, Commo ns AS, O'Neil O.
Fine-needle aspimtion biopsy of cho ndrobl astic os-
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Corynebacteriu.m infection: a case leport. Diaf51l C)'to-
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58. Fulci niti F, Troncone G, Fazioli F, Ve lrani A, Zeppa
P, Manco A, Palo mbini L. Osteomyeli tis by Para-
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60. Rege j D, Shet T, Sawant HV, Nai k LP. CytologiC di
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62. Toda T, Sadi M, Kiyuna M, Egawa H, Tomamoto T,
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'1998; 42:775-780.
CYSTIC LESIONS OF BONE
UNICAMERAL (SIMPLE)
BONE CYST
bone cyst, also referred to as

olitary or simple bone cyst, is an inLramedullary
'pace lined by a thin connective tissue mem-
bra ne. The cavity is fill ed with a clear to
straw-colored fluid thaL is frequently rich in
acid and alkaline phosphatases. These cysts
represent approximately 3% ofbiopsied pri-
mary bone tumors, with over 90% being rec-
ogni zed in the first two decades of life.
l
The
male/female ratio appears to be approxi-
mately 2:1.
1
,2 The most frequent sites of in-
volvement are the upper humerus, upper fe-
mur, pelvis, and bones of the fool.
The most common prese nting symptom is
pain, whi ch may be associated wi th patho-
logic fracture. Less frequently, s\velling or
deformi ty of the affected bone may be the
presenting sign.
Simple bone cysts ge nerally present as cen*
tral radiolucent areas \vithin the medull ary
canal of a major long bone. The lytic areas
are frequently associated with a scall oped,
sclerotic border. The lytic zone often ex-
238
te nds to the growth plate. The cortex sur-
rounding the cyst is thinned, with distention
of the bone contour. Impo rtantly, no soft tis-
sue element is demonstrable radiographi-
call y. When pathologic fracture supervenes,
a fragment of the cortex may be displaced
centrally and drop into the cyst lumen. This
fragment is usually demonstrable radio-
graphi cally in the distal part of the cyst,
where it produces the "fall en fragment"
sign.
HISTOLOGIC FINDINGS
Curetti ngs from the cyst wall a re composed
of a thin layer of fibrous tissue without an
endothelial or e pitheli al lining. The fibrous
tissue membrane contains dilated vessels
and scattered inflammatory cell s including
multinucleated giant cell s and foamy and
pigment-laden macrophages. Fragments of
immature bone and osteoid are often found
within or appl ied to the fibrous membrane.
Tn addition, eosinophilic deposits of fibrin
are frequently seen witl1in the membrane
and may become mineralized without lami-
nations. These have been referred to by
some autl10rs as cementoid bodies and appear
to be characteristi c of simple bone cYSt.
3
,4
CYSTIC LESIONS OF BONE 239
CYrOLOGIC F INDINGS
Few reports exist in the literature regarding
the cytologic findings in simple (unicam-
eral) bone cysts. In most series, aspirates
from these lesions have yielded nondiag-
!lostic specimens.
5
-8 Even when cutting
needle biopsies
9
or direct touch smears from
lining membranes
JO
are obtained, the mate-
rial is usuall y insuffici e nt or nondiagnostic.
The smears of aspirated material have been
markedl y hypocellular, with a proteinaceous
granular background. The predominant cell
type has been a lymphocyte or hi stiocyte. No
fibroblasts , cementoid bodies, or osteoblasts
have been apparent.
8
,lo
PROBLEMS IN DlAGNOS1S
Because the smears are markedly hypocellu-
lar and do not have a characteristic patte rn,
the mate ri al obtained by fin e needle aspira-
tion (FNA) can at most be compatibl e wi th
the diagnosis of simpl e bone cyst. Even when
r the radiograph is consistent with a unicam-
eral bone cyst, hi stologic material should be
obtained in most cases.
6
,9
ANEURYSMAL BONE CYST
Because aspirates from ane urysmal bone
cysts are frequently dominated by blood and
a small number of multinucleated giant
celis, tl1eir clinical, radiographic, histologic
and cytologic features have been described
in Chapter 13. For compleleness, the cyto-
logic findings wi ll be reviewed here as well.
CYrOLOGIC FINDINGS
In the maj ority of cases, FNA aspirates ob-
tained from aneurysmal bone cysts are dom-
inated by fresh blood. The background of
these smears is extensively hemorrhagic and
simil ar in appearance to peripheral blood
smears. Spindl e-shaped cell s with moderate
amounts of cytoplasm and vesicular nuclei
are dispersed withi n the bloody background,
along with a number of osteoclast-type giant
cells (Fig. 13-3) .' Abundant hemosiderin
pigment is found within the giant cells a nd
scattered in the background. The find ings
are relatively nonspecific, a nd in general,
aneurysmal bone cysts cannot be diagnosed
by cytologic examination alone.
1o
In the ap-
propriate clinical and radiographic setting,
FNA can help confirm the radiologic im-
pression .
TEUNGIECTATIC
OSTEOSARCOMA
Telangiectatic osteosarcoma is rare, com-
prising approximatel y 2% of all osteosarco-
mas. I J It is defined by a purely or extensively
lytic expansil e lesion on radiography. In
general, it occurs at the same si tes as typical
osteosarcomas, but in some seri es it has a
prevalence for the di stal e nd of the femur
or the femoral diaphysis.
12
RADIOGRAPH1C FINDI NGS
Most cases of telangiectatic osteosarcoma
appear as a purely lytic lesion occurring
within the meta physeal area of a long bone.
The tumor has infiltrative margins, with cor-
ti cal destruction a nd freque n t soft ti ssue ex-
tension. It may cl osely resemble aneurysmal
bone cyst. 13
HISTOLOGIC F1NDINGS
Low-power exami nation of histologic sec-
tions obtained from telangiectatic osteosar-
comas reveals a sponge-like architecture in
which the septal walls are composed of
anaplastic spindle-shaped a nd oval cel ls ad-
mixed with streamers of osteoid and scat-
tered multinucleated osteoclast-type giant
cell s. The septae surround blood-filled
spaces (Figs. 12-8 and 12-9). In the major-
ity of cases, anaplastic spindle-shaped or
ovoid cell s dominate the histologic picture.
However, in a small fraction of cases, the
stromal cell s have a bland appearance re-
sembling that of reactive fibroblasts or ovoid
osteoblasts. The diagnosis is achi eved by
ide nti rying occasional anaplastic cells (Fig.
12-9) within the septae. These cells may be
mononucleated or appear as anaplastic giant
cell s. Demonstration of these cells all ows
separation from aneurysmal bone cyst.
CYl' OLOGIC FINDINGS
Fine needle aspiration smears obtained from
telangiectatic osteosarcomas contain
dant blood a nd a modest number of pl eo-
morphic tumor cells (Fig. 12-20), freque ntly
with gia nt nucl ei.
14
,15 These sarcomatous
cell s may be mo nonucleated or multinucl e-
ated. Only scanty osteoid is present, a nd in
most cases the smear pattern is simil ar to
the pleomorphic patte rn described by White
et al. 14
DIAGNOSTIC F INDINGS
Abundant blood is present in the back-
ground of smears.
Markedly atypical (pleomorphi c) mono-
nucleated and multinucl eated tumor cells
are presen t.
Osteoid is generally extremely scan ty.
Ben ign osteoclastic gian t cell s may be
present in the background.
[n general, tela ngiectatic osteosarcoma is
easil y recognized as a high-grade sarcoma . .
Correlati o n with the radiographic find ings
establishes the diagnosis of telangiectatic os-
teosarcoma in these cases. Rarely, both the
cytologic and radiologi c findings overlap
those of ane urysmal bo ne cyst. In these cases,
careful study of the smears for rare anaplas-
tic cells is necessary to establ ish the correct
diagnosis. Careful cytologic-radiologic cor-
relati on is necessary for the appropri ate di-
agnosis of these I, ions.

GANGLION CYST
lntraosseous ganglion cysts a re small caviti es
occurring within subchondral regions of
bone near a j oint surface. These lesio ns a re
identi cal in appearance to their soft tissue
counterparts, lack a lining, and are fill ed
with a mucoid viscous fluid. They probably
represe nt a degenerative process and in the
presence of a normal j oint a re referred to as
intraosseous ganglion cysts. Whe n the joint is
involved by osteoarthriti s, these subchondral
cysts are a ma nifestation of the arthriti c pro-
cess and are referred to as osteoarthritic bone
cysts. In either event, the cytology and his-
tology are ide n tical.
Intraosseous gangli o n cysts occur in skele-
tally mature individuals generally over 20
years of age. The peak incide nce occurs in
the fourth or fifth decade of life, and there
is a sli ght male predomi nance. Most exam-
ples have bee n reported in the long tubular
bones, especiall y those around the hip,
knee, a nd a nkl e.
16
-
18
The maj o rity of intra-
osseous gangli o n cysts present with pain,
whi ch is usually aggravated by standing or
exercising.
RADIOGIW'HIC FINDINGS
Radiographi c studi es reveal a well-defi ned
lytic a rea with a pro minent scl e roti c margin .
The lesion is located eccentri call y within the
subcho ndral bone. The cysts are usually ap-
proximately 1 em in diameter; cysts lafger
than 2 em in diameter are extremely un-
usual. The radiogrd.ph ic study does not show
a connection with the joint or adj acent syn-
ovial tissue.
The walls of the cyst are composed of fl at-
te ned fibrous tissue witho ut a n e pithelial o r
e ndotheli al lin ing. In most examples the fi -
brous tissue capsule has two distinct layers.
The o uter layer is composed of compact fi-
brous tissue elements, whil e the inner layer
has a loose myxoid appearance. The osseous
ti ssue surrounding the lesion generally has
the appearance of reactive bone with os-
teoblasti c rimming. Osteoclasti c bone re-
sorption may be prominent
CYTOLOGIC FINDI NGS
The cytologic findings of intraosseous gan-
gli on cysts are ide nti cal to those of the soft
tissues. Aspirates a re characterized by a
thick, cl ear viscous fluid that is initi ally col-
orl ess but may become blood-tinged with ad-
ditional passes.
19
Whe n stained by the Diff-
Quik method, the background has a deep
bright magenta color and a thick mucoid
appearance. T he mucoid substance often
folds upon itself, giving a patte rn reminis-
cent of crinkled plastic food wrap. 19 Withi n
the mucoid substance, the re is a scattering
of hi stiocytes that contain abundant bubbly
cytoplasm and oval o r kidney bean-shaped
nucl ei. The nucl ei often contain small
nucl eoli. There is no evidence of cellul ar
atypia.
cysn c LESIONS OF BONE 241
SUBCHONDRAL
OSTEOARTHRITIC BONE CYSTS
These cysts frequently accompany osteo-
arthri tis and a re a characteristic C01l1pOne nt
of the degenerative process. Histologically
and cytologicall y, their appearance is identi-
cal to that of intra osseous ganglion cysts. The
readef is referred to the preceding section.
INTRAOSSEOUS
EPIDERMAL CYSTS
Rarely, cysts within bo ne are lined by squa-
mous epithelium. Most frequently these cysts
are found within the distal portions of the
fingers. Such cysts may arise as develo p-
mental malformations o r displacement of
squamous e pi thelium into the bone during
embryogenesis. Most cysts in the fingers, are
discovered between the second and fifth
decades, whi le those occurring within the
skull are usually found within the first and
second decades of life.20,21
RADIOGRAPHI C F INDINCS
Plain films demonstrate well-demarcated
lytic defects with scl e rotic margins. The
bone's cortical contour may be expa nded,
but disrupti o n of the cortex is rarely seen.
Histologic sections show a cystic lesion that
is lined by mature-appearing stratifi ed squa-
mous epithelium. The lumen is fi ll ed with
keratotic debris. In a Signifi cant numbe r of
cases the cyst wall is disrupted, with spillage
of keratin mate rial into the adj acent bony
tissue. An inflammatory response with mul-
tinucl eated foreign body giant cells occurs
in areas of spillage.
CYTOLOGIC FI NDINGS
Aspiratio n smears contain large numbers
of anucl eated and nucl eated, keratini zed
squamous cells. The cell s may show reactive
atypia. but nuclear anaplasia a nd membrane
irregulariti es are absent. In some cases, an
inflammatory response domi nated by multi-
nucleated foreign body gia nt cells is seen.
DIAGNOSTIC FINDINGS
Smears are highly cellul ar, with numer-
OllS keratoti c cell s.
The individual cells may be anucleated
or contain a single small , mature-appearing
nucleus.
The nucl eus is frequently pyknotic, with
smooth nucl ear membranes a nd a de nse
chromatin.
-Mitotic fi gures are absent.
Inflammatory cells including neutrophi ls
and multinucleated foreign body-type giant
cells are seen in some smears.
DIAGNOSTIC PROBLEMS
Epidermal cys ts must be differentiated from
me"tastatic squamo us cell carcinoma. In gen-
e ral, nuclear atypia is of significantly greater
degree in exampl es of metastati c squamous
cell carcinoma. The nuclei of the carcinoma
cell s are irregula r, and promine nt nucl eoli
may be present. Whi le degene rative forms
including pyknoti c nuclei are freque ntly
found in the benign cysts, the majori ty of
cell s are mature in a ppearance, with a dark,
conde nsed chromatin. In the majority of
squamous cell carcinomas, at least a few im-
mature and atypical nuclei a re seen.
Radiographic studies are also helpful in
the separation of epidermal cysts from met-
astatic squamous carcinomas. The epidermal
cysts have a scl erotic margin a nd are well cir-
cumscribed. The appearance of metastati c
squamous carcinoma on x-ray is that of a de-
srructive lesion with a more irregular borde r.
REFERENCES
1. Boseker EH, Bickel WH, Dahlin DC. A clini co-
pathologic sLUdy of si mple unicameral bone cysts.
Surg Gynecol Obslet 1968; 127:550-560.
2. Saito Y, Hoshina Y, Nagaminc T, Nakajima T, Suzuki
M, Hayashi T. kSi mpl c" bone cyst: a cli ni cal and his-
topathologic study of fifteen cases. Oral Surg Oral
Med Oral Palhol 1992; 74:487-49 1.
3. MirraJM, Bernard CW, Bullough PC, J ohnston W,
Mink C. Cementum-like bone production in soli-
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bones): repon of three cases-electron micro-
scopi c observation suppo n ing a synovial origi n to
the si mpl e bone cyst. Clin Ortho/J 1978; 135:295-307.
4. Sallcrkin NC. Olel fibrin coagula and their ossifi-
cation in simple bone cyst. ./ Bon.e Joint Surg (Br)
1979; 61:194- 199.
5. Kumar RV, Rao CR, Hazarika D, Mukherjee C,
Gowda BMG. Aspiration biopsy cytology of pri mary
bone lesions. Acta C)tol1993; 37:83-89.
6. Dollahite HA, Tatum L, Moinuddin SM, Carnesale
PC. Aspi ration biopsy o f primal)' neo plasms of
bo ne. J BOI1t' Joint Swg 1989; 71A: 1166-1169.
7. Xiaojing r, XiangchengY Cytodiagnosis of bone tu-
mors by fi ne needl e aspiration. Acta Cp o! 1985;
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8. i\'i elken P\o\J . Fine needle aspiration cytolob')' of
bo ne lesions. Anal ysis of a three-year experience in
rum] Afl-ica. ACla C),lol I990; 34:677- 680.
9. Aya la AC, Zomosa .J. Primary bone tumors: Percu-
taneous needl e biopsy. Rad iologic-pathologic study
of 222 biopsies. Radiology 1983; 149:675-679.
10. S;,\I1 crkin NG, j efTree GM. C)'l%gy oj Bone Tilmours.
II CO/Olll" Alias with Text. Philadelphia: J.B. Lippi n-
cOlt Co. , 1980, pp. 146-15l.
II. Mil lSuno - I ~ Unni KK, McLeod RAJ Dah li n DC.
Tclangiect.atic osteogenic sarcoma. Cancer 1976; 38:
2538-2547.
12. Huvos AC, Rosen G, Brcl5ky 55, Butler A. Telangi-
ectatic osteogenic sarcoma: a clinicopathologic
study of 124 patients. Cancer 1982; 49: 1679-1689.
13. Ka ufman RAJ 1b wbin RB. Telangiectatic OSleosar-
coma Simulating the appearance of an aneurysmal
bone cyst. fhli alrRadi ol1981; 11 :J02-104.
14. White VA, Fanni ng CV, Ayala A, RaYlllond AK, Car-
rasco CH, Mun<lY JA. Osteosarcoma and thc role
of II nc-needle aspi ration. A study of 5 1 cases. COI/ -
("I'r 1988; 62: 1238- 1246.
15. 5ancrkin NC, J efTree Gr ...l. Cpolog)' oJ I1olle TUlll ours.
II Colour II lias with "/ exl. Philadelphia: J.B. Lippin-
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16. Bauer TW, Dorfman HO. Illlraosseo lLs g<.IIlglion: a
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Li e defect.'; of bone . .J Bone .Joint Swg 1973; 55A:
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20. Carroll RE. Epidermoid (epithelial ) cySt of the
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1450.
. T
BONE LESIONS COMPOSED PREDOMINANTLY
OF SPINDLE-SHAPED CELLS
ADAMANTINOMA OF
THE LONG BONES
Adamantinoma of the long bones is a neo-
plasm of intermediate mali gnant potential
displ ayi ng at least focal epitheli al differenti-
ation. The cu rrent nomenclature for thi s le-
sion is based on its resemblance to the more
common ameloblastoma of the j aw. The
simi larity of these two neoplasms is purely
morphologic; Lhey do not appear Lo have a
histogenetic relati onShip. The majori ty of
adamantinomas of bone occur within the
ti bi a, although rare examples in other long
bones have been reported. 1,2
The histogenesis o[ adama ntinoma re-
mains controversial. A variety of theories
have been proposed, whi ch include (I) em-
bryonic rest theory, (2) traumatic implanta-
tion theory, (3) synovial ori gin theory,
(4) endotheli al or angioblastic origin , and
(5) low-grade mesenchymal sa rcoma with fo-
cal epithelial and spindl e cell differentia-
ti0I1.
3
WiLh Lhe appli cation of immunohisto-
chemistry demonstrating islands of cells
showing sLrong keratin staining, the epithe-
lial implantati on theory has gained support.
A possible relationship with osteofibrous dys-
plasia is intriguing since osteofi brous dys-
243
plasia may represe nt a juvenile form of
adamantinoma of the long bones.
3
Adamantinomas occur over a wide age
range, affecting indi viduals between the sec-
ond and sixth decades. 1. 2,4 The average age
is 35 in one large seri es .
2
The male/female
ratio appears to be approximately 1.3:1.
2
The maj ori ty of patienLS present with a com-
plai nt of dull aching pain and swell ing in the
area of the shin. PathOlogic fract ure may be
the presenting sign.
RADIOGIW' I-I1 G F INDI NGS
Ninety perce nt of adamantinomas of long
bones involve the shafts or metaphyseal!
diaphyseal area of the tibia or fibula.
4
At
these si tes, the neoplasm is characteri zed by
a central or ecce ntric elongated zone of ly-
sis. The osteolyti c area is well circumscribed
but may have a honeycomb or bubbly ap-
pearance. Within the tibia, the neoplasm is
usuall y situated in the anterior portion of the
middl e or di stal third of the shaft.'
HISTOLOGIC Fi NDINGS
Adamantinomas show considerable hi sto-
logic di versity but are generally character-
244 CYrOPATHOLOGY OF BONE AND SOFT TISSUE TUMORS
Figure 16-1. Adamantinomas are characterized
by a destructive and infiltrative growth of a col-
lageni zed spindle cell stroma containing scat-
tered nests of e pi thelial elements (H&E, X25) .
ized by a variable admixture of collagenized
spindl e cell stroma a nd nests of epithelial el-
ements (Fig. 16-1 ) . Several di stinct hi sto-
logi c patterns have been described. The
basaloid pattern is the most common, com-
posed of nests of small cuboidal or colum-
nar cells with the central cell s lying in a stel-
late or vesicular arrangement (Fig. 16-2) 6
The squamoid pattern is characterized by a
spindle cell a nd collagenized stroma in
which are de posited nests of cells showing
definitive squamous differentiation, includ-
ing "prickle" cells and cells containing kera-
tohyaline granul es. In the spindle cell pat-
tern, cells are distributed in a vesicular or
he rri ngbone arrangement with a back-
ground of loose fibrous tissue. Infreque ntly,
Figure 16-2. The e pithelial elements fr que mly
have a "basaloid" pattern in which the n sts are
composed of small cuboidal or columl] r cells
( H&E, XIOO). I
a small tubular pattern occurs in which small
gland-li ke SU' uctures are present in an oste-
ofibrous background.' Thi s background
conLains small trabeculae of bone with os-
teoblasti c rimming.
A disti nct form of adamantinoma has
been described in which small nests or cords
of cells resembling Ewing's sarcoma are de-
posited throughout a hyalini zed stroma.
S
,9
Ultrastructural studies have demonstrated
tonofilaments, desmosomes, and basement
membrane substances associated with these
cells.
B
,!}
In a significant number of cases, adaman-
tinomas are characte rized by an extensive
proliferation of spindle cells forming a stori-
for m or cartwheel pattern. Littl e epithelial
differentiation is seen.
10
, ll These cases may
be difficult to identity as examples of ada-
mantinoma because of the extreme scarcity
of the e pithelial component.
CYTOLOGIC FINDINGS
In the majority of reports, fine needle aspi-
rates obtained from examples of adaman-
tinoma have been highly cell ular
12
13
The
neoplastic cells are predominantly spindle-
shaped or ovoid (Fig. 16_3)13.15 These cells
are dispersed singly, as well as for mi ng co-
hesive clusters (Fig. 16-3) 12.15 Neoplastic
(

Figure 16-3. Cytologic preparations from adaman-
tinomas vary greatly in cell ulari ty, and some have
been reported as highly cellular. Other examples
are rather low in cellularity, with the majori ty of
neoplas tic cells being spindle-shaped or ovoid. The
ovoid cells lie singly or in small , cohesive clusters.
These cell s have moderate amount') of cytoplasm
that may have a vacuolated appearance (Diff-Quik,
X200) . The nuclei generally have a bland chro-
matin pattern.
BONE LESIONS COMPOSED OF SPINDLE CELLS 245
cells have absent or indistinct cytoplasm and
the nuclei are darkly stai ning, with a uniformly
dispersed, finely granul ar chromatin.
12
Chro-
mocenters are indistinct, and nucleoli are
generally absent. On Romanowsky stai ning,
narrow strands of metachro matic material fre-
que ntly outline individual tumor cells. Occa-
sionally, the neoplasti c cells surround hyaline
structures, forming a rosette-like arrange-
ment.
12
Mitotic figures are rare o r absent, and
nuclear pleomorphism is minimal. Rarely,
multinucleated osteoclast-type giant cells are
present. Necrotic debris has been reported to
be present in some cases.
12
-
15
The cell clusters
may have an epithelial appearance (Fig. 16-3) ,
which is confirmed with positive cytokeratin
staining. 13
DIAGNOSTIC FINDINGS
Smears are highly cellular, composed of
individually di spe rsed cell s and small clus-
ters of cells.
The majority of cells are short spindl e
celi s, but ovoid and round cells are also
found.
The individual cells have indistinct or
absent cytoplasm.
Immunohistochemical staining for cy-
toke ratins demonstrates positive staining of
some cells witl1in the cohesive groups.
Necrotic debris is variably present in the
background.
Metachromatic material may be seen
surrounding individual cells and in cell clus-
ters when material is stained with Roma-
nowsky stain.
DIAGNOSTIC PROBLEMS
Adamantinomas must be distinguished from
osteofibrous dysplasia, Ewing's sarcoma, and
metastatic carcinoma. Distinguishing some
forms of adamantinoma from Ewing's sar-
coma may be difficult, but immunohisto-
chemical studies for the oncogene protein
product (013) and for cytokeratin are ex-
tremely helpful in this differential diagnosis.
Ewing's sarcoma is 013 positive, while
adamantinoma contains a small component
of cell s that are cytoke ratin positive. These
reactions are most reliable when pe rformed
on cell block material.
Distinguishing adamantinoma from oste-
ofibrous dysplasia can be extremely difficult.
The detection ofa signifi cant component of
keratin-positive cells sU'ongly favors the d i ~
agnosis of adamanti noma of long bone.
Separation of adamantinoma from meta-
static carcinoma can be extremel y difficult
since both lesions demonstrate keratin pos-
itivity. In general, cytologic preparations
from adamantinoma contai n cells with o nly
modest nucl ear atypia and a predominance
of short spindl e-shaped cells. Metastatic car-
cinomas demonstrate greater degrees of nu-
clear atypia and a higher percentage of ep-
itheli al cells with either keratinization or
glandular differentiation. In additi on , the
x-ray findings and characteristic location of
adamantinoma of long bone should help
separate Lhese lesions.
Metastatic oat cell carcinoma is cha rac-
terized cytologi cally by greater degrees of
nuclear molding and a coarser chromatin
pattern than is seen in adamantinoma.
12
Adamantinoma of long bone can be sepa-
rated from metastatic carcinoid tumors by
the extracell ular pe riodic acid-Schiff (PAS)-
positive hyali ne material (metachromatic
on Romanowsky staining) characteri sti c of
adamantinoma but not see n in carcinoid tu-
mors. Ma ny metastati c adenocarcinomas
from bowel or lung are mucin positive, al-
lowing distinction from the mucin-negative
epithelial cells of adamantinoma. 12
INTRAOSSEOUS
DESMOPLASTIC FIBROMA
Desmoplastic fibroma is a rare neoplasm of
bone, accounting for approximately 0.3% of
all benign bone tumors.I
6
It is most fre-
quently diagnosed in the first three decades
oflife.
17
Most desmoplastic fibromas of bone
are asymptomati c and he nce are incide ntal
findings. IS Growth is slow and may result in
swelling, tenderness, or aching pain. In ap-
proximately 10% of cases, pathologic frac-
ture brings the lesion to clinical attention.
Desmoplastic fibroma of bone occurs most
commonly in the mandible;O' the pelvic bones
(i li um) , and the femur. Almost any bone may
be involved, but two-thirds of these neo-
plasms occur in tl1e long bones. 19.20
RADIOLOGIC FINDINGS
The majori ty of tumors occur in the meta-
physes of long bone and may show epiphy-
seal extensio n ,1 6 T hey occur centrally within
the bone and have a purely lytic appearance
with a wel l-defi ned scl e rotic margin.
20
A
honeycomb or soap bubble appearance
within the lytic compo nent is frequent and
occurs most cha racteri sti call y in the pelvic
bones and scapula. Rarely, the tumor is char-
acterized by a permeative pattern of bone
destruction with cortical erosion and a soft
tissue mass.
21
H ISTOLOGIC F INDINGS
Histopathol ogic findings of desmoplastic fi-
broma of bone are ide nti cal to those of soft
ti ssue desmoid tumors. The tumor is com-
posed of small spindle-shaped fibroblasts ir-
regularly di stributed in a backgro und of col-
lage ni zed stro ma. The nucl ei are bland and
ovoid or elongated in shape. The chromatin
has a vesicular pattern, with occasional nu-
clei being moderately enlarged and hyper-
chromatic.
16
Nucl eoli are absent, and mi-
totic figures are exceedingly rare o r abse nt.
The neoplasm erodes into the surrounding
bone and occasionally traps small fragme nts
of residual host bone.
CYTOLOGIC F l NDI NGS
The cytologic featu res obtained o n fine
needle aspiration are ide ntical to those
re ported for the soft tissue counterpart.
Smears are sparsely cellular
22
and contain
spindl e-shaped cell s without nucl ear atypia.
Cel ls may li e individuall y but more fre-
que ntl y are found in clusters, where they are
enmeshed in a network of coll agen fibe rs.
23
The indivi dual cell s have tapered ends and
scanty to rnodest amounts of cytoplasm. The
nucl ei are fusi fo rm and occasionally bent, re-
sembling those seen in nerve sheath tumors.
The chromatin is fine and uniforml y dis-
tributed, with occasio nal cells containing
small , indi stinct nucleoli.
23
MiLotic figures
are not found even after a prolonged search.
There is no signifi cant infl ammatory corn-
ponent, bUL fragments of coll agen fibers may
be found in the background.
DJAGNOSTlC FEATURES
Smears are markedly hypocellular, con-
tai ning scattered individual cell s and cluste rs
of bland spindle-shaped cell s.
The majority of spindl e-shaped cell s
form clusters in which they are e nmeshed in
a network of coll agenous f:ibers.
The background may con lain collagen
fiber debris.
Spindle-shaped cells have bland nuclear
featu res with a fine chromatin pattern and
small , indistinct or absent nucleoli.
Mitotic figures are not found.
Because the mate rial obtained by aspiration
of desmoplastic fibroma of bone is exceed-
ingly scanty, the examining cytopathologist
may designate the specimen as nondiagnos-
tic. Careful correlation with radiographi c
findings may allow the cytopathologist to
support the radiographic impression of a be-
nign lesion. In the majority of instances,
open biopsy is necessary to establi sh the di-
agnosis. Fine needle aspiration is helpful in
excl uding o the r well-circumscribed lyti c le-
sions in the radiologic diffe re ntial diagnosis.
OTHER UNCOMMON
PREDOMINANTLY
SPINDLE CELL LESIONS
AFFECTING BONE
A variety of benign and mali gnant spindl e
cell lesions infreque ntly arise as primary le-
sions of bone. Their appearance in general
is identical to that of the ir soft tissue coun-
terparts. Most common among these are fi-
brosarcoma, malignant fibrous histiocytoma,
a nd leiomyosarcoma. The reader is referred
to the relevant chapte rs describing the hi s-
tology and cytopathol ob'Y of the corre-
spo nding soft tissue lesions.
REFERENCES
1. I-Iazelbag J-IM, Taminiau A1-I, Fleuren GJ, Hogen-
doom Pc. Adamantinoma of the long bone . .! Bone
joint SUTg 1994; 76: 1482-1499.
2. Campanacci M, Gianti A, Bertoni F, Laus M, Cilelis
S. Adamantinorna of the long bones. The experi-
ence of the Istitato Orloped ico Rizzoli. Am J Surg
Palhol \981; 5:533-542.
3. Mirra.JM. Hone Tumors. Clinica.1, Radiologic, ant/Patho-
logic Correlations. Philadelphia: Lea and Fcbigcr,
\ 989, pp. 1215-1217 .
4. Fischer B. Bcr ein primaries adamantinom del'
tibia. Frankfurt 2 Pafho11913; 12:422-441.
5. Braidwood AS, McDougall A. Adamantinoma of the
BONE LESIONS COMPOSED OF SPINDLE CELLS 247
tibia. Report of two cases.) BoneJoint SUig { I3rJ 1974;
56B:735-738.
6. Weiss SW, Dorfman 1-10. Adamantinoma of long
bone. Hum PalftoI1977; 8: 141-[53.
7. Konrad EA, Meister P, StUll S. AdamantinO!1l del'
tibia und reakliv knochenveranderungen. Arch Or-
thoj) TraUilla Surg 1978; 92:297-301.
8. P, Konrad E, 1-lLibner C. Malignant tumor
of humerus with reatures of "adamantinoma" and
Ewing's sacoma. Pal/wi Res Pmcl [979; 166: 1 12-122.
9. Ishida T, Kikuchi F, Oka T, Machinami R, Kojima
T, l Uima T, Hi gaki S, Imamura T. Case reporl727.
.I uxtaconica[ adamantinoma or humerus (simulat-
ing Ewing tumor) . Shelelal Radial 1992; 21 :205-
209.
10. Keeney GL, Unni KK, Beabout .JW, Prichard OJ.
Adamanlinoma oflong bones. Cancer! 989; 64:730-
737.
II. Rock MG, BeaboutJ\"', Un ni KK, Sim FH. Adaman-
tinoma. Orl/wj)etiics 1983; 6:472-477.
12. Hales MS, Ferrell LD. Fine-needle aspiration biopsy
of tibial adamantinoma: a case repon. Diagn Cy-
lolmlho! 1988; 4:67-70.
13. Pel-ez-Ordonez B, Bedard Vc. Metastatic adaman-
tinoma diagnosed by [ine-needle aspiration biopsy
or the lung. Diagn C)'lol)(J.lIwl 1994; 10:347-351.
14. Calera-Davidson H, Fernandez-Rodriguez A, Torres-
Olivera FJ, Gomez-Pascual A, Moreno-Fernandez A
Cytologic diagnosis of a case of recurrent adaman-
tinoma. ArIa C)'lol [989; 33:635-638.
15. Bommer KK, Ramzy I, Mody D. Fine-need[e aspi-
bone lesions. A study of 450 cases. Cancer C),loj)(llhol
1997; SLJ4S-156.
[6. Inwards cy, Unni KK, BeabouLJW, Sim FH. Desmo-
plastic libroma orbone. Cancm- 199 I; 68:1978-1983.
17. Gebhardt MC, Campbell q, Schiller AL, Mankin
1-:1]. Desmoplastic fibroma of bone. A repon of eight
cases and revielV of the literature. J BoneJoint Surg
(Am) 1985; 67:732-747.
18. Greenspan A, Unni KK. Case report 787. Desmo-
plastic fibroma. Skeletal Radio11993; 22:296-299.
19. Crim JR, Cold RH, i\'l irra.JM, EckhardtlI , Bassett
LW. Desmoplastic fibroma of bone: radiographic
analysis . Radiology 1898; [72:827- 832.
20. Nilsonne U, COlhlin C. Desmoplastic fibroma of
bone. Acta Orlitol) Scand 1969; 40:205-215.
21. Rabhan \''IN, Rosai J Desmoplastic fibroma. Repon
often cases and review of the literature . .! Bone.!oint
Swg (A'/II.) 1968; 50:487-502.
22. McLeod DL, GeiSinger KR, Hopkins MB 11[ , Sil-
verman JF. Fine needle aspiration cyLOl06'Y of the fi-
bromatosis: A clinical and cytop<lthoJogic assess-
lnent [abstract]. Acta C)'toI1987; 31:683.
23. Suen KC. AI/as and Text of ASjJimlion l3ioj)sy G)'lology.
Baltimore: Williams and Wilkins, 1990, pp. 78-82.
I
VASCULAR NEOPLASMS OF BONE
HEMANGIOMA
Solitary hemangiomas are the most common
vascul ar lesion of bone. Multifocal lesions
occ ur less frequentl y. Whi le representing the
most common vascular lesion of bone, hem-
angiomas are relatively rare, accounti ng
from less than 1 % of all biopsied p.-imary
neoplasms of bone. I Based on autopsy seri es,
it appears that a significant number of soli-
tary skeletal hemangiomas are asymptomati c
and not recognized cli nically.2 Heman-
giomas occur over a wide age range, with a
peak incidence between the third and sixth
decades of life. The lesions predominantly
involve the vertebral bodies, ribs, and skull
but may also be found wi th some frequency
in the tibia.
s
Multifocal hemangiomas most
frequently involve the vertebral column, af-
fecting adj acent ve rtebral bodies.
RADIOGRAPHI C F INDI NGS
Hernangiomas present as ""ell-demarcated
radiolucent lesions.! When OCCUlTing within
fla t bones, hemangiomas expand the bone
contour, but there is no thinning or di srup-
tion of the cortex. Within the skull , heman-
giomas have a characteristic "sunburst" ap-
pearance, This appearance results from fine
248
spicules of reactive bone arising within the
peri osteum and radiating concentri call y
from the ce nter of the lesion.
H ISTOLOGIC FI NDI NGS
Histologicall y, hemangiomas are character-
ized by aggregates of di lated vascul ar spaces
lined by a single layer of endotheli um (Fig.
17-1). The vascular channels can be large
and dilated (cavernous hemangioma) or
small and capill ary-sized (capill ary heman-
gioma). Most hemangiomas occurring within
bone are of the cavernous or mixed types.
The vessels are seen lying within a loose fi-
brous tissue matrix, which along with the ves-
sels extends through the intra trabecular mar-
row spaces, destroying and replaci ng the
surrounding host bone. The individual vas-
cular channels do not show evidence of pap il-
lations or piling up of endotheli al cells. In
most cases, th e residual trabecular bone is
thickened, resulting in a sclerotic pattern.
Close examination of vessels reveals them
to be separate str.. lctures that do not anas-
tomose. There is no vidence of mitoti c ac-
tivity. In some cases, romboses develop
within the lumen and ay undergo
fi cati on. Secondary n ovascularization of
thrombosed vascular channels can
VASCUlAR NEOPLASMS OF BONE
249
Figure 17- 1. Hemangiomas of bone arc charac-
terized by dilated vascular spaces tha t arc lined
by inconspi cll ous e ndothel ial cells showing no ev-
idence of nucl ear atypia (H&E, X40).
leading to a compl ex, intricate pattern of vas-
cular channels.'1
CvrOLOGIC FiNDI NGS
In the maj ority of cases, smears are ex-
tremel y bloody and on superfici al analysis re-
sembl e peripheral blood smears, With ri g-
orous aspirati on technique, fragments of
mesenchymal tissue can be obtained. The
most characteristic finding in smears from
hemangiomas is a vari abl e number of tissue
fragments composed of moderately cell ular
fibrous tissue arranged in three-dimensional
arcades around empty spaces or forming
short tubular structures (Figs. 17-2 and
17-3).5 The spindl e cells are ar ranged in a
swirling pattern around central lumina.
s
Lining the internal aspect of some of these
spaces are plump cells probably represent-
ing the endothelial cell component. In some
examples of hemangioma, the clusters are
compact and devoid of arcades but contain
finger-like tubular processes enLangl ed in a
serpentine fashi on. Occasionall y, indi vidual
spindl e cell s are found within the bloody
background. These cells have long, wispy cy-
toplasmic processes and fusiform nucl ei with
a fine chromaLin pattern. Nucl eoli are not
seen. Occasionall y, the single cells have
sharply angulated nucl ei.
When aspiration is not suffici entl y vigor-
ous to obtain tissue, the smears may be com-
posed only of blood and are nondiagnostic.
In some studi es, up to two-thirds of aspirates
contain only blood.
5
In hypocell ular smears,
Figure 17-2. Cytologic specimens obLained by
piration from hemangioma of bone are domi-
nated by red blood cells, with only rare tissue frag-
ments being present. These tissue fragments arc
composed of short, bl and spindl e cells that may
have a plump ovoid appearance along the edges
of the ti ss ue fragment (H&E, XlOO).
authors have reported finding oval or spin-
dle-shaped cell s with wispy cytoplasm and
nucl ear grooving. whi ch beli eved to sug-
gest an endoth eli al ori gin.6-8
DIAGNOSTI C F INDINGS
Smears have an extremely bloody back-
ground containing scattered clusters of mes-
enchymal cell s.
Cell clusters characteristicall y display a
swirling pattern around central lumina (ar-
cades) or may show a n10re compact pattern
in which lumina are not clearly visible.
Some tissue clusters appear as aggre-
gates of serpentine cords composed of bun-
Figure 17-3. The tissue fragme nts may have a
branching tubular appearance in some
mens (Diff-Quik, XIOO).
dies of parall el running spindl e cell s. Lu-
mina are not visible in these structures.
Small numbers of indi vidual spindle
cell s with long, wispy cytopl asmic processes
and fusiform nuclei containing a condensed
chromatin a re seen .
Immunohi stochemical stains for endo-
thelial markers such as factor VITI, Ulex eu-
rol}aeus, and CD31 or CD34 are positi ve in
the endothelial cell compone nt and help
suppo rt the diagnosis of a vascular neo-
plasm.
DIAGNOSTIC P ROBLEMS
A maj o r probl em in the diagnosis of hem-
angioma is the difficulty of obtaining ade-
quate material represenLative of the mes-
e nchymal proliferation. Vigorous aspiration
usually obtains cell clusters cha racteristic of
hemangioma.
5
Highly cellular exarnples can
be mistaken for hemangioendotheli oma or
angiosarcoma, but di stinction from most an-
giosaromas of bone is achievable by recog-
nizing the lack of nucl ear atypia in heman-
giomas. Careful correlation with radi ologic
findings is impe rative.
Occasionally, hemangiomas have an e pi-
thelioid appearance and may be mistaken
for epithelial lesio ns. Immunoh istochemi cal
studi es (cytoke ratins, factor VII!, CD31,
CD34) 'should all ow di stinction of these
lesions.
OTHER BENIGN
VASCULAR LESIONS
The cytologic fea tures of skeletal a ngio-
matosis, cystic a ngiomatosis, and massive os-
teolysis (Gorham's disease) a re ide ntical to
those of the hemangiomas described above.
Rosai et al.9 and later Weiss a nd EnzingerlO
descri bed a set of vascular lesions charac-
terized by endothelial cel ls with abundant cy-
toplasm and prominent intracytoplasmic
vacuol es. These neoplasms occur at a wide
variety of body sites, including the soft tis-
sues, lungs, liver, and bones.
9
,lo These neo-
pl asm have come to be known as epithelioid
hernangioendotheliomas and are recognized to
foll ow a clinical course inte rmedi ate in ag-
gressiveness between that of hemangioma
and hi gh-grade angiosarcoma.
Epithelioid hemangioendotheliomas oc-
cur over a wide age range, with an average
age of approximately 32 years. There appears
to be a definite male predominance, and
most cases occur in the lowe r extremi ties. I I
Radiographically, e pi theli oid hemangioe n-
dotheliomas present as a purely lytic lesion
with ,..,ell-demarcated margins. Cortical e ro-
sion and disruption can be seen, and the de-
gree of peripheral scl e rosis varies. The lytic
defects are not infreque ntly multifocal, and
when multiple lesions are present, they tend
to involve a single extremity.
HISTOLOGIC F INDI NGS
These neoplasms are characterized by a pro-
liferation of epitheli oid cells forming cords,
nests, and small , compressed vascular chan-
nels. The connective ti ssue stroma sur-
rounding the epithelioid cells frequently has
a myxoid appearance.
The individual cell s are round o r polygo-
nal, with a hi stiocytoid or epithelioid ap-
pearance.
9
,IO A characteri stic finding within
these epithelioid cells is a si ngle vacuole or
cytoplasmic bl eb, giving a signet ring-like ap-
pearance. This cytoplasmi c vacuole is be-
li eved to be the ini tial step in angiogenesis.
The nucl ei are e nlarged , often \vith sli ght ir-
regularity of nucl ear membranes. Nucleoli
are prominent. There is some cl earing of the
chro matin pattern, with chro matini c mar-
gination. Cellul ar pleomorphism is mi ld or
at most moderate.
Red blood cell s can be found loose in the
backgroiln- stroma and characte risti cally
within the cyt lasmic bl ebs and the small
vascular channe . The background can con-
tain a n infiltrate f inflammatory cells, pre-
dominantly eosi ophil s, lymphocytes, and
plasma cell s. The epitheli oid endotheli al
cell s express U. eurojJaeus lectin, CD3 l ,
CD34, and factor VIII-related anti gen.
12
CYrOLOGIC F INDINGS
Smears a re moderately cellular, with a
bloody background. The neoplastic cells are
predominantly dissociated but also form cel-
lular aggrega tes (Fig. 17-4).13.' " The indi-
vidual cells are ovoid to polygonal, giving
them an epithelioid appearance (Fig. 17-5).
The nucl ei are ovoid to round, often having
a reniform or polylobated-convoluted ap-
VASCULAR NEOPLASMS OF BONE
251
,
Figure 17-4. Cytologic preparations of epi theli-
oid hemangioendotheliomas contain abundant
blood, as well as individual and scattered clusters
of polygonal or ovoid cell s. A small but signifi cant
percentage of these cells have large intracyto-
pl asmic vacuoles representing inci pi ent vascul ar
differentiation (H&E, X 100) .
pearance.
14
Binucleated cells are often pres-
ent. Nucl ear pl eomorphism is mild to mod-
erate. One to three small nucl eoli are seen
in the majority of cells. A small percentage
of the neo plastic cells have a single sharply
demarcated intracytoplasmic vacuole (Fig.
17-6) . 14 Mitotic figures are usually present
but not in large numbers.
While the majority of neoplastic cell s lie ei-
ther singly or in loosely cohesive clusters, some
display tighter aggregation, forming rosette-
like structures or condensing around endo-
Figure 17-5. When the cells aspirated from epi-
thelioid hemangioendotheliomas lie singl y within
t.he smears, t.hey have a polygonal or even plas-
macytoid appearance, often with eccentric nuclei.
The nuclei are bland, with a fine chromatin pat-
tern and occasional small but distinct nucleoli
(H&E, X100) .
Figure 17-6. The characteristic cell seen cytolog-
ically in exampl es of hemangioendothelioma is a
pol ygonal cell with one or more intracytoplasmic
lumina (pale vacuoles) (H&E, X200).
thelium-lined tubular vascular structures.
13
The background can contain metachromatic
stromal fragments as well as inflammatory
cells, most commonly eosinophil s.
DIAGOSTIC CRTTERIA
Smears are moderately cell ular, with a
bloody background.
The monomorphi c cell population li es
either as single dissociated cells or as loosely
cohesive cell clusters.
Occasionally, tighter cell clusters form-
ing rosette-like structures or condensa ti ons
of cells around endothelium-lined tubes may
be seen.
Nucl ear pleomorphism is mild to mod-
erate, and the nucl ei contain one to three
distinct nucleoli.
Mitotic figures are present in most
cases.
T he background contains metachro-
matic stromal debris a nd inflammatory cells
(predominantlyeosinophils) .
Individual neoplastic cells have moder-
ate amounts of cytoplasm, whi ch is ovoid to
round.
A variabl e percentage of cell s have d is-
tinct intracytoplasmic lumina or blebs.
P ROBLEMS IN DIAGNOSIS
Epithelioid hemangioe ndothelioma must be
separated from epitheli oid hemangioma as
well as angiosarcoma. In general, epitheli oid
hemangioendotheli omas are more cell ular
than epithelioid hemangiomas and have
greater degrees of nucl ear atypia. The
ence of mitotic figures precludes the diag-
nosis of epithelioid hemangioma.
Epitheli oid hemangioendotheli oma can
generally be separated from angiosarcoma
on the basis of the degree of nuclear pleo-
morphism. Most primary a ngiosarcomas of
bone are hi gh-grade lesions with signifi cant
nuclear pl eomorphism. Epithelioid heman-
gioendotheli omas have signifi cantly Jess nu-
clear atypi a than is seen in angiosarcomas.
Tn addition, mitotic figures are more abun-
dant in angiosarcomas. Angiosarcomas show
greater variabi li ty in cell shape and size, with
spindle cell forms, polygonal cells, and mul-
tinucleated gia nt cells being present. The
spindle cell and giant cell elements are ab-
sent from epitheli oid hemangioendothe-
lioma. Occasio nal binucl eated cells can be
found in epitheli oid hema ngioendo the-
liomas, but the anaplastic giant cells charac-
teristic of some angiosarcomas are never
found in the hemangioe ndotheli oma.
ANGIOSARCOMA
When defined hi stologically as a high-grade
sarcoma of vascular endothelium, primary
osseous angiosarcoma is very rare, repre-
senting less than 1% of all angiosarcomas
and approximately 1 % of all primary bone
malignancies. IS The maj ority of angiosarco-
mas appear to occur in the long tubul ar
bones and may be multicentric, with either
multipl e si tes of involvement in a single bone
or multiple lesions in adj acent bones.
In the maj ority of cases these are highly
aggressive sarcomas, with rapid progression
of disease and a signifi cant potential fo r met-
astatic behavior.
16
, [7
Radiographi c find ings are nonspecific and
merely reflect the aggressive, destructive,
and permeative nature of the neoplasm. The
individual lesions are lytic, with irregular
borders, and frequently show complete cor-
tical destruction a nd extension into the sur-
rounding soft tissues.
HISTOLOGIC FINDINGS
as defi.ned by Campanicci et
al.I and Wold et aI.,16 are high-grade vaso-
formative mali gnancies in which the prolif-
erating vascular tissue produces an anasto-
mosing network of irregular channels li ned
by plump anaplastic endotheli al cells (Fig.
17-7). Cellular pleomorphism is marked,
and numerous mi totic figures including
atypi cal forms are easily found.
18
Multinu-
cleated anaplastic giant cell s are a frequent
findi ng. The endothelium often forms in-
travascular papillary tufts, while in other ar-
eas soli d sheets with anaplastic spi ndl e cell s
are seen.
Immunoreactivity for factor VIII-related
antigen, CD3I , and CD34 is usually strongly
positive, w'hile th ere is o nl y focal positivity
for U. europaeus.
CYTOLOGIC F INDINGS
Smears are invariably bloody but contain a
significant component of large polygonal to
round a naplasti c cells.
19
-
24
These cells have
large vesicular nucl ei with chromatin clear-
ing and margination. Nucleoli are large and
distinct (Fig. 17-8). The cytoplasm of these
cells is abundant pal e blue-gray (Roma-
nowsky staining) and freque ntly vacuolated.
The cell s range in size from two to nine times
the size of the background red blood cells.
In approximately half of all cases, the mali g-
nant endotheli al cells de monstrate intracyto-
plasmic hemosiderin deposits. A component
of the neoplastic cell s has a spindl e-shaped
morphology with nuclear features simil ar to
Figure 17-7. Angiosarcomas of bone are charac-
terized by an infi ltrative destructive proliferation
of atpyical cells forming sli t-li ke channels, papil-
lary formations, and solid areas. Wh il e the degree
of n uclear atypia can vary greatly, these neo-
plasms are invariably characterized by a vasofor-
mative growth pattern characterized by either vas-
cular channels 0 1" intracytoplasmic lumina (H&E,
X50) .
VASCULAR NEOPLASMS OF BONE 253

Figure 17-8. A<;pirates [rom high-grade angiosar-
comas are composed predominantly of anaplas-
tic polygonal cell s. These cells have moderate
amounts of cytoplasm surrounding large nuclei
with huge nucleoli (Diff-Quik, X200).
those described in the round to ovoid cells
(Fig. 17-9). The cells li e singly or in loose
clusters of six to seven. The tumor cell s oc-
casionally may be binucleated.
24
Spindle cells
with similar nucl ear morphology may domi-
nate in some examples.
2
!:)-28
Some authors have reported the presence
of mi croacinar structures suggestive of vaso-
formation, trabeculae wi th arborizing vessels
or vascular structures, erythrophagocytosis,
and necrosis. [9,20-23 Cell debris and a myx-
aid matrix may occur in the background.
24
D IAGNOSTIC FINDINGS
Smears are bloody, with moderate to
scanty cell ularity of the mesenchymal com-
ponent.
Figure 17-9. A vd.riable percentage of the neo-
plastic cells has a spindle-shaped morphology and
nuclear features simi lar to those seen in the polyg-
onal cell component (Diff-Quik, X200).
Neoplastic cells may form small clusters,
li e individually, or form trabeculae, micro-
acinar vasoformative structures, or atypical
arborizing vessels.
Individual cells are most frequen tly
round to polygonal, but spindle cell forms
occur and may dominate in some examples.
Individual cells have moderate to abun-
dant pale blue-gray cytoplasm (Romanowsky
staining) .
Nuclei are enlarged and anaplastic and
have moderate-sized to large nucleoli. Chro-
matin may be vesicular or at times dense and
hyperchromatic.
Mitotic fi gures including atypical forms
are present.
Necrosis may be present in the back-
ground.
Occasional cells have intracytoplasmic
vacuoles.
Angiosarcomas must be distinguished from
other high-grade malignancies including
melanoma, anaplastic large cell carcinomas,
malignant fibrous histiocytoma, and osteo-
sarcoma.
Radiographic studies and the presence of
osteoid matrix help separate osteosarcoma
from angiosarcoma. Osteosarcomas are gen-
erally more cellular and form more numer-
ous cohesive clusters. Osteosarcomas lack
the vasoformative structures found in some
angiosarcomas .
Melanomas may be difficult to distinguish
from high-grade angiosarcomas since both
may have a predominantly round or polyg-
onal cell morphology. Both may contain pig-
ment. In angiosarcomas this pigment is iron
and is demonstrable by a Pruss ian blue re-
action, whi le in melanomas the pigment is
most often melanin. Melanomas may at
times be extremely hemorrhagic, giving rise
to bloody smears, but in most cases the
amount of blood in angiosarcoma is greater
than that in melanoma. In some cases, im-
munohistochemistry is necessary to establi sh
the diagnosis. Angiosarcomas are positive
for CD3l, CD34, and factor VIII-related
antigen, while melanomas are positive for
S-100 protein and HMB 45.
Some poorly differentiated carcinomas
may have a predominantly polygonal ap-
pearance without further epithelial differen-
tiation. Immunohistochemical demonstra-
tion of cytokeratin is extremely helpful in
separating these carcinomas from angiosar-
comas. In the majority of cases, anaplastic
carcinomas exhibit more cellular cohesion
than is seen with angiosarcomas.
In general, smears obtained from malig-
nant fibrous histiocytomas are more cellular
than those obtained from angiosarcomas.
Both contain highly anaplastic polygonal
cells, bu t malignant fibrous histiocytomas
contain a greater number of anaplastic giant
cells than is characteristically seen in an-
giosarcoma. Immunohistochemical studies
for CD31, CD34, and fac tor VIII-related
antigen are also helpful in separating these
two sarcomas. The demonstration of osteoid
in smears and the radiographic findings
help separate osteosarcoma from angiosar-
coma. While the radiologic findings in an-
giosarcoma are nonspecific, those in osteo-
sarcoma are usually specific enough to allow
its distinction from angiosarcoma. The pres-
ence of a radiographi cally demonstrable
trix within the neoplasm supports the d iag-
nosis of osteosarcoma.
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2. Schmor! G, J unghanns H. The Human Spine in
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Stratton, 1971 , pp. 325-327.
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c.v. Mosby Co., 1998, pp. 729-730.
4. Kuo T, Sayers CP, Rosai j . Masson's "vegetant in-
travascular hemangioendothelioma" lesion often
mistaken for angiosarcoma-study of seventeen
cases located in the skin and soft tissues. Cancer
1976; 38;1227-1236.
5. Layfield l..d, Mooney EE, Dodd LG. Not by blood
alone: diagnosis of hemangiomas by fine needle as-
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6. James LP. Fine-needle aspiration of soft tissue and
bone. In: Atkinson BF, ed. Atlas oj Diagnostic C)'-
lopathology. Philadelphia: W.B. Saunders Co., 1992,
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7. Powers CN, Berard MD, Frable \"0. Fine-needle as-
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cell lesions. Diagn Cylopathol1994; 10:232-241.
8. Frias-Hidvegi D. Guides 10 Clinical Aspiration Biopsy.
Liver and Pancreas. New York: 19aku-Shoin, 1988, pp.
43-68.
9. Rosai .1 , Cold .1 , Landy R. The histiocytoid heman-
giomas: a unifying concept embracing several previ-
ously described entities of skin, soft tissue, large ves-
sels, bone and hearl. Hum Patho11979; 10:707-730.
10. Weiss SW, Enzinger FM. Epithelioid hemangioen-
dothelioma: a vascular tumor often miSu'1ken for
carcinoma. Cancer 1982; 50:970-98l.
11. Dorfman HD, Czerniak B. Bone Tumors. St. Louis:
C.V. Mosby Co., 1998, pp. 769-770.
12. Tsuneyoshi M, Dorfman HD, Bauer TW. Epitheli-
oid hemangioendothelioma of bone: a clinico-
pathologic, ultrastructural and immunohistochem-
ical study. Am] Surg Patho11988; 10:754-764.
13 . .Iayaram C, Kapoor R, Saha MM. Hemangioen-
dothelioma. Cytologic appearances in twO cases
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14. Kilpatrick SE, Koplya)' PO, \Nard WG, Richards F 11.
Epithelioid hemangioendothelioma of bone and
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15. Dorfman HD, Czerniak B. Bone cancers. Cancer
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.IE, Dahlin DC. Hemangioendothelial sarcoma of
bone. Am) Surg Patho11982; 6:59-70.
17. Wu KK, Guise ER. Malignant hemangioendothe-
lioma of bone. Orthopedics 1981; 4:58-64.
18. Campanacci M, Boriani S, Gianti A. Hemangioen-
dothelioma of bone: a study of 29 cases. Cancer
1980; 46;804-814.
19. Gupta RK, Naran S, Dowie C. Needle aspiration cy-
tolo
b
')' and immunocytochemical study in a case of
angiosarcoma of the breast. Diagn O)'lojJf1thol 1991:
7;363-365.
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21. J ayaram G, Kapoor R, Saha MM. Hemangioen-
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sellling with multiple soft tissue and bone lesions.
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22. Mullick SS, Mody DR, Schwartz MR. Angiosarcomas
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23. Liu K, Layfield LJ. Cytomorphologic features of an-
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Cytol1999; 43:407-415.
24. Schindler S, Cajalis RS, Cokaslan ST, Frias-Hidvegi
0 , Yu GH. Fine needle aspiration of primary an-
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phologic aspects of hepatic angiosarcoma: fine
needle aspiration iopsy ofa case. Acta Cyto11982;
26;527-531.
26. Masin M, Masin . Cytology of angiosarcoma of the
breast: a case report. Acta Cyto11 978; 22: 162-164.
27. Randall MB, Geisinger KR. Angiosarcoma of the
heart: pericardial fluid cytology. Diag;n C),lojJalhol
1989;6;58-62.
28. Silverman JF, Lannin DL, Larkin EW, Feldman P,
Frable \-\1]. Fine-needle aspiration cytology of post-
irradiation sarcomas, including angiosarcoma, with
immunocytochemical confirmation. Diagn C)'to-
jJf1thoI1989; 5:275-281.
r"
1-
.... ,
METASTATIC DISEASE
The maj ority of mali gnancies involving bone
represent metastatic disease to bone from
other organs. In a study investigating the ef-
fectiveness of fine needle aspiration biopsy
in the diagonsis and management of bone
lesions, nearly 80% of all aspirates were ob-
tained from metastatic neoplasms. I Others
have reported a simil ar experience.
2
vVhile
the proclivity for metastasis to bone vari es
among malignancies, approximately 30%
of all cancer patients demonstrate metasta-
tic disease to bone duri ng the course of
their disease.
3
,4 Carcinomas of the breast,
prostate, lung, kidney, and gastrointestinal
tract are responsible for SO%
of all metastases to bone.
4
,!) Less frequently,
soft tissue and bone sarcomas are the origin
of bony metastases, accounting for approxi-
mately lS% of cases'"
The radiographic appearance of the bony
deposit may contain clues to the origin of a
metastasis. For instance, purely lytic metas-
tases with a "blowout" appearance are fre-
quently associated with carcinoma of the kid-
ney or thyroid,7 whil e carcinomas arising
within the gastrointestinal tract have a lytic,
nonexpansile appearance. Deposits of met-
astatic prostate carcinoma are well known
for their blastic appearance, while carcino-
mas metastatic from the breast or lung fre-
255
quently produce mixed blastic and lytic le-
sions.
7
The foll owing sections will describe
the most common metastases involving
bone.
BREAST CARCINOMA
Breast carcinomas frequently metastasize to
bone and have characteristic sites of deposi-
tion. Among these the vertebral bodies,
pelvis, proximal femur, and h umerus are the
most frequent. The majority of metastases
from the breast involving bone produce an
osteolytic lesion, but mixed for ms are not in-
frequent.
7
,8
Cytologically, material obtained from bone
deposits of breast carcinoma are composed
of small clusters of round to polygonal cells.
The cells are rather uniform in appearance
and moderate to large in size (Fig. IS- I).
The nuclei are round and show crowding
with overlapping. Cytoplasm is present in
moderate amounts and can be granular to
vacuolated. A characteristic but infrequent
finding is "magenta bodies," which are seen
with Romanowsky staining and consist of in-
tracytoplasmic round globules of magenta-
colored material (Fig. lS-2).
Figure 18-1. Aspirates of metastatic carcinoma of
the breast are characterized by small clusters of
round to polygonal cells with a rather uniform
appearance (Diff-Qui k, X100). These cells have
a high nuclear/ cytoplasmic ratio and are gener-
ally oval.
While metastatic breast carcinomas can
show considerabl e pleomorphism, a com-
mon pattern of metastatic disease is that of
a relatively small to intermediate-sized cell
with a modest amount of cytoplasm and an
overall round to ovoid configuration. Such
cell s are highly suggestive of metastatic
breast or gastri c carcinoma. Occasionally,
metastases from breast carcinoma have a
papillary confi guration, and in the case of
colloid carcinomas produce metastases with
abundant mucin (Fig. I S-3). The cells of
Figure 18-2. A characteristic but infrequent find-
ing in carcinoma of t he breast is the presence of
"magenta bodies." These are best. seen with the
Romanowsky staining technique and appear as
intracytoplasmic round globules of magenta-
colored material (Diff-Quik, X100).
Figure 18-3. Rarely, metastatic adenocarcinomas
of the breast display abundant mucin associated
with single and small nests of round or ovoi d cell s
(Diff-Quik, XIOO).
metastatic breast car cinoma may be positive
for the estrogen and progesterone recep-
tors, B72.3 or BRST-II antigen. These mark-
ers are helpful in suggesting a breast origin.
CARCINOMA OF THE PROSTATE
Adenocarcinoma of the prostate is well
known for its proclivity to give rise to os-
teoblastic bone metastases. Approximately
35% of patients with prostate cancer develop
radiographic evidence of bony disease, with
three-quarters of metastases being blastic.
Cytologically, the majority of smears ob-
tained from bony metastases of prostatic car-
cinoma are of low cellularity due to the dif-
ficulty of obtaining material from blastic
lesions. When carcinoma cells are obtained,
they frequently have a bland appearance
with a cuboidal to low columnar shape and
nuclei showing relatively little atypia or ir-
regularity (Fig. IS-4). ~ c l e O l i are often
prominent. The cells for sheets, clusters,
and occasionally small acina . structures (Fig.
18-4). The presence of a etastatic adeno-
carcinoma with a low-grad appeara nce and
the formation of microaclI1ar structures in a
male patient strongly suggests the diagnosis
of metastatic prostatic carcinoma. Confir-
mation by immunohistochemical staining
for prostatic specific antigen and prostatic
acid phosphatase is helpful.
METASTATIC DISEASE 257
Figure 18-4. Aspirates obtained from metastatic
deposits of prostate carcinoma withi n bone are
generally hypocellular due to the osteoblastic na-
lure of the metastases. However, when material is
obtained, it is composed of small nests and incli-
vidual cells with a relatively bland nuclear mor-
phology. The cells have a cuboidal to low colum-
nar shape, and the nuclei show relatively little
atypia or irregularity (DiffQuik, X 100).
CARCINOMA OF THE LUNG
Approximately 15% of carci nomas arising
within the lungs metastasize to bone. The ma-
jority have a lytic appearance radiographi-
cally.
The cytologic appearance depends on the
histopathologic type of the primary neo-
plasm. Small cell carcinomas are most easi ly
recognized due to the high cellularity of the
smears obtained and the characteristic cyto-
morphology. The cells are relatively small ,
with very scanty cytoplasm surrounding hy-
perchromatic, irregular nuclei (Fig. IS-5).
The nuclei show a considerable amount of
crush artifact. On Papanicolaou staining, the
sa1t-and-pepper chromatin appearance is
characteristic. Nucleoli are occasionally
present but usually are not seen in smear
preparations. Nuclear molding is a charac-
teristic feature of small cell carcinoma of the
lung, and mitotic figures are not infrequent
findings.
Squamous cell carcinomas metastatic to
bone generally demonstrate keratinization
(Fig. IS-6) and large, hyperchromatic, ir-
regular nuclei. Keratin production is most
readily demonstrated 111 Papanicolaou-
stained material. In better-differentiated
forms of squamous cell carcinoma, keratin
Figure 18-5. Small cell carcinomas metastatic to the
bone have a characteristic cytologic appearance.
These cells are small and round in morphology,
with scanty or no visible cytoplasm (DiffQuik,
X 100). The background is bloody and lacks lym-
phoglandular bodies. In some examples there is
considerable nuclear crush and smearing artifact.
pearls and dyskeratotic cell s are frequent. As
differentiation decreases, separation from
poorly differentiated adenocarcinoma be-
comes more difficult, and differential ker-
atin staining is helpful in elucidati ng the ori-
gin of the metastasis.
RENAL CELL CARCINOMA
Nearly one-third of renal cell carcinomas
show metastasis to bone during the course
Figure 18-6. Metastatic deposits of squamous cell
carcinoma in bone show variable cytomorphol-
ogy. Those that demonstrate keratinization are
identifiable as squamous in origin. These exam-
ples have orangophilic cytoplasm and large, hy-
perchromatic nuclei. Necrosis may be prominent
(Papanicolaou, X50).
Figure 18- 7. Aspirates of metastatic renal cel l car-
cinoma are characterized by large neoplastic cell s
that li e singly or form cohesive clusters. The cell s
have moderate to abundant, frequently granular
cytoplasm. The smears often show necrosis with
chroni c inflammation, including scallered foamy
histiocytes (Di ff-Quik, X 100) .
of the disease. Metastases from re nal cell car-
cinoma are freque ntl y hemorrhagic and may
come Lo clinical attenti on before the recog-
nition of the primary. The overwhelming
of re nal cell carci nomas have a
purely lytic appearance radiographicall y,
and the metastasis may have a "blowout" ap-
pearance.
7
Needle aspirates obtained from metastatic
re nal cell carcinoma to bone are frequently
bloody and may contain necrotic debris. The
neoplastic cell s are large and fo rm cohesive
cluste rs and sheets, as well as lying singly
(Fig. 18-7). The indi vid ual cell s have abun-
Figure 18-8. Cywlogic preparations fi'om high-
grade renal cell carcinomas are characterized by
cell s with large nuclei containing very prominent
nucleoli (Di ff-Quik, X500). Often the nucleoli in
these cells are huge and single.
,
,

4('
-.
l-
t

"
,.
4'1
.". ..

Figure 18- 9. Smears from metastatic carcinoma
of the thyroi d often show a follicular appearance
and form either syncytial aggregates or clusters
of mi crofollicles (Diff-Qu ik, XIOO).
dant granular or clear cytoplasm and la rge
nucl ei. In the higher-grade forms (Furh man
grade III and a bove) , the nuclei contain very
distinct macronucl eoli (Fig. 18-8). The pres-
e nce of macronucl eoli in a cell with a clear
cytoplasm is a strong indi cation that the me-
tastasis arose fro m a renal primary. The clear
cell s contain glycogen and/ or lipid.
CARCINOMA OF THE THYROID
Radiographicall y, metastatic deposits from
thyroid carcinoma closely resembl e those
arising from the kidney. Between 7% and
Figure 18- 10. In other examples of papillary car-
cinoma of the thyroid, the aspirates contain frag-
ments of papillary structures. The component
cell s have enlarged, rather pale nuclei with dis-
tinct nucl ear grooves or even in tranuclear cyto-
plasmic pseudoinclusions (Di ff-Quik, XI60) .
METASTATIC DISEASE 259
10% of thyroid carcinomas produce clinicall y
apparent metastases. Favored sites of metas-
tasis include the spine, pelvis, ribs, skull , ster-
num, humerus, femur, and scapula.
Smears obtained from metastati c thyroid
carcinomas often have a folli cular appear-
ance and form either syncyti al aggregates of
cell s or clusters with microfolli cles (Fig.
18-9) . The nuclei a re e nl arged, with a some-
what granula r chromatin a nd prominent nu-
cl eoli. In other cases, the neopl astic cell s
have nuclear features simi la r to those seen
in primary papillary carci nomas of the thy-
roid (Fig. 18-10) . The nucl ei are enlarged,
with chromatin clearing, nucl ear folds or
clefts, and occasio nal intranuclear cytoplas-
mic pseudoinclusions. In my experi ence,
whi le papillary fronds may be seen , they are
di stinctly unusual in metastatic deposits. Im-
munohistochemical staining for thyroglobu-
lin can be of immense aid in identifying the
origin of a metastatic adenocarcinoma as be-
.' ing the thyroid.
SYNOVIAL METASTASES
Metastases to the synovium are rare. Hi sto-
logic types giving rise to metastases include
angiosarcoma, squamous cell carcinoma,
lymphoma, oat cell carcinoma, rhabdo myo-
sarcoma, mela noma, chordo ma, and Ewing's
sarcoma.
IO
The cytologic findings and dif:'
ferential diagnosis are simil ar to those asso-
ciated with bone metastases.
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to. Thompson KS, Reyes CV, j ensen J , Gattuso P, Sacks
R. Synovial melaslasis: diagonsis by fin e-needle as-
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1996; 15:334-337.
Abdominal fibromatosis, 43, 44
Accuracy fine- needl e aspiration, 4, 5, 7
Acquired immune defici ency syndrome, Kaposi's
sa rcoma in, 136
Actin
muscle specific, 9, 10 , 11 , 17,94,98
smooth muscle, 9,10, ] 1,17,9'1,98
Adamantino ma, 243-245
Adenocarcinoma, metastatic, 255-259
Adipose tiss ue, nonnal
cytologic features of, 23
histologic features of, 22
Adul t fibrosarcoma, 49-51
Adult rhabdomyoma,
AIDS, Kaposi' sarcoma in, 136
Alveolar rhabomyosarcoma, 122, 124, 125, 126
cytologi c features of, 126
d iffe rential diagnosis of, 126
hisLOlogic features of; 122
Aneurysmal bone cyst, 2 12, 213, 239
Angiolipoma, 74-75
Angioma, cherry, 131
AngiomaLOid fibrous histiocYLOma, 60-62
Angiomatosis, 131
Angiomyolipo ma, 71
Angiosarcoma, 131, 140, 14 1- 143
Aneriovenolls hemangioma, 131
Askin's tumor, 11 3, 11 4
Bednar 58
Benign fibrous histiocytoma
clinical features of, 53
cytologic features oC 54-55
INDEX
261
differential diagnosis of, 55
Beni gn hemangioma of infancy Uuve nil e
hemangioma),131
Be nign rhabdomyoma, 11 9- 121
Bone cyst
aneurysmal
clinical features of, 2 12
cytol ogic features of, 213
histologic features of, 2 13
radiographic feaLLlres of, 213
telangiect<ltic osteosarcoma simulation of, 240
unicameral
clinical feaLLlres of, 238
difTe rential diagnosis of, 238
radiographic features of, 238
Bone, normal
cYlOlog), of, 32
his tology of, 3 1
Botryoid rhabdomyosarcoma, 122,123,127
Breast , carcinoma, 255, 256
Capillary hemangioma, 131-133
Cartilage-forming lesions, 168- 190,204-205, 219-22 1
Canilage, normal
cytology of, 30
histology oC 29- 30
Cartilaginous tumors, eXlraskeletal
benign, 164, 165
malignant, 162- 164
Cavernous hemangioma, 13]-133
262
CDIA in eosinophilic granuloma, 234
CD34, 11,47
Cellular myxoid liposarcoma, 81, 82, 84, 85, 86, 87
Cellular schwannomCl, 102, 104
Central osteosarcoma, 206
Cherry angioma, 131
Chest \\'all
Ao;kin 's tumor, 114
Chondroblastoma
calcification in , 176, 220
cell nuclei in , 177, 178, 219,220
cytologic fealLlres of, 177- 178, 2 19-220
differential diagnosis of, 220-22 1
gianlcells in, 176, 177, 178
nldiographic features of, 176
secondary aneurismal bone cySt "'ilh, 21 3
Chondro ma
calcification in, 168
chondrocytes of, 169, 170
cl inical signs of, 168
cytologiC features of, \69-170
dirferelllial diagnos iS of, 170
histologic feaLUres of, 168
periosteal, 169
Chondro id lipoma, i7-78
Chondromyxoid fibroma
cli nical features of, 171
cytologic features 01', 171-172
diffe rential diagnosis of, 172-1 73
radiologic features 01', 171
Chondrosarcoma
chondcomyxoid fibcoma dilre rentiation f,-om, 183
clear cell type. 186, 187
cl in ical signs of, 178
cytologic features of, 179, 180, 18 1, 182
dedi fferentiated, 185-186
mesenchymal, 183- [85
calci fication in, 18'1
chond,-oid ponions of, 164
clinica[ signs of, 183
cytologic fealUres of, 184-185
differential diagnosis of, 18,:;
hemangiopericytomatous pattern of, 184
hyali ne canilage of, IS4
radiologic features of, IS3
stag horn-like spaces of, IS4
myxoid stromal quality of, lSI, 182
lllyxoi d subtype, [90
nuclear pleomorphism, 181, 182
ill osteochondl'Oma, cytologic atypia of, 174
radiologic features of, 178
Chondl'os."lrcoma or son pans, 162-164
Chondmsarcoma, eXl!-askeletal , 162- 164
Chordoma
cell cording in, 188
chondmid, 188
clinical signs of, 187
cytoplasmic vacuoles of, IS8, 189
INDEX
cytologic features of, 188, 189
differential diagnosis of, 189, 190
histologic features oC 188
physaliferolls cells oC 188, 189
radiographi c features of, 187
Clear cell chondrosarcoma, ] 86, 187
Clear cell sarcoma, 152-155
COllagen. in fihmsa rcoma, 49
Congenital infamile fibrosarcoma , 49
Conventio nal osteosarcoma, 197, 198- 199,201-204
Cost of fine-needle aspiration, 5
Cutaneous leiomyoma, 89, 90, 91,92
Cyst, bone. See Bone cyst, aneurysmal; Bot}e cyst,
unicameral
CySts
ganglio n, 148, 149
intraosseous epidennal, 241
intraosseo us ganglio n C}'Sl, 240
simple bone CYSt, 238-239
subchondral, 241
un icameral bone cyst, 238- 239
Deditferentiated chondrosarcoma, [85-186
Dediffere ntiated liposarcoma, 82, 83, 85, 86
Deep fibromatoses. 44-46
Deep leiomyoma, 90-92
Dermatofi brosarcoma protuberans, 58-60
cytologic fi ndings, 58-59
differential diagnosis, 59-60
histologic findings , 58
Desmin, 121 , [28
Desmoid, 44-46
Desmoplastic fibroma, intraosseous, 245-246
Diagnostic approach to cytologiC analysis of bone and
soft tissue lesions, 9-19
Di ffuse giant cell lUmOt- of tendon sheath,
clinical fea tures oC 55
cytologic findings , 56-57
differential diagnosis, 57
histologic findin gs, 56
Di ffuse neurofibroma, 105, 106, 107
Dupuytren 's Contracture, 43
DysplaSia, fibrous
clinical featu res of, 208
cytologic featmes of. 209-210
histologic femures of. 209
osteoid of, 209
polyostotic, 208
radiographic features of, 208-209
spindle cell stroma of, 209
vs. low-grade central osteosarcoma, 201
Ectomesenchymoma, 11 6
Elastofibroma. 41
Embt)'onal rhabdomyosarcoma, 122, 123, 126, 127,
128
Endothelial cells, of hemangioma, 132, 3
Eosinophil s, in histiocytosis X, 233-234
Epithelioid angiosarcoma, 141
Epithelioid hemangioendothelioma, 134-13
Epithelioid hemangioma, 132, 133
Epithelioid leiomyoma, 93-94
Epithe[ioid leiomyosarcoma, 92-94
EpitheliOid neurofibroma, 105
Epitheli oid sarcoma
clinical fi ndi ngs of, 157
cytologic findings in, 158, 159
differential diagnosis, 159, 160
histologic findings, 157, 158
EpitheliOid $chwannoma, malignant, 110
Ewing's sarcoma, 225
cytologic findings, 226-228
differential diagnOSiS, 228
histologic findings, 225-226
nuclei of, 226. 227
on ion skin appearance of, 225
permeative nature of, 225
radiographic find ings, 225
roll nd cells of, 225, 226, 227
Extraabdominal fibromatosis
clinica[ features of, 44
cyLOlogic features, 44-45
histologic features, 44
Extrarenal rhabdoid tumor
cytologiC features, 161- 162
histologi c features, 160-161
Extraskelelal chondmma, 164-165
Exu-askeletal chondrosarcoma, 162-164
Extraskeletal Ewing's sarcoma, 11 3- 1 14
Factor VIII-related antigen II , [I
Fasci itis
nodular. 34-37
prol iferative, 37-39
Fetal rhabdomyoma, 119
Fibroblastoma, giant cell , 68-69
Fi brohistiocytic lesions, 53-68
Fibrohystiocytic tumors
benign, 53-55
low-grade malignant, 58-62
malignant, 62-68
Fibromatosis
cytologic features, 44-45
deep, 43
diffe rential diagnOSiS, 45-46
Fi bromatosis colli (torticolis), 44
Fibrosarcoma
adult, 49-5 1
cylOlogic features, 49-50
histologi c features, 49
Fibrosing liposarcoma, 81
Fibrous cortical defect, 221, 223
Fibro us dysplasia, 208-210
Fi brous hamartoma of infancy, 47-49
cytologiC features, 48
hislOloic features, 47-48
INDEX
Fibrous hi stiocytoma
angiomatoid, 60-62
benign, 53-55
malignant, 62-68
Fibrous les ions, 34-51
Fibrous tiss ue, normal
C)'tology of, 28-29
hislOlogy of, 28
Fibrous tumor, solita!)', 46
Fracture callus, 193-195
Gang[ion, 26, 27
Gial1l cell (s), of aneurysmal bone cySt, 213
of benign fibrous histiocytoma, 54, 55
of chondroblastoma, [76, 177, 178
of chondromyxoid fibroma, 171 , 172
of giant cell tumor, 216, 217, 2 18
of histiocytosis X, 233. 234
of hyperparathyroidism, 21 4
263
of malignant fibrous histiocytoma, 62, 63, 64, 65, 66, 67
of osteosarcoma, 223
Giant cel[ fibroblasloma, 68-69
Giam cell reparative granuloma, 2 [5-2 [6
Giant cell tumor, te nosynovia[
cl inical features, 55- 56
histOlogic features, 56
Giant cell tumor of bone
cytologiC features or, 2 17-218
diffe rential diagnosis of, 2 [8, 2 [9
giant cells of, 217, 218
Glandular differelllialion, in ma[ ignam peripheral
nerve sheath tumor, 110
Glomus tumor, 134
Gr-"I ding of sarcomas by fin e-needle aspiration , 7, 8
Granul ar cell tumor, 108-1 10
clinical features, 108
Granu[oma, pyogenic, 13 [
Granu[oma, reparati ve. giant cell , 2 15, 2 [6
Granulomatosis, L"lngerhans' cell, 233, 234
Hamanoma, fibrous, of infancy, 47, 48. 49
Hamartoma, of chest wall , 170
Hazards of fine-needle aspiration, 5
I-Iemangioendothel ioma,
epithelioid, 134- 136
cytologic features of, 135- 136
histologic features of, 134- 135
spindle ceil , 134
Hemangioma
capi llary, 131
cavernous, ] 31
cytologic features of, 132- 134
difierentia[ diagnosis of, 133, 134
epithelioid, 133
intramuscular, 132, 133
264
J-I emangiopericywma
clini cal fealUres of, 138
cytologic features of, 139-140
diffe rential diagnosis of, 140
histologic features of, 138-139
1-lemalOpoielic lesions, 228-231 > 231-232
I-i ibernoma, 78-79
His!..i ocytoma, fibrous
benign, 53-55
malignant, 62-68
Histiocytosis X
eosinophils in, 233
giant cells or, 234
granules of, 233
Langcrhans' cel l of, 233
Hyperparathyroidism, 2 14, 2 15
Infancy
fibrous hamartoma of, 47-49
pigmented neuroectodcnnal tumor of, 235
InElIl1ile fibrosarcoma, 49
Infantile myofibroma and myofibromatosis. 42-43
Inflammatory malignant fibrous histiocytoma, 62, 64
inll<llllusclilar hemangioma, 132, 13J1
Intramuscular lipoma, 73
In tramuscular myxoma, 146 , 147, 148
Kaposi's sarcoma
clinical fe<11Ures of, 136
cytologic featu res of, 136- 138
differential d iagnosis 0[, 137
h istologic featu res of, 136
Langerhans' cell, of histocytosis X, 233-234
Lciomyobl astoma, malignant, 92
Leiomyoma
angiomyoma, 90
cutaneous, 89-90
deep, 90
V'dscular features of, 90
Leiomyosarcoma
deep, 95-98
epithelioid, 92-94
reu'operitoncal a nd intraalxlo milMI , 95
soft tissue, 95-98
spindle cel l, 95-98
Leu 7, 226
Lipoblastoma, 79, 80
Lipoma
angiolipoma, 74-75
chondroid, 77
intramuscular, 73
myelolipoma, 77
pleomorphic, 76
rNDEX
spindle cell , 75-76
te ndon sheath , 74
well-differentiated, 71 - 73
Localized giant ce ll tumor of tendon sheath , 55-57
Locali zed neurofibroma, 105-107
Lungs, carcinoma of, metastatic, 257
Lymphoma, malignant
cl inical signs of, 228
cytologic fealUres of, 229-230
differe ntial d iagnosis of, 230
radiograph ic featu res of, 229
Mali gnant epithel ioid schwannoma, I I I , 112
Malignant fibrous histiocytoma
gia nt cell, 63- 64, 67
innammatory, 64
myxoid , 63, 66-67
storiform/pleomorphic, 62-63, 65-66, 67
Mal ignan t leiomyoblas toma, 92-94
Malignant lymphoma, 228-230
Malignant melanoma of soft parts
cli ni cal features 152
cytologic featu res of, 153-- 154 , 155
differential diagnosis 154
histologic features oC 152-153
Mali gnant per ipheral nerve sheath tumor
clinical features of, I 10
cytologic features 01', 11 1- 11 2
difTerential diagnosis 112-113
histologic fealUres of, 110- 1 I 1
Malignant schwannoma, 110
Mesenchymal chondrosarcoma, extraskeletal, 183
Mesenteric fibromatosis, 44
Mec:aslalic carcinoma, 255-259
MFI-I, See Malignant fibrous histiocytoma
MIC2,226
Morton's neuroma, 100
MPNST, St.'(> Malignant peripheral nerve sheath tumor
Muscle specific actin, 9, 10, ll , 17, 94 , 98
Musc uloaponetl rotic fibromatoses, 43-46
Myelol ipoma, 77
Myeloma
cytOlogic fi ndings of, 231-232
di!1erential diagnosis of, 232
histologi c findings of, 231
nuclear pleomorphism in , 231 , 232
plasmacytic dinerentiation in, 23 1, 232
radiographic features o f, 23 1
Myofibroma and myofibromatosis, 42, 43
Myogenic tumors
smooth muscle
benign, 89-92, 93, 94
malignam, 95-98
stri ated muscle
benign, 119-12 1
malignan t, 12 1- 129
normal , 23- 24
INDEX 265
Myoglobi n, 121 , 128
Myositis, prolife rative, 37-39
Myositis oss ificans, 39-41
Myxoid chondrosarcoma
extras ke letal , 162-164
Myxofibrosarcoma, 51
Myxoid liposarcoma, 8 1, 84, 86
Myxoid malignant fibrous histiocytoma, 62, 63, 66, 67
tvl yxoma, 1'16- 148
N-C..AM, 110
Nen'e sheath tumor, malignant pe riphe ral, 110- 113
Nerve tumors
Morton 's neuroma, 100
traumati c ne uroma, 100
Neurilemmoma
clinical features 100-101
cytologic fe aLUres or, 103- 104
histologic feallires o f, 101 - 103
Neuroectodermal tumors
malignant, 113--116
Neuroepithelioma, PNETj peripheral , 113-116
Neurofibroma
clinical features of, 105-106
cytologic features or, 107
histologic featu l'es, 106-107
Neurofibromatosis (von Recklinghauscn's disease),
103, 110
Neuroma
Morton 's, 100
tnwll1a1i c, 100
Neuron specific enolase, 226
Oilie r's disease, 169
Ossifying fibromyxoid tumor of soft parts, 210
Osteoblastoma
clinical signs 01',195-196
cytologic features 0[, 196
hisLologic features of, 196
Osteochondroma, 173- 175, 208
Osteitis fi brosa cystica, 214
Osteoid-forming lesions, 19;1-210
Osteoid Osteoma, 8, 195
Osteomyelitis
acute, 208, 234
chronic, 208, 234
Osteosarco ma
ce ntral , low-grade, 201 , 206
co nventional
chondroblastic, 204, 207
clinical signs o f, 197
cytologic of, 204-207
ditlere ntial diagnosis of, 207- 208
histologic features of, 198-200
radiographic features of, 197-198
fib ro blastic, vs. fibrosarcoma, 199
paroSleal
differe ntial diagnosis or, 207
fibrous dysplasia simulation by, 207
histologi c features of, 200-20 1
periosteal
cytOlogic features of, 206
difierelllial diagnosis of, 207
histologic fea1ures of, 201
Small cell
cytologic fealUres of, 205
hisLOlogic features of, 205
telangiectatic
aneurysmal bone cyst simulation by, 200
blood-filled spaces of, 200
cYl.ologic features of, 205
differential diagnosis of, 207-208
h istologic featu res of, 200
I-tldiogr"phic features of, 197
Palmar fibromatosis,
Papillary carcinoma, t hyroid, Melastatic, 258, 259
Parosteal osteosarcoma, 197, 200, 20 I, 206, 207
Pcrineuroma, 107- 108
Periosteal chondroma, 169
Periosteal osteosarcoma, 198, 201 , 206, 207
Periphe ral IlI:TVe, normal, 26, 27, 28
Pe ripheral nerve sheath tumor, malignan t., 110-1 13
Periphe ral primitive neuroectodermal Ulmor,
malignant ( PNET)
clinical features of, 11 3
cytOlogic features of, I 14, I IS, I 16
dilfere nti al diagnosis of, 116
histologiC leatlln.;s, 11 ' I
PCI) 9. 5, 9, 10, 110.113
Pigmented ne uroectodermal tumor of infancy, 235
Plantar fibromatosis, 43
Pleomorphi c lipoma, 76, 77
Pleomorphic liposarcoma, 82, 85
Pleomorphi c malignant fibrous histiocytoma, See
sto l' ilorm-pleomorphic malignant fibrou s
histiocytoma,
Pleomorphic dlabdomyosa rcoma, 121 , 124, 128
Plexirorm ncurolibroma, 106
PNET. See Periphe ral pl"imitivc neuroectodermal
lumor, malignant
Proliferative fasciitis, 37- 39
Prqliferativt: myositis, 37-;19
Pyogenic granuloma, 13 1
Reticulin stain in hemangiopcricyto ma, 139
Retinal anlage tumor, SI'(I Pigmented neuroectodermal
tumor of infancy
Rhabdoid tumor, extrarenal, 160- 162
Rhalxlomyoblastic dilfe reJltiation, in malignant
peripheral nerve sheath tumor, 11 0
266
Rhabdomyoma
adult
cl ini cal features of, 11 9-1 20
histologic feaLUres of, 120
fetal , Jig
geni tal, 1 19
Rhabdomyosa rcoma
alvcolar, 122, 126
bOlryoid , 123
embryonal , 122, 126- 127
pleomorphic, 124, 128
spindl e cell , 124
Round cell li posarcoma, 82, 85, 87
$-100 protein stain, in
eosi noph ili c gr<lnuloma, 234
nerye sheath tumors, 103, 105, I 10, 113
Sarcoma
alveolar soft part, 155- 157
angiosarcoma, 141- 143
clear cell, 152- 155
epithelioid, 157- 160
Ewing's, 225-228
extraskelcwl chondrosarcoma, 162- 164
fibrosarcoma, 49-5J
K.t'l.posi's, 136--138
leiom),osa]-coma, 95-98
li posarcoma, 80-87
rhabdomyosarcoma, 121- 129
synovial, 149-152
Schwannoma
clini cal features of, 100, 10J
c),tologic featu res of, 103-104
differential diagnos is, 105
hisLOlogic fealUres of, 101-103
Sclerosi ng liposarcoma, 81
Si mple bone cySt, 238-239
Smooth muscle tumors
benign, 89-92, 93
malignant, 93, 95-98
Smooth muscle, no rmal, 24, 25, 26
Solid aneurysmal bone c),st, 214
Spindle cell <ln giosarcoma, 141 -1 '13
Spindl e cell hemangioendothelioma, 134
Spindle cell lipoma
clinical features o f, 75
histologic fealLlres of, 75
INDEX
Sloriform pleomorphic ma lignant fibrous
histiocytoma, 62, 63, 65, 66
Striated muscle myogeni c tumors
benign, 11 9- 121
malignam, 121-129
Striated muscle, normal, 21, 23
Synaptophysin , 226
Synovial sarcoma
biphasic, 149, 150
cl inical features of, 149
C)' tologic features of, 151- 152
histologic fealures of, 149-150
monophasic fibrous, 149
Synovial tumo rs
malignant, 149- 152
metastasis, 259
Technicallimilations o f fi ne-needle aspiration, 8,15
TelangiecLatic osteosarcoma, 197, 200, 205, 207
Tenosynovial giant cell tumor
C),toiogic featu res of, 56-57
di ffuse type, 55, 56
Thyroid, folli cular carci noma of, mel,astatic, 258-259
Tibia, adamanti no ma of, 243-245
Transplantation, Kaposi's sarcoma and, 137
Trauma, myosi ti s ossificans and, 39
Traumatic ncuro ma, 100
Treatmcnt prolOcols for sarcomas, 6
Unicameral bone CYSt
cli nical features of, 238
cytologic feaLUres of, 239
problems in diagnosis, 239
radiologic featu res of, 238
Vasculal lei omyoma, 90
Vascular lesions, 13 1-1 43
Vascular tumo rs
benign, 13 1-1 34
borderline, 134- 136, 138- 141
malignanl, 14 1- 143
Vc roca), bodies, 101, 103
von Reckli nghausen's d isease (neurofi brornalosis),
103, 110
Well -differentiated liposarcoma, 8 1, 83, 87

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CARTILAGINOUS TUMORS

A varie ty of neoplasms occurring withi n the

bone cyst, also referred to as

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