Copy

right

t 9144 b

The

Journal

Dedifferentiated
BY

LESTER

E.

WOLD,

M.D.*,

From

the

Section

K.

DAVID

of Surgical

UNNI,

C.

malignant

Clinic
records
differentiated

we identified
eleven
parosteal
osteosarcoma.

patients
had
recurrences

cases

Pathology

and

Clinic

Mayo

then

for a definite

grade
undifferentiated
this group of patients

for multiple
parosteal
os-

recurrence

osteosarcoma.

Parosteal
clinicopathological

osteosarcoma
entity

most

in
with

osteosarcomas

described

in

the present
report were found by a review
of the records
of
tumors
occurring
on the surface
of bone
that is, tumors
that lack medullary
involvement
not all of the surface
lesions
in our series were low-grade
parosteal
osteosarcoma.
A variety
of other tumors
develop
on the surface
of bone,
-

including

periosteal

chondroma

periosteal

osteosarcoma,

and various
surface
tumors
that extend
into the
areas of bone and have the histological
appearance
intramedullary

osteosarcoma

reactive
conditions
can occur
on the
marrow.
Previous

of parosteal,

BEABOUT,

medullary
of either
.

or juxtacortical,

M.D.*,

FRANKLIN

H.

SIM,

M.D.*.

MINNESOTA

of Diagnostic

Foundation,

Radiology

and

Orthopedics.

Rochester

patients
in whom
dedifferentiation
coma was evident.
We undertook
clinical
and prognostic
correlates

of parosteal
osteosarthis study to define
the
of histologically
high-

grade malignant
tumors
that coexist
with or are derived
the usual low-grade
parosteal
osteosarcoma.

We identified
osteosarcoma

review
logical

from

Observations

eleven

cases

in fifty-five

for six
sections

ofdedifferentiated

patients

tumors

of the
were

eleven
available

(including
sections
of the
When
necessary,
additional
milled

for evaluation,

or absence

who

parosteal

were

in particular

of evidence

There

were

patients.
and
for review

original
tumor
histological

treated

at the

seven

in five
material
the

female

of them).
was

and

four

male

sub-

presence

involvement.

were obtained
from the referring

of the onset of symptoms

six were in their teen-age

Clinical
from the paphysicians.
patients.

At

or at the first attempt

at
years. three were in their

twenties,
and two were in their thirties.
were those
most commonly
associated
bone
of these

multiple
histofor all patients

to document

of medullary

data and follow-up

information
tients charts and from letters
the time
therapy,

Even such
hematomas
toward
the

or osteochondroma

as ossifying
or calcifying
surface
of bone and extend

studies

W.

ROCHESTER,

Mayo Clinic
for parosteal
osteosarcoma.
These
eleven
patients comprised
perhaps
1 per cent of the approximately
1 ,200 patients
who were seen with osteosarcoma.
Gross
specimens
of the high-grade
recurrence
were available
for

was first described

as a distinct
in 195 1 , but it was called parosteal

of the parosteal

corp()r(It.

Clinical

osteoma8.
Since
that time,
there has been a general
consensus
in the literature
that the tumor
is of low-grade
malignancy,
as pointed
out in reports
of several
small series72.
Although

It

as a high-

osteosarcoma.
The prognosis
was similar
to that in patients

conventional

Osteosarcoma

the Departments

and

of so-called
deTen of the eleven

had a long history

of treatment
of the tumor
as a low-grade
and

.Surgert

JOHN

M.D.*,

Parosteal
osteosarcoma
is an uncomtumor
of bone,
and in a review
of Mayo

ABSTRACT:

teosarcoina

M.D.*,

DAHLIN,

Maw

mon

id Joint

Parosteal

KRISHNAN
AND

of Bot .a,

The

initial symptoms
with neoplasia
of

that is, pain or a mass,

or both. The distribution
tumors
was equivalent
to that associated
with or-

dinary

low-grade

parosteal

in the

distal

of the

part

osteosarcoma:
femur:

two,

eight
in the

tumors

proximal

were
part

of

have included
mention
of the occasional
occurrence
of highgrade anaplastic
tumors
that do not fit the usual patterns
that
are associated
with
parosteal
osteosarcoma579#{176}24.
In
most of these reports
a low-grade
parosteal
osteosarcoma
dedifferentiated
,
after
multiple
recurrences,
to highgrade tumor.
In 1979, Dunham
et al. reported
on a patient

the humerus;

with
into

that had transformed

This had previously
been

second,

such

of the first operation

to the time of dedifferentiation
ranged
from thirty-one
to 396 months,
with a mean of I 53 months
(Table
I). At the time of dedifferentiation.
six patients
had

a large parosteal
osteosarcoma
a high-grade
osteosarcoma.
from

mation

had

the
been

VOL

Mayo

present

66-A,

200

reprint

NO.

First

requests

JANUARY

Clinic;
in three
with

series

Clinic.

address

noted

patients

I2

The

Mayo

of fifteen5

parosteal

to Dr.

954

of

SW.
Wold.

and

transforseven

of

osteosarcoma.

consisted
Street

a so-called

eleven

Rochester.

Mayo
Minnesota

Clinic
55905.

one,

patients,
and

in the proximal

one had
high-grade

part

of the tibia.

coexistent
low-grade
dedifferentiation

Of

parosteal
when
first

seen.

reported

Please

the eleven
osteosarcoma

and

the

Dedifferentiation
time of the first
The

a minimum

was documented
in three patients
recurrence.
in five at the time of

and in two at the time of the third recurrence.

interval
from the onset of symptoms
or the

amount

involvement.
Radiographs
were available

for

(less

than

one

or photographic
seven
of the

centimeter)

at

the

tinie

of medullary

copies
of radiographs
eleven
patients.
Interpre53

54

L.

E.

WOLD,

Fio.
Figs.
1-A. I-B. and
Fig. I-A: Preoperative
femur
is altered.
Fig. 1-B: Appearance

tations

I-C: Dedifferentiated
radiograph
showing
one

of the radiographs

year

after

were

K.

K.

UNNI,

J.

W.

BEABOUT,

were

located

available

osteosarcoma
broad-based.

was

shaved

in the distal part

heavily
mineralized
off

the

for the remaining

of the bone

and had the

typical
characteristics
of parosteal
osteosarcoma.
None had
any evidence
of medullary
involvement.
Serial radiographs
showing
the entire
course
of the tumor
were available
for
two patients
(Figs.
1-A, 1-B, and 1-C). In both of them the
parosteal
osteosarcoma
was originally
thought
to be a benign
tumor
(Fig.
1-A). Follow-up
radiographs
showed
postoperative
changes
(Fig. 1-B) and then a mass appeared
on the
surface
of the bone or in the adjacent
soft tissues
(Fig.
1-C) at the site ofthe
previous
operation.
In all five patients
for whom preoperative
radiographs
could be compared
with
radiographs
made at the time ofdedifferentiation,
the degree
of mineralization
of the tumor matrix
was consistently
less
in the

dedifferentiated

parosteal
osteosarcoma.
All patients
except
as the

patients

initial

were

treatment.

treated

tumor

than

SIM,

AND

it had

D.

C.

FIG.

parosteal
a typical

the tumor

on the surface

H.

1-A

patients,
and all indicated
that the tumor was on the surface
of the bone.
Radiographs
made before
any surgical
procedure
had
been performed
were available
for five patients.
All of the
tumors

F.

been

in the

initial

one (Case 1 1 ) had biopsy or excision

At the time ofdedifferentiation,
nine
with amputation;
one. with disarticu-

surface

DAHLIN

1-B

of the finiur.
parosteal
osteosarcoma

of the

with

lobulation.

The

tubulation

of the

femur.

lation;
and one. with forequarter
amputation.
In general,
the gross appearance
of the tumor
at the time of dedifferentiation
was somewhat
similar
to that of a usual low-grade
parosteal
included

osteosarcoma
(Fig. 2). The
areas of dense
hard tumor,

general
characteristics
a broad
base, a bos-

selated
surface
with or without
a cartilage
tion of surrounding
skeletal
muscle.
Areas

cap. and infiltrathat were proved

histologically
to be dedifferentiated
were grossly
softer.
Histologically
these tumors
often had areas of low-grade
parosteal
osteosarcoma,
characterized
by parallel
arrays
of
irregularly
shaped
osseous
trabeculae
with an intervening
spindle-cell
component
were anaplastic
high-grade
ferentiation
high-grade
areas had

(Fig.
3). Adjacent
foci, often with

and the fine lacelike

osteoid
intramedullary
osteosarcoma
less well formed,
dense
osteoid

to these
spindle-cell

areas
dif-

of conventional
(Fig.
4). These
production
than

did the adjacent

low-grade
portions
of the tumor.
The anaplasia
within
these foci was considered
to be grade 3 or 4
according

to Broders

method.

Six

of the

tumors

the medullary
cavity
at the time of dedifferentiation
5). In two patients
the medullary
component
was
and

in four there was gross

Follow-up
information
THE

involved
(Fig.
minimum

medullary
involvement.
was available
for nine

JOURNAL

OF BONE

AND

JOINT

of the
SURGERY

DEDIFFERENTIATED

OSTEOSARCOMA

55

and free of disease,

five patients
without
and free of disease,

and one could not be followed.

Of the
medullary
involvement,
two were alive
two had died of the disease.
and one

PAROSTEAL

could

not be followed.
Discussion
The 20 per cent incidence
parosteal
osteosarcomas

grade

of dedifferentiation
of lowin patients
at the Mayo Clinic

is evidence

of the importance

of correct

diagnosis

and treat-

ment

the lesion

seen.

incidence

is higher

when

is first

This

than that reported

in other series
but
selection
bias at our institution.
Seven
study
were
dedifferentiation

referred
to the Mayo
was documented.

2, and 3; Table I) who

Clinic
were seen before

as a clinicopathological

surgical

treatment

become

with

more

recurrence

anaplastic

there

Three
centimeter
tumor.

years and three

mass is seen

months
on the

a poorly
mineralized
fourbone.
indicating
a recurrent

hand,

A tumor
of the distal part
the bone.
this dedifferentiated
after amputation.

of

of the femur
parosteal

that recurred
osteosarcoma

rapid

growth

dedifferentiation.

with

they
each
regard
din.

a lesion

or

radiographic

severe
lyric

pain
defects

the classic
appearance
of low-grade
may be helpful
in identifying
pa-

dedifferentiation.

period.
Although
medullary
cavity.
The

dedif-

are generally
lowbut have a tendency
to

At the time

high-grade
component
of these tumors
prognostic
indicator.
A similar
risk of dedifferentiation

twice in a twenty-three-year
now also involves
the

initial
and

recurrence
of a parosteal
with dedifferentiation
On
of

Also,

within tumors
that have
parosteal
osteosarcoma

Inadequate

recurrence

for dedifferentiation.

the

other

at the Mayo
was rec-

index of suspicion
with
there may be no significant

to distinguish
a true
from a recurrence

tients
eleven
patients.
Five had died of the disease
and four patients were alive (Table
I). Ofthe
six patients
with medullary
involvement,
three had died of the disease,
two were alive

a high
because

ical clues
osteosarcoma
suggests

after operation.
surface
of the

is potential
have

time that
(Cases
1,

recurrence354.
Although
malignant
potential,
with

a low-grade

One must
to dedifferentiation

1-C

for

osteosarcomas
at the onset

maintain

at the
patients

entity.

allowed

ferentiation.
Parosteal
grade malignant
tumors
may

FIG.

Clinic
Three

were treated initially

parosteal
osteosarcoma

ognized

thus

this may be due to a

of the patients
in this

a large
patient

of recurrence,

is the most
has

been

the

important
noted

for

portion
of the neoplasm
is on the surface
died of pulmonary
metastases
three years

56

1..

1.

WOI.D.

K.

K.

UNNI,

J.

W.

BEABOUT,

F.

H.

SIM,

AND

D.

C.

DAHLIN

TABLE
ClINICAL

Initial

Site of
Lesion

Case

Sex.

A.e

( Yr.

I)kt.
piO
femur

(I

Ni.

Prox.
part
humerus

of

I)ist. part
fentum

Operation

Date

First
Type

Recurrence

Second

Date

Treatment

Recurrence

Date

Treatment

4 18 27

Excision

I 1/8/28

Amputation

F. 3()

62835

Biopsy

9/4/35

Excision

10/29/35

Excision

of

F.

4,547

Excision

9/18/48

Excision

I 1/21/49

Disartic.

I)ist. part
fetiwr

of

NI. 2()

1971

Excisiont

1974

Amputation

Prox.
part
humerus

of

M.

1945

Excision

1958

Subtotal
removall

2/78

Amputation

1)1st.

of

F.

3(1

1964

Excisioni

I 1/1/78

Aniputation

I)ist. part
fetitur

of

F.

I I

1971

Biopsy

1975

Excisions

8/17/81

Amputation

Dist. part
femur

of

F. 24

1932

Excisionl

1934

Biopsyl

1936

Biopsyl

1)1st. part
fermium

of

F.

16

1956

Excision

1956

Excision

7/22/70

Amputation

part
femur

of

F.

15

1927

Incomplete
removall

1933

Incomplete
removaI

1937

Amputation

4/29/81

Amputation

part

lS

14

19

femur
7

It)

I)ist.

I I

Prox.

the onset

At

Symptoms

1: Performed

and

of svmptonls
preceded

the

or at the
first

initial

operation

operation.

by nine

years.

elsewhere.

well

dedifferentiated

ries

of

had

changed

Unni

NI. 28

metaph.

of tibia
fibula

et

intra-osseous
al.5.

from

three

of

a low-grade

osteosarcoma;
eleven

tumors

to a highly

in the sethat

lesions,
an aggressive
is imperative.
This
al. , who indicated

recurred

undifferentiated

prognosis

tumor.
Because

of the

potential

for

dedifferentiation

of

quacy

these

FIG.

.istn area
and eosin.

of mesidual
X
2 It)).

lots gmade

parosteal

osteosarcotita

s ith parallel

bone

are

the

surgical
approach
to the initial lesion
has been emphasized
by Enneking
et
that the most important
factors
in the
surgical

of the surgical

stage

of the

lesion

and

the

ade-

procedure.

trabeculae

and

intervening

hypercellular

THE

fibrous

JOURNAL

connective

OF

BONE

tissue

AND

(hematoxylin

JOINT

SURGERY

DEDIFFERENTIATED

PAROSTEAL

57

OSTEOSARCOMA

DATA

Third

Recurrence

Date

Treatment

9i24l

Disartic.

Amputation

7646

In our series
as stage

lB

ten ofthe

according

Date

Condition

9/13/30

Died

127

22

No

12843

Died

75

15

Yes

10 1381

No evidence

of disease

31

384

No

12 1 1 8 1

No evidence

of disease

36

84

Yes

4:781

Died

396

36

Yes

180

No

120

Yes

5 52

Died

Slight

220/80

No evidence

Slight

I 1343

Died

No

6 9:82

No evidence

lesions
staging

et al. , because
they were of low grade
into the underlying
marrow
or penetrate

would
system

be classified

cle
that is, the lesion occupied
the potential
paraosseous
space.
In the remaining
patient
(Case
1 1 , Table I), who had
areas of high-grade
tumor when first seen, the lesion would

treatment.

VOL.

66-A,

NO.

1. JANUARY

1984

these

120

228

72
0

14

osteosarcoma

should

for
stimulate

dedifferentiation
increased

of a
interest

control
of the primary
lesion by effective
surgical
In this series,
all ten patients
who had a parosteal
osteosarcoma
when they were first seen had a standard
marginal excision,
as advocated
by Enneking
et al. For local

FIG.

of

168

to

in initial

areas

71

of disease

parosteal

adjacent
to that shown
in Fig. 3. Other
(hematoxylin
and eosin.
x 825).

168

be classified
as stage hA.
Awareness
of the potential

of Enneking

and did not

the overlying

of disease

extend
mus-

A region
osteosarcoma

Time from
Dedifferentiation
Last Follow-up
(Mos.)

No

initial

to the

Time
from
Onset
to
Dedifferentiation
(Mos.)

Follow-up

Medullary
Involvement

tumors

4
were

histologically

identical

to conventional

high-grade

intramedullary

58

L.

E.

WOLD.

K.

K.

UNNI,

J.

W.

BEABOUT,

FIG.

Permeation
thin intervening

control

of the medullary
cavity
neoplastic
trabeculae

of the tumor

and

b a residual
(hematoxylin

prevention

of

surrounding

normal

osteosarcoma.
x 80).

of recurrence

tential
dedifferentiation,
our current
resection
to obtain
a wide surgical
envelope

low-grade
and eosin.

with

tissue.

Unfortunately,

if

the parosteal
lesion dedifferentiates
into a stage-Il
lesion
that is, a tumor
with extracompartmental
extension
-

potential
for a successful
Few of these tumors
are

po-

approach
is wide local
margin
that includes
an

limb-salvage
small enough

F.

H.

SIM,

the

procedure
is lost.
to be treated
ade-

D.

C.

DAHLIN

5
Note

that

the

pre-existing

benign

bone

trabeculae

are

broader

than

the

three,
fifteen,
ten, and fourteen
years;
if high-grade
osteosarcoma
had coexisted
with the original
lesions,
recurrence
would
probably
have been much
earlier.
Moreover,
adequate

sampling

of the

not a problem

AND

recognizable
sarcoma.
densely

because

dedifferentiated

and different
from
The usual
low-grade
ossified;

tumor

the dedifferentiated

in contrast,

areas

the usual
parosteal

the

areas

is generally
are grossly

parosteal
osteoosteosarcoma
is

of dedifferentiation

quately
with resection,
and treatment
for dedifferentiated
parosteal
osteosarcoma
is similar
to that for conventional
high-grade
osteosarcoma
and generally
involves
amputation.
Although
the incidence
of dedifferentiation
to highgrade osteosarcoma
in patients
with recurrent
parosteal
osteosarcoma
is significant,
recognition
of the coexistence
of

are often softer and less densely

ossified.
The survival
rate of patients
with dedifferentiated
parosteal
osteosarcoma
has been worse
than that of patients
with the usual parosteal
osteosarcoma.
The prognosis
for
our patients
appears
to be similar
to that for patients
with

low-grade
first seen.

A variety
of histologically
different
osteosarcomas
develop
on the surface
of bone.
Because
of differences
prognosis,
these tumors
should
be considered
distinct

this

series.

and
Such
This

high-grade
coexistence
emphasizes

tumor
was

is rare when a patient

seen in only one patient

the necessity

pling of a parosteal
osteosarcoma
initially
dedifferentiation
has not already
occurred.
which
many of the patients
were treated
being
referred
to
whether
the initial

of adequate

is
in
sam-

to be certain
that
In this series,
in
elsewhere
before

the Mayo
Clinic,
one must
question
sampling
of the tumor
was adequate
to

rule out the possibility

that some areas of high-grade
malignant
tumor
were present
from the onset.
In addition
to
the patient
with coexistent
low-grade
and high-grade
surface
osteosarcoma,
of the primary

slides
lesion

were available
in five patients.

for adequate
In the five

sampling
remaining

patients,
the original
histological
material
was not available
for review
and the historical
information
was not sufficient
to confirm
that there was no coexistent
high-grade
tumor at
the time
patients,
treatment

that the patient

was originally
treated.
In these five
however,
the intervals
from the time of initial
to the time of dedifferentiation
were ten, thirty-

high-grade
volvement

intramedullary
does not appear

icopathological

entities.

mas can be associated

is restricted

ment
larly,

As a group,
with

to surface

and that
periosteal

are

osteosarcoma
to indicate

Medullary
ina poorer
prognosis.
.

parosteal

can
in
din-

osteosarco-

a good

tumors

histologically
osteosarcomas

prognosis
if the diagnosis
that lack medullary
involvelow-grade
(Fig. 4).
form a less common

Simibut

equally
distinct
group with specific
prognostic
implications
if the diagnosis
is restricted
to surface
tumors
that lack
medullary
involvement
and that are lobulated
and predominantly
chondroblastic.
High-grade
osteosarcomas
may involve
the surface
of
bone in three
ways.
First,
a typical
intramedullary
highgrade
osteosarcoma
may permeate
the
predominantly
extra-osseous
tumor.
We
tumor should
be considered
an ordinary
osteosarcoma.
Second,
on rare occasions
teosarcoma
develops
on the surface
of a
THE

JOURNAL

OF BONE

cortex
and form a
believe
that such a
type of high-grade
a high-grade
osbone without
medAND

JOINT

SURGERY

DEDIFFERENTIATED

ullary

involvement.

Such

a tumor

prognosis
similar
to that of an ordinary
grade
tumor.
Finally,
a high-grade
surface

of bone

can

coexist

to

have

intramedullary
osteosarcoma

forpatients

highon the

with

to be similar
grade tumor.
low-grade

The

as high-grade
lesions
may

prognosis

that

after

I . BOWMAN,
2. BRODERS,

W. E.
A. C.:

these

tumors

is worse

than

a usual

parosteal

osteosarcoma

and appears

to that for patients

with an intramedullary
Therefore,
not all surface
osteosarcomas

of a

with

or be a recurrence

59

OSTEOSARCOMA

usual parosteal
osteosarcoma.
This group ofdedifferentiated
parosteal
osteosarcomas
is the subject
of this report.
for patients

with

appears

PAROSTEAL

(stage-I)

lesions.

A proportion

tumors,
and a significant
dedifferentiate
to become

inadequate

highare

of them

present

number
of low-grade
high-grade
tumors

excision.

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