SOFT TISSUE TUMOURS

By Dr. Fahd Al-Mulla

Understand the classification and types of soft tissue tumours

Understand the necessity for a team-approach
Correlate Pathological findings with clinical presentation
(Clinico-pathological correlation)
Know the most relevant information and know it well

ALL INFORMATION IS ON WEBSIT:

http://www.tumours.com
 Soft Tissue Tumours: Definition

Mesenchymal proliferations that occur in the extraskeletal, nonepithelial

tissues of the body, excluding the viscera, coverings of the brain, and
lymphoreticular system.
Histologic type Benign Malignant
Adipose Tissue Lipoma Liposarcoma

Fibrous tissue Fibromatosis Fibrosarcoma

Nodular fasciitis
Fibrohistiocytic tumours Fibrous histiocytoma Malignant Fibrous
Dermatofibroma Histiocytoma?????
Skeletal Muscle Rhabdomyoma Rhabdomyosarcoma

Smooth Muscle Leiomyoma Leiomyosarcoma

Vascular Haemangioma Angiosarcoma

Lymphangioma
Peripheral nerve Neurofibroma Malignant peripheral
Schwannoma nerve sheath tumour
Uncertain histogenesis Granular cell tumour Synovial Sarcoma
Alveolar soft part
sarcoma
Epithelioid sarcoma
The cause of most soft tissue tumors is unknown. There are documented
associations, however, between radiation therapy and rare instances in
which chemical burns, heat burns, or trauma were associated with
subsequent development of a sarcoma. Exposure to phenoxyherbicides
and chlorophenols has also been implicated in some cases. Kaposi
sarcoma in patients with AIDS and in immunosuppressed patients is
related to viruses and defective immunocompetence. Most soft tissue
tumors occur sporadically, but a small minority are associated with
genetic syndromes, the most notable of which are neurofibromatosis
type 1 (neurofibroma, malignant schwannoma), Gardner syndrome
(fibromatosis), Li-Fraumeni syndrome (soft tissue sarcoma), and
Osler-Weber-Rendu syndrome (telangiectasia).
More recently, Enzinger and Weiss proposed a classification system
based on histogenic origin.

Problems:
1) It is very difficult for competent pathologists to agree on the
histogenesis of these tumors. Some sarcomas have multiple cell types
present in different areas of the tumor.
2) Many tumors are so undifferentiated that to subclassify them into
their histogenic type is close to impossible, even with specialized
techniques such as electron microscopy and immunohistochemistry
However, the major drawback of this classification system is that it
does not really take into account the grade of the tumor and its
implications for prognosis.
After the histologic type of soft-tissue sarcoma has been determined, the
tumor is graded 1 to 4, depending on its degree of differentiation
(How similar it is to the original tissue)

The majority of histologic types can be low-, intermediate-, or high-

grade (grade 1, 2, or 3, respectively). However, some soft-tissue
sarcomas such as well-differentiated liposarcomas and myxoid
liposarcomas are always low-grade, whereas others such as
rhabdomyosarcoma, synovial sarcoma, mesenchymal
chondrosarcoma, and extraskeletal Ewings and osteosarcomas are
always high-grade

The American Joint Committee on Cancer (AJCC) has developed a

clinicopathologic staging system that depends primarily on the grade
and size of soft-tissue sarcomas
Primary tumor (T)
T0 No evidence of primary tumor American Joint Committee on
T1 Tumor <5 cm Cancer
T2 Tumor >5 cm AJCC of soft tissue sarcomas
classification
Lymph nodes (N)
N0 No regional metastasis
N1 Regional node metastasis
Distant metastasis (M)
M0 No distinct metastasis
M1 Distant metastasis
Histopathalogic grading (G)
G1 Well differentiated (low grade)
G2 Moderately differentiated (intermediate grade)
G3 Poorly differentiated (high grade)
G4 Undifferentiated

Stage
IA G1 T1 N0 M0
IB G1 T2 N0 M0
IIA G2 T1 N0 M0
IIB G2 T2 N0 M0
IIIA G3 T1 N0 M0
G4 T1 N0 M0
IIIB G3 T2 N0 M0
G4 T2 N0 M0
IVA Any G Any T N1 M0
IVB Any G Any T Any N M1
 FATTY TUMOURS

Benign tumors of fat, known as lipomas, are the most common soft
tissue tumor of adulthood.

MORPHOLOGY.
The conventional lipoma, the most common subtype, is a well-
encapsulated mass of mature adipocytes that varies considerably in size.
It arises in the subcutis of the proximal extremities and trunk, most
frequently during mid-adulthood. Infrequently, lipomas are large,
intramuscular, and circumscribed. Histologically, they consist of mature
fat cells with no evidence of pleomorphism or abnormal growth.
Lipomas are soft, mobile, and painless (except angiolipoma) and are
usually cured by simple excision.

conventional lipomas often show rearrangements of 12q14-15, 6p, and

13q, and spindle cell and pleomorphic lipomas have rearrangements of
16q and 13q .
Liposarcoma
Liposarcomas are one of the most common sarcomas of adulthood and
appear in the forties to sixties; they are uncommon in children. They
usually arise in the deep soft tissues of the proximal extremities and
retroperitoneum and are notorious for developing into large tumors.

MORPHOLOGY.
Histologically, liposarcomas can be divided into well-differentiated,
myxoid, round cell, and pleomorphic variants. The cells liposarcomas are
readily recognized as lipoblasts, which mimic fetal fat cells
 Fibrous tumours and Fibrohistiocytic tumours

Fibromatoses

SUPERFICIAL FIBROMATOSIS (PALMAR, PLANTAR, AND PENILE

FIBROMATOSES)
Palmar, plantar, and penile fibromatoses, more bothersome than serious lesions,
constitute a small group of superficial fibromatoses. They are characterized by nodular
or poorly defined fascicles of mature-appearing fibroblasts surrounded by abundant
dense collagen. Immunohistochemical and ultrastructural studies indicate that many of
these cells are myofibroblasts
Examples: Dupuytren contracture, plantar fibromatosis

DEEP-SEATED FIBROMATOSIS (DESMOID TUMORS)

Biologically, deep-seated fibromatoses lie in the interface between exuberant fibrous
proliferations and low-grade fibrosarcomas. On the one hand, they present frequently
as large, infiltrative masses that may recur after incomplete excision, and on the other,
they are composed of banal well-differentiated fibroblasts that do not metastasize.
Fibrosarcoma
Fibrosarcomas are rare but may occur anywhere in the body, most
commonly in the retroperitoneum, the thigh, the knee, and the distal
extremities.

MORPHOLOGY.
Typically, these neoplasms are unencapsulated, infiltrative, soft, fish-
flesh masses often having areas of hemorrhage and necrosis. Better-
differentiated lesions may appear deceptively encapsulated. Histologic
examination discloses all degrees of differentiation, from slowly
growing tumors that closely resemble cellular fibromas sometimes
having spindled cells growing in a herringbone fashion to highly cellular
neoplasms dominated by architectural disarray, pleomorphism, frequent
mitoses, and areas of necrosis.
TUMORS OF SKELETAL MUSCLE
Skeletal muscle neoplasms, in contrast to other groups of tumors, are
almost all malignant. The benign variant, rhabdomyoma, is distinctly
rare.
Rhabdomyosarcoma
Rhabdomyosarcomas, the most common soft tissue sarcomas of
childhood and adolescence, usually appear before age 20. They may
arise in any anatomic location, but most occur in the head and neck or
genitourinary tract.

MORPHOLOGY.
Rhabdomyosarcoma is histologically subclassified into the embryonal,
alveolar, and pleomorphic variants. The rhabdomyoblast--the
diagnostic cell in all types--contains eccentric eosinophilic granular
cytoplasm rich in thick and thin filaments. The rhabdomyoblasts may be
round or elongate; the latter are known as tadpole or strap cells
Cytogenetics play an important role in confirming the diagnosis rhabdomyosarcoma. Alveolar
rhabdomyosarcoma is associated with a specific translocation, t(2;13)(q37;q14) or its variant t(1;13)
(p36;q14). Embryonal rhabdomyosarcoma often shows loss of heterozygosity for 11p, but there is no specific
cytogenetic or molecular marker comparable to those for alveolar RMS.
TUMORS OF SMOOTH MUSCLE

Leiomyomas
Leiomyomas, the benign smooth muscle tumors, often arise in the uterus
where they represent the most common neoplasm in women. Leiomyomas
may also arise in the skin and subcutis from the arrector pili muscles found
in the skin, nipples, scrotum, and labia (genital leiomyomas) and less
frequently develop in the deep soft tissues.
They are usually not larger than 1 to 2 cm in greatest dimension and are
composed of fascicles of spindle cells that tend to intersect each other at
right angles. The tumor cells have blunt-ended elongated nuclei and show
minimal atypia and few mitotic figures.
Leiomyosarcoma
Leiomyosarcomas account for 10% to 20% of soft tissue sarcomas. Most
develop in the skin and deep soft tissues of the extremities and
retroperitoneum. Microscopically, the lesion is composed of interlacing
fascicles of mildly pleomorphic, spindle cells with blunt-ended nuclei and
eosinophilic cytoplasm. Average mitotic rate was 3 per 10 hpf. Geographic
areas of necrosis is present
SYNOVIAL SARCOMA
Synovial sarcoma is so named because it was once believed to
recapitulate synovium, but the cell of origin is still unclear. In addition,
although the term synovial sarcoma implies an origin from the joint
linings, less than 10% are intra-articular. Synovial sarcomas account for
approximately 10% of all soft tissue sarcomas and rank as the fourth
most common sarcoma.

MORPHOLOGY.
The histologic hallmark of synovial sarcoma is the biphasic
morphology of the tumor cells (i.e., epithelial-like and spindle cells).

Immunohistochemistry is helpful in identifying these tumors, since the

epithelioid and spindle cell portions yield positive reactions for keratin
and epithelial membrane antigen, differentiating these tumors from most
other sarcomas.
In Summary:

-Soft tissue benign tumours outnumber malignant

Tumours 100:1
-They are aggressive if malignant
-Be a good clinician and always correlate clinical
with pathological findings.
-Work together as a multi-disciplinary team

Any Questions??
 Bone Tumours
WHAT SHOULD YOU KNOW

Understand the clinical algorithm

Correlate clinical presentation with radiological features
Understand the classification and types of bone tumours
Comprehend the management of bone tumours
Understand the necessity for a team-approach
Correlate Pathological findings with clinical presentation
(Clinico-pathological correlation)
 CLASSIFICATIONS OF PRIMARY TUMOURS
INVOLVING BONES
Metastatic cancers are the most frequent malignant tumors found in bone

Histological Types Benign Malignant

Hematopoietic (40%) Myeloma
Malignant lymphoma
Chondrogenic (22%) Osteochondroma Chondrosarcoma
Chondroma Dedifferentiated
Chondroblastoma chondrosarcoma
Chondromyxoid fibroma
Osteogenic (19%) Osteoid osteoma Osteosarcoma
Osteoblastoma
Unknown origin (10%) Giant cell tumour Ewing tumour
Giant cell tumour
Adamantinoma
Histiocytic origin Fibrous histiocytoma MFH
Fibrogenic Fibroma Fibrosarcoma
Notochordal Chordoma
Vascular, Cystic, lipogenic
neurogenic
AGE(probably the most important clinical clue).

Age group Most common benign lesions Most common malignant tumors

Ewing's sarcoma
simple bone cyst
0 - 10 leukemic involvement
eosinophilic granuloma
metastatic neuroblastoma

non-ossifying fibroma
fibrous dysplasia
simple bone cyst
aneurysmal bone cyst osteosarcoma,
10 - 20 osteochondroma (exostosis) Ewing's sarcoma,
osteoid osteoma adamantinoma
osteoblastoma
chondroblastoma
chondromyxoid fibroma

enchondroma
20 - 40 chondrosarcoma
giant cell tumor

metastatic tumors
myeloma
leukemic involvement
40 & above osteoma chondrosarcoma
osteosarcoma (Paget's associated)
MFH
chordoma
 SITE OF LONG BONE INVOLVEMENT
(most primary bone tumors have favored sites within long bones; this may provide a clue to
diagnosis).

Diaphyseal lesions centered in Diaphyseal intramedullary lesions:

the cortex: Favored location for Ewing's sarcoma,
Adamantinoma, osteoid lymphoma, myeloma. Common for
osteoma fibrous dysplasia and enchondroma

Metaphyseal intramedullary lesions:

Osteosarcoma is usually centered in the
metaphysis. Chondrosarcoma and
Metaphyseal lesions centered in the
fibrosarcoma often present as metaphyseal
cortex:
lesions. Osteoblastoma, enchondroma,
Classic location for a non-ossifying
fibrous dysplasia, simple bone cyst, and
fibroma (NOF). Also, a common site for
aneurysmal bone cyst are common in this
osteoid osteoma.
location.

Epiphyseal lesions:
Metaphyseal exostosis: Chondroblastoma (Ch) and Giant
Osteochondroma Cell Tumor (GCT) are almost
invariably centered in the
epiphysis. Chondroblastoma is a rare
tumor seen in children and
adolescents with open growth plates.
GCT is the most common tumor of
epiphyses in skeletally mature
individuals with closed growth
plates. GCT often shows
metaphyseal extension.
 General Histologic Assessment of the Lesion

The following are the most important histologic features to consider:

Pattern of growth (eg., sheets of cells vs. lobular architecture)

Cytologic characteristics of the cells
Presence of necrosis and/or hemorrhage and/or cystic change
Matrix production
Relationship between the lesional tissue and the surrounding bone (eg., sharp
border vs. infiltrative growth)

But remember:
1. Listen to your patients (Is the lesion painful, What is the age of the patient)
2. Listen to the Radiologist (patterns of growth and ask to see the films)
3. Listen to the surgeons (rapid growth, involve the periosteum, soft tissue)
An 11-year-old male was seen in consultation for an increasingly painful distal femoral lesion associated with a soft tissue mass.

Plain radiograph shows an ill-defined

destructive tumor in the distal femur. Fluffy
radiodense infiltrates represent malignant
tumor osteoid.

Biopsy material shows two major

components of this neoplasm: highly
pleomorphic cells and haphazard
deposits of osteoid. Note that the
malignant cells fill the spaces between
osteoid deposits. Lace-like osteoid
deposition is very characteristic of
this neoplasm.
The tan-white tumor fills most of
the medullary cavity of the
metaphysis and proximal
diaphysis. It has infiltrated
through the cortex, lifted the
periosteum, and formed soft
tissue masses on both sides of the
bone.
A 17-year-old male presented with increasing pain in the left upper arm of approximately 3 months' duration and a recent onset of low-grade fever.
On physical examination, there was some local tenderness and soft tissue swelling over the proximal and mid thirds of the left humerus.
Most important here is the patient's age and short duration of symptoms.

Plain radiograph shows a large ill-defined, destructive,

diaphyseal intramedullary lesion with permeative
pattern of bone destruction and periosteal reaction of a
"hair-on-end" type. The lesion is associated with a soft
tissue mass.

Biopsy material showed a highly cellular,

infiltrative neoplasm consisting of sheets of tightly
packed, round cells with very scant cytoplasm
("round blue cell tumor"). Occasional Homer-
Wright rosettes were identified. Other fields
showed extensive necrosis.

The cell population consisted of two distinct cell

types: the larger round cells with a high N/C
ratio, fine chromatin pattern and occasional
small, inconspicuous nucleoli, and the smaller
and darker cells with eosinophilic cytoplasm and
hyperchromatic, "shrunken" nuclei (degenerated
cells, a typical finding in this entity). Mitotic rate
averaged 2 per 10 hpf.
 The following studies are required to support the diagnosis of ES and PNET:

Demonstration of t(11;22) or EWS-FLI-1 fusion transcript (present in both ES and PNET)

Immunostains(both ES and PNET are positive for CD99/O13. In addition, PNET shows positive staining
with neural markers)
EM (ES cells are undifferentiated and show prominent glycogen deposits; PNET shows neural
differentiation)
A 16-year-old boy was seen in consultation for increasing pain in the mid upper arm. Characteristically, the pain intensified at night and subsided
with aspirin.

Plain film shows a small, intracortical,

radiolucent focus (nidus), surrounded by dense
reactive periosteal bone. The lesion is located in
the mid portion of the humeral shaft.

If the nidus is removed intact, it

appears as a circumscribed
portion of red, trabecular bone,
usually less than 1cm in size.

Low-power view shows the lesional tissue ("nidus"), well demarcated

from the surrounding sclerotic bone.

The lesion is composed of thin, often interconnected spicules of

osteoid and woven bone rimmed by osteoblasts. Osteoclast-like
giant cells can be seen. Intervening fibrous stroma shows
prominent vascularity.
A 39-year-old female gave a 2-month history of increasing pain in her knee. There was no evidence of
joint effusion. Laboratory work-up showed normal serum levels of calcium, phosphate and alkaline
phosphatase

Plain radiograph demonstrated a well

defined, lytic lesion eccentrically located in
the distal femoral epiphysis with
subchondral and metaphyseal extension.
There was associated focal thinning of the
cortex

Curettage specimen consisted of fragments of soft,

hemorrhagic, tan-brown tissue with some firm areas and
yellowish speckles. Microscopic examination showed a
cellular lesion composed of numerous multinucleated
giant cells in a background of small, ovoid, mononuclear
stromal cells

Stromal cells had poorly defined

cytoplasmic borders and bland nuclei
resembling those of giant cells. Mitoses
were easily found averaging 4 per 10 hpf.
However, no atypical mitoses were
identified.
A 45-year old female presented with increasing pain and swelling around the knee. She mentioned that the symptoms had progressed over a 4-
month period.
Age of the patient is an important diagnostic clue. If a pathologic fracture is excluded, pain and swelling imply active growth of the lesion.

Plain film demonstrates a large, lobulated, ill-

defined lesion centered in the distal femoral
metaphysis. There is endosteal scalloping and
periosteal thickening. Central stippled and
"ring and arc" calcifications are apparent and
are typical of cartilaginous matrix. Small
radiolucent areas are seen at the periphery of the
lesion.

Low magnification shows a moderately

cellular, lobulated cartilaginous tumor.

High-power view shows scattered

plump, moderately pleomorphic
chondrocytes. Binucleated cells are
present. Mitotic rate averaged 1 per
10 hpf.
The aggressiveness of chondrosarcomas can be predicted by their histologic grade. Grading system is based on three parameters: cellularity,
degree of nuclear atypia and mitotic activity.

Grade 1 (low-grade)
Very similar to enchondroma. However, the cellularity is
higher, and there is mild cellular pleomorphism. The nuclei are
small but often show open chromatin pattern and small
nucleoli. Binucleated cells are frequent. Mitoses are very rare.
Grade 1 chondrosarcomas are locally aggressive and prone to
recurrences, but usually do not metastasize.

Grade 2 (low-grade)
The cellularity is higher than in Grade 1 tumors. Characteristic
findings are moderate cellular pleomorphism, plump nuclei,
frequent bi-nucleated cells, and occasional bizarre cells. Mitoses
are rare. Foci of myxoid change may be seen. Unlike Grade 1
tumors, about 10% to 15% of Grade 2 chondrosarcomas
produce metastases.

Grade 3 (high-grade)
Characteristic findings are high cellularity,
marked cellular pleomorphism, high N/C
ratio, many bizarre cells and frequent
mitoses (more than 1 per hpf). These are
high grade tumors with significant
metastatic potential.
A 14-year-old female was seen in consultation for an increasingly painful left humeral lesion associated with mild joint effusion.
Pay attention to the patient's age, skeletal location, and the presence of joint effusion, which may complicate epiphyseal lesions.

Plain radiograph showed an irregular, but

circumscribed, lytic epiphyseal lesion
surrounded by reactive bone sclerosis.
There was no evidence of bone expansion,
and the cortex was intact. The growth plates
were open.

The cytoplasmic borders were very

distinct with multiple foci of
"chicken-wire" calcification
(calcified reticulin network around
individual tumor cells).
A 20-year-old male presented with a painless, hard subcutaneous mass in the popliteal fossa. He stated that the mass had been present for several
years and did not change in size.
Two words, "painless" and "non-growing" (or very slow growing), suggest that the lesion described here is probably benign.

Plain radiograph demonstrated a

pedunculated bony outgrowth at the
proximal tibial metaphysis. The lesion
had a uniform, cartilagenous cap with
stippled calcifications. The tibial
cortex and medulla were continuous
with those of the lesion.

The specimen consisted of a

pedunculated lesion, 3 x 3 x
2cm, with a lobulated
cartilage cap measuring up to
0.9cm in thickness

Osteochondroma, the most common benign bone tumor, is not a

neoplasm but a hamartoma. It is thought to arise from a portion of
growth plate cartilage entrapped beneath the periosteum during skeletal
growth. These entrapped pieces continue to grow and ossify at the same
rate as the adjacent bone. When skeletal maturity is reached,
osteochondromas usually stop growing.
An incidental finding of a bone lesion in the distal femur of a 38-year old female. The lesion was completely asymptomatic.

Plain radiograph showed an intarmedullary zone

of stippled and ring-shaped calcifications in
the distal femoral metaphysis. This
mineralization pattern with radiodense stipples
and rings is characteristic of mature hyaline
cartilage.

Low-power microscopic examination of

the biopsy specimen shows three
characteristic features of this lesion: a)
vague lobularity; b) abundant cartilaginous
matrix, which can be focally calcified; c)
low cellularity.

High-power view shows clustered and

scattered chondrocytes with small,
uniform, darkly stained nuclei.
Occasional bi-nucleated chondrocytes are
present. Importantly, there were no
mitotic figures.
A 17-year-old male presented with a slowly enlarging, painful lesion of the right clavicle.

Plain radiograph reveals a

circumscribed, loculated,
radiolucent lesion producing
blowout expansion of the bone.

Gross photograph shows a spongy, expansile lesion

containing multiple, blood-filled cavities of varying sizes.

Low-power view demonstrates blood-filled

cystic spaces without recognizable
epithelial lining.
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