PATHOLOGY (Dr.
Montes)
QUESTIONS
Defined as mesenchymal proliferations that occur in the extraskeletal,
nonepithelial tissues of the body, excluding the viscera, coverings of
the brain, and lymphoreticular tissue
TUMORS OF SOFT TISSUE and TUMOR-LIKE LESIONS are classified
according to
Characteristic of TUMORS OF SOFT TISSUE and TUMOR-LIKE LESIONS
TUMORS OF SOFT TISSUE PATHOGENESIS and GENERAL FEATURES
Genetic syndromes to which tumors of soft tissue are associated
Chromosomal and Genetic Abnormalities in Soft-Tissue Sarcomas
BONE AND JOINTS PATHOLOGY (Part 4)
1 APRIL 2017
ANSWERS
TUMORS OF SOFT TISSUE and TUMOR-LIKE LESIONS
tissue they recapitulate
have no normal tissue counterpart
True frequency is difficult to estimate, because most benign lesions are
not removed
benign tumors outnumber their malignant counterparts (sarcomas) by a
ratio of 100:1
in this group of tumors, sarcomas usually metastasize via hematogenous
routes, making the lung and skeleton common sites of dissemination
cause is unknown in most cases
radiation, chemical burns, thermal burns or trauma may be associated
with subsequent development of sarcoma
exposure to phenoxyherbicides and chlorophenols has also been
implicated
Kaposi sarcoma is causally associated with the human HPV 8
Most occur sporadically
40% occur in the lower extremity (thigh), 20% in upper extremities, 10%
in the head and neck, 30% in trunk and retroperitoneum
M:F=1.4:1, 15% occur in children and constitute the 4th most common
malignancy in this age group
Specific sarcomas tend to appear in certain age groups
rhabdomyosarcoma children
synovial sarcoma young adulthood
liposarcoma and fibrosarcoma middle to late adult life
neurofibromatosis type 1 (neurofibroma, MPNST)
Gardner syndrome (fibromatosis)
Li-Fraumeni syndrome (soft-tissue sarcoma)
Osler-Weber-Rendu syndrome (telangiectasia)
Ewing sarcoma/PNET
t(11;22)(q24;q12) FLI1-EWS fusion gene
t(21;22)(q22;q12) ERG-EWS fusion gene
t(7;22)(q22;q12) ETV1-EWS fusion gene
Liposarcoma myxoid and round-cell type
t(12;16)(q13;p11) CHOP/TLS fusion gene
Synovial sarcoma
t(x;18)(p11;q11) SYT-SSX fusion gene
Rhabdomyosarcoma alveolar type
t(2;13)(q35;q14) PAX3-FKHR fusion gene
t(1;13)(p36;q14) PAX7-FKHR fusion gene
Extraskeletal myxoid chondrosarcoma
t(9;22)(q22;q12) CHN-EWS fusion gene
Desmoplastic small round cell tumor
t(11;22)(p13;q12) EWS-WT1 fusion gene
Clear cell sarcoma
t(12;22)(q13;q12) EWS-ETF1 fusion gene
Dermatofibrosarcoma protuberans
t(17;22)(q22;q15) COLA1-PDGFB fusion gene
Alveolar soft part sarcoma
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 t(X;17)(p11.2;q25) TFE3-ASPL fusion gene
Congenital fibrosarcoma
t(12;15)(p13;q23) ETV6-NTRK3 fusion gene
SOFT TISSUE TUMORS GENERAL FEATURES THAT INFLUENCE Accurate histologic classification establishing the prognosis of a
PROGNOSIS sarcoma
histologic grade is important
- usually grades I to III, is based on the degree of differentiation,
average number of mitoses/hpf, cellularity, pleomorphism and
estimate of the extent of necrosis
Staging determines the prognosis and chances of successful excision
of a tumo
SOFT TISSUE TUMORS GENERAL FEATURES THAT INFLUENCE Spindle cell
PROGNOSIS - Rod-shaped, long axis twice as great as short axis
- Fibrous, fibrohistiocytic, smooth muscle, Schwann cell
Small round cell
- Size of a lymphocyte with little cytoplasm
- Rhabdomyosarcoma, PNET
Epithelioid
- Polyhedral with abundant cytoplasm, nucleus is centrally located
- Smooth muscle, Schwann cell, endothelial, epithelioid sarcoma
Smooth muscle
- Fascicles of eosinophilic spindle cells intersecting at right angles
Fibrohistiocytic
- Short fascicles of spindle cells radiating from a central point like spokes
or a wheelstoriform
Schwann cells
- Nuclei arranged in columnspalisading
Fibrosarcoma
- Herringbone
Synovial sarcoma
- Mixture of spindle cells and groups of epithelioid cells--biphasic
SOFT TISSUE TUMORS GENERAL FEATURES tumors arising in superficial locations (e.g.,skin and subcutis) have a
better prognosis than deep-seated lesions
deep-seated, high-grade tumors, metastasis develops in 80%
FATTY TUMORS LIPOMAS
LIPOSARCOMAS
Most common soft tissue tumor of adulthood Lipomas
Lipomas are sub- classified according to morphologic features w/c are: Conventional- show rearrangements of 12q14-q15, 6p, and 13q
Fibrolipoma

Angiolipoma
spindle cell lipoma- rearrangements of 16q13q

myelolipoma
pleomorphic lipoma- rearrangements of 16q13q
LIPOMAS MORPHOLOGY conventional lipoma- the most common subtype, is well encapsulated
mass of mature adipocytes that varies considerably in size
Arises in the subcutis of the proximal extremities and trunk, most
frequently during middle-adulthood
a. Normal fat
b. Lipoma (histology)
c. Lipoma (gross)

LIPOMA CLINICAL Lipomas are soft, mobile and painless (except angiolipoma) and are usually
cured by simple excision
One of the most common sarcomas of adulthood and appear in the Liposarcoma
40s to 60s; they are rare in children

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Liposarcoma usually arise in
LIPOSARCOMA MORPHOLOGY
Well- differentiated liposarcoma is characterized by
In other variants of liposarcoma, characteristics include:
LIPOSARCOMA - CLINICAL
FIBROUS TUMORS AND TUMOR-LIKE LESIONS
Non-neoplastic lesions that either develop in response to some form
of local trauma (physical or ischemic) or are idiopathic
Also known as infiltrative or pseudosarcomatous fasciitis, which is the
most common reactive pseudosarcomas
NODULAR FASCIITIS - MORPHOLOGY
the deep soft tissues of the proximal extremities and retroperitoneum, and are
notorious for developing large tumors
Histologically divided into well-differentiated, myxoid/round, and
pleomorphic variants
cells are known as lipoblasts; they mimic fetal fat cells and contain round
clear cytoplasmic vacuoles or lipid that scallop the nucleus
myxoid and round cell variant has a t(12;16) (q13;p11) chromosomal
abnormality in most cases
cells are readily recognized as lipocytes
the tumor cells frequently contain supernumerary rings and giant rod
chromosomes due to amplification of the 12q14-q15 region containing
the MDM2 oncogene, this inhibits p53
tumor cells that are not obviously adipogenic, but some cells indicative of fatty
differentiation are almost always present
well-differentiated variant is relatively indolent, the myxoid/round cell type
is intermediate in its malignant behavior, and the pleomorphic variant
usually is aggressive and frequently metastasizes
All types recur locally
REACTIVE PSEUDOSARCOMATOUS PROLIFERATIONS
- NODULAR FASCIITIS
- MYOSITIS OSSFICANS
FIBROMATOSES
- SUPERFICIAL FIBROMATOSIS (PALMAR, PLANTAR, PENILE)
- DEEP-SEATED FIBROMATOSIS (DESMOID TUMOR)
FIBROSARCOMA
REACTIVE PSEUDOSARCOMATOUS PROLIFERATIONS
- composed of plump reactive fibroblasts or related
mesenchymal cells
- they develop suddenly and grow rapidly
Nodular fasciitis
- occurs in adults on the volar aspect of the forearm, followed in
order of frequency by the chest and back
- Patients typically present with a several-week history of a
solitary rapidly growing and sometimes painful mass
Arise in the dermis, subcutis or muscle
Gross: Several cm. in greatest dimension, nodular and has poorly
defined margins
Microscopically:
- Richly cellular and consists of plump immature-looking
fibroblasts and myofibroblasts arranged randomly or in short
intersecting fascicles
- The cells vary in size and shape (spindle to stellate) and have
conspicuous nucleoli and abundant mitotic figures
- The stroma is myxoid and contains lymphocytes and RBCs
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MYOSITIS OSSIFICANS is distinguished from other fibroblastic
proliferations by
Myositis ossificans usually develops in what group of population
Pathogenesis of myositis ossificans
Myositis Ossificans
MYOSITIS OSSIFICANS CLINICAL FEATURE
Extraskeletal osteosarcoma vs. myositis ossificans
lesion rarely recurs after excision
presence of metaplastic bone
athletic adolescents and young adults and follows an episode of
trauma in more than 50% of cases and arise in the musculature of
the proximal extremities
In early phase: the involved area is swollen and painful
Subsequent weeks: becomes more circumscribed and firm
Eventually: painless hard well-demarcated mass
Gross:
3 to 6 cm in diameter; have soft glistening centers and a firm gritty
periphery
Microscopic:
Earliest phase: cellular and consists of plump, elongated fibroblast
and myofibroblast-like cells simulating nodular fasciitis
In due course: cells are surrounded by an intermediate zone that
contains osteoblasts, which deposit ill-defined trabeculae of woven
bone
Most peripheral zone contains well-formed, mineralized trabeculae
that resembles cancellous bone
Eventually the entire lesion ossifies, and the intertrabecular spaces
become filled with BM
The mature lesion is completely ossified
BENIGN FIBROUS TISSUE PROLIFERATION PLUS OSSEOUS METAPLASIA
X-ray: initially, soft tissue fullness, in about 3 weeks, patchy flocculent
radiodensities form in the periphery
The radiodensities become more extensive with time and slowly
encroach on the radiolucent center
Treatment: simple excision is usually curative
extraskeletal osteosarcoma, which usually occurs in elderly, the cells are
cytologically malignant, and lacks the zonation of myositis ossificans
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Characterized by nodular or poorly defined fascicles of fibroblasts and
myofibroblasts surrounded by abundant dense collagen
These are irregular or nodular thickenings of the palmar fascia either
unilaterally or bilaterally (50%) causing puckering and dimpling of skin
over several years with flexion contracture of the 4th and 5th fingers
A palpable induration or mass on the dorsolateral aspect, may cause
abnormal curvature of the shaft or constriction of the urethra or both
Sex predilection of superficial fibromatosis
DEEP-SEATED FIBROMATOSIS (DESMOID TUMORS)
Deep seated fibromatosis usually located in
Deep seated fibromatosis is divided into:
Mutation present in the majority of deep seated fibromatosis and have
an important role in their genesis
Desmoid tumors- Morphology
Superficial fibromatosis (palmar, plantar and penile)
- molecular mechanisms are unknown
Palmar variant (Dupuytren contracture)
Penile fibromatosis (Peyronies disease)
Male
Often present as large infiltrative masses that frequently recur after incomplete
excision, and in some, composed of well-differentiated fibroblasts that do not
metastasize
gray zone between benign fibrous proliferations and low-grade fibrosarcomas
and occur at any age but most frequent in the teens to 30s
Extra-abdominal fibromatosis
- men = women frequency
- musculature of the shoulder, chest wall, back and thigh
Abdominal fibromatosis
- women during or after pregnancy
- musculoaponeurotic structures of the anterior abdominal wall
Intra-abdominal desmoids
- mesentery or pelvic walls, often in patients having familial
adenomatous polyposis (Gardners syndrome)
Mutations in the APC or -catenin genes
Grossly:
gray-white, firm, poorly demarcated masses from 1 to 15 cm in
diameter
rubbery and tough and infiltrate surrounding structures
Histologically:
Composed of banal plump fibroblasts
Mitoses may be frequent

Desmoid tumors- Clinical Feature disabling, disfiguring and occasionally painful

Curable by adequate excision
Some tumors responded to tamoxifen, some cases responded to
chemotherapy or irradiation
The rare reports of metastasis of fibromatosis must be interpreted as misdiagnosis of fibrosarcoma
FIBROSARCOMA Occur anywhere in the body, but are most common in the deep soft
tissues of the extremities
aggressive tumors, recurring in more than 50% of the cases and
metastasize in >25%
Fibrosarcoma- Morphology Gross:
Unencapsulated, infiltrative, soft, fish-flesh masses with areas of
hemorrhage and necrosis
Histologic:
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 Varies in degree of differentiation
having spindled cells growing in a herringbone fashion
highly cellular neoplasms dominated by architectural disarray,
pleomorphism, frequent mitoses, and areas of necrosis

FIBROHISTIOCYTIC TUMOR BENIGN FIBROUS HISTIOCYTOMA (DERMATOFIBROMA)

MALIGNANT FIBROUS HISTIOCYTOMA
Painless and slow growing and most often present in middle adult life BENIGN FIBROUS HISTIOCYTOMA (DERMATOFIBROMA)
as a firm small (less than 1cm) mobile nodule that occur in the dermis
and subcutis
Referred to a group of soft-tissue tumors characterized by Malignant Fibrous Histiocytoma (MFH)
considerable cytologic pleomorphism, the presence of bizarre
multinucleate cells, storiform architecture

TUMORS OF SKELETAL MUSCLE RHABDOMYOMA

RHABDOMYOSARCOMA
In contrast to other groups of tumors, are almost always Malignant
Tumor of skeletal muscle frequently seen in individuals with tuberous cardiac rhabdomyoma
sclerosis
benign variant, rhabdomyoma, is distinctly rare

RHABDOMYOSARCOMA most common soft tissue sarcomas of childhood and adolescence,

usually before the age of 20
most occur in the head and neck or GUT
Only in the extremities do they appear in relation to skeletal muscle
Rhabdomyosarcoma- Morphology Histologic classification:
Embryonal
Alveolar
Pleomorphic
rhabdomyoblast contains eccentric eosinophilic granular cytoplasm rich in
thick and thin filaments
Rhabdomyoblasts may be round or elongate (tadpole or strap cells)
EM, contain sarcomere
IHC, stain with Abs to desmin, MYOD1 and myogenin

Morphology of Embryonal variant Most common type, accounts for 66%, includes sarcoma botryoides and
spindle cell and anaplastic variants

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Which variant of embryonal rhabdomyosarcoma that develops in the
walls of hollow mucosal-lined structures such as nasopharynx, CBD,
bladder and vagina?
What do you call the submucosal zone of hypercellularity?
Alveolar rhabdomyosarcoma commonly occur in (age) and (parts)
Histological characteristics of Alveolar rhabdomyosarcoma
This variant of rhabdomyosarcoma is characterized by numerous
large, sometimes multinucleated, bizarre eosinophilic tumorcells
Which variant has the best prognosis?
This benign smooth muscle tumors, often arise in the uterus, which is
the most common neoplasm in women
Leiomyomas develop more common in (population) and arise in
(organs)
This disorder is associated with a germline loss-of-function mutation of
Leiomyomas- morphology
LEIOMYOSARCOMA
Morphologic variants of leiomyoasarcoma
Occurs in children <10 years and arises in the nasal cavity, orbit, middle
ear, prostate and paratesticular region
commonly has parental isodisomy of chromosome 11p15.5, which leads
to overexpression of the imprinted IGFII gene
Sarcoma botryoides
Cambium layer
early to mid-adolescence and arises in the deep musculature of the extremities
and represents approximately 20% of rhabdomyosarcomas
tumor is traversed by a network of fibrous septae that divide the cells into
clusters or aggregates that creates a crude resemblance to pulmonary alveoli
Alveolar rhabdomyosarcoma
Tumor cells are moderate in size, and many have little cytoplasm
Those in the center of the aggregates are dyscohesive, while those
at the periphery adhere to the septae
Cells with cross-striations are identified in about 25% of cases
chromosomal translocation that either fuses the PAX3 to the
FOXO1a gene, t(2;13)(q35;q14) or the PAX7 to the FOXO1a gene,
t(1;13)(p36;q14)
Pleomorphic rhabdomyosarcoma
- variant is rare, has a tendency to arise in the deep soft tissue
of adults
botryoid type
- while the anaplastic emryonal, pleomorphic and alveolar
variants are often fatal
LEIOMYOMAS
develop in 77% of women and may also arise from the arrector pili muscles
(pilar leiomyomas)found in the skin, nipples, scrotum and labia and less
frequently develop in the deep soft tissues and the wall of the gut
fumarate hydratase gene located on chromosome 1q42.3
not larger than 1 to 2 cm in diameter
composed of fascicles of spindle cells that intersect each other at right
angles, with blunt-ended elongated nuclei, minimal atypia and few mitotic
figures
Presents as painless firm masses
Retroperitoneal tumors may be large and bulky and cause abdominal
symptoms
LEIOMYOMAS
Histologically:
characterized by malignant spindle cells that have cigar-shaped
nuclei arranged in interweaving fascicles
Immunohistochemically, they stain with antibodies to smooth muscle actin and
desmin
Account for 10 to 20% of soft tissue sarcomas
adult and affects women
Most develop in the skin and deep soft tissues of the extremities and
retroperitoneum
The MAIN difference between leiomyomas and leiomyosarcomas is the number
of mitoses per high power field! How many do you see here?
myxoid stroma
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 epithelioid variant
LEIOMYOSARCOMA CLINICAL FEATURE Treatment depends on the size, location and grade
Superficial or cutaneous leiomyosarcomas are usually small and have a
good prognosis,
those of the retroperitoneum are large, cannot be entirely
excised, and cause death by both local extension and
metastatic spread
SYNOVIAL SARCOMA recapitulate synovium, but the cell of origin is still unclear
Accounts for 10% of all soft tissue sarcomas, and 4th most common
sarcoma
Majority develop in the deep soft tissue and about 60 to70% involve the
lower extremity, around the knee and thigh
Patients usually present with a deep-seated mass that has been noted
for several years
SYNOVIAL SARCOMA MORPHOLOGY Morphologically biphasic or monophasic

dual lines of differentiation- Histologic hallmark of biphasic
synovial sarcoma
monophasic, lesions composed solely of spindle cells or very
rarely epithelial cells
Lesions composed solely of spindled cells are easily mistaken for
fibrosarcomas or MPNST
Characteristic feature when present is calcified concretions that can
sometimes be detected radiographically
Most show a characteristic chromosomal translocation t(x;18)(p11;q11)
producing SS18-SSX1, SSX2, or SSX4 fusion genes that encode chimeric
transcription factors

SYNOVIAL SARCOMA CLINICAL FEATURE Treated aggressively with limb-sparing therapy and frequently
chemotherapy
Commons sites of metastases are the lung, skeleton, and occasionally the
regional lymph nodes

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