Tumori Tesuturi Moi

Soft tissue - normal
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Definition: nonepithelial extraskeletal tissue, excluding

supportive tissue of organs and lymphoid/hematopoietic
tissue
Includes fibrous tissue, adipose tissue, skeletal muscle,
smooth muscle, blood vessels, lymphatics and peripheral
nervous system
Usually mesodermal in origin; peripheral nerves derive from
neuroectoderm
Soft tissue tumors - approach to diagnosis

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Modified from Sternberg

1) Is lesion reactive or neoplastic?
2) Is lesion malignant? (necrosis favors malignancy)
3) Is malignant lesion a sarcoma? (may be melanoma,
carcinoma, lymphoma)
4) What type of differentiation is present? - assign to
phenotypic category or classify as round cell, spindle cell,
epithelioid, other
5) If sarcoma, what is the grade?
Sarcomas - general - Soft tissue tumors

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9,500 new cases/year in US

Classified based on type of cellular differentiation, although
most arise from multipotent mesenchymal cells that then
differentiate along various cell lines
Diagnostic errors are often due to lack of familiarity with rare
lesions, not failure to perform immunostains (AJCP
2001;116:473)
WHO classification: last revised in 2002 (Histopathology
2006;48:3), Table of Contents of WHO book-2002
World Health Organization classification with comments
(Atlas of Genetics and Cytogenetics)
Recommended to diagnose with FNA, core biopsy or
incisional biopsy so appropriate treatment can be
determined in advance
Congenital soft tissue tumors, even with high grade features,
rarely have malignant behavior
Nodal involvement uncommon
Local recurrences show increased number of genetic
changes, including loss at 9p, gains at 5p and 20q (Mod Path
2001;14:978)
Usually arise de novo, not from benign tumors (MPNST may
be an exception); do not appear to arise from trauma
May be caused by radiation therapy (MFH, extraskeletal
osteosarcoma), foreign bodies (MFH, angiosarcoma) or
chemical carcinogens (angiosarcoma)
Poor prognostic factors: large size, deep seated versus
superficial, retroperitoneum versus extremities, high grade,
high stage, positive margins (associated with local
recurrence)
Treatment: ideally wide local excision with 1-2 cm margin of
normal tissue; if not possible due to anatomic constraints
(neurovascular bundle, bone), a marginal excision (through
pseudocapsule) or focally positive margin is acceptable;
surgery should also remove site of prior incision; pre- or
postoperative radiotherapy are routinely used for large, high-
grade tumors or disseminated disease; amputation is
reserved for unresectable tumors
Surgical resection of pulmonary metastases often has value
Fine needle aspiration: most specimens are recognized as
sarcoma, and subtyping is most accurate in bone sarcomas
and pediatric sarcomas; subtyping is often not possible in
adult specimens, but this usually does not affect initial
therapy (AJCP 2001;115:59)
Staging is discussed in Soft Tissue Tumors-Part 2 (click
here)
Syndromes (molecular / genetic) associated with soft tissue

tumors
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Bannayan Zonana syndrome: OMIM #153480, multiple lipomas and

hemangiomas
Beckwith-Wiedemann syndrome: OMIM #130650, congenital
overgrowth syndrome associated with alveolar
rhabdomyosarcoma (Pediatr Dev Pathol 2001;4:550)
Carney syndrome / complex: autosomal dominant multiple
neoplasia syndrome with myxomas and pigmented lesions of
skin and mucosa, due to mutation in PRKAR1A gene (OMIM
#160980) or 2p16 abnormalities (OMIM #605244)
Carney triad: OMIM # 604287, gastric GIST, pulmonary
chondroma and extra-adrenal paraganglioma (Mayo Clinic
Proceedings 1999;74:543, Mayo Clinic Proceedings;1999;74:638)
Gardner syndrome: OMIM #175100, fibromatosis, familial
adenomatous polyposis and osteomas
Kasabach-Merritt syndrome: OMIM #141000,
microangiopathic hemolytic anemia associated with
childhood hemangioma or kaposiform
hemangioendothelioma
Klippel-Trenaunay-Weber syndrome: OMIM #149000,
hemangiomas with hypertrophy of associated bone and soft
tissue
Launois-Bensaude syndrome: painless symmetrical
diffuse deposits of fat beneath the skin of the neck, upper
trunk, arms and legs; also known as multiple symmetrical
lipomatosis, cephalothoracic lipodystrophy and Madelung
disease
Li Fraumeni syndrome: OMIM #151623, various soft tissue
sarcomas, osteosarcoma, breast cancer, brain tumors,
leukemia and adrenocortical carcinoma; usually due to p53
mutation
Lipomatosis, multiple syndrome: OMIM #151800
Maffucci syndrome: OMIM #166000, hemangiomas,
enchondroma, chondrosarcoma
Mazabraud's syndrome: fibrous dysplasia and
intramuscular myxoma (J Cancer Res Clin Oncol 1998;124:401)
McCune-Albright syndrome: OMIM #174800, major features
are polyostotic fibrous dysplasia, cafe-au-lait skin
pigmentation and precocious puberty; myxomas are minor
feature (see Mazabrauds syndrome)
Multiple endocrine neoplasia 1: OMIM #131100, multiple
lipomas may be a minor feature
Neurofibromatosis type 1: OMIM #162200, neurofibroma,
MPNST
Neurofibromatosis type 2: OMIM #101000, schwannoma,
neurofibroma, meningioma, astrocytoma, rarely
perineurioma (AJSP 2006;30:1624)
Osler-Weber-Rendu syndrome: OMIM #187300,
telangiectasias
Proteus syndrome: various cutaneous and subcutaneous
lesions, including vascular malformations, lipomas,
hyperpigmentation and nevi (eMedicine)
Stewart-Treves syndrome: cutaneous angiosarcoma that
develops in long-standing chronic lymphedema (eMedicine)
Sturge-Weber syndrome: OMIM #185300, port-wine spot of
face
Turner syndrome: cystic hygroma (eMedicine), rarely familial
desmoids or GIST
Grading of sarcomas of soft tissue
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Indicate in pathology report which grading system is used

Grade is most important prognostic factor and indicator of
metastatic risk in adults (Archives 2006;130:1448)
Two grade systems - low grade and high grade

Low grade: usually has limited ability to metastasize
High grade: cellular with mitotic figures and necrosis, but
must evaluate in context of tumor type, age and location;
for example: superficial high grade MFH is unlikely to
metastasize, but deep low grade MPNST is likely to
metastasize
Necrosis usually signifies high grade unless tumor is well
differentiated and lacks pleomorphism
Grading systems - French Federation of Cancer Centers

Sarcoma Group
Grade 1: total score of 2-3 points
Tumor differentiation:
1 point: resembles normal adult mesenchymal tissue, may
be confused with a benign lesion, such as well differentiated
liposarcoma
2 points: histologic typing is certain, such as myxoid
liposarcoma
3 points: synovial sarcoma, osteosarcoma, Ewings
sarcoma/PNET, sarcomas of doubtful tumor type, embryonal
and undifferentiated sarcomas
Mitotic count (count 10 successive high power fields [area of

0.17 mm squared] in most mitotically active areas):
1 point: 0-9 mitoses
2 points: 10-19 mitoses
3 points: 20 or more mitoses
Tumor necrosis:
0 points: no necrosis on any slides
1 point: less than 50% necrosis for all examined tumor
surface
2 points: tumor necrosis of 50% or more of examined tumor
surface
Grading systems - French Federation of Cancer Centers
Sarcoma Group - grades of common sarcoma types:
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Angiosarcoma-poorly differentiated/epithelioid - 3
Angiosarcoma-well differentiated/conventional - 2
Chondrosarcoma-mesenchymal - 3
Clear cell sarcoma - 3
Epithelioid sarcoma - 3
Fibrosarcoma-conventional - 2
Fibrosarcoma-well differentiated - 1
Fibrosarcoma-poorly differentiated - 3
Leiomyosarcoma-conventional - 2
Leiomyosarcoma-epithelioid / poorly differentiated /
pleomorphic - 3
Leiomyosarcoma-well differentiated - 1
Liposarcoma-myxoid - 2
Liposarcoma-pleomorphic - 3
Liposarcoma-round cell - 3
Liposarcoma-well differentiated - 1
Malignant triton tumor - 3
MFH-giant cell - 3
MFH-pleomorphic with storiform pattern - 2
MFH-pleomorphic without storiform pattern - 3
Myxofibrosarcoma - 2
Osteosarcoma - 3
PNET - 3
Rhabdomyosarcoma-alveolar / embryonal / pleomorphic - 3
Synovial sarcoma - 3
Grading systems of soft tissue tumors - National Cancer

Institute (US) tumor grading system
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Grade 1: well differentiated liposarcoma; myxoid

liposarcoma (grade 2 in French system above);
subcutaneous myxoid MFH; well differentiated malignant
hemangiopericytoma with < 1 MF/10 HPF, no necrosis and
no hemorrhagic areas; well differentiated fibrosarcoma with
orderly herringbone pattern or well differentiated
leiomyosarcoma with orderly fascicular pattern plus well
differentiated cytologic features, no pleomorphism, no
necrosis, < 6 MF/10 HPF; malignant schwannoma (MPNST)
if resembles neurofibroma plus mitotic figures plus areas of
high cellularity but < 6 MF/10 HPF; myxoid chondrosarcoma
that is uniformly myxoid and hypocellular with no mitotic
activity
Grade 3: extraskeletal Ewings sarcoma, PNET,
extraskeletal osteosarcoma, mesenchymal chondrosarcoma,
malignant triton tumor, or other histologic types with 15% or
more necrosis
Grade 2: other histologic types with <15% necrosis
References: J Clin Oncol 1997;15:350, J Surg Oncol 1989;41:263
Cell types for soft tissue tumors

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Epithelioid: alveolar soft parts sarcoma, carcinoma

(extension into soft tissue or metastases), clear cell
sarcoma, epithelioid histiocytoma, epithelioid sarcoma,
epithelioid variant of leiomyosarcoma, MFH or MPNST;
extracellular myxoid chondrosarcoma, myxofibrosarcoma,
rhabdoid tumor, schwannoma, synovial sarcoma or vascular
tumors
Pleomorphic: variants of leiomyosarcoma, liposarcoma,
MFH, MPNST, myxofibrosarcoma, PHAT, pleomorphic
lipoma or rhabdomyosarcoma; also melanoma and
metastatic carcinoma
Round cell: desmoplastic small round cell sarcoma,
Ewings/PNET, mesenchymal chondrosarcoma, MPNST,
rhabdomyosarcoma, round cell liposarcoma, schwannoma
with neuroblastoma-like features, synovial sarcoma; also
carcinoma, lymphoma, melanoma, neuroblastoma, poorly
differentiated tumors
Spindle cell: angiosarcoma, benign fibrous histiocytoma,
benign nerve sheath tumor, DFSP, fibroma of tendon sheath
(cellular), fibromatosis, fibrosarcoma, Kaposis sarcoma,
leiomyosarcoma and leiomyoma, MPNST, nodular fasciitis,
spindle cell lipoma, spindle cell variant of embryonal
rhabdomyosarcoma, solitary fibrous tumor, superficial acral
fibromyxoma, synovial sarcoma
Architectural patterns of soft tissue tumors

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Alveolar: alveolar rhabdomyosarcoma, alveolar soft parts

sarcoma
Fascicular: fibromatosis, fibrosarcoma, neural tumors
(benign or malignant), smooth muscle tumors, synovial
sarcoma
Glandular: adenocarcinoma, biphasic synovial sarcoma,
glandular MPNST
Lobular: clear cell sarcoma, epithelioid sarcoma,
extraskeletal myxoid chondrosarcoma
Palisading: palisading intranodal myofibroblastoma,
Schwann cells (neural tumors), smooth muscle tumors,
spindle cell lipoma, synovial sarcoma
Pericytic vascular: mesenchymal chondrosarcoma, MFH,
myopericytoma, solitary fibrous tumor/hemangiopericytoma,
synovial sarcoma
Plexiform: nerve sheath tumors (neurofibroma,
schwannoma), plexiform fibrous histiocytoma
Plexiform vascular: low grade fibromyxoid sarcoma,
myxofibrosarcoma, myxoid liposarcoma, nodular fasciitis
Storiform: dermatofibrosarcoma protuberans (DFSP),
fibrohistiocytic tumors, dedifferentiated liposarcoma, low
grade fibromyxoid sarcoma, MFH, perineurioma
Molecular / cytogenetics of soft tissue tumors

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RT-PCR or FISH of paraffin-embedded tissue for tumor

fusion transcripts is useful (AJSP 2002;26:965, AJSP 2008;32:8)
Note: in table below, gene for first chromosome in
translocation is listed first
Alveolar soft parts sarcoma: t(X;17)(p11.2;q25) - ASPL-

TFE3 fusion gene
Aneurysmal bone cyst, extracellular: t(17;17)(p13;q12)
Angiomatoid fibrous histiocytoma: t(12;16)(q13;p11) -
ATF1-FUS fusion gene or t(12;22)(q13;q12) - ATF1-EWSR1
fusion gene (also present in clear cell sarcoma)
Chondroid lipoma of soft tissue: t(11,16)(q13;p12-13);
also in hibernoma
Chondrosarcoma, myxoid, extraskeletal: t(9;22)(q22;q12)
- CHN-EWS fusion gene
t(9;15)(q22;q21) - CHN-TCF12 fusion gene
t(9;17)(q22;q11) - CHN-RBP56 fusion gene
Clear cell sarcoma: t(12;22)(q13;q12) - ATF1-EWSR1
fusion gene
Congenital fibrosarcoma / mesoblastic nephroma:
t(12;15)(p13;q25) - ETV6-NTRK3 fusion gene
Dermatofibrosarcoma protuberans / giant cell
fibroblastoma: t(17;22)(q22;q13) - COL1A1-PDGFB fusion
gene
Desmoplastic fibroblastoma: occasionally t(2;11)(q31;q12)
or 11q12 abnormalities
Desmoplastic small round cell tumor: t(11;22)(p13;q12) -
WT1-EWS or t(21;22)(q22;q12) - ERG-EWS fusion genes
Ewings sarcoma/PNET, extraosseous:
t(11;22)(q24;q12) - FLI1-EWS fusion gene
t(21;22)(q22;q12) - ERG-EWS fusion gene
t(2;22)(q33;q12) - FEV-EWS fusion gene
t(7,22);(p22;q12) - ETV1-EWS fusion gene
t(17;22)(q12;q12) - E1AF-EWS fusion gene
Inflammatory myofibroblastic tumor: translocations at
2p23 involving ALK gene
Lipoma: t(12;14)(q13-15;q23-24) or related changes
involving HMGA2/HMGIC at 12q13-15
Liposarcoma-myxoid/round cell variants:
t(12;16)(q13;p11) - TLS-CHOP/FUS fusion gene or
t(12;22)(q13;q12) - CHOP-EWS fusion gene
Liposarcoma, well differentiated: marker ring or giant
chromosomes derived from 12q13-15; amplification of
MDM2 and CDK4
Low grade fibromyxoid sarcoma: t(7;16)(q32-34;p11) -
FUS-CREB3L2 or t(11;16)(p11;p11) - FUS-CREB3L1
Rhabdomyosarcoma, alveolar: t(2;13)(q35;q14) - PAX3-
FKHR or t(1;13)(p36;q14) - PAX7-FKHR
Synovial sarcoma: t(X;18)(p11.23;q11) - SYT-SSX1 or
t(X;18)(p11.21;q11) - SYT-SSX2 fusion genes
Tenosynovial giant cell tumor: t(1;2)(p11;q35-37)
References: Archives 2006;130:1199
Infections, inflammation and hematomas of Soft

Tissue
Infections of Soft Tissue - general
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Usually due to direct extension from infections of skin, bone

or viscera, or due to trauma or surgery
Granulomatous infections of soft tissue

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Due to tuberculosis, fungi, atypical mycobacteria (Clin Infect

Dis 1995;21:65, Int J Tuberc Lung Dis 2007;11:96)
Case reports: Brucella gluteal abscess (Intern Med 2008;47:171)
Hematoma of soft tissue

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May clinically resemble a tumor if deep seated
Sites: usually near tensor fascia lata (upper thigh muscle,
image)
Important to exclude a sarcoma with intratumoral
hemorrhage
Pseudoaneurysm may occur after intravascular procedures
Post-operative seromas may persist for years and be
confused with recurrent tumor
Case reports: in tensor fascia lata (Dermatol Online J 2001;7:6),
giant chronic expanding hematoma of thigh (Joint Bone Spine
2008;75:64), mass of thorax (Yonsei Med J 2007;48:337)
Treatment: complete surgical excision, including
pseudocapsule
Clinical images: lesion of lateral thigh
Gross images: perforating vessel (arrow) from tensor
fascia lata appears to run into the mass; lobulation with
dense fibrous pseudocapsule and chocolate-brown fluid
Micro images: cystic cavity with necrotic debris, fibrin
and blood costs; cyst wall has hyalinized fibrous tissue,
chronic inflammation and granulation tissue
Necrotizing fasciitis of soft tissue

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Definition: uncommon fulminant soft tissue infection

characterized by extensive fascial necrosis
Pathophysiology: usually due to group A streptococci, also
community-acquired MRSA (Surg Infect (Larchmt) 2008;9:469)
May be due to Clostridium perfringens and cause gas
gangrene (Cases J 2008 Oct 20;1(1):252)
In children, associated with varicella and speC gene in group
A streptococcal strains (Pediatr Infect Dis J 2009 Apr 14 [Epub ahead
of print])
Clinical: fatal if untreated; 15% mortality even if treated
(Epidemiol Infect 2009 Apr 7:1 [Epub ahead of print])
Particularly serious in patients with badly controlled diabetes
(Diabetes Res Clin Pract 2008;80:218)
Case reports: due to Pseudomonas (Intern Med 2008;47:553)
Treatment: promptly start antibiotics and aggressive
debridement (World J Emerg Surg 2007;2:19, J Am Acad Orthop Surg
2009;17:174)
Clinical images: gas gangrene #1; #2-right shoulder;
left leg
Micro images: gluteal gas gangrene with necrotizing
fasciitis #1; #2; #3-gram stain; #4-gram stain; #5;
necrotic muscle with gas bubbles but minimal
inflammation; infected tissue with gas-inclusion
between the muscle fibers; gram positive rods; leg
lesion #1; #2; #3; #4; #5; #6-septic thrombus; #7-
associated vasculitis; #8-gram stain; #9-gram stain
References: eMedicine #1; #2
PVP granuloma of soft tissue

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Definition: granuloma due to injection of drugs containing

polyvinylpyrrolidone (PVP)
Rare (Am J Surg Pathol 1984;8:393)
Micro: focal cellularity, focally myxoid with foamy histiocytes
containing vacuoles and PVP
Positive stains (histiocytes): mucicarmine, colloidal iron,
GMS, Congo Red, Sudan Black B
DD: myxoid liposarcoma, signet ring carcinoma
Tumoral calcinosis of soft tissue

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Definition: large painless calcified masses in periarticular

soft tissues, including elbows, hips, only rarely knees
Also called calcium hydroxyapatite deposition in soft tissue,
metastatic calcification
Usage is imprecise - refers to hereditary condition associated
with massive periarticular calcification; also any massive
collection of periarticular calcification (Radiographics 2006;26:871)
Clinical: associated with trauma, renal failure,
hyperparathyroidism, metastatic carcinoma, myeloma,
scleroderma, hypermetabolic states, sarcoidosis
Associated with mutations in fibroblast growth factor-23 gene
and other genes (J Bone Joint Surg Am 2009;91:1190, OMIM #212900)
Rarely is familial (AJSP 1993;17:788)
Laboratory: elevated serum calcium, phosphate and
Vitamin D
Local recurrence common
Xray: lobulated calcifications, separate from associated
bone
Gross: large, multinodular, chalky masses
Micro: lobules of calcific material surrounded by histiocytic
giant cells often containing small psammomatous
calcifications
Micro images: low power; calcification with foreign
body inflammation
Differential diagnosis: dystrophic calcification - dead tissue
that is not rapidly absorbed; associated with coagulation
necrosis, caseous necrosis, fat necrosis
Fibroblastic / myofibroblastic tumors of soft

tissue
Normal histology of soft tissue
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Fibrous tissue consists of fibroblasts and extracellular matrix

Extracellular matrix consists of collagen, elastin and ground
substance
Fibrous tissue: loose or dense; dense fibrous tissue
includes tendons (connect muscle to bone), ligaments
(connect bones or cartilage to each other), aponeuroses
(ribbon like tendinous expansion)
Fibroblasts: spindled (along collagen fibers) to stellate (star
shaped-in myxoid areas); produce various collagens;
positive for vimentin, actin
Fibrocytes: quiescent stage of fibroblasts
Myofibroblasts: modified fibroblasts with multiple possible
origins (diagram), including transition from fibroblasts during
tissue repair (J Invest Dermatol 2007;127:526); features are
intermediate between fibroblasts and smooth muscle cells
References: Wikipedia-fibroblasts, Wikipedia-myofibroblasts, Am J
Pathol 2007;170:1807
Fibroblastic / myofibroblastic tumors of soft tissue -

general
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Large subset of mesenchymal tumors

Cells / tumors may have both fibroblastic and myofibroblastic
features
Angiomyofibroblastoma of soft tissue

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Definition: benign, well-circumscribed myofibroblastic

tumor, usually in vulva
May overlap with cellular angiofibroma
First described in 1992 (AJSP 1992;16:373)
Clinical: uncommon slow growing painless mass, usually
females of reproductive age
Sites: usually vulvar, 10-15% in vagina; also scrotum or
paratesticular soft tissue in men (median age 57 years)
Case reports: recurrence in vagina (Eur J Gynaecol Oncol
2007;28:324), pedunculated vulvar mass (Acta Med Okayama
2006;60:237), sarcomatous transformation in vulva ( AJSP
1997;21:1104), 27 year old man with inguinal tumor (Archives
2000;124:1679), 49 year old man with scrotal mass (Univ
Oklahoma)
Treatment: excision, only rarely recurs, does not
metastasize
Gross: well circumscribed but not encapsulated, usually 5-7
cm or less, tan-pink soft cut surface, no necrosis
Micro: thin fibrous pseudocapsule, alternating hyper- and
hypocellular areas with prominent thin walled and ectatic
vessel in edematous stroma; round to spindled tumor cells
have eosinophilic cytoplasm and often bi- or multi-
nucleation; may have plasmacytoid or epithelioid
morphology, or rarely show degenerative changes; tumor
cells are concentrated around vessels; mast cells common;
10% have mature adipose tissue; no/rare mitotic figures,
no/rare red blood cell extravasation, no atypia; post-
menopausal patients have less cellularity, less edema but
more fibrosis and vessel wall hyalinization
Micro images: gross and H&E; fig A: numerous
capillary-like vascular channels, fig B: spindle cells with
occasional multinucleated cells; male inguinal region-
actin, desmin, CD34; scrotal mass-various images;
arising from posterior perivesical space
Positive stains: vimentin, desmin (strong and diffuse, may
be reduced in post-menopausal patients), ER, PR, smooth
muscle actin or pan-muscle actin (focal, Hum Path 1997;28:1046),
occasional CD34
Negative stains: S100, keratin
EM: myofibroblastic and fibroblastic features
Differential diagnosis:
aggressive angiomyxoma - not circumscribed, > 5 cm, less
cellular, less vascular but vessels are large and thick walled,
stromal mucin and RBC extravasation are present,
infrequent plump stromal cells, usually actin negative
cellular angiofibroma - more cellular uniformly, perivascular
hyalinization and large, thick walled vessels, usually
actin/desmin negative
epithelioid leiomyoma - more cellular, no biphasic pattern,
usually no binucleation, no/rare mast cells
Reference: Mod Path 1996;9:284, Stanford School of Medicine
Calcifying aponeurotic fibroma of soft tissue

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Definition: rare, slow growing, painless tumor with

fibroblasts palisading around chondroid or calcified nodules,
usually in hands and feet of children or young adults
Also called juvenile aponeurotic fibroma
Clinical: 50% recur, especially in children; does not
metastasize
May be cartilaginous analog of fibromatosis
Case reports: 16 year old girl with foot tumor (Case of the Week
#47), 36 year old woman with distal phalangeal bone
involvement (Korean J Radiol 2008;9:91)
Treatment: conservative excision with reexcision as
necessary for recurrences
Clinical images: 46 year old woman
Gross: nodular or infiltrative gray-white, gritty mass in
subcutaneous tissue or tendon, may be calcified, usually 3
cm or less in hands or feet, may be larger elsewhere
Gross images: non-encapsulated and ill-defined mass
Micro: nodules of plump or epithelioid fibroblasts palisading
around cartilage and spotty calcification; cells have indistinct
and variable cytoplasm, plump oval nuclei with vesicular
chromatin that may be condensed below nuclear membrane;
fibrocytes in stroma between nodules have dense, evenly
dispersed chromatin; may infiltrate fat or striated muscle at
periphery; frequent osteoclast-like giant cells; rare mitotic
figures, no atypia; more cellular in very young
Micro images: AFIP - poorly circumscribed

fibroproliferative process with scattered, linear and
calcified zones; amorphous calcification surrounded by
palisading cells suggestive of rheumatoid nodule or
crystals; typical zonation pattern has cellular, plump
fibroblastic cells palisading around a hyalinized
collagenous zone, which in turn surrounds the
calcification; cells adjacent to hyalinized layer are
commonly more rounded; chondroid area is adjacent to
calcification
other - spotty calcifications and chondroid-like cells;

palisading tumor cells #1; #2
16 year old girl with foot tumor - #1; #2; #3; #4; #5
Calcifying aponeurotic fibroma of soft tissue (continued)

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Cytology: benign appearing spindle cells, chondroid cells,

multinucleated giant cells and calcified debris (Diagn Cytopathol
2001;24:336)
Positive stains: vimentin, CD68, CD99, S100, muscle
specific actin (50%), smooth muscle actin (50%)
Negative stains (usually): CD34, CD57, PR
EM: chondrocytes, fibroblasts and occasional myofibroblasts
Molecular/cytogenetics: benign, but may be aneuploid
(Cancer 1994;73:1200)
infantile fibromatosis - usually involves head, neck and
proximal extremities in infants, not hands and feet of
children/young adults, background is more myxoid than
chondroid, calcification is rare
superficial [palmar and plantar] and desmoid fibromatosis -
usually lack calcification or chondroid differentiation
chondroma of soft parts - may involve hands, but usually
well circumscribed with more well developed chondroid
differentiation, no infiltration of adjacent tissue, no
surrounding epithelioid cells
fibrous hamartoma of infancy - immature mesenchyme,
fibroblasts are arranged in trabeculae but no palisading, no
cartilage or calcification, not hands and feet
References: Hum Path 1998;29:1504, Acta Orthop Belg 2001;67:412,
Stanford University
Calcifying fibrous tumor of soft tissue

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Definition: benign fibrous lesion with abundant hyalinized

collagen, psammomatous or dystrophic calcifications and
lymphocytic infiltration
Also called calcifying fibrous pseudotumor
Clinical: adolescents/young adults, all sites
Not related to inflammatory myofibroblastic tumor (Mod Path
2001;14:784, Int J Surg Pathol 2002;10:189)
Case reports: 24 year old woman with neck mass (Archives
2000;124:435), tumors of small intestine (Ann Diagn Pathol
2008;12:138), multiple peritoneal tumors #1 (Ann Diagn Pathol
2007;11:460),#2-familial (AJCP 2003;119:811), multiple pleural
tumors (Virchows Arch 2005;446:78, J Thorac Oncol 2008;3:1356)
Treatment: excision, rarely recurs
Gross: well circumscribed but unencapsulated, variable
size, may infiltrate into surrounding tissue, may have gritty
cut surface
Gross images: gray-white tumor with whorled cut
surface; well circumscribed tumor (adrenal gland)
Micro: paucicellular fibroblastic proliferation with
lymphocytes (possibly lymphoid follicles), plasma cells,
eosinophils, mast cells, dense collagenous tissue, varying
degrees of calcification; border is often at least partially
infiltrative
Micro images: AFIP - adrenal gland tumor has

paucicellular fibrous proliferation with focal
microcalcifications; microcalcifications vary in size;
lymphoplasmacytic inflammation is characteristic
other - psammoma body, lymphocytic infiltrate,
hypocellular stroma; figures 1A, 1B, 1E and 1F
(comparison with inflammatory myofibroblastic tumor);
hyalinized collagen with psammoma body; various
images (adrenal gland)
Calcifying fibrous tumor of soft tissue (continued)

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Positive stains: Factor XIIIa, vimentin; also CD34

Negative stains: smooth muscle actin, muscle specific
actin, ALK, desmin, S100, keratin
EM: immature fibroblastic cells, collagen fibrils, dystrophic
and psammomatous calcifications
EM images: figure 2A
inflammatory myofibroblastic tumor - more cellular, no
calcifications, ALK+, actin+
idiopathic retroperitoneal fibrosis and related sclerosing
fibroinflammatory lesions - more inflammation, especially
plasma cells and eosinophils
desmoplastic fibroblastoma - older patients, low cellularity,
larger prominent fibroblasts, no microcalcifications, no
prominent inflammatory infiltrate
calcifying aponeurotic fibroma - more cellular, usually distal
location, usually smaller lesion
References: Stanford University
Cellular angiofibroma of soft tissue
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Definition: benign, highly cellular tumor of vulva and

scrotum/inguinal region with prominent blood vessels
Also called angiomyofibroblastoma-like lesion
First described in 1997 (AJSP 1997;21:636); may be related to
angiomyofibroblastoma and spindle cell lipoma
In women, may arise from hormone receptor positive
mesenchymal cells in lower female genital tract (Histopathology
2004;45:360)
Rare; usually ages 40+ years
Extragenital cases have similar features (APMIS 2007;115:254)
Case reports: 44 year old woman with leiomyomatous
nodules (Virchows Arch 2009;454:595), 51 year old woman with
coexisting Bartholins cyst (Sao Paulo Med J 2005;123:250),
recurrent tumor (J Clin Pathol 2002;55:477)
Treatment: excision with negative margins; usually does not
recur (AJSP 2004;28:1426)
Gross: vulvar lesions are usually up to 3 cm, male lesions
may reach 14 cm; well circumscribed nodules with soft to
rubbery, gray-pink-brown cut surface
Micro: well circumscribed, variable pseudocapsule; cellular
tumor with fascicles or haphazard pattern; bland spindle
cells with scant, lightly eosinophilic cytoplasm with ill defined
borders, oval to fusiform nucleus; may be epithelioid;
prominent small to medium-sized vessels with hyaline
fibrosis in walls; vessels may have degenerative changes of
fibrin thrombi, intramural inflammation, hemosiderin; some
(usually 5% or less) adipose tissue present in 50%; stroma is
usually fine collagenous fibers; scattered mast cells are
common; female lesions may have brisk mitotic activity,
usually absent/rare in males; occasional atypia; no necrosis,
no atypical mitotic figures
Micro images: fusiform cells, thick walled blood vessels
and adipose tissue; fusiform cells with clear cytoplasm
and bland nuclei; various images; recurrent tumor;
ER+
Virtual slides: 63 year old man with scrotal mass
Positive stains: ER, PR, vimentin; smooth muscle actin
(21%), CD34 (30-60%)
Negative stains: S100, desmin, EMA
Cytogenetics: may have 13q14 involvement; similar
changes as spindle cell lipoma (Cancer Genet Cytogenet
2007;177:131)
Cellular angiofibroma of soft tissue (continued)
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aggressive angiomyxoma - usually large and deep,
hypocellular, infiltrative margin, desmin+
angiomyofibroblastoma - less uniform cellularity, smaller
vessels, usually desmin+
solitary fibrous tumor - hyper- and hypocellular areas,
prominent staghorn vessels, hyalinized collagen CD34+
perineurioma
PHAT
leiomyoma - spindled cytoplasm, actin+, desmin+
References: Stanford School of Medicine
Dermatofibrosarcoma protuberans (DFSP) - Soft Tissue

Tumor chapter
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See Skin-Nonmelanocytic tumors chapter
Desmoplastic fibroblastoma of soft tissue

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Definition: fibroblastic lesion centered in subcutaneous

tissue with reactive fibroblasts, low cellularity and abundant
collagen
Also called collagenous fibroma
Epidemiology: rare benign lesion of adult men (70%
between ages 40 and 69 years)
Sites: usually upper extremities, back, feet
Case reports: 41 year old woman with thigh mass (J Cutan
Pathol 2008;35 Suppl 1:70)
Treatment: conservative excision, does not recur or
metastasize
Gross: usually 1-4 cm, well circumscribed, may be
lobulated, has firm and homogeneous gray cut surface
resembling cartilage
Gross images: well circumscribed tumor
Micro: paucicellular, bland spindled (stellate) and reactive
appearing fibroblasts and myofibroblasts separated by
abundant collagen with variable myxoid stroma; fibroblasts
have amphophilic cytoplasm, vesicular nuclei and distinct
nucleoli; 70% of cases involve subcutis, 25% extend into
skeletal muscle
Micro images: AFIP - large, reactive appearing spindled
fibroblasts in fibrous matrix; focus of low cellularity and
dense collagen; more cellular area with reactive type
fibroblasts
other - scattered stellate cells in hypovascular
collagenous matrix; hypocellular lesion with
pseudocapsule and sparse cells separated by abundant
collagen; spindle cells with long nuclei in dense
collagenous stroma; vimentin+; most cells are negative
for smooth muscle actin
Positive stains: vimentin, variable alpha smooth muscle

actin
Negative stains: desmin, EMA, S100, CD34
EM: may have fibronexus junctions, markers of
myofibroblastic differentiation (Ultrastruct Pathol 2004;28:149)
Molecular/cytogenetics: t(2;11)(q31;q12) or 11q12
abnormalities observed rarely (Cancer Genet Cytogenet
2004;149:161)
Differential diagnosis: fibromatosis - not circumscribed,
more cellular, fascicular pattern, prominent vasculature (Adv
Anat Pathol 1999;6:275)
References: Hum Path 1998;29:676, AJSP 1995;19:1077, Stanford
University
Elastofibroma of soft tissue

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Definition: age 55+ years, benign, poorly circumscribed

pseudotumor of subscapular region, composed of collagen
and coarse enlarged elastic fibers; a reactive hyperplasia
involving abnormal elastogenesis
Also called elastofibroma dorsi
First described in 1961 by Jarvi and Saxen (Acta Pathol
Microbiol Scand 1961;51:83)
Epidemiology: associated with hard manual labor; related
changes found at autopsy in 13-17% of elderly; more
common in women
Sites: more common on apex of scapula, usually right sided;
occasionally in deltoid muscle, infraolecranon area, hip,
thigh, stomach
May be multiple, bilateral or familial; may be periosteal in
origin
Slightly different amino acids from elastin; has collagen
types I-III (type II normally restricted to articular cartilage and
ocular structures)
Case reports: 55 year old woman (Case of the week #46), 69 year old
man with tumor of hand (J Bone Joint 1987;89:468), 69 year old woman
with bilateral subscapular tumors and tumor surrounding a stomach ulcer
(AJSP 1985;9:233), 78 year old man with multiple subcutaneous nodules
(J Am Acad Dermatol 2004;50:126)
Treatment: excise if symptomatic, does not recur
Clinical images: shoulder based tumors; typical
location (arrow)
Gross: ill defined, rubbery, gray-white fibrous tissue mixed
with yellow streaks of elastin; up to 15 cm
Gross images: fibrocollagenous areas blend with fat
(AFIP); poorly defined fibroelastic tumor entrapping fat
#1; #2; #3; gray-white fibrous tissue mixed with fat
Micro: collagen bundles alternate with large, thick
eosinophilic elastic cylinders with a dense central core,
elastic fibers may be fragmented into linear globules (beads
on a string); often has irregular interdigitation into adipose
tissue
Elastofibroma of soft tissue (continued)

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Micro images: AFIP - paucicellular fibrous tissue mixed

with fat; thick, densely eosinophilic elastin bands are
mixed with collagen; elastin bands have serrated edges
and are associated with detached globular elastin
arranged like beads on a string; Verhoeff elastin stain
highlights elastin fibers and the bead-like arrangement
of the elastin globules
other - thick bands of fibrous tissue (long arrows)

intermixed with multiple regions of mature adipose
tissue; diagnostic rods of elastic tissue; fibrous tissue
mixed with elastin bands; fibrohyaline mass within
adipose; branched (arrow) and unbranched coarse
elastin fibers mixed with collagen and adipose; H&E
and elastic stain; elastin stain #1; #2; #3; #4
case of the week #46: image #1; #2; #3; #4; #5; #6;
#7; orcein (elastin) stain
Cytology: hypocellular smear with diagnostic aggregates of

globules within a collagenous matrix; altered elastic fibers
have green-yellow autofluorescence with ultraviolet light
(Diagn Cytopathol 2002;26:310)
Positive stains: vimentin, elastic stains (fibers have dense
core and irregular margins), CD34 in spindle cells (Virchows
Arch 2006;448:195)
Negative stains: S100, desmin, smooth muscle actin, p53
EM: cylinders composed of immature amorphous elastic
tissue, central core contains mature fibers, removed by
elastase digestion (J Electron Microsc (Tokyo) 2006;55:89)
Molecular/cytogenetics: Xq12-q22 or #19 gains in 30% (Int
J Mol Med 2002;10:277)
nuchal fibroma - younger than 55 years, between scapula
and vertebrae, dense collagen but no elastic fibers
fibrolipoma - no elastic fibers
desmoid fibromatosis - more cellular, infiltrates skeletal
muscle, no elastic fibers
References: Ann Diagn Path 2002;6:94, World J Surg Oncol 2007;5:15,
Sarcoma 2008;2008:756565, eMedicine, Stanford University
Eosinophilic fasciitis of soft tissue

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Definition: diffuse fasciitis with fibrosis, eosinophilia and

inflammation of skin, subcutaneous tissue and fascia
Rare fibrosing disorder with scleroderma-like induration of
distal extremities
Not a WHO diagnosis
First described by Shulman (Trans Assoc Am Physicians
1975;88:70) [also called Shulmans syndrome]
Epidemiology: mean age 50 years, 75% women
Eosinophilic-myalgia syndrome is different, and is associated
with contaminated L-tryptophan, myalgia and neuritis
(eMedicine)
Presence of morphea-like skin lesions is associated with
residual fibrosis (Clin Rheumatol 2007;26:1445)
Case reports: 76 year old woman (Dermatology Online Journal
9(4):33), paraneoplastic phenomenon associated with
metastatic colorectal carcinoma (Australas J Dermatol 2008;49:27)
Treatment: high dose corticosteroids (Int J Dermatol 2008;47:29)
Gross: woody, firm subcutaneous mass
Micro: eosinophils, lymphocytes, mast cells and histiocytes
in fibrotic or fibromyxoid stroma of subcutis and fascia
Micro images: thickening of fascia with chronic
inflammatory infiltrate #1; #2; #3; #4; #5; #6;
inflammatory infiltrate in deep subcutis #1; #2
References: eMedicine #1; #2
Fibroma of tendon sheath of soft tissue

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Definition: well circumscribed, lobulated fibrous tumor

attached to tendon or tendon sheath
Also called tenosynovial fibroma
Benign, uncommon; may overlap with nodular fasciitis (AJSP
1989;13:472) or giant cell tumor of tendon sheath (Mod Path
1995;8:155)
Epidemiology: 60% men, ages 30-50 years old with nodule
on fingers, hands or wrist
Case reports: tumors of palmar flexor sheath (Internet Journal
of Hand Surgery. 2008 Volume 2 Number 1), medial canthus of eye
(Ophthal Plast Reconstr Surg 2007;23:341)
Treatment: excise to relieve symptoms but preserve
function, may be difficult to remove from adherent tendons;
benign, but up to 24% recur, does not metastasize
Gross: well circumscribed, small fibrous multinodular mass
< 3 cm, cut surface is pale, solid and homogeneous
Micro: well circumscribed nodules of dense fibrous tissue
with occasional spindle or stellate mesenchymal cells in S or
C shaped patterns; cells have scant cytoplasm and elongate
nuclei with evenly distributed fine chromatin; often dilated or
slit-like channels / clefts resembling tenosynovial spaces;
varies from cellular to paucicellular; may have bizarre tumor
cells, extravasated red blood cells, but no atypical mitotic
figures, no necrosis, no hyperchromasia
Micro images: AFIP - multinodular proliferation;

extensive collagenization of nodules produces this
typical, eosinophilic, paucicellular appearance,
incomplete separation of the nodules produces cleft-like
spaces; most cases are paucicellular with scattered
spindled fibroblasts in a densely collagenized matrix
and scattered small vessels; transition from
collagenous to cellular area; cellular area resembles
leiomyosarcoma or fibrosarcoma, but these tumors are
rare in hands and feet; fibroblasts are bland (ruling out
sarcoma) and separated by collagen
other - predominately acellular fibrous tissue with areas

of hyalinization and characteristic slit-like vascular
channels; tumor of finger #1; #2; #3; hypocellular
lesion with abundant collagen; spindled fibroblasts in
collagenous stroma with slit like vascular channels
Fibroma of tendon sheath of soft tissue (continued)

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Cytology images: loose cohesive clusters of bland

spindle cells with variable cytoplasm, oval to elongated
nuclei; spindle cells in hyalinized collagen
Positive stains: smooth muscle actin, vimentin
EM: resembles myofibroblasts and fibroblasts
EM images: spindle cells in collagenous matrix (M) have

oval and convoluted nuclei (N), clefts (C) are present
between cells and nuclei; spindle cell has a convoluted
nucleus (N), rough endoplasmic reticulum (RER),
vacuoles (V) and thin band of myofilaments just beneath
the plasma membrane (arrows); myofilament bundles
(M) show periodic densities (arrows); spindle cell has
rough endoplasmic reticulum (RER), myofilaments (M)
and pinocytotic vesicles (arrows)
Molecular/cytogenetics: may have t(2;11)(q31-32;q12)

(Histopathology 1998;32:433)
sarcoma - rare in hands and feet, usually large masses
with cellularity, marked chromatin abnormalities and
abnormal mitotic figures
benign fibrous histiocytoma - usually not hands or feet,
prominent histiocyte-like cells, foam cells, giant cells and
hemosiderin, CD68+
giant cell tumor of tendon sheath - more cellular, cells have
histiocyte-like nuclei, also prominent giant cells, foam cells,
hemosiderin; no slit-like vascular spaces, no extensive
hyalinized stroma
Fibromatosis of soft tissue - general

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Definition: proliferation of histologically benign appearing

myofibroblasts and fibroblasts or primitive mesenchymal
cells (pediatric fibromatoses) with infiltrative growth,
collagenous stroma, low to moderate mitotic activity,
aggressive behavior with local recurrence, but no
metastases
Divided into adult and pediatric types
Adult types: includes deep (or desmoid) fibromatoses and
superficial fibromatoses (described below); those that arise
within and deep to fascia are called desmoid fibromatoses
(also desmoid tumor or aggressive aponeurotic
fibromatoses); those limited to fascia and superficial soft
tissue plane (palmar, plantar, penile fibromatoses and
knuckle pads) are less aggressive but recur frequently
Pediatric fibromatoses: includes numerous entities
described below including infantile desmoid, inclusion body
(or infantile digital), myofibroma/myofibromatosis, Gardner
fibroma, fibromatosis coli and others; often characterized by
primitive mesenchymal cells in addition to myofibroblasts
and fibroblasts
Fibromatosis superficial, of soft tissue

Palmar fibromatosis (Dupuytrens contracture) - Soft
Tissue Tumor chapter
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Definition: nodular proliferative process of palmar

aponeurosis, surrounding adipose and occasionally dermis,
due to fibroblasts, myofibroblasts and fibrocytes
Most common type of fibromatosis (1-2% of population),
prevalence increases with age (24% at age 65+)
Epidemiology: 75% are men; 50% are bilateral, 10% also
have plantar disease, 1-4% have penile fibromatosis
Clinical: puckers overlying skin as it ages; causes flexion
contracture of digits 4 and 5 due to cord-like expansion of
digital aponeurotic slips; does not involve deep structures
such as tendons or skeletal muscle; may be caused by
fibrogenic cytokines (J Hand Surg [Br] 2005;30:557)
Treatment: observation, excision or incision of contracture
band; often recurs
Clinical images: flexion contracture #1; #2
Gross: small nodules or nodular masses associated with
aponeurosis and subcutaneous fat, with gray-yellow-white
cut surface (color depends on collagen content)
Micro: proliferative phase - uniform, plump, immature
spindle cells (myofibroblasts and fibroblasts) with bland
nuclei and indistinct nucleoli; moderate collagen and
elongated vessels; older lesions - more dense collagen,
less cellularity; variable mitotic figures; occasional
attachment to dermis or cartilaginous metaplasia; usually no
infiltration of surrounding tissue beyond subcutis
Micro images: AFIP - nodule of variably cellular
fibroblastic tissue infiltrates an aponeurosis, with bland,
uniform spindled cells in a dense hyalinized collagen
stroma; mitotic figures may be present in cellular
regions but are never atypical
other - tumor of myofibroblasts and fibroblasts within
fascia #1; #2; #3; various images
Positive stains: vimentin, variable muscle specific and
smooth muscle actin (in proliferative phase)
Negative stains: keratin, CD34
EM: fibroblasts and myofibroblasts
Molecular/cytogenetics: near diploid, often +7 or +8, no
gene amplifications or deletions (Cancer Genet Cytogenet
2008;183:6), reactive not neoplastic (J Transl Med 2006;4:21), no
somatic mutations of beta-catenin genes unlike desmoid
fibromatosis (Mod Path 2001;14:695)
fibrosarcoma - single large mass of deep soft tissue with
intersecting bundles of cells whose nuclei have abnormal
chromatin
epithelioid sarcoma - common in hands, but some cells
have distinctive epithelioid appearance with abundant bright
eosinophilic cytoplasm, also necrosis, keratin+, CD34+
desmoid tumors - rare in hand, dominant mass infiltrates
skeletal muscle
References: eMedicine, Stanford University, Wikipedia
Plantar fibromatosis (Ledderhoses disease) - Soft

Tissue Tumor chapter
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Definition: nodular proliferative process of plantar

aponeurosis and surrounding adipose due to fibroblasts,
myofibroblasts and fibrocytes
Heterogeneous group of conditions with plantar location,
mature collagen and fibroblasts, but no malignant features
(eMedicine)
Epidemiology: common in boys < 10 years old and
teenagers; associated with palmar and penile fibromatosis,
also continuous phenobarbital treatment for epilepsy
(Epilepsia 2008;49:1965); usually NOT associated with
contractures
Clinical: only 10-25% bilateral, may be nodular; often
presents with firm subcutaneous nodule or thickening
associated with pain after standing or walking typically on
the medial aspect of the sole
Clinically resembles melanoma, synovial sarcoma, Kaposis
sarcoma
Treatment: observation, surgery if symptomatic,
fasciectomy has fewer recurrences (25%) than local excision
(100%, Plast Reconstr Surg 2008;122:486)
Clinical images: mass along medial plantar surface;
various images
Gross: 2-3 cm nodules associated with aponeurosis and
subcutis, with gray-yellow-white cut surface (color depends
on collagen content)
Gross images: plantar nodules; nonencapsulated
whitish tumor
Micro: proliferative phase - hypercellular collection of
uniform, plump, immature spindle cells with bland nuclei and
indistinct nucleoli; moderate collagen and elongated vessels;
variable multinucleated giant cells (AJSP 2002;26:244); older
lesions - denser collagen, less cellularity; often prominent
chronic inflammation, variable mitotic figures and
hemosiderin
Positive stains: vimentin, variable muscle specific and
smooth muscle actin
EM: fibroblasts and myofibroblasts
Molecular/cytogenetics: near diploid, often +7 or +8, no
somatic mutations of beta-catenin genes unlike desmoid
fibromatosis (Mod Path 2001;14:695)
monophasic synovial sarcoma - uniformly hypercellular,
often staghorn vascular pattern or ropy collagen
fibrosarcoma - single large mass of deep soft tissue with
intersecting bundles of cells with abnormal chromatin,
herringbone pattern
desmoid fibromatosis - rare in feet, infiltrates skeletal
muscle, > 3 cm, often beta-catenin+
calcifying aponeurotic fibroma - plump or epithelioid
fibroblasts palisading around cartilage and spotty
calcification
References: AJSP 2005;29:1095 (children), Stanford University,
Wikipedia
Penile fibromatosis (Peyronies) - Soft Tissue Tumor

chapter
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Definition: fibrous thickening of dermis and Bucks fascia

between corpora cavernosa and tunica albuginea, causing
curvature towards side of lesion and restricting movement of
these structures during erection
Epidemiology: typically age 40+ years, rarely age 40 or less
(J Androl 2003;24:27)
Various etiologies (microvascular trauma-Int J Impot Res
2002;14:406, urethritis, sclerosing inflammatory process,
idiopathic), appears to differ from other superficial
fibromatoses (Curr Urol Rep 2004;5:478) although associated with
them
Prevalence 3-9% (Int J Impot Res 2002;14:379), associated with
plaques, pain, induration, deviation
Usually dorsolateral penis, 30% have inflammatory
component
Case reports: with ossification (Sao Paulo Med J 2007;125:124)
Treatment: may spontaneously regress, responds to small
amounts of irradiation, steroids, other intralesional injections
(J Androl 2008 Oct 30 [Epub ahead of print]); also plaque excision
and grafting (Eur Urol 2008 Dec 3 [Epub ahead of print])
Micro: disorganization of collagen of tunica albuginea with
formation of nodules, often hyalinizing fibrosis, perivascular
lymphocytic infiltrate in 1/3, linear band of calcification in 1/4
(J Urol 1997;157:282)
Micro images: short abnormal elastin fibers
EM: penile plaques are composed of collagen fibrils,
amorphous particulate material and fibroblasts (Int J Urol
1997;4:274)
DD: epithelioid sarcoma (may clinically appear similar, Int J
Impot Res 2003;15:378)
References: Wikipedia, Knol
Fibromatosis - deep (desmoid type), of soft tissue

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Definition: clonal fibroblastic proliferation of deep soft tissue

with infiltrative growth; locally aggressive (local recurrence,
but no metastases)
See also description at other sites, including breast, colon,
small bowel
"Desmos" (Greek) means tendon-like
Epidemiology: incidence of 2-4 per million population, less
common than superficial fibromatosis
May be familial (associated with Gardners syndrome/FAP
syndrome, Clin Gastroenterol Hepatol 2008;6:215 or familial
desmoid syndrome, Am J Hum Genet 1996;59:1193) or related to
trauma
Usually ages 15-39 years, may be painful; common sites in
children are head and neck
May be fatal due to local effects, particularly in head and
neck
Can be staged based on size, symptoms and
complications (Dis Colon Rectum 2008;51:897)
Abdominal fibromatosis: arises within abdominal wall of
women during or after pregnancy; may see with cesarean
section scar
Extraabdominal fibromatosis: arises outside abdomen and
abdominal wall, usually in muscles of shoulder, chest wall,
back and thigh, equal gender frequencies
Intraabdominal fibromatosis: mesenteric, pelvic or
retroperitoneal locations, associated with Gardners
syndrome (familial adenomatous polyposis, multiple
osteomas); often post-surgical
Case reports: 27 year old woman with post-traumatic
paraspinal mass (World J Surg Oncol 2008;6:28), 29 year old
women with tumor of abdominal wall (Radiology 2005;236:81,
Internet Journal of Surgery 2007;10(2)), 30 year old man with
aggressive mesenteric tumor that responded to
chemotherapy (Jpn J Clin Oncol 2008;38:222), 43 year old woman
with tumor of retroperitoneal space (World J Surg Oncol 2004;2:33)
Treatment: excision with wide margins and possibly frozen
section evaluation of margins (Ann Surg Oncol 2009;16:1642),
inadequate excision may cause recurrence, less recurrence
in abdominal wall than elsewhere but may recur 5-6 times;
may stop growing if stop excising, some recommend
watchful waiting if asymptomatic or not growing, Expert Rev
Anticancer Ther 2009;9:525), may respond to chemotherapy (J Clin
Oncol 2007;25:501), COX2 inhibitors (Urology 2007;70:591.e3),
imatinib (J Cancer Res Clin Oncol 2007;133:533), NSAIDs (World J
Surg Oncol 2008;6:17), radiation (Am J Clin Oncol 2005;28:211),
tamoxifen or watchful waiting (Eur J Surg Oncol 2008;34:462)
Clinical images: swollen calf #1; #2
Gross: large, firm, white cut surface, infiltrative borders;
often in muscular fascia, cuts with gritty sensation, 5-10 cm

(continued)
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Gross images: AFIP - extra-abdominal fibromatosis has

dense white, trabeculated fibrous tissue that invades
skeletal muscle and produces cross section of
alternating white and red patches; desmoid
fibromatosis (left) contrasted with high-grade
fibrosarcoma (right) - fibromatosis has gristle-like
consistency, but fibrosarcoma tends to be white, fleshy
and necrotic with an overlying tendon
other - tumor infiltrates thoracic wall; trunk tumor #1;
#2; thigh tumor; thoracic tumor; gray-white tumor of
Gardner syndrome; gray-glossy cut surface; tumor in
mesentery of small bowel; well defined margin
(uncommon); infiltrative margin; firm white fusiform
mass
Micro: poorly circumscribed with infiltration of adjacent

tissue; uniform cellularity between exuberant fibrous
proliferation and low grade fibrosarcoma; cells are bipolar
fibroblasts and myofibroblasts (amphophilic cytoplasm, open
chromatin, well defined nuclear membrane, one distinct
nucleolus, with reduced cytoplasm that merges with
surrounding collagen; usually more collagenous and less
cellular than nodular fasciitis; mucopolysaccharide matrix
with thin walled, curvilinear, non-branching or ectatic
vessels; stroma varies from collagenous, keloid-like to
myxoid; regenerative muscle cells within lesions may
resemble giant cells; perivascular lymphocytes at edge of
lesion; few mitotic figures, no atypia
Micro images: extra-abdominal fibromatosis - AFIP - low

power shows paucicellular fibrous proliferation in long
fascicles, with numerous slit-like vessels characteristic
of desmoid fibromatosis; fibroblasts have spindled,
dense, wavy nuclei and minimal cytoplasm; margin
shows infiltration of skeletal muscle, a common feature;
atrophic and regenerating muscle fibers at the edge of
the lesion may resemble rhabdomyoblasts; some
tumors are myxoid; cells in myxoid tumors are
uniformly bland, unlike those in malignant myxoid
tumors; cellular tumor has scattered mitotic figures,
none atypical; keloid-type pattern may be observed
focally in deep tumors
extra-abdominal fibromatosis - other sources -
paraspinal tumor #1; #2; thigh mass has spindle cells,
dense collagenous stroma, slit-like vessels and chronic
inflammation; pre-radiation therapy; post-radiation
therapy shows reduced cellularity; breast tumor is
smooth muscle actin+

(continued)
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intra-abdominal (mesenteric) fibromatosis - AFIP - tumor

appears to be extrinsic to bowel muscularis propria,
which distinguishes it from GIST; fibromatosis is
paucicellular and composed of relatively uniform, bland
spindle cells; bland, mitotically active, uniform cells in
myxoid stroma; less commonly bland spindle cells are
within collagen bundles; biopsy of pelvic tumor;
trichrome stain highlights collagen in the fibromatosis
and distinguishes it from overlying normal muscularis
propria
intra-abdominal fibromatosis - other - uniform spindle
cells with moderate collagen #1; #2
abdominal fibromatosis - extension into adjacent

muscle; fascicles of fibroblastic spindle cells with
abundant intercellular collagen
Cytology: bland spindle cells with long, fusiform nuclei and

metachromatic matrix material; tumor cells are individual or
as fragments within matrix (Cancer 2007;111:166); FNA is fairly
reliable for diagnosis but core needle biopsy is better (Acta
Orthop 2006;77:926)
Cytology images: various images
Positive stains: vimentin, variable smooth muscle actin and
muscle specific actin, variable CD117 (AJSP 2002;26:1296, but
depends on antibody used, AJSP 2001;25:549); also nuclear
beta-catenin (sensitive but not specific, AJSP 2005;29:653, AJSP
2002; 26:1296), ER-beta (Cancer 2006;106:208)
Negative stains: keratin, S100, CD34 (J Clin Pathol
2004;57:1119), ALK, desmin
EM: fibroblastic and myofibroblastic features, including
intrareticular collagen fibers, thin filament bundles,
cytoplasmic dense bodies
Molecular/cytogenetics: clonal; associated with Wnt/beta-
catenin (APC-beta-catenin-Tcf) pathways; somatic beta-
catenin point mutations in exon 3, codon 41 or codon 45 in
87% (AJSP 2007;31:1299); also associated with trisomy 20 and 8
(Am J Path 1999;154:729, Cancer Genet Cytogenet 1995;79:139) and loss
of 5q (APC gene)
Molecular/cytogenetic images: trisomy 20 and 8

(continued)
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fibrosarcoma - atypia or mitotic figures present
GIST (strong CD117+, CD34+, AJCP 2004;121:93)
idiopathic retroperitoneal fibrosis - Ormans disease -
inflammatory, strangles the ureters
leiomyoma - bright pink cytoplasm of smooth muscle,
desmin+
low grade fibromyxoid sarcoma - heavily collagenized
stroma with abrupt transition to myxoid areas, often
epithelioid areas or poorly formed but large collagen
rosettes; beta catenin negative
neurofibroma - no myofibroblasts, S100+
schwannoma - palisading Schwann cells, usually minimal
collagen, S100+
sclerosing omentitis - grows like panniculitis, beta catenin
negative
Fibromatosis colli of soft tissue

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Definition: fibromatosis affecting lower 1/3 of

sternocleidomastoid muscle, causing thickened muscle;
appears at birth, often bilateral
Also called congenital torticollis (torticollis: twisting of neck
causing unnatural position of head, usually caused by spasm
of neck muscles)
Epidemiology: associated with congenital anomalies (14%
have congenital dislocations of hip, also breech deliveries)
May be due to birth injury (breech presentation, forceps)
Uncommon (0.4% of live births), usually diagnosed by age 6
months
Recommended to diagnose by FNA since excision usually is
not required
Treatment: early - stretching and physiotherapy, resolves in
70%; some cases require resection of affected muscle; does
not recur
Gross: tan gritty mass of muscle up to 3 cm, no hemorrhage
or necrosis
Micro: diffuse proliferation of uniform plump fibroblasts and
myofibroblasts and scar like collagen in muscle, with
entrapped reactive and degenerating skeletal muscle fibers
(loss of cross striations, nuclear enlargement and
hypercellularity, multinucleation, atrophy); surgical
specimens are usually less cellular than FNA specimens
because they are obtained later in time course of disease
Micro images: AFIP - multinodular proliferation of
acellular collagenized tissue replaces part of
sternocleidomastoid muscle; skeletal muscle fibers are
trapped at advancing edge of lesion; scattered, bland
fibrocytes are widely separated by dense collagen
Cytology: early - cellular specimen with clusters or parallel
arrays of bland appearing spindle cells in fibromyxoid matrix;
also atrophic skeletal muscle in clean background, frequent
muscle giant cells, bland bare nuclei and collagen (Acta Cytol
2003;47:359); usually no significant inflammation (Diagn
Cytopathol 2000;23:338)
Positive stains: vimentin, actins
fibromatosis - no muscle fibers, which are replaced by
fibrous tissue except at periphery, does not typically affect
sternocleidomastoid muscle
proliferative myositis - doesnt affect this site, stroma
resembles granulation tissue and is not collagenous
fibrodysplasia ossificans progressiva - doesnt affect this
site, hand malformations are present, bone is present
Fibrosarcoma of soft tissue - adult

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Definition: malignant tumor of fibroblasts with herringbone

architecture and variable collagen
Rare (up to 3% of adult sarcomas)
Some limit diagnosis to those age 10+ years, most patients
are ages 40-55 years
Many cases formerly called fibrosarcoma are actually
dedifferentiated liposarcoma, fibromatosis, fibrosarcomatous
DFSP, low-grade fibromyxoid sarcoma, MPNST, synovial
sarcoma or MFH-pleomorphic
Usually deep soft tissue of lower extremities or trunk, only
rarely in retroperitoneum or mediastinum
50% recur, 25% metastasize (lung, bone); more metastases
if more cellular and higher mitotic activity
Survival: 5 year-41%, 10 year-29%; better if tumor is
superficial and better differentiated, low mitotic rate, no
necrosis
Treatment: radical excision, radiation if residual tumor or
positive margins; possibly chemotherapy if high grade
Gross: may appear well circumscribed but
nonencapsulated; fleshy, hemorrhagic, necrotic, white-tan
Gross images: AFIP - desmoid fibromatosis (left) is
contrasted with high-grade fibrosarcoma (right),
fibromatosis has gristle-like consistency, but
fibrosarcoma tends to be white, fleshy and necrotic with
an overlying tendon
other - well circumscribed tumor
Micro: highly cellular fibroblastic proliferation in herringbone
pattern (cells in columns of short parallel lines with all the
lines in one column sloping one way and lines in adjacent
columns sloping the other way); cells have scant cytoplasm,
tapering elongated dark nuclei with increased granular
chromatin, variable nucleoli; mitotic activity present, often
with abnormal forms; variable collagen; usually no giant
cells; no pleomorphism (or call pleomorphic MFH), no other
distinct cell types
Patterns: keloid-like (thick hyalinized collagen fibers), loose
fascicular, focally myxoid
Micro images: AFIP - atypical uniform cells in

herringbone pattern; cells are clearly malignant, with
coarse chromatin but minimal pleomorphism; grade I
tumor has minimal pleomorphism and low mitotic index,
but is more cellular than fibromatosis #1; #2; grade II
tumor has intermediate features #1; #2; grade III tumor
has high grade atypia and high mitotic index #1; #2
other - well differentiated tumor; nuclear pleomorphism
Virtual slides: fibrosarcoma
Fibrosarcoma of soft tissue - adult

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Positive stains: reticulin stain demonstrates fibers

surrounding each cell; phosphotungstic acid-hematoxylin
demonstrates abundant cytoplasmic fibrils; also vimentin,
type 1 collagen, p53; high Ki-67; may be CD34+ if arises
from DFSP or solitary fibrous tumor
Negative stains: S100, keratin; smooth muscle markers,
histiocytic markers, basal lamina
EM: fibroblasts with prominent rough endoplasmic reticulum
but no myofilaments, no external lamina, no intercellular
junction; no distinct myofibroblasts (if present, call
myofibrosarcoma)
Molecular/cytogenetics: aneuploid
Differential diagnosis (other tumors with
fibrosarcomatous areas):
dedifferentiated liposarcoma
fibromatosis - less cellular, less hyperchromasia, no atypia,
<1 mitotic figure/HPF
low grade fibromyxoid sarcoma
MFH-pleomorphic
MPNST
synovial sarcoma
References: eMedicine
Fibrosarcoma of soft tissue - infantile

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Definition: resembles adult fibrosarcoma morphologically,

but better prognosis
Age cutoff between infantile and adult forms usually varies
between 5 and 10 years
Epidemiology: usually presents before age 2 years in axial
regions or extremities with vary rapid growth
Related to congenital mesoblastic nephroma, which has
same translocation
Clinical: 40-50% recur but only rarely metastasizes
Survival is 90%+
Case reports: premature newborn with large facial mass
(Archives 2003;127:e281)
Treatment: surgery and chemotherapy (J Pediatr Hematol Oncol
2002;24:722, Pediatr Blood Cancer 2009;53:23)
Gross: may exceed 30 cm (grotesquely large compared to
size of child) with tense erythematous and ulcerated
overlying skin; firm to soft cut surface is fleshy, gray-tan with
myxoid change, cystic degeneration, hemorrhage and
necrosis
Gross images: AFIP - fleshy white mass similar to adult
fibrosarcoma
Micro: poorly circumscribed, lobulated mass of small to
large spindled cells in fascicles or herringbone pattern with
high cellularity, nuclear atypia and pleomorphism; increased
mitotic figures, hemorrhage and necrosis; resembles adult
fibrosarcoma; may have prominent hemangiopericytoma-like
areas, dystrophic calcification, extramedullary
hematopoiesis; infiltrates adjacent soft tissue with irregular
margins
Micro images: AFIP - biphasic pattern with fibroblastic

and cellular myxoid areas; high power of myxoid area;
infiltration of fat; infiltration of muscle; spindle cells;
plump cells have granular chromatin; less cellular
tumor which overlaps with infantile fibromatosis,
although it almost never metastasizes #1; #2;
other - areas of variable cellularity; leg tumor #1; #2;
#3; cellular tumor with mitotic figures; fig 1: facial
tumor involves eye and maxilla, fig 2: undifferentiated
cells with loose myxoid stroma with arborizing vessels,
fig 3: foci of fusiform spindle cells
Fibrosarcoma of soft tissue - infantile (continued)

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Positive stains: vimentin; variable focal smooth muscle

actin, desmin, S100 and CD34
EM: fibroblastic and myofibroblastic features
Molecular/cytogenetics: 70% have t(12;15)(p13;q26),
causes ETV6-NTRK3 gene fusion transcript (ETS variant
gene 6 and neurotrophic tyrosine receptor kinase type 3)
detectable by FISH (Mod Path 2001;14:1246) or RT-PCR (AJSP
2000;24:937, AJCP 2001;115:348); similar translocation also
present in secretory breast carcinoma (Mod Pathol 2009;22:291);
also trisomy 8, 11, 17 and 20
Molecular images: ideogram of fusion transcript and
FISH
adult type fibrosarcoma - usually age 10+, no t(12;15)
infantile fibromatosis - no pleomorphism, no mitotic figures,
no t(12;15)
myofibromatosis - myofibroblastic features, no t(12;15)
(Pediatr Dev Pathol 2008;11:355)
Fibrous hamartoma of infancy of soft tissue

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Definition: poorly circumscribed proliferation of immature

spindle cells in organoid pattern with fat and dense
fibrocollagenous tissue
Epidemiology: rare; usually age 2 years or less (25%
discovered at birth), does not occur after puberty, 2/3 male
Sites: axilla, shoulder and inguinal region (J Urol 1994;152:990);
not hands and feet
Solitary, rapidly growing, freely movable mass of subcutis or
dermis
Case reports: 6 month old girl with arm mass (Univ Oklahoma),
6 month old girl with multiple nodules with overlying
hypertrichosis (J Dermatol 2006;33:427), 6 month old boy with
recurrent tumor (Pediatr Surg Int 2005;21:119), 11 month old boy
with thigh mass (The Internet Journal of Dermatology 2001;1:2)
Treatment: excision, need not be aggressive as recurrence
is uncommon (J Am Acad Dermatol 2006;54:800)
Gross: poorly circumscribed, gray-white with yellow fat,
usually 5 cm or less
Gross/clinical images: untreated tumors - axillary tumor
in 6 month old Nigerian boy; scapular tumor in 7 year
old Nigerian girl #1; #2-at surgery showing well
developed capsule
Micro: poorly circumscribed, organoid with 3 components -
(1) trabecular or stellate immature mesenchymal cells with
scant cytoplasm and bland straight or wavy nuclei in myxoid
matrix, (2) fibrocollagenous tissue composed of bland
fibroblasts or myofibroblasts, (3) mature fat; overlying
epidermis usually has eccrine changes, including
hyperplasia, duct dilation, intraluminal papillary formations
and squamous syringometaplasia (J Cutan Pathol 2007;34:39);
no/scant mitotic figures
Micro images: AFIP - triphasic pattern of fibrous spindle

cells delimiting islands of mature fat and primitive
spindle cells; primitive spindle cells may infiltrate fat;
primitive spindle cells and fibrous spindle cells are
bland and uniform with no/rare mitotic figures
other - three cell types #1; #2; #3; mature adipose and
fibrous tissue; plump mesenchymal cells; various
images; collagenous tissue and immature
mesenchymal cells; H&E and t(2;3) karyotype
Fibrous hamartoma of infancy of soft tissue (continued)

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Cytology: moderate cellularity, adipose tissue fragments,

clusters of fibroblastic cells, myxoid and collagenous matrix;
no mitotic figures, no atypia (Diagn Cytopathol 2003;28:272, Acta
Cytol 2008;52:201)
Positive stains: vimentin; spindle cells in fibrous trabeculae
may be actin+
Negative stains: beta-catenin (Pediatr Dev Pathol 2008 Oct 21:1
[Epub ahead of print])
EM: fibrous trabeculae are composed of fibroblasts and
myofibroblasts, primitive mesenchymal cells have slender
cytoplasmic processes with few organelles
Cytogenetics: rarely complex translocations (Cancer Genet
Cytogenet 2006;171:115), rarely t(2;3) (Archives 2005;129:520)
calcifying aponeurotic fibroma - almost always hands or
feet, prominent calcification, no primitive cells within myxoid
stroma
myofibroma - prominent hemangiopericytoma-like pattern,
usually no fat
Focal myositis of soft tissue

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Definition: inflammatory condition of skeletal muscle with

degeneration and regeneration, inflammatory cells and
fibrosis
Not a WHO diagnosis
Epidemiology: mean age 41 years, range 7-94 years
Clinical: usually healthy patients with no history of trauma;
evolves over weeks to a localized, painful soft tissue
swelling, usually of lower extremity
Solitary, self-limited, may be related to denervation
Case reports: due to statins (Int J Cardiol 2009;133:e33), due to
Lyme disease (Arthritis Rheum 2006;54:2697), recurrent disease
of peroneal muscles (Rheumatology (Oxford) 2002;41:1318), post
bCG vaccination (Rheumatology (Oxford) 2002;41:1074), in
pregnancy (Rheumatology (Oxford) 2000;39:211), 16 year old girl (J
R Coll Surg Edinb 2000;45:339)
Treatment: usually none; spontaneously regresses
Gross: pale, ill-defined; mean 4 cm, range 1 to 20 cm
Micro: degeneration and regeneration of muscle fibers
associated with interstitial inflammation and fibrosis; also
focal neurogenic changes; occasionally prominent
eosinophils; markedly inflamed cases have B cells or
CD123+ dendritic plasma cells
Micro images: focal interstitial muscle inflammation

associated with extensive proliferation of endomysial
connective tissue; venlafaxine associated myositis
shows regenerating muscle fibers and CD3+ (T) cells;
associated with bCG vaccination #1; #2; focal
perivascular chronic inflammatory infiltrate; various
images
Cytology: inflammatory cells, skeletal muscle fibers with

degenerative and regenerative changes, fibrous tissue (Acta
Cytol 2005;49:653)
Positive stains: CD163+ macrophages; lymphocytes are
CD3+ and CD4+
Negative stains: macrophages are S100- and CD1a-;
lymphocytes are negative for TIA1, granzymeB, EBV and
ALK1 (Am J Surg Pathol 2009 Apr 9 [Epub ahead of print])
Molecular: no B or T cell rearrangement
DD: poliomyelitis
Gardner type fibroma of soft tissue

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Definition: benign soft tissue lesion with thick, haphazard

collagen and bland fibroblasts that entrap adjacent tissue;
90% associated with FAP / Gardners syndrome / APC
germline mutation
Uncommon; affects infants, children and teenagers
May be initial diagnostic clue to Gardners syndrome and
APC mutations (AJSP 2001;25:645); 45% develop desmoid-type
fibromatosis
Similar histology to nuchal-type fibroma (Pathol Int 2004;54:523,
AJSP 2000;24:1563)
Sites: superficial or deep soft tissue; various sites
Case reports: post-surgical desmoid tumor in Gardners
syndrome patient (J Neurooncol 2009;91:107)
Gross: 1-10 cm, poorly circumscribed, firm, rubbery, plaque-
like, white to tan-pink cut surface with trapped fat in yellow
areas
Micro: thick, haphazardly arranged collagen bundles,
hypocellular bland fibroblasts, small blood vessels, plaque-
like growth pattern with infiltration of adjacent structures
Micro images: image1
Positive stains: CD34, cyclin D1, vimentin, nuclear beta-
catenin (64%)
Negative stains: muscle specific actin, smooth muscle
actin, desmin, ER, PR
References: AJSP 2007;31:410, Stanford University
Giant cell angiofibroma of soft tissue

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Definition: uncommon benign neoplasm of multinucleated

giant cells and ectatic vascular spaces
May be related to solitary fibrous tumor (AJSP 2000;24:971, Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:685, Ophthal Plast
Reconstr Surg 2008;24:325)
Epidemiology: median age 45 years; more common in men
in eyelid/orbital sites, more common in women elsewhere
Often slow growing painful mass
Case reports: 44 year old man with buccal mucosa tumor
(Med Oral Patol Oral Cir Bucal 2008;13:E540), 50 year old woman
with inguinal tumor (Ann Diagn Pathol 2000;4:240), 57 year old
woman with eyelid tumor extending into orbit (Can J Ophthalmol
2006;41:216)
Treatment: excision, does not recur
Sites: eyelid, nasolacrimal duct (Ophthal Plast Reconstr Surg
2001;17:202), lacrimal sac or orbit (AJSP 1995;19:1286)
Gross: well circumscribed with variable capsule, median 3
cm (larger in extra-orbital regions), may have hemorrhagic or
cystic cut surface
Micro: cellular areas with bland round to spindle cells in
myxocollagenous stroma with small-medium thick walled
vessels and multinucleated giant stromal cells that line
ectatic vascular spaces
Micro images: various images #1; #2
Positive stains: CD34, CD99, vimentin, variable bcl2
Negative stains: CD31, CD68, c-kit/CD117, muscle specific
actin, S100, desmin
Cytogenetics: rarely t(12;17)(q15;q23) (Cancer Genet Cytogenet
2006;165:157), rarely 6q13 abnormalities (Cancer Genet Cytogenet
2000;116:47)
Giant cell fibroblastoma of soft tissue

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Definition: rare childhood fibroblastic tumor of intermediate

malignancy with floret-like giant cells and ectatic
pseudovascular spaces lined by stromal cells and giant cells
Part of WHO classification for skin tumors, not soft tissue
tumors
Appears to evolve into DFSP by genomic gains of COL1A1-
PDGFB (Genes Chromosomes Cancer 2008;47:260); considered the
juvenile form of DFSP, as both have the same translocation
(AJSP 2003;27:27)
Epidemiology: usually children less than 10 years old, 2/3
male
Painless nodule of subcutis, usually in trunk, extremities,
head and neck
50% recur but recurrences are controllable, no metastases
Case reports: 3 year old boy with recurrent knee lesion
(Pathol Oncol Res 2003;9:249), 28 year old woman with vulvar
tumor (J Low Genit Tract Dis 2007;11:112)
Gross: poorly circumscribed, gray to yellow mucoid mass
that is difficult to completely excise, usually in subcutis
Micro: dermis and subcutis contains hyperchromatic spindle
or stellate shaped cells in a collagenous or myxoid matrix
with scattered hyperchromatic, multinucleated, floret-like
giant cells with prominent nucleoli, similar to those in
pleomorphic lipomas; ectatic pseudovascular spaces are
lined by a discontinuous row of floret-like cells and tumor
cells; honeycomb or parallel pattern of infiltration; also
hyalinized area, perivascular lymphocytes in onionskin
pattern, intralesional hemorrhage; often foci of DFSP; no
histiocyte-like cells, no mitotic figures
Micro images: AFIP - ectatic pseudovascular spaces are
lined by giant cells #1; #2; #3; stroma has giant cells
and myxoid stroma; stroma is fibrotic with giant cells
but sparse angiectoid spaces in this case;
multinucleated stromal giant cells have vesicular nuclei
and prominent nucleoli, but smaller spindle cells have
indistinct nucleoli
other - trunk tumor #1; #2; #3; tumor cells line
pseudovascular spaces #1; #2
Giant cell fibroblastoma of soft tissue (continued)

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Cytology: moderately cellular smears with mononuclear

cells, usually single but occasionally in clusters; most cells
have no/scanty cytoplasm, bland nuclei with small nucleoli;
nuclear membranes often have notches, creases or folds;
rare multinucleated giant cells with bland oval nuclei; no
necrosis, no mitotic figures (Diagn Cytopathol 2002;26:398, Archives
2001;125:1091)
Cytology images: various images (fig a-c)
Positive stains: vimentin, CD34, CD99 (40%, J Cutan Pathol
2008;35:647), variable actin
Negative stains: S100, CD31, Factor VIII, keratin, desmin,
HMB45
Molecular/cytogenetics: t(17,22)(q22;q13) - creates fusion
of collagen type 1 alpha 1 gene and platelet derived growth
factor B chain gene; also supernumerary ring chromosomes
derived from t(17;22)
EM: myofibroblasts or fibroblasts
neurofibroma with ancient change - no ectatic vascular
spaces, S100+
pleomorphic liposarcoma - pleomorphic cells are similar,
but remaining lesion has lipoblasts and lacks collagenous
matrix
angiosarcoma - older adults in head and neck, vascular
tumor, cells have enlarged atypical nuclei, mitotic figures
present
hemangioma - vascular tumor, no giant cells, CD31+
References: Archives 1996;120:1052, Ann Diagn Pathol 2007;11:81,
Stanford University
Hemangiopericytoma of soft tissue

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Definition: controversial entity; rare lesions similar to

cellular solitary fibrous tumor - may not actually differ
Diagnosis of exclusion (Histopathology 2006;48:63)
Historically defined as lesions with thin walled, branching
vascular pattern, although this pattern is common in many
lesions
Probably not a lesion of pericytes, except at sinonasal
location
See myofibroma / myofibromatosis for infantile lesions
See also discussions in these chapters: Bone, Breast, CNS,
Heart, Nasal cavity, Thyroid gland
Epidemiology: middle aged adults, more common in
women
Most common in deep soft tissue, particularly pelvic
retroperitoneum, also limb or limb girdles and head and neck
Occasionally associated with hypoglycemia (J Clin Endocrinol
Metab 1996;81:919)
5 year survival was 86% in 2002 (Cancer 2002;95:1746)
70% have benign behavior
Poor prognostic factors may be 4+ mitotic figures/10 HPF,
necrosis, nuclear pleomorphism with size > 5 cm
Case reports: omental tumor with metastases (World J Surg
Oncol 2007;5:63)
Gross: well circumscribed, yellow-tan cut surface, fleshy or
spongy with hemorrhage but no necrosis, up to 15 cm
Gross images: encapsulated omental tumor #1; #2;
patient with 3 tumors - (a) greater omentum tumor
(under forceps); (b) small jejunal tumor; (c)
retroperitoneal tumor with portions of diaphragm and
liver
Micro: uniformly cellular (similar to cellular areas of solitary
fibrous tumor) with numerous, variably ectatic or
compressed, thin walled branching vessels with staghorn
configuration; tumor cells are spindled to round with small
amounts of pale or eosinophilic cytoplasm, indistinct
margins, bland vesicular nuclei; stromal hyalinization is not
prominent; variable mitotic activity; no atypia
Hemangiopericytoma of soft tissue (continued)

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Micro images: staghorn vessels are prominent #1; #2;
uniform cells around branched, thin-walled, staghorn
vessels; various images (many from CNS); meningeal
tumors; reticulin stain; hemangiopericytoma of CNS is
CD34+ (figure 3) / CD31 neg (figure 4)
Cytology: cellular; single and tightly packed clusters of oval
to spindle cells aggregated around branched capillaries;
often basement membrane material present; nuclei are
uniform, oval, with finely granular chromatin and indistinct
nucleoli; no mitotic figures, no necrosis (Cancer 1999;87:190)
Cytology images: irregular fragments of tissue, loose

cellular aggregates and single cells; uniform oval or
spindled cells with indistinct borders, high N/C ratio,
and capillary vessels with long and hyperchromatic
nuclei Diff-Quik, 400); metachromatic basement
membrane material within the fragments separates
tumor cells from endothelial cells
Virtual slides: hemangiopericytoma

Positive stains: CD99, variable CD34 (Hum Path 1998;29:636);
reticulin surrounds individual cells
Negative stains: Factor VIII, CD31, usually actin and
desmin (except in sinonasal hemangiopericytoma)
EM: no true pericytic differentiation; has fibroblastic or
undifferentiated spindle cell features
solitary fibrous tumor - more prominent collagen, less
prominent vessels
monophasic synovial sarcoma - similar vascular pattern,
characteristic translocation
myopericytoma - predominant growth pattern is concentric
perivascular arrangement of plump spindle cells (J Clin Pathol
2006;59:67)
deep fibrous histiocytoma - storiform pattern, fibrohistiocytic
lesion
mesenchymal chondrosarcoma - malignant chondrocytes
present
endometrial stromal sarcoma (CD10+, ER+, Mod Path
2005;18:40)
References: eMedicine, Orphanet
Lipomatous hemangiopericytoma
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Definition: variant with mature adipose tissue

Also called adipocytic variant of solitary fibrous tumor
Epidemiology: uncommon; 2/3 males, usually thigh, lower
extremity and retroperitoneum
Only rarely recurs, does not metastasize
Case reports: 41 year old woman with thigh tumor (Arch
Pathol Lab Med 1999;123:941), 56 year old man with
retroperitoneal mass (Case of the Week #16), mediastinal tumor
(J Postgrad Med 2006;52:71), in skull base and parapharyngeal
space (Otol Neurotol 2006;27:560)
Gross: solid, tan-yellow
Gross images: circumscribed mass has lipid-rich and
lipid poor areas
Micro: well circumscribed, patternless cellular areas,
prominent hemangiopericytoma-like vessels, mature adipose
tissue, variable collagen
Micro images: retroperitoneal mass (Case of Week) -
image #1; #2; #3; #4; #5; #6; #7; #8; #9; #10;
mediastinal tumor #1; #2
other - classic hemangiopericytoma features; lipid rich
component; multivacuolated fat cells; with metaplastic
bone
Cytology: may resemble myxoid liposarcoma (Diagn
Cytopathol 2003;29:287)
Positive stains: vimentin, CD99, CD34 (75%), bcl2 (60%)
Negative stains: CD31, desmin, keratin, actins, S100,
GFAP
EM: features of pericytes, no lipoblasts
DD: various lipomas, liposarcoma
References: Hum Path 2000;31:1108, AJSP 1999;23:1201
Inclusion body fibromatosis of soft tissue

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Definition: dermal fibroblastic and myofibroblastic lesion

with cytoplasmic eosinophilic inclusions, usually in digits of
infants
Also called infantile digital fibromatosis, infantile digital
fibroma (J Hand Surg [Am] 1995;20:1014)
Clinical: rare; lesions usually present at birth or in first 2
years; similar lesions in adults; often are multiple
Sites: usually exterior surface of distal phalanges of fingers
and toes, but not thumb or great toe, also oral cavity and
breast
50% recur, do not metastasize
Similar inclusions reported in breast fibroadenoma (Archives
2007;131:1126), breast phyllodes tumor (AJSP 1994;18:506),
cervical polyp (Pathology 1998;30:215), GI leiomyomas (Cesk Patol
2006;42:139)
Case reports: spontaneous regression (J Dermatol 1998;25:523),
post-surgical tumors in all extremities (Ann Plast Surg
2008;61:472)
Treatment: excision, but preserve function because
recurrences are not destructive and tumors do not
metastasize (Am J Surg Pathol 2009;33:1)
Clinical images: #1; various images
Gross: nodules with stretched overlying skin, lesions are ill
defined, white-tan, usually 2 cm or less; no hemorrhage or
necrosis
Micro: nonencapsulated, dermal proliferation of hypocellular
sheets or fascicles of fibroblasts and myofibroblasts with
variable collagen; some spindle cells have peculiar
eosinophilic (hyaline) cytoplasmic inclusions the size of a
lymphocyte nucleus; usually mitotic figures; may infiltrate
into adjacent tissue; no atypia
Micro images: AFIP - proliferation extends from
epidermis to deep dermis or subcutis; fibroblastic cells
swirl around and engulf an eccrine duct; cells are bland
and monomorphic; inclusions resemble red blood cells
Positive stains: inclusions - trichrome (stain red), PTAH,
variable staining for actins; spindle cells - vimentin, muscle
actins (tram track pattern), calponin, desmin, CD99; often
CD117
Negative stains: inclusions - PAS; spindle cells - keratin,
ER, PR, beta-catenin
EM: spindle cells are myofibroblasts with rough endoplasmic
reticulum and free lying inclusions composed of compact
masses of actin granules and filaments without a limiting
membrane (Am J Pathol 1979;94:19)
infantile fibrosarcoma - not digits, usually > 2 cm, more
cellular, chromatin is denser and more irregular, more mitotic
figures, no inclusions
infantile desmoid fibromatosis - rare on hand, usually > 2
cm, more cellular, no inclusions
Inflammatory myofibroblastic tumor of soft tissue

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Definition: tumor of myofibroblasts with plasma cells,
lymphocytes and eosinophils
Also called inflammatory fibrosarcoma, inflammatory
pseudotumor, plasma cell granuloma
See also discussions in these chapters: Bladder, Bone,
Breast nonmalignant, CNS-tumor, Colon-tumor, Eye
(orbit), Heart-tumor, Kidney-tumor, Liver-tumor, Lung-
tumor, Lymph node-not lymphoma, Mediastinum,
Pancreas, Salivary glands, Small bowel, Spleen, Thyroid
gland
Retroperitoneum (omentum) and mesentery in children and
young adults (mean age 10 years); also lung, GI, GU, other
sites
Clinical: 1/3 have associated fever, growth failure, malaise,
weight loss, anemia, thrombocytosis, polyclonal
hyperglobulinemia and elevated sedimentation rate;
symptoms disappear after excision of mass (J Korean Med Sci
2002;17:699)
Poor prognostic factors: abdominal or pelvic sites, ALK
negative (AJSP 2007;31:509)
Case reports: 6 year old boy with abdominal wall tumor
(Surg Today 2007;37:352), 7 year old girl whose abdominopelvic
tumor has t(1;2)(q21; p23) (Archives 2006;130:1042), 18 year old
man with omental tumor and bone marrow involvement
(Archives 2003 Jul;127:865), 46 year old woman with
retroperitoneal tumor (World J Surg Oncol 2005;3:66), 63 year old
man with mesenteric tumor (World J Gastroenterol 2007;13:3645)
Treatment: excision (J Pediatr Surg 2005;40:1581), 25-35% recur,
rare metastases (or may be evidence of multifocality)
Gross: circumscribed, not encapsulated; white tan mass
with whorled fleshy or myxoid cut surface; may have focal
hemorrhage, necrosis or calcification, mean 6 cm
Gross: 19 cm mesenteric tumor (fig 2-4)
Micro: myofibroblastic and fibroblastic spindle cells with
inflammatory infiltrate of lymphocytes, plasma cells,
eosinophils, histiocytes; background of abundant blood
vessels; mixture of three patterns: (1) resembling nodular
fasciitis with elongated myofibroblasts containing abundant
eosinophilic cytoplasm and vesicular nuclei, loose myxoid
stroma with neutrophils, lymphocytes and eosinophils, but
few plasma cells; (2) cellular with spindled myofibroblasts
and fibroblasts in more compact stroma, arranged as islands
surrounded by fibromyxoid stroma with prominent plasma
cells and mitotic figures; (3) densely hyalinized stroma with
few spindle cells, few plasma cells or lymphocytes; may
have ganglion-cell like myofibroblasts; all 3 patterns have no
nuclear pleomorphism, no atypical mitotic figures
malignant behavior - associated with highly atypical
polygonal cells with oval nuclei, prominent nucleoli, Reed-
Sternberg like cells, atypical mitotic figures
Inflammatory myofibroblastic tumor of soft tissue

(continued)
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Micro images: AFIP - typical appearance of spindled

myofibroblastic cells and inflammatory infiltrate #1; #2;
inflammation obscures the underlying myofibroblastic
proliferation; spindle cells are evident at high power;
tumor with more fibrous stroma
other - myofibroblasts and inflammatory cells #1; #2;
#3; #4; #5; various images; retroperitoneal tumor #1;
#2; #3; #4; peritoneal tumor with bone marrow
involvement; H&E and ALK1; H&E, ALK1, p80; ALK1
and p80
Virtual slides: inflammatory myofibroblastic tumor

Positive stains: vimentin (diffuse, strong), usually alpha
smooth muscle actin, muscle specific actin and calponin
(Hum Path 2008;39:846), ALK1 / p80 in 40%, but not specific (Mod
Path 2002;15:931), keratin and desmin in 1/3
Negative stains: S100, CD117, HHV8 (Mod Path 2007;20:995),
CD34, h-caldesmon
EM: myofibroblastic cells and activated fibroblasts
EM images: fig b: filamentous bundles, attachment
densities, pinocytotic vesicles and basal lamina
Molecular/cytogenetics: clonal abnormalities of 2p23
(Cancer Res 1999;59:2776), including t(2;5)(p23;q35) involving
ALK and NPM; also t(2;17)(p23;q23) involving ALK and
CLTC (Am J Path 2001;159:411) and t(2;19)(p23;p13.1) involving
ALK and TPM4 (Am J Path 2000;157:377); associated with ALK
deregulation and younger patients; see Atlas of Genetics
Molecular images: t(2;5) schematic; t(2;5) karyotype;
ALK translocation is indicated by separation of green
and orange probes of ALK gene in inflammatory
myofibroblastic tumor (a), but not leiomyosarcoma (b);
ALK staining, FISH and karyotype; FISH for ALK
calcifying fibrous pseudotumor - calcification, no
myofibroblastic proliferation, actin negative (Mod Path
2001;14:784)
nodular fasciitis - smaller size, older patients, less
inflammation
low grade myofibroblastic sarcoma - more uniform
appearance with higher cellularity, more prominent
hyperchromasia, more infiltrative, ALK (Hum Pathol 2008;39:846)
Intranodal palisaded myofibroblastoma of soft tissue

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Definition: benign myofibroblastic spindle cell tumor arising

within lymph nodes (usually in the groin) associated with
amianthoid fibers and resembling schwannoma
Also called intranodal hemorrhagic spindle cell tumor with
amianthoid fibers; formerly called intranodal schwannoma
Amianthoid: resembles amianthus, a type of asbestos with
particularly fine fibers (image #1; #2); tumor fibers are
extracellular collagen
Described by Weiss et al (AJSP 1989;13:341) and Suster et al
(AJSP 1989;13:347)
Epidemiology: 2/3 male, 2/3 ages 45-55 years (Arch Pathol
Lab Med 2007;131:306)
Sites: occurs primarily in the groin, but also other sites
Case reports: 49 year old woman with renal transplant and
recurrence (Arch Pathol Lab Med 1999;123:433), 62 year old man
with supraclavicular mass (UPMC Case #121), 71 year old man
with inguinal mass (Archives 2003;127:1040)
Treatment: local excision is almost always curative
Gross: well circumscribed, gray-white with hemorrhage and
peripheral nodal tissue
Micro: benign spindle cells with scant cytoplasm, elongated
nuclei arranged in fascicles; spindle cells have
myofibroblastic or smooth muscle features; large amianthoid
fibers (strongly eosinophilic, extracellular matrix deposits
composed of crystalline fibers) around which the cells
palisade; areas of acute hemorrhage and hemosiderosis;
peripheral lymph node tissue; no/rare mitotic figures, no
atypia, no slit like vascular spaces, no extravasated red
blood cells
Micro images: various images #1; #2; #3; #4;

peripheral rim of nodal tissue; original and recurrent
tumor; focal palisading and metaplastic bone
formation; H&E and cyclin D1; smooth muscle actin+,
cyclin D1+, EM images; amianthoid fibers composed of
a central vessel surrounded by a core of collagen with
peripheral spokes, strongly stained by Van Gieson;
Intranodal palisaded myofibroblastoma of soft tissue
(continued)
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Cytology: moderately cellular with benign appearing,

dissociated, single spindle cells with elongated nuclei,
pointed ends and occasional twisted forms; in pale fibrillary
matrix with hemosiderin granules, no atypia (Acta Cytol
2002;46:1143)
Positive stains: spindle cells - smooth muscle actin,
vimentin, cyclin D1 (Arch Pathol Lab Med 2003;127:1040), variable
factor XIIIa; amianthoid fibers - elastic stains, trichrome,
collagen type I/III, smooth muscle actin
Negative stains: S100, synaptophysin, GFAP, Ki-67 (<5%),
desmin, EMA, keratin
EM: spindle cells with long, indented nucleus and collagen
fibrils from the crystalline deposits; pinocytotic vesicles,
microfilament aggregates, well-developed rough
endoplasmic reticulum with dilated cisternae; amianthoid
fibers contain collagen fibrils arranged in orderly parallel
fashion; long, frequently indented nuclei (Ultrastruct Pathol
1996;20:79)
EM images: collagen fibrils are prominent
schwannoma - often biphasic, no amianthoid fibers, not
nodal, S100+
Kaposis sarcoma - curved fascicles of spindle cells with
atypia and PAS+ hyaline globules, brisk mitotic activity, slit-
like vessels with extravasated red blood cells; no amianthoid
fibers, HHV8+, FLI1+
dendritic cell sarcoma - nests or whorls of plump cells with
scattered inflammatory cells, no prominent hemorrhage, no
amianthoid fibers, CD21+, CD35+
benign metastasizing leiomyoma - smooth muscle cells are
more ovoid with more prominent eosinophilic cytoplasm, no
hemorrhage, no amianthoid fibers
spindle cell carcinoma, melanoma or sarcoma (atypia and
mitotic figures)
References: J Clin Pathol 1991;44:761
Ischemic fasciitis of soft tissue

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Definition: sarcoma-like fibroblastic proliferation, usually of

soft tissue, overlying bony prominences
Also spelled ischaemic
First described in 1992 as atypical decubital fibroplasia
(AJSP1992;16:708)
Epidemiology: occurs primarily in immobilized and elderly
patients due to chronic pressure and impaired circulation,
but also occurs in younger people not debilitated (Am J Surg
Pathol 2008;32:1546) or with physical disabilities (Path Int
1998;48:160, Int J Gynecol Pathol 2004;23:65)
Sites: usually pressure points on shoulder, chest wall and
sacrococcygeal region
Case reports: 45 year old woman with post-mastectomy
axillary mass (The Internet Journal of Pathology 2008;7:1), 55 year
old man with hip mass (Case of Week #64), 76 year old woman
with thigh mass (Archives 2004;128:e139)
Treatment: local excision is curative, although may recur
due to continuation of underlying ischemia and injury
Gross: usually 1 to 8 cm, poorly circumscribed, often
myxoid; usually involves deep subcutis, may extend into
adjacent skeletal muscle; ulceration is uncommon (i.e.
overlying skin is intact)
Micro: zones of fibrinoid necrosis with uneven borders
staining deep red/violet and prominent myxoid areas
surrounded by ectatic, thin walled vessels and proliferating
fibroblasts; endothelial cells may be atypical; fibroblasts
have degenerative features of abundant, basophilic
cytoplasm, enlarged nuclei with smudged chromatin and
prominent nucleoli (resembling proliferating fasciitis or
ganglion cells); may have frequent mitotic activity, but no
atypical mitotic figures; fibrin thrombi are common within
peripheral vessels, which may show fibrinoid necrosis and
recanalization but no vasculitis; may have multivacuolated
macrophages, but no lipoblasts; no primary vasculitis or
myositis
Micro images: AFIP - cellular, fibrin-rich proliferation

centered on subcutaneous fibrous septum and
extending into adjacent fat; hyalinized focus with large
ganglion-like cells, suggestive of proliferative fasciitis;
fibrin is adjacent to foci of ganglion-like cells in
collagenous stroma
other - central area of ischemic fasciitis filled with fibrin

and surrounded by proliferating vascular fibrous tissue;
fibrinoid necrosis with few viable cells; spindle cells
with large nuclei with prominent nucleoli resembling
proliferative fasciitis; capillaries lined by plump
endothelial cells and surrounded by large
fibroblasts/myofibroblasts enmeshed in a loose
collagenous stroma (figure 5); post-mastectomy axillary
mass-various images
hip mass in 55 year old bedridden man - image #1; #2;

#3; #4; #5; #6
Ischemic fasciitis of soft tissue (continued)

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Cytology: spindled and ovoid cells with ample cytoplasm

and occasional nuclear atypia (Acta Cytol 1997;41:598)
Positive stains: vimentin, actin, CD68; variable CD34 in
enlarged fibroblasts, desmin
Negative stains: keratin, S100
epithelioid sarcoma - young adults on distal extremities,
more cellular with central necrosis, cells have eosinophilic
cytoplasm, atypical mitotic figures, keratin+
myxoid liposarcoma - prominent plexiform vasculature and
lipoblasts
myxofibrosarcoma - marked atypia, but no smudgy
chromatin or fibrin thrombi; lacks zonation
proliferative fasciitis - younger patients, lesions not
associated with pressure; zonation, myofibroblasts and
fibroblasts with tissue culture type growth, also large
ganglion cells
References: Mod Path 1993;6:69, Stanford University
Juvenile hyaline fibromatosis of soft tissue

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Definition: hereditary infantile disorder with extracellular

hyaline material in skin, soft tissue and bone, due to aberrant
fibroblasts
Also called fibromatosis hyalinica multiplex
Called infantile systemic hyalinosis if organ involvement, but
some cases overlap (Pediatr Dermatol 2004;21:154)
Epidemiology: very rare, associated with consanguineous
parents
Due to mutations in CMG2 / capillary morphogenesis protein
2 gene (Am J Hum Genet 2003;73:791, Am J Hum Genet 2003;73:957),
which cause protein to remain in endoplasmic reticulum (Hum
Mutat 2009;30:583)
Clinical: cutaneous nodules (face and neck), gingival
hypertrophy, flexure contractures (due to masses in
periarticular soft tissue) and bone lesions (skull, long bones,
phalanges)
Case reports: disease in 2 siblings of first-degree
consanguineous marriage (Indian J Dermatol Venereol Leprol
2005;71:115), 14 year old girl without prominent hyaline
changes (J Cutan Pathol 2005;32:235)
Clinical images: multiple subcutaneous nodules;
nodules on pinna of ear; large ulcerated nodules on
back; gingival hyperplasia #1; #2; multiple skin
papules
Gross: solid, white, waxy nodules
Micro: well circumscribed hypocellular nodules that
obliterate normal tissue; nodules are composed of plump
fibroblasts and uniform eosinophilic, non-fibrillar hyaline
material; lesions are more cellular in young and early in
disease; fibroblasts may have fascicular patterns or clear
cytoplasm; no atypia, no necrosis
Micro images: amorphous hyaline matrix in dermis with
fibroblasts; chondroid-like cells due to cytoplasmic
retraction
Cytology: benign spindle cells with background eosinophilic
ground substance (Acta Cytol 2007;51:624)
Positive stains: PAS (diastase resistant), vimentin
Negative stains: muscle actin, S100, beta-catenin
EM: fibroblasts with fibril-filled balls (dilated ER with
numerous cisternae containing filamentous material similar
to extracellular ground substance)
DD: gingival fibromatosis - limited to gums, collagen-rich
fibrous tissue
References: OMIM #228600, Stanford University
Lipofibromatosis of soft tissue

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Definition: pediatric tumor with adipose tissue and

fibroblasts in adipose septa and skeletal muscle
Also called infantile fibromatosis of nondesmoid type
Epidemiology: rare childhood tumor (first surgery usually at
age 1), 2/3 male, often of distal extremities
Clinical: associated with macrodactyly of foot (Foot Ankle
1991;12:40)
Clinically resembles lymphatic malformation, lymphedema or
lipedema
Recurs locally, no metastases
Case reports: foot of male infant (Skeletal Radiol 2008;37:555),
forearm of 10 month old boy (Ups J Med Sci 2005;110:259)
Gross: white-tan or yellow, 1-3 cm
Micro: bland fibroblasts in septa of adipose tissue, may
have minute small vacuolated cells between fibroblasts and
adipose; no atypia, no/rare mitotic figures
Positive stains: spindle cells - CD34, CD99, smooth muscle
actin; variable bcl2, S100, EMA and muscle specific actin
Negative stains: desmin, keratin, beta-catenin
Molecular/cytogenetics: three-way t(4;9;6) translocation in
a 5-year-old boy (rare, Cancer Genet Cytogenet 2007;179:136)
fibrous hamartoma of infancy - has primitive oval cell
component
fibromatosis - solid fibrous growth, no fat
Low grade fibromyxoid sarcoma of soft tissue

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Definition: low grade sarcoma with fibrous and myxoid

areas, whorled growth pattern, low cellularity, bland
fibroblastic cells and curvilinear vessels
Also called fibrosarcoma-low grade fibromyxoid type, Evans
tumor, hyalinizing spindle cell tumor with giant rosettes (AJSP
2003;27:1229); may be related to some cases of sclerosing
epithelioid fibrosarcoma with same translocation (AJSP
2007;31:1387)
Rare, first described by Evans in 1987 (AJCP 1987;88:615)
Prolonged preclinical stage
Epidemiology: in trunk and deep extremities of young to
middle-aged adults (median age 34 years, range 3-78
years), also intrathoracic (Hum Path 2008;39:623)
Clinical: local recurrence (9%) and metastases (6%) are
less common in prospective studies due to more aggressive
surgery
Presence of focal intermediate to high grade sarcoma does
not affect prognosis (AJSP 2000;24:1353)
Superficial cases may be more common than previously
recognized, and have a better prognosis (AJSP 2005;29:204)
Case reports: 12 year old girl with massive tumor of chest
cavity (Pediatr Radiol 2009;39:396), 37 year old man with tumor of
falciform ligament (BMC Surg 2003;3:7), 44 year old woman with
tumor on epicardial surface of heart (Hum Path 2008;39:623)
Treatment: complete excision
Clinical images: swelling of lower left leg
Gross: often > 6 cm, well circumscribed, fibromyxoid cut
surface, may be grossly infiltrative
Gross images: tumor of falciform ligament #1; #2; #3;
well circumscribed with myxoid cut surface and cystic
change; well circumscribed tumor of leg; well
circumscribed tumor with giant rosettes
Contributed by Mark Rodacker: Low grade fibromyxoid

sarcoma
Micro: low to moderately cellular, bland fusiform or spindled

cells with focal to diffuse whirling in heavily collagenized
stroma with abrupt transition to myxoid areas, 45% have
epithelioid areas; 40% contain poorly formed but large
collagen rosettes; often infiltrates adjacent skeletal muscle;
occasionally has areas of increased cellularity, atypia,
necrosis or mitotic activity characteristic of intermediate to
high grade sarcoma

(continued)
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Micro images: AFIP - characteristic features include

fibrous and myxoid areas, a swirling whorled growth
pattern, low to moderate cellularity and bland cells with
minimal nuclear pleomorphism; the swirling growth
pattern is storiform; there is a relatively linear cell
arrangement in this area, but other areas have the
characteristic swirling and whorled pattern
other - alternating fibrous and myxoid areas in swirling

pattern; storiform pattern; predominantly fibrous area;
myxoid area; bland spindle cells in fibromyxoid
stroma; whirled fibroblastic cells in a myxoid
background with prominent capillaries #1; #2; rosettes
in spindled stroma #1; #2; various images #1; #2; lung
metastasis is more cellular but still bland; vimentin+;
staining of vessels but not tumor by CD34, smooth
muscle actin; cells forming rosettes are PGP 9.5+,
Factor XIII negative
Contributed by Mark Rodacker: Low grade fibromyxoid

sarcoma #1, #2, #3, #4
Cytology: cellular with spindle cells containing scant wispy
cytoplasm, uniform elongated nuclei, small inconspicuous
nucleoli; prominent myxoid background; no significant
nuclear pleomorphism or mitoses (Acta Cytol 2006;50:208, Cancer
1999;87:75); cannot diagnosis based only on cytomorphology
(Cytopathology 2008 Jul 14 [Epub ahead of print])
Cytology images: ovoid to spindle cells with tapered
cytoplasm and bland nuclei in myxoid background;
hypercellular three dimensional tissue fragment in
myxoid background; bland spindle cells in myxoid
background #1 (Diff-Quik); #2
Virtual slides: low grade fibromyxoid sarcoma
Positive stains: vimentin, CD99 (90%), bcl2 (90%)
Negative stains: S100, desmin, keratin, CD34, MDM2,
smooth muscle actin, h-caldesmon, CD117, nuclear beta
catenin
EM: fibroblastic differentiation
EM images: rosette forming cells have dense core
granules; elongated irregular nucleus and prominent
dilated rough endoplasmic reticulum are characteristic
of fibroblasts
Molecular/cytogenetics: t(7;16)(q32-34;p11)-FUS-
CREB3L2 in 90% or more, also t(11;16)(p11;p11)-FUS-
CRE3L1 by RT-PCR (Lab Invest 2005;85:408, AJSP 2007;31:1387,
Diagn Mol Pathol 2008;17:237) or FISH (AJSP 2008;32:8)
Molecular/cytogenetic images: complex karyotype
includes t(7;16)

(continued)
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myxofibrosarcoma - more myxoid and less fibrous, more
nuclear pleomorphism and hyperchromatism, more
developed vascular network (Histopathology 2004;45:29)
desmoid fibromatosis - no myxoid areas, fibrous cells are
aligned straighter, cells appear more like reactive fibroblasts,
distinct slit-like vessels present, diffuse or occasionally focal
nuclear beta catenin staining (AJSP 2005;29:653)
neurofibroma - wavy nuclei, background of thick collagen
bundles, S100+
fibrosarcoma-low grade fibroblastic type - no myxoid
component, a diagnosis of exclusion (Histopathology 2006;49:152)
References: Stanford University, Arch Pathol Lab Med 2006;130:1358
Low grade myofibroblastic sarcoma of soft tissue
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Definition: rare tumor of malignant myofibroblasts

Also called myofibrosarcoma
Deep intramuscular tumor of head and neck (tongue and
oral cavity) and extremities, rarely abdominopelvic (J Clin
Pathol 2008;61:301)
Commonly recurs, only rarely metastasizes
Gross: firm, pale, fibrous cut surface, ill defined margins
Micro: diffusely infiltrative with fascicles or storiform growth
of spindled tumor cells; cells have ill defined pale
eosinophilic cytoplasm, fusiform nuclei that are elongated or
wavy with evenly distributed chromatin or round and
vesicular with indentations and small nucleoli; at least focal
moderate nuclear atypia with hyperchromasia and irregular
nuclear membranes; collagenous matrix with prominent
hyalinization; may have numerous thin walled capillaries, 1-6
MF/10 HPF; no histiocytic giant cells or prominent
inflammation
Micro images: breast - H&E shows fascicular growth (fig
1A), alpha smooth muscle actin+ (fig 1B) and vimentin+
(insert), fibronectin+ matrix (fig 1C), type IV collagen
negative (fig 1D)
Positive stains: at least one myogenic marker (desmin,
alpha smooth muscle actin, muscle specific actin or
calponin)
Negative stains: S100, EMA, h-caldesmon, ALK
EM: myofibroblastic features of indented and clefted nuclei,
variable rough endoplasmic reticulum, discontinuous basal
lamina
Molecular: gains at 1p11p36.3 (66%), 12p12.2p13.2
(45%), 5p13.2p15.3 (31%), +22 (28%), loss at
15q25q26.2 (24%) (Am J Clin Pathol 2009;131:701)
fibromatosis / myofibromatosis
nodular fasciitis - not infiltrative, not deep, lacks
chromosomal anomalies
leiomyosarcoma - alternating fascicular pattern
solitary fibrous tumor
fibrosarcoma
inflammatory myofibroblastic tumor - more heterogeneous,
less cellular, less hyperchromasia, less infiltrative, ALK+
(Hum Pathol 2008;39:846)
References: AJSP 1998;22:1228
Mammary type myofibroblastoma of soft tissue

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Definition: benign myofibroblastic lesion with hyalinized

collagenous stroma and often adipose tissue, identical to
breast lesion
See also Breast-nonmalignant chapter
Epidemiology: median age 55 years, 80% men, usually
incidental finding in hernia repair surgery
Usually inguinal / groin region or along milk line, also
abdominal wall, buttock, back, vaginal wall
Usually subcutis, but may be deeper
May be related to hormonal status (gynecomastia or anti-
androgen therapy in men)
Different entity: superficial cervicovaginal
myofibroblastoma
Case reports: head and neck tumor resembling spindle cell
lipoma (Head Neck 2009 Jan 8 [Epub ahead of print])
Treatment: excision, does not appear to recur, but follow up
has been short
Gross: median 6 cm, unencapsulated but well
circumscribed, firm, white-pink-tan-brown, nodular or whirled
cut surface
Micro: identical to breast lesion; fascicles of myofibroblastic
spindle cells with eosinophilic to amphophilic cytoplasm and
poorly defined borders, oval to tapered nuclei with fine
chromatin and small nucleoli; stroma has haphazard bands
of collagen; may have epithelioid features (Am J Surg Pathol
2009 Apr 22 [Epub ahead of print]), focal nuclear atypia with
enlarged nuclei or multinucleation, small vessels with
perivascular lymphocytes, prominent adipose tissue, mitotic
figures (but no atypical forms) (Arch Pathol Lab Med 2008;132:1813)
Micro images (breast): AFIP - circumscribed border;

fascicles of spindle cells separated by dense collagen
bundles
other (breast) - fascicles of spindled and oval cells
separated by bands of thick collagen #1; #2; #3;
classic features; variants #1; #2; epithelioid type #1;
#2; #3; CD34+; predominantly fatty variant #1; #2
(inset-desmin); fig 1: sharply circumscribed tumor with
fibrous pseudocapsule, fig 2: composed of bland
spindle cells in collagenous or myxoid stroma, fig 3A:
CD34+, fig 3B: bcl2+, fig 4: desmin+ (focal)
Mammary type myofibroblastoma of soft tissue

(continued)
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Cytology (breast): abundant random single and clustered

benign spindle mesenchymal cells with scant cytoplasm and
elongated or oval nuclei with finely granular chromatin and
inconspicuous nucleoli (Diagn Cytopathol 2004;30:406)
Cytology images (breast): loose groups of cells with
abundant eosinophilic granular cytoplasm and bland
nuclei
Positive stains: desmin, CD34, variable smooth muscle
actin
Molecular/cytogenetics: may have 13q and 16q changes
(also spindle cell lipoma, Virchows Arch 2006;449:244)
angiofibroma - thicker, hyalinized vessels, no
myofibroblastic spindle cells
lipomatous hemangiopericytoma - larger ectatic vessels, no
myofibroblastic spindle cells
solitary fibrous tumor - hypo- and hypercellular areas, large
ectatic vessels
Myofibroma / myofibromatosis of soft tissue

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Definition: myofibroblastic/smooth muscle tumor (solitary,

multifocal or generalized) composed of spindle cell areas
that may alternate with hemangiopericytoma-like areas,
usually before age 2 years
Formerly called infantile myofibromatosis, infantile
hemangiopericytoma
Solitary (myofibroma) or multiple (myofibromatosis) nodules
in skin (Mod Path 1989;2:603), soft tissues, bone or viscera
Epidemiology: 60% congenital, most before 2 years; most
common fibrous tumor of infancy
May regress spontaneously
Sites: 50% of myofibromas in head and neck, trunk,
extremities; 15% of myofibromatosis in deep soft tissues and
viscera
Oral soft tissue: mean age 22 years (J Oral Pathol Med
2007;36:304)
Orbit: may cause bony destruction (Ophthal Plast Reconstr Surg
2006;22:292)
Generalized myofibromatosis is characterized by visceral
lesions, especially lung, may cause morbidity and death
Case reports: large fetal neck tumor (J Med Assoc Thai
2007;90:376), newborn with mass compressing inferior vena
cava (Adv Neonatal Care 2008;8:13), 5 month old girl with orbital
tumor and death due to metastases (Ophthal Plast Reconstr Surg
2008;24:147), 63 year old man with cutaneous myofibroma of
leg (Indian J Dermatol Venereol Leprol 2008;74:56)
Treatment: conservative excision for solitary lesions (Arch
Otolaryngol Head Neck Surg 1999;125:39); chemotherapy for
multiple or visceral lesions (Cancer 2001;92:2692); also interferon
(J Pediatr Hematol Oncol 2008;30:179)
Clinical: purple macules resemble a vascular neoplasm
Clinical images: multiple nodules of lower limb in 8 year
old boy
Gross: mean 2.5 cm, firm, fibrous, gray-white-brown cut
surface, often central necrosis / cystic spaces with cheesy
material or hemorrhage, better defined in dermis than deep
soft tissue or viscera
Micro: nodular or multinodular proliferation with zonal
appearance; peripheral areas have short fascicles or whirls
of plump myofibroblasts with pale pink cytoplasm and long,
tapering nuclei with vesicular chromatin and 1-2 small
nucleoli, but no atypia or pleomorphism; often associated
with hyalinization; center of nodules has round, polygonal or
spindle cells with scant cytoplasm, hyperchromatic nuclei,
arranged around thin walled branching vessels resembling
hemangiopericytoma; usually calcification, necrosis,
hyalinization; often apparent intravascular growth (is actually
subendothelial) but still benign; no/rare mitotic figures
Myofibroma / myofibromatosis of soft tissue (continued)

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Micro images: AFIP - solitary cutaneous lesion features

zones of fibrous tissue with bundles of myofibroblasts
and prominent thin-walled vessels; high power shows
interface with normal collagen; biphasic with immature
cells in hemangiopericytoma pattern and bundles of
myofibroblastic cells; central hemangiopericytic area is
rimmed by hyalinized myofibroblastic area; junction
between myofibroblastic cells and immature spindled
cells; myofibroblastic spindle cells and immature cells
are arranged in hemangiopericytic pattern
other - arm tumor #1; #2; poorly circumscribed nodular

tumor; fascicles of spindle cells resemble leiomyoma;
well circumscribed tumor; cellular and keloid-like areas
#1; #2; #3; #4; various images #1; #2; infant lesion
#1; #2; #3; dermis is infiltrated by fascicles of smooth
muscle-like cells; trichrome stain (fig B) highlights
prominent collagen not seen on H&E (fig A); intracranial
tumor
48 year old woman with nodules on scalp -

myofibroblasts around capillaries and sclerosing areas
#1; #2; #3; tumor infiltrates skeletal muscle;
hemangiopericytoma-like vascular pattern; fascicles of
myofibroblastic cells with oval nuclei; smooth muscle
actin+; vessels are CD34+; desmin negative (vessel is
positive)
Positive stains: myofibroblasts - vimentin, smooth muscle

actin, HHF35; cells in central zone - vimentin and smooth
muscle actin
Negative stains: S100, cytokeratin, desmin
EM: continuum from fibroblasts to myofibroblasts to smooth
muscle, with prominent dilated rough endoplasmic reticulum,
longitudinal filament bundles with dense bodies, focal basal
lamina
smooth muscle tumor - single lesion, no zonation, minimal
fibrous tissue with trichrome stain (J Formos Med Assoc
2008;107:767)
inflammatory myofibroblastic tumor - prominent
inflammation with plasma cells, no primitive cells with
hemangiopericytic vascular pattern
myopericytoma - predominant growth pattern is concentric
perivascular arrangement of plump spindle cells (J Clin Pathol
2006;59:67)
Myositis ossificans
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Definition: focal intramuscular reparative lesion composed

of cellular fibrous tissue and metaplastic bone
See also Bone chapter
Also called benign fibro-osseous lesion or heterotopic
ossification (better terms since may not involve muscle or
inflammation)
In subcutis, called panniculitis ossificans; in fascia or
tendons, called fasciitis ossificans
Various forms: circumscripta (localized, either traumatic or
atraumatic) or progressiva (also called fibrodysplasia
ossificans progressiva, inherited disorder with increasing
involving of muscle groups over time)
Epidemiology: usually physically active young males with
rapid growth of mass; 60-75% have history of trauma in prior
4-6 weeks; may also occur after elective surgery, severe
burns, neurological injury
Fibro-osseous pseudotumor of digits: similar entity that
affects fingers of older adults with occupations that require
repetitive manual use (Ann Diagn Pathol 2008;12:21), less likely to
contain fibrinous material (Int J Surg Pathol 2003;11:187)
Sites: upper extremity flexors, quadriceps, thigh adductors,
gluteal muscles, soft tissues of hand
Xray: periosteal reaction with eggshell calcification at
periphery 3-6 weeks after injury; recommended to review
Xrays before diagnosis
Case reports: 9 year old boy with thigh pain (UPMC Case #72),
10 year old girl with progressiva form (Internet Journal of
Orthopedic Surgery 2009;12(1)), 11 year old boy with thigh mass
(Eur J Pediatr 2009;168:523), 46 year old man with tumor of
sternocleidomastoid muscle after clavicle fracture (Cases J
2008 Dec 22;1(1):413), multiple tumors at autopsy due to trauma
(Leg Med (Tokyo) 2008;10:274)
Treatment: excision, although may regress without
treatment; rarely recurs if incompletely excised
Gross: well circumscribed, soft center, gritty periphery,
usually 3-5 cm
Gross images: bone fragment from abdominal wall; in
muscle
Micro: cellular stroma with new bone, atypia and mitotic
figures, rarely cartilage; zonation often present, although
zones may be poorly demarcated
early lesions (3 weeks): inner cellular zone resembling
nodular fasciitis or osteosarcoma, with short fascicles or
haphazard fibroblasts that are uniform with faint eosinophilic
cytoplasm, tapering processes, vesicular or finely granular
nuclei and variable nucleoli, usually numerous mitotic figures
but none atypical; stroma is vascular, myxoid or edematous
with extravasated red blood cells, fibrin, scattered
inflammatory cells and osteoclast-like giant cells;
intermediate zone has osteoblasts depositing woven bone,
and outer zone has mineralized trabeculae
later: bone matures with formation of marrow and
myofibroblasts are less prominent
Myositis ossificans (continued)

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Micro images: AFIP - mature bone at periphery, fibrous
tissue resembling nodular fasciitis at center, osteoid in
between #1; #2; fibroblastic and myofibroblastic cells
in center of lesion resemble nodular fasciitis, with
nuclear uniformity #1; #2; osteoid is broader than in
osteosarcoma; osteoblasts have large nuclei with
prominent nucleoli, but clues to benign nature of lesion
are reactive fibrous areas; osteoid deposition is
uniform, and nuclei are enlarged but not pleomorphic;
osteoid undergoing mineralization
other - bone and marrow elements; zonation; highly

cellular deep focus resembles sarcoma; midportion
shows osteoid formation by plump osteoblasts;
peripheral zone shows well formed bone; image #1;
#2; #3; various images (9 year old boy with thigh
lesion); fig 8: central fibroblasts/myofibroblasts merge
with woven bone at periphery, note the prominent
osteoblastic rimming
Cytology images: hip mass with FNA showing crystals

consistent with calcium
Virtual slides: myositis ossificans
Positive stains: fibroblasts and myofibroblasts express
vimentin and variable actin and desmin, osteoclasts express
vimentin
EM: fibroblasts and myofibroblasts have dilated rough
endoplasmic reticulum and aggregates of cytoplasmic
filaments variably associated with dense bodies; osteoblasts
have numerous mitochondria and abundant dilated rough
ER
Molecular: usually polyclonal (Virchows Arch 2005;446:438), but
some cases have clonal USP6 rearrangements, and may be
better classified as soft tissue aneurysmal bone cysts
(Skeletal Radiol 2008;37:321, Cancer Res 2004;64:1920)
Progressiva variant due to mutations in ACVR1 and NOG
genes (Genet Couns 2009;20:53)
extraosseous osteosarcoma - rare, age 40+ years, different
radiologic findings, malignant cytology, atypical mitotic
figures, no or reverse zonation
juxtacortical osteosarcoma - bone tumor, no zonation
osseous muscle metastasis (AJR Am J Roentgenol 2001;176:1165)
References: eMedicine
Myxofibrosarcoma of soft tissue
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Definition: spectrum of malignant fibroblastic lesions with

myxoid stroma, pleomorphism and curvilinear vessels
Formerly called myxoid malignant fibrous histiocytoma
(MFH)
See also Heart chapter
Epidemiology: usually ages 60-69 years, in skeletal muscle
and subcutis of extremities, rarely cutaneous (Am J
Dermatopathol 2003;25:281)
Retroperitoneal masses may actually be dedifferentiated
liposarcoma
Clinical: 2/3 recur, 1/4 metastasize (lung, bone); better
prognosis than storiform-pleomorphic MFH
Local recurrences show increase in tumor grade and more
complex karyotypes (Mod Path 2006;19:407)
Low grade myxofibrosarcoma differs clinically (older
patients) and histologically from low grade fibromyxoid
sarcoma (Histopathology 2004;45:29)
Poor prognosis: deep seated and high grade lesions (more
metastases), epithelioid variant (AJSP 2007;31:99); for low
grade tumors, tumor necrosis and size of 5 cm or more (Hum
Path 2004;35:612)
Case reports: 31 year old man with tibial tumor (Archives
2004;128:e65), 44 year old woman with low grade tumor and
invasion into skeletal muscle (J Dermatol 2007;34:561), 75 year
old man with progression from myxoid pleomorphic fibroma
(Australas J Dermatol 2003;44:287), diffuse infiltrative forearm
tumor causing carpal tunnel syndrome (J Hand Surg [Am]
2008;33:269), extension along perineurium of nerve (Acta Chir
Belg 2007;107:442)
Treatment: wide local excision
Gross: superficial tumors are multiple mucoid nodules, deep
tumors are a single mass with infiltrative margins; high grade
tumors have tumor necrosis
Gross images: thigh tumor; lower extremity tumor;
subcutaneous tumor #1; #2; multinodular tumor
Myxofibrosarcoma of soft tissue (continued)

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Micro: multinodular growth of myofibroblast or lipoblast-like

cells (not true lipoblasts) that are well differentiated to
pleomorphic; also typical MFH areas, curvilinear vessels
(thick walled with broad arc) with condensation of cells
around vessels, incomplete fibrous septa, myxoid stroma (at
least 10% of tumor) and infiltrating immature dendritic cells
(AJCP 2003;119:540); has infiltrative periphery and often sends
out long tentacles with frequent positive margins; high grade
tumors are more cellular with atypical mitotic figures,
hemorrhage, necrosis and possibly bizarre multinucleated
giant cells; rarely epithelioid
low grade: minimal cellular atypia; 30% or more myxoid
component, 20% or less solid component, 10% or less tumor
necrosis, although grading is not predictive of outcome
Micro images: AFIP - myxoid areas may have

pleomorphic cells and variable cellularity; moderate
cellularity with pleomorphic cells; grade I tumor has the
minimal pleomorphism required for diagnosis of MFH
#1; #2; grade II tumor #1; #2-myxoid areas alternate
with solid area that is not as pleomorphic as usual
MFH; grade III tumor with markedly pleomorphic areas
(left) and myxoid areas (right), myxoid areas may lack
pleomorphic cells; typical cellular areas with occasional
giant cells #1; #2
other - cellular and myxoid foci; moderate

pleomorphism; lipoblast-like tumor cells; grade I tumor
- fig 1: yellow gray gelatinous cut surface, fig 2: nodular
with prominent myxoid areas, fig 3: spindle cells with
mild atypia and rare mitotic figures, fig 4: vimentin+;
various images
resembling ischemic or proliferative fasciitis (AFIP) -

myxoid stroma with low density of ganglion-like cells;
bizarre cells are strongly suggestive of malignancy, not
a reactive condition
not myxoid MFH due to lack of pleomorphism (AFIP) -

these lesions are called juxta-articular myxoma, cellular
intramuscular myxoma or myxoid lesion with recurrent
potential, they may recur but do not metastasize #1; #2
Myxofibrosarcoma of soft tissue (continued)

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Cytology: variable cellularity, myxoid granular to

filamentous background in all cases, but less in high grade
tumors; tumor cells are round to spindled with variable
shapes and sizes; cytoplasm varies from scant to dense and
tapering; nuclei are large, pleomorphic and hyperchromatic,
often with prominent nucleoli; occasional multinucleated
giant cells; high grade tumors resemble other adult
pleomorphic sarcomas (Diagn Cytopathol 1999;20:6)
Positive stains: vimentin, acid mucins, CD34 (38%, J Clin
Pathol 2003;56:666)
Negative stains: fat stains (positive in cytoplasmic vacuoles
of lipoblasts in liposarcoma), S100
EM: fibroblastic differentiation in most cells; low grade
tumors have spindled to plump cells with abundant
cytoplasm, rich in well-developed rough endoplasmic
reticulum cisternae, often distended and sometimes
cystically dilated, containing electron lucent granular
material, consistent with fibroblastic differentiation; also cells
with rough ER, well developed Golgi, lysosomes and
filopodia, consistent with fibroblasts with histiocytic
properties (Ultrastruct Pathol 2004;28:321)
Molecular/cytogenetics: highly complex karyotypes, often
6p-, 9q+, 12q+
nodular fasciitis - no atypical cells, no atypical mitotic
figures
myxoma - no atypia, less prominent vasculature, few
mitotic figures, normal karyotype (J Cell Mol Med 2009 Mar 13
[Epub ahead of print])
myxoid liposarcoma - lipoblasts with clear cytoplasmic
vacuoles, plexiform vasculature, no bizarre cells
metastatic carcinoma from kidney or adrenal gland
Myxoinflammatory fibroblastic sarcoma of soft tissue

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Definition: rare low grade sarcoma of hands and feet with

myxoid stroma, inflammation and virocyte-like cells
Also called inflammatory myxohyaline tumor of the distal
extremities with virocyte or Reed-Sternberg-like cells, acral
myxoinflammatory fibroblastic sarcoma
First described in 1998 (Mod Pathol 1998;11:384)
Epidemiology: rare; men and women of all ages (mean age 48
years) with slow growing mass, 77% in hands or feet (J Cutan
Pathol 2008;35:192)
Case reports: 13 year old girl with back tumor (Int J Dermatol
2008;47:68), 29 year old man with finger mass (Archives
2005;129:1343), 30 year old man with elbow mass (Archives
2006;130:e35)
Treatment: wide local excision; may recur locally, distant
metastases are rare (J Cutan Pathol 2008;35:186)
Gross: multinodular, poorly defined, up to 8 cm, often
involves joints and tendons; white and gelatinous with
fibrous and myxoid zones
Micro: multinodular tumor of polymorphous cells with
infiltrative margins in subcutis and often dermis, but only
rarely skeletal muscle; three types of tumor cells: (a)
epithelioid or spindled, occasionally large with bizarre nuclei
and prominent nucleoli resembling viral inclusions or Reed-
Sternberg cells, (b) multivacuolated cells resembling
pleomorphic lipoblasts and (c) giant cells with emperipolesis;
also acute and chronic inflammatory cells, distinct myxoid
and hyaline zones; 0-1 MF/10 HPF, no atypical forms,
no/rare necrosis
Micro images: AFIP - myxoid nodule has characteristic

ganglion-type cells with prominent nucleoli
other - fibrous region with inflammatory cells; myxoid

region with inflammatory cells; acute inflammatory
cells, larger cells with vesicular nuclei and
multinucleated giant cell; nodules of tumor cells
infiltrating along ulnar nerve; spindle cells, ganglion-
like cells, Reed-Sternberg-like cells and lymphocytes
surrounding tendon sheaths; spindle cells with
prominent nucleoli in myxoid stroma; various images
29 year old man - fig 1: atypical epithelioid cells in

background of lymphocytes, plasma cells and
eosinophils; fig 2: Reed-Sternberg like cells; fig 3: cords
of cells resembling extraskeletal myxoid
chondrosarcoma alternating with lipoblast-like cells; fig
4: gray-white tumor involving subcutis, skeletal muscle
and superficial bone
30 year old man - figure 1: background of lymphocytes,

plasma cells, neutrophils and eosinophils; figure 2:
Reed-Sternberg / virocyte-like cells; figure 3:
multivacuolated cells; figure 4: giant cells containing
neutrophils and eosinophils
Myxoinflammatory fibroblastic sarcoma of soft tissue

(continued)
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Cytology: spindle, epithelioid, lipoblast-like and ganglion-
like cells in myxoid background with prominent inflammatory
infiltrate, cases may not display all features, must be
cautious in diagnosis of soft tissue lesions by cytology alone
(Acta Cytol 2007;51:231, Cytopathology 2003;14:73)
Positive stains: vimentin, usually CD34, CD163 and EGFR;
variable CD68, occasionally keratin
Negative stains (tumor cells): CD45, T and B cell markers
EM: fibroblastic features of abundant rough endoplasmic
reticulum and mitochondria, intermediate filaments; lipoblast
like cells have cytoplasmic pseudoinclusions with
extracellular mucin
Cytogenetics: complex and heterogeneous karyotypes,
inconsistent between cases, including aneuploidy (Virchows
Arch 2007;451:923), ring chromosomes (Cancer Genet Cytogenet
2004;152:61), t(2,6) (Cancer Genet Cytogenet 2007;177:139)
Hodgkins lymphoma - lacks giant cells and lipoblast-like
cells, tumor cells have different staining patterns
myxofibrosarcoma or pleomorphic liposarcoma - rare in soft
tissues of hands and feet, more frequent mitotic figures with
atypical forms, no inflammatory infiltrate
Rosai-Dorfman disease - emperipolesis, but no intranuclear
or cytoplasmic vacuoles, S100+
epithelioid sarcoma - most cells are round with bright
eosinophilic cytoplasm, strongly keratin+
tenosynovitis - no enlarged atypical cells
References: AJSP 1998;22:911, Virchows Arch 2003;442:25
Nodular fasciitis of soft tissue

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Definition: highly cellular, reactive lesion of fibroblasts and

myofibroblasts in myxoid stroma with granulation tissue-like
vascular proliferation, lymphocytes and extravasated red
blood cells, usually in young adults in fascia and subcutis,
with rapid growth to 2-3 cm
Common lesion that typically presents as a rapidly growing
mass on the flexor forearm, chest, back or elsewhere
Arises from superficial fascia, occasionally intramuscular or
intravascular
May also develop within bladder (Hinyokika Kiyo 1994;40:427),
breast (Breast 2005;14:384), cervix, intra-articular (AJSP
2006;30:237), prostate, vagina, vulva (Int J Gynecol Path
1997;16:117)
Epidemiology: peaks at age 40 years; prior trauma in 10%
of cases
Benign behavior, but frequently misdiagnosed as sarcoma
based on cellularity, mitotic figures and rapid growth
Case reports: 37 year old woman with wrist mass (Case of the
Week #65), 44 year old man with shoulder mass (The Internet
Journal of Plastic Surgery 2007;3(1)); regression after biopsy (J
Craniofac Surg 2008;19:1167)
Treatment: excision (curative even if incomplete resection);
recurs in 1% after incomplete excision but recurrence should
suggest review of diagnosis; no metastases
Gross: tan-white-gray, myxoid appearance, usually 2 cm or
less, relatively well circumscribed, no capsule; may be
centered in subcutis, may grow into skeletal muscle
Gross images: scapular lesion; intraoperative mass
within deltoid muscle
Micro: zonation effect with hypocellular central region and
hypercellular periphery; composed of uniform, plump,
immature fibroblasts or myofibroblasts without atypia, with a
feathery, tissue-culture like growth pattern due to abundant
ground substance; often with mucoid pools (microcysts);
uniform elongated nuclei with prominent nucleoli; cellular
areas may have storiform or fascicular patterns (S or C
shaped); often frequent mitotic figures (but no atypical
forms), lymphocytes and macrophages, red blood cell
extravasation, bands of keloid-type collagen; vasculature is
usually prominent; walls of small to medium sized vessels
are involved by reactive process at periphery of lesion; may
infiltrate adjacent fat; may have metaplastic bone, focal
cystic areas, ganglion type cells but no cells with large,
hyperchromatic, atypical nuclei; no/rare plasma cells and
neutrophils; does not extend to skin except on face
Nodular fasciitis of soft tissue (continued)

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Micro images: AFIP - subcutaneous tumor is partially

circumscribed nodule infiltrating focally along fascial
planes; focal infiltration into fat, with evenly distributed
granulation tissue-like vessels throughout the lesion;
gently curving C and S shaped fascicles of
myofibroblastic cells exhibit a characteristic torn
Kleenex pattern; focal storiform pattern is suggestive
of fibrous histiocytoma; plump spindled
myofibroblastic cells and extravasated red blood cells;
mitotic figures but no abnormal forms; focally more
collagenous stroma with skeletal muscle involvement;
cystic degeneration #1; #2; osteoclastic giant cells are
present in less collagenous areas, suggesting a variant
of MFH; hyalinized variant resembles keloid or
fibromatosis; vague zonation pattern with bone
formation in lower right; island of new bone surrounded
by myofibroblastic cells
other - leg lesion #1; #2; #3; #4; #5-resembles

fibroblast culture; spindled fibroblasts and
extravasated red blood cells in myxoid background, with
giant cells (blue arrows) and mitotic figures (red
arrows); myofibroblasts and staghorn blood vessels;
small ill-defined lesion centered in subcutis; very
cellular lesion; myxoid areas; keloid like collagen
deposition; blood vessel involvement; figures 10A/B:
H&E and CD68
Case of Week #65 / tumor of wrist - image #1; #2; #3;

#4; #5; #6
Cytology: markedly hypercellular smear with clusters of

overlapping, relatively monomorphic spindle or epithelioid
cells resembling sarcoma (AJCP 2005;123:388); also
inflammatory cells, single mesenchymal cells, myxoid stroma
(Acta Cytol 2004;48:473)
Positive stains: fibroblasts/myofibroblasts - smooth
muscle actin (Ann Diagn Pathol 2002;6:94), muscle specific actin,
vimentin and calponin (Am J Dermatopathol 2006;28:105);
macrophages - CD68 (not specific for histiocytes-also
fibroblasts that have acquired phagocytic properties)
Negative stains: S100, desmin, keratin and CD34 (AJSP
1993;17:1039); caldesmon, ALK, p53
EM: cells resemble myofibroblasts, are elongated with
abundant, often dilated rough endoplasmic reticulum, may
have cytoplasmic filaments with dense bodies, pinocytotic
vesicles and cell junctions
Molecular/cytogenetics: diploid, no/few genetic aberrations
(Am J Clin Pathol 2009;131:701)
Nodular fasciitis of soft tissue (continued)

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benign fibrous histiocytoma - based in dermis, storiform
pattern, infiltrative borders, prominent xanthoma cells and
often Touton giant cells, no microcysts
fibromatosis - usually large tumor that infiltrates
surrounding soft tissue, spindled cells are separated by
abundant collagen, no loose tissue culture appearance
inflammatory MFH - larger size, slower growth, more
pleomorphic cells, presence of neutrophils, plasma cells,
foam cells and atypical mitotic figures, no RBC
extravasation, no keloid-type collagen
inflammatory myofibroblastic tumor - no rapid growth, no
zonation, no prominent myxoid stroma; larger tumor size,
has mixed inflammatory infiltrate
myositis ossificans (early) - centered in muscle,
calcification
myxofibrosarcoma - large, regularly arborizing vessels,
atypia and pleomorphism
other sarcoma - atypia is prominent
reactive spindle cell nodules - post-biopsy
Cranial fasciitis
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Definition: variant of nodular fasciitis that usually affects

scalp and skull of infants or children < 2 years old
Rare; usually boys, erodes outer table of cranium and may
infiltrate dura
Some cases show dysregulation of Wnt/beta-catenin
pathway, and may be related to desmoid fibromatosis (Mod
Pathol 2008;21:1330)
May be related to birth trauma, craniectomy or be
spontaneous (J Neurosurg Pediatr 2008;2:370)
Grows quickly like nodular fasciitis, but same benign
behavior (Cancer 1980;45:401)
Xray: lytic defect of skull with sclerotic rim
Case reports: 7 month old boy (AJNR Am J Neuroradiol
2003;24:1465), 3 year old girl with epidural mass (Pediatr
Neurosurg 2008;44:148)
Gross: circumscribed, rubbery to firm; variably myxoid or
cystic
Micro: fibroblasts, giant cells, myxoid matrix; may have
osseous metaplasia
Positive stains: nuclear beta-catenin (some cases)
References: Hum Pathol 1999;30:87
Intravascular fasciitis
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Definition: variant of nodular fasciitis that involves wall and

lumen of small to medium-sized veins and arteries (AJSP
1981;5:29)
Usually subcutaneous
Rare; usually age 30 years or less
Slower growth than classic nodular fasciitis but same
behavior
Case reports: pregnant woman with hand lesion (World J Surg
Oncol 2007;5:7)
Gross: usually 2 cm or less; nodular or plexiform
Micro: resembles nodular fasciitis, often more prominent
osteoclast-like giant cells; may be intra- or extravascular
Micro images: AFIP - large focus of nodular fasciitis
protrudes into vascular space; cellular proliferation has
edematous background characteristic of nodular
fasciitis
other - intravascular proliferation of spindle cells #1;
#2; #3
Proliferative funiculitis
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Definition: pseudosarcomatous myofibroblastic proliferation

of spermatic cord
Usually incidental at herniorrhaphy
Ages 52-76 years; may be due to ischemia, torsion or
extension of vasitis
Resembles nodular fasciitis
Similar lesions in epididymis
Micro: may contain malignant appearing glandular
structures composed of keratin+ mesothelial cells (Int J Surg
Pathol 2008;16:48), rarely has proliferation of mast cells (Pathol Int
2003;53:897)
Positive stains: myofibroblasts - smooth muscle actin
Nuchal fibrocartilaginous pseudotumor of soft tissue

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Definition: fibrocartilaginous metaplasia of nuchal ligament

overlying lower cervical vertebrae
Some consider it the same entity as nuchal type fibroma
Not a distinct WHO diagnosis
First described in 1997 (AJSP 1997;21:836); very rare
May be due to trauma (automobile accident) or chronic
mechanical stress (Mod Path 1999;12:663)
Case reports: 10 year old girl post neck trauma (Archives
2000;124:1217), 30 year old woman with neck trauma (J
Neurosurg Sci 2003;47:173)
Treatment: simple excision, does not recur
Micro: poorly defined, moderately cellular fibrocartilaginous
nodules, no atypia, no mitotic activity
Micro images: fibrocartilage surrounded by
disorganized collagen bundles
Positive stains: CD34, vimentin, focal S100 in
chondrocytes (Pathol Int 2001;51:723)
Negative stains: CD99, desmin, alpha smooth muscle actin
EM: fibroblastic and chondroblastic features, no
myofibroblastic features
Nuchal type fibroma of soft tissue

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Definition: bundles of thick collagen fibers in posterior neck

Also called collagenosis nuchae
Nuchal: nape (posterior) of neck
Epidemiology: rare benign lesion of dermis and subcutis in
posterior neck, upper back or other regions, more common
in men, mean 40 years; associated with diabetes in 44%
(Cancer 1999;85:156)
Case reports: associated with DFSP (J Cutan Pathol 2004;31:62)
Treatment: excision, recurs but does not metastasize
Gross: usually 3 cm or less, hard and white,
unencapsulated, poorly circumscribed
Micro: no capsule, hypocellular, thick collagen fibers with
delicate elastic fibers, entrapped adipose and entrapped
nerves, resembling traumatic neuroma, may infiltrate into
skeletal muscle, may have scattered lymphocytes
Micro images: AFIP - strands of acellular collagen mixed
with fat; lesion is very hypocellular, differentiating it
from fibromatosis
other - paucicellular with haphazard collagen fibers;

central areas have collagen fibers organized in several
planes of section, with criss crossing bundles often
forming lobules; small entrapped islands of adipose are
common; skeletal muscle involvement; often contains
small nerves with haphazardly arranged fascicles,
resembling traumatic neuroma; often contains delicate
web of elastic fibers running parallel to collagen fibers;
fibrous tissue replaces subcutaneous fat
Positive stains: vimentin, CD34, CD99

Negative stains: actin, desmin
fibrolipoma - circumscribed, different location
fibromatosis - deep soft tissue, not back of neck, more
cellular
solitary fibrous tumor - patternless pattern, more cellular,
staghorn type vessels
Ossifying fibromyxoid tumor of soft tissue

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Definition: uncommon fibromyxoid soft tissue tumor of

uncertain lineage, usually with peripheral bone present
First described in 1989 (AJSP 1989;13:817), now 300+ cases
reported (Am J Surg Pathol 2008;32:996)
Epidemiology: median age 49 years, range 14-83 years,
usually men with small painless mass in trunk or proximal
extremities
Usually histologically benign with benign clinical course;
local recurrences in 17%, malignant behavior in 5%
May have neuroectodermal origin due to CD56+, CD99+ (Int
J Surg Pathol 2007;15:437)
Poor prognostic factors: high cellularity, high nuclear
grade, > 2 mitotic figures/50 HPF (AJSP 2003;27:421)
Case reports: 21 year old woman with gingival mass (J
Periodontol 2009;80:687), invasive spinal tumor (Skeletal Radiol
2008;37:1137)
Treatment: excision
Gross: well circumscribed, median 4 cm, usually involves
deep soft tissue, also cutaneous (Am J Dermatopathol
2007;29:156) or subcutaneous (J Cutan Pathol 2006;33:749)
Micro: nests/cords of round/oval cells with indistinct
cytoplasm in myxoid matrix with fibrosis and osteoid
formation; lobulated at low power; surrounded by partial
capsule of lamellar and woven bone; usually minimal atypia
and minimal mitotic figures, but may have necrosis, vascular
invasion or high nuclear grade
Micro images: tumor cells are bordered by metaplastic
bone; moderately atypical cells in hyaline matrix
Cytology: clusters, cords or small aggregates of round,
polygonal or spindle cells in myxoid background with
osteoid-like material (Diagn Cytopathol 2004;30:41); malignant
cases may show significant nuclear pleomorphism with
coarse chromatin, irregular contours and 1-2 distinct nucleoli
(Acta Cytol 2001;45:745)
Positive stains: vimentin, S100 (60%) (94% in tumors with
conventional histology, Am J Surg Pathol 2008;32:996),
Leu7/CD57 (focal), GFAP (focal), desmin (focal)
Negative stains: keratin, EMA; alpha smooth muscle actin
(usually, may be weak, J Laryngol Otol 1993;107:75)
EM: complex cell processes, reduplicated basal lamina
(Ultrastruct Pathol 2007;31:233)
Cytogenetics: may have complex aberrations (Cancer Genet
Cytogenet 2007;176:156, Cancer Genet Cytogenet 2002;133:124)
Pleomorphic fibroma of skin - Soft Tissue Tumor

chapter
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Definition: polypoid or dome-shaped cutaneous nodule with

sparse cellularity and cytologic atypia of fibroblasts
Not a WHO diagnosis
Usually trunk, extremity or head (Clin Exp Dermatol 1998;23:22)
Case reports: 38 year old woman (Arch Pathol Lab Med
2005;129:e21), 66 year old woman with subungual tumor (J
Cutan Pathol 2003;30:569)
Micro: resembles fibroepithelial polyp but with enlarged,
bizarre, smudged, hyperchromatic nuclei, thick collagen
bundles and rare mitotic figures; may be sclerotic (Am J
Dermatopathol 2002;24:54) or have myxoid foci (Am J Dermatopathol
1998;20:502)
Micro images - AFIP - large pleomorphic cells separated
by collagen; atypical cells have smudged chromatin,
mitoses are absent/rare, compare to sarcomas with
abnormal (but not degenerative) nuclei and frequent
mitotic figures, some atypical; anal skin;
other - stromal cells have atypical nuclei; various
images
Positive stains: vimentin, actin, CD34
Negative stains: S100
atypical fibrous histiocytoma - storiform pattern, more
cellular, foam cells, hemosiderin laden macrophages (Am J
Dermatopathol 1999;21:414)
atypical fibroxanthoma - more cellular, more mitotic figures
giant cell fibroblastoma - young children
angiofibroma - pleomorphic cells are similar, but have
marked vascularity
Proliferative fasciitis - Soft Tissue Tumor chapter

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Definition: subcutaneous or fascial proliferation similar to

nodular fasciitis, but with large basophilic cells resembling
ganglion cells
Similar to proliferative myositis
Epidemiology: usually adults (mean age 50 years); forearm
is most common location, also trunk or proximal extremities,
rare in patients under 15 years old (but see childhood variant
below)
Rapid growth but benign behavior
Case reports: with rapid involution (Skeletal Radiol 2004;33:300)
Treatment: local excision
Gross: usually 3 cm or less, poorly circumscribed deep
tissue mass that may extend horizontally along fascia
Micro: resembles nodular fasciitis due to zonation effect,
tissue culture type growth and plump fibroblastic and
myofibroblastic spindle cells, but has large ganglion type
cells with abundant amphophilic to basophilic cytoplasm,
round vesicular nuclei (occasionally 2-3 nuclei) and
prominent nucleoli; stroma is collagenous or myxoid, often
arborizing vascular pattern; variable mitotic figures but no
atypical ones; ill defined margins
Micro images: AFIP - prominent hemorrhage and vague

centering of cellular proliferation on interlobar septa of
subcutaneous fat; mixture of ganglion-like cells,
myofibroblasts and inflammatory cells; ganglion cells
have abundant amphophilic cytoplasm and prominent
nucleoli; ganglion cells mixed with inflammatory cells
within myxohyaline matrix; condensed around thin
walled vascular channel
other - myofibroblasts and fibroblasts with tissue

culture appearance; ganglion-like cells #1 (figure 2);
#2; #3; #4
stains - van Gieson stain; Alcian blue-PAS
Proliferative fasciitis - Soft Tissue Tumor chapter

(continued)
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Cytology: cellular smear with spindle cells and large cells

with abundant cytoplasm, one to two eccentric nuclei and
macronucleoli (Acta Cytol 1985;29:882)
Positive stains: spindle cells-smooth muscle actin, muscle
specific actin; ganglion-like cells-vimentin, actin
Negative stains: keratin, S100, desmin
nodular fasciitis - no ganglion-type cells
proliferative myositis - identical but intramuscular
ganglioneuroma - different stroma, ganglion cells are
positive for neural markers
rhabdomyosarcoma - cross striations in ganglion-type cells,
desmin+
sarcoma - large mass, actual pleomorphism not just dual
cell population, nuclear chromatin and membrane
abnormalities, atypical mitotic figures
References: Cancer 1975;36:1450, Stanford University
Childhood variant
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Gross: circumscribed mass

Micro: more cellular and lobulated than classic form with
more prominent ganglion-like cells resembling
rhabdomyoblasts and more mitotic figures; may have acute
inflammatory cells and focal necrosis; often no/minimal
fibroblasts
DD: rhabdomyosarcoma
Proliferative myositis of soft tissue

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Definition: intramuscular mass similar to nodular fasciitis,

but with large basophilic cells resembling ganglion cells
Affects skeletal muscle, usually of shoulder, chest or thigh
Children or adults
Treatment: conservative surgery is curative, may have
spontaneous resolution (Head Neck 2007;29:416), recurrence
suggests diagnostic error
Gross: poorly circumscribed, scar-like induration of muscle,
usually 3-4 cm
Gross images: ill defined white material between
skeletal muscle fibers
Micro: cellular with plump fibroblasts and myofibroblasts
surrounding individual muscle fibers creating a checkerboard
pattern; also large ganglion-like cells with abundant
amphophilic to basophilic cytoplasm, vesicular nuclei and
prominent nucleoli; stroma is collagenous or myxoid;
variable mitotic figures but no atypical ones; ill defined
margins; may have metaplastic bone
Micro images: AFIP - characteristic checkerboard

pattern is produced by reactive proliferation expanding
spaces between muscle bundles and individual muscle
fibers #1; #2; with metaplastic bone, resembling
myositis ossificans; large ganglion cells with crowding
and molding resembling carcinoma; cells have
abundant amphophilic cytoplasm and prominent
nucleoli
other - checkerboard pattern; ganglion cells #1; #2;

#3; #4 (figure 3)
spindle cell sarcoma resembling proliferative fasciitis -

AFIP - checkerboard pattern produced by infiltration of
tumor cells between muscle bundles without myocyte
necrosis; cellular proliferation of atypical spindle cells
differs from bland spindle cells of proliferative myositis
Proliferative myositis of soft tissue (continued)

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Cytology: loose clusters of uniform fibroblast-like spindle

cells and large, ganglion-like cells with eccentric nuclei,
prominent nucleoli and abundant cytoplasm (Acta Cytol
1995;39:535)
Positive stains: vimentin, smooth muscle actin, muscle
specific actin
Negative stains: keratin, S100, desmin
EM: fibroblasts and myofibroblasts, ganglion-like cells are
fibroblasts or myofibroblasts with abundant dilated rough
endoplasmic reticulum but no neuronal characteristics (AJSP
1991;15:654)
sarcoma - large mass, marked atypia
proliferative fasciitis - not in muscle
nodular fasciitis - completely obliterates muscle, no
ganglion-type cells
desmoid fibromatosis - 3 cm or larger, completely replaces
muscle, no ganglion-type cells; stroma is collagenous,
skeletal muscle at periphery is injured
Proliferative peribursitis of soft tissue

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Definition: angiomyxoid tumor-like mass near joints and

ligaments
Not a WHO diagnosis
No PubMed references identified
Associated with prior joint disease, dislocation or trauma
Micro: separate vascular and nonvascular regions; vascular
region has cluster of thick vessels with pericyte cuff in
myxoid substance; high power shows evenly disbursed
spindle cells with bipolar and stellate cells, occasional
lymphocytes and histiocytes; histiocytes may contain
vacuoles and resemble lipoblasts; may have cysts with or
without ganglion cells, synovial lining, dense scar
Positive stains: actin (spindle cells)
myxoma - stellate cells only; no prominent vasculature
myxoid liposarcoma - uniform appearance of lipoblasts, no
stellate myofibroblasts
Sclerosing epithelioid fibrosarcoma of soft tissue

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Definition: rare, slow growing, intermediate-grade sarcoma

of deep soft tissue with epithelioid tumor cells in nests and
cords and hyalinized fibrous stroma
Epidemiology: usually age 20+ years, no gender
preference
Sites: limb/limb girdle, head and neck, back/chest wall, base
of penis, cranium
50% have persistent disease or local recurrence; 43-86%
develop distant metastases (lung, bone and soft tissue,
breast, pericardium, brain), 25-57% die of disease within 16-
86 months (AJSP 2001;25:699)
Case reports: 29 year old man with tumor related ascites (J
Med Case Reports 2008 Jul 25;2:248), 30 year old man with
metastatic disease (Sarcoma 2009;2009:953750), 48 year old
woman with sacral tumor (J Clin Path 2004;57:90), 62 year old
Chernobyl cleanup worker with cecal tumor (Archives
2007;131:1825), 90 year old woman with ankle mass (Case of
Week #3)
Gross: mean 9 cm, range 4-22 cm, appears circumscribed
but is not; firm, gray-white cut surface, may invade bone;
usually no necrosis
Gross images: gray-white tumor
Micro: nests or cords of small to medium sized, round to
ovoid, relatively uniform epithelioid cells, often with clear
cytoplasm and uniform bland nuclei embedded in a
hyalinized fibrous stroma; hypo- and hypercellular areas;
tumor cells are often in single file pattern resembling
carcinoma; bone invasion and tumor necrosis are present;
has areas resembling fibroma, low grade fibromyxoid
sarcoma, conventional fibrosarcoma; 4 MF/10 HPF; may
have hemangiopericytoma-like vasculature, vascular
invasion
grade I: cell nuclei slightly larger and more abnormal than
fibromatosis, no necrosis or hemorrhage
grade III: closely packed cells with markedly dense
chromatin and no/minimal collagenous stroma, numerous
mitotic figures
grade II: intermediate between grade I and III
Micro images: ankle mass; cecal tumor; sacral tumor;
single file pattern; keratin MNF 116
Sclerosing epithelioid fibrosarcoma of soft tissue

(continued)
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Positive stains: vimentin, p53, bcl2; variable EMA, S100

and keratin
Negative stains: CD34, CD45, HMB45, desmin, alpha
smooth muscle actin; low Ki-67
EM: fibroblastic features of parallel arrays of rough
endoplasmic reticulum and prominent networks of
intermediate filaments that may form perinuclear whorls
Molecular: may be related to low grade fibromyxoid
sarcoma as same FUS-CREB3L2 translocation is detectable
in some cases (Am J Surg Pathol 2007;31:1387)
low-grade fibromyxoid sarcoma - monotonous and
hypocellular, with alternating myxoid and collagenous
stroma, only focal epithelioid cells
synovial sarcoma - no large areas of sclerotic collagen
sclerosing lymphoma - positive for lymphocytic markers
poorly differentiated carcinoma - positive for keratin
lobular breast carcinoma - single file pattern, but cells are
low grade; usually ER+, PR+, keratin+
References: Histopathology 1998;33:354, Stanford University
Solitary fibrous tumor (extrapleural) of soft tissue

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Definition: fibroblast like cells with patternless pattern, thin

strip-like bands of collagen and gaping vessels
Similar to pleural tumor
Distinction from hemangiopericytoma has become
increasingly blurred
See also discussion in Bladder, CNS, Ear, Eye, Kidney-
Tumor, Liver-Tumor, Nasal Cavity, Oral Cavity, Pleura,
Prostate and Thyroid gland chapters
See also related lesions - giant cell angiofibroma,
hemangiopericytoma
Epidemiology: usually adults (median age 50 years)
Wide anatomic distribution; derives from pleura and various
serosa or sites without any serosa
Rarely causes paraneoplastic hypoglycemia due to insulin-
like growth factor production
Slow growing painless mass, usually benign; histologically
malignant tumors may be grossly infiltrative and up to 50%
may metastasize
Poor prognostic factors: size > 10 cm, >4 MF/10 HPF,
cellular atypia, positive margins, malignant histology (Cancer
2002;94:1057), although histology has less significance in
retroperitoneum (Urol Oncol 2008;26:254)
Case reports: 33 year old woman with mass in check (Case
of Week #29 (dermal tumor), 63 year old woman with thigh tumor
(Diagn Pathol 2007;2:19)
Treatment: excision, but behavior may be unpredictable
(AJSP 1998;22:1501)
Gross: well circumscribed, partially encapsulated, up to 25
cm with multinodular, white, firm, whorled cut surface;
necrosis and infiltrative margins are associated with locally
aggressive or malignant tumors
Gross images: well circumscribed tan-white tumor with
focal necrosis; tumor of omentum #1; #2; pleural
tumor
Micro: patternless architecture of hypo- and hypercellular
areas separated by thick, hyalinized collagen with cracking
artifact and hemangiopericytoma-like vessels; bland and
uniform spindle cells are dispersed along thin parallel
collagen strands, cells have minimal cytoplasm, small
elongated nuclei and indistinct nucleoli; some have myxoid
change (Virchows Arch 2009;454:189), mast cells, adipose tissue
or multinucleated giant cells; minimal pleomorphism; no
atypia, no/rare mitotic figures
malignant SFT - hypercellular, moderate to marked atypia
and pleomorphism, tumor cell necrosis, 4+ mitotic figures/10
HPF, infiltrative margins
Solitary fibrous tumor (extrapleural) of soft tissue

(continued)
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Micro images: AFIP - moderately cellular fibroblastic

appearance; parallel arrays of collagen are separated
by fibroblastic nuclei; cellular variant has cells with
scant cytoplasm and uniform spindled nuclei, note the
thin bands of intercellular collagen;
other - patternless pattern and collagenous stroma;

patternless and myxoid patterns with
hemangiopericytoma-like vessels; fibroblastic cells in
fibrous, partly hyalinized matrix with
hemangiopericytoma-like blood vessels; thick bands of
keloid-type collagen; hemangiopericytoma-like vascular
pattern; tumors without (fig A/B) and with (fig C/D)
malignant components; comparison of immunostains
with GIST; ear-H&E, CD34, CD99 and bcl2; larynx-H&E,
CD34, CD99; thigh-H&E, CD34, bcl2; H&E, CD34, beta-
catenin
Virtual slides: malignant tumor

Positive stains: CD34 (90%), CD99 (60-70%, myxoid-Mod
Path 1999;12:463, oral soft tissue-AJSP 2001;25:900); variable bcl-2,
EMA and actin (Mod Path 1997;10:443)
Negative stains: desmin, keratin, S100, CD117, CD31 (Hum
Path 1995;26:440); vessels are D2-40 negative (Virchows Arch
2006;448:459)
EM: myofibroblasts, fibroblasts
Molecular/cytogenetics: cytogenetic abnormalities in most
tumors 10 cm or larger
synovial sarcoma - usually no thick collagen bands;
keratin+, CD34-
smooth muscle tumors - fascicles of cells with more
abundant cytoplasm, blunted nuclei, desmin+, actin+
benign neural tumors - S100+
References: Mod Path 2002;15:324, Mod Path 1997;10:1028
Superficial acral fibromyxoma of soft tissue

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Definition: name is accurate - superficial tumor of fingers

and toes with bland fibromyxoid histology
Also called digital fibromyxoma
Not a WHO diagnosis
First described in 2001 (Hum Path 2001;32:704)
Slow growing and painless mass of superficial fingers, toes
and palm; often involves nail region (Br J Dermatol 2008;159:1315)
Epidemiology: 2/3 male, mean age 43 years, range 14-72
years
May recur (J Cutan Pathol 2008;35:1020), may develop
persistent/progressive disease after partial excision
Case reports: tumor of big toe (J Eur Acad Dermatol Venereol
2008;22:255), 2 cases (Dermatology Online Journal 2008;14(2):27)
Gross: solitary mass 1-5 cm
Micro: dermal or subcutaneous tumor composed of bland
spindled cells with random loose storiform and fascicular
growth patterns; myxoid or collagenous matrix with
prominent vessels and mast cells, mild nuclear atypia,
occasional multinuclear stromal cells, rare mitotic figures
Micro images: tumor at tip of big toe; spindle cells and
mast cells in myxoid matrix; tumor (fig C/D) compared
to myxoid DFSP (fig A/B); H&E, CD10 and nestin;
CD34+; CD99+
Positive stains: CD34, CD99, Alcian blue (mucinous
material, Dermatology 2002;205:285), variable EMA
Negative stains: actin, desmin, keratin, HMB45, S100
fibrous histiocytoma - more storiform, lacks abundant
myxoid matrix, CD34 negative
DFSP - hands and feet are unusual sites, tight storiform
pattern at least focally, infiltrative, EMA-
acquired digital fibrokeratoma - some tumors are multifocal
and associated with tuberous sclerosis; others are small,
superficial, exophytic, less vascular, less cellular, more
collagenized, may be early stage of superficial acral
fibromyxoma
sclerosing perineurioma - young adults, dense collagen,
onion-bulb spindle cells, CD34-
cutaneous myxoma / superficial angiomyxoma - may be
associated with Carney complex, nodular and abundant
mucin
myxoinflammatory fibroblastic sarcoma - rare, usually
subcutaneous and deep soft tissue, multinodular growth,
some spindle cells with large pleomorphic vesicular nuclei
with prominent inclusion like nucleoli, prominent
inflammation, EMA-
Benign vascular tumors

Hemangioma
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Common benign tumor, particularly in childhood; many may
actually be hamartomas
Usually superficial (head/neck), may occur internally (1/3 in
liver), malignant transformation rare
Usually localized, but may involve large segments of body
(termed angiomatosis)
Most pediatric angiomas are present at birth and expand with
growth of child, may regress at puberty
Micro: increased number of vessels (normal/abnormal);
readily recognizable vascular structures with red blood cells or
transudate; lined by monolayer of non-atypical endothelial cells
Capillary hemangioma
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Blood vessels resemble capillaries
Present in skin, subcutaneous tissue, mucous membranes of
lips, mouth, internal viscera
Strawberry type is seen in juveniles in 1/200 births, may be
multiple, grow in first year, fade at ages 1-3, regress by age 7 in
75%
Micro: closely packed spindle cells with spaces containing
little blood; lumens may be thrombosed or organized, hemosiderin
present due to rupture; scant fibrous stroma
Micro images: figures 1A, 1B
References: Mod Path 2000;13:180
Cavernous hemangioma
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In skin, called port-wine nevus or nevus flammeus
Present at birth, grows slowly with patient; does not regress
In deep locations may thrombose, ulcerate, become infected;
associated with thrombocytopenia, intravascular coagulation
Associated with von Hippel Lindau disease, which has
cavernous hemangiomas in cerebellum, brain stem, eye grounds
Sinusoidal hemangiomas: cavernous hemangiomas with
dilated, interconnected, thin-walled channels with occasional
pseudopapillary projections
Gross: 1-2 cm (larger than capillary), sharply defined
Micro: large cystically dilated vessels with thin walls;
intravascular thrombosis or calcification is common
Intramuscular hemangioma
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Resemble cavernous hemangiomas
May resemble angiosarcoma due to high cellularity with
mitotic figures, intraluminal papillary projections, plump
endothelial cells, perineurial infiltration, but no atypia
Also, angiosarcomas extremely uncommon in skeletal
muscle
Large vessel hemangioma

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Veins, arteries or a mixture
May have abnormal vascular wall structure that defies
classification
Back, gluteal region, thigh; occasionally entire extremity
Thrombosis and calcification common
Klippel-Trenaunay syndrome: varicose veins, dysplastic
cutaneous hemangiomas and soft tissue and bone
hypertrophy
Pyogenic granuloma
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Aka lobular capillary hemangioma
Rapidly growing, exophytic red nodule, attached by a stalk to
skin or gingival mucosa
Bleeds easily, ulcerates
1/3 due to trauma (1-2 cm after 1-2 weeks)
Pregnancy tumor: aka granuloma gravidarum, a pyogenic
granuloma found in 1% of pregnant women, regresses after
delivery
Micro: vessels, edema, acute and chronic inflammation;
resembles granulation tissue
Lymphangiomyoma
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Benign, women only
Fka lymphangiopericytoma
Localized form present in mediastinum and retroperitoneum, associated
with thoracic duct, causes chylothorax, chylous ascities and chyluria
Diffuse form is lymphangioleiomyomatosis (see lung)
Treatment: progesterone, oophorectomy
Micro: proliferation of intermingled blood vessels and smooth muscle;
tumor cells plumper and paler than leiomyoma
Positive stains: actin, desmin, HMB45
DD: angioleiomyoma
Lymphangiosarcoma
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Typically ~10 years post-axillary nodal dissection or radiation therapy for
breast cancer with long-standing massive lymphedema
Also after chronic lymphedema of lower leg
5 year survival < 10%
Gross: blue/purple papules in edematous skin, often multiple
Micro: angiosarcoma-like areas and endothelium-lined spaces without
red blood cells; early - resembles benign collection of vessels, call
atypical vascular proliferation
later - freely anastomosing vascular channels lined by atypical
endothelial cells, often with solid areas resembling breast carcinoma
Glomus tumor
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Usually benign; excision curative
Subungual tumors are exquisitely painful due to abundant
nerve fibers
Arises from modified smooth muscle cells of glomus body, a
specialized arteriovenous anastomosis involved in
thermoregulation
Usually under fingernails; also skin, flexor arm/knee, GI tract
Glomangioma: glomus tumors that resemble cavernous
hemangiomas
Glomangiomatosis: diffuse angiomatosis resembling
angiomatosis with excess glomus cells; often associated with
considerable fat and pain; probably represents vascular
malformations
Gross: less than 1 cm, rounded, red-blue, firm; resembles
fresh hemorrhage under the nail
Micro: branching vascular channels separated by stroma
containing glomus cells in nests, aggregates; glomus cells are
arranged around vessels; have small, regular, round, indistinct
nucleoli; more infiltrative in children; may have secondary myxoid
change
Positive stains: smooth muscle actin, type 4 collagen,
vimentin; CD34 in 20% only
Negative stains: cytokeratin, desmin
EM: resemble smooth muscle cells
Grading scheme for glomus

tumors
All should have areas of typical glomus tumor, usually at
periphery
Malignant glomus tumor (glomangiosarcoma)

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Deep (to muscular fascia) and 2 cm or larger
OR atypical mitotic figures
OR moderate/high nuclear grade and 5+ MF/50 HPF
38% had metastases in one series, no metastases in
symplastic, uncertain, glomangiomatosis
Symplastic glomus tumor

High nuclear grade only, may be degenerative
Glomus tumor of uncertain

malignant potential
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High (5+/50 HPF) mitotic activity and superficial
OR 2 cm+ only
OR deep only
Vascular ectasias
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Localized dilation of preformed vessels
Hereditary hemorrhagic telangiectasia: aka Osler-Rendu-

Weber syndrome; autosomal dominant disorder in which localized
capillary dilation causes arterial blood to be shunted directly into
postcapillary venules
from birth; dilated capillaries and veins are present over skin
and mucous membranes of oral cavity, lips, respiratory, GI, GU;
may bleed into gut, urine, nose; patients have mutations in two
transforming growth factor -beta binding proteins including
endoglin
Nevus flammeus: aka salmon patch; ordinary birthmark,

usually on head and neck, represents dilated dermal vessels;
usually regress
Port-wine stain: type of nevus flammeus; may grow

proportionately with the child and thicken the skin surface; those in
distribution of trigeminal nerve are associated with Sturge-Weber
syndrome (encephalotrigeminal angiomatosis), a rare congenital
disorder with venous angiomatous masses in leptomeninges over
cortex, ipsilateral port-wine nevi, mental retardation, seizures,
hemiplegia, skull radiopacities; attributed to faulty development of
mesodermal and ectodermal elements
Spider telangiectasia: non-neoplastic vascular lesion,

composed of radial, pulsatile array of dilated subcutaneous
arteries or arterioles around a central core that blanches with
pressure applied to its center
Usually on face, neck, upper chest of pregnant women and
patients with cirrhosis; may be associated with hyperestrinism
Telangiectasias: group of abnormally prominent capillaries,

venules and arterioles that creates a small focal red lesion, usually
in skin or mucous membranes; congenital anomalies or
exaggerations of preexisting vessels; not true neoplasms
Bacillary angiomatosis
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First described in AIDS
Opportunistic infection of immunocompromised, manifesting
as vascular proliferations in skin, bone, brains, other organs
Caused by infection with Bartonella species (gram negative
rods), either Bartonella henselae (causes cat-scratch disease,
reservoir in cats, vector is cat flea), B. quintana (cause of trench
fever during WW I, reservoir is humans, vector is human body
louse) or other species; transmitted via traumatic inoculation of
skin
Bacillary peliosis: related vascular lesion of liver and spleen
Treatment: erythromycin
Gross: moist, eruptive, cutaneous lesion
Micro: acute neutrophilic inflammation with vascular
proliferation and prominent endothelial cells with nuclear atypia
and mitotic figures; nuclear dust and granular material (bacteria)
present; bacteria highlighted by silver stain
DD: pyogenic granuloma, Kaposi sarcoma, angiosarcoma
Myopericytoma
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Also called perivascular myoid tumor
Usually adults, 60% male, median age 52 years, youngest case was age
10
Affects skin (dermis or subcutis) or soft tissues of extremities, rarely head
or trunk
Treatment: excision; only rarely recurs
Micro: thin walled vessels and concentric, perivascular arrangement of
plump spindle to round myoxid cells; may have hemangiopericytoma-like
areas; occasional prominent atypia and mitotic activity; rarely infiltrative;
no giant cells (Am J Surg Pathol 2006;30:104)
Positive stains: alpha smooth muscle actin, h-caldesmon; rarely focal
desmin
DD: angioleiomyoma, myofibroma
Low/intermediate grade vascular tumors

Giant cell angioblastoma
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Rare, congenital/neonatal soft-tissue tumor, infiltrative but
slow growing; appears to be benign
Hand, palate, scalp
Treatment: surgery, interferon-alpha
Gross: ulcerated tumors infiltrating soft tissue and bone
Micro: solid, nodular, and plexiform proliferation of oval-to-
spindle cells with striking, concentric aggregation around small
vascular channels; cells resemble undifferentiated mesenchymal
cells, fibroblasts, myofibroblasts, pericytes; also large
mononuclear and multinucleate giant cells with histiocytic features
Positive stains: CD68 (large mononuclear and multinucleate
giant cells)
DD: giant cell fibroblastoma (CD34+, molecular
rearrangements of #17 and #22), epithelioid
hemangioendothelioma with osteoclast-like giant cells (Factor 8+
cells that dont resemble oval-spindle cells of giant cell
angioblastoma, no concentric aggregation around vessels),
plexiform fibrohistiocytic tumor (children/young adults, no onion-
skin layering of tumor cells around vessels), myopericytoma (older
age group, no giant cells), bacillary angiomatosis (positive special
stains for organisms, patients usually immunosuppressed)

Hemangioendothelioma
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Intermediate grade vascular tumor with variable histologic
features and clinical behavior
40% recur, 20% metastasize, 15% die of tumors
Positive stains: FLI-1 (nuclear stain, AJSP 2001;25:1061)
Composite hemangioendothelioma
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Definition: mixtures of benign, low-grade malignant and
malignant vascular components; predominant components
resemble epithelioid and retiform hemangioendothelioma
Very rare
Usually women, median age 43 years, range 22-75 years
Usually superficial dermis or subcutaneous, usually in hands
or feet
Recur locally, may metastasize, no deaths after median
follow-up of 5 years
Must sample extensively to obtain correct diagnosis
Treatment: excision, may recur locally, but no/rare
metastases (Am J Surg Pathol 2007;31:1567)
Positive stains: CD31, CD34, Factor VIII
Epithelioid/histiocytic hemangioendothelioma
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Intermediate grade vascular malignancies that are closely
associated with or arise from a vein in 50% of cases
Usually adults, 60% women
Most commonly affect extremities (60%); also head and neck,
mediastinum, trunk, elsewhere
Unpredictable clinical course, but less aggressive than
angiosarcoma
13% recur, 20-30% metastasize (lung, lymph node most
common), 13% die of disease (AJSP 1997;21:363); for lung, mortality
is 65%
High risk (> 3 MF/50 HPF and size > 3 cm) have 5 year
disease specific survival of 59% versus 100% for low risk (Am J
Surg Pathol 2008;32:924)
Case reports: Case of the Week #77
Treatment: low grade tumors - wide local excision; high
grade tumors - radical local excision with possible neck dissection
Gross: variable size, up to 18 cm
Micro: cords or small nests of round endothelial cells with
abundant eosinophilic cytoplasm; tumors arising from vessels
extend outward from the lumen towards soft tissue; tumor cells
often have intracytoplasmic vacuoles representing small vascular
lumina, which may resemble mucin; nuclei are round and may be
indented; usually minimal mitotic activity, atypia or necrosis, but
25% of cases exhibit frank malignant features of prominent
nuclear pleomorphism, mitotic activity, focal spindling or necrosis;
stroma may be scanty or myxoid; may have peripheral
inflammatory infiltrate with germinal centers and eosinophils,
multi-nucleated giant cells
Micro images: low power - #1; #2; #3; #4; #5; CD31
Positive stains: vimentin, CD31, von Willebrand factor,
keratin (30%, focal), reticulin (nests and cords of cells are invested
by a reticulin sheath)
Molecular: occasional tumors may demonstrate
t(1;3)(p36.3;q25) (AJSP 2001;25:684).
DD: metastatic carcinoma (more marked atypia, mitotic
activity, usually not angiocentric, keratin+, CD31-), melanoma
(S100+, HMB45+, CD31-), epithelioid sarcoma (distal extremities
of young adults, tumor cells merge with collagenous stroma,
keratin+ (strong), CD31-), epithelioid angiosarcoma (irregular
sinusoidal vascular channels, solid sheets of cells with marked
atypia and prominent mitotic activity, necrosis)
Endovascular papillary hemangioendothelioma

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Aka Dabskas tumor
Very rare tumor of children in skin or soft tissue
Good prognosis, with only rare nodal metastases
Micro: papillary tufts lined by plump endothelial cells
(epithelioid- or histiocytic-like) within dilated vascular lumina;
may have glomeruloid appearance
Micro images: figure 4A, 4B
Positive stains: vascular endothelial growth factor receptor-3
References: Mod Path 2000;13:180, AJSP 2001;25:1061
Kaposiform hemangioendothelioma
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Rare, locally aggressive; tumor of infants and children; affects
skin (75%), retroperitoneum (18%), bone
Death due to extensive disease and severe coagulopathy
(Kasabach-Merritt syndrome), although no metastatic potential
Usually initial tumor is cutaneous
Micro: infiltrating nodules and sheets of compact spindle cells
with formation of slit-like lumen
Micro images: figure 4C, 4D
Micro images: image1, image2, image3, image4
Positive stains: vascular endothelial growth factor receptor-3
DD: Kaposi's sarcoma
References: Mod Path 2001;14:1087, Mod Path 2000;13:180
Polymorphous hemangioendothelioma
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<10 cases reported
Lymph nodes and soft tissue
Recurs locally, rare metastases
Micro: combinations of solid, primitive vascular and angiomatous
patterns; uniform cytologic features; no epithelioid, spindle cell or
angiosarcoma-like areas
Retiform hemangioendothelioma
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Low grade variant of angiosarcoma
Usually distal extremities of young individuals
Weiss and Goldblum use term hobnail
hemangioendothelioma for retiform and Dabska-type tumors,
which they believe to be closely related
Rarely multiple (Am J Dermatopathol 1996;18:606)
2/3 recur, particularly without wide local excision; low rate of
metastases, no tumor related deaths
Treatment: wide local excision;
Gross: lesion of reticular dermis and subcutaneous tissue
Micro: retiform (net-like, similar to rete testis) pattern of blood
vessels that disperse through reticular dermis and subcutis;
vessels lined by monomorphic hobnail endothelial cells with scant
cytoplasm and rounded, naked-type nuclei; often prominent
lymphocytic infiltrate; no epithelioid areas or cytoplasmic vacuoles
(AJSP 1994;18:115)
Micro images: #1; #2; #3; #4; #5; CD31 #1; #2
Positive stains: endothelial cells - CD34 (strong), CD31,
vWF
Negative stains: endothelial cells - keratin.
DD: angiosarcoma (may focally have low grade features, but
also exhibits areas of marked atypia and pleomorphism; also
dissects between individual collagen bundles and has mitotic
activity), hobnail hemangioma (smaller, more superficial and more
localized, with papillary dermal vessels that disappear into
reticular dermis)
Spindle cell hemangioendothelioma

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Any age, usually males, usually distal extremities
Low grade lesion: recur commonly and may be multicentric,
but only one reported metastases after repeated
recurrence and radiation therapy
May be a hamartoma due to aberrations in local blood blow;
perhaps should be called spindle cell hemangioma
Associated with Mafuccis syndrome
Gross: dermal or subcutaneous tumor
Micro: cavernous hemangioma and Kaposi sarcoma like
features; cavernous spaces with solid areas composed
predominantly of bland spindle cells, with a minor
component of epithelioid, often vacuolated, endothelial cells,
usually associated with irregular fascicles of smooth muscle
fibers and adjacent malformed vessels
Positive stains: endothelial markers
Kaposi sarcoma
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Subtypes: chronic, lymphadenopathic, transplant-associated,
AIDS-associated
Vascular proliferative disorder mediated by inflammatory
cytokines and angiogenic growth factors in patients with HHV-8 /
Kaposi sarcoma associated herpesvirus infection, influenced by
immune status
May originate from cell type capable of undergoing lymphatic
differentiation based on D2-40 staining, a lymphatic specific
marker (Mod Path 2002;15:434)
Usually limited to skin; may involve mucus membranes, visceral organs,
lymph nodes
HHV-8 also positive in multicentric Castlemans disease, primary effusion
lymphoma, some multiple myeloma
Micro images: figures 1C, 1D; H&E and D2-40
Positive stains: FLI-1 (nuclear stain, AJSP 2001;25:1061),
vascular endothelial growth factor receptor-3
DD: angiosarcoma (may have Kaposi-like features but is
HHV-8 negative (Archives 2002; 126:191)
Chronic/classic
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Classic type seen in Europeans
Described by Kaposi in 1872
90% occur in older men from Eastern Europe, often
Ashkenazic Jews; rare in US
Associated with second malignant tumor or altered immune
state, but not with HIV
Multiple red-purple skin plaques or nodules in distal lower
extremity, slowing increasing in size and spreading proximally
Locally persistent with remission and relapses, but usually
stay localized to skin
Lymphadenopathic
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Aka African endemic
Occurs in young Bantu children in South Africa (same
population gets Burkitt lymphoma)
Presents with localized or systemic lymphadenopathy
Extremely aggressive disease; rarely is restricted just to
lymph nodes; skin involvement is unusual
Transplant-associated
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Occurs months to years after high-dose immunosuppressive
therapy; 0.2-1.0% of kidney transplants
Skin or metastatic lesions present
Skin lesions may regress if immunosuppression is stopped
Usually fatal if spreads to viscera
AIDS associated (epidemic)

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Historically, 40% of homosexual men with AIDS got Kaposi
vs. 5% of others with AIDS
Incidence of Kaposi has been decreasing over time, Archives
2002;126:182
Early involvement of lymph nodes and gut and wide
dissemination
Usually not a direct cause of death, although 1/3 develop
lymphoma or another second malignancy
Gross: indolent disease has 3 stages: early - macule/patch,
intermediate - plaque, late - nodule/tumor
Macule/patch: pink-purple macules of lower extremity or feet
Micro: dilated irregular blood vessels in background of
lymphocytes, plasma cells, macrophages; resembles granulation
tissue; disease spreads proximally, converts to raised
Macule/patch: superficial or mid-dermal proliferation of
collagen-dissecting jagged capillary vessels with inconspicuous
spindle cell component; may be confluence of vessels
Plaque: dermal, dilated, jagged vascular channels that
dissect collagen fibers and contain isolated or small groups of
spindle cells; red blood cell extravasation prominent; also
hemosiderin laden macrophages, pink hyaline globules
Nodule/tumor: more distinctly neoplastic, most of lesion
composed of spindle cells with intersecting fascicle like pattern in
a background of inflammatory cells and red blood cells; small
vessels and slitlike spaces with hyaline droplets and rows of red
blood cells; mitotic figures common; may involve lymph nodes and
viscera (African and AIDS variants)
Positive stains: smooth muscle actin
Negative stains: Factor 8
Molecular: detect HHV8 by PCR or in-situ hybridization
High grade vascular lesions
Angiosarcoma
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Well differentiated (hemangiosarcoma) to anaplastic tumor
resembling melanoma or carcinoma
Rare; older adults, skin (scalp, face), soft tissue, breast, liver,
bone, spleen
Very rare in children and young adults, but similar histology
and poor prognosis (Am J Surg Pathol 2009;33:264)
May arise from inferior vena cava, pulmonary artery, aorta
(usually undifferentiated, solid, difficult to identify as endothelial)
Arises from endothelial cells of blood vessels
Treatment: early surgery, but survival >5 years is rare
Risk factors: chronic lymphedema, sun exposure, radiation,
Thorotrast, PVC
Nodal metastases in 14% of cases (high rate for sarcomas);
also metastases to lungs, liver, bone
Breast: 3-12 years after radiation therapy for carcinoma;
incidence is 1 per 1000-2000; usually in women age 60+ with low
grade, low stage lesions; poor prognosis with 41% 3 year survival
Extremities: associated with lymphedema ~ 10 years after
radical mastectomy for breast cancer, arising from dilated
lymphatics (lymphangiosarcomas, aka Stewart-Treves syndrome),
not associated with radiation therapy
Kidney: case report of renal angiosarcoma, Archives
2002;126:478
Liver: associated with arsenic, Thorotrast, PVC; latent period
of years
Also associated with radiation to other sites, introduction of
foreign material
Lung: rarely presents as diffuse pulmonary hemorrhage due
to metastases in young adults, Archives 2001;125:1562;
lung metastases often multiple peripheral nodules
accompanied by infiltrates, primary tumor usually not
identified at presentation; tumor cells may have minimal
atypia, may be keratin positive, primary site of lung
metastases is often the heart, Mod Path 2001;14:1216;
Skin: Cases related to chronic lymphedema are usually in
extremities; lymphedema due to radical mastectomy,
postfilarial, congenital; cases unrelated to lymphedema are
often in head and face
Case report associated with chronic lymphedema due to
morbid obesity, Archives 2001;125:531
Gross: early - small, sharply demarcated, asymptomatic,
multiple red nodules
late - fleshy, gray-white with hemorrhage, necrosis, deeply
invasive
Gross image: Figure 1A
Micro: atypical vascular spaces lined by endothelial cells with
cytologic atypia, multilayering; in more solid areas are
intracytoplasmic lumina containing red blood cells; involves
subcutaneous tissue; variable grade; multinucleated cells may
have prominent hyaline globules containing alpha-1-antitrypsin
and alpha-1-antichymotrypsin; brisk mitotic activity and necrosis
are common; post-radiation lesions usually high grade
Micro images: image1, image2, image3, image4, image5
Micro images: lung metastases - image1, image2, image3,
image4, image5, image6
FNA images: image1
Positive stains: Factor 8 related protein, CD31, Ki-67, FLI-1
(nuclear stain, AJSP 2001;25:1061), thrombomodulin, CD34 (not
specific), c-kit (50%)
DD: atypical vascular lesions (circumscribed, no atypia, no
mitotic figures), hemangiomas (usually < 2 cm, well circumscribed,
contain fibrous septa and thick-walled vessels, not invasive), MFH
(intratumoral macrophages from non-vascular tumors may be
CD31+, AJSP 2001;25:1167, image), florid vascular proliferation
of colon due to intussusception, Mod Path 2001;14:1114
Epithelioid angiosarcoma
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Positive stains: CD34, keratin
Hemangiopericytoma (HPC)
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Adult tumor, usually deep-seated, often in thigh, pelvic
retroperitoneum, orbit
Derived from pericytes, cells normally arranged around
capillaries and venules
Slowly enlarging, painless mass, usually thigh, lower
extremity, retroperitoneum
20-50% metastasize to lungs, liver, bone
Gross: 4-8 cm, solitary, solid, gray/white to red/brown;
hemorrhage, necrosis, cystic degeneration common; usually well-
circumscribed or encapsulated
Micro: branching capillary channels, large gaping sinusoidal
spaces (staghorn configuration) surrounded by spindle shaped
cells; may have extensive fibrosis, hyalinization, myxoid change
Positive stains: with silver stain, spindle cells are outside the
endothelial basement membrane and hence are pericytes, not
endothelial cells; vimentin
Negative stains: trichrome (no myofibrils), desmin, actin
EM: pericytic features (cytoplasmic filaments and processes,
pinocytotic vesicles, basal lamina, poorly formed intercellular
junctions)
Molecular: 12q13-15 alterations in some cases
DD (HPC vascular pattern): mesenchymal chondrosarcoma
(islands of mature cartilage), synovial sarcoma, infantile
fibrosarcoma, MFH, solitary fibrous tumor, MPNST, thymoma
(epithelial foci)
Variants:
Infantile/congenital hemangiopericytoma
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Typically superficial, multilobulated
Benign behavior
Micro: immature cytology, frequent mitotic figures, necrosis,
possibly neoplastic endothelial cells
Lipomatous hemangiopericytoma
HPC with myxoid and sclerotic areas and islands of mature
adipose tissue
Phosphaturic mesenchymal tumor

HPC areas associated with osteoclast-like cells, cartilage
Peripheral Nerve Tumors

Nerve - normal
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Composed of axons, Schwann cells, perineurial cells and
fibroblasts in epineurium (outer sheath)
Perineurium: surrounds each nerve fascicle, is continuous
with pia mater of CNS
Perineurial cells: derived from fibroblasts; EMA+, S100-
Schwann cells: neuroectodermally derived cells that
resemble fibroblasts, but strongly S100+, intimately related to
axons (by EM), have continuous basal lamina that coats the cell
facing the endoneurium
Lymphoma-diffuse large B cell
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Rare in peripheral nerve, <20 lymphomas reported of any subtype
Mean age 55 years, no gender preference
Case report: primaries of sciatic nerve, radial nerve, sympathetic
chain/spinal nerve (Am J Surg Pathol 2000;24:1257)
Stains: CD56 negative, variable CDKN2A/p16
Malignant peripheral nerve sheath tumor (MPNST)
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Aka malignant schwannoma, MPNST
Bulky deep-seated tumor usually arising from major nerves in
neck, forearm, lower leg, buttock
50% associated with neurofibromatosis (NF), 50% arise de
novo
May be due to radiation; rarely arise from ganglioneuromas
Usually adults, also children
High clinical suspicion for MPNST if NF1 patient or tumor
arising within anatomic component of a major nerve or contiguous
with neurofibroma
Recur locally, distant metastases frequent
Plexiform variant in children has better prognosis, otherwise
cannot predict prognosis
Gross: large mass producing a fusiform enlargement of a
major nerve (often sciatic)
Micro: monomorphic serpentine cells, palisading, large
gaping vascular spaces, perivascular plump tumor cells,
geographic necrosis with tumor palisading at the edges
(resembles glioblastoma multiforme)
frequent mitotic figures; may have bizarre cells; 15% have
metaplastic cartilage, bone, muscle
May have glandular differentiation (positive for keratin, EMA,
CEA, chromogranin); if so, presume malignant
May have melanin in tumor cells, particularly if arise from
spinal nerve roots (overlaps with primary melanoma of nerves)
Note: some have no discernable Schwannian features at any
level
Micro images: post-implant
Positive stains: S100 (62%), Leu7/CD57 (in neurofibroma-
like areas), p53, CD57 (55%), collagen IV, CD99/O13 (86%),
protein gene product 9.5 (Archives 2001;125:1321, but PGP9.5
not specific)
Negative stains: EMA (usually), keratin (usually), CD19
Molecular: t(X;18) negative, Mod Path 2002;15:589
EM: infoldings of cell membrane with lamellar configuration,
discontinuous basal lamina, conspicuous intercellular junctions,
occasional dense-core granules
DD: pleomorphic liposarcoma, MFH, synovial sarcoma
(usually positive for CK7 and CK19, Am J Clin Pathol 1999;112:641)
Epithelioid MPNST
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5% of MPNST
Plump epithelioid cells with acidophilic cytoplasm
Most neurofibromas with malignant transformation are
epithelioid, but most epithelioid MPNST are NOT associated with
NF1
Positive stains: HMB45 (DD: desmoplastic melanoma),
protein gene product 9.5 (Archives 2001;125:1321, but PGP9.5
not specific)
Negative stains: S100 (often), INI1 (50%, Am J Surg Pathol
2009;33:542)
DD: epithelioid angiosarcoma (CD31+, CD34+, vWF+, S100-
), melanoma
Malignant triton tumor

MPNST with well developed skeletal muscle
Myxopapillary ependymoma
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Usually spinal cord tumor, may arise is soft tissue in
sacrococcygeal area separate from cord
Resembles pilonidal cyst clinically, but 20% metastasize
Gross: well circumscribed , easily enucleated
Micro: resembles CNS tumor; small blue cells forming well
defined perivascular structures, surrounded by dense fibrous
tissue
DD: ependymal rests (clusters of cells < 0.5 cm in
dermis/subcutaneous tissue near pilonidal sinuses)
Nerve sheath myxoma
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Controversial tumor
Skin, soft tissue, intraspinal
Resembles myxoma but plumper, epithelial-like cells;
fascicular or plexiform arrangement
May be similar to neurothekeoma
DD: perineurioma, myxoid neurofibroma (S100+)
Neurofibroma
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Solitary tumor suggests patient does NOT have
neurofibromatosis type 1
Malignant transformation rare in sporadic neurofibromas
Gross: not encapsulated, softer (more gelatinous) than
schwannoma
Superficial tumors are small, pedunculated nodules protruding
from skin (molluscum pendulum)
Deeper tumors are larger, may cause tortuous enlargement of
peripheral nerves (plexiform neurofibromas)
Micro: Non-encapsulated; proliferation of all elements of
peripheral nerves; Schwann cells with wire like collagen fibrils
(wavy serpentine nuclei, pointed ends), stromal mucosubstances,
mast cells, Wagner-Meissner corpuscles, Pacinian corpuscles,
axons (highlight with silver or acetylcholinesterase stain, NSE,
neurofilament), fibroblasts and collagen; perineurial cells in
plexiform types, mitotic figures are rare; may be infiltrative; less of
a fascicular pattern than fibromatosis
May have myxoid areas; no Verocay bodies, no nuclear
palisading, no hyalinized thickening of vessel walls
Rarely has skeletal differentiation (neuromuscular
hamartoma)
Positive stains: S100, CD34+ (focal), Factor 13a (focal)
Negative stains: EMA (except in plexiform neurofibromas)
EM: Schwann cells enclose axons in plasmalemmal
invaginations (mesaxons)
DD (myxoid areas): myxoma, myxoid liposarcoma
Diffuse cutaneous
Traps adnexa, infiltrates into fat
Focal cutaneous
Intraneural
Neurofibromatosis type 1
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von Recklinghausen disease, NF1
Defect in neurofibromin gene at 17q11.2; protein is a widely
expressed tumor suppressor gene with highest levels in neural
tissue that downregulates p21 ras oncoprotein; numerous sites of
mutation in the gene; variable phenotypic expression
1/3000 individuals, 50% from autosomal dominant
inheritance, 50% are new mutations
2-4x increased risk of other tumors (ganglioneuromas,
pheochromocytomas, meningiomas, rhabdomyosarcoma,
childhood CML)
5-13% develop MPNST
Clinical: (1) multiple neurofibromas (plexiform, solitary), (2) 6
or more cafe au lait spots over nerve trunks, 1.5 cm or larger; (3)
Lisch nodules (pigmented iris hamartomas, 94% by age 6); (4)
unilateral acoustic neuromas (schwannomas), optic nerve
gliomas, plexiform neurofibromas (relatively specific), skeletal
lesions (30%-spinal deformities [kyphoscoliosis], bone cysts); also
congenital malformations, megacolon, fibrosing alveolitis, lipoma,
carcinoid tumor, GIST, Wilms tumor; increased nerve growth
factor
Cafe au lait spot: increase in melanin in epidermal basal
layer, may overlie a neurofibroma, smooth delicate margins;
solitary caf au lait spots are normal
DD of cafe au lait spots: Albrights syndrome (polyostotic
fibrous dysplasia of bone, patchy dermal pigmentation, endocrine
dysfunction)
Neurofibromatosis type 2
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Aka NF2, aka acoustic neurofibromatosis
Autosomal dominant, 1/40K incidence
Mutation in merlin gene at 22q12; similar to cytoskeletal
protein; function unknown but protein widely distributed
Nonsense mutations usually more severe than missense
mutations
Signs/symptoms: bilateral acoustic neuromas or multiple
meningiomas, spinal cord ependymomas; also schwannosis
(ingrowth of Schwann cells into cord), meningioangiomatosis
(meningeal cells and blood vessel proliferation into the brain), glial
hamartia (microscopic nodular collections of glial cells in cerebral
cortex); cafe au lait spots, but no Lisch nodules
Neuroma
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Benign nonneoplastic overgrowth of nerve fibers and
Schwann cells
Usually post-traumatic; proximal nerve regenerates and if it
fails to meet the distal end, a tangled mass of nerve fibers results
Painful
Micro: axons, Schwann cells, perineurial fibroblasts, also
scar
Positive stains: CD68 (Schwann cells-become phagocytic)
Amputation neuroma
Due to partial/total amputation
Granular cell traumatic neuroma

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Case report of 2 lesions in mastectomy scars with features of
both granular cell tumor and traumatic neuroma at Archives
2000;124:709
Micro: nests of large granular cells, in background of fibrous
tissue with sparse inflammatory infiltrates; several tortuous
hypertrophic nerve bundles were embedded in fibrous tissue,
some with degenerative changes and containing granular cells
Positive stains (granular cells): S100, NSE, vimentin, CD68
Mortons neuroma
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Aka Mortons metatarsalgia
More common in adult women
Due to repeated mild trauma to interdigital plantar nerve,
usually between toes 3 and 4
Gross: affected nerve is markedly distorted
Micro: extensive concentric perineurial fibrosis, thickened
arterioles with thrombi
Palisaded encapsulated neuroma

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Aka solitary circumscribed neuroma
Small, solitary, asymptomatic skin papule, in face of middle-
aged
Micro: dermal lesion with proliferation of Schwann cells
(S100+) and axons (neurofilament+), encapsulated by
perineurium (EMA+)
Neurothekeoma
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Superficial tumor, originally of purported nerve sheath
derivation
First described in 1980
60% women, mean age 17 years (range 2-85 years), 80% are
< age 30 at initial diagnosis
May derive from fibroblasts with ability to differentiate into
myofibroblasts and to recruit histiocytes (Am J Surg Pathol
2007;31:1103)
Clinical: solitary, superficial, slow growing mass up to 2 cm
Sites: usually head, upper extremities or shoulder girdle
Treatment: excision, may recur
Micro: cellular, myxoid or mixed subtypes; involves dermis or
subcutis; multinodular mass with myxoid matrix and peripheral
fibrosis; whorled or focally fascicular patterns of spindled and
epithelioid mononuclear cells with abundant cytoplasm, indistinct
cell borders; margins usually positive; usually occasional
multinucleated giant cells; variable nuclear atypia; median 4
MF/25 HPF, may have 10+ MF/25 HPF, may be atypical
Positive stains: vimentin, NKI/C3, CD10, MiTF
Negative stains: S100, GFAP, MelanA
DD: nerve sheath myxoma
Perineurioma
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Uncommon, benign tumor of peripheral nerve composed
primarily of perineurial cells, first described in 1978
Adults, more common in females
Extremities and trunk most common sites
Case reports: 30 year old man with thigh mass and
neurofibromatosis 2 (Am J Surg Pathol 2006;30:1624)
Gross: well circumscribed, variable size, usually NOT
associated with a nerve
Micro: bland, elongated cells in parallel bundles, resembles
neurofibroma or pacinian neurofibroma; may have storiform
growth; no atypia, rare mitotic figures; suspect if myxoid lesion of
soft tissue with storiform or fascicular growth pattern; may have
collagenous stroma with pericellular cracking / clefting
Positive stains: EMA, CD34 (33%)
EM: non-branching, thin cytoplasmic processes, coated by
external lamina, joined at ends by tight junctions, few organelles,
actin and vimentin filaments, numerous pinocytotic vesicles
Molecular: monosomy 22, deletion of 22q11-13.1
Reticular variant
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Median age 43, range 34-61, 2/3 women in small study
Upper extremity, gingiva, inguinal region
Appears to have benign behavior
Gross: median 4 cm, range 1.5 to 10 cm
Micro: lace-like or reticular (net-like) growth pattern of
anastomosing cords of fusiform cells with bipolar cytoplasmic
processes and palely eosinophilic cytoplasm; central nuclei; all
cases had transitions to more cellular areas; collagenous to
myxoid stroma; cystic areas common; no mitotic figures;
mild/moderate nuclear atypia (may be degenerative)
Positive stains: EMA, alcian blue (myxoid stroma)
DD: myoepithelial tumors (variable S100+, keratin; acinar or
ductal component), extraskeletal myxoid chondrosarcoma (deep
seated tumor, subfascial or intramuscular, cord/lace like
architecture, larger cells with abundant eosinophilic cytoplasm, no
microcystic change, typical t(9;22)), myxoid synovial sarcoma

(deep soft tissue, younger age group, more nuclear atypia, EMA+,
CK+, CD99+, bcl2+)

Sclerosing perineurioma
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Usually small tumors in dermis of hands
Micro: various
Schwannoma
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Aka neurilemoma
Encapsulated biphasic nerve sheath tumor derived from
Schwann cells with highly ordered cellular component (Antoni A)
that palisades (Verocay bodies), plus myxoid component (Antoni
B)
Small tumors may be all Antoni A
Recurrence rare, so attempt to preserve the nerve if clinically
significant
Ages 20-50; M=F
Head, neck, flexor upper and lower extremities,
retroperitoneum, posterior spinal roots, cerebellopontine angle
May be due to alteration/loss of NF2 gene product
Slow growing; no symptoms until becomes large; may wax
and wane in size
Pain or rapid enlargement of preexisting lesion are suggestive
of malignant change
Dumbbell tumor in posterior mediastinum, originates from or
extends into vertebral canal
Treatment: excision; usually do not recur
Gross: usually solitary; large tumors may be cystic; nerve of
origin present in periphery - does not penetrate substance of
tumor
Micro: large irregularly spaced vessels are most prominent in
Antoni B areas; gaping tortuous lumina have thickened hyalinized
walls and may have thrombus; tumor cells have dense chromatin,
ill defined cytoplasm; rare mitotic figures, no axons except where
nerve is attached; may have foamy macrophages; often displays
degenerative nuclear atypia (ancient change); rarely have
plexiform, glandular (may be entrapped sweat glands), pigmented,
epithelioid areas or rosettes; amianthoid fibers or collagenous
spherules: large nodular masses of collagen with radiating edges
Positive stains: EMA (capsule), S100 (Schwann cells),
calcinurin, laminin, type 4 collagen, vimentin, CD68, GFAP
Negative stains: keratin, neurofilament, desmin
EM: elongated cells with continuous basal lamina, thin
cytoplasmic processes, aggregates of intracytoplasmic
microfibrils, peculiar intracytoplasmic lamellar bodies, extracellular
long-spacing collagen; contains lipid
DD palisading patterns: leiomyoma, leiomyosarcoma,
fibrous histiocytoma, calcifying aponeurotic fibroma, appendiceal
smooth muscle
Ancient Schwannoma
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Degenerative change to tumors, usually large and of long
duration, deep within retroperitoneum
Cyst formation, calcification, hemorrhage (stromal
hemosiderin), hyalinization, histiocytic infiltration, severe nuclear
atypia (nuclear hyperchromasia, irregular nuclear shapes)
No mitotic figures
Cellular schwannoma
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Primarily Antoni A areas without Verocay bodies; usually in
retroperitoneum, pelvis, mediastinum;
May have nuclear atypia and focal necrosis
0-3 mitotic figures/10HPF; 5% recur, no metastases
Malignant transformation
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Occurs even without neurofibromatosis, tumors usually have
epithelioid features
Sites: limb, limb girdles or head/neck; contain areas of benign
schwannoma
Transform to MPNST, angiosarcoma or epithelioid malignant
change (EMC)

Epithelioid malignant change large epithelioid cells with
abundant eosinophilic cytoplasm, vesicular chromatin, prominent
nucleoli, resembles epithelioid MPNST; strongly S100+
May recur locally, may be a precursor lesion to MPNST since
younger age than MPNST
Suggest sign out as atypical schwannoma with epithelioid
cells
Criteria for MPNST in schwannoma: benign schwannoma

present, no primary tumor that may have metastasized to
schwannoma, histologically malignant cells resembling epithelioid
MPNST; 5 year survival < 20%

Criteria for angiosarcoma in schwannoma: benign
schwannoma present, transition to angiosarcoma (irregular
vasoformative structures lined by multilayered cells with nuclear
atypia or atypical endothelial cells with a solid growth pattern);
cytoplasmic staining for CD31, CD34 or vWF
DD: pleomorphic hyalinizing angiectatic tumor (PHAT)
Microcystic-reticular variant
First described in 2008 (Am J Surg Pathol 2008;32:1080)
Median age 63 years, range 11-93 years
Often arises in GI tract submucosa; also other sites
Not associated with neurofibromatosis types 1 or 2
Gross: median 4 cm, range 0.4 to 23 cm
Micro: circumscribed, unencapsulated tissue (encapsulated if
in subcutis); infiltrative in visceral locations; microcystic and
reticular growth pattern with anastomosing and intersecting
spindle cells, distributed around islands of myxoid or
collagenous/hyalinized stroma; round/oval nuclei with tapering,
indistinct nucleoli; 0-3 MF/50 HPF; no necrosis, no pleomorphism
Positive stains: S100, variable GFAP
Negative stains: muscle markers, keratin, p63
Pigmented schwannoma
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Pigmented tumor cells have widely scattered, coarse pigment, reactive
with Fontana Masson stain (melanin stain), nonreactive with Prussian
blue (iron stain)
Positive stains: S100 (strong), vimentin, Fontana Masson
Negative stains: Prussian blue, tyrosinase, HMB45
References: Archives 2002;126:816
Plexiform schwannoma
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Only 5% of schwannomas
Pattern not strongly associated with neurofibromatosis 1 or 2
Usually superficial, in dermis or subcutaneous tissue
Micro: plexiform architecture with nuclear palisading;
biphasic pattern may not be prominent; often cellular with
hyperchromatic nuclei and mitotic activity; no necrosis, no
myxoid change
Micro images: plexiform architecture; nuclear
palisading; cellular areas
Positive stains: S100 (strong staining of nodules but not
intervening stroma)
DD: plexiform neurofibroma (early childhood, associated with
neurofibromatosis type 1; found with grossly enlarged and
tortuous nerves; hypocellular with myxoid background; no biphasic
pattern; may occasionally show nuclear palisading; S100+ but
only scattered cells); MPNST (may be multinodular, S100
weak/negative, should be sampled extensively to rule out a
plexiform schwannoma, AJSP 2005;29:1042)
Psammomatous melanotic schwannoma

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Part of Carneys syndrome of functioning extra-adrenal
paraganglioma, gastric epithelioid leiomyosarcomas, lung
hamartoma
Arises from spinal nerve roots
Low grade malignancy: recurs locally, rarely metastasizes
Perivascular epithelioid cell family of tumors

(PEComas) of soft tissue
Perivascular epithelioid cell tumors-general
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Definition: mesenchymal tumor with perivascular clear cell
and epithelioid features that coexpresses melanocytic and muscle
markers
Concept first proposed by Bonetti (AJSP 1992;16:307)
Tumor family includes angiomyolipoma (renal and extrarenal),
clear cell sugar tumor (lung and extrapulmonary) and
lymphangioleiomyomatosis; these tumors are relatively common
and are associated with tuberous sclerosis
Family also includes tumors of falciform ligament /
ligamentum teres (see below), skin (Histopathology 2005;46:498),
uterus (Mod Path 2005;18:1336) and other viscera and soft tissue;
these tumors are rare, and are not associated with tuberous
sclerosis
No known normal counterpart to the perivascular epithelioid
cell
Epidemiology: 80-90% females (Histopathology 2006;48:75),
median age 46 years (range 15-97 years)
Prognosis: usually benign, but some cases have malignant
behavior and simulate high grade sarcoma (Pathology 2006;38:415)
Poor prognostic factors: tumor size > 5-8 cm, infiltrative
growth pattern, high nuclear grade, >1 mitotic figure/50 HPF or
atypical mitotic figures, coagulative cell necrosis (AJSP
2005;29:1558)
Case reports: thigh tumor (AJSP 2002;26:809), uterine tumor
with late pulmonary metastases (J Clin Pathol 2003;56:627), uterine
leiomyosarcoma that became HMB45+ in metastasis (Ann Diagn
Pathol 2005;9:43)
Treatment: excision is usually curative if tumors are benign
Gross images: uterus - polypoid gray-white mass;
polypoid mass
Micro: perivascular tumor cells may have radial arrangement
around lumen; epithelioid cells (closest to vessel) and spindle cells
(remote from vessel) with clear to granular eosinophilic cytoplasm;
small, central, round/oval nuclei with small nucleoli; often
multinucleated giant cells; may have malignant features with
marked atypia, mitotic activity and necrosis
Pecosis: continuous layer of perivascular clear cells remote
from tumor, transitioning to invasive nests and PEComa; cells are
in apposition to and in direct contact with abluminal surface of
capillary basal lamina (Virchows Arch 2007;450:463)
Pecomatosis: nests of perivascular clear to eosinophilic cells
(World J Surg Oncol 2004;2:35); may simulate mesothelioma (Ann
Diagn Pathol 2006;10:352)
Micro images: bladder - epithelioid tumor cells with
abundant eosinophilic cytoplasm; MelanA+; smooth muscle
actin+
cervix - mass with central circular core; infiltrative
border; spindled to epithelioid areas; degenerative atypia;
pecomatosis-nests of cells; HMB45+
kidney - MelanA+ tumor
prostate - epithelioid cells with clear to granular
cytoplasm are HMB45+
uterus - malignant case-epithelioid cells with eosinophilic
cytoplasm and prominent nucleoli #1; #2; actin+ (red) and
HMB45+ (brown); HMB45+ recurrent tumor
Positive stains: melanocytic markers (HMB45 and MelanA;
microphthalmia transcription factor-50%; also NKI/C3, tyrosinase,
S100-33%), smooth muscle markers (MyoD1 [Appl
Immunohistochem Mol Morphol 2003;11:156], smooth muscle actin-
80%, desmin-40%, calponin), vimentin (80%)
Negative stains: cytokeratin, CD117/c-kit, CD34
Molecular: gross chromosomal aberrances in most/all cases;
most frequent imbalances are 19-, 16p-, 17p-, 1p-, 18p-, X+,
12q+, 3q+, 5+, 2q+; 16p- indicates loss of TSC2 gene (Hum Path
2006;37:606)
EM: abundant cytoplasmic glycogen, premelanosomes, thin
filaments with occasional dense bodies, hemidesmosomes, poorly
formed cellular junctions
DD: undifferentiated / high grade sarcoma, clear cell /
oxyphilic carcinoma (cytokeratin+), melanoma (strong S100+),
epithelioid/clear cell smooth muscle tumors (HMB45-)
References: Fletcher: Pathology and Genetics of Tumours of Soft Tissue
and Bone (2003, WHO, Volume 5)
Sclerosing PEComa
Definition: variant with extensive stromal hyalinization
First described in 2008 (Am J Surg Pathol 2008;32:493)
Women, mean age 49 years (range 34-73 years)
77% occur in retroperitoneal, usually pararenal
Treatment: excision; may recur/metastasize if high grade
morphology)
Gross: median 10 cm, well circumscribed
Micro: cords and trabeculae of bland, uniform, epithelioid
cells with pale eosinophilic, granular to clear cytoplasm and round
nuclei with small nucleoli; tumor cells are arranged at least focally
around blood vessels; abundant densely sclerotic stroma; often
has spindle cell component; no/rare mitotic figures; rarely necrosis
Positive stains: desmin (diffuse), smooth muscle actin,
caldesmon, HMB45 (scattered cells)
Negative stains: S100 (usually), EMA, keratin, CD117/c-kit
PEComa - abdominopelvic sarcoma
top
Tumors in 4 women ages 19-41 years (Mod Path 2001;14:563,
free full text)
Tumor masses involve serosa of ileum, uterus or pelvic
cavity
Nodal and metastatic disease present
One patient had tuberous sclerosis
Case reports: 16 year old girl with abdominopelvic tumor
exhibiting extensive necrosis, nodal metastases and tissue
invasion (Kaohsiung J Med Sci 2005;21:277)
Micro: sheets of large polygonal cells with glycogen-rich clear
or eosinophilic cytoplasm, moderately pleomorphic nuclei, delicate
vasculature (resembles clear cell carcinoma); also focal
coagulative necrosis and occasional mitotic figures;
intracytoplasmic brown pigment present in 2/4 cases;
angiolymphatic invasion present; no spindle cells, smooth muscle
or fat
Micro images: various images #1; #2; nodal metastasis
Positive stains: HMB45, MART1 (50%)
Negative stains: keratin, EMA, S100, vimentin, muscle
specific actin, desmin, chromogranin A
PEComa - falciform ligament / ligamentum teres
top
Usually in or immediately adjacent to falciform ligament or
ligamentum teres (AJSP 2000;24:1239)
Epidemiology: usually females, median age 11 years, range
3-21 years
Case reports: malignant tumor of broad ligament (Virchows
Arch 2006;448:867)
Usually indolent behavior
Gross: median 8 cm, range 5-20 cm
Micro: fascicular or nested groups of spindle cells (usually no
epithelioid cells) with lightly eosinophilic, fibrillar cytoplasm with
cytoplasmic clearing and small but distinct nucleoli in delicate
capillary network similar to renal cell carcinoma; rare mitotic
figures; no necrosis, no angiolymphatic invasion
Positive stains: HMB45 (100%), MelanA (50%),
microphthalmic transcription factor (50%), smooth muscle actin
(50%), myosin (50%)
Negative stains: desmin, S100
DD: angiomyolipoma (thick walled blood vessels, lipid
distended tumor cells, spindled cells), leiomyoma (distinctly
eosinophilic, cigar-shaped nuclei with blunt ends and perinuclear
vacuoles; thick walled blood vessels), leiomyosarcoma (large
deep seated mass with obvious nuclear pleomorphism and mitotic
activity, often with necrosis; negative for HMB45, MelanA,
microphthalmic transcription factor, positive for desmin), cellular
schwannoma (true capsule, thick-walled hyalinized blood vessels,
strong S100 staining), clear cell sarcoma of tendons and
aponeuroses (epithelioid and spindled areas with tumor giant
cells, S100+, positive for melanocytic markers but negative for
smooth muscle actin and myosin; t(12,22) present)
Mesenchymal tumors
Mesenchymoma
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Definition: tumors composed of two or more different
histological mesenchymal elements
See also description in Bone or Eye chapters
May be benign or malignant
AFIP Third Fascicle and WHO dislike this terminology, and
recommend (a) describing as mixed mesenchymal neoplasm and
specifying the components or (b) classifying based on
predominant mode of differentiation and mentioning the other
component(s)
Benign mesenchymoma
top
Definition: tumors composed of two or more different
histological benign mesenchymal elements
See also description in Bone or Eye chapters
Also called hamartoma, but mesenchymal hamartoma of liver
(also called mesenchymoma) is a different entity
Most frequent type is angiomyolipoma, which is described
separately
May recur if inadequately excised
Case reports: translocation of HMGI-C (HMGA2) gene in
chondrolipoangioma (Virchows Arch 2002;440:485), mediastinal tumor
of mature adipose tissue separated by fascicular bundles of
spindle cells mixed with cartilage and bone (Zhonghua Yi Xue Za Zhi
(Taipei) 1996;58:213), stomach tumor (J Clin Pathol 1983;36:504)
Micro: dense fibrous tissue, woven bone and cartilage
like areas; loose vascular mesenchyme, smooth muscle and
fat; smooth muscle with cytoplasmic fat
Malignant mesenchymoma
top
Definition: rare tumors with two or more sarcomatous
elements, including osteosarcoma, chondrosarcoma,
leiomyosarcoma, rhabdomyosarcoma and liposarcoma; each
element must be sufficiently differentiated to clearly recognize its
histogenic type; cannot count fibrosarcoma as one of the elements
since these areas are present in most sarcomas; excludes
dedifferentiated liposarcoma, dedifferentiated chondrosarcoma,
malignant Triton tumor and myoblastic differentiation in
liposarcoma or chondrosarcoma
First described by Stout in 1948 (Ann Surg 1948;127:278)
According to Harry Evans, do not form a distinct
clinicopathologic entity and should be classified in other ways
(Fletcher: Pathology and Genetics of Tumours of Soft Tissue and Bone
2003; WHO, Volume 5, page 215)
Sites: frequently in retroperitoneum or chest wall
Prognosis: usually high grade and aggressive (Cancer
1996;77:467); frequently recurs (2/3), metastasizes (1/3) and causes
death (50%)
Poor prognostic factors: age < 40 years,
rhabdomyosarcomatous component (Oncol Rep 2003;10:803)
Must sample generously to find various components and rule
out dedifferentiated tumors
Case reports: 24 year old man with lower leg tumor
containing myoblastic sarcoma and chondrosarcoma (J Clin Pathol
2001;54:877), retroperitoneal mass with osteosarcoma,
leiomyosarcoma, liposarcoma and fibrosarcoma (Korean J Radiol
2002;3:264), tumor with rhabdomyosarcoma and osteosarcoma
components 21 years after breast cancer radiotherapy (Br J Radiol
1997;70:424), with well differentiated liposarcomatous component
and ring chromosomes (Cancer Genet Cytogenet 1999;109:119), 15
year old boy with osteosarcoma and liposarcoma in tibia (J Bone
Joint Surg Br 1968;50:639)
Treatment: complete resection
Micro images: various sarcomatous components;
osteosarcoma and liposarcoma
Phosphaturic mesenchymal tumor
top
Definition: benign tumor of bone or soft tissue associated
with rickets and osteomalacia
Epidemiology: extremely rare, median age 53 years, range
9-80 years, slight female predominance
Most cases of tumor associated oncogenic osteomalacia are
due to phosphaturic mesenchymal tumor, which produces
fibroblast growth factor-2, a protein that inhibits renal tubular
phosphate reabsorption (AJSP 2004;28:1) or dentin matrix protein 1
(Mod Path 2004;17:573)
Laboratory: low serum phosphate, renal phosphate wasting,
low 1,25-dihydroxy Vitamin D3
Treatment: complete excision causes dramatic reversal of
signs and symptoms
Gross: 2-14 cm, arises in soft tissue and bone
Micro: hypocellular tumor of bland spindle cells with small
nuclei, indistinct nucleoli; has hemangiopericytoma-like
vasculature, osteoclast-like giant cells, distinctive grungy
calcified matrix, fat, microcysts, hemorrhage, incomplete rim of
membranous ossification, metaplastic bone; infiltrative; no/rare
mitotic activity, no atypia
Malignant cases: rare cases with nuclear atypia, 5+ mitotic
figures/10 HPF, high cellularity, resembles MFH
Positive stains: fibroblast growth factor-23, dentin matrix
protein 1
DD: hemangiopericytoma, osteosarcoma, giant cell tumor
Extraskeletal bone tumors

Extraskeletal aneurysmal bone cyst
top
Features identical to intraosseous aneurysmal bone cyst
Mean 28 years, range 8-37 years
Deep soft tissue of upper extremities, thigh, groin
Rapidly growing mass without involvement of adjacent bones
May recur locally if incompletely excised
Gross: median 4 cm, range 2.5-9 cm, surrounded by thin rim
of bone; hemorrhagic cystic spaces with fibrous septa
Micro: cystic spaces filled with blood; fibrous septa
composed of fibroblasts, osteoclast-type giant cells, woven bone
Molecular: 46,XY,t(17;17)(p13;q12), similar to intraosseous
aneurysmal bone cyst
DD: extraskeletal osteosarcoma
Extraskeletal chondroma
top
Adults, hands and feet
Benign, but recur locally
Gross: lobulated, hyaline and calcified
Micro: lobulated on low power; plump tumor cells with fine
punctate calcification; nuclear hyperchromasia common; may
have focal fibrosis; may have osteoclast-like giant cells, histiocyte-
like cells, vacuoles resembling lipoblasts
DD: chondrosarcoma (rare in hands and feet), calcifying
aponeurotic fibroma
Extraskeletal chondrosarcoma
top
Less aggressive than bone tumors
Usually adult extremities; also children and trunk
Metastases to lung
Micro: usually myxoid; cords of small cells with acidophilic
cytoplasm, occasional vacuoles, usually in myxoid stroma; usually
no obvious chondrocytes
Positive stains: S100, Leu7/CD57, lysozyme, glycogen, acid
mucins
Negative stains: keratin
Molecular: t(9;22)(q22-31;q11-12) - CHN-EWS fusion gene
EM: well developed endoplasmic reticulum, cytoplasmic
filaments, glycogen
Variants:
Embryonal chondrosarcoma
top
Rare
Primitive appearance
Mesenchymal chondrosarcoma
top
Orbit, dura, trunk, retroperitoneum, extremities, kidney
Poor prognosis
Micro: clusters of undifferentiated small blue cells often with
hemangiopericytoma appearance mixed with islands of mature-
appearing hyaline cartilage
Molecular: Robertsonian translocation der(13;21)(q10;q10)
found in skeletal and extraskeletal cases, Mod Path 2002;15:572
Molecular images: image1, image2
Myxoid chondrosarcoma
top
Rare, first described in 1972
50-65% males, median age 50-52 years, range 6-89 years
80% in proximal extremities or limb girdles, 20% in trunk
Local recurrence in 48%, metastases in 46%
Survival of 90% at 5 years, 70-78% at 10 years
Adverse prognostic factors: older age, larger tumor size (>10 cm),
proximal extremity /limb girdle location, anaplastic cytology
Case report of tumor with neuroendocrine features and
t(9;17)(q22;q11.2), representing fusion of CHN and RBP56 genes, AJSP
2000;24:1020
Gross: median 7-10 cm (range 1-25 cm) in deep subcutaneous or
deeper soft tissue
Micro: most have low cellularity; may have focal hypercellular areas and
> 2 mitotic figures/10 HPF; may have rhabdoid features if INI1 negative
Positive stains: vimentin (90%), S100 (17-50%),
synaptophysin (22-72%), EMA (0-28%)
Negative stains: AE1/AE3, CAM5.2, EMA; often INI1 (Am J
Surg Pathol 2008;32:1168)
Molecular: EWSR1 translocation in 46% (Am J Surg Pathol
2008;32:8); often involves t(9;22)(q31;q12) EWSR1-NR4A3; EWS-
CHN or TAF2N-CHN fusion gene transcripts
References: Hum Path 2001;32:1116, Mod Path
2000;13:900, AJSP 1999;23:636
Parachordoma
top
Rare (<50 cases reported), resembles extraskeletal myxoid
chondrosarcoma and chordoma
Develops next to tendon, synovium, osseous structures in
extremities
Mean age 35 years, range 7-62 years
Surgical excision usually adequate
Micro: well circumscribed lobules of large, round and
eosinophilic cells, focally resembling physaliferous cells or
cartilaginous cells in myxoid to densely hyaline matrix; also
spindly cells
Positive stains: Alcian blue at pH 2.5 (matrix), abolished with
hyaluronidase predigestion; CK 8/18, EMA, S100, vimentin, type 4
collagen around nests of cells
Negative stains: smooth muscle actin, GFAP, CK 1/10
Molecular: trisomy 15 (one case), monosomy 1, 16, 17;
DD: extraskeletal myxoid chondrosarcoma [t(9;22)+, type 4
collagen negative], chordoma [monosomy 3, 4, 10 or 13; type 4
collagen negative]

Extraskeletal chordoma
top
Very rare
Positive stains: CK9, S100, brachyury (notochord marker,
Am J Surg Pathol 2008;32:572)
Extraskeletal Ewing sarcoma/PNET
top
Rare soft tissue tumor, morphologically indistinguishable from
Ewing sarcoma of bone, may represent extension of bone tumor
into soft tissue
Usually age 30 or less, occasionally age 50+
Chest wall, lower extremities, and paravertebral region; also pelvis, hip
region, retroperitoneum, upper extremities
Case reports: 29 year old man with neck tumor exhibiting focal
squamous differentiation (Am J Surg Pathol 2008;32:1742)
Aggressive; common metastases to lung, bones
Gross image: #1
Micro: small round/oval cells with scanty cytoplasm containing glycogen;
peritheliomatous pattern (concentration around blood vessels); usually
more neuroepithelial features than similar bone tumors
Micro images: image1, figure 1
Positive stains: glycogen, vimentin, CD99 / O13 / mic2, S100, keratin
(20%)
Negative stains: CK7, CK19 (usually), AJSP 2000;24:1174
Molecular: t(11;22)(q24;q12) fusion transcript by RT-PCR of
FLI1-EWS genes; also
t(21;22)(q12q12) of ERG-EWS genes, t(7;22)(p22;q12) of ETV1-
EWS genes
t(17;22)(q12;q12) - E1AF-EWS genes, t (2;22)(q33;q12) - FEV-
EWS genes
EM: primitive cells, abundant cytoplasmic glycogen, poorly
developed cell junctions, no neural features
DD: rhabdomyosarcoma (solid embryonal), lymphoma,
rhabdoid tumor
References: Archives 2001;125:1358; AJSP 2000;24:1657
Extraskeletal osteosarcoma
top
Adults, extremities
May occur after Xray exposure
60% mortality, worse than chondrosarcoma
Subtypes: osteoblastic, chondroblastic, fibroblastic, MFH-like,
telangiectactic, well-differentiated (parosteal)
Micro: osteoid and bone formation produced by tumor cells,
without interposition of cartilage
DD: myositis ossificans (no nuclear atypia, zonal), other
sarcomas producing metaplastic bone (MFH, synovial sarcoma,
fibrosarcoma)
Other tumors
Alveolar soft parts sarcoma
top
0.5-1.0 % of all soft tissue tumors
Tumor of deep soft tissues of thigh/leg, oral cavity, pharynx,
mediastinum, elsewhere
Usually young females
Highly malignant, although clinical course is slow/indolent
Metastases up to 30 years later to veins, lungs, other
Lung metastases may be presenting feature
Prognostic variables: size, presence of 17q25 abnormality
Gross: well circumscribed, large, gray-yellow, hemorrhage,
necrosis
Micro: well defined nests of cells separated by fibrous
stroma; alveolar pattern if cells discohesive; composed of large
polygonal cells with granular eosinophilic cytoplasm, vesicular
nuclei, prominent nucleoli; no/rare mitotic figures, minimal
pleomorphism; also characteristic rod-shaped crystalloids
Micro images: figure 6

Positive stains: PAS positive, diastase resistant needle-like
structures, MyoD1 (cytoplasmic only)
Molecular: changes in #1, 5, 13, 17
EM: membrane-bound crystals with periodicity of 58-100 nm
and cross grid pattern; numerous electron dense vesicles near
Golgi; smooth tubular aggregates associated with plasmalemmal
invaginations; no features of skeletal muscle differentiation
Clear cell sarcoma
top
Aka melanoma of soft parts
Rare aggressive tumor of adolescents / young adults
Median age 30 years, range 13-73 years; 60% male
Deep soft tissues of extremites, trunk or limb girdles, tends to
occur near tendon, fascia or aponeuroses
Slow progression, frequent local recurrences; eventually
nodal and distant metastases
5 year overall survival is 63% (Am J Surg Pathol 2008;32:452)
Gross: firm, well circumscribed, gray-white, gritty sensation
when cutting; median 4 cm
Micro: distinctly nested growth pattern with mixture of
spindle, epithelioid and tumor giant cells; melanin pigment in 2/3;
may have floret-like multinucleated giant cells; often rhabdoid
cells, bizarre pleomorphic cells; usually necrosis; mean 4 MF/10
HPF
Micro images: image1, image2, figure 7
Cytology: variable cellularity, may form microacinar
structures resembling adenocarcinoma (Am J Clin Pathol
2002;117:217)
Positive stains: S100, HMB45, microphthalmic transcription
factor (75%), melanoma-cell adhesion molecule, MelanA (43%),
iron (intra- and extracellular), Leu7/CD57, vimentin, keratin
(variable)
Negative stains: alpha-smooth muscle actin, desmin, CAM
5.2
Molecular: t(12;22)(q13;q12) - ATF1 and EWS (not seen in
melanoma); usually diploid or less aneuploidy than metastatic
melanoma to soft tissue; tumors in GI tract may have a variant
fusion gene EWSR1-CREB1
EM: melanosomes
DD: melanoma
Desmoplastic small round cell tumor
top
Distinctive neoplastic condition; not strictly a sarcoma
Children and young adults, often adolescent boys
Large mass in abdomen or pelvis, accompanied by widespread
peritoneal tumor implants
Other locations include pleura, thorax, scrotum, CNS
Micro: solid nests of round/oval cells surrounded by cellular
desmoplastic stroma; also necrosis, cystic degeneration, glandular
arrangements, signet ring-like cells, pseudorosette formations, rhabdoid
cells, extensive areas of predominantly spindle cell morphology,
carcinoid-like differentiation, adenoid cystic-like configuration, no
remarkable desmoplasia
Micro images: figure 2
Positive stains: WT (C-19) (also positive in nephroblastomas)
Molecular: t(11;22)(p13;q11.2 or q12) - WT1-EWS, AJSP
2000;24:830; also t(21;22)(q22;q12) - ERG-EWS
Epithelioid sarcoma
top
Uncommon, usually mass in deep soft tissues of distal
extremities of young adults, often hand, M/F = 2:1
Carcinoma of soft tissue, like synovial sarcoma and
adamantinoma of soft tissue
Typically recur, metastases in 45% of cases, usually to lungs,
skin (including scalp), lymph nodes
Poor prognosis; death from disease in 31%
Frequently underdiagnose
May derive from mesenchymal cells undergoing epithelial
differentiation
Poor prognostic features: proximal/axial tumor, large size,
deep tumor, hemorrhage, mitotic figures, necrosis, rhabdoid
features, angiolymphatic invasion
Treatment: excision, radiation therapy
Micro: epithelioid tumor cells in granuloma like fashion
around areas of necrosis and central hyalinization; striking
acidophilic tissue due to cytoplasmic staining and
desmoplasia; tumor usually in reticular dermis, sometimes
deeper soft tissue around fascial plans, aponeuroses,
tendon sheaths
Positive stains: keratin, EMA, vimentin, CD34 (Histopathology
1998;33:425), rarely CD31 (Virchows Arch 2003;443:93)
Negative stains: factor VIII related antigen (Virchows Arch A
Pathol Anat Histopathol 1987;410:309); INI1 / hSNF5 / SMARCB1 (86-
93%, both proximal and conventional, Am J Clin Pathol 2009;131:222,
Am J Surg Pathol 2009;33:542)
Molecular: usually DNA copy number changes, gains >
losses, including +11q13, 1q21-q23, 6p21.3, 9q31-qter, losses at
9pter-p23, 13q22-q32, others (Mod Path 2000;13:1092)
EM: abundant intermediate filaments, desmosome-like
junctions, small intercellular spaces with microvilli
DD: granuloma (due to necrosis)
Cutaneous
top
Confined to skin or subcutaneous fat, with little/no
involvement of deep soft tissues
20% have history of prior trauma
Accurate diagnosis usually established only after repeated
biopsies
Gross: ulcerated papule or nodule on distal extremity of
young adult
Micro: pseudogranulomatous pattern, bland cytology;
monomorphous cell population; hyalinized focally calcified stroma;
mummified remnants of necrotic epithelioid cells present
Micro images: image1 (4A-vimentin, 4B-EMA)
Positive stains: keratin, EMA, vimentin
DD: granulomatous inflammation
Proximal type
top
Arises in soft tissue of proximal limbs or trunks
Frequently with epithelioid features and rhabdoid phenotype
Worse prognosis than distal type (Mod Path 2001;14:655, free
full text)
May be variant of extrarenal malignant rhabdoid tumor
Aggressive behavior; metastases frequently lead to death
Case reports: Case of the Week #69; scrotum - Eur Urol
2006;49:406, Diagn Cytopathol 2001;24:36
Gross images: pubic tumor with ill defined multinodular
masses
Micro: composed primarily of large epithelioid cells with more
atypia than classic epithelioid sarcoma; resembles rhabdoid tumor
due to intracytoplasmic hyaline inclusions; large areas of necrosis
and a multinodular pattern are common, but a granuloma-like
pattern is uncommon
Micro images: sheets of large round/polygonal cells with
prominent nucleoli (A) and aggregates of rhabdoid cells (B);
large areas of necrosis; granuloma-like pattern #1; #2;
rhabdoid cells; infiltrative margins; angiomatoid
appearance; keratin, CD34, neurofilament and p53; EMA;
CD34; PLAP negative
Positive stains: keratin, EMA, vimentin; variable desmin,
CD34 and smooth muscle actin
DD: epithelioid MPNST (S100+, rarely EMA+, keratin
negative), epithelioid angiosarcoma, melanoma (S100+, usually
HMB45+)
Fibrous hamartoma of infancy
top
Tumorlike condition in newborns to 2 year olds
Usually boys, in shoulder, axilla or upper arm
Benign, although may recur locally
Gross: solitary, poorly circumscribed, gray/white fibrous
tissue and adipose tissue
Micro: mixture of well differentiated spindle cells resembling
fibroblasts or myofibroblasts surrounded by collagen, mature
adipose tissue, primitive mesenchyme in whirls
Positive stains: vimentin (fibrous and mesenchyme areas),
actin/desmin (spindle cell areas)
Granular cell tumor
top
Classic location is tongue, also most other tissues
Blacks may have multiple lesions
Congenital tumors occur in gingiva, but are rare; occasionally
congenital tumors are systemic
Usually benign, although malignant tumors also look benign;
those that appear malignant may be alveolar soft part sarcomas
May reflect degenerative change that can occur in Schwann
cells, smooth muscle cells or tumors
Gross: hard, ill defined margins, usually < 5 cm, may be
ulcerated, may appear malignant
Micro: large cells with highly granular cytoplasm, small
regular granules plus larger eosinophilic PAS+ round droplets;
associated with secondary epithelial hyperplasia when grow near
an epithelial surface; may see stromal elastosis
Positive stains: S100 (nuclear and cytoplasmic), acid
phosphatase, luxol fast blue, PAS
EM: granules resemble lysosomes, also angulated bodies
with Gaucher cell-like appearance, replicated basal lamina around
granular cells
Metastases to soft tissue
top
Unusual to be presenting feature of carcinomas
Usually from renal, lung, colonic carcinoma
Myospherulosis
top
Click here
Myxoma
top
Rare, benign mesenchymal tumor, resembles fetal umbilical
cord
Usually solitary, multiple myxomas associated with McCune-
Albright syndrome (polyostotic fibrous dysplasia) and Carney's
syndrome
Usually adults, females > males
Often in skeletal muscle of thigh
Question diagnosis if : not intramuscular or juxta-articular,
more than occasional vessels, hypercellular, atypia, mitotic activity
Treatment: excision is curative
Gross: mucoid, poorly circumscribed, may have infiltrative
borders
Micro: hypocellular, composed of bland cells, no mitotic
activity, no lipoblasts, scantly blood vessels; may have focal
histiocytes
Cytology: viscous, gelatinous quality when first applied to
glass slide; paucicellular, often finely granular myxoid stroma with
few cells, usually macrophages and bland spindle cells (Am J Clin
Pathol 2005;123:858)
Positive stains: vimentin

Negative stains: S100, desmin
EM: fibroblast-like cell with prominent Golgi, endoplasmic
reticulum, cytoplasmic filaments
DD: tumors with myxoid features/subtypes (liposarcoma,
MFH, chondrosarcoma, leiomyoma, leiomyosarcoma, embryonal
rhabdomyosarcoma, neurofibroma, aggressive angiomyxoma
[female genital tract, vascular, not associated with skeletal
muscle]), focal mucinous degeneration of skin / soft tissues
(nodular fasciitis, myxedema, cyst, ganglion, mucinosis)
Cardiac myxoma
top
Pedunculated masses, usually attached to left atrial wall by a
pedicle; more vascular and cellular than other myxomas; may
embolize; may arise from endocardial subendothelial cells
Carney complex associated

top
Carney complex: autosomal dominant disorder with multiple
cardiac and skin myxomas, spotty pigmentation of skin, endocrine
overactivity (pigmented nodular adrenocortical disease, large cell
calcifying Sertoli cell tumor of the testis, pituitary adenoma), blue
nevi, psammomatous melanotic schwannoma, bone tumors
Fibromyxomas
top
Myxomas of bone
Rare; well circumscribed lytic lesions of metaphysis, usually
femur, pelvis, tibia
Intramuscular myxoma
top
Painless, slow growing mass within large muscle groups of
thigh, shoulder, pelvis
Usually women 40-60
Cell of origin may be fibroblast incapable of producing mature
collagen that produce mucopolysaccharides instead
Micro: stellate or spindle cells with poorly defined cytoplasm,
myxoid stroma; minimal pleomorphism or mitotic activity
Jaw myxomas
top
Odontogenic origin, frequently recur
Mazabraud's syndrome
associated
top
Syndrome rare, associated with soft tissue myxomas
(multiple, intramuscular, right side of body), usually polyostotic
dysplasia precedes the myxomas; may be associated with
McCune-Albright syndrome also
DD: chondrosarcoma (bone or soft tissue tumor that

resembles chordoma with rows of cuboidal cells separated by
myxoid background; S100+, vimentin+, keratin-); myxoid
leiomyosarcoma (rare; gelatinous, well circumscribed; invasive,
highly myxomatous; see typical smooth muscle cells alternating
with mesenchymal cells), liposarcoma (commonly in thigh / lower
extremities; few mitotic figures but see lipoblasts, matrix contains
lipopolysaccharides and matrix; prominent vascular component;
t(12;1)(q13;p11)), myxoid MFH
DD of large retroperitoneal tumor: liposarcoma, MFH,

leiomyosarcoma
Ossifying fibromyxoid tumor
top
Adults
Small, painless mass in extremities
Usually indolent, local recurrences in 25%, rare malignant
behavior
Gross: well circumscribed, subcutaneous tissue or muscle
Micro: nests/cords of round/oval cells in myxoid matrix with
fibrosis and osteoid formation; lobulated at low power;
surrounded by partial capsule of mature bone; minimal
atypia, minimal mitotic figures
Positive stains: S100, vimentin, Leu7/CD57 (focal), GFAP
(focal)
EM: complex cell processes, basement membrane
deposition
Rhabdoid tumor
top
Kidney, soft tissues and other sites
Usually infants/children
Probably represents emergence of an aggressive
phenotype of various tumors (epithelioid sarcoma,
intraabdominal desmoplastic round cell tumor,
rhabdomyosarcoma, melanoma, carcinoma)
Early metastases to lung, liver, lymph nodes
Very aggressive, poor response to therapy, usually fatal
Micro: solid sheets of large cells with deep eosinophilic
cytoplasm, possible laterally displaced nucleus, prominent
nucleoli; myxoid, hyalinized, pseudoalveolar areas
Positive stains: vimentin, keratin, EMA
Negative stains: S100, muscle markers
EM: prominent intermediate filaments
Sinus histiocytosis with massive lymphadenopathy

top
Aka Rosai-Dorfman disease
May present as soft tissue mass with nodal involvement in
25%
Usually women, mean 46 years, range 24-66 years
Usually extremities (52%), also trunk (26%), head and neck
(13%), retroperitoneum (9%)
May recur after surgery
Difficult diagnosis to make due to altered morphology
compared to nodal tissue
Case report at Pathology 1998;30:14
Gross images: extranodal #1; #2
Micro: large histiocytic cells, frequently spindled, with less
conspicuous emperipolesis than nodal lesions; fibroinflammatory
component, AJSP 1992;16:122
Micro images: extranodal #1; #2; #3; CD68; S100
Positive stains: S100, CD68, lysozyme
DD: inflammatory pseudotumor
Synovial sarcoma
top
Usually a deep seated mass present for years around large
joints (80% in knee and ankle) in young adults (age 20-40); only
10% actually involve the joint
Represent 10% of adult soft-tissue tumors
Minute (< 1 cm) tumors of hands and feet: 2/3 female,
median age 29 years, 2/3 monophasic, 40% have
microcalcifications; EMA+, keratin+; have clinically favorable
course if completely excised (Am J Surg Pathol 2006;30:721)
5 year survival is 50-70%; 10 year survival 40%; recurs
locally, 10-15% metastasize to lung and pleura, bone, regional
nodes
M/F = 1.5:1
Tumor cells detected in peripheral blood monocytes in one
case by nested PCR (AJSP 2001;25:406)
May be radiation associated, Mod Path 2002;15:998
Poor prognostic factors: high histologic grade based on
MIB-1 index and necrosis associated with lung metastases, Hum
Path 2001;32:257, SYT-SSX1 vs. SYT-SSX2 gene fusion, Mod
Path 2000;13:482
Treatment: wide local excision plus radiation
Gross: well circumscribed, firm, gray-pink; focal calcifications
on Xray; rarely within major nerves
Micro: biphasic or monophasic or undifferentiated; biphasic
have spindle cells resembling synoviocytes and plump epithelial
cells forming glands/cords; monophasic lack the epithelial cells
Spindle cells are arranged in plump fascicles with
hyalinization and distinct lobulation accompanied by mast cells,
occasional osseous or cartilaginous metaplasia, focal whorling
May have hemangiopericytomatous vascular pattern
Poorly differentiated histology

predicts poor outcome
Micro images: image1, figure 8
Micro images: image
Positive stains: mucin in spindle cell areas, PAS positive in
epithelium, reticulin highlights biphasic pattern; cytokeratin 7,
8/18, 19 [both components], AE1/AE3 (70% of monophasic
fibrous, 46% of poorly differentiated), EMA (epithelial areas,
100% of monophasic fibrous, 92% of poorly differentiated),
CD99 / O13 (Ewings/PNET marker, 90-100% of monophasic
fibrous or poorly differentiated), vimentin (spindle cells),
CEA, bcl-2 (both components, 90% of monophasic fibrous or
poorly differentiated)
also TLE1 (97%, Am J Surg Pathol 2007;31:240), CD57 (neural
marker in 72%), E-cadherin (50%), S100 (30-40%), c-kit
(children), nuclear beta-catenin
Negative stains: CD34 (94% monophasic fibrous, 100%
poorly differentiated), desmin (98% monophasic fibrous,
100% poorly differentiated), h-caldesmon, CD141, WT1, FLI-
1
Note: normal synovium is cytokeratin negative
EM: glandular formation of epithelioid tumor cells with sparse
luminal microvilli
Molecular: t(X;18)(p11.2; q11) - SYT-SSX1 genes in 90%;
can detect via PCR;
also t(X;18)(p11.21;q11) - SYT-SSX2 fusion genes;
variants can be detected by optimizing RT-PCR, Mod Path
2002;15:679, Hum Path 2001;32:105),
p16INK4A gene deletion in 74% (Am J Clin Pathol 2006;126:866)
Molecular images: image
DD: MPNST - usually negative for CK7 and CK19 (Am J Clin
Pathol 1999;112:641), negative for SYT-SSX fusion products (Am J
Clin Pathol 1999;112:43)
, fibrous variant resembles other sarcomas, metastatic
adenocarcinoma (if primarily epithelial component)
References: AJSP 2002;26:1434; AJSP 2002;26:486; Archives
1999;123:1246; AJSP 2001;25:1150
Calcifying synovial sarcoma

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Heavy stromal calcification, 5 year survival of 84% is better
than classic tumor
Good prognosis: young, distal tumor, < 5 cm, < 15 MF/10
HPF, <50% necrosis, no rhabdoid cells, diploid
Teratoma
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Usually females
Congenital or early childhood
May be associated with twins or malformations
Sacrococcygeal area, head and neck, retroperitoneum,
mediastinum, CNS
75% benign
Neck during infancy: massive but benign vs. adult neck:
usually malignant
Staging
Staging
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This staging system applies to soft tissue sarcomas, but
excludes fibromatosis (desmoid tumor), GIST, infantile
fibrosarcoma, inflammatory myofibroblastic tumor, Kaposis
sarcoma, mesothelioma and sarcomas arising from the dura
mater, brain, parenchymatous organs or hollow viscera
References: AJCC Cancer Staging Manual (7th ed)
Primary tumor (T)

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TX: Primary tumor cannot be assessed

T0: No evidence of primary tumor
T1: Tumor 5 cm or less in greatest dimension
T1a: Superficial tumor
T1b: Deep tumor
T2: Tumor more than 5 cm
T2a: Superficial tumor
T2b: Deep tumor
Notes: Superficial tumor is located exclusively above the

superficial fascia without invasion of the fascia; deep tumor is
located either exclusively beneath the superficial fascia, superficial
to the fascia with invasion of or through the fascia, or both
superficial yet beneath the fascia.
Regional lymph nodes (N)

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NX: Regional lymph nodes cannot be assessed

N0: No regional lymph node metastasis
N1: Regional lymph node metastasis
Note: the presence of positive nodes (N1) in M0 tumors is

considered stage III
Distant metastasis (M)
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M0: No distant metastasis

M1: Distant metastasis
Histologic grade (G)

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GX: Grade cannot be assessed

G1: Grade 1 of 3 (low grade)
G2: Grade 2 of 3
G3: Grade 3 of 3 (high grade)
Stage grouping
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IA: T1a-b N0 M0 G1, GX

IB: T2a-b N0 M0 G1, GX
IIA: T1a-b N0 M0 G2-3
IIB: T2a-b N0 M0 G2
III: T2a-b N0 M0 G3 or Any T N1 M0 Any G
IV: Any T Any N M1 Any G

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Soft tissue - normal

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Definition: nonepithelial extraskeletal tissue, excluding

Soft tissue tumors - approach to diagnosis

Modified from Sternberg

Sarcomas - general - Soft tissue tumors

9,500 new cases/year in US

Syndromes (molecular / genetic) associated with soft tissue

Bannayan Zonana syndrome: OMIM #153480, multiple lipomas and

Indicate in pathology report which grading system is used

Two grade systems - low grade and high grade

Grading systems - French Federation of Cancer Centers

Mitotic count (count 10 successive high power fields [area of

Grading systems of soft tissue tumors - National Cancer

Grade 1: well differentiated liposarcoma; myxoid

References: J Clin Oncol 1997;15:350, J Surg Oncol 1989;41:263

Cell types for soft tissue tumors

Epithelioid: alveolar soft parts sarcoma, carcinoma

Architectural patterns of soft tissue tumors

Alveolar: alveolar rhabdomyosarcoma, alveolar soft parts

Molecular / cytogenetics of soft tissue tumors

RT-PCR or FISH of paraffin-embedded tissue for tumor

Alveolar soft parts sarcoma: t(X;17)(p11.2;q25) - ASPL-

References: Archives 2006;130:1199

Infections, inflammation and hematomas of Soft

Usually due to direct extension from infections of skin, bone

Granulomatous infections of soft tissue

Due to tuberculosis, fungi, atypical mycobacteria (Clin Infect

Hematoma of soft tissue

Necrotizing fasciitis of soft tissue

Definition: uncommon fulminant soft tissue infection

References: eMedicine #1; #2

PVP granuloma of soft tissue

Definition: granuloma due to injection of drugs containing

Tumoral calcinosis of soft tissue

Definition: large painless calcified masses in periarticular

Fibroblastic / myofibroblastic tumors of soft

Fibrous tissue consists of fibroblasts and extracellular matrix

Fibroblastic / myofibroblastic tumors of soft tissue -

Large subset of mesenchymal tumors

Angiomyofibroblastoma of soft tissue

Definition: benign, well-circumscribed myofibroblastic

Calcifying aponeurotic fibroma of soft tissue

Definition: rare, slow growing, painless tumor with

Micro images: AFIP - poorly circumscribed

other - spotty calcifications and chondroid-like cells;

Calcifying aponeurotic fibroma of soft tissue (continued)

Cytology: benign appearing spindle cells, chondroid cells,

Calcifying fibrous tumor of soft tissue

Definition: benign fibrous lesion with abundant hyalinized

Micro images: AFIP - adrenal gland tumor has

Calcifying fibrous tumor of soft tissue (continued)

Positive stains: Factor XIIIa, vimentin; also CD34

Definition: benign, highly cellular tumor of vulva and

Dermatofibrosarcoma protuberans (DFSP) - Soft Tissue

See Skin-Nonmelanocytic tumors chapter

Desmoplastic fibroblastoma of soft tissue

Definition: fibroblastic lesion centered in subcutaneous

Positive stains: vimentin, variable alpha smooth muscle

Elastofibroma of soft tissue

Definition: age 55+ years, benign, poorly circumscribed

Elastofibroma of soft tissue (continued)

Micro images: AFIP - paucicellular fibrous tissue mixed

other - thick bands of fibrous tissue (long arrows)