Soft Tissue Tumors Part 1

Introduction, Fibrous, Fibrohistiocytic and Adipose tumors

Last revised 12 July 2008

Last major update May 2008 - next update May09

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Triphasic pattern seen in Fibrous Hamartoma of Infancy

 

Table of Contents for Soft Tissue Tumors Part 1

Introduction: primary references, soft tissue-normal, approach to diagnosis, sarcomas-general, syndromes, grading, cell types, architectural patterns, molecular

Infections, inflammation and hematoma: general, granulomatous, hematoma, necrotizing fasciitis, PVP granuloma, tumoral calcinosis

Fibroblastic/myofibroblastic: normal, general, angiomyofibroblastoma, calcifying aponeurotic fibroma, calcifying fibrous tumor, cellular angiofibroma, dermatofibrosarcoma protuberans, desmoplastic fibroblastoma, elastofibroma, eosinophilic fasciitis, fibroma of tendon sheath, fibromatosis-general, fibromatosis-superficial, fibromatosis-deep, fibromatosis colli, fibrosarcoma-adult, fibrosarcoma-infantile, fibrous hamartoma of infancy, focal myositis, Gardner fibroma, giant cell angiofibroma, giant cell fibroblastoma, hemangiopericytoma, inclusion body fibromatosis, inflammatory myofibroblastic tumor, ischemic fasciitis, juvenile hyaline fibromatosis, lipofibromatosis, low grade fibromyxoid sarcoma, low grade myofibroblastic sarcoma, mammary type myofibroblastoma, myofibroma / myofibromatosis, myositis ossificans, myxofibrosarcoma, myxoinflammatory fibroblastic sarcoma, nodular fasciitis and related lesions, nuchal fibrocartilaginous pseudotumor, nuchal type fibroma, ossifying fibromyxoid tumor, pleomorphic fibroma, proliferative fasciitis, proliferative myositis, proliferative peribursitis, sclerosing epithelioid fibrosarcoma, solitary fibrous tumor, superficial acral fibromyxoma

Fibrohistiocytic: general, atypical fibrous histiocytoma, atypical fibroxanthoma, benign fibrous histiocytoma (superficial), deep benign fibrous histiocytoma, giant cell tumor of soft tissue, giant cell tumor of tendon sheath-diffuse, giant cell tumor of tendon sheath-localized, MFH-giant cell, MFH-inflammatory, MFH-pleomorphic, pleomorphic hyalinizing angiectatic tumor, plexiform fibrohistiocytic tumor

Adipose tissue-benign: embryology & physiology, white fat , brown fat

lipoma and variants: lipoma, angiolipoma, chondroid, fibrolipoma, intramuscular, lipoma arborescens, lipoma of tendon sheath, lipomatosis, lipomatosis of nerve, lumbosacral, myelolipoma, myolipoma, myxoid, nevus lipomatosus, pelvic, pleomorphic/spindle cell

other benign lesions: hemosiderotic fibrohistiocytic lipomatous lesion, hibernoma, lipoblastoma, subconjunctival herniated orbital fat

Adipose tissue-liposarcoma: general, atypical lipomatous tumor/well differentiated, dedifferentiated, myxoid, pleomorphic, mixed type, sclerosing poorly differentiated

 

Go to Soft Tissue Tumors Part 2 - Muscle, Vascular, Nerve, Other

 

Primary references - Soft tissue tumors Part 1

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American Journal of Clinical Pathology (AJCP) [free full text and no registration after 1 year], January 2000 to May 2008

American Journal of Surgical Pathology (AJSP), January 2000 to May 2008

Archives of Pathology and Laboratory Medicine (Archives) [always free full text and no registration]; January 1999 to May 2008

Biomed Central [always free full text and no registration]; 24 July 2001 to 1 May 2008

Human Pathology (Hum Path), January 2000 to May 2008

Modern Pathology (Mod Path) [free full text and no registration after 1 year]; Jan 2000 to May 2008

Fletcher: Pathology and Genetics of Tumours of Soft Tissue and Bone (AFIP 3rd Series, Vol 30), 2004

Fletcher: Pathology and Genetics of Tumours of Soft Tissue and Bone (WHO, Vol 5), Chapter 1-adipocytic tumors, Chapter 2-fibroblastic/myofibroblastic tumors, Chapter 3-fibrohistiocytic tumors
Rosai, J: Ackerman’s Surgical Pathology (9th Ed, 2004)

Sternberg, S: Diagnostic Surgical Pathology (4th Ed, 2004)

Websites with images: PathoPic, PEIR digital library; virtual slides - ASCP, OSU, USCAP

Journal search terms: each disease entity listed

 

Please refer to these primary references for more detailed discussions and photographs

 

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, 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

 

Sarcomas - general

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7,000/year in US

Classified based on type of cellular differentiation, although most arise not from differentiated cells, but 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, classification

Recommended to diagnose with FNA 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) or foreign bodies (MFH, angiosarcoma)

Poor prognostic factors: large size, deep seated versus superficial, retroperitoneum versus extremities, high grade, high stage, positive margins (associated with local recurrence)

Treatment: enucleation acceptable only for schwannomas; for other small tumors, must excise with 1-2 cm rim of normal tissue; surgery should also remove site of prior FNA or incision

Wide local excision for infiltrative lesions (fibromatosis, DFSP); amputation is less commonly performed now than in the past

Radiation and chemotherapy may also be used

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 leiomyosarcoma, pulmonary chondroma and extra-adrenal paraganglioma

Gardner syndrome: OMIM #175100, fibromatosis and familial adenomatous polyposis

Kasabach-Merritt syndrome: OMIM #141000, microangiopathic hemolytic anemia associated with childhood hemangioma

Klippel-Trenaunay-Weber syndrome: OMIM #149000, hemangiomas with hypertrophy of associated bone and soft tissue

Li Fraumeni syndrome: OMIM #151623, various soft tissue sarcomas, osteosarcoma, breast cancer, brain tumors, leukemia and adrenocortical carcinoma

Lipomatosis, multiple syndrome: OMIM #151800

Maffucci syndrome: OMIM #166000, hemangiomas, enchondroma, chondrosarcoma

Mazabraud's syndrome: fibrous dysplasia and intramuscular myxoma (eMedicine)

McCune-Albright syndrome: OMIM #174800, myxomas are minor feature (see Mazabraud’s syndrome), major features are polyostotic fibrous dysplasia cafe-au-lait skin pigmentation and precocious puberty

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

Sturge-Weber syndrome: OMIM #185300, port-wine spot of face

Turner syndrome: cystic hygroma (eMedicine)

 

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)

Grading is currently not considered appropriate for needle biopsies

 

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

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Grade 1: total score of 2-3

Grade 2: total score of 4-5

Grade 3: total score of 6-8

 

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, Ewing’s sarcoma/PNET, sarcomas of doubtful tumor type, embryonal and undifferentiated sarcomas

 

Mitotic count (count 10 successive high power fields [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 Ewing’s 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, carcinomas (extension into soft tissue or metastases), epithelioid sarcoma, rhabdoid tumors, synovial sarcoma; epithelioid variants of leiomyosarcoma, MPNST or vascular tumors

Pleomorphic: variants of leiomyosarcoma, liposarcoma, MFH, MPNST or rhabdomyosarcoma; also melanoma and metastatic carcinoma

Round cell: desmoplastic small round cell sarcoma, Ewings/PNET, mesenchymal chondrosarcoma, rhabdomyosarcoma, round cell liposarcoma; also carcinoma, lymphoma, melanoma, neuroblastoma

Spindle cell: benign nerve sheath tumor, DFSP, fibroma of tendon sheath (cellular), fibromatosis, fibrosarcoma, leiomyosarcoma and leiomyoma, MPNST, nodular fasciitis, spindle cell variant of embryonal rhabdomyosarcoma, 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, myxoid chondrosarcoma

Palisading: Schwann cells (neural tumors), smooth muscle tumors, spindle cell lipoma

Plexiform: nerve sheath tumors, plexiform fibrous histiocytoma

Plexiform vascular: myxofibrosarcoma, myxoid liposarcoma, nodular fasciitis

Storiform: fibrohistiocytic tumors, dedifferentiated liposarcoma, low grade fibromyxoid sarcoma, 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

Angiomatoid fibrous histiocytoma: t(12;16)(q13;p11) - FUS-ATF1 fusion gene or t(12;22)(q13;q12) - FUS-EWS fusion gene

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-EWS 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 small round cell tumor: t(11;22)(p13;q12) - WT1-EWS or t(21;22)(q22;q12) - ERG-EWS fusion genes

Ewing’s 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

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 in Turkey (Intern Med 2008;47:171)

 

Hematoma of soft tissue

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May clinically resemble a tumor if deep seated

Usually near tensor fascia lata (upper thigh muscle, image)

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 masslobulation with dense fibrous pseudocapsule and chocolate-brown fluid

Micro images: cystic cavity with necrotic debris, fibrin and blood costscyst 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

Fatal if untreated

Particularly serious in patients with badly controlled diabetes (Diabetes Res Clin Pract 2008;80:218)

Usually due to group A streptococci, also community-acquired MRSA (Surg Infect (Larchmt) 2008 Apr 9 [Epub ahead of print])

Case reports: due to Pseudomonas (Intern Med 2008;47:553)

Treatment: start promptly to minimize morbidity (World J Emerg Surg 2007;2:19)

Micro images: gluteal gas gangrene with necrotizing fasciitis #1#2#3-gram stain#4-gram stain#5necrotic muscle with gas bubbles but minimal inflammationleg lesion #1#2#3#4#5#6-septic thrombus#7-associated vasculitis#8-gram stain#9-gram stain 

References: eMedicine #1#2

 

PVP granuloma

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Definition: granuloma due to injection of drugs containing polyvinylpyrrolidone (PVP)

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

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Definition: large painless calcified masses in periarticular soft tissues, including elbows, hips, only rarely knees

Autosomal dominant

Local recurrence common

Elevated serum calcium, hyperphosphatemia, elevated serum Vitamin D levels

Xray: lobulated calcifications, separate from associated bone

Gross: large, multinodular, chalky masses

 

 

Fibroblastic / myofibroblastic tumors of soft tissue

Normal histology

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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)

Uncommon slow growing painless mass, usually females of reproductive age

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), scrotal mass, 27 year old man with tumor of inguinal region (Archives 2000;124:1679)

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 concentrated around vessels, with eosinophilic cytoplasm and often bi- or multi-nucleation; mast cells common; may have plasmacytoid or epithelioid morphology, or rarely show degenerative changes; 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&Efig A: numerous capillary-like vascular channels, fig B: spindle cells with occasional multinucleated cells;  male inguinal regionscrotal mass

Positive stains: vimentin, desmin (strong and diffuse, may be reduced in post-menopausal patients), ER, PgR, smooth muscle or pan-muscle actin (focal, Hum Path 1997;28:1046), occasional CD34

Negative stains: S100, keratin

EM: myofibroblastic and fibroblastic features

DD: aggressive angiomyxoma (not circumscribed, less cellular, less vascular, stromal mucin and RBC extravasation are present, infrequent plump stromal 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

50% recur, especially in children; does not metastasize

May be cartilaginous analog of fibromatosis

Case reports: 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

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

Cytology: benign appearing spindle cells, chondroid cells, multinucleated giant cells and calcified debris (Diagn Cytopathol 2001;24:336)

Micro images: poorly circumscribed fibroproliferative process with scattered, linear and calcified zonesamorphous calcification surrounded by palisading cells suggestive of rheumatoid nodule or crystalstypical zonation pattern has  cellular, plump fibroblastic cells palisading around a hyalinized collagenous zone, which in turn surrounds the calcificationcells adjacent to hyalinized layer are commonly more roundedchondroid area is adjacent to calcification

16 year old girl with foot tumor - image1image2image3image4image5

Positive stains: vimentin, CD68, CD99, S100, muscle specific actin (50%), smooth muscle actin (50%) ]

Negative stains (usually): CD34, CD57, progesterone receptor

EM: chondrocytes, fibroblasts and occasional myofibroblasts

Molecular/cytogenetics: benign, but may be aneuploid (Cancer 1994;73:1200)

DD: 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; in older patients, fibromatosis usually lacks 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), fibrous hamartoma of infancy (immature mesenchyme, fibroblasts are arranged in trabeculae, 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

First described in 1993 (AJSP 1993;17:502)

Adolescents/young adults, all sites

Unrelated to inflammatory myofibroblastic tumor, based on histology and immunoreactivity (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), tumor 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)

Treatment: excision, rarely recurs

Gross: well circumscribed but unencapsulated, variable size, may infiltrate into surrounding tissue, may have gritty cut surface

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: psammoma body, lymphocytic infiltrate, hypocellular stromafigures 1A, 1B, 1E and 1F (comparison with inflammatory myofibroblastic tumor)adrenal gland tumor has paucicellular fibrous proliferation with focal microcalcificationsmicrocalcifications vary in size;   lymphoplasmacytic inflammation is characteristic

Positive stains: Factor XIIIa, vimentin

Negative stains: smooth muscle actin, muscle specific actin, ALK, desmin, S100, keratin

EM: immature fibroblastic cells, collagen fibrils, dystrophic and psammatous calcifications

EM images: figure 2A

DD: inflammatory myofibroblastic tumor (more cellular, no calcifications, ALK+, actin+), 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

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: 51 year old woman with coexisting Bartholin’s 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; occasional atypia; 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; females may have brisk mitotic activity, usually none/rare in males; no necrosis, no atypical mitotic figures

Micro images: fusiform cells, thick walled blood vessels and adipose tissuefusiform cells with clear cytoplasm and bland nucleivarious imagesrecurrent tumorER+

Virtual slides: 63 year old man with scrotal mass

Positive stains: ER, PgR, vimentin; smooth muscle actin (21%), CD34 (30-60%)

Negative stains: S100, actin, desmin, EMA

Cytogenetics: may have 13q14 involvement; similar changes as spindle cell lipoma (Cancer Genet Cytogenet 2007;177:131)

DD: aggressive angiomyxoma, angiomyofibroblastoma (less uniform cellularity, smaller vessels, usually desmin+), solitary fibrous tumor, perineuroma, leiomyoma

References: Stanford School of Medicine

 

Dermatofibrosarcoma protuberans (DFSP) - Soft Tissue Tumor chapter

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Definition: low to intermediate grade malignancy, usually of dermis, with prominent storiform pattern of monomorphic fibroblast-like cells that invade into subcutis

Also called intermediate (borderline) fibrous histiocytoma

Part of WHO classification for skin tumors, not soft tissue tumors

Slow growing, low-grade malignant neoplasm of trunk and various sites but not hands and feet

Rare, usually adults 20-40 years, more common in blacks in US (J Am Acad Dermatol 2007;56:968)

Can occur in infants (Arch Dermatol 2007;143:203) and children (J Plast Reconstr Aesthet Surg 2007 Dec 18 [Epub ahead of print])

May be a peculiar type of nerve sheath tumor since CD34 positive                                           

Locally aggressive, low rate of metastasis (only after repeated failures at local control); may progress to fibrosarcoma or MFH

Giant cell fibroblastoma is considered the juvenile variant of DFSP as it has the same translocation (AJSP 2003;27:27)

Bednar’s tumor: 5-10% of cases; pigmented variant due to dendritic cells with melanin, S100+ only in pigmented cells, HMB45 negative; associated with black patients

Case reports: atrophic variant (J Dermatol 2006;33:486), granular cell variant (AJSP 2002;26:932), myoid differentiation in fibrosarcomatous DFSP (Acta Dermatovenerol Alp Panonica Adriat 2006;15:39), sclerosing variant (Int J Dermatol 2006;45:59)

Treatment: must excise subcutaneous fat (wide local excision with 2-3 cm margins) to prevent recurrence (Plast Reconstr Surg 2007;119:1779), three dimensional histologic evaluation of margins recommended (Ann Surg Oncol 2004;11:438), imatinib may be effective although tumor is CD117 negative (J Clin Oncol 2005;23:866)

Clinical images: papulonodular thigh lesions

Gross: nodular, polypoid or plaque-like, centered in dermis, can occur in deep soft tissue; mean 5 cm, gray-white (brown/black if melanocytes present), may appear circumscribed; hemorrhage and necrosis are rare

 

Dermatofibrosarcoma protuberans (DFSP) - Soft Tissue Tumor chapter (continued)

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Micro: non circumscribed, highly cellular, “tight” storiform pattern in every field (cells radiating in spokes at right angles around a central point that often contains a vessel) that infiltrates deeply into subcutaneous tissue and entraps fat cells; storiform pattern may be absent in early plaque stage; cells are monomorphic, thin and spindly with scant eosinophilic cytoplasm and hyperchromatic nuclei resembling neurofibroma; may have numerous mitotic figures, but not atypical ones; collagen usually non-polarizable and thin; only mild pleomorphism and focal atypia; may coexist with giant cell fibroblastoma; usually no significant pleomorphism, no/rare histiocytes, no histiocyte-like cells, no foam cells, no giant cells or other inflammatory cells

Variants: atrophic (depressed lesion), collagenous (with central thick collagen bundles), granular cell (S100 negative), myxoid (see below), palisading, pigmented, sclerosing

Cytology: homogeneous with isolated spindle cells, often tissue fragments with storiform pattern, fibrillary stromal fragments, naked nuclei; occasional slight to moderate atypia (Diagn Cytopathol 2004;30:261)

Micro images: small uniform cells radiating like pinwheels from central area that often has a blood vessel is characteristicuniform cells with no significant pleomorphism, minimal intercellular collagen, no/rare foam cells or giant cells, which are characteristic of benign fibrous histiocytomafine strands of collagen are presentinfiltration of fat causes tumor cells to surround fat cells #1#2#3#4-residual fat cells are in linear arrangement resembling a string of pearls, which is characteristic of DFSP but not benign fibrous histiocytomaDFSP with diminished storiform pattern but CD34+ (not shown)pigmented cells are not commonvariants-with fibrosarcoma, myxoid, pigmented

frozen sections: intradermal and extension into adipose tissue

Positive stains: CD34 (strong in 95%), vimentin; also actin (focal), ApoD (AJSP 2004;28:1063), bcl2, NKI-C3 (AJCP 1992;97:478), CD99 (J Cutan Pathol 2008 Jan 14 [Epub ahead of print])

Negative stains: Factor XIIIa (usually), keratin, EMA, S100, HMB45, desmin, CD117 (J Cutan Pathol 2007;34:857)

EM: stellate or spindle cells with long, slender, ramified cell processes joined by primitive junctions, often with subplasmalemmal densities; commonly multivesicular buds (Ultrastruct Pathol 2006;30:283)

Molecular/cytogenetics: t(17,22)(q21;q13) [collagen type 1 alpha 1 gene and platelet derived growth factor beta chain gene, OMIM #607907] found in almost all cases using multiplex RT-PCR (Hum Path 2008;39:184); also supernumerary ring chromosomes derived from t(17;22) (Oncogene 2001;20:2965), rarely other translocations (Virchows Arch 2008 Feb 6 [Epub ahead of print])

 

Dermatofibrosarcoma protuberans (DFSP) - Soft Tissue Tumor chapter (continued)

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DD: benign fibrous histiocytoma (also storiform but non-infiltrative, less cellular than DFSP, Factor XIIIa positive, CD34 negative,), thymoma (storiform but different location, CD34 negative). MFH-pleomorphic or atypical fibroxanthoma (storiform pattern but also moderate/marked pleomorphism and nuclear atypia)

References: eMedicine

 

Indeterminate lesions between DFSP and dermatofibroma - Soft Tissue Tumor chapter

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Report of 10 tumors with features of both tumors, all Factor XIIIa+, CD34+, although in different cells (AJSP 2000;24:996)

Clinically, one recurrence at mean 22 months follow-up

Recommend complete excision

 

Myxoid variant of DFSP - Soft Tissue Tumor chapter

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Definition: DFSP with 50%+ myxoid stroma

Uncommon

Median age 40 years, male and female

Extremities, head and neck, trunk, anogenital region

Associated with recurrent tumor

Similar prognosis as classic DFSP (AJSP 2007;31:1371)

Gross: median 3 cm, white-tan-gray-yellow, firm to gelatinous

Micro: infiltrative, often hypocellular, sheet-like, bland spindle cells with pale eosinophilic cytoplasm, spindled nuclei, no pleomorphism; stroma is myxoid with prominent thin walled vessels; diffuse infiltration of fat; also cellular areas typical of DFSP

Micro images: various images

Virtual slides: myxoid DFSP

Positive stains: CD34

Negative stains: S100, muscle markers, CD99

 

Sarcomas arising in DFSP - Soft Tissue Tumor chapter

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Usually resembles fibrosarcoma; rarely MFH-pleomorphic

In cases with wide local excision and negative margins, 20% recur, metastatic rate varies from 0% (AJSP 2000;24:1125), to 10% (AJSP 2006;30:436)

Report as “DFSP with areas of fibrosarcoma”, indicate extent of fibrosarcomatous change, nuclear grade, level of mitotic activity

Case reports: 42 year old woman with abdominal mass (Archives 2006;130:882)

Treatment: wide local excision

Micro: in fibrosarcomatous areas, spindle cells intersect at acute angles, chromatin is coarser than usual, increased mitotic activity

Micro images: fibrosarcoma arising in DFSP - DFSP cells trap fat cells, fibrosarcoma cells are more uniform #1#2#3fibrosarcoma cells are spindled, uniform and hyperchromatic and arranged in herringbone pattern #1#2uncommon finding is myoid nodules containing cells with eosinophilic cytoplasm, present in DFSP or fibrosarcomatous areas, cells are actin+, CD34-, desmin-H&E and FISH

pleomorphic sarcoma arising in DFSP - tumor cells are pleomorphic and have granular chromatin

Virtual slides: fibrosarcoma arising in DFSP

 

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

Rare benign lesion of adult men (70% between ages 40 and 69 years)

Usually upper extremities, back, feet

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 and reactive appearing fibroblasts and myofibroblasts separated by  abundant collagen with variable myxoid stroma;  fibroblasts have amphophilic cytoplasm, hyperchromatic nuclei and distinct nucleoli; 70% of cases involve subcutis, 25% extend into skeletal muscle

Micro images: large, reactive appearing spindled fibroblasts in fibrous matrixfocus of low cellularity and dense collagenmore cellular area with reactive type fibroblastsscattered stellate cells in hypovascular collagenous matrix

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)

DD: fibromatosis (more cellular, fascicular pattern, prominent vasculature, Adv Anat Pathol 1999;6:275)

References: Hum Path 1998;29:676, AJSP 1995;19:1077

 

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)

Slow growing; more common on apex of scapula, usually right sided; associated with hard manual labor

Occasionally in deltoid muscle, infraolecranon area, hip, thigh, stomach

Related changes found at autopsy in 13-17% of elderly; more common in women

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: Case of the week #46, tumor of hand, multiple subcutaneous nodules (J Am Acad Dermatol 2004;50:126), patient with bilateral subscapular tumors and tumor surrounding a stomach ulcer (AJSP 1985;9:233)

Treatment: excise if symptomatic, does not recur

Clinical images: shoulder based tumorstypical 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 fatpoorly defined fibroelastic tumor entrapping fat #1#2gray-white fibrous tissue mixed with fat

Micro: collagen bundles alternate with large and thick eosinophilic elastic cylinders with a dense central core, elastic fibers may be fragmented into linear globules (beads on a string); may entrap fat cells

Micro images: paucicellular fibrous tissue mixed with fat #1#2thick, densely eosinophilic elastin bands are mixed with collagen #1#2branched (arrow) and unbranched coarse elastin fibers mixed with collagen and adiposeelastin bands have serrated edges and are associated with detached globular elastin arranged like beads on a stringH&E and elastic stainVerhoeff elastin stain highlights elastin fibers and the bead-like arrangement of the elastin globuleselastin stain highlights branched and unbranched elastin fibers #1#2 

case of the week #46: image #1#2#3#4#5#6#7orcein (elastin) stain

Virtual slides: elastofibroma #1#2#3#4#5-elastin stain

 

Elastofibroma of soft tissue (continued)

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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)

DD: 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 - Soft Tissue Tumor chapter

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Definition: diffuse fasciitis with fibrosis, eosinophilia and inflammation of skin, subcutaneous tissue and fascia

Not a WHO diagnosis

First described by Shulman (Trans Assoc Am Physicians 1975;88:70)

Rare fibrosing disorder with scleroderma-like induration of distal extremities

Mean age 50 years, 75% female

Eosinophilic-myalgia syndrome is different - 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;  marked thickening and replacement of the entire dermis with sclerotic collagensclerosis at dermosubcutaneous junction, thickened subcutaneous septa and fascia, and a perivascular and interstitial infiltrate of lymphocytes and plasma cellsinflammatory infiltrate in deep subcutisfascia has heavy inflammatory infiltration with numerous eosinophils, lymphocytes, and occasional plasma cellsentrapment of subcutaneous fat by intersecting thick bands of fibrosis, also thickening and fibrosis of fascia and lymphoid aggregates

References: eMedicine #1#2

 

Fibroma of tendon sheath - Soft Tissue Tumor chapter

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Definition: well circumscribed, lobulated tumor attached to tendon or tendon sheath

Also called tenosynovial fibroma

Benign; may overlap with nodular fasciitis (AJSP 1989;13:472) or giant cell tumor of tendon sheath (Mod Path 1995;8:155)

Uncommon, 60% men, ages 30-50 years old with nodule on fingers, hands or wrist

Up to 24% recur, does not metastasize

Case reports: mass of 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

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: multinodular proliferationextensive collagenization of nodules produces this typical, eosinophilic, paucicellular appearance, incomplete separation of the nodules produces cleft-like spacesmost cases are paucicellular with scattered spindled fibroblasts in a densely collagenized matrix and scattered small vesselstransition from collagenous to cellular areacellular area resembles leiomyosarcoma or fibrosarcoma, but these tumors are rare in hands and feetfibroblasts are bland (ruling out sarcoma) and separated by collagenpredominately acellular fibrous tissue with areas of hyalinization and characteristic slit-like vascular channelstumor of finger #1#2#3

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 nucleispindle 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: 50% have t(2;11)(q31-32;q12) (Histopathology 1998;32:433)

DD: sarcoma (cellular, but rare in hands and feet, usually large masses with 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)

References: Stanford University

 

Fibromatosis of soft tissue - general

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Definition: proliferation of well differentiated fibroblasts with infiltrative growth, collagenous stroma, no atypia, no/rare mitotic figures, aggressive behavior with local recurrence

Also called musculoaponeurotic fibromatosis (since usually in intimate contact with skeletal muscle), desmoid tumors (classically in abdominal wall during pregnancy)

Neoplastic, locally aggressive (repeated recurrences, no distant metastases); resembles scar tissue

May arise after trauma or in the scar of a surgical excision

May arise post-radiation and feature bizarre cells with large hyperchromatic nuclei

Present in Gardner’s syndrome (multiple colonic polyposis, multiple osteomas); usually involves omentum or mesentery after surgery

Juvenile fibromatosis: similar to adult fibromatosis but (a) more common, (b) has variants of fibromatosis colli, infantile digital fibromatosis and infantile myofibromatosis

Treatment: radical excision with wide margins; less recurrence in abdominal wall than elsewhere; may recur 5-6 times; may stop growing if stop excising; suggestion - don’t excise if it asymptomatic or isn’t growing

Also radiation therapy for local control (external or iridium implants); tamoxifen therapy

Gross: large, firm, white cut surface, infiltrative borders; often in muscular fascia

Micro: lobulated proliferation of fibroblasts or myofibroblasts (amphophilic cytoplasm due to rough ER, open chromatin, well defined nuclear membrane, one distinct nucleoli), usually more collagenous and less cellular than nodular fasciitis; mucopolysaccharide matrix with thin walled, curvilinear, non-branching or ectatic vessels; infiltrative borders, perivascular lymphocytes at edge of lesion; few mitotic figures, no atypia

DD: GIST tumor (in abdomen), fibrosarcoma (5+ MF/10 HPF)

 

Fibromatosis - superficial of soft tissue

Palmar fibromatosis (Dupuytren’s 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 (in 24% age 65+)

75% men

50% bilateral, 10% also have plantar disease, 1-4% have penile fibromatosis

May be nodular; puckers overlying skin as it ages; causes flexion contracture of digits 4 and 5 due to cords of fibrous tissue between nodules and tendons

May be caused by fibrogenic cytokines (J Hand Surg [Br] 2005;30:557)

Treatment: excision

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: nodule of variably cellular fibroblastic tissue infiltrates an aponeurosis, with bland, uniform spindled cells in a dense hyalinized collagen stromamitotic figures may be present in cellular regions but are never atypicaltumor of myofibroblasts and fibroblasts within fascia #1#2#3various 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; appears to be reactive not neoplastic (J Transl Med 2006;4:21), no somatic mutations of beta-catenin genes, unlike desmoid fibromatosis (Mod Path 2001;14:695)

DD: 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

 

Plantar fibromatosis (Ledderhose’s 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

Considered a heterogeneous group of conditions with plantar location, mature collagen and fibroblasts but without malignant features (eMedicine)

Common in boys < 10 years old and teenagers

Only 10-25% bilateral, may be nodular

Often presents with firm subcutaneous nodule or thickening associated with pain after standing or walking

Clinically resembles melanoma, synovial sarcoma, Kaposi’s sarcoma

Usually NOT associated with contractures, but is associated with palmar and penile fibromatosis

Increased risk of recurrence if multiple nodules, bilateral lesions, family history

Treatment: excision

Clinical images: mass along medial plantar surfaceheel mass

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

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 - more dense 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)

DD: monophasic synovial sarcoma, fibrosarcoma, desmoid fibromatosis (infiltrates skeletal muscle, > 3 cm), calcifying aponeurotic fibroma

References: AJSP 2005;29:1095 (children), Stanford University, Wikipedia

 

Penile fibromatosis (Peyronie’s) - Soft Tissue Tumor chapter

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Definition: fibrous thickening of dermis and Buck’s fascia between corpora cavernosa and tunica albuginea, causing curvature towards side of lesion and restricting movement of these structures during erection

Fibrotic condition of varying 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)

Prevalence up to 3% (Int J Impot Res 2002;14:379), associated with plaques, pain, induration, deviation; also Dupuytren’s contracture

Typically age 40+ years, rarely age 40 or less (J Androl 2003;24:27)

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, excision

Micro: disorganization of collagen of tunica albuginea with formation of nodules, perivascular lymphocytic infiltrate in 1/3, linear band of calcification in 1/4 (J Urol 1997;157:282)

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

 

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

2-4 per million population, less common than superficial fibromatosis

May be familial (associated with Gardner’s syndrome/FAP syndrome-Clin Gastroenterol Hepatol 2008;6:215) 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

Abdominal wall fibromatosis: arises within abdominal wall-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 Gardner’s syndrome (familial adenomatous polyposis, multiple osteomas); often post-surgical

Case reports: 43 year old woman with tumor of retroperitoneal space (World J Surg Oncol 2004;2:33), post-traumatic paraspinal mass (World J Surg Oncol 2008;6:28), aggressive mesenteric tumor that responded to chemotherapy (Jpn J Clin Oncol 2008;38:222), tumor of abdominal wall (Radiology 2005;236:81)

Treatment: excision (inadequate excision may cause recurrence), 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)

Gross: solitary, gray-white and glistening, firm, poorly circumscribed, rubbery; more fibrotic centrally and cellular peripherally; cuts with gritty sensation, 5-10 cm

Gross images: extra-abdominal fibromatosis has dense white, trabeculated fibrous tissue that invades skeletal muscle and produces cross section of alternating white and red patchestumor infiltrates thoracic walltrunk tumor #1#2thigh tumorthoracic tumor;  gray-white tumor of Gardner syndromegray-glossy cut surfacetumor in mesentery of small bowelwell defined margin (uncommon)infiltrative margindesmoid 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

 

Fibromatosis - deep (desmoid type) of soft tissue (continued)

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Micro: poorly circumscribed with infiltration of adjacent tissue; uniform cellularity between exuberant fibrous proliferation and low grade fibrosarcoma; cells are bipolar fibroblasts and myofibroblasts with reduced cytoplasm that merges with surrounding collagen; variable mitotic activity but no atypia; stroma varies from collagenous, keloid-like to myxoid; regenerative muscle cells within lesions may resemble giant cells

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 fairly reliable for diagnosis but core needle biopsy is better (Acta Orthop 2006;77:926)

Micro images: extra-abdominal fibromatosis - low power shows paucicellular fibrous proliferation in long fascicles, with numerous slit-like vessels characteristic of desmoid fibromatosisfibroblasts have spindled, dense, wavy nuclei and minimal cytoplasmmargin shows infiltration of skeletal muscle, a common featureatrophic and regenerating muscle fibers at the edge of the lesion may resemble rhabdomyoblastssome tumors are myxoidcells in myxoid tumors are uniformly bland, unlike those in malignant myxoid tumorscellular tumor has scattered mitotic figures, none atypicalkeloid-type pattern may be observed focally in deep tumorsparaspinal tumor #1#2thigh mass has spindle cells, dense collagenous stroma, slit-like vessels and chronic inflammationpre-radiation therapypost-radiation therapy shows reduced cellularitybreast-smooth muscle actin+

intra-abdominal (mesenteric) fibromatosis - tumor appears to be extrinsic to bowel muscularis propria, which distinguishes it from GISTfibromatosis is paucicellular and composed of relatively uniform, bland spindle cells #1#2#3bland, mitotically active, uniform cells in myxoid stromaless commonly bland spindle cells are within collagen bundlesbiopsy of pelvic tumortrichrome stain highlights collagen in the fibromatosis and distinguishes it from overlying normal muscularis propria

abdominal wall fibromatosis - extension into adjacent musclefascicles of fibroblastic spindle cells with abundant intercellular collagen

Cytology images: various images

Virtual slides: abdominal fibromatosis

 

Fibromatosis - deep (desmoid type) of soft tissue (continued)

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Positive stains: vimentin, variable smooth muscle actin and muscle specific actin, 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 in extra-abdominal tumors (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; 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

DD: idiopathic retroperitoneal fibrosis (Orman’s disease - inflammatory, strangles the ureters), sclerosing omentitis (grows like panniculitis, beta catenin negative); leiomyoma (bright pink cytoplasm), schwannoma, neurofibroma (no myofibroblasts), fibrosarcoma (atypia or mitotic figures present), low grade fibromyxoid sarcoma (beta catenin negative), GIST (AJCP 2004;121:93)

 

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)

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

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)

Micro images: multinodular proliferation of acellular collagenized tissue replaces part of sternocleidomastoid muscleskeletal muscle fibers are trapped at advancing edge of lesionscattered, bland fibrocytes are widely separated by dense collagen

Positive stains: vimentin, actins

DD: fibromatosis (no muscle fibers - they are replaced by fibrous tissue except at periphery, does not typically affect sternocleidomastoid muscle), proliferative myositis (doesn’t affect this site, stroma resembles granulation tissue and is not collagenous), fibrodysplasia ossificans progressiva (doesn’t 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 fibromatosis, 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: 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

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: atypical uniform cells in herringbone patterncells 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#2grade II tumor has intermediate features #1#2grade III tumor has high grade atypia and high mitotic index #1#2

Virtual slides: fibrosarcoma

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; also smooth muscle markers, histiocytic markers, basal lamina

EM: fibroblasts with prominent rough endoplasmic reticulum but no myofilaments, no external lamina, no intercellular junction; also no distinct myofibroblasts (if present, call myofibrosarcoma)

Molecular/cytogenetics: aneuploid

DD (other tumors with fibrosarcomatous areas): synovial sarcoma, liposarcoma, MFH-pleomorphic, MPNST, fibromatosis (less cellular, less hyperchromasia, no atypia, <1 mitotic figure/HPF)

 

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

Usually presents before age 2 years in axial regions or extremities with vary rapid growth

Related to congenital mesoblastic nephroma, which has same translocation

40-50% recur but only rarely metastasizes

Survival is 90%+

Case reports: premature newborn with large facial mass (Archives 2003;127:e281)

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: 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: biphasic pattern with fibroblastic and cellular myxoid areashigh power of myxoid areainfiltration of fatinfiltration of muscleareas of variable cellularityspindle cellsplump cells have granular chromatinless cellular tumor which overlaps with infantile fibromatosis, although it almost never metastasizes #1#2leg tumor #1#2#3fig 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  

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; also trisomy 8, 11, 17 and 20

Molecular images: ideogram of fusion transcript and FISH

DD: (none have t(12;15) - adult type fibrosarcoma (usually age 10+), infantile fibromatosis, myofibromatosis

 

Fibrous hamartoma of infancy - Soft Tissue Tumor chapter

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Definition: poorly circumscribed proliferation of immature spindle cells in organoid pattern with fat and dense fibrocollagenous tissue

Rare; usually age 2 years or less (25% discovered at birth), does not occur after puberty, 2/3 male

Solitary, rapidly growing, freely movable mass of subcutis or dermis

Sites: axilla, shoulder and inguinal region (J Urol 1994;152:990); not hands and feet

Case reports: 11 month old boy with thigh mass (The Internet Journal of Dermatology 2001;1:2), 6 month old girl with arm mass, multiple nodules with overlying hypertrichosis (J Dermatol 2006;33:427), recurrent tumor (Pediatr Surg Int 2005;21:119)

Treatment: excision, need not be radical 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; no/scant mitotic figures; overlying epidermis usually has eccrine changes, including hyperplasia, duct dilation, intraluminal papillary formations and squamous syringometaplasia (J Cutan Pathol 2007;34:39)

Cytology: adipose tissue fragments, clusters of fibroblastic cells, myxoid and collagenous matrix (Diagn Cytopathol 2003;28:272)

Micro images: triphasic pattern of fibrous spindle cells delimiting islands of mature fat and primitive spindle cellsprimitive spindle cells may infiltrate fatprimitive spindle cells and fibrous spindle cells are bland and uniform with no/rare mitotic figuresthree cell types are present #1#2#3various images #1#2collagenous tissue and immature mesenchymal cellsH&E and t(2;3) karyotype

Positive stains: vimentin; spindle cells in fibrous trabeculae may be actin+

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), t(2;3) (Archives 2005;129:520)

DD: calcifying aponeurotic fibroma (almost always hands or feet, prominent calcification, no primitive cells within myxoid stroma), myofibroma (prominent hemangiopericytoma-like pattern, usually no fat)

References: Stanford University

 

Focal myositis - Soft Tissue Tumor chapter

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Definition: inflammatory condition of skeletal muscle with degeneration and regeneration, inflammatory cells and fibrosis

Not a WHO diagnosis

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 2007 Dec 21 [Epub ahead of print]), 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), idiopathic focal myositis in pregnancy (Rheumatology (Oxford) 2000;39:211), 16 year old girl with mass in sternocleidomastoid

Gross: pale, ill-defined

Micro: degeneration and regeneration of muscle fibers associated with interstitial inflammation and fibrosis

Micro images: focal interstitial muscle inflammation associated with extensive proliferation of endomysial connective tissuevenlafaxine associated myositis shows regenerating muscle fibers and CD3+ (T) cellsassociated with bCG vaccination #1#2focal perivascular chronic inflammatory infiltrate

Cytology: inflammatory cells, skeletal muscle fibers with degenerative and regenerative changes, fibrous tissue (Acta Cytol 2005;49:653)

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 / Gardner syndrome / APC germline mutation

Uncommon; affects infants, children and teenagers

May be initial diagnostic clue to Gardner 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 of paraspinal area, back, chest, flank, head and neck, extremities

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

Positive stains: CD34, cyclin D1, vimentin, nuclear beta-catenin (64%)

Negative stains: muscle specific actin, smooth muscle actin, desmin, ER, PgR

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)

Median age 45 years; more common in men in eyelid/orbital sites, more common in women elsewhere

Often slow growing painful mass

Case reports: 57 year old woman with eyelid tumor extending into orbit (Can J Ophthalmol 2006;41:216), 50 year old woman with inguinal tumor (Ann Diagn Pathol 2000;4:240)

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

Positive stains: CD34, CD99, vimentin, variable bcl2

Negative stains: CD68, c-kit/CD117, muscle specific actin, S100, desmin

Cytogenetics: rarely t(12;17)(q15;q23) (Cancer Genet Cytogenet 2006;165:157), 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)

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

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)

Micro images: ectatic pseudovascular spaces are lined by giant cells #1#2#3stroma has giant cells and myxoid stromastroma is fibrotic with giant cells but sparse angiectoid spaces in this casemultinucleated stromal giant cells have vesicular nuclei and prominent nucleoli, but smaller spindle cells have indistinct nucleolitrunk tumor #1;  #2#3various images

Cytology images: various images (fig a-c)

 

Giant cell fibroblastoma of soft tissue (continued)

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Positive stains: vimentin, CD34, CD99 (40%, J Cutan Pathol 2008 Jan 14 [Epub ahead of print]), 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 supranumerary ring chromosomes derived from t(17;22)

EM: myofibroblasts or fibroblasts

DD: neurofibroma with ancient change (no ectatic vascular spaces, S100+), liposarcoma, angiosarcoma (older adults in head and neck, cells have enlarged atypical nuclei, mitotic figures present), hemangioma (no giant cells, CD31+)

References: Archives 1996;120:1052, Ann Diagn Pathol 2007;11:81

 

Hemangiopericytoma of soft tissue

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Definition: controversial entity; rare lesions similar to cellular solitary fibrous tumor - may not actually differ from SFT

Diagnosis of exclusion (Histopathology 2006;48:63)

Historically defined as lesions with thin walled, branching vascular pattern, although this is common in many lesions

Probably not a lesion of pericytes, except at sinonasal location

Infantile lesions now called myofibroma / myofibromatosis

See also discussions in these chapters: Bone, Breast, CNS, Heart, Nasal cavity, Thyroid gland

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#2patient 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

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)

 

Hemangiopericytoma of soft tissue (continued)

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Micro images: staghorn vessels are prominentuniform cells around branched, thin-walled, staghorn vesselsvarious images (many from CNS)reticulin stainhemangiopericytoma of CNS is CD34+ (figure 3) / CD31 neg (figure 4)

Cytology images: irregular fragments of tissue, loose cellular aggregates and single cellsuniform 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 cellsmalignant cells radiating from vessels (also gross, Xray, H&E)

Virtual slides: hemangiopericytoma

Positive stains: CD34 (Hum Path 1998;29:636), CD99; reticulin surrounds individual cells

Negative stains: Factor VIII, CD31, CD34, usually actin and desmin (except in sinonasal hemangiopericytoma)

EM: no true pericytic differentiation; has fibroblastic or undifferentiated spindle cell features

DD: solitary fibrous tumor (more prominent collagen, less prominent vessels), monophasic synovial sarcoma, myopericytoma, deep fibrous histiocytoma, mesenchymal chondrosarcoma, endometrial stromal sarcoma (Mod Path 2005;18:40)

 

Lipomatous hemangiopericytoma

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Definition: variant with mature adipose tissue

Also called adipocytic variant of solitary fibrous tumor

First described in 1995 (AJSP 1995;19:748)

Uncommon; 2/3 males, usually thigh, lower extremity and retroperitoneum

Only rarely recurs, does not metastasize

Case reports: Case of the Week #16, mediastinum (J Postgrad Med 2006;52:71), skull base and parapharyngeal space (Otol Neurotol 2006;27:560)

Gross: solid, tan-yellow

Micro: well circumscribed, patternless cellular areas, prominent hemangiopericytoma-like vessels, mature adipose tissue, variable collagen

Cytology: may resemble myxoid liposarcoma (Diagn Cytopathol 2003;29:287)

Micro images: retroperitoneal mass (Case of Week) - image #1#2#3#4#5#6#7#8#9#10mediastinal tumor #1#2

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)

Rare; lesions usually present at birth or in first 2 years; similar lesions in adults; often are multiple

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)

Treatment: excision, but preserve function because recurrences are not destructive and tumors do not metastasize

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: proliferation extends from epidermis to deep dermis or subcutisfibroblastic cells swirl around and engulf an eccrine ductcells are bland and monomorphicinclusions resemble red blood cells

Positive stains: inclusions - trichrome (stain red), PTAH, variable staining for actins; spindle cells - vimentin, muscle actins (tram track pattern)

Negative stains: inclusions - PAS

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)

DD: 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)

References: Stanford University

 

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

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: anterior abdominal wall (Surg Today 2007;37:352), mesenteric tumor (World J Gastroenterol 2007;13:3645), retroperitoneal tumor (World J Surg Oncol 2005;3:66), t(1;2)(q21; p23) with unusual features (Archives 2006;130:1042), bone marrow involvement (Archives 2003 Jul;127:865)

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

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Micro images: typical appearance of spindled myofibroblastic cells and inflammatory infiltrate #1#2#3#4#5#6inflammation obscures the underlying myofibroblastic proliferationspindle cells are evident at high powertumor with more fibrous stromavarious imagesretroperitoneal tumor #1#2#3#4peritoneal tumor with bone marrow involvementH&E and ALK1H&E, ALK1, p80ALK1 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 Apr 7 [Epub ahead of print]), 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 laminae

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) schematict(2;5) karyotypeALK 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 karyotypeFISH for ALK

DD: calcifying fibrous pseudotumor (Mod Path 2001;14:784), nodular fasciitis (smaller size, older patients, less inflammation)

 

Ischemic fasciitis - Soft Tissue Tumor chapter

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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)

Occurs primarily in immobilized and elderly patients due to chronic pressure and impaired circulation

Most common sites are pressure points on shoulder, chest wall and sacrococcygeal region

Rarely occurs in young adults with physical disabilities: 25 year old man with melorheostosis (rare progressive disease of hyperostosis)- Path Int 1998;48:160, 20 year old with vulvovaginal lesion (Int J Gynecol Pathol 2004;23:65)

Case reports: Case of Week #64, Archives 2004;128:e139, 45 year old woman with post-mastectomy axillary mass (The Internet Journal of Pathology 2008;7:1)

Treatment: local excision is curative, although recurrences may occur 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); may have frequent mitotic activity, but no atypical mitotic figures; fibrin thrombi are common within peripheral vessels, which may show fibrinoid necrosis and recanalization; may have multivacuolated macrophages, but no lipoblasts; no primary vasculitis or myositis

Micro images: cellular, fibrin-rich proliferation centered on subcutaneous fibrous septum and extending into adjacent fathyalinized focus with large ganglion-like cells, suggestive of proliferative fasciitisfibrin is adjacent to foci of ganglion-like cells in collagenous stromacentral area of ischemic fasciitis filled with fibrin and surrounded by proliferating vascular fibrous tissuefibrinoid necrosis with few viable cellsspindle cells with large nuclei with prominent nucleoli resembling proliferative fasciitiscapillaries lined by plump endothelial cells and surrounded by large fibroblasts/myofibroblasts enmeshed in a loose collagenous stroma (figure 5)central area of ischemic fasciitis filled with fibrin and surrounded by proliferating vascular fibrous tissue (figure 4)post-mastectomy axillary mass-various images

hip mass in 55 year old bedridden man - image #1#2#3#4#5#6

 

Ischemic fasciitis - Soft Tissue Tumor chapter (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

Negative stains: keratin, desmin, S100

DD: epithelioid sarcoma (more cellular with central necrosis, but typically occurs in young adults on the distal extremities, composed of cells with prominent eosinophilic cytoplasm that are keratin positive, atypical mitotic figures), myxoid liposarcoma (prominent plexiform vasculature and lipoblasts), myxofibrosarcoma (marked atypia, but no smudgy chromatin or fibrin thrombi; lacks zonation), proliferative fasciitis (ganglion cells show less atypia)

References: Mod Path 1993;6:69, Stanford University

 

Juvenile hyaline fibromatosis of soft tissue

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Definition: 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)

Very rare, associated with consanguineous parents                                                                

Due to mutations in capillary morphogenesis protein 2 (Am J Hum Genet 2003;73:791, Am J Hum Genet 2003;73:957)

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 nodulesnodules on pinna of earlarge ulcerated nodules on backgingival hyperplasia

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

Cytology: benign spindle cells with background eosinophilic ground substance (Acta Cytol 2007;51:624)

Micro images: amorphous hyaline matrix in dermis with fibroblastsfibrous dermis with homogenous eosinophilic matrixeosinophilic hyaline matrixchondroid-like cells due to cytoplasmic retraction

Positive stains: PAS (diastase resistant), vimentin

Negative stains: muscle actin, S100

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: fibroblastic cells in septa and skeletal muscle mixed with adipose tissue

Also called infantile fibromatosis of nondesmoid type

First described in 2000 (AJSP 2000;24:1491)

Rare childhood tumor (first surgery usually at age 1), 2/3 male, often of distal extremities

Associated with macrodactyly of foot (Foot Ankle 1991;12:40)

Recurs locally, no metastases

Case reports: forearm of 10 month old boy (Ups J Med Sci 2005;110:259), foot of male infant (Skeletal Radiol 2008 Feb 16 [Epub ahead of print])

Gross: white-tan or yellow, 1-3 cm

Micro: bland fibroblasts involving septa of adipose tissue mixed with adipose tissue, may have minute small vacuolated cells between fibroblasts and adipose; no atypia, no/rare mitotic figures

Micro images: various images (figure 5)

Positive stains: spindle cells - CD34, CD99, smooth muscle actin; variable bcl2, S100, EMA, muscle specific actin

Negative stains: desmin, keratin

Molecular/cytogenetics: three-way t(4;9;6) translocation in a 5-year-old boy (rare, Cancer Genet Cytogenet 2007;179:136)

DD: fibrous hamartoma of infancy (has primitive oval cell component), fibromatosis (solid fibrous growth, no fat)

References: Stanford University

 

Low grade fibromyxoid sarcoma of soft tissue

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Definition: variant of fibrosarcoma with fibrous and myxoid areas, whorled growth pattern, low cellularity, bland fibroblastic cells and curvilinear vessels

Also called fibrosarcoma-low grade fibromyxoid type, Evan’s tumor, hyalinizing spindle cell tumor with giant rosettes

Rare, first described by Evans in 1987 (AJCP 1987;88:615)

Prolonged preclinical stage

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)

Local recurrence (9%) and metastases (6%) are less common in prospective studies due to more aggressive surgery

Includes hyalinizing spindle cell tumor with giant rosettes (similar histology and translocation but with collagen-containing rosettes-AJSP 2003;27:1229); may be related to some cases of sclerosing epithelioid fibrosarcoma with same translocation (AJSP 2007;31:1387)

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)

Fibrosarcoma-low grade fibroblastic type-no myxoid component, a diagnosis of exclusion (Histopathology 2006;49:152)

Case reports: epicardial surface of heart (Hum Path 2008;39:623), falciform ligament (BMC Surg 2003;3:7)

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#3well circumscribed with myxoid cut surface and cystic changewell circumscribed tumor of legwell circumscribed tumor with giant rosettes

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

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)

 

Low grade fibromyxoid sarcoma of soft tissue (continued)

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Micro images: characteristic features include fibrous and myxoid areas, a swirling whorled growth pattern, low to moderate cellularity and bland cells with minimal nuclear pleomorphism #1#2the swirling growth pattern is storiform #1#2bland spindle cells in fibromyxoid stromathere is a relatively linear cell arrangement in this area, but other areas have the characteristic swirling and whorled patternwhirled fibroblastic cells in a myxoid background with prominent capillaries #1#2rosettes in spindled stromacells forming rosettes are PGP 9.5+, Factor XIII negativevarious images #1#2lung metastasis is more cellular but still blandvimentin+staining of vessels but not tumor by CD34, smooth muscle actin

Cytology images: ovoid to spindle cells with tapered cytoplasm and bland nuclei in myxoid backgroundhypercellular three dimensional tissue fragment in myxoid backgroundbland 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 granuleselongated 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 Mar 28 [Epub ahead of print]) or FISH (AJSP 2008;32:8)

Molecular/cytogenetic images: complex karyotype includes t(7;16)

DD: myxofibrosarcoma (more myxoid and less fibrous, more nuclear pleomorphism and hyperchromatism, more developed vascular network, Histopathology 2004;45:29), desmoid fibromatosis (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+)

References: Stanford University

 

Low grade myofibroblastic sarcoma of soft tissue

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Definition: rare tumor of malignant myofibroblasts

Also called myofibrosarcoma

Deep intramuscular tumors of head and neck (tongue and oral cavity) and extremities, rarely abdominopelvic (J Clin Pathol 2008;61:301)

Commonly recurs, only rarely metastasizes

Diagnostic criteria: predominantly myofibroblasts, distinct from fibrosarcoma and MFH-pleomorphic

Gross: firm, pale, fibrous cut surface, ill defined margins

Micro: diffusely infiltrative pattern, 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)

Virtual slides: tumor of buttocks #1#2

Positive stains: at least one myogenic marker (desmin, alpha smooth muscle actin, muscle specific actin, calponin)

Negative stains: S100, EMA, h-caldesmon, ALK

EM: myofibroblastic features of indented and clefted nuclei, variable rough endoplasmic reticulum, discontinuous basal lamina

DD: fibromatosis, myofibromatosis, nodular fasciitis (not infiltrative, not deep), leiomyosarcoma (alternating fascicular pattern), solitary fibrous tumor, fibrosarcoma, inflammatory myofibroblastic tumor (more heterogeneous, less cellular, less hyperchromasia, less infiltrative, Hum Path 2008 Apr 7 [Epub ahead of print])

References: AJSP 1998;22:1228

 

Mammary type myofibroblastoma of soft tissue

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Definition: benign myofibroblastic lesion with mast cells in hyalinized collagenous stroma and adipose tissue, identical to breast lesion

See also Breast-nonmalignant, Lymph nodes-not lymphoma chapters

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)

Appears to differ from superficial cervicovaginal myofibroblastoma

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 with poorly defined borders, oval to tapered nuclei with fine chromatin and small nucleoli; stroma has haphazard bands of collagen; may have epithelioid features, focal nuclear atypia with enlarged nuclei or multinucleation, small vessels with perivascular lymphocytes, prominent adipose tissue, mitotic figures (but no atypical forms)

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)

Micro images (breast): circumscribed borderfascicles of spindle cells separated by dense collagen bundles #1#2#3epithelioid type #1#2#3CD34+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)

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)

DD: angiofibroma (thicker, hyalinized vessels), lipomatous hemangiopericytoma (larger ectatic vessels)

References: AJSP 2001;25:1022, Stanford University

 

Myofibroma / myofibromatosis of soft tissue

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Definition: smooth muscle nodules that alternate with fibroblastic foci and 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

60% congenital, most before 2 years, but mean age 22 years in oral soft tissues (J Oral Pathol Med 2007;36:304)

Most common fibrous tumor of infancy

May regress spontaneously; orbital lesions may cause bony destruction (Ophthal Plast Reconstr Surg 2006;22:292); visceral lesions, especially lung, may cause morbidity and rarely death

Sites: 50% of myofibromas in head and neck, trunk, extremities; 15% of myofibromatosis in deep soft tissues and viscera

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: 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: solitary cutaneous lesion features zones of fibrous tissue with bundles of myofibroblasts and prominent thin-walled vesselshigh power shows interface with normal collagenbiphasic with immature cells in hemangiopericytoma pattern and bundles of myofibroblastic cellscentral hemangiopericytic area is rimmed by hyalinized myofibroblastic areajunction between myofibroblastic cells and immature spindled cellsmyofibroblastic spindle cells and immature cells are arranged in hemangiopericytic patterndermal aggregates of plump spindle cells arranged in fasciclesarm tumor #1#2poorly circumscribed nodular tumorfascicles of spindle cells resemble leiomyomawell circumscribed tumorcellular and keloid-like areas #1#2#3#4infant lesion #1#2#3dermis is infiltrated by fascicles of smooth muscle-like cellstrichrome stain (fig B) highlights prominent collagen not seen on H&E (fig A)various imagesintracranial tumor

48 year old woman with nodules on scalp - myofibroblasts around capillaries and sclerosing areas #1#2#3tumor infiltrates skeletal musclehemangiopericytoma-like vascular patternfascicles of myofibroblastic cells with oval nucleismooth muscle actin+vessels are CD34+desmin negative (vessel is positive)

Positive stains: myofibroblasts - vimentin, smooth muscle actin, HHF45; 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

DD: smooth muscle tumor (single lesion, no zonation), 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 and fibro-osseous pseudotumor of digits - Soft Tissue Tumor chapter

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Definition: focal intramuscular reparative lesion composed of cellular fibrous tissue and metaplastic bone

See also Bone chapter

Usually physically active young males with rapid growth of mass; 60-75% have history of trauma in prior 4-6 weeks

Also called benign fibro-osseous lesion (better term since may not involve muscle or inflammation)

In subcutis, called panniculitis ossificans; in fascia or tendons, called fasciitis ossificans

Fibrodysplasia ossificans progressiva (myositis ossificans progressiva) is similar but inherited, occurs without injury

Fibro-osseous pseudotumor of digits is similar, but usually older age, bone is randomly distributed throughout the lesion, less likely to contain fibrinous material (Int J Surg Pathol 2003;11:187)

Recommended to review Xrays before making diagnosis of myositis ossificans

Sites: upper extremity flexors, quadriceps, thigh adductors, gluteal muscles, soft tissues of hand

Xray: periosteal reaction with eggshell type calcification at periphery 3-6 weeks after injury

Case reports: 9 year old boy with thigh pain, autopsy findings due to abuse (Leg Med (Tokyo) 2008 Apr 26 [Epub ahead of print])

Treatment: excision; rarely recurs if incompletely excised; may regress completely without treatment

Gross: well circumscribed, soft center, gritty periphery, usually 3-5 cm

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) have inner 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 present

Micro images: mature bone at periphery, fibrous tissue resembling nodular fasciitis at center, osteoid in between #1#2fibroblastic and myofibroblastic cells in center of lesion resemble nodular fasciitis, with nuclear uniformity #1#2osteoid is broader than in osteosarcomaosteoblasts have large nuclei with prominent nucleoli, but clues to benign nature of lesion are reactive fibrous areasosteoid deposition is uniform, and nuclei are enlarged but not pleomorphicosteoid undergoing mineralizationimage #1#2#3various images (9 year old boy with thigh lesion)central fibroblasts/myofibroblasts merge with woven bone at periphery, note the prominent osteoblastic rimming (figure 8)

 

Myositis ossificans and fibro-osseous pseudotumor of digits - Soft Tissue Tumor chapter (continued)

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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)

DD: extraosseous osteosarcoma (rare, age 40+ years, different radiologic findings, malignant cytology, atypical mitotic figures, no or reverse zonation), juxtacortical osteosarcoma (no zonation), osseous muscle metastasis (AJR Am J Roentgenol 2001;176:1165)

 

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

See also Heart chapter

Usually ages 60-69 years in skeletal muscle of extremities, rarely cutaneous (Am J Dermatopathol 2003;25:281)

Lesions in retroperitoneum may actually represent dedifferentiated liposarcoma

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), 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), low grade tumor with invasion into skeletal muscle (J Dermatol 2007;34:561), progression from myxoid pleomorphic fibroma (Australas J Dermatol 2003;44:287)

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 tumorlower extremity tumorsubcutaneous tumor #1#2

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 stroma around vessels, incomplete fibrous septa, myxoid stroma (at least 10% of tumor) and infiltrating immature dendritic cells (AJCP 2003;119:540); 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

 

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)

Micro images: myxoid areas may have pleomorphic cells and variable cellularitymoderate cellularity with pleomorphic cellsgrade I tumor has the minimal pleomorphism required for diagnosis of MFH #1#2#3 - 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+grade II tumor #1#2-myxoid areas alternate with solid area that is not as pleomorphic as usual MFHgrade III tumor with markedly pleomorphic areas (left) and myxoid areas (right), myxoid areas may lack pleomorphic cellstypical cellular areas with occasional giant cells #1#2various images

resembling ischemic or proliferative fasciitis - myxoid stroma with low density of ganglion-like cellsbizarre cells are strongly suggestive of malignancy not a reactive condition

not myxoid MFH due to lack of pleomorphism - lesions are called juxta-articular myxoma, cellular intramuscular myxoma or myxoid lesion with recurrent potential, lesions may recur but do not metastasize #1#2

Virtual slides: tumor

Positive stains: vimentin, acid mucins, CD34 (38%, J Clin Pathol 2003;56:666),

Negative stains: fat stains (positive in lipoblasts in cytoplasmic vacuoles), 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+

DD: nodular fasciitis (no atypical cells, no atypical mitotic figures); myxoma (no atypia, less prominent vasculature, few mitotic figures), myxoid liposarcoma (lipoblasts, no bizarre cells, clear matrix, plexiform vasculature), metastatic carcinoma from kidney or adrenal gland

 

Myxoinflammatory fibroblastic sarcoma of soft tissue

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Definition: rare low grade sarcoma with myxoid stroma, inflammation and virocyte-like cells that primarily involves hands and feet

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)

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: 29 year old man with finger mass (Archives 2005;129:1343), 30 year old man with elbow mass (Archives 2006;130:e35), 13 year old girl with back lesion (Int J Dermatol 2008;47:68)

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

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)

Micro images: myxoid nodule has characteristic ganglion-type cells with prominent nucleolifibrous region with inflammatory cellsmyxoid region with inflammatory cellsacute inflammatory cells, larger cells with vesicular nuclei and multinucleated giant cellnodules of tumor cells infiltrating along ulnar nervespindle cells, ganglion-like cells, Reed-Sternberg-like cells and lymphocytes surrounding tendon sheathsspindle cells with prominent nucleoli in myxoid stromavarious imagesfigure 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 eosinophilsfig 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

Virtual slides: tumor nodules #1#2  

 

Myxoinflammatory fibroblastic sarcoma of soft tissue (continued)

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Positive stains: vimentin, usually CD34, CD163, 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)

DD: Hodgkin’s lymphoma, 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 - Soft Tissue Tumor chapter

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Definition: highly cellular, reactive lesion of fibroblasts and myofibroblasts in myxoid stroma with vascular proliferation, lymphocytes and extravasated red blood cells, commonly in young adults in 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, usually subcutaneous

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)

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: Case of the Week #65, intramuscular tumor (The Internet Journal of Plastic Surgery 2007;3(1))

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 lesionintraoperative 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; 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

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)

 

Nodular fasciitis - Soft Tissue Tumor chapter (continued)

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Micro images: subcutaneous tumor is partially circumscribed nodule infiltrating focally along fascial planesfocal infiltration into fat, with evenly distributed granulation tissue-like vessels throughout the lesiongently curving C and S shaped fascicles of myofibroblastic cells exhibit a characteristic “torn Kleenex” patternfocal storiform pattern is suggestive of fibrous histiocytomaplump spindled myofibroblastic cells and extravasated red blood cellsmitotic figures but no abnormal formsfocally more collagenous stroma with skeletal muscle involvement #1#2 with cystic degeneration#3osteoclastic giant cells are present in less collagenous areas, suggesting a variant of MFHhyalinized variant resembles keloid or fibromatosisvague zonation pattern with bone formation in lower rightisland of new bone surrounded by myofibroblastic cellsleg lesion #1#2#3#4#5-resembles fibroblast culturefigures 10A/B: H&E and CD68

tumor of wrist - image #1#2#3#4#5#6

Virtual slides: superficial chest lesion

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

DD: 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;  myositis ossificans (early);  myxofibrosarcoma (large, regularly arborizing vessels, atypia and pleomorphism);  other sarcoma (atypia is prominent);  reactive spindle cell nodules (post-biopsy) 

References: Stanford University

 

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

May be related to birth trauma

Grows quickly like nodular fasciitis, but same benign behavior (Cancer 1980;45:401)

Xray: lytic defect of skull with sclerotic rim

Case reports: 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

 

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: large focus of nodular fasciitis protrudes into vascular spacecellular proliferation has edematous background characteristic of nodular fasciitisintravascular proliferation of spindle cells

 

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

References: AJSP 1992;16:448

 

Nuchal fibrocartilaginous pseudotumor of soft tissue

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Definition: fibrocartilaginous metaplasia of nuchal ligament overlying lower cervical vertebrae

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: 30 year old woman with neck trauma (J Neurosurg Sci 2003;47:173), 10 year old girl post neck trauma (Archives 2000;124:1217)

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

Rare benign lesion of dermis and subcutis in posterior neck, upper back or other regions, more common in men, mean 40 years (Cancer 1999;85:156)

Associated with diabetes in 44%

Histologically identical to Gardner fibroma

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: strands of acellular collagen mixed with fatlesion is very hypocellular, differentiating it from fibromatosispaucicellular with haphazard collagen fiberscentral areas have collagen fibers organized in several planes of section, with criss crossing bundles often forming lobulessmall entrapped islands of adipose are commonskeletal muscle involvementoften contains small nerves with haphazardly arranged fascicles, resembling traumatic neuromaoften contains delicate web of elastic fibers running parallel to collagen fibers

Positive stains: vimentin, CD34, CD99

Negative stains: actin, desmin

DD: fibrolipoma (circumscribed, different location), fibromatosis (deep soft tissue, not back of neck, more cellular), solitary fibrous tumor (patternless pattern, more cellular)

References: AJSP 1995;19:313, Stanford University

 

Ossifying fibromyxoid tumor of soft tissue

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Definition: uncommon fibromyxoid soft tissue tumor of uncertain lineage, usually with peripheral bone present

Not a WHO diagnosis

First described in 1989 (AJSP 1989;13:817), <200 cases reported

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)

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

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)

Micro images: various images #1#2

Positive stains: vimentin, S100 (60%), Leu7/CD57 (focal), GFAP (focal), desmin (13%)

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)

References: Stanford University

 

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

First described in 1989 (AJSP 1989;13:107)

Usually trunk, extremity or head (Clin Exp Dermatol 1998;23:22)

Case reports: 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: large pleomorphic cells separated by collagenatypical cells have smudged chromatin, mitoses are absent/rare, compare to sarcomas with abnormal (but not degenerative) nuclei and frequent mitotic figures, some atypicalanal skin #1#2various images #1#2

Positive stains: vimentin, actin, CD34

Negative stains: S100

DD: atypical fibrous histiocytoma (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)

 

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

Affects children (see below) or adults (mean age 50 years) in trunk or proximal extremities

Rapid growth but benign behavior

Case reports: with rapid involution of mass (Skeletal Radiol 2004;33:300)

Treatment: excision

Gross: usually 3 cm or less, poorly circumscribed mass of deep tissue 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

Cytology: cellular smear with spindle cells and large cells with abundant cytoplasm, one to two eccentric nuclei and macronucleoli (Acta Cytol 1985;29:882)

Micro images: prominent hemorrhage and vague centering of cellular proliferation on interlobar septa of subcutaneous fatmixture of ganglion-like cells, myofibroblasts and inflammatory cells #1#2van Gieson stainAlcian blue-PAS

ganglion-like cells - cells have abundant amphophilic cytoplasm and prominent nucleoli #1#2 (figure 2)#3#4mixed with inflammatory cells within myxohyaline matrixcondensed around thin walled vascular channel

Positive stains: spindle cells-smooth muscle actin, muscle specific actin; ganglion-like cells-vimentin, actin

Negative stains: keratin, S100, desmin

DD: 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: 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

References: AJSP 1992;16:364

 

Proliferative myositis - Soft Tissue Tumor chapter

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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

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

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)

Micro images: characteristic checkerboard pattern is produced by reactive proliferation expanding spaces between muscle bundles and individual muscle fibers #1#2with metaplastic bone, resembling myositis ossificans

large ganglion like cells - with crowding and molding resembling carcinomacells have abundant amphophilic cytoplasm and prominent nucleoli #1#2#3#4 (figure 3)  

spindle cell sarcoma resembling proliferative fasciitis - checkerboard pattern produced by infiltration of tumor cells between muscle bundles without myocyte necrosiscellular proliferation of atypical spindle cells differs from bland spindle cells of proliferative myositis

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)

DD: 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)

References: Stanford University

 

Proliferative peribursitis - Soft Tissue Tumor chapter

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Definition: angiomyxoid tumor-like mass near joints and ligaments

Not a WHO diagnosis

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)

DD: myxoma, 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

First described in 1995 (AJSP 1995;19:979)

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: Case of Week #3, cecal tumor in Chernobyl cleanup worker (Archives 2007;131:1825), sacral tumor (J Clin Path 2004;57:90)

Gross: mean 9 cm, range 4-22 cm, appears circumscribed but is not, and may invade bone; firm, gray-white cut surface, usually no necrosis

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 masscecal tumorsacral tumor

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

DD: 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, poorly differentiated carcinoma

References: Histopathology 1998;33:354, Stanford University

 

Solitary fibrous tumor (extrapleural) - Soft Tissue Tumor chapter

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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 giant cell angiofibroma, hemangiopericytoma

Usually adults (median age 50 years), 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, positive margins, malignant histology (Cancer 2002;94:1057), although histology has less significance in retroperitoneum (Urol Oncol 2008;26:254)

Case reports: 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 necrosistumor of omentum #1#2

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 nuclei; often myxoid change, 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) - Soft Tissue Tumor chapter (continued)

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Micro images: patternless pattern and collagenous stromapatternless and myxoid patterns with hemangiopericytoma-like vesselsmoderately cellular fibroblastic appearance #1#2parallel arrays of collagen are separated by fibroblastic nucleicellular variant has cells with scant cytoplasm and uniform spindled nuclei, note the thin bands of intercellular collagentumors without (fig A/B) and with (fig C/D) malignant componentscomparison of immunostains with GISTear-H&E, CD34, CD99 and bcl2larynx-H&E, CD34, CD99thigh-H&E, CD34, bcl2H&E, CD34, beta-catenin   

Virtual slides: tumormalignant 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

DD: 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

2/3 male, mean age 43 years, range 14-72 years

May recur, may develop persistent/progressive disease after partial excision

Case reports: tumor of big toe (J Eur Acad Dermatol Venereol 2008;22:255)

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 toetumor (fig C/D) compared to DFSP (fig A/B)H&E, CD10 and nestin

Positive stains: CD34, CD99, Alcian blue (mucinous material, Dermatology 2002;205:285), variable EMA

Negative stains: actin, desmin, keratin, HMB45, S100

DD: fibrous histiocytoma (lacks abundant myxoid matrix, more storiform, 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 (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-)

 

 

Fibrohistiocytic tumors - Soft Tissue Tumor chapter

General

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Composed of cells with morphologic features of fibroblasts and histiocytes

Cells are actually fibroblasts, myofibroblasts and primitive mesenchymal cells (not histiocytes), but may exhibit phagocytic properties by EM or immunohistochemical studies

 

Atypical fibrous histiocytoma - Soft Tissue Tumor chapter

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Definition: cellular, circumscribed dermal lesion of spindled fibroblasts, myofibroblasts, histiocyte-like cells and often giant cells with marked nuclear pleomorphism and mitotic figures (often atypical), but no tumor cell necrosis and no vascular invasion

Rare variant of cutaneous fibrous histiocytoma, also called pseudosarcomatous fibrous histiocytoma, dermatofibroma with monster cells

Part of WHO classification for skin tumors, not soft tissue tumors

First described in 1983 (J Cutan Pathol 1983;10:327)

May be misdiagnosed as sarcoma (Histopathology 1990;17:167)

Median age 38 years (range 5-79 years), no gender preference

Solitary lesions usually arise on extremities or trunk (Am J Dermatopathol 1986;8:467); also head and neck, vulva

Occasional local recurrence (14%) or distant metastasis (AJSP 2002;26:35)

Case reports: 25 year old woman with recurrent leg lesion (Eur J Dermatol 1998;8:122), 62 year old woman with leg lesion (Tokai J Exp Clin Med 2004;29:49), 64 year old woman with 3 cm back lesion (Am J Dermatopathol 2002;24:36), 79 year old woman with leg lesion (Am J Dermatopathol 1997;19:312), 90 year old man with scrotal lesion (Ann Diagn Pathol 2003;7:370)

Treatment: complete excision with negative margins

Gross: median 1.5 cm (0.4 to 8 cm), nodular or polypoid

Micro: involvement of dermis and superficial subcutaneous tissue by pleomorphic, plump, spindle or polyhedral cells with large hyperchromatic, irregular or bizarre nuclei; background of classic fibrous histiocytoma including spindle cells with storiform pattern and entrapped thick collagen bundles, especially at the periphery; variable multinucleated giant cells, often with bizarre nuclei and foamy or hemosiderin-rich cytoplasm; 0-15 mitotic figures/10 HPF, frequently atypical; necrosis occasionally present

Micro images: enlarged cells with hyperchromatic nuclei, but no/rare mitotic figures #1#2#3

Positive stains: vimentin, CD34 (occasionally)

Negative stains: CD68, S100, keratin (MNF116), EMA; <1% positive for MIB1 (Am J Dermatopathol 2004;26:367)

DD: pleomorphic sarcoma, pleomorphic fibroma, atypical fibroxanthoma (sun damaged areas of head and neck in elderly, presents as dome shaped or ulcerated nodule, tumor cells abut epidermis without a grenz zone [relatively normal collagen forming a boundary between normal epidermis and a dermal lesion], also marked actinic elastosis, no classic features of fibrous histiocytoma)

References: Am J Dermatopathol 1987;9:380

 

Atypical fibroxanthoma (AFX) - Soft Tissue Tumor chapter

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Definition: dermal variant of MFH-pleomorphic with low grade behavior

Also called intermediate fibrous histiocytoma

Part of WHO classification for skin tumors, not soft tissue tumors

See also Ear chapter

Rapidly growing dome-shaped or polypoid nodule on sun-damaged areas of head and neck of elderly

Rarely presents as large mass in limb or trunk of younger individuals, or post radiation therapy

May clinically resemble carcinoma

Must exclude tumors with AFX like patterns, other lines of differentiation, significant involvement of subcutis, necrosis, vascular invasion or infiltrative margins

Poor prognostic indicators: history of immunosuppression, recurrence

Case reports: 81 year old woman with lower leg lesion (Dermatology Online Journal 14(1)), 63 year old man with metastatic tumor from eyebrow area to face (Archives 2006;130:735), 81 year old man with widespread peritoneal metastases (AJSP 2006;30:1041)

Treatment: local excision; rarely recurs or metastasizes

Gross: polypoid, ulcerated, usually small

Gross images: irregular polypoid tumorred, beefy, sessile nodule with adjacent sun damaged skin

Micro: bizarre tumor cells in hypercellular, spindly stroma with frequent mitotic figures, many atypical; also smaller fibroblastic, myofibroblastic and histiocyte-like cells with pleomorphism and angulated nuclei; histologically identical to MFH-pleomorphic but centered in dermis; background stroma appears inflammatory or reactive; pushes aside surrounding pilosebaceous units and eccrine glands; typically does not involve epidermis or subcutaneous tissue; no grenz zone; lacks classic features of fibrous histiocytoma (entrapped hyalinized collagen bundles and epidermal hyperplasia); no necrosis, no vascular invasion, no infiltrative margins

variants: clear cell (J Cutan Pathol 2006;33:343), granular cell (Am J Dermatopathol 2007;29:84)

 

Atypical fibroxanthoma (AFX) - Soft Tissue Tumor chapter (continued)

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Micro images: exophytic cellular nodule with ulcerationfascicles of atypical spindle cellstumor is limited to dermis but otherwise resembles MFH-pleomorphic with marked cellularity, prominent pleomorphism, mitotic figures and clumped chromatinmarked cellularity and pleomorphismcharacteristic bizarre cellsspindle variant has less pleomorphismvarious imagesclear cell variantspindle and epithelioid cells with atypiaulcerated tumor #1#2#3#4#5nodular spindle cell tumor #1;  #281 year old woman with lower leg lesionfig A: edge of lesion shows hyperchromatic cells next to elastotic dermis (arrow), fig B/C: atypical spindle cells and histiocytes, atypical mitotic figure (arrow), fig D: alpha-1-antichymotrypsin positivefigure 1: eyebrow primary, figures 2-4: facial metastasis (fig 4 is CD68)CD68Factor XIIIap53

Positive stains: vimentin, CD68, alpha-1-antitrypsin, alpha-1-antichymotrypsin, Factor XIIIa (focal), CD117 (Am J Dermatopathol 2008;30:34), CD99 (73%, AJCP 2002;117:126), CD10 (Australas J Dermatol 2005;46:235), calponin (30%, Virchows Arch 2002;440:404), desmin (30%), smooth muscle actin (30%)

Negative stains: keratin, EMA, S100 (although S100+ Langerhans cells may be present), HMB45 (rarely positive, J Cutan Pathol 2004;31:284), caldesmon

EM: myofibroblasts, fibroblasts and primitive mesenchymal cells

Molecular: diploid

DD: squamous cell carcinoma-spindle cell type; desmoplastic melanoma (may have focal AFX-type features and stain negative for melanocytic markers, Am J Dermatopathol 2007;29:551), atypical fibrous histiocytoma

References: eMedicine

 

Benign fibrous histiocytoma (superficial) - Soft Tissue Tumor chapter

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Definition: storiform pattern of bland spindle cells and foamy histiocytes centered in dermis with possible extension to subcutis, with variable hemosiderin, multinucleated giant cells, chronic inflammatory cells and pseudoepitheliomatous hyperplasia

Also called dermatofibroma (particularly if sclerotic and hypocellular), dermal fibrous histiocytoma

Part of WHO classification for skin tumors, not soft tissue tumors

See also Bone, Eye-Conjunctiva, Eye-Orbit and Heart chapters

Very common benign, indolent tumor of adults, common site is legs of women 20-50 years old

May be associated with trauma

Line of differentiation is uncertain

Case reports: balloon cell fibrous histiocytoma (Am J Dermatopathol 2007;29:197)

Treatment: excision; local recurrence rare even with involved margins; rarely is locally aggressive or metastatic (more common for facial lesions, extension into subcutis or cellular and mitotically active)

Gross: tan-brown, firm, mobile, painless papule < 2 cm in dermis; size varies slightly with time, may dimple upon lateral compression Gross images: inward dimpling is due to tumor binding to subcutis (arrow)

Micro: well defined but non-encapsulated; storiform pattern of spindled and bland fibroblasts and histiocyte-like cells in mid-dermis and subcutaneous tissue with infiltrative margins but sparing epidermis; spindle cells have scant cytoplasm, thin elongated nuclei with pointed ends; nuclei almost touch each other unlike smooth muscle lesions; also foamy histiocytes with variable hemosiderin, some multinucleated giant cells, branching vessels, chronic inflammatory cells, pseudoepitheliomatous hyperplasia and epidermal hyperpigmentation; may be cellular but scant mitotic figures

Micro images: tumor is often more basophilic than surrounding dermisbasophilia is due to increased cellularitysharp border between tumor and subcutissome fat may be entrapped at edge of lesion (must differentiate from infiltration of DFSP)tumor cells are mostly fibrous in this focustumor cells in this focus are composed of histiocyte-like cells and foam cellsrandomly arranged foam cells, fibroblasts and histiocyte-like cells, note that foam cells are somewhat specific for this lesionfoam cells with vacuolated cytoplasmfoam cells vary from none (top), mixed (middle) to predominating (bottom)fibroblastic cells with vacuolated cytoplasm in collagenous stromatumor with hyperplastic epithelium #1#2less common finding of predominantly foam cells and cholesterol cleftshyperplastic epidermis and sclerotic stroma #1#2#3epithelial hyperplasia-left side shows squamous/basaloid differentiation, right side shows follicular differentiationspindle cell nodulepaucicellular dermal tumorspindle cells in dense collagenous stromacellularity changes over time from subtle increase in fibroblasts (fig A) to cellular tumor (fig B/C) to sclerotic lesion (fig D-right side)vulvar tumor has uniform spindle cells confined to dermislow Ki-67 compared to DFSP and AFX

 

Benign fibrous histiocytoma (superficial) - Soft Tissue Tumor chapter (continued)

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Positive stains: vimentin, Factor XIIIa; also tenascin at dermoepidermal junction (Hum Path 2001;32:50), calponin (65%); variable actin, desmin and myosin

Negative stains: CD68, CD34, bcl2; Ki-67 < 10% (Archives 2006;130:831)

Molecular/cytogenetics: often clonal

DD: Kaposi’s sarcoma, dermatofibrosarcoma protuberans, leiomyoma or leiomyosarcoma (confusion based primarily on immunostaining of fibrous histiocytomas), malignant fibrous histiocytoma, atypical fibroxanthoma, Rosai-Dorman disease

References: AJSP 2002;26:35

 

Variants of benign fibrous histiocytoma

Aneurysmal variant of benign fibrous histiocytoma - Soft Tissue Tumor chapter

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Definition: rare variant with dermal spindle cells and lakes of blood, but no endothelium

First described in 1981 (Cancer 1981;47:2053)

Early lesion also called hemosiderin variant

Similar to sclerosing hemangioma variant (which has more prominent capillaries), but differs from lung lesion called sclerosing hemangioma

Usually extremities or trunk; often rapid growth and pain (J Clin Pathol 1996;49:313)

Tends to recur after excision; rarely metastasizes

Case reports: 48 year old woman with recurrent tumor (J Clin Pathol 2004;57:312), abdominal lesion (Dermatology 2007;214:82)

Gross: blue, black or dark red; cystic

Gross images: nodule resembles melanoma

Micro: storiform pattern of fibrohistiocytic cells (as in classic fibrous histiocytoma), also large cystic spaces filled with blood, but without an endothelial lining, often bizarre cells present; may have hemangiopericytoma-like vascular pattern; may have up to 10 MF/10 HPF

Micro images: non-endothelial lined clefts or lakes containing blood #1#2fibrohistiocytic cellular proliferation with numerous blood filled cysts #1#2cysts lack an endothelial liningcysts have a squamous lining #1 (unusual finding)#2hemangiopericytoma-like pattern #1#2large amounts of hemosiderinhemosiderin plus marked sclerosis

Positive stains: vimentin, Factor XIIIa (in non cystic areas, J Dermatol 2002;29:744), NKI-C3 (60%), smooth muscle actin (45%)

Negative stains: CD31, CD34

EM: hemosiderin containing histiocyte-like cells, fibroblast-like cells and intermediate cells; no prominent proliferation of endothelial cells (Am J Dermatopathol 1995;17:179)

Cytogenetics: single case report of recurrent tumor with t(12;19) (Cancer Genet Cytogenet 2006;164:155)

DD: Kaposi’s sarcoma, angiosarcoma (APMIS 2006;114:744), melanoma

References: Histopathology 1995;26:323

 

Angiomatoid fibrous histiocytoma - Soft Tissue Tumor chapter

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Definition: uncommon variant with thick pseudocapsule, marked chronic inflammatory infiltrate and cystic areas of hemorrhage

First described in 1979 (Cancer 1979;44:2147)

Not a WHO diagnosis

Formerly called angiomatoid malignant fibrous histiocytoma

Teens/young adults, often on extremities in areas of lymphoid tissue (popliteal fossa, decubital fossa) or neck

Often fever, malaise, anorexia or paraproteinemia

Considered to have low to intermediate malignant potential; may recur locally (10%), distant metastases are rare (1%)

May not actually be fibrohistiocytic - Rosai believes origin is vessel related myoid cells with inflammatory features

Case reports: mediastinal tumor (Ann Thorac Surg 2001;72:283), pleomorphic tumor with minimal angiomatoid or lymphoid features (J Cutan Pathol 2008 Apr 16 [Epub ahead of print]), cystic structures of sweat duct origin (Pathol Int 2007;57:513), 25 year old man with t(12;22) and intracerebral primary (AJSP 2008;32:478)

Gross: circumscribed, multinodular or multicystic hemorrhagic mass; median 2 cm, usually subcutaneous

Micro: thick fibrous pseudocapsule surrounds nodules of monomorphic bland spindle to ovoid eosinophilic cells, often highly cellular with hemorrhagic cyst like spaces, large aggregates of chronic inflammatory cells at edge of tumor in lymphoid follicles; may have moderate pleomorphism and mitotic activity

Cytology: histiocyte-like cells in clusters or dispersed, also eosinophilic mesenchymal fragments in bloody background with lymphocytes; tumor cells have moderate pleomorphism with abundant fragile cytoplasm and prominent nucleoli (Diagn Cytopathol 2005;33:116)

Micro images: tumor with heavy chronic inflammatory infiltrate resembles a lymph node - consider angiomatoid fibrous histiocytoma in an apparent lymph node that is out of place in soft tissuechronic inflammatory cells are accompanied by nodules of cells with round/oval nuclei that surround hemorrhagic cystic spaces #1#2cells surrounding cystic spaces are uniform with round/oval nucleisome tumors have moderate pleomorphismmediastinal tumorvarious images #1#2#3

Virtual slides: angiomatoid fibrous histiocytoma

Positive stains: CD68, desmin (40-50%), EMA (40%), CD99 (45%), actin (14%)

Negative stains: Factor VIII, CD34, keratin

Cytogenetics/molecular: usually t(12:16)(q13:p11) [ATF1-FUS] or t(12:22)(q13:q12) [ATF1-EWSR1], which is also present in GI clear cell sarcoma; also EWSR1-CREB1 (Genes Chromosomes Cancer 2007;46:1051, Clin Cancer Res 2007;13:7322

Cytogenetics/molecular images: t(12;16) karyotypediagram

DD: aneursymal variant of benign fibrous histiocytoma (no thick pseudocapsule, no inflammatory cells, no significant pleomorphism)

References: Archives 2008;132:273, Hum Path 1999;30:1336, Atlas of Genetics and Cytogenetics

 

Atypical fibrous histiocytoma - Soft Tissue Tumor chapter

See above

 

Cellular variant of benign fibrous histiocytoma - Soft Tissue Tumor chapter

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Definition: more cellular than usual fibrous histiocytoma, elongated cells are arranged in storiform pattern or fascicles

5% of dermal fibrous histiocytomas

Young or middle-aged adults, 60% men

Extremities or head and neck are most common

20% recur; rare metastases (AJSP 1996;20:1361)

Gross: up to 2.5 cm

Micro: fascicular or storiform but no “tight” storiform pattern, cells plumper than DFSP with eosinophilic cytoplasm and tapering nuclei; mean 3 mitotic figures/10 HPF but may be >10 MF/10 HPF, extension into subcutaneous fat in 1/3 cases; at least focal inflammatory cells, foam cells or giant cells; epidermal changes in 58%, focal central necrosis in 12%

Micro images: elongated cells are arranged in fascicles or storiform patternstoriform growthspindled tumor resembles a leiomyomadeep tumor extensionmore cellular than classic tumortumor cells are more histiocyte-like and foam cells are presenthyperplastic and acanthotic epitheliumDFSP (fig A-C) versus cellular fibrous histiocytoma (fig D-F) with H&E, CD34 and APOD (new marker)

Positive stains: vimentin, CD163, CD68 (83%, J Cutan Pathol 2006;33:353), CD63/NKI-C3 (50%), Factor XIIIa (48%), focal smooth muscle actin

Negative staining: CD34, CD117 (J Cutan Pathol 2007;34:857), desmin, S100, keratin

DD: dermatofibrosarcoma protuberans (tight storiform pattern, cells more spindly than cellular fibrous histiocytoma, CD34+ [strong], Factor XIIIa negative), leiomyosarcoma

References: AJSP 1994;18:668

 

Epithelioid variant of benign fibrous histiocytoma - Soft Tissue Tumor chapter

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Definition: variant with 50% or more of tumor cells having epithelioid morphology

Uncommon, usually presents as small (1 cm or less), solitary, elevated nodule in extremities

Mean/median age 40-42 years (Br J Dermatol 1989;120:185), no gender preference

May arise from dermal microvascular unit (J Cutan Pathol 2003;30:415)

Case reports: Case of the Week #116, underlying a damaged artery (J Dermatol 2005;32:721)

Treatment: excision, only rarely recurs (Histopathology 1994;24:123)

Micro: circumscribed with uniform, medium to large angulated epithelioid cells (50%+ of tumor cells) that are often perivascular; overlying epidermal effacement, minimal inflammation, no prominent giant cells

Micro images: histiocyte-like cells with abundant cytoplasm, no/rare spindle cells #1#2#3various images #1#2epithelioid cells in hyalinized stromalow power - #1#2high power - #3#4vimentinFactor XIIIa+CD68 negativekeratin negativeMelanA negative

Positive stains: Factor XIIIa, vimentin

Negative stains: keratin, S100, myogenic markers, CD68, CD163

DD: solitary epithelioid histiocytoma (dense eosinophilic and glassy cytoplasm, often with spiked cytoplasmic extensions, variable nuclear grooves and multinucleated cells, frequent lymphocytes and neutrophils, CD68+, CD163+ AJSP 2006;30:521), Rosai-Dorfman disease (multiple skin lesions and adenopathy, histiocytes are S100+ and pleomorphic with emperipolesis, also prominent B cells and plasma cells), granulomas (epithelioid histiocytes in well formed clusters, surrounded by lymphocytes), melanoma (tight clustering of atypical cells, S100+, HMB45+), epithelioid sarcoma (deep seated, granuloma-type clusters with necrosis, more atypia, keratin+, CD163-), histiocytic sarcoma (marked atypia and mitotic activity)

References: AJSP 1994;18:583 

 

Juvenile xanthogranuloma - Soft Tissue Tumor chapter

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Definition: benign, usually self-limited, non-Langerhans cell histiocytic disorder of skin

Also called nevoxanthoendothelioma

See also Breast-nonmalignant, Eye-uvea, Liver-tumor and Skin-tumor chapters

Proliferative disorder of dendrocytes

Uncommon (< 0.5% of pediatric tumors in one study)

Usually infants (median age 5 months) with a congenital mark, although 10-30% occur in adults; male/female = 1.4:1

Skin of face or trunk, less commonly in subcutis, skeletal muscle, eye, peripheral nerve or testis

20% of patients have multiple lesions, usually males

May spontaneously regress leaving depressed area of skin with variable hyperpigmentation

In neonates, rarely associated with giant cell hepatitis and tumor in liver and viscera, requiring chemotherapy

Case reports: Case of Week #5

Treatment: conservative excision; multisystemic disease requires Langerhans cell histiocytosis-type chemotherapy (Pediatr Blood Cancer 2008;51:130)

Gross: up to 2 cm, yellow-red, papulonodular

Gross images: well circumscribed yellow nodule in scalp of 2 year old boy that subsequently regressed10 year old girl with 6 cm arm lesion

Micro: dense dermal infiltrate of lymphocytes, histiocytes, Touton giant cells (usually), eosinophils and neutrophils, which may extend into subcutis; late - epidermis thins out, rete ridges become elongated; deep lesions - more cellular and monotonous with fewer Touton cells

Cytology: deep seated mass - vague, granulomatous aggregates with monotonous, CD68+ histiocytic cells (Acta Cytol 2007;51:473)

Micro images: various imagesfoam cells, Touton giant cells and scattered lymphocytes #1#2adult patientlow powermedium power #1#2high power #1#2 

comparison of histiocytic giant cell types - Touton type-ring (wreath) of nuclei surrounding foamy cytoplasm with cytoplasm usually also visible around the nuclei; Langhans type-nuclei form a horseshoe arrangement, not necessary a distinct category from Touton type, foreign-body type-haphazard nuclear arrangement

 

Juvenile xanthogranuloma - Soft Tissue Tumor chapter (continued)

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Positive stains: CD68, HAM56, Factor XIIIa; also NKI-C3/CD63 (60%)

Negative stains: S100, CD1a

EM: no Birbeck granules, may have cytoplasmic lipid

DD: Langerhans cell histiocytosis (more common, tumor cells have coffee bean nuclei/nuclear grooves, no Touton giant cells, are S100+ and CD1a+ and negative for CD68, HAM56 and Factor XIIIa, have Birbeck granules by EM), xanthomas (associated with hyperlipidemia, uniform collection of foam cells and variable Touton giant cells, but no other inflammatory cells)

References: AJSP 2003;27:579, AJSP 2005;29:21, eMedicine #1#2

 

Deep benign fibrous histiocytoma- Soft Tissue Tumor chapter

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Definition: benign fibrous histiocytoma of subcutaneous tissue, deep soft tissue or parenchymal organs, with no dermal involvement

Rare, <1% of fibrohistiocytic tumors

Usually adult males > 25 years

Head and neck and lower limb

Treatment: excision; may recur if incompletely excised, rare metastases

Gross: well circumscribed with pseudo-capsule, typically 4 cm, variable hemorrhage

Micro: prominent storiform pattern of uniform spindle cells with ill defined eosinophilic cytoplasm and bland, elongated or plump vesicular nuclei with no atypia; often hemangiopericytoma-like vasculature; scattered lymphocytes, either multinucleated giant cells, osteoclastic giant cells or foam cells in 59%; usually less than 5 mitotic figures/10 HPF; stroma is myxoid or hyaline; borders are non-infiltrative, with no trapping of fat cells; necrosis or angiolymphatic invasion are rare

Micro images: circumscribed tumor with no trapped fatcellular tumortumor with more fibrous stromafoam cells help distinguish from DFSPfocal storiform pattern and cellular uniformityhemangiopericytoma-like vascular pattern #1#2 

Positive stains: CD34 (40%), smooth muscle actin (38%)

Negative stains: keratin, EMA, desmin, S100

DD: solitary fibrous tumor, dermatofibrosarcoma protuberans (DFSP) (not circumscribed, usually infiltrative borders, little cellular heterogeneity, usually no foam cells, CD34+, Factor XIIIa negative, Semin Cutan Med Surg 1999;18:91)

References: AJSP 2008;32:354, AJSP 1994;18:677, AJSP 1990;14:801

 

Giant cell tumor of soft tissue

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Definition: soft tissue counterpart of giant cell tumor of bone (Mod Path 1999;12:894)

Not a WHO diagnosis

Also called soft tissue giant cell tumor of low malignant potential

See also Bone chapter

Usually age 40+ years, in superficial soft tissue of extremities (70%)

Recurs in 12% (associated with incomplete excision), rare metastases and death

Case reports: metastatic tumor associated with immunosuppression (Virchows Arch 2006;448:847), breast tumor with fatal outcome (Ann Diagn Pathol 2007;11:345)

Gross: up to 10 cm, usually dermis or subcutis, 30% are below superficial fascia; well circumscribed, nodular, fleshy, red-brown-gray, gritty at periphery due to calcification

Micro: multinodular with fibrous tissue containing siderophages separating nodules; nodules contain round/oval mononuclear cells and multinucleated osteoclast-like giant cells with similar nuclei; stroma is vascularized; up to 30 mitotic figures/10 HPF, often metaplastic bone, blood lakes, vascular invasion; no/rare atypia, pleomorphism or necrosis

Cytology: numerous osteoclast-like giant cells and mononuclear cells with bland and vesicular nuclei, occasional/rare fragment of branching vasculature, mitotic figures (Acta Cytol 2003;47:1103)

Micro images: tumor resembles giant cell tumor of bone with osteoclast-like giant cells but no pleomorphism #1#2#3

giant cell tumor of bone - giant cells in background of spindled mononuclear cells #1#2#3classic featuresquiz casemultinucleated giant cells and mononuclear cellsKi-67 staining in mononuclear cells

Positive stains: vimentin, CD68 (strong in multinucleated giant cells), smooth muscle actin; also alkaline phosphatase, osteoprotegerin, RANKL, TRAIL and TRAP (Hum Path 2005;36:945)

Cytogenetics/molecular: telomeric association involving multiple chromosomes in a case (Pediatr Dev Pathol 2005;8:718)

 

Giant cell tumor of tendon sheath-diffuse type - Soft Tissue Tumor chapter

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Definition: destructive villonodular hyperplasia with synovial mononuclear cells mixed with multinucleated giant cells, foam cells, siderophages and inflammatory cells, occurs near a joint

Also called tenosynovial giant cell tumor, pigmented villonodular synovitis

Note: terminology of giant cell tumors is inconsistent in literature

See also Joints chapter

Rare; usually < age 40 years, also children (Iowa Orthop J 2007;27:90)

Develops in synovial lining of joints, tendon sheaths and bursae, usually of knee (80%), ankle, hip, shoulder or elbow joint

Almost always monoarticular

Occasionally invades underlying bone; may cause bone cyst formation, loss of bone and cartilage

Locally aggressive; often recurs, but only rarely has malignant behavior

Case reports: temporomandibular joint (Archives 2002;126:195), vertebral column (Archives 1984;108:228)

Treatment: excision, may recur if inadequate excision; radiation therapy for recurrences

Gross: brown-yellow spongy tissue, firm and nodular, often 5 cm or larger

Gross images: synovectomy specimen from a knee joint has diffuse involvement with villous areas and a few nodules, flat shiny surface represents uninvolved synoviummultinodular brown tumorbrown villous tissue with white-gray cartilage (arrow)

Micro: diffuse expansive sheets of cells with infiltrative borders and variable cellularity; also hyperplastic synovium with papillary projections composed of foamy histiocytes and hemosiderin containing macrophages; also large clefts, pseudoglandular or alveolar spaces lined by synovial cells, osteoclast-like multinucleated (10-70 nuclei) giant cells, epithelioid cells; abundant collagen may be present, but lymphocytes and plasma cells are sparse; may have 5+ mitotic figures/10 HPF, rarely chondroid metaplasia (Mod Path 2007;20:545)

Cytology: round, spindled and multinucleated cells without atypia; round cells have minimal cytoplasm and eccentric nuclei; occasional cytoplasmic hemosiderin; no mitotic figures

 

Giant cell tumor of tendon sheath-diffuse type - Soft Tissue Tumor chapter

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Micro images: villi have cellular cores and variable width and shapevilli are lined by an attenuated layer of synovial cells, also present are histiocytes, giant cells and lymphocytespapillary tumor #1#2sheet-like growth of mononuclear and multinucleated giant cells within collagenized stroma;  various images, including chondroid metaplasiamononuclear cells containing hemosiderinshoulder tumor #1#2#3#4#5#6CD68+, S100+ cells in chondroid areasmalignant cases

Cytology images: cytology, H&E  

Positive stains: CD68 (stromal and giant cells, Hum Path 2003;34:65), desmin (35-40%)
Negative stains:
S100 (chondroid areas are S100+), CD45/LCA,
EMA, keratin, HMB45, CD34, smooth muscle actin

Molecular/cytogenetics: neoplastic and reactive features; neoplastic due to CSF1 overexpression (AJSP 2007;31:970) or 1p13 (CSF1) rearrangements, often with COL6A3 at 2q35 (Proc Natl Acad Sci USA 2006;103:690); also reactive features (Hum Path 2003;34:65)

DD: hemosiderotic synovitis (associated with hemophilia and intraarticular bleeding, no mononuclear or giant cell nodular proliferation, hemosiderin primarily in synovial lining cells), fibrosarcoma, synovial sarcoma

References: more information #1, #2, eMedicine

 

Malignant giant cell tumor of tendon sheath-diffuse type - Soft Tissue Tumor chapter

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Definition: rare tumor with coexisting or prior benign giant cell tumor plus sarcomatous areas

Not a WHO diagnosis

Mean 61 years, male and female

Usually extra-articular, near large joints or extremities

Often metastasizes or recurs (AJSP 2008 Feb 7 [Epub ahead of print])

Gross: mean 9 cm

Micro: benign areas with gradual or abrupt change to frank sarcoma containing pleomorphic, spindle or enlarged oval cells resembling MFH, fibrosarcoma, myxosarcoma or giant cell tumor with large nuclei and prominent nucleoli, also necrosis and atypical mitotic figures

Micro images: benign and malignant areas

Cytogenetics: trisomy 5 and 7 (Archives 2000;124:1636)

References: AJSP 1997;21:153

 

Giant cell tumor of tendon sheath-localized - Soft Tissue Tumor chapter

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Definition: circumscribed proliferation of synovial like mononuclear cells with osteoclast-like giant cells, foam cells, siderophages and inflammatory cells, usually in digits

Also called fibrous histiocytoma of tendon sheath

See also Joints chapter

Family of lesions arising from joint synovium, bursae and tendon sheath; giant cell tumor of bone, giant cell tumor of tendon sheath and pigmented villonodular synovitis may have common cell lineage (Ultrastruct Pathol 2006;30:151)

Common, usually ages 30-50 years, 2/3 female, primarily affects the fingers

#2 most common tumor of hand after ganglion cyst

Rare in children, in whom recurrence is uncommon (J Pediatr Orthop 2007;27:67)

Treatment: excision, 4-30% recur (treat with reexcision)

Clinical images: hand tumor at surgeryankle tumor at surgery

Gross: localized tumors are up to 4 cm in small joints (larger elsewhere), circumscribed, lobulated, white-gray-brown (color depends on amount of yellow-orange-red hemosiderin); may have shallow grooves along deep surface due to underlying tendons

Gross images: multinodular tumor of handankle tumor

Micro: well circumscribed, lobulated, partially encapsulated; variable proportions of mononuclear cells (small, round to spindled, with pale cytoplasm and round or grooved nuclei), osteoclast-like giant cells with 3-50 nuclei, foam cells, siderophages, epithelioid cells with glassy cytoplasm and round vesicular nuclei; up to 20 mitotic figures/10 HPF; stroma is hyalinized

Cytology: polymorphic population of mononuclear histiocyte-like cells, hemosiderin laden macrophages, foamy macrophages and a few multinucleated giant cells (Diagn Cytopathol 2004;30:14); stromal cells are dispersed, polygonal to spindle shaped, with intranuclear cytoplasmic inclusions and occasional nuclear grooves and convolutions (Diagn Cytopathol 2003;29:105)

 

Giant cell tumor of tendon sheath-localized (continued)

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Micro images: various images #1#2multiple synovial lined clefts and hemosiderin deposits in subsynovial layersheets of round/polygonal cells, variable giant cells and hypocellular collagenized zonesoccasional mononuclear cells, scattered giant cells and hemosiderin-containing xanthoma cells

Virtual slides: site unspecified #1#2thumbfinger #1#2#3

Positive stains: mononuclear cells - CD68 and variable muscle specific actin and desmin; osteoclast-like giant cells - CD68, CD45 (Mod Path 1995;8:155), TRAP

EM: histiocyte-like cells, fibroblast-like cells, multinucleated giant cells, foam cells

Molecular/cytogenetics: near diploid or pseudodiploid, often t(1;2) (Fetal Pediatr Pathol 2004;23:171)

References: eMedicine

 

Malignant fibrous histiocytoma of soft tissue - giant cell type

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Definition: diagnosis of exclusion - an undifferentiated pleomorphic sarcoma with prominent osteoclast-like giant cells

Also called malignant giant cell tumor of soft parts, malignant osteoclastoma

Number of cases is declining as specific sarcoma types are identified

Osteoclast-like cells have functional features of osteoclasts (J Pathol 1989;159:53)

Extremities and trunk

Case reports: disseminated tumor (Indian J Pathol Microbiol 2007;50:795)

Gross: hemorrhagic and necrotic

Micro: resembles pleomorphic MFH plus evenly dispersed osteoclast-like giant cells with 20-100 uniform nuclei that are small and round/oval, accompanied by smaller stromal cells with similar nuclei; 2-3 MF/10 HPF, may have angiolymphatic invasion, rarely small foci of neoplastic bone or cartilage (some designate these tumors as osteosarcoma or chondrosarcoma); no xanthoma cells or siderophages, no necrosis

Micro images: osteoclast-like giant cells with uniform nuclei in a pleomorphic MFH #1#2tumor cells may form neoplastic bone and osteoid #1#2

Cytology images: multinucleated osteoclast-like giant cells

DD: pleomorphic MFH (no osteoclast-like cells with uniform nuclei), osteoclast-rich carcinoma, extraskeletal osteosarcoma, melanoma, giant cell tumor of soft tissue (no pleomorphic MFH features), leiomyosarcoma

 

Malignant fibrous histiocytoma of soft tissue - inflammatory

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Definition: neoplastic histiocyte-like cells mixed with and often obscured by neutrophils and other inflammatory cells

Most of these tumors are probably dedifferentiated liposarcomas (J Pathol 2004;203:822, see also Pathol Int 1997;47:642)

Diagnosis of exclusion; recommended to take many sections and use immunohistochemistry to rule out mimics

Very rare, usually age 40+ years, often retroperitoneal

May be associated with fever, leukocytosis (leukemoid reaction) and eosinophilia

Very aggressive with poorest prognosis of all MFH types (2/3 die of disease, 1/4 have distant metastases) although these studies probably included other morphologically similar disorders

May occur in skin with predominance of lymphocytes (Am J Dermatopathol 2002;24:251)

Case reports: 4 year old boy with chest wall swelling (Fetal Pediatr Pathol 2004;23:319)

Gross: 8-10 cm, yellow due to xanthoma cells, firm, lobulated

Micro: commonly has storiform pattern, background of inflammatory cells (histiocyte-like, xanthoma, neutrophils, lymphocytes, eosinophils, plasma cells) may obscure tumor cells; tumor cytoplasm may contain phagocytized neutrophils, nuclei are large and vesicular with prominent nucleoli; may have bizarre giant cells or atypical mitotic figures but no necrosis

Micro images: acute inflammatory cells and large histiocyte-like cellslarge histiocyte-like cells with prominent nucleoli resembling lymphoma or carcinoma, with variable fibroblastsnumerous histiocyte-like cells resembling lymphomaassociated with orthopedic implant

Positive stains: MDM2, CDK4

Molecular/cytogenetics: 12q13-15 amplification or gain

DD: myxoid or dedifferentiated liposarcoma (may need to submit additional sections of normal appearing fat to identify, perform MDM2 or CDK4 or cytogenetics), irradiated osteosarcoma, metastatic renal or adrenal carcinoma, reactive abscess-like lesion, xanthogranulomatous pyelonephritis (Int J Urol 2006;13:1000), inflammatory myofibroblastic tumor, Hodgkin’s or anaplastic lymphoma, melanoma

 

Malignant Fibrous Histiocytoma of soft tissue - pleomorphic

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Definition: pleomorphic sarcoma composed of fibroblasts, myofibroblasts and histiocyte-like cells, excludes tumors with any recognizable line of differentiation other than fibroblasts or myofibroblasts

Also called undifferentiated pleomorphic sarcoma

See also Bone, Eye-conjunctiva and Heart-tumor chapters

First described in 1964 (Cancer 1964;17:1445)

Pleomorphic: variation in cytoplasmic and nuclear size throughout the tumor, not just “funny looking cells”

Diagnosis of exclusion; must sample generously and search for other components to rule out a dedifferentiated tumor or evidence of specific differentiation

When occurs in skin, is difficult to differentiate from atypical fibroxanthoma or DFSP

Historically considered the most common adult soft tissue sarcoma

Usually age 50+ years in extremities or retroperitoneum, large and deep-seated with progressive enlargement

Sarcomas adjacent to orthopedic implants or post-radiation are usually osteosarcoma or MFH (Mod Path 2001;14:969)

Recurs locally, may metastasize to lungs or regional lymph nodes, almost never presents as metastasis with unknown small primary

5 year survival is 50-60% for all high grade pleomorphic sarcomas, better for some subtypes (dedifferentiated liposarcoma)

Call “borderline” if features are between fibrous histiocytoma and MFH, and treat with wide local excision

Good prognostic factors: superficial, small size, low grade

Xray images: tumor surrounds intramedullary nail 

Treatment: wide local excision is occasionally curative in extremities

Gross: large, may appear circumscribed (but is not); subcutaneous lesions are usually 5 cm or less, retroperitoneal lesions may be 20 cm; cut surface is fibrous or fleshy with hemorrhage, necrosis or myxoid change

Gross images: implant related MFH is tan and fleshy and surrounds femurbuttock tumor #1#2

 

Malignant Fibrous Histiocytoma of soft tissue - pleomorphic (continued)

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Micro: variable cellularity, storiform pattern (cells emanate from a central focus) of very pleomorphic, bizarre cells with foamy cytoplasm and marked atypia in background of inflamed collagenous stroma; may represent end stage of various sarcomas with common morphologic features of pleomorphism and storiform growth pattern; numerous mitotic figures, including atypical forms; rarely metaplastic (not neoplastic) bone or cartilage

diagnoses to rule out: myxofibrosarcoma (10%+ myxoid foci), MFH-giant cell (if numerous osteoclast-like giant cells), MFH-inflammatory (if marked inflammatory cells), other sarcomas (if evidence of specific differentiation)

Cytology: single cells to large storiform fragments; cells are spindled, plasmacytoid and pleomorphic (often multinucleated), all with malignant nuclear morphology (Cancer 1997;81:228)

Micro images: striking low power appearance due to cellularity, whorled pattern, marked pleomorphism with bizarre nucleicharacteristic giant cells with bizarre nucleimixture of fibroblasts and histiocyte like cells including multinucleated formsvague storiform pattern is often focally presenttumor cells have abundant eosinophilic cytoplasm and bizarre nuclei, and resemble a muscle tumor #1;  #2-strap like cells resemble rhabdomyoblastsfeatures of a pleomorphic sarcoma without specific differentiation #1#2numerous mitotic figures are common, including bizarre atypical formstumor cell necrosis is frequent, and not seen in benign fibrous histiocytomapost-implant tumor shows whorling

Cytology images: storiform pattern #1#2large pleomorphic tumor cell with phagocytosis of neutrophilsmarked anisonucleosis and irregularity of nuclear membraneslarge cells with pleomorphic nuclei and bizarre mitotic figures

Virtual slides: tumor

Positive stains (not useful for diagnosis): vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, Factor XIIIa, CD68 (may be due to lysosomal granules in non-histiocytic cells); also CD10, CD34, CD99 (35%, J Cutan Pathol 2006;33:24)

Negative stains: keratin (usually), melanocytic markers, CD45, S100

EM: no features of a specific lineage; relatively undifferentiated fibroblastic, myofibroblastic or primitive mesenchymal cells, some with phagocytic properties

EM images: tumor cell has fibroblastic features

Molecular/cytogenetics: highly complex karyotype, usually triploid or tetraploid; gene expression profiles may be somewhat similar to other sarcomas (Mod Path 2007;20:749)

DD: atypical fibroxanthoma (cutaneous, small and superficial), leiomyosarcoma (smooth muscle differentiation), malakoplakia, silica reaction, histioid leprosy, metastatic renal cell carcinoma

 

Pleomorphic hyalinizing angiectatic tumor- Soft Tissue Tumor chapter

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Definition: rare tumor (< 50 cases reported) of subcutis, with ectatic blood filled spaces surrounded by hyalinized stroma and pleomorphic spindle cells

Part of WHO classification for skin tumors, not soft tissue tumors

First described in 1996 (AJSP 1996;20:21)

Low grade malignancy of adults (median age 51 years), often in extremities or trunk

May be derived from stromal fibroblasts

Case reports: 83 year old woman with thigh tumor (Path Int 2002;52:664), sarcomatous component (Pathol Int 2007;57:281)

Treatment: wide local excision; 20% recur, may recur as sarcoma

Micro: unencapsulated with infiltrative margins; atypical spindle cells that contain hemosiderin and resemble MFH-pleomorphic and schwannoma, have intranuclear and cytoplasmic inclusions; also large ectatic spaces with blood and fibrin and perivascular hyalinization; abundant mast cells, occasional fat; may have monomorphic partially myxoid spindle cell component as precursor lesion (hemosiderotic fibrohistiocytic lipomatous lesion, see below, AJSP 2004;28:1417); no/rare mitotic figures

Micro images: various images

Virtual slides: tumor with sarcomatous areas

Positive stains: CD34 (strong, Archives 2000;124:423), vimentin, VEGF, CD99, Factor XIIIa (focal)

Negative stains: S100, CD31; Ki-67 < 2% (Chin Med J (Engl) 2007;120:876)

 

Plexiform fibrohistiocytic tumor - Soft Tissue Tumor chapter

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Definition: dermal or subcutaneous, plexiform or multinodular proliferation of fibrohistiocytic cells and osteoclast-like giant cells with chronic inflammatory infiltrate

Also called plexiform fibrous histiocytoma

First described in 1988 (AJSP 1988;12:818)

Usually children and young adults

Small, slow growing dermal or subcutaneous mass, often upper extremity (65%) or lower extremity (27%)

Recurs locally, rarely has nodal or pulmonary metastases (AJSP 1999;23:662)

Case reports: myxoid tumor without giant cells (Archives 2004;128:931); recurrent tumor

Gross: multinodular, poorly circumscribed, firm, dermal or subcutaneous, 3 cm or less

Micro: deep dermal or subcutaneous tumor with ray like extension into skeletal muscle or adipose tissue, overlying epidermis and dermis is usually normal; plexiform or multinodular proliferation of fibrohistiocytic cells with minimal atypia plus osteoclast-like giant cells and chronic inflammatory infiltrate; nodules or clusters are interconnected in characteristic plexiform arrangement; vascular invasion in 10-20%; prominent dilated vessels; more sclerotic than MFH; often hemorrhage and hemosiderin; usually 0-2 MF/10 HPF, no necrosis; subtypes are fibrohistiocytic (histiocyte-like cells and giant cells), fibroblastic (fibroblast-like cells) and mixed

Cytology: plump fibroblastic cells and histiocyte-like cells within a finely granular myxoid background; also osteoclast-like giant cells (Acta Cytol 1999;43:867)

Micro images: subcutaneous proliferation of bland fibrous tissue which radiates outward from center of lesion #1#2#3most tumors have nodules of histiocyte-like cells and giant cells, also fibrous tissue and hemorrhagehistiocyte-like cells have pale staining cytoplasm, giant cells are also presentnodules may be composed of cells with elongated nucleitumor with nodules and fibrous tissue #1#2fibrous tissue may resemble desmoid fibromatosis12 year old girl with upper arm lesion #1#2#3axillary lymph node-multiple plexiform nodules within and outside the nodal parenchyma #1#2-nodules are composed of plump cells and multinucleated giant cellsmyxoid tumor without giant cells: H&E, CD68 (fig 3), CD34 (fig 4)H&E, CD68 and vimentin; various images #1#2#3#4alpha smooth muscle actin (staining of tumor cells around nests) 

 

Plexiform fibrohistiocytic tumor - Soft Tissue Tumor chapter (continued)

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Cytology images: various images

Virtual slides: plexiform fibrohistiocytic tumor

Positive stains: vimentin, CD68 (giant cells and mononuclear histiocyte-like cells), smooth muscle actin (fibroblast-like cells, Histopathology 1991;19:503)

Negative stains: S100, keratin, CD45, Factor VIII, desmin

EM: resembles myofibroblasts, fibroblasts and undifferentiated cells

DD: benign fibrous histiocytoma (older patients, prominent foam cells, no plexiform extensions of fibrous tissue, no nodules of histiocyte like cells, no multinucleated giant cells), cellular neurothekeoma (uniform population of epithelioid cells, no distinct nodules of histiocytoid cells or osteoclast-like giant cells, AJSP 2007;31:329), epithelioid sarcoma, fibromatosis, fibrous hamartoma of infancy (immature cells present, also myxoid stroma), giant cell tumor, neurofibroma

References: Ann Diagn Pathol 2007;11:313

 

 

Tumors of adipose tissue in soft tissue

Embryology and physiology of adipose tissue

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Stage I: prior to 14 weeks of gestation, loose spindle cells and ground substance are present

Stage II: aggregates of mesenchymal cells condense around proliferating primitive blood vessels

Stage III: capillaries proliferate into rich network, preadipocytes become stellate and organize into lobules

Stage IV: fine lipid vacuoles develop within cytoplasm

Stage V: adipocytes accumulate within rich capillary network and perilobular mesenchyme condenses at periphery of lobule to form fibrovascular septa at week 24

Brown fat has similar development, but contains large mitochondria with uncoupling protein 1 (OMIM 113730); brown fat deposits are well established by month 5 of gestation, particularly in posterior cervical, axillary, suprailiac and perirenal regions

Adipocyte development is closely associated with angiogenesis: (a) fat appears first in well vascularized regions; (b) adipocytes synthesize lipoprotein lipase (transports serum triglycerides into adipocytes), which is transferred to luminal surface of capillary endothelium

Fat development is controlled by CHOP gene, which mediates differentiation of fibroblasts into adipocytes and growth arrest of terminally differentiated adipocytes; translocation of CHOP in myxoid liposarcomas may remove normal inhibition on CHOP

At birth, amount of adipose tissue increases for next 10 years with overall growth; at puberty, adipocytes increase in size and number

Brown fat is widely distributed in children in interscapular region, around neck vessels and muscles, around mediastinal structures, near lung hila and around abdominal viscera

Some adipocytes may originate from neural crest (Development 2007;134:2283)

References: Early Hum Dev 1983;8:1

 

Normal white fat - Soft Tissue Tumor chapter

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Also called White Adipose Tissue (WAT); cells are called adipocytes

Main function is energy storage

Triglycerides circulate in blood in form of chylomicrons; lipoprotein lipase, an enzyme produced by adipocytes and present on luminal surface of endothelium, converts triglycerides to free fatty acids; free fatty acids are taken up by adipocytes and converted to triacylglycerol, which is stored within cytoplasmic lipid droplet of adipocytes

Adipocytes also secrete leptin and IL6, but their effects in humans are not well defined

Stromal cells also convert androstenedione to estrone, the main source of estrogen in men and postmenopausal women

Sites: subcutaneous, mediastinum, abdomen, retroperitoneum

Gross: homogeneous, yellow, greasy surface, faint fibrous septa

Micro: uniform large spherical cells up to 120 microns in which lipid droplet pushes nucleus to periphery and deforms it to a thin crescent; cytoplasm has single, clearly delimited vacuole; clear because cytoplasmic fat dissolves during tissue processing; nucleus may have central vacuole or Lochkern; very thin membranes between cells

Micro images: mature adipose tissue with transparent cytoplasm and thin fibrovascular septa #1#2adipocytes along arteriole in mesenteryfat emboli in lung-Oil Red O stain

Virtual slides: adipose tissue

Positive stains: Oil red O and Sudan Black for neutral fat (must use frozen tissue as tissue processing removes fat); Nile blue sulfate stains neutral fat pink-red and fatty acids/phospholipids blue; vimentin (nonspecific), S100 (primarily for mature adipocytes), vimentin, calretinin (also stains lipoma and liposarcoma, Hum Path 2006;37:312); basement membrane is highlighted by PAS and reticulin

Note: Oil red O also stains most carcinomas

Negative stains: CD31, keratin, desmin, muscle specific actin

EM: pre-adipocytes - spindle cells with abundant endoplasmic reticulum and small spherical mitochondria

mature adipocyte - large lipid droplet flattens nucleus against cytoplasmic membrane, variable pinocytotic vesicles; capillaries are close to adipocyte basement membrane

EM images: subcutaneous adipocytes

 

Normal brown fat - Soft Tissue Tumor chapter

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Also called Brown Adipose Tissue (BAT)

Main function is heat production (nonshivering thermogenesis), mediated through a dense vascular system and sympathetic nerves

Brown fat mitochondria express uncoupling protein (UCP1), which uncouples fatty oxidation from ATP generation, which causes energy to be dissipated as heat; cold exposure leads to sympathetic stimulation of brown fat via norepinephrine binding to beta adrenergic receptors, then oxidation of fatty acids and heat production

Sites: more conspicuous in infants (5% of body weight, diagram) and children; replaced with white fat over time

Persists in adults in interscapular region, neck, mediastinum, axilla, retroperitoneum (perirenal)

Increased presence is associated with alcohol abuse, malnourishment and cachexia (may maintain body temperature in those with diminished subcutaneous fat), cardiovascular disease (Archives 1992;116:1152); also Duchenne’s muscular dystrophy (Archives 1988;112:550)

Brown fat thermogenesis is visible with a thermal (infrared) camera in infants over neck and interscapular area; also important in animals coming out of hibernation, allowing them to rewarm quickly

Gross: red-brown (less lipid) to tan (more lipid) due to vascularity and numerous mitochondria; has glandular and lobular appearance

Micro: lobules of adipocytes, capillaries, nerves and connective tissue; adipocytes are smaller (25-40 microns) than in white fat, are polygonal with acidophilic multivacuolated and granular cytoplasm and central spherical nucleus with fine indentations

Micro images: multivacuolated cytoplasm #1#2#3CD31 (figures 1-3)

Positive stains: CD31 (Archives 2006;130:480); also mitochondrial membrane uncoupling protein (J Histochem Cytochem 1993;41:759)

EM: numerous mitochondria

References: Wikipedia

 

 

Lipoma and variants - Soft Tissue Tumor chapter

Lipoma of soft tissue

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Definition: benign tumor composed of mature white adipocytes with uniform nuclei resembling normal white fat

Most common mesenchymal and soft tissue tumor (100x more common than liposarcoma)

Epidemiology: adults age 40+; associated with obesity; no gender or ethnic preference; rare in children

Multiple lipomas: 5%, more common in women, often familial, associated with neurofibromatosis, multiple endocrine neoplasia syndromes, Bannayan syndrome (macrocephaly, hemangiomas and lipomas)

Sites: usually trunk, back, shoulder, neck, proximal extremities; rare on hands, feet, face or lower leg; also rare in retroperitoneum

Usually subcutaneous (liposarcomas are usually deep seated)

Relatively static after initial growth period; don’t regress even with starvation

Become hard after application of ice

Prognosis: benign, but 1-4% recur

Treatment: excision

Gross: bright yellow homogeneous fat with fine fibrous capsule (superficial lesions only) and trabeculae; may be very large (particularly if deep); greasy cut surface

Gross images: encapsulated mass #1;  #2fatty mass with surgery related hemorrhage;  cardiacparapharyngeal;  subcutaneousunknown site

Micro: mature white adipose tissue without atypia; 2-5x variation in cell size (more than normal white adipose tissue), with obvious large cells up to 300 microns; cytoplasmic vacuoles are relatively uniform; may have intranuclear vacuoles, thickened fibrous septa in buttocks, foot or hand; may contain areas of fat necrosis with histiocytes, infarct or calcification; rarely contains bone or cartilage; no mitotic figures

Note: diagnosis of lipoma requires presence of a mass

Micro images: unencapsulated subcutaneous lipomanormal adult fat cells in a masssite unspecifiedendobronchial lipomalipoma of thoraxretroperitoneal lipoma-various images

Virtual slides: lipomaretroperitoneal lipoma

 

Lipoma of soft tissue (continued)

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Positive stains: vimentin, S100, CD34 (slender spindle cells); also leptin, PAS (highlights capillaries), reticulin (surrounds each adipocyte)

Molecular/cytogenetics: 55%-75% of solitary lipomas have t(12;14)(q13-15;q23-24) or related changes involving HMGA2/HMGIC at 12q13-15, 10% have 6p changes, 10% have aberrations of HMGA2 and LPP including t(3;12)(q27;q14-15); marker ring or giant chromosomes are extremely rare; multiple lipomas usually have normal phenotype

EM: univacuolar mature adipocytes that compress peripheral nuclei (Cancer 1982;50:102), pinocytotic vessels, cells are surrounded by external lamina

DD: normal fat (not circumscribed or encapsulated, not a mass), pneumatosis cystoides intestinalis in small bowel (not actually adipocytes), mesenchymal cells producing acid mucopolysaccharide (vacuoles contain fluid and are not clear, nuclei are not deformed)

References: eMedicine #1, #2, Atlas of Genetics and Cytogenetics

 

Angiolipoma of soft tissue

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Definition: subcutaneous nodule composed of mature adipocytes, thin walled vessels and fibrin thrombi

See also Breast chapter

Epidemiology: arises shortly before puberty or in young adults; rare in children or older adults

5% familial

Sites: usually skin, 2/3 in forearm and chest wall

Painful, usually multiple subcutaneous nodules (other painful nodules are angioleiomyoma, eccrine spiradenoma, glomus tumor and traumatic neuroma)

May actually be hemangiomas containing fat, not mixed tumors

Case reports: cellular tumor with minimal adipose (Am J Dermatopathol 1995;17:312), epidural (J Clin Pathol 2005;58:882), foot (World J Surg Oncol 2008;6:11)

Treatment: excision; does not recur or metastasize

Clinical images: mass on plantar surface of foot

Gross: encapsulated, small (< 2 cm), yellow-red nodule in subcutaneous tissue

Gross images: foot mass with vascular pediclelobulated fat with thin fibrous septae and brown spots representing thrombosed capillary vesselssmall bowel tumormediastinal tumor   

Micro: mature adipose tissue, branching capillaries and thick walled vessels with pericytes, particularly at periphery; hyaline/fibrin thrombi are an important diagnostic sign; cellular tumors are usually encapsulated with septation and fibrin thrombi (AJSP 1990;14:75); mast cells are present; fibrosis in older lesions

Micro images: mature adipose tissue and prominent vasculature #1#2prominent vascular thrombi #1#2#3#4#5various imagesfoot tumor #1#2#3#4#5

Virtual slides: angiolipoma #1#2

EM: may be reduced number of Weibel-Palade bodies in endothelial cells (Hum Path 1981;12:739)

Molecular/cytogenetics: almost always normal karyotype

DD: Kaposi’s sarcoma and angiosarcoma (not circumscribed, usually not subcutaneous, atypia present, no scattered adipocytes)

References: Stanford University

 

Infiltrating (intramuscular) angiolipoma of soft tissue

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No longer acceptable terminology because it represents a different lesion

May be an intramuscular large vessel hemangioma in which muscle has been replaced by fat (J Pediatr Orthop 1986;6:172)

Treatment: interferon alfa (Arch Dis Child 2003;88:67), usually not resectable

 

Chondroid lipoma of soft tissue

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Definition: benign tumor of mature adipocytes, lipoblasts and myxochondroid stroma

Rare, slow growing, painless, benign mass

First described as a distinct entity in 1993 (AJSP 1993;17:1103)

Epidemiology: 80% female; median age 36 years, range 14 to 70 years

Sites: proximal extremities and limb girdles; intramuscular or subcutaneous

Case reports: Case of the Week #52, oral cavity (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:331), trunk (Skeletal Radiol 2004;33:666), incidental finding at hip replacement surgery (J Surg Orthop Adv 2004;13:42)

Treatment: excision is curative - does not recur, metastasize or transform

Gross: median 4 cm, up to 11 cm, encapsulated, yellow or white

Gross images: yellow tumor #1#2lipomatous (arrows) and chondroid (*) areas

Micro: well circumscribed, nests and cords of small to medium, multivacuolated cells resembling lipoblasts, chondroblasts or hibernoma cells within a prominent chondromyxoid matrix with variable mature fat; usually prominent vasculature with variable wall thickness; may have hemorrhage and fibrosis; no pleomorphism, no atypia, no/rare mitotic activity, no mature hyaline cartilage

Cytology: mature lipocytes and lipoblast-like cells within a chondromyxoid matrix (Archives 2001;125:1224)

Micro images: well circumscribed tumorclusters of small to medium cells with vacuolated cytoplasm #1#2mature fat cells are presentimage #1#2#3#4#5#6#7mature fat cells (*), lipoblast-like cells (arrowheads) and chondroid tissue (C)

Virtual slides: chondroid lipoma

Positive stains: S100 (mature adipocytes stain stronger than lipoblasts) and vimentin, PAS+ glycogen, Alcian blue and toluidine blue (stain chondroitin substrate); variable focal CD68 and keratin (Hum Path 1995;26:706)

Negative stains: EMA, HMB45, smooth muscle actin, Ki-67 (or low)

Cytogenetics: t(11;16) - also in hibernomas (AJSP 1999;23:1300, Mod Path 1999;12:88). 

Cytogenetics images: t(11;16) plus other changes

 

Chondroid lipoma of soft tissue (continued)

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EM: abundant intracytoplasmic lipid and glycogen and numerous pinocytotic vesicles, characteristic of white adipocytes (AJSP 1995;19:1272); resembles embryonal fat and to a lesser extent embryonal cartilage; cells have knob like protrusions of cell membrane containing granular, amorphous and fibrillar material; no prominent mitochondria, no lysosomes (Hum Path 1995;26:706)

DD: myxoid liposarcoma (different sites, usually no prominent cords or clusters of cells; has delicate plexiform capillary matrix); extraskeletal myxoid chondrosarcoma (prominent fibrous septa; chondroblasts typically lack intracytoplasmic vacuoles, no mature fat; frequently has mitotic figures and necrosis), extraskeletal chondroma (distal extremities, mature hyaline cartilage, no fat), mixed tumor (foci of epithelial differentiation, keratin+, no lipoblasts)

References: Radiographics 2004;24:1433

 

Fibrolipoma of soft tissue

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Definition: lipoma with prominent bundles of mature fibrous tissue traversing fatty lobules

Not a WHO diagnosis

Fibrovascular polyps of esophagus are also called fibrolipomas

See also lipomatosis of nerve below

Sites: common in neck

Case reports: giant fibrolipoma of parotid gland (World J Surg Oncol 2006;4:28), giant fibrolipoma of leg (Anticancer Res 2006;26:3649)

Gross images: intraoperative photo of parotid tumorencapsulated mass

Micro: lipoma with fibrous tissue component

Micro images: mature adipose tissue and dense bands of fibrosis

DD: spindle cell lipoma; lipoma of hands, feet or buttocks (typically has dense fibrous tissue at these sites), well differentiated liposarcoma (atypical cells present in fibrous areas)

 

Intramuscular lipoma of soft tissue

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Definition: lipoma that infiltrates within muscle belly; called intermuscular lipoma if between muscle fascicles

Also called invasive or infiltrative lipoma

Not a WHO diagnosis

Intramuscular: affects thigh, trunk, head and neck of middle-aged adults

Intermuscular: affects abdominal wall of middle-aged adults; doesn’t recur if completely excised

Benign, but 20% recur due to incomplete excision

Infiltration may be due to muscular degeneration and endomysial fatty growth secondary to atrophy (BMC Musculoskelet Disord 2004;18:20)

Case reports: giant infiltrative tumor of face (AJNR Am J Neuroradiol 2003;24:283), in pectoralis major muscle simulating a breast mass (Ann Acad Med Singapore 2005;34:275), well circumscribed tumor of sternocleidomastoid muscle (Auris Nasus Larynx 2004;31:283)

Gross: intramuscular - poorly circumscribed, extends between and around skeletal muscle fibers

Gross images: tumor of faceyellow adipose tissue within skeletal muscle #1#2irregular lobulated tumor without encapsulationdeep tumor of calf

Micro: mature lipocytes that infiltrate skeletal muscle; no atypia, no mitotic figures

Micro images: adipocytes and atrophic muscle #1#2#3#4mature adipocytes, inflammatory cells and striated muscle 

DD: intramuscular hemangioma (adolescents and young adults, usually head and neck, prominent vasculature, variable adipose tissue)

 

Lipoma arborescens - Soft Tissue Tumor chapter

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Definition: fatty infiltration of subsynovial connective tissue in a large joint

Also called villous lipomatous proliferation of synovial membrane, diffuse lipoma of joint

Not a WHO diagnosis

Epidemiology: rare; older patients, usually male, associated with joint trauma, degenerative joint disease and chronic arthritis

Sites: usually knee

May be reactive process

MRI is useful in diagnosis (Radiol Med (Torino) 2005;109:540)

Case reports: bilateral (Knee 2005;12:394), multifocal (Skeletal Radiol 2005;34:536)

Treatment: synovectomy; may recur since often is a reactive process

Gross: yellow fat in villous fronds

Gross images: villous architecture of synovium #1 (fig 2)#2 (fig 3)

Micro: hypertrophic villous projections of fat lined by synovial cells, variable scattered inflammatory cells

Micro images: hypertrophied synovial tissue with synovial lining cells, containing adipose tissuesynovial tissue replaced by adipose (figure 2C)various images (fig 3-4)#2

References: Stanford University

 

Lipoma of tendon sheath - Soft Tissue Tumor chapter

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Definition: lipoma attached to tendon

Not a WHO diagnosis

Very rare; adults age 40 years or less

Sites: tendons of hands and wrist; less often ankle and foot

Case reports: causing carpal tunnel syndrome (Orthop Rev 1988;17:1083)

Gross: focal lipomatous mass resembling lipoma

Gross images: nodular masses attached to tendon that resembles lipoma arborescens (fig 1A)

Micro: resembles lipoma

Micro images: polypoid masses resembling lipoma arborescens (fig 1B)

DD: lipoma arborescens (usually not a discrete mass, affects knee, not hands/wrist)

 

Lipomatosis - Soft Tissue Tumor chapter

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Definition: diffuse overgrowth of mature adipose tissue

Epidemiology: rare disorder of children under 2 years or adults

Associated with obesity, Cushing’s disease, steroid therapy, protease inhibitors for HIV

See also pelvic lipomatosis

Sites: limb (may cause massive enlargement) or trunk

Treatment: palliative surgical removal of excess fat; may recur; may lead to amputation of extremity due to distortion or loss of function

Gross: poorly circumscribed aggregates of normal appearing fat in subcutaneous and skeletal muscle (but not confined to muscle); does not affect nerves

Micro: sheets and lobules of white adipose tissue that may infiltrate skeletal muscle; may involve bone

Micro images: lipomatosis infiltrating skeletal muscle

Positive stains: S100, vimentin

References: Stanford University

 

Adiposis dolorosa - Soft Tissue Tumor chapter

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Definition: tender accumulations of subcutaneous fat, often in pelvis and lower extremities of postmenopausal women

Also called Dercum’s disease

Epidemiology: associated with women, obesity, hypercholesterolemia

Case reports: obese woman with recurrent abdominal pain treated medically (Dtsch Med Wochenschr 2006;131:434), obese woman with multiple painful subcutaneous lipomas (Ann Ital Med Int 2005;20:187)

References: dercum.net, eMedicine, OMIM 103200

 

Multiple symmetric lipomatosis - Soft Tissue Tumor chapter

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Definition: multiple non-encapsulated lipomas with symmetric distribution and sparing of distal arms and legs

Also called Madelung’s disease, Launois-Bensaude syndrome

Epidemiology: rare, usually men, ages 40+ years; associated with high ethanol intake (Int J Obes Relat Metab Disord 2002;26:253); in women is more common in proximal arms (91%) and legs (54%) and also associated with high ethanol intake (Int J Obes Relat Metab Disord 2003;27:1419)

Prognosis: associated with significant morbidity, including metabolic disturbances, neuropathy, malignancy and sudden death

Case reports: 8 year old girl with bilateral neck swellings (Dentomaxillofac Radiol 2007;36:51), post-liver transplant for cirrhosis (Dermatology 2008;216:337), familial disease with normal karyotype (Cutis 2007;79:227), 89 year old man with familial disease (Dermatol Online J 2003;9:9)

Treatment: liposuction or surgery, not diet (Acta Dermatovenerol Croat 2008;16:31); possibly fibrate drugs (Obes Surg 2008;18:240)

Clinical images: multiple neck masses 

Gross: involves subcutaneous and deep soft tissue

Gross images: neck tumor

Micro: unencapsulated masses of mature adipose tissue

Micro images: resembling well differentiated liposarcoma #1#2adipose surrounding nervemature adipose tissue (slow loading)

Molecular/cytogenetics: may be associated with mitochondrial DNA abnormalities (Neurology 1994;44:862)

References: OMIM 151800

 

Lipomatosis of nerve - Soft Tissue Tumor chapter

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Definition: infiltration of epineurium of a major nerve by adipose and fibrous tissue

Also called fibrolipoma of nerve, fibrolipomatous hamartoma of nerve

Epidemiology: may be noted at birth; almost always age 30 years or less

Associated  with macrodactyly (abnormal enlargement) of digits innervated by affected nerve in 30-67%

Sites: 85% of patients have involvement of median nerve and its digital branches in hand, wrist and forearm; also ulnar nerve

Treatment: benign, but often no effective treatment as resection causes sensory and motor deficits; carpal tunnel release may relieve symptoms of median nerve involvement; amputation if severe deformity

Gross: fusiform enlargement of nerve by yellow adipose tissue, confined within epineurium

Gross images: lipomatosis of median nerve with macrodactylyexcised tissuethickened median nerve #1#2#3

Micro: infiltration of epineurium and perineurium by adipose and fibrous tissue, causing enlargement of nerve; concentric perineurial fibrous tissue and pseudo-onion bulb formation

Micro images: tumor of second digit #1#2 with osseous and soft-tissue hypertrophy and predominance of fatlipomatous infiltration around nerve fascicles #1#2 

DD of macrodactyly: angiomatosis, neurofibromatosis type 1, Klippel-Trenaunay-Weber syndrome, Proteus syndrome

 

Lumbosacral lipoma - Soft Tissue Tumor chapter

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Definition: diffuse overgrowth of mature fat overlying lumbosacral spine

Not a WHO diagnosis

Epidemiology: infants and children (incidence of 4-8 per 100K population), peaks at ages 0-2 and 7-8 years; associated with spina bifida or laminar defect

Usually connected to spinal cord or cauda equina through defect

Micro: may contain numerous vessels or smooth muscle cells

References: Childs Nerv Syst 2002;18:326

 

Myelolipoma of soft tissue

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See adrenal gland chapter

 

Myolipoma of soft tissue

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Definition: benign tumor of mature adipocytes and mature smooth muscle

First described in 1991 (AJSP 1991;15:121)

Very rare tumor of adults in abdomen, retroperitoneum or abdominal wall

Called lipoleiomyoma in uterus

Case reports: 34 year old woman with tumor of iliac fossa (World J Surg Oncol 2005;3:72), presenting as inguinal hernia

Treatment: excision; does not recur, metastasize or transform

Gross: often 9 cm or more, completely or partially encapsulated, yellow-white

Gross images: large lobulated mass with thin pseudocapsulefatty tissue with bands and nodules of firm white tissue

Micro: mature adipose tissue and mature (well differentiated) smooth muscle in short fascicles;