Soft Tissue Tumors Part 1:

Introduction, Infections &

Fibroblastic / myofibroblastic tumors

Last revised 29 May 2009

Last major update May 2009 - next update May 2010

Copyright (c) 2002-2009, PathologyOutlines.com, Inc.

Reviewed by David Lucas, M.D. in January 2009 (see Reviewers page)

See also Bone and Joints chapters

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Table of Contents for Soft Tissue Tumors Part 1

 

Introduction: primary referencessoft tissue-normal,  approach to diagnosissarcomas-generalsyndromesgradingcell typesarchitectural patternsmolecular

 

Infections, inflammation and hematoma: generalgranulomatoushematomanecrotizing fasciitisPVP granuloma, tumoral calcinosis

 

Fibroblastic / myofibroblastic: normalgeneralangiomyofibroblastomacalcifying aponeurotic fibroma,  calcifying fibrous tumorcellular angiofibromadermatofibrosarcoma protuberansdesmoplastic fibroblastomaelastofibromaeosinophilic fasciitisfibroma of tendon sheathfibromatosis-generalfibromatosis-superficialfibromatosis-deepfibromatosis collifibrosarcoma-adultfibrosarcoma-infantilefibrous hamartoma of infancyfocal myositisGardner fibromagiant cell angiofibromagiant cell fibroblastomahemangiopericytomainclusion body fibromatosisinflammatory myofibroblastic tumorintranodal palisaded myofibroblastomaischemic fasciitisjuvenile hyaline fibromatosislipofibromatosislow grade fibromyxoid sarcomalow grade myofibroblastic sarcomamammary type myofibroblastomamyofibroma / myofibromatosismyositis ossificansmyxofibrosarcoma,  myxoinflammatory fibroblastic sarcomanodular fasciitis and related lesionsnuchal fibrocartilaginous pseudotumornuchal type fibromaossifying fibromyxoid tumorpleomorphic fibroma,  proliferative fasciitisproliferative myositisproliferative peribursitissclerosing epithelioid fibrosarcomasolitary fibrous tumorsuperficial acral fibromyxoma

 

Index (table of contents in alphabetical order)

A-F:  angiomyofibroblastomaapproach to diagnosisarchitectural patternscalcifying aponeurotic fibromacalcifying fibrous tumorcell types, cellular angiofibromadermatofibrosarcoma protuberansdesmoplastic fibroblastomaelastofibromaeosinophilic fasciitisfibroblastic/myofibroblastic - generalfibroblastic/myofibroblastic - normalfibroma of tendon sheathfibromatosis collifibromatosis-deepfibromatosis-generalfibromatosis-superficialfibrosarcoma-adultfibrosarcoma-infantilefibrous hamartoma of infancyfocal myositis

 

G-O:  Gardner fibromagiant cell angiofibromagiant cell fibroblastomagradinggranulomatoushemangiopericytomahematomainclusion body fibromatosisinfection, inflammation, and hematoma - generalinflammatory myofibroblastic tumorintranodal palisaded myofibroblastomaischemic fasciitisjuvenile hyaline fibromatosislipofibromatosislow grade fibromyxoid sarcomalow grade myofibroblastic sarcomamammary type myofibroblastomamolecularmyofibroma / myofibromatosismyositis ossificansmyxofibrosarcoma,  myxoinflammatory fibroblastic sarcomanecrotizing fasciitisnodular fasciitis and related lesionsnuchal fibrocartilaginous pseudotumornuchal type fibromaossifying fibromyxoid tumor

 

P-Z:  pleomorphic fibroma,  primary referencesproliferative fasciitisproliferative myositisproliferative peribursitisPVP granulomasarcomas-generalsclerosing epithelioid fibrosarcomasoft tissue-normal,  solitary fibrous tumorsuperficial acral fibromyxomasyndromestumoral calcinosis

 

Go to Soft Tissue Tumors Part 2 - Fibrohistiocytic and Adipose (benign & malignant)

Go to Soft Tissue Tumors Part 3 - Muscle, Vascular, Nerve, Other

 

Primary references - Soft tissue tumors Part 1

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American Journal of Clinical Pathology (AJCP), January 2000 to May 2009

American Journal of Surgical Pathology (AJSP), January 2000 to May 2009

Archives of Pathology and Laboratory Medicine (Archives) [always free full text and no registration]; January 1999 to April 2009

Biomed Central [always free full text and no registration]; 24 July 2001 to 22 April 2009

Human Pathology (Hum Path), January 2000 to May 2009

Modern Pathology (Mod Path) [free full text and no registration after 1 year]; Jan 2000 to May 2009

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), 2002, WHO link
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, 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, smooth muscle, blood vessels, lymphatics and peripheral nervous system

Usually mesodermal in origin; peripheral nerves derive from neuroectoderm

 

Soft tissue tumors - approach to diagnosis

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Modified from Sternberg

1) Is lesion reactive or neoplastic?

2) Is lesion malignant? (necrosis favors malignancy)

3) Is malignant lesion a sarcoma? (may be melanoma, carcinoma, lymphoma)

4) What type of differentiation is present? - assign to phenotypic category or classify as round cell, spindle cell, epithelioid, other

5) If sarcoma, what is the grade?

 

Sarcomas - general - Soft tissue tumors

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9,500 new cases/year in US

Classified based on type of cellular differentiation, although most arise from multipotent mesenchymal cells that then differentiate along various cell lines

Diagnostic errors are often due to lack of familiarity with rare lesions, not failure to perform immunostains (AJCP 2001;116:473)

WHO classification: last revised in 2002 (Histopathology 2006;48:3), Table of Contents of WHO book-2002

World Health Organization classification with comments (Atlas of Genetics and Cytogenetics)

Recommended to diagnose with FNA, core biopsy or incisional biopsy so appropriate treatment can be determined in advance

Congenital soft tissue tumors, even with high grade features, rarely have malignant behavior

Nodal involvement uncommon

Local recurrences show increased number of genetic changes, including loss at 9p, gains at 5p and 20q (Mod Path 2001;14:978)

Usually arise de novo, not from benign tumors (MPNST may be an exception); do not appear to arise from trauma

May be caused by radiation therapy (MFH, extraskeletal osteosarcoma), foreign bodies (MFH, angiosarcoma) or chemical carcinogens (angiosarcoma)

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

Treatment: ideally wide local excision with 1-2 cm margin of normal tissue; if not possible due to anatomic constraints (neurovascular bundle, bone), a marginal excision (through pseudocapsule) or focally positive margin is acceptable; surgery should also remove site of prior incision; pre- or postoperative radiotherapy are routinely used for large, high-grade tumors or disseminated disease; amputation is reserved for unresectable tumors

Surgical resection of pulmonary metastases often has value

Fine needle aspiration: most specimens are recognized as sarcoma, and subtyping is most accurate in bone sarcomas and pediatric sarcomas; subtyping is often not possible in adult specimens, but this usually does not affect initial therapy (AJCP 2001;115:59)

Staging is discussed in Soft Tissue Tumors-Part 2 (click here)

 

Syndromes (molecular / genetic) associated with soft tissue tumors

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

Beckwith-Wiedemann syndrome: OMIM #130650, congenital overgrowth syndrome associated with alveolar rhabdomyosarcoma (Pediatr Dev Pathol 2001;4:550)

Carney syndrome / complex: autosomal dominant multiple neoplasia syndrome with myxomas and pigmented lesions of skin and mucosa, due to mutation in PRKAR1A gene (OMIM #160980) or 2p16 abnormalities (OMIM #605244)

Carney triad: OMIM # 604287, gastric GIST, pulmonary chondroma and extra-adrenal paraganglioma (Mayo Clinic Proceedings 1999;74:543, Mayo Clinic Proceedings;1999;74:638)

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

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

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

Launois-Bensaude syndrome: painless symmetrical diffuse deposits of fat beneath the skin of the neck, upper trunk, arms and legs; also known as multiple symmetrical lipomatosis, cephalothoracic lipodystrophy and Madelung disease

Li Fraumeni syndrome: OMIM #151623, various soft tissue sarcomas, osteosarcoma, breast cancer, brain tumors, leukemia and adrenocortical carcinoma; usually due to p53 mutation

Lipomatosis, multiple syndrome: OMIM #151800

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

Mazabraud's syndrome: fibrous dysplasia and intramuscular myxoma (J Cancer Res Clin Oncol 1998;124:401)

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

Multiple endocrine neoplasia 1: OMIM #131100, multiple lipomas may be a minor feature

Neurofibromatosis type 1: OMIM #162200, neurofibroma, MPNST

Neurofibromatosis type 2: OMIM #101000, schwannoma, neurofibroma, meningioma, astrocytoma, rarely perineurioma (AJSP 2006;30:1624)

Osler-Weber-Rendu syndrome: OMIM #187300, telangiectasias

Proteus syndrome: various cutaneous and subcutaneous lesions, including vascular malformations, lipomas, hyperpigmentation and nevi (eMedicine)

Stewart-Treves syndrome: cutaneous angiosarcoma that develops in long-standing chronic lymphedema (eMedicine)

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

Turner syndrome: cystic hygroma (eMedicine), rarely familial desmoids or GIST

 

Grading of sarcomas of soft tissue

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Indicate in pathology report which grading system is used

Grade is most important prognostic factor and indicator of metastatic risk in adults (Archives 2006;130:1448)

 

Two grade systems - low grade and high grade

Low grade: usually has limited ability to metastasize

High grade: cellular with mitotic figures and necrosis, but must evaluate in context of tumor type, age and location;

for example: superficial high grade MFH is unlikely to metastasize, but deep low grade MPNST is likely to metastasize

Necrosis usually signifies high grade unless tumor is well differentiated and lacks pleomorphism

 

Grading systems - French Federation of Cancer Centers Sarcoma Group

Grade 1: total score of 2-3 points

Grade 2: total score of 4-5 points

Grade 3: total score of 6-8 points

 

Tumor differentiation:

1 point: resembles normal adult mesenchymal tissue, may be confused with a benign lesion, such as well differentiated liposarcoma

2 points: histologic typing is certain, such as myxoid liposarcoma

3 points: synovial sarcoma, osteosarcoma, Ewing’s sarcoma/PNET, sarcomas of doubtful tumor type, embryonal and undifferentiated sarcomas

 

Mitotic count (count 10 successive high power fields [area of 0.17 mm squared] in most mitotically active areas):

1 point: 0-9 mitoses

2 points: 10-19 mitoses

3 points: 20 or more mitoses

 

Tumor necrosis:

0 points: no necrosis on any slides

1 point: less than 50% necrosis for all examined tumor surface

2 points: tumor necrosis of 50% or more of examined tumor surface

 

Grading systems - French Federation of Cancer Centers Sarcoma Group - grades of common sarcoma types:

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Angiosarcoma-poorly differentiated/epithelioid - 3

Angiosarcoma-well differentiated/conventional - 2

Chondrosarcoma-mesenchymal - 3

Clear cell sarcoma - 3

Epithelioid sarcoma - 3

Fibrosarcoma-conventional - 2

Fibrosarcoma-well differentiated - 1

Fibrosarcoma-poorly differentiated - 3

Leiomyosarcoma-conventional - 2

Leiomyosarcoma-epithelioid / poorly differentiated / pleomorphic - 3

Leiomyosarcoma-well differentiated - 1

Liposarcoma-myxoid - 2

Liposarcoma-pleomorphic - 3

Liposarcoma-round cell - 3

Liposarcoma-well differentiated - 1

Malignant triton tumor - 3

MFH-giant cell - 3

MFH-pleomorphic with storiform pattern - 2

MFH-pleomorphic without storiform pattern - 3

Myxofibrosarcoma - 2

Osteosarcoma - 3

PNET - 3

Rhabdomyosarcoma-alveolar / embryonal / pleomorphic - 3

Synovial sarcoma - 3

 

Grading systems of soft tissue tumors - National Cancer Institute (US) tumor grading system

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Grade 1: well differentiated liposarcoma; myxoid liposarcoma (grade 2 in French system above); subcutaneous myxoid MFH; well differentiated malignant hemangiopericytoma with < 1 MF/10 HPF, no necrosis and no hemorrhagic areas; well differentiated fibrosarcoma with orderly herringbone pattern or well differentiated leiomyosarcoma with orderly fascicular pattern plus well differentiated cytologic features, no pleomorphism, no necrosis, < 6 MF/10 HPF; malignant schwannoma (MPNST) if resembles neurofibroma plus mitotic figures plus areas of high cellularity but < 6 MF/10 HPF; myxoid chondrosarcoma that is uniformly myxoid and hypocellular with no mitotic activity

Grade 3: extraskeletal 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, carcinoma (extension into soft tissue or metastases), clear cell sarcoma, epithelioid histiocytoma, epithelioid sarcoma, epithelioid variant of leiomyosarcoma, MFH or MPNST; extracellular myxoid chondrosarcoma, myxofibrosarcoma, rhabdoid tumor, schwannoma, synovial sarcoma or vascular tumors

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

Round cell: desmoplastic small round cell sarcoma, Ewings/PNET, mesenchymal chondrosarcoma, MPNST, rhabdomyosarcoma, round cell liposarcoma, schwannoma with neuroblastoma-like features, synovial sarcoma; also carcinoma, lymphoma, melanoma, neuroblastoma, poorly differentiated tumors

Spindle cell: angiosarcoma, benign fibrous histiocytoma, benign nerve sheath tumor, DFSP, fibroma of tendon sheath (cellular), fibromatosis, fibrosarcoma, Kaposi’s sarcoma, leiomyosarcoma and leiomyoma, MPNST, nodular fasciitis, spindle cell lipoma, spindle cell variant of embryonal rhabdomyosarcoma, solitary fibrous tumor, superficial acral fibromyxoma, synovial sarcoma

 

Architectural patterns of soft tissue tumors

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Alveolar: alveolar rhabdomyosarcoma, alveolar soft parts sarcoma

Fascicular: fibromatosis, fibrosarcoma, neural tumors (benign or malignant), smooth muscle tumors, synovial sarcoma

Glandular: adenocarcinoma, biphasic synovial sarcoma, glandular MPNST

Lobular: clear cell sarcoma, epithelioid sarcoma, extraskeletal myxoid chondrosarcoma

Palisading: palisading intranodal myofibroblastoma, Schwann cells (neural tumors), smooth muscle tumors, spindle cell lipoma, synovial sarcoma

Pericytic vascular: mesenchymal chondrosarcoma, MFH, myopericytoma, solitary fibrous tumor/hemangiopericytoma, synovial sarcoma

Plexiform: nerve sheath tumors (neurofibroma, schwannoma), plexiform fibrous histiocytoma

Plexiform vascular: low grade fibromyxoid sarcoma, myxofibrosarcoma, myxoid liposarcoma, nodular fasciitis

Storiform: dermatofibrosarcoma protuberans (DFSP), fibrohistiocytic tumors, dedifferentiated liposarcoma, low grade fibromyxoid sarcoma, MFH, perineurioma

 

Molecular / cytogenetics of soft tissue tumors

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RT-PCR or FISH of paraffin-embedded tissue for tumor fusion transcripts is useful (AJSP 2002;26:965, AJSP 2008;32:8)

Note: in table below, gene for first chromosome in translocation is listed first

 

Alveolar soft parts sarcoma: t(X;17)(p11.2;q25) - ASPL-TFE3 fusion gene

Aneurysmal bone cyst, extracellular: t(17;17)(p13;q12)

Angiomatoid fibrous histiocytoma: t(12;16)(q13;p11) - ATF1-FUS fusion gene or t(12;22)(q13;q12) - ATF1-EWSR1 fusion gene (also present in clear cell sarcoma)

Chondroid lipoma of soft tissue: t(11,16)(q13;p12-13); also in hibernoma

Chondrosarcoma, myxoid, extraskeletal: t(9;22)(q22;q12) - CHN-EWS fusion gene

     t(9;15)(q22;q21) - CHN-TCF12 fusion gene

     t(9;17)(q22;q11) - CHN-RBP56 fusion gene

Clear cell sarcoma: t(12;22)(q13;q12) - ATF1-EWSR1 fusion gene

Congenital fibrosarcoma / mesoblastic nephroma: t(12;15)(p13;q25) - ETV6-NTRK3 fusion gene

Dermatofibrosarcoma protuberans / giant cell fibroblastoma: t(17;22)(q22;q13) - COL1A1-PDGFB fusion gene

Desmoplastic fibroblastoma: occasionally t(2;11)(q31;q12) or 11q12 abnormalities

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

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; amplification of MDM2 and CDK4

Low grade fibromyxoid sarcoma: t(7;16)(q32-34;p11) - FUS-CREB3L2 or t(11;16)(p11;p11) - FUS-CREB3L1

Rhabdomyosarcoma, alveolar: t(2;13)(q35;q14) - PAX3-FKHR or t(1;13)(p36;q14) - PAX7-FKHR

Synovial sarcoma: t(X;18)(p11.23;q11) - SYT-SSX1 or t(X;18)(p11.21;q11) - SYT-SSX2 fusion genes

Tenosynovial giant cell tumor: t(1;2)(p11;q35-37)

 

References: Archives 2006;130:1199

 

 

Infections, inflammation and hematomas of Soft Tissue

Infections of Soft Tissue - general

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Usually due to direct extension from infections of skin, bone or viscera, or due to trauma or surgery

 

Granulomatous infections of soft tissue

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Due to tuberculosis, fungi, atypical mycobacteria (Clin Infect Dis 1995;21:65, Int J Tuberc Lung Dis 2007;11:96)

Case reports: Brucella gluteal abscess (Intern Med 2008;47:171)

 

Hematoma of soft tissue

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May clinically resemble a tumor if deep seated

Sites: usually near tensor fascia lata (upper thigh muscle, image)

Important to exclude a sarcoma with intratumoral hemorrhage

Pseudoaneurysm may occur after intravascular procedures

Post-operative seromas may persist for years and be confused with recurrent tumor

Case reports: in tensor fascia lata (Dermatol Online J 2001;7:6), giant chronic expanding hematoma of thigh (Joint Bone Spine 2008;75:64), mass of thorax (Yonsei Med J 2007;48:337)

Treatment: complete surgical excision, including pseudocapsule

Clinical images: lesion of lateral thigh

Gross images: perforating vessel (arrow) from tensor fascia lata appears to run into the 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

Pathophysiology: usually due to group A streptococci, also community-acquired MRSA (Surg Infect (Larchmt) 2008;9:469)

May be due to Clostridium perfringens and cause gas gangrene (Cases J 2008 Oct 20;1(1):252)

In children, associated with varicella and speC gene in group A streptococcal strains (Pediatr Infect Dis J 2009 Apr 14 [Epub ahead of print])

Clinical: fatal if untreated; 15% mortality even if treated (Epidemiol Infect 2009 Apr 7:1 [Epub ahead of print])

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

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

Treatment: promptly start antibiotics and aggressive debridement (World J Emerg Surg 2007;2:19, J Am Acad Orthop Surg 2009;17:174)

Clinical images: gas gangrene #1#2-right shoulderleft leg

 

Micro images: gluteal gas gangrene with necrotizing fasciitis #1#2#3-gram stain#4-gram stain#5necrotic muscle with gas bubbles but minimal inflammationinfected tissue with gas-inclusion between the muscle fibersgram positive rodsleg lesion #1#2#3#4#5#6-septic thrombus#7-associated vasculitis#8-gram stain#9-gram stain 

 

References: eMedicine #1#2

 

PVP granuloma of soft tissue

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

Rare (Am J Surg Pathol 1984;8:393)

Micro: focal cellularity, focally myxoid with foamy histiocytes containing vacuoles and PVP

Positive stains (histiocytes): mucicarmine, colloidal iron, GMS, Congo Red, Sudan Black B

DD: myxoid liposarcoma, signet ring carcinoma

 

Tumoral calcinosis of soft tissue

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

Also called calcium hydroxyapatite deposition in soft tissue, metastatic calcification

Usage is imprecise - refers to hereditary condition associated with massive periarticular calcification; also any massive collection of periarticular calcification (Radiographics 2006;26:871)

Clinical: associated with trauma, renal failure, hyperparathyroidism, metastatic carcinoma, myeloma, scleroderma, hypermetabolic states, sarcoidosis

Associated with mutations in fibroblast growth factor-23 gene and other genes (J Bone Joint Surg Am 2009;91:1190, OMIM #212900)

Rarely is familial (AJSP 1993;17:788)

Laboratory: elevated serum calcium, phosphate and Vitamin D

Local recurrence common

Xray: lobulated calcifications, separate from associated bone

Gross: large, multinodular, chalky masses

Micro: lobules of calcific material surrounded by histiocytic giant cells often containing small psammomatous calcifications

Micro images: low powercalcification with foreign body inflammation

Differential diagnosis: dystrophic calcification - dead tissue that is not rapidly absorbed; associated with coagulation necrosis, caseous necrosis, fat necrosis

 

 

Fibroblastic / myofibroblastic tumors of soft tissue

Normal histology of soft tissue

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Fibrous tissue consists of fibroblasts and extracellular matrix

Extracellular matrix consists of collagen, elastin and ground substance

Fibrous tissue: loose or dense; dense fibrous tissue includes tendons (connect muscle to bone), ligaments (connect bones or cartilage to each other), aponeuroses (ribbon like tendinous expansion)

Fibroblasts: spindled (along collagen fibers) to stellate (star shaped-in myxoid areas); produce various collagens; positive for vimentin, actin

Fibrocytes: quiescent stage of fibroblasts

Myofibroblasts: modified fibroblasts with multiple possible origins (diagram), including transition from fibroblasts during tissue repair (J Invest Dermatol 2007;127:526); features are intermediate between fibroblasts and smooth muscle cells

References: Wikipedia-fibroblasts, Wikipedia-myofibroblasts, Am J Pathol 2007;170:1807

 

Fibroblastic / myofibroblastic tumors of soft tissue - general

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Large subset of mesenchymal tumors

Cells / tumors may have both fibroblastic and myofibroblastic features

 

Angiomyofibroblastoma of soft tissue

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Definition: benign, well-circumscribed myofibroblastic tumor, usually in vulva

May overlap with cellular angiofibroma

First described in 1992 (AJSP 1992;16:373)

Clinical: uncommon slow growing painless mass, usually females of reproductive age

Sites: usually vulvar, 10-15% in vagina; also scrotum or paratesticular soft tissue in men (median age 57 years)

Case reports: recurrence in vagina (Eur J Gynaecol Oncol 2007;28:324), pedunculated vulvar mass (Acta Med Okayama 2006;60:237), sarcomatous transformation in vulva (AJSP 1997;21:1104), 27 year old man with inguinal tumor (Archives 2000;124:1679), 49 year old man with scrotal mass (Univ Oklahoma)

Treatment: excision, only rarely recurs, does not metastasize

Gross: well circumscribed but not encapsulated, usually 5-7 cm or less, tan-pink soft cut surface, no necrosis

Micro: thin fibrous pseudocapsule, alternating hyper- and hypocellular areas with prominent thin walled and ectatic vessel in edematous stroma; round to spindled tumor cells have eosinophilic cytoplasm and often bi- or multi-nucleation; may have plasmacytoid or epithelioid morphology, or rarely show degenerative changes; tumor cells are concentrated around vessels; mast cells common; 10% have mature adipose tissue; no/rare mitotic figures, no/rare red blood cell extravasation, no atypia; post-menopausal patients have less cellularity, less edema but more fibrosis and vessel wall hyalinization

Micro images: gross and H&Efig A: numerous capillary-like vascular channels, fig B: spindle cells with occasional multinucleated cells;  male inguinal region-actin, desmin, CD34scrotal mass-various imagesarising from posterior perivesical space

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

Negative stains: S100, keratin

EM: myofibroblastic and fibroblastic features

Differential diagnosis:

▪ aggressive angiomyxoma - not circumscribed, > 5 cm, less cellular, less vascular but vessels are large and thick walled, stromal mucin and RBC extravasation are present, infrequent plump stromal cells, usually actin negative

▪ cellular angiofibroma - more cellular uniformly, perivascular hyalinization and large, thick walled vessels, usually actin/desmin negative

▪ epithelioid leiomyoma - more cellular, no biphasic pattern, usually no binucleation, no/rare mast cells

Reference: Mod Path 1996;9:284, Stanford School of Medicine

 

Calcifying aponeurotic fibroma of soft tissue

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Definition: rare, slow growing, painless tumor with fibroblasts palisading around chondroid or calcified nodules, usually in hands and feet of children or young adults

Also called juvenile aponeurotic fibroma

Clinical: 50% recur, especially in children; does not metastasize

May be cartilaginous analog of fibromatosis

Case reports: 16 year old girl with foot tumor (Case of the Week #47), 36 year old woman with distal phalangeal bone involvement (Korean J Radiol 2008;9:91)

Treatment: conservative excision with reexcision as necessary for recurrences

Clinical images: 46 year old woman

Gross: nodular or infiltrative gray-white, gritty mass in subcutaneous tissue or tendon, may be calcified, usually 3 cm or less in hands or feet, may be larger elsewhere

Gross images: non-encapsulated and ill-defined mass

Micro: nodules of plump or epithelioid fibroblasts palisading around cartilage and spotty calcification; cells have indistinct and variable cytoplasm, plump oval nuclei with vesicular chromatin that may be condensed below nuclear membrane; fibrocytes in stroma between nodules have dense, evenly dispersed chromatin; may infiltrate fat or striated muscle at periphery; frequent osteoclast-like giant cells; rare mitotic figures, no atypia; more cellular in very young

 

Micro images: AFIP - poorly circumscribed fibroproliferative process with scattered, linear and calcified 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

 

other - spotty calcifications and chondroid-like cellspalisading tumor cells #1#2

 

16 year old girl with foot tumor - #1#2#3#4#5

 

Calcifying aponeurotic fibroma of soft tissue (continued)

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

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

Negative stains (usually): CD34, CD57, PR

EM: chondrocytes, fibroblasts and occasional myofibroblasts

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

Differential diagnosis:

▪ infantile fibromatosis - usually involves head, neck and proximal extremities in infants, not hands and feet of children/young adults, background is more myxoid than chondroid, calcification is rare

▪ superficial [palmar and plantar] and desmoid fibromatosis - usually lack calcification or chondroid differentiation

▪ chondroma of soft parts - may involve hands, but usually well circumscribed with more well developed chondroid differentiation, no infiltration of adjacent tissue, no surrounding epithelioid cells

▪ fibrous hamartoma of infancy - immature mesenchyme, fibroblasts are arranged in trabeculae but no palisading, no cartilage or calcification, not hands and feet

References: Hum Path 1998;29:1504, Acta Orthop Belg 2001;67:412, Stanford University

 

Calcifying fibrous tumor of soft tissue

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Definition: benign fibrous lesion with abundant hyalinized collagen, psammomatous or dystrophic calcifications and lymphocytic infiltration

Also called calcifying fibrous pseudotumor

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

Clinical: adolescents/young adults, all sites

Not related to inflammatory myofibroblastic tumor (Mod Path 2001;14:784, Int J Surg Pathol 2002;10:189)

Case reports: 24 year old woman with neck mass (Archives 2000;124:435), tumors of small intestine (Ann Diagn Pathol 2008;12:138), multiple peritoneal tumors #1 (Ann Diagn Pathol 2007;11:460), #2-familial (AJCP 2003;119:811), multiple pleural tumors (Virchows Arch 2005;446:78, J Thorac Oncol 2008;3:1356)

Treatment: excision, rarely recurs

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

Gross images: gray-white tumor with whorled cut surfacewell circumscribed tumor (adrenal gland)

Micro: paucicellular fibroblastic proliferation with lymphocytes (possibly lymphoid follicles), plasma cells, eosinophils, mast cells, dense collagenous tissue, varying degrees of calcification; border is often at least partially infiltrative

 

Micro images: AFIP - adrenal gland tumor has paucicellular fibrous proliferation with focal microcalcificationsmicrocalcifications vary in size;   lymphoplasmacytic inflammation is characteristic

other - psammoma body, lymphocytic infiltrate, hypocellular stromafigures 1A, 1B, 1E and 1F (comparison with inflammatory myofibroblastic tumor)hyalinized collagen with psammoma bodyvarious images (adrenal gland)

 

Calcifying fibrous tumor of soft tissue (continued)

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Positive stains: Factor XIIIa, vimentin; also CD34

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

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

EM images: figure 2A

Differential diagnosis:

▪ inflammatory myofibroblastic tumor - more cellular, no calcifications, ALK+, actin+

▪ idiopathic retroperitoneal fibrosis and related sclerosing fibroinflammatory lesions - more inflammation, especially plasma cells and eosinophils

▪ desmoplastic fibroblastoma - older patients, low cellularity, larger prominent fibroblasts, no microcalcifications, no prominent inflammatory infiltrate

▪ calcifying aponeurotic fibroma - more cellular, usually distal location, usually smaller lesion

References: Stanford University

 

Cellular angiofibroma of soft tissue

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Definition: benign, highly cellular tumor of vulva and scrotum/inguinal region with prominent blood vessels

Also called angiomyofibroblastoma-like lesion

First described in 1997 (AJSP 1997;21:636); may be related to angiomyofibroblastoma and spindle cell lipoma

In women, may arise from hormone receptor positive mesenchymal cells in lower female genital tract (Histopathology 2004;45:360)

Rare; usually ages 40+ years

Extragenital cases have similar features (APMIS 2007;115:254)

Case reports: 44 year old woman with leiomyomatous nodules (Virchows Arch 2009;454:595), 51 year old woman with coexisting 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; prominent small to medium-sized vessels with hyaline fibrosis in walls; vessels may have degenerative changes of fibrin thrombi, intramural inflammation, hemosiderin; some (usually 5% or less) adipose tissue present in 50%; stroma is usually fine collagenous fibers; scattered mast cells are common; female lesions may have brisk mitotic activity, usually absent/rare in males; occasional atypia; no necrosis, no atypical mitotic figures

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

Virtual slides: 63 year old man with scrotal mass

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

Negative stains: S100, desmin, EMA

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

 

Cellular angiofibroma of soft tissue (continued)

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Differential diagnosis:

▪ aggressive angiomyxoma - usually large and deep, hypocellular, infiltrative margin, desmin+

▪ angiomyofibroblastoma - less uniform cellularity, smaller vessels, usually desmin+

▪ solitary fibrous tumor - hyper- and hypocellular areas, prominent staghorn vessels, hyalinized collagen CD34+

▪ perineurioma

▪ PHAT

▪ leiomyoma - spindled cytoplasm, actin+, desmin+

References: Stanford School of Medicine

 

Dermatofibrosarcoma protuberans (DFSP) - Soft Tissue Tumor chapter

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See Skin-Nonmelanocytic tumors chapter

 

Desmoplastic fibroblastoma of soft tissue

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Definition: fibroblastic lesion centered in subcutaneous tissue with reactive fibroblasts, low cellularity and abundant collagen

Also called collagenous fibroma

Epidemiology: rare benign lesion of adult men (70% between ages 40 and 69 years)

Sites: usually upper extremities, back, feet

Case reports: 41 year old woman with thigh mass (J Cutan Pathol 2008;35 Suppl 1:70)

Treatment: conservative excision, does not recur or metastasize

Gross: usually 1-4 cm, well circumscribed, may be lobulated, has firm and homogeneous gray cut surface resembling cartilage

Gross images: well circumscribed tumor

Micro: paucicellular, bland spindled (stellate) and reactive appearing fibroblasts and myofibroblasts separated by abundant collagen with variable myxoid stroma; fibroblasts have amphophilic cytoplasm, vesicular nuclei and distinct nucleoli; 70% of cases involve subcutis, 25% extend into skeletal muscle

 

Micro images: AFIP - large, reactive appearing spindled fibroblasts in fibrous matrixfocus of low cellularity and dense collagenmore cellular area with reactive type fibroblasts

other - scattered stellate cells in hypovascular collagenous matrixhypocellular lesion with pseudocapsule and sparse cells separated by abundant collagenspindle cells with long nuclei in dense collagenous stromavimentin+most cells are negative for smooth muscle actin

 

Positive stains: vimentin, variable alpha smooth muscle actin

Negative stains: desmin, EMA, S100, CD34

EM: may have fibronexus junctions, markers of myofibroblastic differentiation (Ultrastruct Pathol 2004;28:149)

Molecular/cytogenetics: t(2;11)(q31;q12) or 11q12 abnormalities observed rarely (Cancer Genet Cytogenet 2004;149:161)

Differential diagnosis: fibromatosis - not circumscribed, more cellular, fascicular pattern, prominent vasculature (Adv Anat Pathol 1999;6:275)

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

 

Elastofibroma of soft tissue

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Definition: age 55+ years, benign, poorly circumscribed pseudotumor of subscapular region, composed of collagen and coarse enlarged elastic fibers; a reactive hyperplasia involving abnormal elastogenesis

Also called elastofibroma dorsi

First described in 1961 by Jarvi and Saxen (Acta Pathol Microbiol Scand 1961;51:83)

Epidemiology: associated with hard manual labor; related changes found at autopsy in 13-17% of elderly; more common in women

Sites: more common on apex of scapula, usually right sided; occasionally in deltoid muscle, infraolecranon area, hip, thigh, stomach

May be multiple, bilateral or familial; may be periosteal in origin

Slightly different amino acids from elastin; has collagen types I-III (type II normally restricted to articular cartilage and ocular structures)

Case reports: 55 year old woman (Case of the week #46), 69 year old man with tumor of hand (J Bone Joint 1987;89:468), 69 year old woman with bilateral subscapular tumors and tumor surrounding a stomach ulcer (AJSP 1985;9:233), 78 year old man with multiple subcutaneous nodules (J Am Acad Dermatol 2004;50:126)

Treatment: excise if symptomatic, does not recur

Clinical images: shoulder based 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 fat (AFIP)poorly defined fibroelastic tumor entrapping fat #1#2#3gray-white fibrous tissue mixed with fat

Micro: collagen bundles alternate with large, thick eosinophilic elastic cylinders with a dense central core, elastic fibers may be fragmented into linear globules (beads on a string); often has irregular interdigitation into adipose tissue

 

Elastofibroma of soft tissue (continued)

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Micro images: AFIP - paucicellular fibrous tissue mixed with fatthick, densely eosinophilic elastin bands are mixed with collagenelastin bands have serrated edges and are associated with detached globular elastin arranged like beads on a stringVerhoeff elastin stain highlights elastin fibers and the bead-like arrangement of the elastin globules

 

other - thick bands of fibrous tissue (long arrows) intermixed with multiple regions of mature adipose tissuediagnostic rods of elastic tissuefibrous tissue mixed with elastin bandsfibrohyaline mass within adiposebranched (arrow) and unbranched coarse elastin fibers mixed with collagen and adiposeH&E and elastic stainelastin stain #1#2#3#4

 

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

 

Cytology: hypocellular smear with diagnostic aggregates of globules within a collagenous matrix; altered elastic fibers have green-yellow autofluorescence with ultraviolet light (Diagn Cytopathol 2002;26:310)

Positive stains: vimentin, elastic stains (fibers have dense core and irregular margins), CD34 in spindle cells (Virchows Arch 2006;448:195)

Negative stains: S100, desmin, smooth muscle actin, p53

EM: cylinders composed of immature amorphous elastic tissue, central core contains mature fibers, removed by elastase digestion (J Electron Microsc (Tokyo) 2006;55:89)

Molecular/cytogenetics: Xq12-q22 or #19 gains in 30% (Int J Mol Med 2002;10:277)

Differential diagnosis:

▪ nuchal fibroma - younger than 55 years, between scapula and vertebrae, dense collagen but no elastic fibers

▪ fibrolipoma - no elastic fibers

▪ desmoid fibromatosis - more cellular, infiltrates skeletal muscle, no elastic fibers

References: Ann Diagn Path 2002;6:94, World J Surg Oncol 2007;5:15, Sarcoma 2008;2008:756565, eMedicine, Stanford University

 

Eosinophilic fasciitis of soft tissue

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

Rare fibrosing disorder with scleroderma-like induration of distal extremities

Not a WHO diagnosis

First described by Shulman (Trans Assoc Am Physicians 1975;88:70) [also called Shulman’s syndrome]

Epidemiology: mean age 50 years, 75% women

Eosinophilic-myalgia syndrome is different, and is associated with contaminated L-tryptophan, myalgia and neuritis (eMedicine)

Presence of morphea-like skin lesions is associated with residual fibrosis (Clin Rheumatol 2007;26:1445)

Case reports: 76 year old woman (Dermatology Online Journal 9(4):33), paraneoplastic phenomenon associated with metastatic colorectal carcinoma (Australas J Dermatol 2008;49:27)

Treatment: high dose corticosteroids (Int J Dermatol 2008;47:29)

Gross: woody, firm subcutaneous mass

Micro: eosinophils, lymphocytes, mast cells and histiocytes in fibrotic or fibromyxoid stroma of subcutis and fascia

Micro images: thickening of fascia with chronic inflammatory infiltrate #1#2#3#4#5#6inflammatory infiltrate in deep subcutis #1#2

References: eMedicine #1#2

 

Fibroma of tendon sheath of soft tissue

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

Also called tenosynovial fibroma

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

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

Case reports: tumors of palmar flexor sheath (Internet Journal of Hand Surgery. 2008 Volume 2 Number 1), medial canthus of eye (Ophthal Plast Reconstr Surg 2007;23:341)

Treatment: excise to relieve symptoms but preserve function, may be difficult to remove from adherent tendons; benign, but up to 24% recur, does not metastasize

Gross: well circumscribed, small fibrous multinodular mass < 3 cm, cut surface is pale, solid and homogeneous

Micro: well circumscribed nodules of dense fibrous tissue with occasional spindle or stellate mesenchymal cells in S or C shaped patterns; cells have scant cytoplasm and elongate nuclei with evenly distributed fine chromatin; often dilated or slit-like channels / clefts resembling tenosynovial spaces; varies from cellular to paucicellular; may have bizarre tumor cells, extravasated red blood cells, but no atypical mitotic figures, no necrosis, no hyperchromasia

 

Micro images: AFIP - multinodular 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 collagen

 

other - predominately acellular fibrous tissue with areas of hyalinization and characteristic slit-like vascular channelstumor of finger #1#2#3hypocellular lesion with abundant collagenspindled fibroblasts in collagenous stroma with slit like vascular channels

 

Fibroma of tendon sheath of soft tissue (continued)

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Cytology images: loose cohesive clusters of bland spindle cells with variable cytoplasm, oval to elongated nucleispindle cells in hyalinized collagen

Positive stains: smooth muscle actin, vimentin

EM: resembles myofibroblasts and fibroblasts

 

EM images: spindle cells in collagenous matrix (M) have oval and convoluted nuclei (N), clefts (C) are present between cells and 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: may have t(2;11)(q31-32;q12) (Histopathology 1998;32:433)

Differential diagnosis:

▪ sarcoma - rare in hands and feet, usually large masses with cellularity, marked chromatin abnormalities and abnormal mitotic figures

▪ benign fibrous histiocytoma - usually not hands or feet, prominent histiocyte-like cells, foam cells, giant cells and hemosiderin, CD68+

▪ giant cell tumor of tendon sheath - more cellular, cells have histiocyte-like nuclei, also prominent giant cells, foam cells, hemosiderin; no slit-like vascular spaces, no extensive hyalinized stroma

References: Stanford University

 

Fibromatosis of soft tissue - general

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Definition: proliferation of histologically benign appearing myofibroblasts and fibroblasts or primitive mesenchymal cells (pediatric fibromatoses) with infiltrative growth, collagenous stroma, low to moderate mitotic activity, aggressive behavior with local recurrence, but no metastases

Divided into adult and pediatric types

Adult types: includes deep (or desmoid) fibromatoses and superficial fibromatoses (described below); those that arise within and deep to fascia are called desmoid fibromatoses (also desmoid tumor or aggressive aponeurotic fibromatoses); those limited to fascia and superficial soft tissue plane (palmar, plantar, penile fibromatoses and knuckle pads) are less aggressive but recur frequently

Pediatric fibromatoses: includes numerous entities described below including infantile desmoid, inclusion body (or infantile digital), myofibroma/myofibromatosis, Gardner fibroma, fibromatosis coli and others; often characterized by primitive mesenchymal cells in addition to myofibroblasts and fibroblasts

 

Fibromatosis – superficial, of soft tissue

Palmar fibromatosis (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 (24% at age 65+)

Epidemiology: 75% are men; 50% are bilateral, 10% also have plantar disease, 1-4% have penile fibromatosis

Clinical: puckers overlying skin as it ages; causes flexion contracture of digits 4 and 5 due to cord-like expansion of digital aponeurotic slips; does not involve deep structures such as tendons or skeletal muscle; may be caused by fibrogenic cytokines (J Hand Surg [Br] 2005;30:557)

Treatment: observation, excision or incision of contracture band; often recurs

Clinical images: flexion contracture #1#2

Gross: small nodules or nodular masses associated with aponeurosis and subcutaneous fat, with gray-yellow-white cut surface (color depends on collagen content)

Micro: proliferative phase - uniform, plump, immature spindle cells (myofibroblasts and fibroblasts) with bland nuclei and indistinct nucleoli; moderate collagen and elongated vessels; older lesions - more dense collagen, less cellularity; variable mitotic figures; occasional attachment to dermis or cartilaginous metaplasia; usually no infiltration of surrounding tissue beyond subcutis

Micro images: AFIP - nodule of variably cellular fibroblastic tissue infiltrates an aponeurosis, with bland, uniform spindled cells in a dense hyalinized collagen stromamitotic figures may be present in cellular regions but are never atypical

other - tumor 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, no gene amplifications or deletions (Cancer Genet Cytogenet 2008;183:6), reactive not neoplastic (J Transl Med 2006;4:21), no somatic mutations of beta-catenin genes unlike desmoid fibromatosis (Mod Path 2001;14:695)

Differential diagnosis:

▪ fibrosarcoma - single large mass of deep soft tissue with intersecting bundles of cells whose nuclei have abnormal chromatin

▪ epithelioid sarcoma - common in hands, but some cells have distinctive epithelioid appearance with abundant bright eosinophilic cytoplasm, also necrosis, keratin+, CD34+

▪ desmoid tumors - rare in hand, dominant mass infiltrates skeletal muscle

References: eMedicine, Stanford University, Wikipedia

 

Plantar fibromatosis (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

Heterogeneous group of conditions with plantar location, mature collagen and fibroblasts, but no malignant features (eMedicine)

Epidemiology: common in boys < 10 years old and teenagers; associated with palmar and penile fibromatosis, also continuous phenobarbital treatment for epilepsy (Epilepsia 2008;49:1965); usually NOT associated with contractures

Clinical: only 10-25% bilateral, may be nodular; often presents with firm subcutaneous nodule or thickening associated with pain after standing or walking typically on the medial aspect of the sole

Clinically resembles melanoma, synovial sarcoma, Kaposi’s sarcoma

Treatment: observation, surgery if symptomatic, fasciectomy has fewer recurrences (25%) than local excision (100%, Plast Reconstr Surg 2008;122:486)

Clinical images: mass along medial plantar surfacevarious images

Gross: 2-3 cm nodules associated with aponeurosis and subcutis, with gray-yellow-white cut surface (color depends on collagen content)

Gross images: plantar nodulesnonencapsulated whitish tumor

Micro: proliferative phase - hypercellular collection of uniform, plump, immature spindle cells with bland nuclei and indistinct nucleoli; moderate collagen and elongated vessels; variable multinucleated giant cells (AJSP 2002;26:244); older lesions - denser collagen, less cellularity; often prominent chronic inflammation, variable mitotic figures and hemosiderin

Positive stains: vimentin, variable muscle specific and smooth muscle actin

EM: fibroblasts and myofibroblasts

Molecular/cytogenetics: near diploid, often +7 or +8, no somatic mutations of beta-catenin genes unlike desmoid fibromatosis (Mod Path 2001;14:695)

Differential diagnosis:

▪ monophasic synovial sarcoma - uniformly hypercellular, often staghorn vascular pattern or ropy collagen

▪ fibrosarcoma - single large mass of deep soft tissue with intersecting bundles of cells with abnormal chromatin, herringbone pattern

▪ desmoid fibromatosis - rare in feet, infiltrates skeletal muscle, > 3 cm, often beta-catenin+

▪ calcifying aponeurotic fibroma - plump or epithelioid fibroblasts palisading around cartilage and spotty calcification

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

 

Penile fibromatosis (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

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

Various etiologies (microvascular trauma-Int J Impot Res 2002;14:406, urethritis, sclerosing inflammatory process, idiopathic), appears to differ from other superficial fibromatoses (Curr Urol Rep 2004;5:478) although associated with them

Prevalence 3-9% (Int J Impot Res 2002;14:379), associated with plaques, pain, induration, deviation

Usually dorsolateral penis, 30% have inflammatory component

Case reports: with ossification (Sao Paulo Med J 2007;125:124)

Treatment: may spontaneously regress, responds to small amounts of irradiation, steroids, other intralesional injections (J Androl 2008 Oct 30 [Epub ahead of print]); also plaque excision and grafting (Eur Urol 2008 Dec 3 [Epub ahead of print])

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

Micro images: short abnormal elastin fibers

EM: penile plaques are composed of collagen fibrils, amorphous particulate material and fibroblasts (Int J Urol 1997;4:274)

DD: epithelioid sarcoma (may clinically appear similar, Int J Impot Res 2003;15:378)

References: Wikipedia, Knol

 

Fibromatosis - deep (desmoid type), of soft tissue

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Definition: clonal fibroblastic proliferation of deep soft tissue with infiltrative growth; locally aggressive (local recurrence, but no metastases)

See also description at other sites, including breast, colon, small bowel

"Desmos" (Greek) means tendon-like

Epidemiology: incidence of 2-4 per million population, less common than superficial fibromatosis

May be familial (associated with Gardner’s syndrome/FAP syndrome, Clin Gastroenterol Hepatol 2008;6:215 or familial desmoid syndrome, Am J Hum Genet 1996;59:1193) or related to trauma

Usually ages 15-39 years, may be painful; common sites in children are head and neck

May be fatal due to local effects, particularly in head and neck

Can be “staged” based on size, symptoms and complications (Dis Colon Rectum 2008;51:897)

Abdominal fibromatosis: arises within abdominal wall of women during or after pregnancy; may see with cesarean section scar

Extraabdominal fibromatosis: arises outside abdomen and abdominal wall, usually in muscles of shoulder, chest wall, back and thigh, equal gender frequencies

Intraabdominal fibromatosis: mesenteric, pelvic or retroperitoneal locations, associated with Gardner’s syndrome (familial adenomatous polyposis, multiple osteomas); often post-surgical

Case reports: 27 year old woman with post-traumatic paraspinal mass (World J Surg Oncol 2008;6:28), 29 year old women with tumor of abdominal wall (Radiology 2005;236:81, Internet Journal of Surgery 2007;10(2)), 30 year old man with aggressive mesenteric tumor that responded to chemotherapy (Jpn J Clin Oncol 2008;38:222), 43 year old woman with tumor of retroperitoneal space (World J Surg Oncol 2004;2:33)

Treatment: excision with wide margins and possibly frozen section evaluation of margins (Ann Surg Oncol 2009;16:1642), inadequate excision may cause recurrence, less recurrence in abdominal wall than elsewhere but may recur 5-6 times; may stop growing if stop excising, some recommend watchful waiting if asymptomatic or not growing, Expert Rev Anticancer Ther 2009;9:525), may respond to chemotherapy (J Clin Oncol 2007;25:501), COX2 inhibitors (Urology 2007;70:591.e3), imatinib (J Cancer Res Clin Oncol 2007;133:533), NSAIDs (World J Surg Oncol 2008;6:17), radiation (Am J Clin Oncol 2005;28:211), tamoxifen or watchful waiting (Eur J Surg Oncol 2008;34:462)

Clinical images: swollen calf #1#2

Gross: large, firm, white cut surface, infiltrative borders; often in muscular fascia, cuts with gritty sensation, 5-10 cm

 

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

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Gross images: AFIP - extra-abdominal fibromatosis has dense white, trabeculated fibrous tissue that invades skeletal muscle and produces cross section of alternating white and red patchesdesmoid fibromatosis (left) contrasted with high-grade fibrosarcoma (right) - fibromatosis has gristle-like consistency, but fibrosarcoma tends to be white, fleshy and necrotic with an overlying tendon

other - tumor infiltrates thoracic walltrunk tumor #1#2thigh tumorthoracic tumor;  gray-white tumor of Gardner syndromegray-glossy cut surfacetumor in mesentery of small bowelwell defined margin (uncommon)infiltrative marginfirm white fusiform mass

 

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

 

Micro images: extra-abdominal fibromatosis - AFIP - low power shows paucicellular fibrous proliferation in long fascicles, with numerous slit-like vessels characteristic of desmoid 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 tumors

extra-abdominal fibromatosis - other sources - paraspinal tumor #1#2thigh mass has spindle cells, dense collagenous stroma, slit-like vessels and chronic inflammationpre-radiation therapypost-radiation therapy shows reduced cellularitybreast tumor is smooth muscle actin+ 

 

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

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intra-abdominal (mesenteric) fibromatosis - AFIP - tumor appears to be extrinsic to bowel muscularis propria, which distinguishes it from GISTfibromatosis is paucicellular and composed of relatively uniform, bland spindle cellsbland, 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

intra-abdominal fibromatosis - other - uniform spindle cells with moderate collagen #1#2

 

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

 

Cytology: bland spindle cells with long, fusiform nuclei and metachromatic matrix material; tumor cells are individual or as fragments within matrix (Cancer 2007;111:166); FNA is fairly reliable for diagnosis but core needle biopsy is better (Acta Orthop 2006;77:926)

Cytology images: various images

Positive stains: vimentin, variable smooth muscle actin and muscle specific actin, variable CD117 (AJSP 2002;26:1296, but depends on antibody used, AJSP 2001;25:549); also nuclear beta-catenin (sensitive but not specific, AJSP 2005;29:653, AJSP 2002; 26:1296), ER-beta (Cancer 2006;106:208)

Negative stains: keratin, S100, CD34 (J Clin Pathol 2004;57:1119), ALK, desmin

EM: fibroblastic and myofibroblastic features, including intrareticular collagen fibers, thin filament bundles, cytoplasmic dense bodies

Molecular/cytogenetics: clonal; associated with Wnt/beta-catenin (APC-beta-catenin-Tcf) pathways; somatic beta-catenin point mutations in exon 3, codon 41 or codon 45 in 87% (AJSP 2007;31:1299); also associated with trisomy 20 and 8 (Am J Path 1999;154:729, Cancer Genet Cytogenet 1995;79:139) and loss of 5q (APC gene)

Molecular/cytogenetic images: trisomy 20 and 8

 

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

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Differential diagnosis:

▪ fibrosarcoma - atypia or mitotic figures present

▪ GIST (strong CD117+, CD34+, AJCP 2004;121:93)

▪ idiopathic retroperitoneal fibrosis - Orman’s disease - inflammatory, strangles the ureters

▪ leiomyoma - bright pink cytoplasm of smooth muscle, desmin+

▪ low grade fibromyxoid sarcoma - heavily collagenized stroma with abrupt transition to myxoid areas, often epithelioid areas or poorly formed but large collagen rosettes; beta catenin negative

▪ neurofibroma - no myofibroblasts, S100+

▪ schwannoma - palisading Schwann cells, usually minimal collagen, S100+

▪ sclerosing omentitis - grows like panniculitis, beta catenin negative

 

Fibromatosis colli of soft tissue

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Definition: fibromatosis affecting lower 1/3 of sternocleidomastoid muscle, causing thickened muscle; appears at birth, often bilateral

Also called congenital torticollis (torticollis: twisting of neck causing unnatural position of head, usually caused by spasm of neck muscles)

Epidemiology: associated with congenital anomalies (14% have congenital dislocations of hip, also breech deliveries)

May be due to birth injury (breech presentation, forceps)

Uncommon (0.4% of live births), usually diagnosed by age 6 months

Recommended to diagnose by FNA since excision usually is not required

Treatment: early - stretching and physiotherapy, resolves in 70%; some cases require resection of affected muscle; does not recur

Gross: tan gritty mass of muscle up to 3 cm, no hemorrhage or necrosis

Micro: diffuse proliferation of uniform plump fibroblasts and myofibroblasts and scar like collagen in muscle, with entrapped reactive and degenerating skeletal muscle fibers (loss of cross striations, nuclear enlargement and hypercellularity, multinucleation, atrophy); surgical specimens are usually less cellular than FNA specimens because they are obtained later in time course of disease

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

Cytology: early - cellular specimen with clusters or parallel arrays of bland appearing spindle cells in fibromyxoid matrix; also atrophic skeletal muscle in clean background, frequent muscle giant cells, bland bare nuclei and collagen (Acta Cytol 2003;47:359); usually no significant inflammation (Diagn Cytopathol 2000;23:338)

Positive stains: vimentin, actins

Differential diagnosis:

▪ fibromatosis - no muscle fibers, which 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 dedifferentiated liposarcoma, fibromatosis, fibrosarcomatous DFSP, low-grade fibromyxoid sarcoma, MPNST, synovial sarcoma or MFH-pleomorphic

Usually deep soft tissue of lower extremities or trunk, only rarely in retroperitoneum or mediastinum

50% recur, 25% metastasize (lung, bone); more metastases if more cellular and higher mitotic activity

Survival: 5 year-41%, 10 year-29%; better if tumor is superficial and better differentiated, low mitotic rate, no necrosis

Treatment: radical excision, radiation if residual tumor or positive margins; possibly chemotherapy if high grade

Gross: may appear well circumscribed but nonencapsulated; fleshy, hemorrhagic, necrotic, white-tan

Gross images: AFIP - desmoid fibromatosis (left) is contrasted with high-grade fibrosarcoma (right), fibromatosis has gristle-like consistency, but fibrosarcoma tends to be white, fleshy and necrotic with an overlying tendon

other - well circumscribed tumor

Micro: highly cellular fibroblastic proliferation in herringbone pattern (cells in columns of short parallel lines with all the lines in one column sloping one way and lines in adjacent columns sloping the other way); cells have scant cytoplasm, tapering elongated dark nuclei with increased granular chromatin, variable nucleoli; mitotic activity present, often with abnormal forms; variable collagen; usually no giant cells; no pleomorphism (or call pleomorphic MFH), no other distinct cell types

Patterns: keloid-like (thick hyalinized collagen fibers), loose fascicular, focally myxoid

 

Micro images: AFIP - atypical uniform cells in herringbone patterncells are clearly malignant, with coarse chromatin but minimal pleomorphismgrade 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

other - well differentiated tumornuclear pleomorphism

Virtual slides: fibrosarcoma

 

Fibrosarcoma of soft tissue - adult

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Positive stains: reticulin stain demonstrates fibers surrounding each cell; phosphotungstic acid-hematoxylin demonstrates abundant cytoplasmic fibrils; also vimentin, type 1 collagen, p53; high Ki-67; may be CD34+ if arises from DFSP or solitary fibrous tumor

Negative stains: S100, keratin; smooth muscle markers, histiocytic markers, basal lamina

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

Molecular/cytogenetics: aneuploid

Differential diagnosis (other tumors with fibrosarcomatous areas):

▪ dedifferentiated liposarcoma

▪ fibromatosis - less cellular, less hyperchromasia, no atypia, <1 mitotic figure/HPF

▪ low grade fibromyxoid sarcoma

▪ MFH-pleomorphic

▪ MPNST

▪ synovial sarcoma

References: eMedicine

 

Fibrosarcoma of soft tissue - infantile

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Definition: resembles adult fibrosarcoma morphologically, but better prognosis

Age cutoff between infantile and adult forms usually varies between 5 and 10 years

Epidemiology: usually presents before age 2 years in axial regions or extremities with vary rapid growth

Related to congenital mesoblastic nephroma, which has same translocation

Clinical: 40-50% recur but only rarely metastasizes

Survival is 90%+

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

Treatment: surgery and chemotherapy (J Pediatr Hematol Oncol 2002;24:722, Pediatr Blood Cancer 2009;53:23)

Gross: may exceed 30 cm (grotesquely large compared to size of child) with tense erythematous and ulcerated overlying skin; firm to soft cut surface is fleshy, gray-tan with myxoid change, cystic degeneration, hemorrhage and necrosis

Gross images: AFIP - fleshy white mass similar to adult fibrosarcoma

Micro: poorly circumscribed, lobulated mass of small to large spindled cells in fascicles or herringbone pattern with high cellularity, nuclear atypia and pleomorphism; increased mitotic figures, hemorrhage and necrosis; resembles adult fibrosarcoma; may have prominent hemangiopericytoma-like areas, dystrophic calcification, extramedullary hematopoiesis; infiltrates adjacent soft tissue with irregular margins

 

Micro images: AFIP - biphasic pattern with fibroblastic and cellular myxoid areashigh power of myxoid areainfiltration of fatinfiltration of musclespindle cellsplump cells have granular chromatinless cellular tumor which overlaps with infantile fibromatosis, although it almost never metastasizes #1#2

other - areas of variable cellularityleg tumor #1#2#3cellular tumor with mitotic figuresfig 1: facial tumor involves eye and maxilla, fig 2: undifferentiated cells with loose myxoid stroma with arborizing vessels, fig 3: foci of fusiform spindle cells  

 

Fibrosarcoma of soft tissue - infantile (continued)

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Positive stains: vimentin; variable focal smooth muscle actin, desmin, S100 and CD34

EM: fibroblastic and myofibroblastic features

Molecular/cytogenetics: 70% have t(12;15)(p13;q26), causes ETV6-NTRK3 gene fusion transcript (ETS variant gene 6 and neurotrophic tyrosine receptor kinase type 3) detectable by FISH (Mod Path 2001;14:1246) or RT-PCR (AJSP 2000;24:937, AJCP 2001;115:348); similar translocation also present in secretory breast carcinoma (Mod Pathol 2009;22:291); also trisomy 8, 11, 17 and 20

Molecular images: ideogram of fusion transcript and FISH

Differential diagnosis:

▪ adult type fibrosarcoma - usually age 10+, no t(12;15)

▪ infantile fibromatosis - no pleomorphism, no mitotic figures, no t(12;15)

▪ myofibromatosis - myofibroblastic features, no t(12;15) (Pediatr Dev Pathol 2008;11:355)

References: Stanford University

 

Fibrous hamartoma of infancy of soft tissue

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

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

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

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

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

Treatment: excision, need not be aggressive as recurrence is uncommon (J Am Acad Dermatol 2006;54:800)

Gross: poorly circumscribed, gray-white with yellow fat, usually 5 cm or less

Gross/clinical images: untreated tumors - axillary tumor in 6 month old Nigerian boy;  scapular tumor in 7 year old Nigerian girl #1#2-at surgery showing well developed capsule

Micro: poorly circumscribed, organoid with 3 components - (1) trabecular or stellate immature mesenchymal cells with scant cytoplasm and bland straight or wavy nuclei in myxoid matrix, (2) fibrocollagenous tissue composed of bland fibroblasts or myofibroblasts, (3) mature fat; overlying epidermis usually has eccrine changes, including hyperplasia, duct dilation, intraluminal papillary formations and squamous syringometaplasia (J Cutan Pathol 2007;34:39); no/scant mitotic figures

 

Micro images: AFIP - triphasic pattern of fibrous spindle cells delimiting islands of mature fat and primitive spindle cellsprimitive spindle cells may infiltrate fatprimitive spindle cells and fibrous spindle cells are bland and uniform with no/rare mitotic figures

other - three cell types #1#2#3mature adipose and fibrous tissueplump mesenchymal cellsvarious imagescollagenous tissue and immature mesenchymal cellsH&E and t(2;3) karyotype

 

Fibrous hamartoma of infancy of soft tissue (continued)

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Cytology: moderate cellularity, adipose tissue fragments, clusters of fibroblastic cells, myxoid and collagenous matrix; no mitotic figures, no atypia (Diagn Cytopathol 2003;28:272, Acta Cytol 2008;52:201)

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

Negative stains: beta-catenin (Pediatr Dev Pathol 2008 Oct 21:1 [Epub ahead of print])

EM: fibrous trabeculae are composed of fibroblasts and myofibroblasts, primitive mesenchymal cells have slender cytoplasmic processes with few organelles

Cytogenetics: rarely complex translocations (Cancer Genet Cytogenet 2006;171:115), rarely t(2;3) (Archives 2005;129:520)

Differential diagnosis:

▪ 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 of soft tissue

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

Not a WHO diagnosis

Epidemiology: mean age 41 years, range 7-94 years

Clinical: usually healthy patients with no history of trauma; evolves over weeks to a localized, painful soft tissue swelling, usually of lower extremity

Solitary, self-limited, may be related to denervation

Case reports: due to statins (Int J Cardiol 2009;133:e33), due to Lyme disease (Arthritis Rheum 2006;54:2697), recurrent disease of peroneal muscles (Rheumatology (Oxford) 2002;41:1318), post bCG vaccination (Rheumatology (Oxford) 2002;41:1074), in pregnancy (Rheumatology (Oxford) 2000;39:211), 16 year old girl (J R Coll Surg Edinb 2000;45:339)

Treatment: usually none; spontaneously regresses

Gross: pale, ill-defined; mean 4 cm, range 1 to 20 cm

Micro: degeneration and regeneration of muscle fibers associated with interstitial inflammation and fibrosis; also focal neurogenic changes; occasionally prominent eosinophils; markedly inflamed cases have B cells or CD123+ dendritic plasma cells

 

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

 

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

Positive stains: CD163+ macrophages; lymphocytes are CD3+ and CD4+

Negative stains: macrophages are S100- and CD1a-; lymphocytes are negative for TIA1, granzymeB, EBV and ALK1 (Am J Surg Pathol 2009 Apr 9 [Epub ahead of print])

Molecular: no B or T cell rearrangement

DD: poliomyelitis

 

Gardner type fibroma of soft tissue

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Definition: benign soft tissue lesion with thick, haphazard collagen and bland fibroblasts that entrap adjacent tissue; 90% associated with FAP / Gardner’s syndrome / APC germline mutation

Uncommon; affects infants, children and teenagers

May be initial diagnostic clue to Gardner’s syndrome and APC mutations (AJSP 2001;25:645); 45% develop desmoid-type fibromatosis

Similar histology to nuchal-type fibroma (Pathol Int 2004;54:523, AJSP 2000;24:1563)

Sites: superficial or deep soft tissue; various sites

Case reports: post-surgical desmoid tumor in Gardner’s syndrome patient (J Neurooncol 2009;91:107)

Gross: 1-10 cm, poorly circumscribed, firm, rubbery, plaque-like, white to tan-pink cut surface with trapped fat in yellow areas

Micro: thick, haphazardly arranged collagen bundles, hypocellular bland fibroblasts, small blood vessels, plaque-like growth pattern with infiltration of adjacent structures

Micro images: image1

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

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

References: AJSP 2007;31:410, Stanford University

 

Giant cell angiofibroma of soft tissue

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Definition: uncommon benign neoplasm of multinucleated giant cells and ectatic vascular spaces

May be related to solitary fibrous tumor (AJSP 2000;24:971, Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:685, Ophthal Plast Reconstr Surg 2008;24:325)

Epidemiology: median age 45 years; more common in men in eyelid/orbital sites, more common in women elsewhere

Often slow growing painful mass

Case reports: 44 year old man with buccal mucosa tumor (Med Oral Patol Oral Cir Bucal 2008;13:E540), 50 year old woman with inguinal tumor (Ann Diagn Pathol 2000;4:240), 57 year old woman with eyelid tumor extending into orbit (Can J Ophthalmol 2006;41:216)

Treatment: excision, does not recur

Sites: eyelid, nasolacrimal duct (Ophthal Plast Reconstr Surg 2001;17:202), lacrimal sac or orbit (AJSP 1995;19:1286)

Gross: well circumscribed with variable capsule, median 3 cm (larger in extra-orbital regions), may have hemorrhagic or cystic cut surface

Micro: cellular areas with bland round to spindle cells in myxocollagenous stroma with small-medium thick walled vessels and multinucleated giant stromal cells that line ectatic vascular spaces

Micro images: various images #1#2

Positive stains: CD34, CD99, vimentin, variable bcl2

Negative stains: CD31, CD68, c-kit/CD117, muscle specific actin, S100, desmin

Cytogenetics: rarely t(12;17)(q15;q23) (Cancer Genet Cytogenet 2006;165:157), rarely 6q13 abnormalities (Cancer Genet Cytogenet 2000;116:47)

                                                                                                                                          

Giant cell fibroblastoma of soft tissue

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Definition: rare childhood fibroblastic tumor of intermediate malignancy with floret-like giant cells and ectatic pseudovascular spaces lined by stromal cells and giant cells

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

Appears to evolve into DFSP by genomic gains of COL1A1-PDGFB (Genes Chromosomes Cancer 2008;47:260); considered the juvenile form of DFSP, as both have the same translocation (AJSP 2003;27:27)

Epidemiology: usually children less than 10 years old, 2/3 male

Painless nodule of subcutis, usually in trunk, extremities, head and neck

50% recur but recurrences are controllable, no metastases

Case reports: 3 year old boy with recurrent knee lesion (Pathol Oncol Res 2003;9:249), 28 year old woman with vulvar tumor (J Low Genit Tract Dis 2007;11:112)

Gross: poorly circumscribed, gray to yellow mucoid mass that is difficult to completely excise, usually in subcutis

Micro: dermis and subcutis contains hyperchromatic spindle or stellate shaped cells in a collagenous or myxoid matrix with scattered hyperchromatic, multinucleated, floret-like giant cells with prominent nucleoli, similar to those in pleomorphic lipomas; ectatic pseudovascular spaces are lined by a discontinuous row of floret-like cells and tumor cells; honeycomb or parallel pattern of infiltration; also hyalinized area, perivascular lymphocytes in onionskin pattern, intralesional hemorrhage; often foci of DFSP; no histiocyte-like cells, no mitotic figures

Micro images: AFIP - ectatic pseudovascular spaces are lined by giant cells #1#2#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 nucleoli

other - trunk tumor #1#2#3tumor cells line pseudovascular spaces #1#2

 

Giant cell fibroblastoma of soft tissue (continued)

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Cytology: moderately cellular smears with mononuclear cells, usually single but occasionally in clusters; most cells have no/scanty cytoplasm, bland nuclei with small nucleoli; nuclear membranes often have notches, creases or folds; rare multinucleated giant cells with bland oval nuclei; no necrosis, no mitotic figures (Diagn Cytopathol 2002;26:398, Archives 2001;125:1091)

Cytology images: various images (fig a-c)

Positive stains: vimentin, CD34, CD99 (40%, J Cutan Pathol 2008;35:647), variable actin

Negative stains: S100, CD31, Factor VIII, keratin, desmin, HMB45

Molecular/cytogenetics: t(17,22)(q22;q13) - creates fusion of collagen type 1 alpha 1 gene and platelet derived growth factor B chain gene; also supernumerary ring chromosomes derived from t(17;22)

EM: myofibroblasts or fibroblasts

Differential diagnosis:

▪ neurofibroma with ancient change - no ectatic vascular spaces, S100+

▪ pleomorphic liposarcoma - pleomorphic cells are similar, but remaining lesion has lipoblasts and lacks collagenous matrix

▪ angiosarcoma - older adults in head and neck, vascular tumor, cells have enlarged atypical nuclei, mitotic figures present

▪ hemangioma - vascular tumor, no giant cells, CD31+

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

 

Hemangiopericytoma of soft tissue

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

Diagnosis of exclusion (Histopathology 2006;48:63)

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

Probably not a lesion of pericytes, except at sinonasal location

See myofibroma / myofibromatosis for infantile lesions

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

Epidemiology: middle aged adults, more common in women

Most common in deep soft tissue, particularly pelvic retroperitoneum, also limb or limb girdles and head and neck

Occasionally associated with hypoglycemia (J Clin Endocrinol Metab 1996;81:919)

5 year survival was 86% in 2002 (Cancer 2002;95:1746)

70% have benign behavior

Poor prognostic factors may be 4+ mitotic figures/10 HPF, necrosis, nuclear pleomorphism with size > 5 cm

Case reports: omental tumor with metastases (World J Surg Oncol 2007;5:63)

Gross: well circumscribed, yellow-tan cut surface, fleshy or spongy with hemorrhage but no necrosis, up to 15 cm

Gross images: encapsulated omental tumor #1#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

 

Hemangiopericytoma of soft tissue (continued)

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Micro images: staghorn vessels are prominent #1#2uniform cells around branched, thin-walled, staghorn vesselsvarious images (many from CNS)meningeal tumorsreticulin stainhemangiopericytoma of CNS is CD34+ (figure 3) / CD31 neg (figure 4)

Cytology: cellular; single and tightly packed clusters of oval to spindle cells aggregated around branched capillaries; often basement membrane material present; nuclei are uniform, oval, with finely granular chromatin and indistinct nucleoli; no mitotic figures, no necrosis (Cancer 1999;87:190)

 

Cytology images: irregular fragments of tissue, loose cellular aggregates and single 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 cells

 

Virtual slides: hemangiopericytoma

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

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

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

Differential diagnosis:

▪ solitary fibrous tumor - more prominent collagen, less prominent vessels

▪ monophasic synovial sarcoma - similar vascular pattern, characteristic translocation

▪ myopericytoma - predominant growth pattern is concentric perivascular arrangement of plump spindle cells (J Clin Pathol 2006;59:67)

▪ deep fibrous histiocytoma - storiform pattern, fibrohistiocytic lesion

▪ mesenchymal chondrosarcoma - malignant chondrocytes present

▪ endometrial stromal sarcoma (CD10+, ER+, Mod Path 2005;18:40)

References: eMedicine, Orphanet

 

Lipomatous hemangiopericytoma

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Definition: variant with mature adipose tissue

Also called adipocytic variant of solitary fibrous tumor

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

Epidemiology: uncommon; 2/3 males, usually thigh, lower extremity and retroperitoneum

Only rarely recurs, does not metastasize

Case reports: 41 year old woman with thigh tumor (Arch Pathol Lab Med 1999;123:941), 56 year old man with retroperitoneal mass (Case of the Week #16), mediastinal tumor (J Postgrad Med 2006;52:71), in skull base and parapharyngeal space (Otol Neurotol 2006;27:560)

Gross: solid, tan-yellow

Gross images: circumscribed mass has lipid-rich and lipid poor areas

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

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

other - classic hemangiopericytoma featureslipid rich componentmultivacuolated fat cellswith metaplastic bone

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

Positive stains: vimentin, CD99, CD34 (75%), bcl2 (60%)

Negative stains: CD31, desmin, keratin, actins, S100, GFAP

EM: features of pericytes, no lipoblasts

DD: various lipomas, liposarcoma

References: Hum Path 2000;31:1108, AJSP 1999;23:1201

 

Inclusion body fibromatosis of soft tissue

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Definition: dermal fibroblastic and myofibroblastic lesion with cytoplasmic eosinophilic inclusions, usually in digits of infants

Also called infantile digital fibromatosis, infantile digital fibroma (J Hand Surg [Am] 1995;20:1014)

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

Sites: usually exterior surface of distal phalanges of fingers and toes, but not thumb or great toe, also oral cavity and breast

50% recur, do not metastasize

Similar inclusions reported in breast fibroadenoma (Archives 2007;131:1126), breast phyllodes tumor (AJSP 1994;18:506), cervical polyp (Pathology 1998;30:215), GI leiomyomas (Cesk Patol 2006;42:139)

Case reports: spontaneous regression (J Dermatol 1998;25:523), post-surgical tumors in all extremities (Ann Plast Surg 2008;61:472)

Treatment: excision, but preserve function because recurrences are not destructive and tumors do not metastasize (Am J Surg Pathol 2009;33:1)

Clinical images: #1various images

Gross: nodules with stretched overlying skin, lesions are ill defined, white-tan, usually 2 cm or less; no hemorrhage or necrosis

Micro: nonencapsulated, dermal proliferation of hypocellular sheets or fascicles of fibroblasts and myofibroblasts with variable collagen; some spindle cells have peculiar eosinophilic (hyaline) cytoplasmic inclusions the size of a lymphocyte nucleus; usually mitotic figures; may infiltrate into adjacent tissue; no atypia

Micro images: AFIP - proliferation extends from epidermis to deep dermis or 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), calponin, desmin, CD99; often CD117

Negative stains: inclusions - PAS; spindle cells - keratin, ER, PR, beta-catenin

EM: spindle cells are myofibroblasts with rough endoplasmic reticulum and free lying inclusions composed of compact masses of actin granules and filaments without a limiting membrane (Am J Pathol 1979;94:19)

Differential diagnosis:

▪ infantile fibrosarcoma - not digits, usually > 2 cm, more cellular, chromatin is denser and more irregular, more mitotic figures, no inclusions

▪ infantile desmoid fibromatosis - rare on hand, usually > 2 cm, more cellular, no inclusions

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

Clinical: 1/3 have associated fever, growth failure, malaise, weight loss, anemia, thrombocytosis, polyclonal hyperglobulinemia and elevated sedimentation rate; symptoms disappear after excision of mass (J Korean Med Sci 2002;17:699)

Poor prognostic factors: abdominal or pelvic sites, ALK negative (AJSP 2007;31:509)

Case reports: 6 year old boy with abdominal wall tumor (Surg Today 2007;37:352), 7 year old girl whose abdominopelvic tumor has t(1;2)(q21; p23) (Archives 2006;130:1042), 18 year old man with omental tumor and bone marrow involvement (Archives 2003 Jul;127:865), 46 year old woman with retroperitoneal tumor (World J Surg Oncol 2005;3:66), 63 year old man with mesenteric tumor (World J Gastroenterol 2007;13:3645)

Treatment: excision (J Pediatr Surg 2005;40:1581), 25-35% recur, rare metastases (or may be evidence of multifocality)

Gross: circumscribed, not encapsulated; white tan mass with whorled fleshy or myxoid cut surface; may have focal hemorrhage, necrosis or calcification, mean 6 cm

Gross: 19 cm mesenteric tumor (fig 2-4)

Micro: myofibroblastic and fibroblastic spindle cells with inflammatory infiltrate of lymphocytes, plasma cells, eosinophils, histiocytes; background of abundant blood vessels; mixture of three patterns: (1) resembling nodular fasciitis with elongated myofibroblasts containing abundant eosinophilic cytoplasm and vesicular nuclei, loose myxoid stroma with neutrophils, lymphocytes and eosinophils, but few plasma cells; (2) cellular with spindled myofibroblasts and fibroblasts in more compact stroma, arranged as islands surrounded by fibromyxoid stroma with prominent plasma cells and mitotic figures; (3) densely hyalinized stroma with few spindle cells, few plasma cells or lymphocytes; may have ganglion-cell like myofibroblasts; all 3 patterns have no nuclear pleomorphism, no atypical mitotic figures

malignant behavior - associated with highly atypical polygonal cells with oval nuclei, prominent nucleoli, Reed-Sternberg like cells, atypical mitotic figures

 

Inflammatory myofibroblastic tumor of soft tissue (continued)

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Micro images: AFIP - typical appearance of spindled myofibroblastic cells and inflammatory infiltrate #1#2inflammation obscures the underlying myofibroblastic proliferationspindle cells are evident at high powertumor with more fibrous stroma  

other - myofibroblasts and inflammatory cells #1#2#3#4#5various 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;39:846), ALK1 / p80 in 40%, but not specific (Mod Path 2002;15:931), keratin and desmin in 1/3

Negative stains: S100, CD117, HHV8 (Mod Path 2007;20:995), CD34, h-caldesmon

EM: myofibroblastic cells and activated fibroblasts

EM images: fig b: filamentous bundles, attachment densities, pinocytotic vesicles and basal lamina

Molecular/cytogenetics: clonal abnormalities of 2p23 (Cancer Res 1999;59:2776), including t(2;5)(p23;q35) involving ALK and NPM; also t(2;17)(p23;q23) involving ALK and CLTC (Am J Path 2001;159:411) and t(2;19)(p23;p13.1) involving ALK and TPM4 (Am J Path 2000;157:377); associated with ALK deregulation and younger patients; see Atlas of Genetics

Molecular images: t(2;5) 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

Differential diagnosis:

▪ calcifying fibrous pseudotumor - calcification, no myofibroblastic proliferation, actin negative (Mod Path 2001;14:784)

▪ nodular fasciitis - smaller size, older patients, less inflammation

▪ low grade myofibroblastic sarcoma - more uniform appearance with higher cellularity, more prominent hyperchromasia, more infiltrative, ALK (Hum Pathol 2008;39:846)

 

Intranodal palisaded myofibroblastoma of soft tissue

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Definition: benign myofibroblastic spindle cell tumor arising within lymph nodes (usually in the groin) associated with amianthoid fibers and resembling schwannoma

Also called intranodal hemorrhagic spindle cell tumor with amianthoid fibers; formerly called intranodal schwannoma

Amianthoid: resembles amianthus, a type of asbestos with particularly fine fibers (image #1#2); tumor fibers are extracellular collagen

Described by Weiss et al (AJSP 1989;13:341) and Suster et al (AJSP 1989;13:347)

Epidemiology: 2/3 male, 2/3 ages 45-55 years (Arch Pathol Lab Med 2007;131:306)

Sites: occurs primarily in the groin, but also other sites

Case reports: 49 year old woman with renal transplant and recurrence (Arch Pathol Lab Med 1999;123:433), 62 year old man with supraclavicular mass (UPMC Case #121), 71 year old man with inguinal mass (Archives 2003;127:1040)

Treatment: local excision is almost always curative

Gross: well circumscribed, gray-white with hemorrhage and peripheral nodal tissue

Micro: benign spindle cells with scant cytoplasm, elongated nuclei arranged in fascicles; spindle cells have myofibroblastic or smooth muscle features; large amianthoid fibers (strongly eosinophilic, extracellular matrix deposits composed of crystalline fibers) around which the cells palisade; areas of acute hemorrhage and hemosiderosis; peripheral lymph node tissue; no/rare mitotic figures, no atypia, no slit like vascular spaces, no extravasated red blood cells

 

Micro images: various images #1#2#3#4peripheral rim of nodal tissueoriginal and recurrent tumor;  focal palisading and metaplastic bone formationH&E and cyclin D1smooth muscle actin+, cyclin D1+, EM imagesamianthoid fibers composed of a central vessel surrounded by a core of collagen with peripheral spokes, strongly stained by Van Gieson

 

Intranodal palisaded myofibroblastoma of soft tissue (continued)

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Cytology: moderately cellular with benign appearing, dissociated, single spindle cells with elongated nuclei, pointed ends and occasional twisted forms; in pale fibrillary matrix with hemosiderin granules, no atypia (Acta Cytol 2002;46:1143)

Positive stains: spindle cells - smooth muscle actin, vimentin, cyclin D1 (Arch Pathol Lab Med 2003;127:1040), variable factor XIIIa; amianthoid fibers - elastic stains, trichrome, collagen type I/III, smooth muscle actin

Negative stains: S100, synaptophysin, GFAP, Ki-67 (<5%), desmin, EMA, keratin