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 references, soft tissue-normal, approach to diagnosis, sarcomas-general, syndromes, grading, cell types, architectural patterns, molecular
Infections, inflammation and hematoma: general, granulomatous, hematoma, necrotizing fasciitis, PVP granuloma, tumoral calcinosis
Fibroblastic / myofibroblastic: normal, general, angiomyofibroblastoma, calcifying aponeurotic fibroma, calcifying fibrous tumor, cellular angiofibroma, dermatofibrosarcoma protuberans, desmoplastic fibroblastoma, elastofibroma, eosinophilic fasciitis, fibroma of tendon sheath, fibromatosis-general, fibromatosis-superficial, fibromatosis-deep, fibromatosis colli, fibrosarcoma-adult, fibrosarcoma-infantile, fibrous hamartoma of infancy, focal myositis, Gardner fibroma, giant cell angiofibroma, giant cell fibroblastoma, hemangiopericytoma, inclusion body fibromatosis, inflammatory myofibroblastic tumor, intranodal palisaded myofibroblastoma, ischemic fasciitis, juvenile hyaline fibromatosis, lipofibromatosis, low grade fibromyxoid sarcoma, low grade myofibroblastic sarcoma, mammary type myofibroblastoma, myofibroma / myofibromatosis, myositis ossificans, myxofibrosarcoma, myxoinflammatory fibroblastic sarcoma, nodular fasciitis and related lesions, nuchal fibrocartilaginous pseudotumor, nuchal type fibroma, ossifying fibromyxoid tumor, pleomorphic fibroma, proliferative fasciitis, proliferative myositis, proliferative peribursitis, sclerosing epithelioid fibrosarcoma, solitary fibrous tumor, superficial acral fibromyxoma
Index (table of contents in alphabetical order)
A-F: angiomyofibroblastoma, approach to diagnosis, architectural patterns, calcifying aponeurotic fibroma, calcifying fibrous tumor, cell types, cellular angiofibroma, dermatofibrosarcoma protuberans, desmoplastic fibroblastoma, elastofibroma, eosinophilic fasciitis, fibroblastic/myofibroblastic - general, fibroblastic/myofibroblastic - normal, fibroma of tendon sheath, fibromatosis colli, fibromatosis-deep, fibromatosis-general, fibromatosis-superficial, fibrosarcoma-adult, fibrosarcoma-infantile, fibrous hamartoma of infancy, focal myositis
G-O: Gardner fibroma, giant cell angiofibroma, giant cell fibroblastoma, grading, granulomatous, hemangiopericytoma, hematoma, inclusion body fibromatosis, infection, inflammation, and hematoma - general, inflammatory myofibroblastic tumor, intranodal palisaded myofibroblastoma, ischemic fasciitis, juvenile hyaline fibromatosis, lipofibromatosis, low grade fibromyxoid sarcoma, low grade myofibroblastic sarcoma, mammary type myofibroblastoma, molecular, myofibroma / myofibromatosis, myositis ossificans, myxofibrosarcoma, myxoinflammatory fibroblastic sarcoma, necrotizing fasciitis, nodular fasciitis and related lesions, nuchal fibrocartilaginous pseudotumor, nuchal type fibroma, ossifying fibromyxoid tumor
P-Z: pleomorphic fibroma, primary references, proliferative fasciitis, proliferative myositis, proliferative peribursitis, PVP granuloma, sarcomas-general, sclerosing epithelioid fibrosarcoma, soft tissue-normal, solitary fibrous tumor, superficial acral fibromyxoma, syndromes, tumoral 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
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
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
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
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
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
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:
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
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
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
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
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
Usually due to direct extension from infections of skin, bone or viscera, or due to trauma or surgery
Granulomatous infections of soft tissue
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)
May clinically resemble a tumor if deep seated
Sites: usually near tensor fascia lata (upper thigh muscle, image)
Important to exclude a sarcoma with intratumoral hemorrhage
Pseudoaneurysm may occur after intravascular procedures
Post-operative seromas may persist for years and be confused with recurrent tumor
Case reports: in tensor fascia lata (Dermatol Online J 2001;7:6), giant chronic expanding hematoma of thigh (Joint Bone Spine 2008;75:64), mass of thorax (Yonsei Med J 2007;48:337)
Treatment: complete surgical excision, including pseudocapsule
Clinical images: lesion of lateral thigh
Gross images: perforating vessel (arrow) from tensor fascia lata appears to run into the mass; lobulation with dense fibrous pseudocapsule and chocolate-brown fluid
Micro images: cystic cavity with necrotic debris, fibrin and blood costs; cyst wall has hyalinized fibrous tissue, chronic inflammation and granulation tissue
Necrotizing fasciitis of soft tissue
Definition: uncommon fulminant soft tissue infection characterized by extensive fascial necrosis
Pathophysiology: usually due to group A streptococci, also community-acquired MRSA (Surg Infect (Larchmt) 2008;9:469)
May be due to Clostridium perfringens and cause gas gangrene (Cases J 2008 Oct 20;1(1):252)
In children, associated with varicella and speC gene in group A streptococcal strains (Pediatr Infect Dis J 2009 Apr 14 [Epub ahead of print])
Clinical: fatal if untreated; 15% mortality even if treated (Epidemiol Infect 2009 Apr 7:1 [Epub ahead of print])
Particularly serious in patients with badly controlled diabetes (Diabetes Res Clin Pract 2008;80:218)
Case reports: due to Pseudomonas (Intern Med 2008;47:553)
Treatment: promptly start antibiotics and aggressive debridement (World J Emerg Surg 2007;2:19, J Am Acad Orthop Surg 2009;17:174)
Clinical images: gas gangrene #1; #2-right shoulder; left leg
Micro images: gluteal gas gangrene with necrotizing fasciitis #1; #2; #3-gram stain; #4-gram stain; #5; necrotic muscle with gas bubbles but minimal inflammation; infected tissue with gas-inclusion between the muscle fibers; gram positive rods; leg lesion #1; #2; #3; #4; #5; #6-septic thrombus; #7-associated vasculitis; #8-gram stain; #9-gram stain
References: eMedicine #1; #2
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
Definition: large painless calcified masses in periarticular soft tissues, including elbows, hips, only rarely knees
Also called calcium hydroxyapatite deposition in soft tissue, metastatic calcification
Usage is imprecise - refers to hereditary condition associated with massive periarticular calcification; also any massive collection of periarticular calcification (Radiographics 2006;26:871)
Clinical: associated with trauma, renal failure, hyperparathyroidism, metastatic carcinoma, myeloma, scleroderma, hypermetabolic states, sarcoidosis
Associated with mutations in fibroblast growth factor-23 gene and other genes (J Bone Joint Surg Am 2009;91:1190, OMIM #212900)
Rarely is familial (AJSP 1993;17:788)
Laboratory: elevated serum calcium, phosphate and Vitamin D
Local recurrence common
Xray: lobulated calcifications, separate from associated bone
Gross: large, multinodular, chalky masses
Micro: lobules of calcific material surrounded by histiocytic giant cells often containing small psammomatous calcifications
Micro images: low power; calcification with foreign body inflammation
Differential diagnosis: dystrophic calcification - dead tissue that is not rapidly absorbed; associated with coagulation necrosis, caseous necrosis, fat necrosis
Fibroblastic / myofibroblastic tumors of soft tissue
Normal histology of soft tissue
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
Large subset of mesenchymal tumors
Cells / tumors may have both fibroblastic and myofibroblastic features
Angiomyofibroblastoma of soft tissue
Definition: benign, well-circumscribed myofibroblastic tumor, usually in vulva
May overlap with cellular angiofibroma
First described in 1992 (AJSP 1992;16:373)
Clinical: uncommon slow growing painless mass, usually females of reproductive age
Sites: usually vulvar, 10-15% in vagina; also scrotum or paratesticular soft tissue in men (median age 57 years)
Case reports: recurrence in vagina (Eur J Gynaecol Oncol 2007;28:324), pedunculated vulvar mass (Acta Med Okayama 2006;60:237), sarcomatous transformation in vulva (AJSP 1997;21:1104), 27 year old man with inguinal tumor (Archives 2000;124:1679), 49 year old man with scrotal mass (Univ Oklahoma)
Treatment: excision, only rarely recurs, does not metastasize
Gross: well circumscribed but not encapsulated, usually 5-7 cm or less, tan-pink soft cut surface, no necrosis
Micro: thin fibrous pseudocapsule, alternating hyper- and hypocellular areas with prominent thin walled and ectatic vessel in edematous stroma; round to spindled tumor cells have eosinophilic cytoplasm and often bi- or multi-nucleation; may have plasmacytoid or epithelioid morphology, or rarely show degenerative changes; tumor cells are concentrated around vessels; mast cells common; 10% have mature adipose tissue; no/rare mitotic figures, no/rare red blood cell extravasation, no atypia; post-menopausal patients have less cellularity, less edema but more fibrosis and vessel wall hyalinization
Micro images: gross and H&E; fig A: numerous capillary-like vascular channels, fig B: spindle cells with occasional multinucleated cells; male inguinal region-actin, desmin, CD34; scrotal mass-various images; arising from posterior perivesical space
Positive stains: vimentin, desmin (strong and diffuse, may be reduced in post-menopausal patients), ER, PR, smooth muscle actin or pan-muscle actin (focal, Hum Path 1997;28:1046), occasional CD34
Negative stains: S100, keratin
EM: myofibroblastic and fibroblastic features
Differential diagnosis:
▪ aggressive angiomyxoma - not circumscribed, > 5 cm, less cellular, less vascular but vessels are large and thick walled, stromal mucin and RBC extravasation are present, infrequent plump stromal cells, usually actin negative
▪ cellular angiofibroma - more cellular uniformly, perivascular hyalinization and large, thick walled vessels, usually actin/desmin negative
▪ epithelioid leiomyoma - more cellular, no biphasic pattern, usually no binucleation, no/rare mast cells
Reference: Mod Path 1996;9:284, Stanford School of Medicine
Calcifying aponeurotic fibroma of soft tissue
Definition: rare, slow growing, painless tumor with fibroblasts palisading around chondroid or calcified nodules, usually in hands and feet of children or young adults
Also called juvenile aponeurotic fibroma
Clinical: 50% recur, especially in children; does not metastasize
May be cartilaginous analog of fibromatosis
Case reports: 16 year old girl with foot tumor (Case of the Week #47), 36 year old woman with distal phalangeal bone involvement (Korean J Radiol 2008;9:91)
Treatment: conservative excision with reexcision as necessary for recurrences
Clinical images: 46 year old woman
Gross: nodular or infiltrative gray-white, gritty mass in subcutaneous tissue or tendon, may be calcified, usually 3 cm or less in hands or feet, may be larger elsewhere
Gross images: non-encapsulated and ill-defined mass
Micro: nodules of plump or epithelioid fibroblasts palisading around cartilage and spotty calcification; cells have indistinct and variable cytoplasm, plump oval nuclei with vesicular chromatin that may be condensed below nuclear membrane; fibrocytes in stroma between nodules have dense, evenly dispersed chromatin; may infiltrate fat or striated muscle at periphery; frequent osteoclast-like giant cells; rare mitotic figures, no atypia; more cellular in very young
Micro images: AFIP - poorly circumscribed fibroproliferative process with scattered, linear and calcified zones; amorphous calcification surrounded by palisading cells suggestive of rheumatoid nodule or crystals; typical zonation pattern has cellular, plump fibroblastic cells palisading around a hyalinized collagenous zone, which in turn surrounds the calcification; cells adjacent to hyalinized layer are commonly more rounded; chondroid area is adjacent to calcification
other - spotty calcifications and chondroid-like cells; palisading tumor cells #1; #2
16 year old girl with foot tumor - #1; #2; #3; #4; #5
Calcifying aponeurotic fibroma of soft tissue (continued)
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
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 surface; well circumscribed tumor (adrenal gland)
Micro: paucicellular fibroblastic proliferation with lymphocytes (possibly lymphoid follicles), plasma cells, eosinophils, mast cells, dense collagenous tissue, varying degrees of calcification; border is often at least partially infiltrative
Micro images: AFIP - adrenal gland tumor has paucicellular fibrous proliferation with focal microcalcifications; microcalcifications vary in size; lymphoplasmacytic inflammation is characteristic
other - psammoma body, lymphocytic infiltrate, hypocellular stroma; figures 1A, 1B, 1E and 1F (comparison with inflammatory myofibroblastic tumor); hyalinized collagen with psammoma body; various images (adrenal gland)
Calcifying fibrous tumor of soft tissue (continued)
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
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 tissue; fusiform cells with clear cytoplasm and bland nuclei; various images; recurrent tumor; ER+
Virtual slides: 63 year old man with scrotal mass
Positive stains: ER, PR, vimentin; smooth muscle actin (21%), CD34 (30-60%)
Negative stains: S100, desmin, EMA
Cytogenetics: may have 13q14 involvement; similar changes as spindle cell lipoma (Cancer Genet Cytogenet 2007;177:131)
Cellular angiofibroma of soft tissue (continued)
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
See Skin-Nonmelanocytic tumors chapter
Desmoplastic fibroblastoma of soft tissue
Definition: fibroblastic lesion centered in subcutaneous tissue with reactive fibroblasts, low cellularity and abundant collagen
Also called collagenous fibroma
Epidemiology: rare benign lesion of adult men (70% between ages 40 and 69 years)
Sites: usually upper extremities, back, feet
Case reports: 41 year old woman with thigh mass (J Cutan Pathol 2008;35 Suppl 1:70)
Treatment: conservative excision, does not recur or metastasize
Gross: usually 1-4 cm, well circumscribed, may be lobulated, has firm and homogeneous gray cut surface resembling cartilage
Gross images: well circumscribed tumor
Micro: paucicellular, bland spindled (stellate) and reactive appearing fibroblasts and myofibroblasts separated by abundant collagen with variable myxoid stroma; fibroblasts have amphophilic cytoplasm, vesicular nuclei and distinct nucleoli; 70% of cases involve subcutis, 25% extend into skeletal muscle
Micro images: AFIP - large, reactive appearing spindled fibroblasts in fibrous matrix; focus of low cellularity and dense collagen; more cellular area with reactive type fibroblasts
other - scattered stellate cells in hypovascular collagenous matrix; hypocellular lesion with pseudocapsule and sparse cells separated by abundant collagen; spindle cells with long nuclei in dense collagenous stroma; vimentin+; most cells are negative for smooth muscle actin
Positive stains: vimentin, variable alpha smooth muscle actin
Negative stains: desmin, EMA, S100, CD34
EM: may have fibronexus junctions, markers of myofibroblastic differentiation (Ultrastruct Pathol 2004;28:149)
Molecular/cytogenetics: t(2;11)(q31;q12) or 11q12 abnormalities observed rarely (Cancer Genet Cytogenet 2004;149:161)
Differential diagnosis: fibromatosis - not circumscribed, more cellular, fascicular pattern, prominent vasculature (Adv Anat Pathol 1999;6:275)
References: Hum Path 1998;29:676, AJSP 1995;19:1077, Stanford University
Definition: age 55+ years, benign, poorly circumscribed pseudotumor of subscapular region, composed of collagen and coarse enlarged elastic fibers; a reactive hyperplasia involving abnormal elastogenesis
Also called elastofibroma dorsi
First described in 1961 by Jarvi and Saxen (Acta Pathol Microbiol Scand 1961;51:83)
Epidemiology: associated with hard manual labor; related changes found at autopsy in 13-17% of elderly; more common in women
Sites: more common on apex of scapula, usually right sided; occasionally in deltoid muscle, infraolecranon area, hip, thigh, stomach
May be multiple, bilateral or familial; may be periosteal in origin
Slightly different amino acids from elastin; has collagen types I-III (type II normally restricted to articular cartilage and ocular structures)
Case reports: 55 year old woman (Case of the week #46), 69 year old man with tumor of hand (J Bone Joint 1987;89:468), 69 year old woman with bilateral subscapular tumors and tumor surrounding a stomach ulcer (AJSP 1985;9:233), 78 year old man with multiple subcutaneous nodules (J Am Acad Dermatol 2004;50:126)
Treatment: excise if symptomatic, does not recur
Clinical images: shoulder based tumors; typical location (arrow)
Gross: ill defined, rubbery, gray-white fibrous tissue mixed with yellow streaks of elastin; up to 15 cm
Gross images: fibrocollagenous areas blend with fat (AFIP); poorly defined fibroelastic tumor entrapping fat #1; #2; #3; gray-white fibrous tissue mixed with fat
Micro: collagen bundles alternate with large, thick eosinophilic elastic cylinders with a dense central core, elastic fibers may be fragmented into linear globules (beads on a string); often has irregular interdigitation into adipose tissue
Elastofibroma of soft tissue (continued)
Micro images: AFIP - paucicellular fibrous tissue mixed with fat; thick, densely eosinophilic elastin bands are mixed with collagen; elastin bands have serrated edges and are associated with detached globular elastin arranged like beads on a string; Verhoeff elastin stain highlights elastin fibers and the bead-like arrangement of the elastin globules
other - thick bands of fibrous tissue (long arrows) intermixed with multiple regions of mature adipose tissue; diagnostic rods of elastic tissue; fibrous tissue mixed with elastin bands; fibrohyaline mass within adipose; branched (arrow) and unbranched coarse elastin fibers mixed with collagen and adipose; H&E and elastic stain; elastin stain #1; #2; #3; #4
case of the week #46: image #1; #2; #3; #4; #5; #6; #7; orcein (elastin) stain
Cytology: hypocellular smear with diagnostic aggregates of globules within a collagenous matrix; altered elastic fibers have green-yellow autofluorescence with ultraviolet light (Diagn Cytopathol 2002;26:310)
Positive stains: vimentin, elastic stains (fibers have dense core and irregular margins), CD34 in spindle cells (Virchows Arch 2006;448:195)
Negative stains: S100, desmin, smooth muscle actin, p53
EM: cylinders composed of immature amorphous elastic tissue, central core contains mature fibers, removed by elastase digestion (J Electron Microsc (Tokyo) 2006;55:89)
Molecular/cytogenetics: Xq12-q22 or #19 gains in 30% (Int J Mol Med 2002;10:277)
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
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; #6; inflammatory infiltrate in deep subcutis #1; #2
References: eMedicine #1; #2
Fibroma of tendon sheath of soft tissue
Definition: well circumscribed, lobulated fibrous tumor attached to tendon or tendon sheath
Also called tenosynovial fibroma
Benign, uncommon; may overlap with nodular fasciitis (AJSP 1989;13:472) or giant cell tumor of tendon sheath (Mod Path 1995;8:155)
Epidemiology: 60% men, ages 30-50 years old with nodule on fingers, hands or wrist
Case reports: tumors of palmar flexor sheath (Internet Journal of Hand Surgery. 2008 Volume 2 Number 1), medial canthus of eye (Ophthal Plast Reconstr Surg 2007;23:341)
Treatment: excise to relieve symptoms but preserve function, may be difficult to remove from adherent tendons; benign, but up to 24% recur, does not metastasize
Gross: well circumscribed, small fibrous multinodular mass < 3 cm, cut surface is pale, solid and homogeneous
Micro: well circumscribed nodules of dense fibrous tissue with occasional spindle or stellate mesenchymal cells in S or C shaped patterns; cells have scant cytoplasm and elongate nuclei with evenly distributed fine chromatin; often dilated or slit-like channels / clefts resembling tenosynovial spaces; varies from cellular to paucicellular; may have bizarre tumor cells, extravasated red blood cells, but no atypical mitotic figures, no necrosis, no hyperchromasia
Micro images: AFIP - multinodular proliferation; extensive collagenization of nodules produces this typical, eosinophilic, paucicellular appearance, incomplete separation of the nodules produces cleft-like spaces; most cases are paucicellular with scattered spindled fibroblasts in a densely collagenized matrix and scattered small vessels; transition from collagenous to cellular area; cellular area resembles leiomyosarcoma or fibrosarcoma, but these tumors are rare in hands and feet; fibroblasts are bland (ruling out sarcoma) and separated by collagen
other - predominately acellular fibrous tissue with areas of hyalinization and characteristic slit-like vascular channels; tumor of finger #1; #2; #3; hypocellular lesion with abundant collagen; spindled fibroblasts in collagenous stroma with slit like vascular channels
Fibroma of tendon sheath of soft tissue (continued)
Cytology images: loose cohesive clusters of bland spindle cells with variable cytoplasm, oval to elongated nuclei; spindle cells in hyalinized collagen
Positive stains: smooth muscle actin, vimentin
EM: resembles myofibroblasts and fibroblasts
EM images: spindle cells in collagenous matrix (M) have oval and convoluted nuclei (N), clefts (C) are present between cells and nuclei; spindle cell has a convoluted nucleus (N), rough endoplasmic reticulum (RER), vacuoles (V) and thin band of myofilaments just beneath the plasma membrane (arrows); myofilament bundles (M) show periodic densities (arrows); spindle cell has rough endoplasmic reticulum (RER), myofilaments (M) and pinocytotic vesicles (arrows)
Molecular/cytogenetics: may have t(2;11)(q31-32;q12) (Histopathology 1998;32:433)
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
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
Definition: nodular proliferative process of palmar aponeurosis, surrounding adipose and occasionally dermis, due to fibroblasts, myofibroblasts and fibrocytes
Most common type of fibromatosis (1-2% of population), prevalence increases with age (24% at age 65+)
Epidemiology: 75% are men; 50% are bilateral, 10% also have plantar disease, 1-4% have penile fibromatosis
Clinical: puckers overlying skin as it ages; causes flexion contracture of digits 4 and 5 due to cord-like expansion of digital aponeurotic slips; does not involve deep structures such as tendons or skeletal muscle; may be caused by fibrogenic cytokines (J Hand Surg [Br] 2005;30:557)
Treatment: observation, excision or incision of contracture band; often recurs
Clinical images: flexion contracture #1; #2
Gross: small nodules or nodular masses associated with aponeurosis and subcutaneous fat, with gray-yellow-white cut surface (color depends on collagen content)
Micro: proliferative phase - uniform, plump, immature spindle cells (myofibroblasts and fibroblasts) with bland nuclei and indistinct nucleoli; moderate collagen and elongated vessels; older lesions - more dense collagen, less cellularity; variable mitotic figures; occasional attachment to dermis or cartilaginous metaplasia; usually no infiltration of surrounding tissue beyond subcutis
Micro images: AFIP - nodule of variably cellular fibroblastic tissue infiltrates an aponeurosis, with bland, uniform spindled cells in a dense hyalinized collagen stroma; mitotic figures may be present in cellular regions but are never atypical
other - tumor of myofibroblasts and fibroblasts within fascia #1; #2; #3; various images
Positive stains: vimentin, variable muscle specific and smooth muscle actin (in proliferative phase)
Negative stains: keratin, CD34
EM: fibroblasts and myofibroblasts
Molecular/cytogenetics: near diploid, often +7 or +8, no gene amplifications or deletions (Cancer Genet Cytogenet 2008;183:6), reactive not neoplastic (J Transl Med 2006;4:21), no somatic mutations of beta-catenin genes unlike desmoid fibromatosis (Mod Path 2001;14:695)
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
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 surface; various images
Gross: 2-3 cm nodules associated with aponeurosis and subcutis, with gray-yellow-white cut surface (color depends on collagen content)
Gross images: plantar nodules; nonencapsulated whitish tumor
Micro: proliferative phase - hypercellular collection of uniform, plump, immature spindle cells with bland nuclei and indistinct nucleoli; moderate collagen and elongated vessels; variable multinucleated giant cells (AJSP 2002;26:244); older lesions - denser collagen, less cellularity; often prominent chronic inflammation, variable mitotic figures and hemosiderin
Positive stains: vimentin, variable muscle specific and smooth muscle actin
EM: fibroblasts and myofibroblasts
Molecular/cytogenetics: near diploid, often +7 or +8, no somatic mutations of beta-catenin genes unlike desmoid fibromatosis (Mod Path 2001;14:695)
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
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)
Fibromatosis - deep (desmoid type), of soft tissue
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)
Gross images: AFIP - extra-abdominal fibromatosis has dense white, trabeculated fibrous tissue that invades skeletal muscle and produces cross section of alternating white and red patches; desmoid fibromatosis (left) contrasted with high-grade fibrosarcoma (right) - fibromatosis has gristle-like consistency, but fibrosarcoma tends to be white, fleshy and necrotic with an overlying tendon
other - tumor infiltrates thoracic wall; trunk tumor #1; #2; thigh tumor; thoracic tumor; gray-white tumor of Gardner syndrome; gray-glossy cut surface; tumor in mesentery of small bowel; well defined margin (uncommon); infiltrative margin; firm white fusiform mass
Micro: poorly circumscribed with infiltration of adjacent tissue; uniform cellularity between exuberant fibrous proliferation and low grade fibrosarcoma; cells are bipolar fibroblasts and myofibroblasts (amphophilic cytoplasm, open chromatin, well defined nuclear membrane, one distinct nucleolus, with reduced cytoplasm that merges with surrounding collagen; usually more collagenous and less cellular than nodular fasciitis; mucopolysaccharide matrix with thin walled, curvilinear, non-branching or ectatic vessels; stroma varies from collagenous, keloid-like to myxoid; regenerative muscle cells within lesions may resemble giant cells; perivascular lymphocytes at edge of lesion; few mitotic figures, no atypia
Micro images: extra-abdominal fibromatosis - AFIP - low power shows paucicellular fibrous proliferation in long fascicles, with numerous slit-like vessels characteristic of desmoid fibromatosis; fibroblasts have spindled, dense, wavy nuclei and minimal cytoplasm; margin shows infiltration of skeletal muscle, a common feature; atrophic and regenerating muscle fibers at the edge of the lesion may resemble rhabdomyoblasts; some tumors are myxoid; cells in myxoid tumors are uniformly bland, unlike those in malignant myxoid tumors; cellular tumor has scattered mitotic figures, none atypical; keloid-type pattern may be observed focally in deep tumors
extra-abdominal fibromatosis - other sources - paraspinal tumor #1; #2; thigh mass has spindle cells, dense collagenous stroma, slit-like vessels and chronic inflammation; pre-radiation therapy; post-radiation therapy shows reduced cellularity; breast tumor is smooth muscle actin+
Fibromatosis - deep (desmoid type), of soft tissue (continued)
intra-abdominal (mesenteric) fibromatosis - AFIP - tumor appears to be extrinsic to bowel muscularis propria, which distinguishes it from GIST; fibromatosis is paucicellular and composed of relatively uniform, bland spindle cells; bland, mitotically active, uniform cells in myxoid stroma; less commonly bland spindle cells are within collagen bundles; biopsy of pelvic tumor; trichrome stain highlights collagen in the fibromatosis and distinguishes it from overlying normal muscularis propria
intra-abdominal fibromatosis - other - uniform spindle cells with moderate collagen #1; #2
abdominal fibromatosis - extension into adjacent muscle; fascicles of fibroblastic spindle cells with abundant intercellular collagen
Cytology: bland spindle cells with long, fusiform nuclei and metachromatic matrix material; tumor cells are individual or as fragments within matrix (Cancer 2007;111:166); FNA is fairly reliable for diagnosis but core needle biopsy is better (Acta Orthop 2006;77:926)
Cytology images: various images
Positive stains: vimentin, variable smooth muscle actin and muscle specific actin, variable CD117 (AJSP 2002;26:1296, but depends on antibody used, AJSP 2001;25:549); also nuclear beta-catenin (sensitive but not specific, AJSP 2005;29:653, AJSP 2002; 26:1296), ER-beta (Cancer 2006;106:208)
Negative stains: keratin, S100, CD34 (J Clin Pathol 2004;57:1119), ALK, desmin
EM: fibroblastic and myofibroblastic features, including intrareticular collagen fibers, thin filament bundles, cytoplasmic dense bodies
Molecular/cytogenetics: clonal; associated with Wnt/beta-catenin (APC-beta-catenin-Tcf) pathways; somatic beta-catenin point mutations in exon 3, codon 41 or codon 45 in 87% (AJSP 2007;31:1299); also associated with trisomy 20 and 8 (Am J Path 1999;154:729, Cancer Genet Cytogenet 1995;79:139) and loss of 5q (APC gene)
Molecular/cytogenetic images: trisomy 20 and 8
Fibromatosis - deep (desmoid type), of soft tissue (continued)
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
Definition: fibromatosis affecting lower 1/3 of sternocleidomastoid muscle, causing thickened muscle; appears at birth, often bilateral
Also called congenital torticollis (torticollis: twisting of neck causing unnatural position of head, usually caused by spasm of neck muscles)
Epidemiology: associated with congenital anomalies (14% have congenital dislocations of hip, also breech deliveries)
May be due to birth injury (breech presentation, forceps)
Uncommon (0.4% of live births), usually diagnosed by age 6 months
Recommended to diagnose by FNA since excision usually is not required
Treatment: early - stretching and physiotherapy, resolves in 70%; some cases require resection of affected muscle; does not recur
Gross: tan gritty mass of muscle up to 3 cm, no hemorrhage or necrosis
Micro: diffuse proliferation of uniform plump fibroblasts and myofibroblasts and scar like collagen in muscle, with entrapped reactive and degenerating skeletal muscle fibers (loss of cross striations, nuclear enlargement and hypercellularity, multinucleation, atrophy); surgical specimens are usually less cellular than FNA specimens because they are obtained later in time course of disease
Micro images: AFIP - multinodular proliferation of acellular collagenized tissue replaces part of sternocleidomastoid muscle; skeletal muscle fibers are trapped at advancing edge of lesion; scattered, bland fibrocytes are widely separated by dense collagen
Cytology: early - cellular specimen with clusters or parallel arrays of bland appearing spindle cells in fibromyxoid matrix; also atrophic skeletal muscle in clean background, frequent muscle giant cells, bland bare nuclei and collagen (Acta Cytol 2003;47:359); usually no significant inflammation (Diagn Cytopathol 2000;23:338)
Positive stains: vimentin, actins
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
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
other - well circumscribed tumor
Micro: highly cellular fibroblastic proliferation in herringbone pattern (cells in columns of short parallel lines with all the lines in one column sloping one way and lines in adjacent columns sloping the other way); cells have scant cytoplasm, tapering elongated dark nuclei with increased granular chromatin, variable nucleoli; mitotic activity present, often with abnormal forms; variable collagen; usually no giant cells; no pleomorphism (or call pleomorphic MFH), no other distinct cell types
Patterns: keloid-like (thick hyalinized collagen fibers), loose fascicular, focally myxoid
Micro images: AFIP - atypical uniform cells in herringbone pattern; cells are clearly malignant, with coarse chromatin but minimal pleomorphism; grade I tumor has minimal pleomorphism and low mitotic index, but is more cellular than fibromatosis #1; #2; grade II tumor has intermediate features #1; #2; grade III tumor has high grade atypia and high mitotic index #1; #2
other - well differentiated tumor; nuclear pleomorphism
Virtual slides: fibrosarcoma
Fibrosarcoma of soft tissue - adult
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
Definition: resembles adult fibrosarcoma morphologically, but better prognosis
Age cutoff between infantile and adult forms usually varies between 5 and 10 years
Epidemiology: usually presents before age 2 years in axial regions or extremities with vary rapid growth
Related to congenital mesoblastic nephroma, which has same translocation
Clinical: 40-50% recur but only rarely metastasizes
Survival is 90%+
Case reports: premature newborn with large facial mass (Archives 2003;127:e281)
Treatment: surgery and chemotherapy (J Pediatr Hematol Oncol 2002;24:722, Pediatr Blood Cancer 2009;53:23)
Gross: may exceed 30 cm (grotesquely large compared to size of child) with tense erythematous and ulcerated overlying skin; firm to soft cut surface is fleshy, gray-tan with myxoid change, cystic degeneration, hemorrhage and necrosis
Gross images: AFIP - fleshy white mass similar to adult fibrosarcoma
Micro: poorly circumscribed, lobulated mass of small to large spindled cells in fascicles or herringbone pattern with high cellularity, nuclear atypia and pleomorphism; increased mitotic figures, hemorrhage and necrosis; resembles adult fibrosarcoma; may have prominent hemangiopericytoma-like areas, dystrophic calcification, extramedullary hematopoiesis; infiltrates adjacent soft tissue with irregular margins
Micro images: AFIP - biphasic pattern with fibroblastic and cellular myxoid areas; high power of myxoid area; infiltration of fat; infiltration of muscle; spindle cells; plump cells have granular chromatin; less cellular tumor which overlaps with infantile fibromatosis, although it almost never metastasizes #1; #2;
other - areas of variable cellularity; leg tumor #1; #2; #3; cellular tumor with mitotic figures; fig 1: facial tumor involves eye and maxilla, fig 2: undifferentiated cells with loose myxoid stroma with arborizing vessels, fig 3: foci of fusiform spindle cells
Fibrosarcoma of soft tissue - infantile (continued)
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
Definition: poorly circumscribed proliferation of immature spindle cells in organoid pattern with fat and dense fibrocollagenous tissue
Epidemiology: rare; usually age 2 years or less (25% discovered at birth), does not occur after puberty, 2/3 male
Sites: axilla, shoulder and inguinal region (J Urol 1994;152:990); not hands and feet
Solitary, rapidly growing, freely movable mass of subcutis or dermis
Case reports: 6 month old girl with arm mass (Univ Oklahoma), 6 month old girl with multiple nodules with overlying hypertrichosis (J Dermatol 2006;33:427), 6 month old boy with recurrent tumor (Pediatr Surg Int 2005;21:119), 11 month old boy with thigh mass (The Internet Journal of Dermatology 2001;1:2)
Treatment: excision, need not be aggressive as recurrence is uncommon (J Am Acad Dermatol 2006;54:800)
Gross: poorly circumscribed, gray-white with yellow fat, usually 5 cm or less
Gross/clinical images: untreated tumors - axillary tumor in 6 month old Nigerian boy; scapular tumor in 7 year old Nigerian girl #1; #2-at surgery showing well developed capsule
Micro: poorly circumscribed, organoid with 3 components - (1) trabecular or stellate immature mesenchymal cells with scant cytoplasm and bland straight or wavy nuclei in myxoid matrix, (2) fibrocollagenous tissue composed of bland fibroblasts or myofibroblasts, (3) mature fat; overlying epidermis usually has eccrine changes, including hyperplasia, duct dilation, intraluminal papillary formations and squamous syringometaplasia (J Cutan Pathol 2007;34:39); no/scant mitotic figures
Micro images: AFIP - triphasic pattern of fibrous spindle cells delimiting islands of mature fat and primitive spindle cells; primitive spindle cells may infiltrate fat; primitive spindle cells and fibrous spindle cells are bland and uniform with no/rare mitotic figures
other - three cell types #1; #2; #3; mature adipose and fibrous tissue; plump mesenchymal cells; various images; collagenous tissue and immature mesenchymal cells; H&E and t(2;3) karyotype
Fibrous hamartoma of infancy of soft tissue (continued)
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
Definition: inflammatory condition of skeletal muscle with degeneration and regeneration, inflammatory cells and fibrosis
Not a WHO diagnosis
Epidemiology: mean age 41 years, range 7-94 years
Clinical: usually healthy patients with no history of trauma; evolves over weeks to a localized, painful soft tissue swelling, usually of lower extremity
Solitary, self-limited, may be related to denervation
Case reports: due to statins (Int J Cardiol 2009;133:e33), due to Lyme disease (Arthritis Rheum 2006;54:2697), recurrent disease of peroneal muscles (Rheumatology (Oxford) 2002;41:1318), post bCG vaccination (Rheumatology (Oxford) 2002;41:1074), in pregnancy (Rheumatology (Oxford) 2000;39:211), 16 year old girl (J R Coll Surg Edinb 2000;45:339)
Treatment: usually none; spontaneously regresses
Gross: pale, ill-defined; mean 4 cm, range 1 to 20 cm
Micro: degeneration and regeneration of muscle fibers associated with interstitial inflammation and fibrosis; also focal neurogenic changes; occasionally prominent eosinophils; markedly inflamed cases have B cells or CD123+ dendritic plasma cells
Micro images: focal interstitial muscle inflammation associated with extensive proliferation of endomysial connective tissue; venlafaxine associated myositis shows regenerating muscle fibers and CD3+ (T) cells; associated with bCG vaccination #1; #2; focal perivascular chronic inflammatory infiltrate; various images
Cytology: inflammatory cells, skeletal muscle fibers with degenerative and regenerative changes, fibrous tissue (Acta Cytol 2005;49:653)
Positive stains: CD163+ macrophages; lymphocytes are CD3+ and CD4+
Negative stains: macrophages are S100- and CD1a-; lymphocytes are negative for TIA1, granzymeB, EBV and ALK1 (Am J Surg Pathol 2009 Apr 9 [Epub ahead of print])
Molecular: no B or T cell rearrangement
DD: poliomyelitis
Gardner type fibroma of soft tissue
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
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
Definition: rare childhood fibroblastic tumor of intermediate malignancy with floret-like giant cells and ectatic pseudovascular spaces lined by stromal cells and giant cells
Part of WHO classification for skin tumors, not soft tissue tumors
Appears to evolve into DFSP by genomic gains of COL1A1-PDGFB (Genes Chromosomes Cancer 2008;47:260); considered the juvenile form of DFSP, as both have the same translocation (AJSP 2003;27:27)
Epidemiology: usually children less than 10 years old, 2/3 male
Painless nodule of subcutis, usually in trunk, extremities, head and neck
50% recur but recurrences are controllable, no metastases
Case reports: 3 year old boy with recurrent knee lesion (Pathol Oncol Res 2003;9:249), 28 year old woman with vulvar tumor (J Low Genit Tract Dis 2007;11:112)
Gross: poorly circumscribed, gray to yellow mucoid mass that is difficult to completely excise, usually in subcutis
Micro: dermis and subcutis contains hyperchromatic spindle or stellate shaped cells in a collagenous or myxoid matrix with scattered hyperchromatic, multinucleated, floret-like giant cells with prominent nucleoli, similar to those in pleomorphic lipomas; ectatic pseudovascular spaces are lined by a discontinuous row of floret-like cells and tumor cells; honeycomb or parallel pattern of infiltration; also hyalinized area, perivascular lymphocytes in onionskin pattern, intralesional hemorrhage; often foci of DFSP; no histiocyte-like cells, no mitotic figures
Micro images: AFIP - ectatic pseudovascular spaces are lined by giant cells #1; #2; #3; stroma has giant cells and myxoid stroma; stroma is fibrotic with giant cells but sparse angiectoid spaces in this case; multinucleated stromal giant cells have vesicular nuclei and prominent nucleoli, but smaller spindle cells have indistinct nucleoli
other - trunk tumor #1; #2; #3; tumor cells line pseudovascular spaces #1; #2
Giant cell fibroblastoma of soft tissue (continued)
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
Definition: controversial entity; rare lesions similar to cellular solitary fibrous tumor - may not actually differ
Diagnosis of exclusion (Histopathology 2006;48:63)
Historically defined as lesions with thin walled, branching vascular pattern, although this pattern is common in many lesions
Probably not a lesion of pericytes, except at sinonasal location
See myofibroma / myofibromatosis for infantile lesions
See also discussions in these chapters: Bone, Breast, CNS, Heart, Nasal cavity, Thyroid gland
Epidemiology: middle aged adults, more common in women
Most common in deep soft tissue, particularly pelvic retroperitoneum, also limb or limb girdles and head and neck
Occasionally associated with hypoglycemia (J Clin Endocrinol Metab 1996;81:919)
5 year survival was 86% in 2002 (Cancer 2002;95:1746)
70% have benign behavior
Poor prognostic factors may be 4+ mitotic figures/10 HPF, necrosis, nuclear pleomorphism with size > 5 cm
Case reports: omental tumor with metastases (World J Surg Oncol 2007;5:63)
Gross: well circumscribed, yellow-tan cut surface, fleshy or spongy with hemorrhage but no necrosis, up to 15 cm
Gross images: encapsulated omental tumor #1; #2; patient with 3 tumors - (a) greater omentum tumor (under forceps); (b) small jejunal tumor; (c) retroperitoneal tumor with portions of diaphragm and liver
Micro: uniformly cellular (similar to cellular areas of solitary fibrous tumor) with numerous, variably ectatic or compressed, thin walled branching vessels with staghorn configuration; tumor cells are spindled to round with small amounts of pale or eosinophilic cytoplasm, indistinct margins, bland vesicular nuclei; stromal hyalinization is not prominent; variable mitotic activity; no atypia
Hemangiopericytoma of soft tissue (continued)
Micro images: staghorn vessels are prominent #1; #2; uniform cells around branched, thin-walled, staghorn vessels; various images (many from CNS); meningeal tumors; reticulin stain; hemangiopericytoma of CNS is CD34+ (figure 3) / CD31 neg (figure 4)
Cytology: cellular; single and tightly packed clusters of oval to spindle cells aggregated around branched capillaries; often basement membrane material present; nuclei are uniform, oval, with finely granular chromatin and indistinct nucleoli; no mitotic figures, no necrosis (Cancer 1999;87:190)
Cytology images: irregular fragments of tissue, loose cellular aggregates and single cells; uniform oval or spindled cells with indistinct borders, high N/C ratio, and capillary vessels with long and hyperchromatic nuclei Diff-Quik, ×400); metachromatic basement membrane material within the fragments separates tumor cells from endothelial cells
Virtual slides: hemangiopericytoma
Positive stains: CD99, variable CD34 (Hum Path 1998;29:636); reticulin surrounds individual cells
Negative stains: Factor VIII, CD31, usually actin and desmin (except in sinonasal hemangiopericytoma)
EM: no true pericytic differentiation; has fibroblastic or undifferentiated spindle cell features
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
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; #10; mediastinal tumor #1; #2
other - classic hemangiopericytoma features; lipid rich component; multivacuolated fat cells; with metaplastic bone
Cytology: may resemble myxoid liposarcoma (Diagn Cytopathol 2003;29:287)
Positive stains: vimentin, CD99, CD34 (75%), bcl2 (60%)
Negative stains: CD31, desmin, keratin, actins, S100, GFAP
EM: features of pericytes, no lipoblasts
DD: various lipomas, liposarcoma
References: Hum Path 2000;31:1108, AJSP 1999;23:1201
Inclusion body fibromatosis of soft tissue
Definition: dermal fibroblastic and myofibroblastic lesion with cytoplasmic eosinophilic inclusions, usually in digits of infants
Also called infantile digital fibromatosis, infantile digital fibroma (J Hand Surg [Am] 1995;20:1014)
Clinical: rare; lesions usually present at birth or in first 2 years; similar lesions in adults; often are multiple
Sites: usually exterior surface of distal phalanges of fingers and toes, but not thumb or great toe, also oral cavity and breast
50% recur, do not metastasize
Similar inclusions reported in breast fibroadenoma (Archives 2007;131:1126), breast phyllodes tumor (AJSP 1994;18:506), cervical polyp (Pathology 1998;30:215), GI leiomyomas (Cesk Patol 2006;42:139)
Case reports: spontaneous regression (J Dermatol 1998;25:523), post-surgical tumors in all extremities (Ann Plast Surg 2008;61:472)
Treatment: excision, but preserve function because recurrences are not destructive and tumors do not metastasize (Am J Surg Pathol 2009;33:1)
Clinical images: #1; various images
Gross: nodules with stretched overlying skin, lesions are ill defined, white-tan, usually 2 cm or less; no hemorrhage or necrosis
Micro: nonencapsulated, dermal proliferation of hypocellular sheets or fascicles of fibroblasts and myofibroblasts with variable collagen; some spindle cells have peculiar eosinophilic (hyaline) cytoplasmic inclusions the size of a lymphocyte nucleus; usually mitotic figures; may infiltrate into adjacent tissue; no atypia
Micro images: AFIP - proliferation extends from epidermis to deep dermis or subcutis; fibroblastic cells swirl around and engulf an eccrine duct; cells are bland and monomorphic; inclusions resemble red blood cells
Positive stains: inclusions - trichrome (stain red), PTAH, variable staining for actins; spindle cells - vimentin, muscle actins (tram track pattern), calponin, desmin, CD99; often CD117
Negative stains: inclusions - PAS; spindle cells - keratin, ER, PR, beta-catenin
EM: spindle cells are myofibroblasts with rough endoplasmic reticulum and free lying inclusions composed of compact masses of actin granules and filaments without a limiting membrane (Am J Pathol 1979;94:19)
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
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)
Micro images: AFIP - typical appearance of spindled myofibroblastic cells and inflammatory infiltrate #1; #2; inflammation obscures the underlying myofibroblastic proliferation; spindle cells are evident at high power; tumor with more fibrous stroma
other - myofibroblasts and inflammatory cells #1; #2; #3; #4; #5; various images; retroperitoneal tumor #1; #2; #3; #4; peritoneal tumor with bone marrow involvement; H&E and ALK1; H&E, ALK1, p80; ALK1 and p80
Virtual slides: inflammatory myofibroblastic tumor
Positive stains: vimentin (diffuse, strong), usually alpha smooth muscle actin, muscle specific actin and calponin (Hum Path 2008;39:846), ALK1 / p80 in 40%, but not specific (Mod Path 2002;15:931), keratin and desmin in 1/3
Negative stains: S100, CD117, HHV8 (Mod Path 2007;20:995), CD34, h-caldesmon
EM: myofibroblastic cells and activated fibroblasts
EM images: fig b: filamentous bundles, attachment densities, pinocytotic vesicles and basal lamina
Molecular/cytogenetics: clonal abnormalities of 2p23 (Cancer Res 1999;59:2776), including t(2;5)(p23;q35) involving ALK and NPM; also t(2;17)(p23;q23) involving ALK and CLTC (Am J Path 2001;159:411) and t(2;19)(p23;p13.1) involving ALK and TPM4 (Am J Path 2000;157:377); associated with ALK deregulation and younger patients; see Atlas of Genetics
Molecular images: t(2;5) schematic; t(2;5) karyotype; ALK translocation is indicated by separation of green and orange probes of ALK gene in inflammatory myofibroblastic tumor (a), but not leiomyosarcoma (b); ALK staining, FISH and karyotype; FISH for ALK
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
Definition: benign myofibroblastic spindle cell tumor arising within lymph nodes (usually in the groin) associated with amianthoid fibers and resembling schwannoma
Also called intranodal hemorrhagic spindle cell tumor with amianthoid fibers; formerly called intranodal schwannoma
Amianthoid: resembles amianthus, a type of asbestos with particularly fine fibers (image #1; #2); tumor fibers are extracellular collagen
Described by Weiss et al (AJSP 1989;13:341) and Suster et al (AJSP 1989;13:347)
Epidemiology: 2/3 male, 2/3 ages 45-55 years (Arch Pathol Lab Med 2007;131:306)
Sites: occurs primarily in the groin, but also other sites
Case reports: 49 year old woman with renal transplant and recurrence (Arch Pathol Lab Med 1999;123:433), 62 year old man with supraclavicular mass (UPMC Case #121), 71 year old man with inguinal mass (Archives 2003;127:1040)
Treatment: local excision is almost always curative
Gross: well circumscribed, gray-white with hemorrhage and peripheral nodal tissue
Micro: benign spindle cells with scant cytoplasm, elongated nuclei arranged in fascicles; spindle cells have myofibroblastic or smooth muscle features; large amianthoid fibers (strongly eosinophilic, extracellular matrix deposits composed of crystalline fibers) around which the cells palisade; areas of acute hemorrhage and hemosiderosis; peripheral lymph node tissue; no/rare mitotic figures, no atypia, no slit like vascular spaces, no extravasated red blood cells
Micro images: various images #1; #2; #3; #4; peripheral rim of nodal tissue; original and recurrent tumor; focal palisading and metaplastic bone formation; H&E and cyclin D1; smooth muscle actin+, cyclin D1+, EM images; amianthoid fibers composed of a central vessel surrounded by a core of collagen with peripheral spokes, strongly stained by Van Gieson;
Intranodal palisaded myofibroblastoma of soft tissue (continued)
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