Soft Tissue Tumors Part 1:
Introduction, Infections &
Fibroblastic / myofibroblastic tumors
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Last revised 29 May 2009
Last major update May 2009 - next update May 2010
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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
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)
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
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
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
Gross: nodular or infiltrative gray-white, gritty mass in subcutaneous tissue or tendon, may be calcified, usually 3 cm or less in hands or feet, may be larger elsewhere
Micro: nodules of plump or epithelioid fibroblasts palisading around cartilage and spotty calcification; cells have indistinct and variable cytoplasm, plump oval nuclei with vesicular chromatin that may be condensed below nuclear membrane; fibrocytes in stroma between nodules have dense, evenly dispersed chromatin; may infiltrate fat or striated muscle at periphery; frequent osteoclast-like giant cells; rare mitotic figures, no atypia; more cellular in very young
Cytology: benign appearing spindle cells, chondroid cells, multinucleated giant cells and calcified debris (Diagn Cytopathol 2001;24:336)
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
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
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
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
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)
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
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
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
Gross: ill defined, rubbery, gray-white fibrous tissue mixed with yellow streaks of elastin; up to 15 cm
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
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
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
Positive stains: smooth muscle actin, vimentin
EM: resembles myofibroblasts and fibroblasts
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
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
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)
Gross: 2-3 cm nodules associated with aponeurosis and subcutis, with gray-yellow-white cut surface (color depends on collagen content)
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)
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)
Gross: large, firm, white cut surface, infiltrative borders; often in muscular fascia, cuts with gritty sensation, 5-10 cm
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
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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
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)
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
Micro: uniformly cellular (similar to cellular areas of solitary fibrous tumor) with numerous, variably ectatic or compressed, thin walled branching vessels with staghorn configuration; tumor cells are spindled to round with small amounts of pale or eosinophilic cytoplasm, indistinct margins, bland vesicular nuclei; stromal hyalinization is not prominent; variable mitotic activity; no atypia
Cytology: cellular; single and tightly packed clusters of oval to spindle cells aggregated around branched capillaries; often basement membrane material present; nuclei are uniform, oval, with finely granular chromatin and indistinct nucleoli; no mitotic figures, no necrosis (Cancer 1999;87:190)
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
Micro: well circumscribed, patternless cellular areas, prominent hemangiopericytoma-like vessels, mature adipose tissue, variable collagen
Cytology: may resemble myxoid liposarcoma (Diagn Cytopathol 2003;29:287)
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)
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
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
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
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
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
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
Cytology: moderately cellular with benign appearing, dissociated, single spindle cells with elongated nuclei, pointed ends and occasional twisted forms; in pale fibrillary matrix with hemosiderin granules, no atypia (Acta Cytol 2002;46:1143)
Positive stains: spindle cells - smooth muscle actin, vimentin, cyclin D1 (Arch Pathol Lab Med 2003;127:1040), variable factor XIIIa; amianthoid fibers - elastic stains, trichrome, collagen type I/III, smooth muscle actin
Negative stains: S100, synaptophysin, GFAP, Ki-67 (<5%), desmin, EMA, keratin
EM: spindle cells with long, indented nucleus and collagen fibrils from the crystalline deposits; pinocytotic vesicles, microfilament aggregates, well-developed rough endoplasmic reticulum with dilated cisternae; amianthoid fibers contain collagen fibrils arranged in orderly parallel fashion; long, frequently indented nuclei (Ultrastruct Pathol 1996;20:79)
Differential diagnosis:
▪ schwannoma - often biphasic, no amianthoid fibers, not nodal, S100+
▪ Kaposi’s sarcoma - curved fascicles of spindle cells with atypia and PAS+ hyaline globules, brisk mitotic activity, slit-like vessels with extravasated red blood cells; no amianthoid fibers, HHV8+, FLI1+
▪ dendritic cell sarcoma - nests or whorls of plump cells with scattered inflammatory cells, no prominent hemorrhage, no amianthoid fibers, CD21+, CD35+
▪ benign metastasizing leiomyoma - smooth muscle cells are more ovoid with more prominent eosinophilic cytoplasm, no hemorrhage, no amianthoid fibers
▪ spindle cell carcinoma, melanoma or sarcoma (atypia and mitotic figures)
References: J Clin Pathol 1991;44:761
Ischemic fasciitis of soft tissue
Definition: sarcoma-like fibroblastic proliferation, usually of soft tissue, overlying bony prominences
Also spelled ischaemic
First described in 1992 as atypical decubital fibroplasia (AJSP1992;16:708)
Epidemiology: occurs primarily in immobilized and elderly patients due to chronic pressure and impaired circulation, but also occurs in younger people not debilitated (Am J Surg Pathol 2008;32:1546) or with physical disabilities (Path Int 1998;48:160, Int J Gynecol Pathol 2004;23:65)
Sites: usually pressure points on shoulder, chest wall and sacrococcygeal region
Case reports: 45 year old woman with post-mastectomy axillary mass (The Internet Journal of Pathology 2008;7:1), 55 year old man with hip mass (Case of Week #64), 76 year old woman with thigh mass (Archives 2004;128:e139)
Treatment: local excision is curative, although may recur due to continuation of underlying ischemia and injury
Gross: usually 1 to 8 cm, poorly circumscribed, often myxoid; usually involves deep subcutis, may extend into adjacent skeletal muscle; ulceration is uncommon (i.e. overlying skin is intact)
Micro: zones of fibrinoid necrosis with uneven borders staining deep red/violet and prominent myxoid areas surrounded by ectatic, thin walled vessels and proliferating fibroblasts; endothelial cells may be atypical; fibroblasts have degenerative features of abundant, basophilic cytoplasm, enlarged nuclei with smudged chromatin and prominent nucleoli (resembling proliferating fasciitis or ganglion cells); may have frequent mitotic activity, but no atypical mitotic figures; fibrin thrombi are common within peripheral vessels, which may show fibrinoid necrosis and recanalization but no vasculitis; may have multivacuolated macrophages, but no lipoblasts; no primary vasculitis or myositis
Cytology: spindled and ovoid cells with ample cytoplasm and occasional nuclear atypia (Acta Cytol 1997;41:598)
Positive stains: vimentin, actin, CD68; variable CD34 in enlarged fibroblasts, desmin
Negative stains: keratin, S100
Differential diagnosis:
▪ epithelioid sarcoma - young adults on distal extremities, more cellular with central necrosis, cells have eosinophilic cytoplasm, atypical mitotic figures, keratin+
▪ myxoid liposarcoma - prominent plexiform vasculature and lipoblasts
▪ myxofibrosarcoma - marked atypia, but no smudgy chromatin or fibrin thrombi; lacks zonation
▪ proliferative fasciitis - younger patients, lesions not associated with pressure; zonation, myofibroblasts and fibroblasts with tissue culture type growth, also large ganglion cells
References: Mod Path 1993;6:69, Stanford University
Juvenile hyaline fibromatosis of soft tissue
Definition: hereditary infantile disorder with extracellular hyaline material in skin, soft tissue and bone, due to aberrant fibroblasts
Also called fibromatosis hyalinica multiplex
Called infantile systemic hyalinosis if organ involvement, but some cases overlap (Pediatr Dermatol 2004;21:154)
Epidemiology: very rare, associated with consanguineous parents
Due to mutations in CMG2 / capillary morphogenesis protein 2 gene (Am J Hum Genet 2003;73:791, Am J Hum Genet 2003;73:957), which cause protein to remain in endoplasmic reticulum (Hum Mutat 2009;30:583)
Clinical: cutaneous nodules (face and neck), gingival hypertrophy, flexure contractures (due to masses in periarticular soft tissue) and bone lesions (skull, long bones, phalanges)
Case reports: disease in 2 siblings of first-degree consanguineous marriage (Indian J Dermatol Venereol Leprol 2005;71:115), 14 year old girl without prominent hyaline changes (J Cutan Pathol 2005;32:235)
Gross: solid, white, waxy nodules
Micro: well circumscribed hypocellular nodules that obliterate normal tissue; nodules are composed of plump fibroblasts and uniform eosinophilic, non-fibrillar hyaline material; lesions are more cellular in young and early in disease; fibroblasts may have fascicular patterns or clear cytoplasm; no atypia, no necrosis
Cytology: benign spindle cells with background eosinophilic ground substance (Acta Cytol 2007;51:624)
Positive stains: PAS (diastase resistant), vimentin
Negative stains: muscle actin, S100, beta-catenin
EM: fibroblasts with fibril-filled balls (dilated ER with numerous cisternae containing filamentous material similar to extracellular ground substance)
DD: gingival fibromatosis - limited to gums, collagen-rich fibrous tissue
References: OMIM #228600, Stanford University
Lipofibromatosis of soft tissue
Definition: pediatric tumor with adipose tissue and fibroblasts in adipose septa and skeletal muscle
Also called infantile fibromatosis of nondesmoid type
First described in 2000 (AJSP 2000;24:1491)
Epidemiology: rare childhood tumor (first surgery usually at age 1), 2/3 male, often of distal extremities
Clinical: associated with macrodactyly of foot (Foot Ankle 1991;12:40)
Clinically resembles lymphatic malformation, lymphedema or lipedema
Recurs locally, no metastases
Case reports: foot of male infant (Skeletal Radiol 2008;37:555), forearm of 10 month old boy (Ups J Med Sci 2005;110:259)
Gross: white-tan or yellow, 1-3 cm
Micro: bland fibroblasts in septa of adipose tissue, may have minute small vacuolated cells between fibroblasts and adipose; no atypia, no/rare mitotic figures
Positive stains: spindle cells - CD34, CD99, smooth muscle actin; variable bcl2, S100, EMA and muscle specific actin
Negative stains: desmin, keratin, beta-catenin
Molecular/cytogenetics: three-way t(4;9;6) translocation in a 5-year-old boy (rare, Cancer Genet Cytogenet 2007;179:136)
Differential diagnosis:
▪ fibrous hamartoma of infancy - has primitive oval cell component
▪ fibromatosis - solid fibrous growth, no fat
References: Stanford University
Low grade fibromyxoid sarcoma of soft tissue
Definition: low grade sarcoma with fibrous and myxoid areas, whorled growth pattern, low cellularity, bland fibroblastic cells and curvilinear vessels
Also called fibrosarcoma-low grade fibromyxoid type, Evan’s tumor, hyalinizing spindle cell tumor with giant rosettes (AJSP 2003;27:1229); may be related to some cases of sclerosing epithelioid fibrosarcoma with same translocation (AJSP 2007;31:1387)
Rare, first described by Evans in 1987 (AJCP 1987;88:615)
Prolonged preclinical stage
Epidemiology: in trunk and deep extremities of young to middle-aged adults (median age 34 years, range 3-78 years), also intrathoracic (Hum Path 2008;39:623)
Clinical: local recurrence (9%) and metastases (6%) are less common in prospective studies due to more aggressive surgery
Presence of focal intermediate to high grade sarcoma does not affect prognosis (AJSP 2000;24:1353)
Superficial cases may be more common than previously recognized, and have a better prognosis (AJSP 2005;29:204)
Case reports: 12 year old girl with massive tumor of chest cavity (Pediatr Radiol 2009;39:396), 37 year old man with tumor of falciform ligament (BMC Surg 2003;3:7), 44 year old woman with tumor on epicardial surface of heart (Hum Path 2008;39:623)
Treatment: complete excision
Gross: often > 6 cm, well circumscribed, fibromyxoid cut surface, may be grossly infiltrative
Micro: low to moderately cellular, bland fusiform or spindled cells with focal to diffuse whirling in heavily collagenized stroma with abrupt transition to myxoid areas, 45% have epithelioid areas; 40% contain poorly formed but large collagen rosettes; often infiltrates adjacent skeletal muscle; occasionally has areas of increased cellularity, atypia, necrosis or mitotic activity characteristic of intermediate to high grade sarcoma
Cytology: cellular with spindle cells containing scant wispy cytoplasm, uniform elongated nuclei, small inconspicuous nucleoli; prominent myxoid background; no significant nuclear pleomorphism or mitoses (Acta Cytol 2006;50:208, Cancer 1999;87:75); cannot diagnosis based only on cytomorphology (Cytopathology 2008 Jul 14 [Epub ahead of print])
Positive stains: vimentin, CD99 (90%), bcl2 (90%)
Negative stains: S100, desmin, keratin, CD34, MDM2, smooth muscle actin, h-caldesmon, CD117, nuclear beta catenin
EM: fibroblastic differentiation
Molecular/cytogenetics: t(7;16)(q32-34;p11)-FUS-CREB3L2 in 90% or more, also t(11;16)(p11;p11)-FUS-CRE3L1 by RT-PCR (Lab Invest 2005;85:408, AJSP 2007;31:1387, Diagn Mol Pathol 2008;17:237) or FISH (AJSP 2008;32:8)
Differential diagnosis:
▪ myxofibrosarcoma - more myxoid and less fibrous, more nuclear pleomorphism and hyperchromatism, more developed vascular network (Histopathology 2004;45:29)
▪ desmoid fibromatosis - no myxoid areas, fibrous cells are aligned straighter, cells appear more like reactive fibroblasts, distinct slit-like vessels present, diffuse or occasionally focal nuclear beta catenin staining (AJSP 2005;29:653)
▪ neurofibroma - wavy nuclei, background of thick collagen bundles, S100+
▪ fibrosarcoma-low grade fibroblastic type - no myxoid component, a diagnosis of exclusion (Histopathology 2006;49:152)
References: Stanford University, Arch Pathol Lab Med 2006;130:1358
Low grade myofibroblastic sarcoma of soft tissue
Definition: rare tumor of malignant myofibroblasts
Also called myofibrosarcoma
Deep intramuscular tumor of head and neck (tongue and oral cavity) and extremities, rarely abdominopelvic (J Clin Pathol 2008;61:301)
Commonly recurs, only rarely metastasizes
Gross: firm, pale, fibrous cut surface, ill defined margins
Micro: diffusely infiltrative with fascicles or storiform growth of spindled tumor cells; cells have ill defined pale eosinophilic cytoplasm, fusiform nuclei that are elongated or wavy with evenly distributed chromatin or round and vesicular with indentations and small nucleoli; at least focal moderate nuclear atypia with hyperchromasia and irregular nuclear membranes; collagenous matrix with prominent hyalinization; may have numerous thin walled capillaries, 1-6 MF/10 HPF; no histiocytic giant cells or prominent inflammation
Positive stains: at least one myogenic marker (desmin, alpha smooth muscle actin, muscle specific actin or calponin)
Negative stains: S100, EMA, h-caldesmon, ALK
EM: myofibroblastic features of indented and clefted nuclei, variable rough endoplasmic reticulum, discontinuous basal lamina
Molecular: gains at 1p11àp36.3 (66%), 12p12.2àp13.2 (45%), 5p13.2àp15.3 (31%), +22 (28%), loss at 15q25àq26.2 (24%) (Am J Clin Pathol 2009;131:701)
Differential diagnosis:
▪ fibromatosis / myofibromatosis
▪ nodular fasciitis - not infiltrative, not deep, lacks chromosomal anomalies
▪ leiomyosarcoma - alternating fascicular pattern
▪ solitary fibrous tumor
▪ fibrosarcoma
▪ inflammatory myofibroblastic tumor - more heterogeneous, less cellular, less hyperchromasia, less infiltrative, ALK+ (Hum Pathol 2008;39:846)
References: AJSP 1998;22:1228
Mammary type myofibroblastoma of soft tissue
Definition: benign myofibroblastic lesion with hyalinized collagenous stroma and often adipose tissue, identical to breast lesion
See also Breast-nonmalignant chapter
Epidemiology: median age 55 years, 80% men, usually incidental finding in hernia repair surgery
Usually inguinal / groin region or along milk line, also abdominal wall, buttock, back, vaginal wall
Usually subcutis, but may be deeper
May be related to hormonal status (gynecomastia or anti-androgen therapy in men)
Different entity: superficial cervicovaginal myofibroblastoma
Case reports: head and neck tumor resembling spindle cell lipoma (Head Neck 2009 Jan 8 [Epub ahead of print])
Treatment: excision, does not appear to recur, but follow up has been short
Gross: median 6 cm, unencapsulated but well circumscribed, firm, white-pink-tan-brown, nodular or whirled cut surface
Micro: identical to breast lesion; fascicles of myofibroblastic spindle cells with eosinophilic to amphophilic cytoplasm and poorly defined borders, oval to tapered nuclei with fine chromatin and small nucleoli; stroma has haphazard bands of collagen; may have epithelioid features (Am J Surg Pathol 2009 Apr 22 [Epub ahead of print]), focal nuclear atypia with enlarged nuclei or multinucleation, small vessels with perivascular lymphocytes, prominent adipose tissue, mitotic figures (but no atypical forms) (Arch Pathol Lab Med 2008;132:1813)
Cytology (breast): abundant random single and clustered benign spindle mesenchymal cells with scant cytoplasm and elongated or oval nuclei with finely granular chromatin and inconspicuous nucleoli (Diagn Cytopathol 2004;30:406)
Positive stains: desmin, CD34, variable smooth muscle actin
Molecular/cytogenetics: may have 13q and 16q changes (also spindle cell lipoma, Virchows Arch 2006;449:244)
Differential diagnosis:
▪ angiofibroma - thicker, hyalinized vessels, no myofibroblastic spindle cells
▪ lipomatous hemangiopericytoma - larger ectatic vessels, no myofibroblastic spindle cells
▪ solitary fibrous tumor - hypo- and hypercellular areas, large ectatic vessels
References: AJSP 2001;25:1022, Stanford University
Myofibroma / myofibromatosis of soft tissue
Definition: myofibroblastic/smooth muscle tumor (solitary, multifocal or generalized) composed of spindle cell areas that may alternate with hemangiopericytoma-like areas, usually before age 2 years
Formerly called infantile myofibromatosis, infantile hemangiopericytoma
Solitary (myofibroma) or multiple (myofibromatosis) nodules in skin (Mod Path 1989;2:603), soft tissues, bone or viscera
Epidemiology: 60% congenital, most before 2 years; most common fibrous tumor of infancy
May regress spontaneously
Sites: 50% of myofibromas in head and neck, trunk, extremities; 15% of myofibromatosis in deep soft tissues and viscera
Oral soft tissue: mean age 22 years (J Oral Pathol Med 2007;36:304)
Orbit: may cause bony destruction (Ophthal Plast Reconstr Surg 2006;22:292)
Generalized myofibromatosis is characterized by visceral lesions, especially lung, may cause morbidity and death
Case reports: large fetal neck tumor (J Med Assoc Thai 2007;90:376), newborn with mass compressing inferior vena cava (Adv Neonatal Care 2008;8:13), 5 month old girl with orbital tumor and death due to metastases (Ophthal Plast Reconstr Surg 2008;24:147), 63 year old man with cutaneous myofibroma of leg (Indian J Dermatol Venereol Leprol 2008;74:56)
Treatment: conservative excision for solitary lesions (Arch Otolaryngol Head Neck Surg 1999;125:39); chemotherapy for multiple or visceral lesions (Cancer 2001;92:2692); also interferon (J Pediatr Hematol Oncol 2008;30:179)
Clinical: purple macules resemble a vascular neoplasm
Gross: mean 2.5 cm, firm, fibrous, gray-white-brown cut surface, often central necrosis / cystic spaces with cheesy material or hemorrhage, better defined in dermis than deep soft tissue or viscera
Micro: nodular or multinodular proliferation with zonal appearance; peripheral areas have short fascicles or whirls of plump myofibroblasts with pale pink cytoplasm and long, tapering nuclei with vesicular chromatin and 1-2 small nucleoli, but no atypia or pleomorphism; often associated with hyalinization; center of nodules has round, polygonal or spindle cells with scant cytoplasm, hyperchromatic nuclei, arranged around thin walled branching vessels resembling hemangiopericytoma; usually calcification, necrosis, hyalinization; often apparent intravascular growth (is actually subendothelial) but still benign; no/rare mitotic figures
Positive stains: myofibroblasts - vimentin, smooth muscle actin, HHF35; cells in central zone - vimentin and smooth muscle actin
Negative stains: S100, cytokeratin, desmin
EM: continuum from fibroblasts to myofibroblasts to smooth muscle, with prominent dilated rough endoplasmic reticulum, longitudinal filament bundles with dense bodies, focal basal lamina
Differential diagnosis:
▪ smooth muscle tumor - single lesion, no zonation, minimal fibrous tissue with trichrome stain (J Formos Med Assoc 2008;107:767)
▪ inflammatory myofibroblastic tumor - prominent inflammation with plasma cells, no primitive cells with hemangiopericytic vascular pattern
▪ myopericytoma - predominant growth pattern is concentric perivascular arrangement of plump spindle cells (J Clin Pathol 2006;59:67)
Definition: focal intramuscular reparative lesion composed of cellular fibrous tissue and metaplastic bone
See also Bone chapter
Also called benign fibro-osseous lesion or heterotopic ossification (better terms since may not involve muscle or inflammation)
In subcutis, called panniculitis ossificans; in fascia or tendons, called fasciitis ossificans
Various forms: circumscripta (localized, either traumatic or atraumatic) or progressiva (also called fibrodysplasia ossificans progressiva, inherited disorder with increasing involving of muscle groups over time)
Epidemiology: usually physically active young males with rapid growth of mass; 60-75% have history of trauma in prior 4-6 weeks; may also occur after elective surgery, severe burns, neurological injury
Fibro-osseous pseudotumor of digits: similar entity that affects fingers of older adults with occupations that require repetitive manual use (Ann Diagn Pathol 2008;12:21), less likely to contain fibrinous material (Int J Surg Pathol 2003;11:187)
Sites: upper extremity flexors, quadriceps, thigh adductors, gluteal muscles, soft tissues of hand
Xray: periosteal reaction with eggshell calcification at periphery 3-6 weeks after injury; recommended to review Xrays before diagnosis
Case reports: 9 year old boy with thigh pain (UPMC Case #72), 10 year old girl with progressiva form (Internet Journal of Orthopedic Surgery 2009;12(1)), 11 year old boy with thigh mass (Eur J Pediatr 2009;168:523), 46 year old man with tumor of sternocleidomastoid muscle after clavicle fracture (Cases J 2008 Dec 22;1(1):413), multiple tumors at autopsy due to trauma (Leg Med (Tokyo) 2008;10:274)
Treatment: excision, although may regress without treatment; rarely recurs if incompletely excised
Gross: well circumscribed, soft center, gritty periphery, usually 3-5 cm
Micro: cellular stroma with new bone, atypia and mitotic figures, rarely cartilage; zonation often present, although zones may be poorly demarcated
early lesions (3 weeks): inner cellular zone resembling nodular fasciitis or osteosarcoma, with short fascicles or haphazard fibroblasts that are uniform with faint eosinophilic cytoplasm, tapering processes, vesicular or finely granular nuclei and variable nucleoli, usually numerous mitotic figures but none atypical; stroma is vascular, myxoid or edematous with extravasated red blood cells, fibrin, scattered inflammatory cells and osteoclast-like giant cells; intermediate zone has osteoblasts depositing woven bone, and outer zone has mineralized trabeculae
later: bone matures with formation of marrow and myofibroblasts are less prominent
Positive stains: fibroblasts and myofibroblasts express vimentin and variable actin and desmin, osteoclasts express vimentin
EM: fibroblasts and myofibroblasts have dilated rough endoplasmic reticulum and aggregates of cytoplasmic filaments variably associated with dense bodies; osteoblasts have numerous mitochondria and abundant dilated rough ER
Molecular: usually polyclonal (Virchows Arch 2005;446:438), but some cases have clonal USP6 rearrangements, and may be better classified as soft tissue aneurysmal bone cysts (Skeletal Radiol 2008;37:321, Cancer Res 2004;64:1920)
Progressiva variant due to mutations in ACVR1 and NOG genes (Genet Couns 2009;20:53)
Differential diagnosis:
▪ extraosseous osteosarcoma - rare, age 40+ years, different radiologic findings, malignant cytology, atypical mitotic figures, no or reverse zonation
▪ juxtacortical osteosarcoma - bone tumor, no zonation
▪ osseous muscle metastasis (AJR Am J Roentgenol 2001;176:1165)
References: eMedicine
Myxofibrosarcoma of soft tissue
Definition: spectrum of malignant fibroblastic lesions with myxoid stroma, pleomorphism and curvilinear vessels
Formerly called myxoid malignant fibrous histiocytoma (MFH)
See also Heart chapter
Epidemiology: usually ages 60-69 years, in skeletal muscle and subcutis of extremities, rarely cutaneous (Am J Dermatopathol 2003;25:281)
Retroperitoneal masses may actually be dedifferentiated liposarcoma
Clinical: 2/3 recur, 1/4 metastasize (lung, bone); better prognosis than storiform-pleomorphic MFH
Local recurrences show increase in tumor grade and more complex karyotypes (Mod Path 2006;19:407)
Low grade myxofibrosarcoma differs clinically (older patients) and histologically from low grade fibromyxoid sarcoma (Histopathology 2004;45:29)
Poor prognosis: deep seated and high grade lesions (more metastases), epithelioid variant (AJSP 2007;31:99); for low grade tumors, tumor necrosis and size of 5 cm or more (Hum Path 2004;35:612)
Case reports: 31 year old man with tibial tumor (Archives 2004;128:e65), 44 year old woman with low grade tumor and invasion into skeletal muscle (J Dermatol 2007;34:561), 75 year old man with progression from myxoid pleomorphic fibroma (Australas J Dermatol 2003;44:287), diffuse infiltrative forearm tumor causing carpal tunnel syndrome (J Hand Surg [Am] 2008;33:269), extension along perineurium of nerve (Acta Chir Belg 2007;107:442)
Treatment: wide local excision
Gross: superficial tumors are multiple mucoid nodules, deep tumors are a single mass with infiltrative margins; high grade tumors have tumor necrosis
Micro: multinodular growth of myofibroblast or lipoblast-like cells (not true lipoblasts) that are well differentiated to pleomorphic; also typical MFH areas, curvilinear vessels (thick walled with broad arc) with condensation of cells around vessels, incomplete fibrous septa, myxoid stroma (at least 10% of tumor) and infiltrating immature dendritic cells (AJCP 2003;119:540); has infiltrative periphery and often sends out long tentacles with frequent positive margins; high grade tumors are more cellular with atypical mitotic figures, hemorrhage, necrosis and possibly bizarre multinucleated giant cells; rarely epithelioid
low grade: minimal cellular atypia; 30% or more myxoid component, 20% or less solid component, 10% or less tumor necrosis, although grading is not predictive of outcome
Cytology: variable cellularity, myxoid granular to filamentous background in all cases, but less in high grade tumors; tumor cells are round to spindled with variable shapes and sizes; cytoplasm varies from scant to dense and tapering; nuclei are large, pleomorphic and hyperchromatic, often with prominent nucleoli; occasional multinucleated giant cells; high grade tumors resemble other adult pleomorphic sarcomas (Diagn Cytopathol 1999;20:6)
Positive stains: vimentin, acid mucins, CD34 (38%, J Clin Pathol 2003;56:666)
Negative stains: fat stains (positive in cytoplasmic vacuoles of lipoblasts in liposarcoma), S100
EM: fibroblastic differentiation in most cells; low grade tumors have spindled to plump cells with abundant cytoplasm, rich in well-developed rough endoplasmic reticulum cisternae, often distended and sometimes cystically dilated, containing electron lucent granular material, consistent with fibroblastic differentiation; also cells with rough ER, well developed Golgi, lysosomes and filopodia, consistent with fibroblasts with histiocytic properties (Ultrastruct Pathol 2004;28:321)
Molecular/cytogenetics: highly complex karyotypes, often 6p-, 9q+, 12q+
Differential diagnosis:
▪ nodular fasciitis - no atypical cells, no atypical mitotic figures
▪ myxoma - no atypia, less prominent vasculature, few mitotic figures, normal karyotype (J Cell Mol Med 2009 Mar 13 [Epub ahead of print])
▪ myxoid liposarcoma - lipoblasts with clear cytoplasmic vacuoles, plexiform vasculature, no bizarre cells
▪ metastatic carcinoma from kidney or adrenal gland
Myxoinflammatory fibroblastic sarcoma of soft tissue
Definition: rare low grade sarcoma of hands and feet with myxoid stroma, inflammation and virocyte-like cells
Also called inflammatory myxohyaline tumor of the distal extremities with virocyte or Reed-Sternberg-like cells, acral myxoinflammatory fibroblastic sarcoma
First described in 1998 (Mod Pathol 1998;11:384)
Epidemiology: rare; men and women of all ages (mean age 48 years) with slow growing mass, 77% in hands or feet (J Cutan Pathol 2008;35:192)
Case reports: 13 year old girl with back tumor (Int J Dermatol 2008;47:68), 29 year old man with finger mass (Archives 2005;129:1343), 30 year old man with elbow mass (Archives 2006;130:e35)
Treatment: wide local excision; may recur locally, distant metastases are rare (J Cutan Pathol 2008;35:186)
Gross: multinodular, poorly defined, up to 8 cm, often involves joints and tendons; white and gelatinous with fibrous and myxoid zones
Micro: multinodular tumor of polymorphous cells with infiltrative margins in subcutis and often dermis, but only rarely skeletal muscle; three types of tumor cells: (a) epithelioid or spindled, occasionally large with bizarre nuclei and prominent nucleoli resembling viral inclusions or Reed-Sternberg cells, (b) multivacuolated cells resembling pleomorphic lipoblasts and (c) giant cells with emperipolesis; also acute and chronic inflammatory cells, distinct myxoid and hyaline zones; 0-1 MF/10 HPF, no atypical forms, no/rare necrosis
Cytology: spindle, epithelioid, lipoblast-like and ganglion-like cells in myxoid background with prominent inflammatory infiltrate, cases may not display all features, must be cautious in diagnosis of soft tissue lesions by cytology alone (Acta Cytol 2007;51:231, Cytopathology 2003;14:73)
Positive stains: vimentin, usually CD34, CD163 and EGFR; variable CD68, occasionally keratin
Negative stains (tumor cells): CD45, T and B cell markers
EM: fibroblastic features of abundant rough endoplasmic reticulum and mitochondria, intermediate filaments; lipoblast like cells have cytoplasmic pseudoinclusions with extracellular mucin
Cytogenetics: complex and heterogeneous karyotypes, inconsistent between cases, including aneuploidy (Virchows Arch 2007;451:923), ring chromosomes (Cancer Genet Cytogenet 2004;152:61), t(2,6) (Cancer Genet Cytogenet 2007;177:139)
Differential diagnosis:
▪ Hodgkin’s lymphoma - lacks giant cells and lipoblast-like cells, tumor cells have different staining patterns
▪ myxofibrosarcoma or pleomorphic liposarcoma - rare in soft tissues of hands and feet, more frequent mitotic figures with atypical forms, no inflammatory infiltrate
▪ Rosai-Dorfman disease - emperipolesis, but no intranuclear or cytoplasmic vacuoles, S100+
▪ epithelioid sarcoma - most cells are round with bright eosinophilic cytoplasm, strongly keratin+
▪ tenosynovitis - no enlarged atypical cells
References: AJSP 1998;22:911, Virchows Arch 2003;442:25
Nodular fasciitis of soft tissue
Definition: highly cellular, reactive lesion of fibroblasts and myofibroblasts in myxoid stroma with granulation tissue-like vascular proliferation, lymphocytes and extravasated red blood cells, usually in young adults in fascia and subcutis, with rapid growth to 2-3 cm
Common lesion that typically presents as a rapidly growing mass on the flexor forearm, chest, back or elsewhere
Arises from superficial fascia, occasionally intramuscular or intravascular
May also develop within bladder (Hinyokika Kiyo 1994;40:427), breast (Breast 2005;14:384), cervix, intra-articular (AJSP 2006;30:237), prostate, vagina, vulva (Int J Gynecol Path 1997;16:117)
Epidemiology: peaks at age 40 years; prior trauma in 10% of cases
Benign behavior, but frequently misdiagnosed as sarcoma based on cellularity, mitotic figures and rapid growth
Case reports: 37 year old woman with wrist mass (Case of the Week #65), 44 year old man with shoulder mass (The Internet Journal of Plastic Surgery 2007;3(1)); regression after biopsy (J Craniofac Surg 2008;19:1167)
Treatment: excision (curative even if incomplete resection); recurs in 1% after incomplete excision but recurrence should suggest review of diagnosis; no metastases
Gross: tan-white-gray, myxoid appearance, usually 2 cm or less, relatively well circumscribed, no capsule; may be centered in subcutis, may grow into skeletal muscle
Micro: zonation effect with hypocellular central region and hypercellular periphery; composed of uniform, plump, immature fibroblasts or myofibroblasts without atypia, with a feathery, tissue-culture like growth pattern due to abundant ground substance; often with mucoid pools (microcysts); uniform elongated nuclei with prominent nucleoli; cellular areas may have storiform or fascicular patterns (S or C shaped); often frequent mitotic figures (but no atypical forms), lymphocytes and macrophages, red blood cell extravasation, bands of keloid-type collagen; vasculature is usually prominent; walls of small to medium sized vessels are involved by reactive process at periphery of lesion; may infiltrate adjacent fat; may have metaplastic bone, focal cystic areas, ganglion type cells but no cells with large, hyperchromatic, atypical nuclei; no/rare plasma cells and neutrophils; does not extend to skin except on face
Cytology: markedly hypercellular smear with clusters of overlapping, relatively monomorphic spindle or epithelioid cells resembling sarcoma (AJCP 2005;123:388); also inflammatory cells, single mesenchymal cells, myxoid stroma (Acta Cytol 2004;48:473)
Positive stains: fibroblasts/myofibroblasts - smooth muscle actin (Ann Diagn Pathol 2002;6:94), muscle specific actin, vimentin and calponin (Am J Dermatopathol 2006;28:105); macrophages - CD68 (not specific for histiocytes-also fibroblasts that have acquired phagocytic properties)
Negative stains: S100, desmin, keratin and CD34 (AJSP 1993;17:1039); caldesmon, ALK, p53
EM: cells resemble myofibroblasts, are elongated with abundant, often dilated rough endoplasmic reticulum, may have cytoplasmic filaments with dense bodies, pinocytotic vesicles and cell junctions
Molecular/cytogenetics: diploid, no/few genetic aberrations (Am J Clin Pathol 2009;131:701)
Differential diagnosis:
▪ benign fibrous histiocytoma - based in dermis, storiform pattern, infiltrative borders, prominent xanthoma cells and often Touton giant cells, no microcysts
▪ fibromatosis - usually large tumor that infiltrates surrounding soft tissue, spindled cells are separated by abundant collagen, no loose tissue culture appearance
▪ inflammatory MFH - larger size, slower growth, more pleomorphic cells, presence of neutrophils, plasma cells, foam cells and atypical mitotic figures, no RBC extravasation, no keloid-type collagen
▪ inflammatory myofibroblastic tumor - no rapid growth, no zonation, no prominent myxoid stroma; larger tumor size, has mixed inflammatory infiltrate
▪ myositis ossificans (early) - centered in muscle, calcification
▪ myxofibrosarcoma - large, regularly arborizing vessels, atypia and pleomorphism
▪ other sarcoma - atypia is prominent
▪ reactive spindle cell nodules - post-biopsy
References: Stanford University
Cranial fasciitis
Definition: variant of nodular fasciitis that usually affects scalp and skull of infants or children < 2 years old
Rare; usually boys, erodes outer table of cranium and may infiltrate dura
Some cases show dysregulation of Wnt/beta-catenin pathway, and may be related to desmoid fibromatosis (Mod Pathol 2008;21:1330)
May be related to birth trauma, craniectomy or be spontaneous (J Neurosurg Pediatr 2008;2:370)
Grows quickly like nodular fasciitis, but same benign behavior (Cancer 1980;45:401)
Xray: lytic defect of skull with sclerotic rim
Case reports: 7 month old boy (AJNR Am J Neuroradiol 2003;24:1465), 3 year old girl with epidural mass (Pediatr Neurosurg 2008;44:148)
Gross: circumscribed, rubbery to firm; variably myxoid or cystic
Micro: fibroblasts, giant cells, myxoid matrix; may have osseous metaplasia
Positive stains: nuclear beta-catenin (some cases)
References: Hum Pathol 1999;30:87
Intravascular fasciitis
Definition: variant of nodular fasciitis that involves wall and lumen of small to medium-sized veins and arteries (AJSP 1981;5:29)
Usually subcutaneous
Rare; usually age 30 years or less
Slower growth than classic nodular fasciitis but same behavior
Case reports: pregnant woman with hand lesion (World J Surg Oncol 2007;5:7)
Gross: usually 2 cm or less; nodular or plexiform
Micro: resembles nodular fasciitis, often more prominent osteoclast-like giant cells; may be intra- or extravascular
Proliferative funiculitis
Definition: pseudosarcomatous myofibroblastic proliferation of spermatic cord
Usually incidental at herniorrhaphy
Ages 52-76 years; may be due to ischemia, torsion or extension of vasitis
Resembles nodular fasciitis
Similar lesions in epididymis
Micro: may contain malignant appearing glandular structures composed of keratin+ mesothelial cells (Int J Surg Pathol 2008;16:48), rarely has proliferation of mast cells (Pathol Int 2003;53:897)
Positive stains: myofibroblasts - smooth muscle actin
References: AJSP 1992;16:448
Nuchal fibrocartilaginous pseudotumor of soft tissue
Definition: fibrocartilaginous metaplasia of nuchal ligament overlying lower cervical vertebrae
Some consider it the same entity as nuchal type fibroma
Not a distinct WHO diagnosis
First described in 1997 (AJSP 1997;21:836); very rare
May be due to trauma (automobile accident) or chronic mechanical stress (Mod Path 1999;12:663)
Case reports: 10 year old girl post neck trauma (Archives 2000;124:1217), 30 year old woman with neck trauma (J Neurosurg Sci 2003;47:173)
Treatment: simple excision, does not recur
Micro: poorly defined, moderately cellular fibrocartilaginous nodules, no atypia, no mitotic activity
Positive stains: CD34, vimentin, focal S100 in chondrocytes (Pathol Int 2001;51:723)
Negative stains: CD99, desmin, alpha smooth muscle actin
EM: fibroblastic and chondroblastic features, no myofibroblastic features
Nuchal type fibroma of soft tissue
Definition: bundles of thick collagen fibers in posterior neck
Also called collagenosis nuchae
Nuchal: nape (posterior) of neck
Epidemiology: rare benign lesion of dermis and subcutis in posterior neck, upper back or other regions, more common in men, mean 40 years; associated with diabetes in 44% (Cancer 1999;85:156)
Case reports: associated with DFSP (J Cutan Pathol 2004;31:62)
Treatment: excision, recurs but does not metastasize
Gross: usually 3 cm or less, hard and white, unencapsulated, poorly circumscribed
Micro: no capsule, hypocellular, thick collagen fibers with delicate elastic fibers, entrapped adipose and entrapped nerves, resembling traumatic neuroma, may infiltrate into skeletal muscle, may have scattered lymphocytes
Positive stains: vimentin, CD34, CD99
Negative stains: actin, desmin
Differential diagnosis:
▪ fibrolipoma - circumscribed, different location
▪ fibromatosis - deep soft tissue, not back of neck, more cellular
▪ solitary fibrous tumor - patternless pattern, more cellular, staghorn type vessels
References: AJSP 1995;19:313, Stanford University
Ossifying fibromyxoid tumor of soft tissue
Definition: uncommon fibromyxoid soft tissue tumor of uncertain lineage, usually with peripheral bone present
First described in 1989 (AJSP 1989;13:817), now 300+ cases reported (Am J Surg Pathol 2008;32:996)
Epidemiology: median age 49 years, range 14-83 years, usually men with small painless mass in trunk or proximal extremities
Usually histologically benign with benign clinical course; local recurrences in 17%, malignant behavior in 5%
May have neuroectodermal origin due to CD56+, CD99+ (Int J Surg Pathol 2007;15:437)
Poor prognostic factors: high cellularity, high nuclear grade, > 2 mitotic figures/50 HPF (AJSP 2003;27:421)
Case reports: 21 year old woman with gingival mass (J Periodontol 2009;80:687), invasive spinal tumor (Skeletal Radiol 2008;37:1137)
Treatment: excision
Gross: well circumscribed, median 4 cm, usually involves deep soft tissue, also cutaneous (Am J Dermatopathol 2007;29:156) or subcutaneous (J Cutan Pathol 2006;33:749)
Micro: nests/cords of round/oval cells with indistinct cytoplasm in myxoid matrix with fibrosis and osteoid formation; lobulated at low power; surrounded by partial capsule of lamellar and woven bone; usually minimal atypia and minimal mitotic figures, but may have necrosis, vascular invasion or high nuclear grade
Cytology: clusters, cords or small aggregates of round, polygonal or spindle cells in myxoid background with osteoid-like material (Diagn Cytopathol 2004;30:41); malignant cases may show significant nuclear pleomorphism with coarse chromatin, irregular contours and 1-2 distinct nucleoli (Acta Cytol 2001;45:745)
Positive stains: vimentin, S100 (60%) (94% in tumors with conventional histology,