Soft Tissue Tumors Part 1
Introduction, Fibrous, Fibrohistiocytic and Adipose tumors
Last revised 12 July 2008
Last major update May 2008 - next update May09
Copyright (c) 2002-2008, PathologyOutlines.com, Inc.
See also Bone and Joints chapters
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Triphasic pattern seen in Fibrous Hamartoma of Infancy
Table of Contents for Soft Tissue Tumors Part 1
Introduction: primary references, soft tissue-normal, approach to diagnosis, sarcomas-general, syndromes, grading, cell types, architectural patterns, molecular
Infections, inflammation and hematoma: general, granulomatous, hematoma, necrotizing fasciitis, PVP granuloma, tumoral calcinosis
Fibroblastic/myofibroblastic: normal, general, angiomyofibroblastoma, calcifying aponeurotic fibroma, calcifying fibrous tumor, cellular angiofibroma, dermatofibrosarcoma protuberans, desmoplastic fibroblastoma, elastofibroma, eosinophilic fasciitis, fibroma of tendon sheath, fibromatosis-general, fibromatosis-superficial, fibromatosis-deep, fibromatosis colli, fibrosarcoma-adult, fibrosarcoma-infantile, fibrous hamartoma of infancy, focal myositis, Gardner fibroma, giant cell angiofibroma, giant cell fibroblastoma, hemangiopericytoma, inclusion body fibromatosis, inflammatory myofibroblastic tumor, ischemic fasciitis, juvenile hyaline fibromatosis, lipofibromatosis, low grade fibromyxoid sarcoma, low grade myofibroblastic sarcoma, mammary type myofibroblastoma, myofibroma / myofibromatosis, myositis ossificans, myxofibrosarcoma, myxoinflammatory fibroblastic sarcoma, nodular fasciitis and related lesions, nuchal fibrocartilaginous pseudotumor, nuchal type fibroma, ossifying fibromyxoid tumor, pleomorphic fibroma, proliferative fasciitis, proliferative myositis, proliferative peribursitis, sclerosing epithelioid fibrosarcoma, solitary fibrous tumor, superficial acral fibromyxoma
Fibrohistiocytic: general, atypical fibrous histiocytoma, atypical fibroxanthoma, benign fibrous histiocytoma (superficial), deep benign fibrous histiocytoma, giant cell tumor of soft tissue, giant cell tumor of tendon sheath-diffuse, giant cell tumor of tendon sheath-localized, MFH-giant cell, MFH-inflammatory, MFH-pleomorphic, pleomorphic hyalinizing angiectatic tumor, plexiform fibrohistiocytic tumor
Adipose tissue-benign: embryology & physiology, white fat , brown fat
lipoma and variants: lipoma, angiolipoma, chondroid, fibrolipoma, intramuscular, lipoma arborescens, lipoma of tendon sheath, lipomatosis, lipomatosis of nerve, lumbosacral, myelolipoma, myolipoma, myxoid, nevus lipomatosus, pelvic, pleomorphic/spindle cell
other benign lesions: hemosiderotic fibrohistiocytic lipomatous lesion, hibernoma, lipoblastoma, subconjunctival herniated orbital fat
Adipose tissue-liposarcoma: general, atypical lipomatous tumor/well differentiated, dedifferentiated, myxoid, pleomorphic, mixed type, sclerosing poorly differentiated
Go to Soft Tissue Tumors Part 2 - Muscle, Vascular, Nerve, Other
Primary references - Soft tissue tumors Part 1
American Journal of Clinical Pathology (AJCP) [free full text and no registration after 1 year], January 2000 to May 2008
American Journal of Surgical Pathology (AJSP), January 2000 to May 2008
Archives of Pathology and Laboratory Medicine (Archives) [always free full text and no registration]; January 1999 to May 2008
Biomed Central [always free full text and no registration]; 24 July 2001 to 1 May 2008
Human Pathology (Hum Path), January 2000 to May 2008
Modern Pathology (Mod Path) [free full text and no registration after 1 year]; Jan 2000 to May 2008
Fletcher: Pathology and Genetics of Tumours of Soft Tissue and Bone (AFIP 3rd Series, Vol 30), 2004
Fletcher:
Pathology and Genetics of Tumours of Soft Tissue and Bone (WHO, Vol 5), Chapter 1-adipocytic
tumors, Chapter
2-fibroblastic/myofibroblastic tumors, Chapter 3-fibrohistiocytic
tumors
Rosai,
J: Ackerman’s Surgical Pathology (9th Ed, 2004)
Sternberg, S: Diagnostic Surgical Pathology (4th Ed, 2004)
Websites with images: PathoPic, PEIR digital library; virtual slides - ASCP, OSU, USCAP
Journal search terms: each disease entity listed
Please refer to these primary references for more detailed discussions and photographs
Definition: nonepithelial extraskeletal tissue, excluding supportive tissue of organs and lymphoid/hematopoietic tissue
Includes fibrous tissue, adipose tissue, skeletal muscle, blood vessels, lymphatics and peripheral nervous system
Usually mesodermal in origin; peripheral nerves derive from neuroectoderm
Soft tissue tumors - approach to diagnosis
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
7,000/year in US
Classified based on type of cellular differentiation, although most arise not from differentiated cells, but from multipotent mesenchymal cells that then differentiate along various cell lines
Diagnostic errors are often due to lack of familiarity with rare lesions, not failure to perform immunostains (AJCP 2001;116:473)
WHO classification: last revised in 2002 - Histopathology 2006;48:3, classification
Recommended to diagnose with FNA or incisional biopsy so appropriate treatment can be determined in advance
Congenital soft tissue tumors, even with high grade features, rarely have malignant behavior
Nodal involvement uncommon
Local recurrences show increased number of genetic changes, including loss at 9p, gains at 5p and 20q (Mod Path 2001;14:978)
Usually arise de novo, not from benign tumors (MPNST may be an exception); do not appear to arise from trauma
May be caused by radiation therapy (MFH, extraskeletal osteosarcoma) or foreign bodies (MFH, angiosarcoma)
Poor prognostic factors: large size, deep seated versus superficial, retroperitoneum versus extremities, high grade, high stage, positive margins (associated with local recurrence)
Treatment: enucleation acceptable only for schwannomas; for other small tumors, must excise with 1-2 cm rim of normal tissue; surgery should also remove site of prior FNA or incision
Wide local excision for infiltrative lesions (fibromatosis, DFSP); amputation is less commonly performed now than in the past
Radiation and chemotherapy may also be used
Surgical resection of pulmonary metastases often has value
Fine needle aspiration: most specimens are recognized as sarcoma, and subtyping is most accurate in bone sarcomas and pediatric sarcomas; subtyping is often not possible in adult specimens, but this usually does not affect initial therapy (AJCP 2001;115:59)
Staging is discussed in Soft Tissue Tumors - Part 2 (click here)
Syndromes (molecular / genetic) associated with soft tissue tumors
Bannayan Zonana syndrome: OMIM #153480, multiple lipomas and hemangiomas
Beckwith-Wiedemann syndrome: OMIM #130650, congenital overgrowth syndrome associated with alveolar rhabdomyosarcoma (Pediatr Dev Pathol 2001;4:550)
Carney syndrome / complex: autosomal dominant multiple neoplasia syndrome with myxomas and pigmented lesions of skin and mucosa, due to mutation in PRKAR1A gene (OMIM #160980) or 2p16 abnormalities (OMIM #605244)
Carney triad: OMIM # 604287, gastric leiomyosarcoma, pulmonary chondroma and extra-adrenal paraganglioma
Gardner syndrome: OMIM #175100, fibromatosis and familial adenomatous polyposis
Kasabach-Merritt syndrome: OMIM #141000, microangiopathic hemolytic anemia associated with childhood hemangioma
Klippel-Trenaunay-Weber syndrome: OMIM #149000, hemangiomas with hypertrophy of associated bone and soft tissue
Li Fraumeni syndrome: OMIM #151623, various soft tissue sarcomas, osteosarcoma, breast cancer, brain tumors, leukemia and adrenocortical carcinoma
Lipomatosis, multiple syndrome: OMIM #151800
Maffucci syndrome: OMIM #166000, hemangiomas, enchondroma, chondrosarcoma
Mazabraud's syndrome: fibrous dysplasia and intramuscular myxoma (eMedicine)
McCune-Albright syndrome: OMIM #174800, myxomas are minor feature (see Mazabraud’s syndrome), major features are polyostotic fibrous dysplasia cafe-au-lait skin pigmentation and precocious puberty
Multiple endocrine neoplasia 1: OMIM #131100, multiple lipomas may be a minor feature
Neurofibromatosis type 1: OMIM #162200, neurofibroma, MPNST
Neurofibromatosis type 2: OMIM #101000, schwannoma, neurofibroma, meningioma, astrocytoma, rarely perineurioma (AJSP 2006;30:1624)
Osler-Weber-Rendu syndrome: OMIM #187300, telangiectasias
Sturge-Weber syndrome: OMIM #185300, port-wine spot of face
Turner syndrome: cystic hygroma (eMedicine)
Grading of sarcomas of soft tissue
Indicate in pathology report which grading system is used
Grade is most important prognostic factor and indicator of metastatic risk in adults (Archives 2006;130:1448)
Grading is currently not considered appropriate for needle biopsies
Two grade systems - low grade and high grade
Low grade: usually has limited ability to metastasize
High grade: cellular with mitotic figures and necrosis, but must evaluate in context of tumor type, age and location; for example: superficial high grade MFH is unlikely to metastasize, but deep low grade MPNST is likely to metastasize
Necrosis usually signifies high grade unless tumor is well differentiated and lacks pleomorphism
Grading systems - French Federation of Cancer Centers Sarcoma Group
Grade 1: total score of 2-3
Grade 2: total score of 4-5
Grade 3: total score of 6-8
Tumor differentiation:
1 point: resembles normal adult mesenchymal tissue, may be confused with a benign lesion, such as well differentiated liposarcoma
2 points: histologic typing is certain, such as myxoid liposarcoma
3 points: synovial sarcoma, osteosarcoma, Ewing’s sarcoma/PNET, sarcomas of doubtful tumor type, embryonal and undifferentiated sarcomas
Mitotic count (count 10 successive high power fields [0.17 mm squared] in most mitotically active areas):
1 point: 0-9 mitoses
2 points: 10-19 mitoses
3 points: 20 or more mitoses
Tumor necrosis:
0 points: no necrosis on any slides
1 point: less than 50% necrosis for all examined tumor surface
2 points: tumor necrosis of 50% or more of examined tumor surface
Grading systems - French Federation of Cancer Centers Sarcoma Group - grades of common sarcoma types:
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, carcinomas (extension into soft tissue or metastases), epithelioid sarcoma, rhabdoid tumors, synovial sarcoma; epithelioid variants of leiomyosarcoma, MPNST or vascular tumors
Pleomorphic: variants of leiomyosarcoma, liposarcoma, MFH, MPNST or rhabdomyosarcoma; also melanoma and metastatic carcinoma
Round cell: desmoplastic small round cell sarcoma, Ewings/PNET, mesenchymal chondrosarcoma, rhabdomyosarcoma, round cell liposarcoma; also carcinoma, lymphoma, melanoma, neuroblastoma
Spindle cell: benign nerve sheath tumor, DFSP, fibroma of tendon sheath (cellular), fibromatosis, fibrosarcoma, leiomyosarcoma and leiomyoma, MPNST, nodular fasciitis, spindle cell variant of embryonal rhabdomyosarcoma, synovial sarcoma
Architectural patterns of soft tissue tumors
Alveolar: alveolar rhabdomyosarcoma, alveolar soft parts sarcoma
Fascicular: fibromatosis, fibrosarcoma, neural tumors (benign or malignant), smooth muscle tumors, synovial sarcoma
Glandular: adenocarcinoma, biphasic synovial sarcoma, glandular MPNST
Lobular: clear cell sarcoma, epithelioid sarcoma, myxoid chondrosarcoma
Palisading: Schwann cells (neural tumors), smooth muscle tumors, spindle cell lipoma
Plexiform: nerve sheath tumors, plexiform fibrous histiocytoma
Plexiform vascular: myxofibrosarcoma, myxoid liposarcoma, nodular fasciitis
Storiform: fibrohistiocytic tumors, dedifferentiated liposarcoma, low grade fibromyxoid sarcoma, perineurioma,
Molecular / cytogenetics of soft tissue tumors
RT-PCR or FISH of paraffin-embedded tissue for tumor fusion transcripts is useful (AJSP 2002;26:965, AJSP 2008;32:8)
Note: in table below, gene for first chromosome in translocation is listed first
Alveolar soft parts sarcoma: t(X;17)(p11.2;q25) - ASPL-TFE3 fusion gene
Angiomatoid fibrous histiocytoma: t(12;16)(q13;p11) - FUS-ATF1 fusion gene or t(12;22)(q13;q12) - FUS-EWS fusion gene
Chondrosarcoma, myxoid, extraskeletal: t(9;22)(q22;q12) - CHN-EWS fusion gene
t(9;15)(q22;q21) - CHN-TCF12 fusion gene
t(9;17)(q22;q11) - CHN-RBP56 fusion gene
Clear cell sarcoma: t(12;22)(q13;q12) - ATF1-EWS fusion gene
Congenital fibrosarcoma / mesoblastic nephroma: t(12;15)(p13;q25) - ETV6-NTRK3 fusion gene
Dermatofibrosarcoma protuberans / giant cell fibroblastoma: t(17;22)(q22;q13) - COL1A1-PDGFB fusion gene
Desmoplastic small round cell tumor: t(11;22)(p13;q12) - WT1-EWS or t(21;22)(q22;q12) - ERG-EWS fusion genes
Ewing’s sarcoma/PNET, extraosseous: t(11;22)(q24;q12) - FLI1-EWS fusion gene
t(21;22)(q22;q12) - ERG-EWS fusion gene
t(2;22)(q33;q12) - FEV-EWS fusion gene
t(7,22);(p22;q12) - ETV1-EWS fusion gene
t(17;22)(q12;q12) - E1AF-EWS fusion gene
Inflammatory myofibroblastic tumor: translocations at 2p23 involving ALK gene
Lipoma: t(12;14)(q13-15;q23-24) or related changes involving HMGA2/HMGIC at 12q13-15
Liposarcoma-myxoid/round cell variants: t(12;16)(q13;p11) - TLS-CHOP/FUS fusion gene or t(12;22)(q13;q12) - CHOP-EWS fusion gene
Liposarcoma, well differentiated: marker ring or giant chromosomes derived from 12q13-15
Low grade fibromyxoid sarcoma: t(7;16)(q32-34;p11) - FUS-CREB3L2 or t(11;16)(p11;p11) - FUS-CREB3L1
Rhabdomyosarcoma, alveolar: t(2;13)(q35;q14) - PAX3-FKHR or t(1;13)(p36;q14) - PAX7-FKHR
Synovial sarcoma: t(X;18)(p11.23;q11) - SYT-SSX1 or t(X;18)(p11.21;q11) - SYT-SSX2 fusion genes
Tenosynovial giant cell tumor: t(1;2)(p11;q35-37)
References: Archives 2006;130:1199
Infections, inflammation and hematomas of Soft Tissue
Infections of Soft Tissue - general
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 in Turkey (Intern Med 2008;47:171)
May clinically resemble a tumor if deep seated
Usually near tensor fascia lata (upper thigh muscle, image)
Case reports: in tensor fascia lata (Dermatol Online J 2001;7:6), giant chronic expanding hematoma of thigh (Joint Bone Spine 2008;75:64), mass of thorax (Yonsei Med J 2007;48:337)
Treatment: complete surgical excision, including pseudocapsule
Clinical images: lesion of lateral thigh
Gross images: perforating vessel (arrow) from tensor fascia lata appears to run into the mass; lobulation with dense fibrous pseudocapsule and chocolate-brown fluid
Micro images: cystic cavity with necrotic debris, fibrin and blood costs; cyst wall has hyalinized fibrous tissue, chronic inflammation and granulation tissue
Necrotizing fasciitis of soft tissue
Definition: uncommon fulminant soft tissue infection characterized by extensive fascial necrosis
Fatal if untreated
Particularly serious in patients with badly controlled diabetes (Diabetes Res Clin Pract 2008;80:218)
Usually due to group A streptococci, also community-acquired MRSA (Surg Infect (Larchmt) 2008 Apr 9 [Epub ahead of print])
Case reports: due to Pseudomonas (Intern Med 2008;47:553)
Treatment: start promptly to minimize morbidity (World J Emerg Surg 2007;2:19)
Micro images: gluteal gas gangrene with necrotizing fasciitis #1; #2; #3-gram stain; #4-gram stain; #5; necrotic muscle with gas bubbles but minimal inflammation; leg lesion #1; #2; #3; #4; #5; #6-septic thrombus; #7-associated vasculitis; #8-gram stain; #9-gram stain
References: eMedicine #1; #2
PVP granuloma
Definition: granuloma due to injection of drugs containing polyvinylpyrrolidone (PVP)
Micro: focal cellularity, focally myxoid with foamy histiocytes containing vacuoles and PVP
Positive stains (histiocytes): mucicarmine, colloidal iron, GMS, Congo Red, Sudan Black B
DD: myxoid liposarcoma, signet ring carcinoma
Tumoral calcinosis
Definition: large painless calcified masses in periarticular soft tissues, including elbows, hips, only rarely knees
Autosomal dominant
Local recurrence common
Elevated serum calcium, hyperphosphatemia, elevated serum Vitamin D levels
Xray: lobulated calcifications, separate from associated bone
Gross: large, multinodular, chalky masses
Fibroblastic / myofibroblastic tumors of soft tissue
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)
Uncommon slow growing painless mass, usually females of reproductive age
Usually vulvar, 10-15% in vagina; also scrotum or paratesticular soft tissue in men (median age 57 years)
Case reports: recurrence in vagina (Eur J Gynaecol Oncol 2007;28:324), pedunculated vulvar mass (Acta Med Okayama 2006;60:237), sarcomatous transformation in vulva (AJSP 1997;21:1104), scrotal mass, 27 year old man with tumor of inguinal region (Archives 2000;124:1679)
Treatment: excision, only rarely recurs, does not metastasize
Gross: well circumscribed but not encapsulated, usually 5-7 cm or less, tan-pink soft cut surface, no necrosis
Micro: thin fibrous pseudocapsule, alternating hyper- and hypocellular areas with prominent thin walled and ectatic vessel in edematous stroma; round to spindled tumor cells concentrated around vessels, with eosinophilic cytoplasm and often bi- or multi-nucleation; mast cells common; may have plasmacytoid or epithelioid morphology, or rarely show degenerative changes; 10% have mature adipose tissue; no/rare mitotic figures, no/rare red blood cell extravasation, no atypia; post-menopausal patients have less cellularity, less edema but more fibrosis and vessel wall hyalinization
Micro images: gross and H&E; fig A: numerous capillary-like vascular channels, fig B: spindle cells with occasional multinucleated cells; male inguinal region; scrotal mass
Positive stains: vimentin, desmin (strong and diffuse, may be reduced in post-menopausal patients), ER, PgR, smooth muscle or pan-muscle actin (focal, Hum Path 1997;28:1046), occasional CD34
Negative stains: S100, keratin
EM: myofibroblastic and fibroblastic features
DD: aggressive angiomyxoma (not circumscribed, less cellular, less vascular, stromal mucin and RBC extravasation are present, infrequent plump stromal cells)
Reference: Mod Path 1996;9:284, Stanford School of Medicine
Calcifying aponeurotic fibroma of soft tissue
Definition: rare, slow growing, painless tumor with fibroblasts palisading around chondroid or calcified nodules, usually in hands and feet of children or young adults
Also called juvenile aponeurotic fibroma
50% recur, especially in children; does not metastasize
May be cartilaginous analog of fibromatosis
Case reports: Case of the Week #47, 36 year old woman with distal phalangeal bone involvement (Korean J Radiol 2008;9:91)
Treatment: conservative excision with reexcision as necessary for recurrences
Clinical images: 46 year old woman
Gross: nodular or infiltrative gray-white, gritty mass in subcutaneous tissue or tendon, may be calcified, usually 3 cm or less in hands or feet, may be larger elsewhere
Micro: nodules of plump or epithelioid fibroblasts palisading around cartilage and spotty calcification; cells have indistinct and variable cytoplasm, plump oval nuclei with vesicular chromatin that may be condensed below nuclear membrane; fibrocytes in stroma between nodules have dense, evenly dispersed chromatin; may infiltrate fat or striated muscle at periphery; frequent osteoclast-like giant cells; rare mitotic figures, no atypia; more cellular in very young
Cytology: benign appearing spindle cells, chondroid cells, multinucleated giant cells and calcified debris (Diagn Cytopathol 2001;24:336)
Micro images: poorly circumscribed fibroproliferative process with scattered, linear and calcified zones; amorphous calcification surrounded by palisading cells suggestive of rheumatoid nodule or crystals; typical zonation pattern has cellular, plump fibroblastic cells palisading around a hyalinized collagenous zone, which in turn surrounds the calcification; cells adjacent to hyalinized layer are commonly more rounded; chondroid area is adjacent to calcification
16 year old girl with foot tumor - image1; image2; image3; image4; image5
Positive stains: vimentin, CD68, CD99, S100, muscle specific actin (50%), smooth muscle actin (50%) ]
Negative stains (usually): CD34, CD57, progesterone receptor
EM: chondrocytes, fibroblasts and occasional myofibroblasts
Molecular/cytogenetics: benign, but may be aneuploid (Cancer 1994;73:1200)
DD: fibromatosis (usually involves head, neck and proximal extremities in infants, not hands and feet of children/young adults, background is more myxoid than chondroid, calcification is rare; in older patients, fibromatosis usually lacks calcification or chondroid differentiation), chondroma of soft parts (may involve hands, but usually well circumscribed with more well developed chondroid differentiation, no infiltration of adjacent tissue), fibrous hamartoma of infancy (immature mesenchyme, fibroblasts are arranged in trabeculae, no cartilage or calcification, not hands and feet)
References: Hum Path 1998;29:1504, Acta Orthop Belg 2001;67:412, Stanford University
Calcifying fibrous tumor of soft tissue
Definition: benign fibrous lesion with abundant hyalinized collagen, psammomatous or dystrophic calcifications and lymphocytic infiltration
Also called calcifying fibrous pseudotumor
First described in 1993 (AJSP 1993;17:502)
Adolescents/young adults, all sites
Unrelated to inflammatory myofibroblastic tumor, based on histology and immunoreactivity (Mod Path 2001;14:784, Int J Surg Pathol 2002;10:189)
Case reports: 24 year old woman with neck mass (Archives 2000;124:435), tumor of small intestine (Ann Diagn Pathol 2008;12:138), multiple peritoneal tumors #1 (Ann Diagn Pathol 2007;11:460), #2-familial (AJCP 2003;119:811), multiple pleural tumors (Virchows Arch 2005;446:78)
Treatment: excision, rarely recurs
Gross: well circumscribed but unencapsulated, variable size, may infiltrate into surrounding tissue, may have gritty cut surface
Micro: paucicellular fibroblastic proliferation with lymphocytes (possibly lymphoid follicles), plasma cells, eosinophils, mast cells, dense collagenous tissue, varying degrees of calcification; border is often at least partially infiltrative
Micro images: psammoma body, lymphocytic infiltrate, hypocellular stroma; figures 1A, 1B, 1E and 1F (comparison with inflammatory myofibroblastic tumor); adrenal gland tumor has paucicellular fibrous proliferation with focal microcalcifications; microcalcifications vary in size; lymphoplasmacytic inflammation is characteristic
Positive stains: Factor XIIIa, vimentin
Negative stains: smooth muscle actin, muscle specific actin, ALK, desmin, S100, keratin
EM: immature fibroblastic cells, collagen fibrils, dystrophic and psammatous calcifications
EM images: figure 2A
DD: inflammatory myofibroblastic tumor (more cellular, no calcifications, ALK+, actin+), desmoplastic fibroblastoma (older patients, low cellularity, larger prominent fibroblasts, no microcalcifications, no prominent inflammatory infiltrate), calcifying aponeurotic fibroma (more cellular, usually distal location, usually smaller lesion)
References: Stanford University
Cellular angiofibroma of soft tissue
Definition: benign, highly cellular tumor of vulva and scrotum/inguinal region with prominent blood vessels
First described in 1997 (AJSP 1997;21:636); may be related to angiomyofibroblastoma and spindle cell lipoma
In women, may arise from hormone receptor positive mesenchymal cells in lower female genital tract (Histopathology 2004;45:360)
Rare; usually ages 40+ years
Extragenital cases have similar features (APMIS 2007;115:254)
Case reports: 51 year old woman with coexisting Bartholin’s cyst (Sao Paulo Med J 2005;123:250), recurrent tumor (J Clin Pathol 2002;55:477)
Treatment: excision with negative margins; usually does not recur (AJSP 2004;28:1426)
Gross: vulvar lesions are usually up to 3 cm, male lesions may reach 14 cm; well circumscribed nodules with soft to rubbery, gray-pink-brown cut surface
Micro: well circumscribed, variable pseudocapsule; cellular tumor with fascicles or haphazard pattern; bland spindle cells with scant lightly eosinophilic cytoplasm with ill defined borders, oval to fusiform nucleus; may be epithelioid; occasional atypia; prominent small to medium-sized vessels with hyaline fibrosis in walls; vessels may have degenerative changes of fibrin thrombi, intramural inflammation, hemosiderin; some (usually 5% or less) adipose tissue present in 50%; stroma is usually fine collagenous fibers; scattered mast cells are common; females may have brisk mitotic activity, usually none/rare in males; no necrosis, no atypical mitotic figures
Micro images: fusiform cells, thick walled blood vessels and adipose tissue; fusiform cells with clear cytoplasm and bland nuclei; various images; recurrent tumor; ER+
Virtual slides: 63 year old man with scrotal mass
Positive stains: ER, PgR, vimentin; smooth muscle actin (21%), CD34 (30-60%)
Negative stains: S100, actin, desmin, EMA
Cytogenetics: may have 13q14 involvement; similar changes as spindle cell lipoma (Cancer Genet Cytogenet 2007;177:131)
DD: aggressive angiomyxoma, angiomyofibroblastoma (less uniform cellularity, smaller vessels, usually desmin+), solitary fibrous tumor, perineuroma, leiomyoma
References: Stanford School of Medicine
Dermatofibrosarcoma protuberans (DFSP) - Soft Tissue Tumor chapter
Definition: low to intermediate grade malignancy, usually of dermis, with prominent storiform pattern of monomorphic fibroblast-like cells that invade into subcutis
Also called intermediate (borderline) fibrous histiocytoma
Part of WHO classification for skin tumors, not soft tissue tumors
Slow growing, low-grade malignant neoplasm of trunk and various sites but not hands and feet
Rare, usually adults 20-40 years, more common in blacks in US (J Am Acad Dermatol 2007;56:968)
Can occur in infants (Arch Dermatol 2007;143:203) and children (J Plast Reconstr Aesthet Surg 2007 Dec 18 [Epub ahead of print])
May be a peculiar type of nerve sheath tumor since CD34 positive
Locally aggressive, low rate of metastasis (only after repeated failures at local control); may progress to fibrosarcoma or MFH
Giant cell fibroblastoma is considered the juvenile variant of DFSP as it has the same translocation (AJSP 2003;27:27)
Bednar’s tumor: 5-10% of cases; pigmented variant due to dendritic cells with melanin, S100+ only in pigmented cells, HMB45 negative; associated with black patients
Case reports: atrophic variant (J Dermatol 2006;33:486), granular cell variant (AJSP 2002;26:932), myoid differentiation in fibrosarcomatous DFSP (Acta Dermatovenerol Alp Panonica Adriat 2006;15:39), sclerosing variant (Int J Dermatol 2006;45:59)
Treatment: must excise subcutaneous fat (wide local excision with 2-3 cm margins) to prevent recurrence (Plast Reconstr Surg 2007;119:1779), three dimensional histologic evaluation of margins recommended (Ann Surg Oncol 2004;11:438), imatinib may be effective although tumor is CD117 negative (J Clin Oncol 2005;23:866)
Clinical images: papulonodular thigh lesions
Gross: nodular, polypoid or plaque-like, centered in dermis, can occur in deep soft tissue; mean 5 cm, gray-white (brown/black if melanocytes present), may appear circumscribed; hemorrhage and necrosis are rare
Dermatofibrosarcoma protuberans (DFSP) - Soft Tissue Tumor chapter (continued)
Micro: non circumscribed, highly cellular, “tight” storiform pattern in every field (cells radiating in spokes at right angles around a central point that often contains a vessel) that infiltrates deeply into subcutaneous tissue and entraps fat cells; storiform pattern may be absent in early plaque stage; cells are monomorphic, thin and spindly with scant eosinophilic cytoplasm and hyperchromatic nuclei resembling neurofibroma; may have numerous mitotic figures, but not atypical ones; collagen usually non-polarizable and thin; only mild pleomorphism and focal atypia; may coexist with giant cell fibroblastoma; usually no significant pleomorphism, no/rare histiocytes, no histiocyte-like cells, no foam cells, no giant cells or other inflammatory cells
Variants: atrophic (depressed lesion), collagenous (with central thick collagen bundles), granular cell (S100 negative), myxoid (see below), palisading, pigmented, sclerosing
Cytology: homogeneous with isolated spindle cells, often tissue fragments with storiform pattern, fibrillary stromal fragments, naked nuclei; occasional slight to moderate atypia (Diagn Cytopathol 2004;30:261)
Micro images: small uniform cells radiating like pinwheels from central area that often has a blood vessel is characteristic; uniform cells with no significant pleomorphism, minimal intercellular collagen, no/rare foam cells or giant cells, which are characteristic of benign fibrous histiocytoma; fine strands of collagen are present; infiltration of fat causes tumor cells to surround fat cells #1; #2; #3; #4-residual fat cells are in linear arrangement resembling a string of pearls, which is characteristic of DFSP but not benign fibrous histiocytoma; DFSP with diminished storiform pattern but CD34+ (not shown); pigmented cells are not common; variants-with fibrosarcoma, myxoid, pigmented
frozen sections: intradermal and extension into adipose tissue
Positive stains: CD34 (strong in 95%), vimentin; also actin (focal), ApoD (AJSP 2004;28:1063), bcl2, NKI-C3 (AJCP 1992;97:478), CD99 (J Cutan Pathol 2008 Jan 14 [Epub ahead of print])
Negative stains: Factor XIIIa (usually), keratin, EMA, S100, HMB45, desmin, CD117 (J Cutan Pathol 2007;34:857)
EM: stellate or spindle cells with long, slender, ramified cell processes joined by primitive junctions, often with subplasmalemmal densities; commonly multivesicular buds (Ultrastruct Pathol 2006;30:283)
Molecular/cytogenetics: t(17,22)(q21;q13) [collagen type 1 alpha 1 gene and platelet derived growth factor beta chain gene, OMIM #607907] found in almost all cases using multiplex RT-PCR (Hum Path 2008;39:184); also supernumerary ring chromosomes derived from t(17;22) (Oncogene 2001;20:2965), rarely other translocations (Virchows Arch 2008 Feb 6 [Epub ahead of print])
Dermatofibrosarcoma protuberans (DFSP) - Soft Tissue Tumor chapter (continued)
DD: benign fibrous histiocytoma (also storiform but non-infiltrative, less cellular than DFSP, Factor XIIIa positive, CD34 negative,), thymoma (storiform but different location, CD34 negative). MFH-pleomorphic or atypical fibroxanthoma (storiform pattern but also moderate/marked pleomorphism and nuclear atypia)
References: eMedicine
Indeterminate lesions between DFSP and dermatofibroma - Soft Tissue Tumor chapter
Report of 10 tumors with features of both tumors, all Factor XIIIa+, CD34+, although in different cells (AJSP 2000;24:996)
Clinically, one recurrence at mean 22 months follow-up
Recommend complete excision
Myxoid variant of DFSP - Soft Tissue Tumor chapter
Definition: DFSP with 50%+ myxoid stroma
Uncommon
Median age 40 years, male and female
Extremities, head and neck, trunk, anogenital region
Associated with recurrent tumor
Similar prognosis as classic DFSP (AJSP 2007;31:1371)
Gross: median 3 cm, white-tan-gray-yellow, firm to gelatinous
Micro: infiltrative, often hypocellular, sheet-like, bland spindle cells with pale eosinophilic cytoplasm, spindled nuclei, no pleomorphism; stroma is myxoid with prominent thin walled vessels; diffuse infiltration of fat; also cellular areas typical of DFSP
Micro images: various images
Virtual slides: myxoid DFSP
Positive stains: CD34
Negative stains: S100, muscle markers, CD99
Sarcomas arising in DFSP - Soft Tissue Tumor chapter
Usually resembles fibrosarcoma; rarely MFH-pleomorphic
In cases with wide local excision and negative margins, 20% recur, metastatic rate varies from 0% (AJSP 2000;24:1125), to 10% (AJSP 2006;30:436)
Report as “DFSP with areas of fibrosarcoma”, indicate extent of fibrosarcomatous change, nuclear grade, level of mitotic activity
Case reports: 42 year old woman with abdominal mass (Archives 2006;130:882)
Treatment: wide local excision
Micro: in fibrosarcomatous areas, spindle cells intersect at acute angles, chromatin is coarser than usual, increased mitotic activity
Micro images: fibrosarcoma arising in DFSP - DFSP cells trap fat cells, fibrosarcoma cells are more uniform #1; #2; #3; fibrosarcoma cells are spindled, uniform and hyperchromatic and arranged in herringbone pattern #1; #2; uncommon finding is myoid nodules containing cells with eosinophilic cytoplasm, present in DFSP or fibrosarcomatous areas, cells are actin+, CD34-, desmin-; H&E and FISH
pleomorphic sarcoma arising in DFSP - tumor cells are pleomorphic and have granular chromatin
Virtual slides: fibrosarcoma arising in DFSP
Desmoplastic fibroblastoma of soft tissue
Definition: fibroblastic lesion centered in subcutaneous tissue with reactive fibroblasts, low cellularity and abundant collagen
Also called collagenous fibroma
Rare benign lesion of adult men (70% between ages 40 and 69 years)
Usually upper extremities, back, feet
Treatment: conservative excision, does not recur or metastasize
Gross: usually 1-4 cm, well circumscribed, may be lobulated, has firm and homogeneous gray cut surface resembling cartilage
Gross images: well circumscribed tumor
Micro: paucicellular, bland spindled and reactive appearing fibroblasts and myofibroblasts separated by abundant collagen with variable myxoid stroma; fibroblasts have amphophilic cytoplasm, hyperchromatic nuclei and distinct nucleoli; 70% of cases involve subcutis, 25% extend into skeletal muscle
Micro images: large, reactive appearing spindled fibroblasts in fibrous matrix; focus of low cellularity and dense collagen; more cellular area with reactive type fibroblasts; scattered stellate cells in hypovascular collagenous matrix
Positive stains: vimentin, variable alpha smooth muscle actin
Negative stains: desmin, EMA, S100, CD34
EM: may have fibronexus junctions, markers of myofibroblastic differentiation (Ultrastruct Pathol 2004;28:149)
Molecular/cytogenetics: t(2;11)(q31;q12) or 11q12 abnormalities observed rarely (Cancer Genet Cytogenet 2004;149:161)
DD: fibromatosis (more cellular, fascicular pattern, prominent vasculature, Adv Anat Pathol 1999;6:275)
References: Hum Path 1998;29:676, AJSP 1995;19:1077
Definition: age 55+ years, benign, poorly circumscribed pseudotumor of subscapular region, composed of collagen and coarse enlarged elastic fibers; a reactive hyperplasia involving abnormal elastogenesis
Also called elastofibroma dorsi
First described in 1961 by Jarvi and Saxen (Acta Pathol Microbiol Scand 1961;51:83)
Slow growing; more common on apex of scapula, usually right sided; associated with hard manual labor
Occasionally in deltoid muscle, infraolecranon area, hip, thigh, stomach
Related changes found at autopsy in 13-17% of elderly; more common in women
May be multiple, bilateral or familial; may be periosteal in origin
Slightly different amino acids from elastin; has collagen types I-III (type II normally restricted to articular cartilage and ocular structures)
Case reports: Case of the week #46, tumor of hand, multiple subcutaneous nodules (J Am Acad Dermatol 2004;50:126), patient with bilateral subscapular tumors and tumor surrounding a stomach ulcer (AJSP 1985;9:233)
Treatment: excise if symptomatic, does not recur
Clinical images: shoulder based tumors; typical location (arrow)
Gross: ill defined, rubbery, gray-white fibrous tissue mixed with yellow streaks of elastin; up to 15 cm
Gross images: fibrocollagenous areas blend with fat; poorly defined fibroelastic tumor entrapping fat #1; #2; gray-white fibrous tissue mixed with fat
Micro: collagen bundles alternate with large and thick eosinophilic elastic cylinders with a dense central core, elastic fibers may be fragmented into linear globules (beads on a string); may entrap fat cells
Micro images: paucicellular fibrous tissue mixed with fat #1; #2; thick, densely eosinophilic elastin bands are mixed with collagen #1; #2; branched (arrow) and unbranched coarse elastin fibers mixed with collagen and adipose; elastin bands have serrated edges and are associated with detached globular elastin arranged like beads on a string; H&E and elastic stain; Verhoeff elastin stain highlights elastin fibers and the bead-like arrangement of the elastin globules; elastin stain highlights branched and unbranched elastin fibers #1; #2
case of the week #46: image #1; #2; #3; #4; #5; #6; #7; orcein (elastin) stain
Virtual slides: elastofibroma #1; #2; #3; #4; #5-elastin stain
Elastofibroma of soft tissue (continued)
Cytology: hypocellular smear with diagnostic aggregates of globules within a collagenous matrix; altered elastic fibers have green-yellow autofluorescence with ultraviolet light (Diagn Cytopathol 2002;26:310)
Positive stains: vimentin, elastic stains (fibers have dense core and irregular margins), CD34 in spindle cells (Virchows Arch 2006;448:195)
Negative stains: S100, desmin, smooth muscle actin, p53
EM: cylinders composed of immature amorphous elastic tissue, central core contains mature fibers, removed by elastase digestion (J Electron Microsc (Tokyo) 2006;55:89)
Molecular/cytogenetics: Xq12-q22 or #19 gains in 30% (Int J Mol Med 2002;10:277)
DD: nuchal fibroma (younger than 55 years, between scapula and vertebrae, dense collagen but no elastic fibers), fibrolipoma (no elastic fibers), desmoid fibromatosis (more cellular, infiltrates skeletal muscle, no elastic fibers)
References: Ann Diagn Path 2002;6:94, World J Surg Oncol 2007;5:15, Sarcoma 2008;2008:756565, eMedicine, Stanford University
Eosinophilic fasciitis - Soft Tissue Tumor chapter
Definition: diffuse fasciitis with fibrosis, eosinophilia and inflammation of skin, subcutaneous tissue and fascia
Not a WHO diagnosis
First described by Shulman (Trans Assoc Am Physicians 1975;88:70)
Rare fibrosing disorder with scleroderma-like induration of distal extremities
Mean age 50 years, 75% female
Eosinophilic-myalgia syndrome is different - associated with contaminated L-tryptophan, myalgia and neuritis (eMedicine)
Presence of morphea-like skin lesions is associated with residual fibrosis (Clin Rheumatol 2007;26:1445)
Case reports: 76 year old woman (Dermatology Online Journal 9(4):33), paraneoplastic phenomenon associated with metastatic colorectal carcinoma (Australas J Dermatol 2008;49:27)
Treatment: high dose corticosteroids (Int J Dermatol 2008;47:29)
Gross: woody, firm subcutaneous mass
Micro: eosinophils, lymphocytes, mast cells and histiocytes in fibrotic or fibromyxoid stroma of subcutis and fascia
Micro images: thickening of fascia with chronic inflammatory infiltrate #1; #2; #3; marked thickening and replacement of the entire dermis with sclerotic collagen; sclerosis at dermosubcutaneous junction, thickened subcutaneous septa and fascia, and a perivascular and interstitial infiltrate of lymphocytes and plasma cells; inflammatory infiltrate in deep subcutis; fascia has heavy inflammatory infiltration with numerous eosinophils, lymphocytes, and occasional plasma cells; entrapment of subcutaneous fat by intersecting thick bands of fibrosis, also thickening and fibrosis of fascia and lymphoid aggregates
References: eMedicine #1; #2
Fibroma of tendon sheath - Soft Tissue Tumor chapter
Definition: well circumscribed, lobulated tumor attached to tendon or tendon sheath
Also called tenosynovial fibroma
Benign; may overlap with nodular fasciitis (AJSP 1989;13:472) or giant cell tumor of tendon sheath (Mod Path 1995;8:155)
Uncommon, 60% men, ages 30-50 years old with nodule on fingers, hands or wrist
Up to 24% recur, does not metastasize
Case reports: mass of medial canthus of eye (Ophthal Plast Reconstr Surg 2007;23:341)
Treatment: excise to relieve symptoms but preserve function, may be difficult to remove from adherent tendons
Gross: well circumscribed, small fibrous multinodular mass < 3 cm, cut surface is pale, solid and homogeneous
Micro: well circumscribed nodules of dense fibrous tissue with occasional spindle or stellate mesenchymal cells in S or C shaped patterns; cells have scant cytoplasm and elongate nuclei with evenly distributed fine chromatin; often dilated or slit-like channels / clefts resembling tenosynovial spaces; varies from cellular to paucicellular; may have bizarre tumor cells, extravasated red blood cells, but no atypical mitotic figures, no necrosis, no hyperchromasia
Micro images: multinodular proliferation; extensive collagenization of nodules produces this typical, eosinophilic, paucicellular appearance, incomplete separation of the nodules produces cleft-like spaces; most cases are paucicellular with scattered spindled fibroblasts in a densely collagenized matrix and scattered small vessels; transition from collagenous to cellular area; cellular area resembles leiomyosarcoma or fibrosarcoma, but these tumors are rare in hands and feet; fibroblasts are bland (ruling out sarcoma) and separated by collagen; predominately acellular fibrous tissue with areas of hyalinization and characteristic slit-like vascular channels; tumor of finger #1; #2; #3
Positive stains: smooth muscle actin, vimentin
EM: resembles myofibroblasts and fibroblasts
EM images: spindle cells in collagenous matrix (M) have oval and convoluted nuclei (N), clefts (C) are present between cells and nuclei; spindle cell has a convoluted nucleus (N), rough endoplasmic reticulum (RER), vacuoles (V) and thin band of myofilaments just beneath the plasma membrane (arrows); myofilament bundles (M) show periodic densities (arrows); spindle cell has rough endoplasmic reticulum (RER), myofilaments (M) and pinocytotic vesicles (arrows)
Molecular/cytogenetics: 50% have t(2;11)(q31-32;q12) (Histopathology 1998;32:433)
DD: sarcoma (cellular, but rare in hands and feet, usually large masses with marked chromatin abnormalities and abnormal mitotic figures), benign fibrous histiocytoma (usually not hands or feet, prominent histiocyte-like cells, foam cells, giant cells and hemosiderin, CD68+), giant cell tumor of tendon sheath (more cellular, cells have histiocyte-like nuclei, also prominent giant cells, foam cells, hemosiderin; no slit-like vascular spaces, no extensive hyalinized stroma)
References: Stanford University
Fibromatosis of soft tissue - general
Definition: proliferation of well differentiated fibroblasts with infiltrative growth, collagenous stroma, no atypia, no/rare mitotic figures, aggressive behavior with local recurrence
Also called musculoaponeurotic fibromatosis (since usually in intimate contact with skeletal muscle), desmoid tumors (classically in abdominal wall during pregnancy)
Neoplastic, locally aggressive (repeated recurrences, no distant metastases); resembles scar tissue
May arise after trauma or in the scar of a surgical excision
May arise post-radiation and feature bizarre cells with large hyperchromatic nuclei
Present in Gardner’s syndrome (multiple colonic polyposis, multiple osteomas); usually involves omentum or mesentery after surgery
Juvenile fibromatosis: similar to adult fibromatosis but (a) more common, (b) has variants of fibromatosis colli, infantile digital fibromatosis and infantile myofibromatosis
Treatment: radical excision with wide margins; less recurrence in abdominal wall than elsewhere; may recur 5-6 times; may stop growing if stop excising; suggestion - don’t excise if it asymptomatic or isn’t growing
Also radiation therapy for local control (external or iridium implants); tamoxifen therapy
Gross: large, firm, white cut surface, infiltrative borders; often in muscular fascia
Micro: lobulated proliferation of fibroblasts or myofibroblasts (amphophilic cytoplasm due to rough ER, open chromatin, well defined nuclear membrane, one distinct nucleoli), usually more collagenous and less cellular than nodular fasciitis; mucopolysaccharide matrix with thin walled, curvilinear, non-branching or ectatic vessels; infiltrative borders, perivascular lymphocytes at edge of lesion; few mitotic figures, no atypia
DD: GIST tumor (in abdomen), fibrosarcoma (5+ MF/10 HPF)
Fibromatosis - superficial of soft tissue
Palmar fibromatosis (Dupuytren’s contracture) - Soft Tissue Tumor chapter
Definition: nodular proliferative process of palmar aponeurosis, surrounding adipose and occasionally dermis, due to fibroblasts, myofibroblasts and fibrocytes
Most common type of fibromatosis (1-2% of population), prevalence increases with age (in 24% age 65+)
75% men
50% bilateral, 10% also have plantar disease, 1-4% have penile fibromatosis
May be nodular; puckers overlying skin as it ages; causes flexion contracture of digits 4 and 5 due to cords of fibrous tissue between nodules and tendons
May be caused by fibrogenic cytokines (J Hand Surg [Br] 2005;30:557)
Treatment: excision
Clinical images: flexion contracture #1; #2
Gross: small nodules or nodular masses associated with aponeurosis and subcutaneous fat, with gray-yellow-white cut surface (color depends on collagen content)
Micro: proliferative phase - uniform, plump, immature spindle cells (myofibroblasts and fibroblasts) with bland nuclei and indistinct nucleoli; moderate collagen and elongated vessels; older lesions - more dense collagen, less cellularity; variable mitotic figures; occasional attachment to dermis or cartilaginous metaplasia; usually no infiltration of surrounding tissue beyond subcutis
Micro images: nodule of variably cellular fibroblastic tissue infiltrates an aponeurosis, with bland, uniform spindled cells in a dense hyalinized collagen stroma; mitotic figures may be present in cellular regions but are never atypical; tumor of myofibroblasts and fibroblasts within fascia #1; #2; #3; various images
Positive stains: vimentin, variable muscle specific and smooth muscle actin (in proliferative phase)
Negative stains: keratin, CD34
EM: fibroblasts and myofibroblasts
Molecular/cytogenetics: near diploid, often +7 or +8; appears to be reactive not neoplastic (J Transl Med 2006;4:21), no somatic mutations of beta-catenin genes, unlike desmoid fibromatosis (Mod Path 2001;14:695)
DD: fibrosarcoma (single large mass of deep soft tissue with intersecting bundles of cells whose nuclei have abnormal chromatin), epithelioid sarcoma (common in hands, but some cells have distinctive epithelioid appearance with abundant bright eosinophilic cytoplasm, also necrosis, keratin+, CD34+), desmoid tumors (rare in hand, dominant mass infiltrates skeletal muscle)
References: eMedicine, Stanford University
Plantar fibromatosis (Ledderhose’s disease) - Soft Tissue Tumor chapter
Definition: nodular proliferative process of plantar aponeurosis and surrounding adipose due to fibroblasts, myofibroblasts and fibrocytes
Considered a heterogeneous group of conditions with plantar location, mature collagen and fibroblasts but without malignant features (eMedicine)
Common in boys < 10 years old and teenagers
Only 10-25% bilateral, may be nodular
Often presents with firm subcutaneous nodule or thickening associated with pain after standing or walking
Clinically resembles melanoma, synovial sarcoma, Kaposi’s sarcoma
Usually NOT associated with contractures, but is associated with palmar and penile fibromatosis
Increased risk of recurrence if multiple nodules, bilateral lesions, family history
Treatment: excision
Clinical images: mass along medial plantar surface; heel mass
Gross: 2-3 cm nodules associated with aponeurosis and subcutis, with gray-yellow-white cut surface (color depends on collagen content)
Gross images: plantar nodules
Micro: proliferative phase - hypercellular collection of uniform, plump, immature spindle cells with bland nuclei and indistinct nucleoli; moderate collagen and elongated vessels; variable multinucleated giant cells (AJSP 2002;26:244); older lesions - more dense collagen, less cellularity; often prominent chronic inflammation, variable mitotic figures and hemosiderin
Positive stains: vimentin, variable muscle specific and smooth muscle actin
EM: fibroblasts and myofibroblasts
Molecular/cytogenetics: near diploid, often +7 or +8, no somatic mutations of beta-catenin genes, unlike desmoid fibromatosis (Mod Path 2001;14:695)
DD: monophasic synovial sarcoma, fibrosarcoma, desmoid fibromatosis (infiltrates skeletal muscle, > 3 cm), calcifying aponeurotic fibroma
References: AJSP 2005;29:1095 (children), Stanford University, Wikipedia
Penile fibromatosis (Peyronie’s) - Soft Tissue Tumor chapter
Definition: fibrous thickening of dermis and Buck’s fascia between corpora cavernosa and tunica albuginea, causing curvature towards side of lesion and restricting movement of these structures during erection
Fibrotic condition of varying etiologies (microvascular trauma-Int J Impot Res 2002;14:406, urethritis, sclerosing inflammatory process, idiopathic), appears to differ from other superficial fibromatoses (Curr Urol Rep 2004;5:478)
Prevalence up to 3% (Int J Impot Res 2002;14:379), associated with plaques, pain, induration, deviation; also Dupuytren’s contracture
Typically age 40+ years, rarely age 40 or less (J Androl 2003;24:27)
Usually dorsolateral penis, 30% have inflammatory component
Case reports: with ossification (Sao Paulo Med J 2007;125:124)
Treatment: may spontaneously regress, responds to small amounts of irradiation, steroids, excision
Micro: disorganization of collagen of tunica albuginea with formation of nodules, perivascular lymphocytic infiltrate in 1/3, linear band of calcification in 1/4 (J Urol 1997;157:282)
EM: penile plaques are composed of collagen fibrils, amorphous particulate material and fibroblasts (Int J Urol 1997;4:274)
DD: epithelioid sarcoma (may clinically appear similar, Int J Impot Res 2003;15:378)
References: Wikipedia
Fibromatosis - deep (desmoid type) of soft tissue
Definition: clonal fibroblastic proliferation of deep soft tissue with infiltrative growth; locally aggressive (local recurrence, but no metastases)
See also description at other sites, including breast, colon, small bowel
"Desmos" (Greek) means tendon-like
2-4 per million population, less common than superficial fibromatosis
May be familial (associated with Gardner’s syndrome/FAP syndrome-Clin Gastroenterol Hepatol 2008;6:215) or related to trauma
Usually ages 15-39 years, may be painful; common sites in children are head and neck
May be fatal due to local effects, particularly in head and neck
Abdominal wall fibromatosis: arises within abdominal wall-women during or after pregnancy; may see with cesarean section scar
Extraabdominal fibromatosis: arises outside abdomen and abdominal wall, usually in muscles of shoulder, chest wall, back and thigh, equal gender frequencies
Intraabdominal fibromatosis: mesenteric, pelvic or retroperitoneal locations, associated with Gardner’s syndrome (familial adenomatous polyposis, multiple osteomas); often post-surgical
Case reports: 43 year old woman with tumor of retroperitoneal space (World J Surg Oncol 2004;2:33), post-traumatic paraspinal mass (World J Surg Oncol 2008;6:28), aggressive mesenteric tumor that responded to chemotherapy (Jpn J Clin Oncol 2008;38:222), tumor of abdominal wall (Radiology 2005;236:81)
Treatment: excision (inadequate excision may cause recurrence), may respond to chemotherapy (J Clin Oncol 2007;25:501), COX2 inhibitors (Urology 2007;70:591.e3), imatinib (J Cancer Res Clin Oncol 2007;133:533), NSAIDs (World J Surg Oncol 2008;6:17), radiation (Am J Clin Oncol 2005;28:211), tamoxifen or watchful waiting (Eur J Surg Oncol 2008;34:462)
Gross: solitary, gray-white and glistening, firm, poorly circumscribed, rubbery; more fibrotic centrally and cellular peripherally; cuts with gritty sensation, 5-10 cm
Gross images: extra-abdominal fibromatosis has dense white, trabeculated fibrous tissue that invades skeletal muscle and produces cross section of alternating white and red patches; tumor infiltrates thoracic wall; trunk tumor #1; #2; thigh tumor; thoracic tumor; gray-white tumor of Gardner syndrome; gray-glossy cut surface; tumor in mesentery of small bowel; well defined margin (uncommon); infiltrative margin; desmoid fibromatosis (left) contrasted with high-grade fibrosarcoma (right) - fibromatosis has gristle-like consistency, but fibrosarcoma tends to be white, fleshy and necrotic with an overlying tendon
Fibromatosis - deep (desmoid type) of soft tissue (continued)
Micro: poorly circumscribed with infiltration of adjacent tissue; uniform cellularity between exuberant fibrous proliferation and low grade fibrosarcoma; cells are bipolar fibroblasts and myofibroblasts with reduced cytoplasm that merges with surrounding collagen; variable mitotic activity but no atypia; stroma varies from collagenous, keloid-like to myxoid; regenerative muscle cells within lesions may resemble giant cells
Cytology: bland spindle cells with long, fusiform nuclei and metachromatic matrix material; tumor cells are individual or as fragments within matrix (Cancer 2007;111:166); FNA fairly reliable for diagnosis but core needle biopsy is better (Acta Orthop 2006;77:926)
Micro images: extra-abdominal fibromatosis - low power shows paucicellular fibrous proliferation in long fascicles, with numerous slit-like vessels characteristic of desmoid fibromatosis; fibroblasts have spindled, dense, wavy nuclei and minimal cytoplasm; margin shows infiltration of skeletal muscle, a common feature; atrophic and regenerating muscle fibers at the edge of the lesion may resemble rhabdomyoblasts; some tumors are myxoid; cells in myxoid tumors are uniformly bland, unlike those in malignant myxoid tumors; cellular tumor has scattered mitotic figures, none atypical; keloid-type pattern may be observed focally in deep tumors; paraspinal tumor #1; #2; thigh mass has spindle cells, dense collagenous stroma, slit-like vessels and chronic inflammation; pre-radiation therapy; post-radiation therapy shows reduced cellularity; breast-smooth muscle actin+
intra-abdominal (mesenteric) fibromatosis - tumor appears to be extrinsic to bowel muscularis propria, which distinguishes it from GIST; fibromatosis is paucicellular and composed of relatively uniform, bland spindle cells #1; #2; #3; bland, mitotically active, uniform cells in myxoid stroma; less commonly bland spindle cells are within collagen bundles; biopsy of pelvic tumor; trichrome stain highlights collagen in the fibromatosis and distinguishes it from overlying normal muscularis propria
abdominal wall fibromatosis - extension into adjacent muscle; fascicles of fibroblastic spindle cells with abundant intercellular collagen
Cytology images: various images
Virtual slides: abdominal fibromatosis
Fibromatosis - deep (desmoid type) of soft tissue (continued)
Positive stains: vimentin, variable smooth muscle actin and muscle specific actin, CD117 (AJSP 2002;26:1296, but depends on antibody used, AJSP 2001;25:549); also nuclear beta-catenin (sensitive but not specific, AJSP 2005;29:653, AJSP 2002; 26:1296), ER-beta in extra-abdominal tumors (Cancer 2006;106:208)
Negative stains: keratin, S100, CD34 (J Clin Pathol 2004;57:1119), ALK, desmin
EM: fibroblastic and myofibroblastic features, including intrareticular collagen fibers, thin filament bundles, cytoplasmic dense bodies
Molecular/cytogenetics: clonal; somatic beta-catenin point mutations in exon 3, codon 41 or codon 45 in 87% (AJSP 2007;31:1299); also associated with trisomy 20 and 8 (Am J Path 1999;154:729, Cancer Genet Cytogenet 1995;79:139) and loss of 5q (APC gene)
Molecular/cytogenetic images: trisomy 20 and 8
DD: idiopathic retroperitoneal fibrosis (Orman’s disease - inflammatory, strangles the ureters), sclerosing omentitis (grows like panniculitis, beta catenin negative); leiomyoma (bright pink cytoplasm), schwannoma, neurofibroma (no myofibroblasts), fibrosarcoma (atypia or mitotic figures present), low grade fibromyxoid sarcoma (beta catenin negative), GIST (AJCP 2004;121:93)
Fibromatosis colli of soft tissue
Definition: fibromatosis affecting lower 1/3 of sternocleidomastoid muscle, causing thickened muscle; appears at birth, often bilateral
Also called congenital torticollis (torticollis: twisting of neck causing unnatural position of head, usually caused by spasm of neck muscles)
Associated with congenital anomalies (14% have congenital dislocations of hip, also breech deliveries)
May be due to birth injury (breech presentation, forceps)
Uncommon (0.4% of live births), usually diagnosed by age 6 months
Recommended to diagnose by FNA since excision usually is not required
Treatment: early - stretching and physiotherapy, resolves in 70%; some cases require resection of affected muscle; does not recur
Gross: tan gritty mass of muscle up to 3 cm, no hemorrhage or necrosis
Micro: diffuse proliferation of uniform plump fibroblasts and myofibroblasts and scar like collagen in muscle, with entrapped reactive and degenerating skeletal muscle fibers (loss of cross striations, nuclear enlargement and hypercellularity, multinucleation, atrophy); surgical specimens are usually less cellular than FNA specimens because they are obtained later in time course of disease
Cytology: early - cellular specimen with clusters or parallel arrays of bland appearing spindle cells in fibromyxoid matrix; also atrophic skeletal muscle in clean background, frequent muscle giant cells, bland bare nuclei and collagen (Acta Cytol 2003;47:359); usually no significant inflammation (Diagn Cytopathol 2000;23:338)
Micro images: multinodular proliferation of acellular collagenized tissue replaces part of sternocleidomastoid muscle; skeletal muscle fibers are trapped at advancing edge of lesion; scattered, bland fibrocytes are widely separated by dense collagen
Positive stains: vimentin, actins
DD: fibromatosis (no muscle fibers - they are replaced by fibrous tissue except at periphery, does not typically affect sternocleidomastoid muscle), proliferative myositis (doesn’t affect this site, stroma resembles granulation tissue and is not collagenous), fibrodysplasia ossificans progressiva (doesn’t affect this site, hand malformations are present, bone is present)
Fibrosarcoma of soft tissue - adult
Definition: malignant tumor of fibroblasts with herringbone architecture and variable collagen
Rare (up to 3% of adult sarcomas)
Some limit diagnosis to those age 10+ years, most patients are ages 40-55 years
Many cases formerly called fibrosarcoma are actually fibromatosis, MPNST, synovial sarcoma or MFH-pleomorphic
Usually deep soft tissue of lower extremities or trunk, only rarely in retroperitoneum or mediastinum
50% recur, 25% metastasize (lung, bone); more metastases if more cellular and higher mitotic activity
Survival: 5 year-41%, 10 year-29%; better if tumor is superficial and better differentiated, low mitotic rate, no necrosis
Treatment: radical excision, radiation if residual tumor or positive margins; possibly chemotherapy if high grade
Gross: may appear well circumscribed but nonencapsulated; fleshy, hemorrhagic, necrotic, white-tan
Micro: highly cellular fibroblastic proliferation in herringbone pattern (cells in columns of short parallel lines with all the lines in one column sloping one way and lines in adjacent columns sloping the other way); cells have scant cytoplasm, tapering elongated dark nuclei with increased granular chromatin, variable nucleoli; mitotic activity present, often with abnormal forms; variable collagen; usually no giant cells; no pleomorphism (or call pleomorphic MFH), no other distinct cell types
Patterns: keloid-like (thick hyalinized collagen fibers), loose fascicular, focally myxoid
Micro images: atypical uniform cells in herringbone pattern; cells are clearly malignant, with coarse chromatin but minimal pleomorphism; grade I tumor has minimal pleomorphism and low mitotic index, but is more cellular than fibromatosis #1; #2; grade II tumor has intermediate features #1; #2; grade III tumor has high grade atypia and high mitotic index #1; #2
Virtual slides: fibrosarcoma
Positive stains: reticulin stain demonstrates fibers surrounding EACH cell; phosphotungstic acid-hematoxylin demonstrates abundant cytoplasmic fibrils; also vimentin, type 1 collagen, p53; high Ki-67; may be CD34+ if arises from DFSP or solitary fibrous tumor
Negative stains: S100, keratin; also smooth muscle markers, histiocytic markers, basal lamina
EM: fibroblasts with prominent rough endoplasmic reticulum but no myofilaments, no external lamina, no intercellular junction; also no distinct myofibroblasts (if present, call myofibrosarcoma)
Molecular/cytogenetics: aneuploid
DD (other tumors with fibrosarcomatous areas): synovial sarcoma, liposarcoma, MFH-pleomorphic, MPNST, fibromatosis (less cellular, less hyperchromasia, no atypia, <1 mitotic figure/HPF)
Fibrosarcoma of soft tissue - infantile
Definition: resembles adult fibrosarcoma morphologically, but better prognosis
Age cutoff between infantile and adult forms usually varies between 5 and 10 years
Usually presents before age 2 years in axial regions or extremities with vary rapid growth
Related to congenital mesoblastic nephroma, which has same translocation
40-50% recur but only rarely metastasizes
Survival is 90%+
Case reports: premature newborn with large facial mass (Archives 2003;127:e281)
Gross: may exceed 30 cm (grotesquely large compared to size of child) with tense erythematous and ulcerated overlying skin; firm to soft cut surface is fleshy, gray-tan with myxoid change, cystic degeneration, hemorrhage and necrosis
Gross images: fleshy white mass similar to adult fibrosarcoma
Micro: poorly circumscribed, lobulated mass of small to large spindled cells in fascicles or herringbone pattern with high cellularity, nuclear atypia and pleomorphism; increased mitotic figures, hemorrhage and necrosis; resembles adult fibrosarcoma; may have prominent hemangiopericytoma-like areas, dystrophic calcification, extramedullary hematopoiesis; infiltrates adjacent soft tissue with irregular margins
Micro images: biphasic pattern with fibroblastic and cellular myxoid areas; high power of myxoid area; infiltration of fat; infiltration of muscle; areas of variable cellularity; spindle cells; plump cells have granular chromatin; less cellular tumor which overlaps with infantile fibromatosis, although it almost never metastasizes #1; #2; leg tumor #1; #2; #3; fig 1: facial tumor involves eye and maxilla, fig 2: undifferentiated cells with loose myxoid stroma with arborizing vessels, fig 3: foci of fusiform spindle cells
Positive stains: vimentin; variable focal smooth muscle actin, desmin, S100 and CD34
EM: fibroblastic and myofibroblastic features
Molecular/cytogenetics: 70% have t(12;15)(p13;q26), causes ETV6-NTRK3 gene fusion transcript (ETS variant gene 6 and neurotrophic tyrosine receptor kinase type 3) detectable by FISH (Mod Path 2001;14:1246) or RT-PCR (AJSP 2000;24:937, AJCP 2001;115:348; also trisomy 8, 11, 17 and 20
Molecular images: ideogram of fusion transcript and FISH
DD: (none have t(12;15) - adult type fibrosarcoma (usually age 10+), infantile fibromatosis, myofibromatosis
Fibrous hamartoma of infancy - Soft Tissue Tumor chapter
Definition: poorly circumscribed proliferation of immature spindle cells in organoid pattern with fat and dense fibrocollagenous tissue
Rare; usually age 2 years or less (25% discovered at birth), does not occur after puberty, 2/3 male
Solitary, rapidly growing, freely movable mass of subcutis or dermis
Sites: axilla, shoulder and inguinal region (J Urol 1994;152:990); not hands and feet
Case reports: 11 month old boy with thigh mass (The Internet Journal of Dermatology 2001;1:2), 6 month old girl with arm mass, multiple nodules with overlying hypertrichosis (J Dermatol 2006;33:427), recurrent tumor (Pediatr Surg Int 2005;21:119)
Treatment: excision, need not be radical as recurrence is uncommon (J Am Acad Dermatol 2006;54:800)
Gross: poorly circumscribed, gray-white with yellow fat, usually 5 cm or less
Gross/clinical images: untreated tumors - axillary tumor in 6 month old Nigerian boy; scapular tumor in 7 year old Nigerian girl #1; #2-at surgery showing well developed capsule
Micro: poorly circumscribed, organoid with 3 components - (1) trabecular or stellate immature mesenchymal cells with scant cytoplasm and bland straight or wavy nuclei in myxoid matrix, (2) fibrocollagenous tissue composed of bland fibroblasts or myofibroblasts, (3) mature fat; no/scant mitotic figures; overlying epidermis usually has eccrine changes, including hyperplasia, duct dilation, intraluminal papillary formations and squamous syringometaplasia (J Cutan Pathol 2007;34:39)
Cytology: adipose tissue fragments, clusters of fibroblastic cells, myxoid and collagenous matrix (Diagn Cytopathol 2003;28:272)
Micro images: triphasic pattern of fibrous spindle cells delimiting islands of mature fat and primitive spindle cells; primitive spindle cells may infiltrate fat; primitive spindle cells and fibrous spindle cells are bland and uniform with no/rare mitotic figures; three cell types are present #1; #2; #3; various images #1; #2; collagenous tissue and immature mesenchymal cells; H&E and t(2;3) karyotype
Positive stains: vimentin; spindle cells in fibrous trabeculae may be actin+
EM: fibrous trabeculae are composed of fibroblasts and myofibroblasts, primitive mesenchymal cells have slender cytoplasmic processes with few organelles
Cytogenetics: rarely complex translocations (Cancer Genet Cytogenet 2006;171:115), t(2;3) (Archives 2005;129:520)
DD: calcifying aponeurotic fibroma (almost always hands or feet, prominent calcification, no primitive cells within myxoid stroma), myofibroma (prominent hemangiopericytoma-like pattern, usually no fat)
References: Stanford University
Focal myositis - Soft Tissue Tumor chapter
Definition: inflammatory condition of skeletal muscle with degeneration and regeneration, inflammatory cells and fibrosis
Not a WHO diagnosis
Evolves over weeks to a localized, painful soft tissue swelling, usually of lower extremity
Solitary, self-limited, may be related to denervation
Case reports: due to statins (Int J Cardiol 2007 Dec 21 [Epub ahead of print]), due to Lyme disease (Arthritis Rheum 2006;54:2697), recurrent disease of peroneal muscles (Rheumatology (Oxford) 2002;41:1318), post bCG vaccination (Rheumatology (Oxford) 2002;41:1074), idiopathic focal myositis in pregnancy (Rheumatology (Oxford) 2000;39:211), 16 year old girl with mass in sternocleidomastoid
Gross: pale, ill-defined
Micro: degeneration and regeneration of muscle fibers associated with interstitial inflammation and fibrosis
Micro images: focal interstitial muscle inflammation associated with extensive proliferation of endomysial connective tissue; venlafaxine associated myositis shows regenerating muscle fibers and CD3+ (T) cells; associated with bCG vaccination #1; #2; focal perivascular chronic inflammatory infiltrate
Cytology: inflammatory cells, skeletal muscle fibers with degenerative and regenerative changes, fibrous tissue (Acta Cytol 2005;49:653)
DD: poliomyelitis
Gardner type fibroma of soft tissue
Definition: benign soft tissue lesion with thick, haphazard collagen and bland fibroblasts that entrap adjacent tissue; 90% associated with FAP / Gardner syndrome / APC germline mutation
Uncommon; affects infants, children and teenagers
May be initial diagnostic clue to Gardner syndrome and APC mutations (AJSP 2001;25:645); 45% develop desmoid-type fibromatosis
Similar histology to nuchal-type fibroma (Pathol Int 2004;54:523, AJSP 2000;24:1563)
Sites: superficial or deep soft tissue of paraspinal area, back, chest, flank, head and neck, extremities
Gross: 1-10 cm, poorly circumscribed, firm, rubbery, plaque-like, white to tan-pink cut surface with trapped fat in yellow areas
Micro: thick, haphazardly arranged collagen bundles, hypocellular bland fibroblasts, small blood vessels, plaque-like growth pattern with infiltration of adjacent structures
Positive stains: CD34, cyclin D1, vimentin, nuclear beta-catenin (64%)
Negative stains: muscle specific actin, smooth muscle actin, desmin, ER, PgR
References: AJSP 2007;31:410, Stanford University
Giant cell angiofibroma of soft tissue
Definition: uncommon benign neoplasm of multinucleated giant cells and ectatic vascular spaces
May be related to solitary fibrous tumor (AJSP 2000;24:971)
Median age 45 years; more common in men in eyelid/orbital sites, more common in women elsewhere
Often slow growing painful mass
Case reports: 57 year old woman with eyelid tumor extending into orbit (Can J Ophthalmol 2006;41:216), 50 year old woman with inguinal tumor (Ann Diagn Pathol 2000;4:240)
Treatment: excision, does not recur
Sites: eyelid, nasolacrimal duct (Ophthal Plast Reconstr Surg 2001;17:202), lacrimal sac or orbit (AJSP 1995;19:1286)
Gross: well circumscribed with variable capsule, median 3 cm (larger in extra-orbital regions), may have hemorrhagic or cystic cut surface
Micro: cellular areas with bland round to spindle cells in myxocollagenous stroma with small-medium thick walled vessels and multinucleated giant stromal cells that line ectatic vascular spaces
Micro images: various images
Positive stains: CD34, CD99, vimentin, variable bcl2
Negative stains: CD68, c-kit/CD117, muscle specific actin, S100, desmin
Cytogenetics: rarely t(12;17)(q15;q23) (Cancer Genet Cytogenet 2006;165:157), 6q13 abnormalities (Cancer Genet Cytogenet 2000;116:47)
Giant cell fibroblastoma of soft tissue
Definition: rare childhood fibroblastic tumor of intermediate malignancy with floret-like giant cells and ectatic pseudovascular spaces lined by stromal cells and giant cells
Part of WHO classification for skin tumors, not soft tissue tumors
Appears to evolve into DFSP by genomic gains of COL1A1-PDGFB (Genes Chromosomes Cancer 2008;47:260); considered the juvenile form of DFSP, as both have the same translocation (AJSP 2003;27:27)
Usually children less than 10 years old, 2/3 male
Painless nodule of subcutis, usually in trunk, extremities, head and neck
50% recur but recurrences are controllable, no metastases
Case reports: 3 year old boy with recurrent knee lesion (Pathol Oncol Res 2003;9:249), 28 year old woman with vulvar tumor (J Low Genit Tract Dis 2007;11:112)
Gross: poorly circumscribed, gray to yellow mucoid mass that is difficult to completely excise, usually in subcutis
Micro: dermis and subcutis contains hyperchromatic spindle or stellate shaped cells in a collagenous or myxoid matrix with scattered hyperchromatic multinucleated floret-like giant cells with prominent nucleoli, similar to those in pleomorphic lipomas; ectatic pseudovascular spaces are lined by a discontinuous row of floret-like cells and tumor cells; honeycomb or parallel pattern of infiltration; also hyalinized area, perivascular lymphocytes in onionskin pattern, intralesional hemorrhage; often foci of DFSP; no histiocyte-like cells, no mitotic figures
Cytology: moderately cellular smears with mononuclear cells, usually single but occasionally in clusters; most cells have no/scanty cytoplasm, bland nuclei with small nucleoli; nuclear membranes often have notches, creases or folds; rare multinucleated giant cells with bland oval nuclei; no necrosis, no mitotic figures (Diagn Cytopathol 2002;26:398, Archives 2001;125:1091)
Micro images: ectatic pseudovascular spaces are lined by giant cells #1; #2; #3; stroma has giant cells and myxoid stroma; stroma is fibrotic with giant cells but sparse angiectoid spaces in this case; multinucleated stromal giant cells have vesicular nuclei and prominent nucleoli, but smaller spindle cells have indistinct nucleoli; trunk tumor #1; #2; #3; various images
Cytology images: various images (fig a-c)
Giant cell fibroblastoma of soft tissue (continued)
Positive stains: vimentin, CD34, CD99 (40%, J Cutan Pathol 2008 Jan 14 [Epub ahead of print]), variable actin
Negative stains: S100, CD31, Factor VIII, keratin, desmin, HMB45
Molecular/cytogenetics: t(17,22)(q22;q13) - creates fusion of collagen type 1 alpha 1 gene and platelet derived growth factor B chain gene; also supranumerary ring chromosomes derived from t(17;22)
EM: myofibroblasts or fibroblasts
DD: neurofibroma with ancient change (no ectatic vascular spaces, S100+), liposarcoma, angiosarcoma (older adults in head and neck, cells have enlarged atypical nuclei, mitotic figures present), hemangioma (no giant cells, CD31+)
References: Archives 1996;120:1052, Ann Diagn Pathol 2007;11:81
Hemangiopericytoma of soft tissue
Definition: controversial entity; rare lesions similar to cellular solitary fibrous tumor - may not actually differ from SFT
Diagnosis of exclusion (Histopathology 2006;48:63)
Historically defined as lesions with thin walled, branching vascular pattern, although this is common in many lesions
Probably not a lesion of pericytes, except at sinonasal location
Infantile lesions now called myofibroma / myofibromatosis
See also discussions in these chapters: Bone, Breast, CNS, Heart, Nasal cavity, Thyroid gland
Middle aged adults, more common in women
Most common in deep soft tissue, particularly pelvic retroperitoneum, also limb or limb girdles and head and neck
Occasionally associated with hypoglycemia (J Clin Endocrinol Metab 1996;81:919)
5 year survival was 86% in 2002 (Cancer 2002;95:1746)
70% have benign behavior
Poor prognostic factors may be 4+ mitotic figures/10 HPF, necrosis, nuclear pleomorphism with size > 5 cm
Case reports: omental tumor with metastases (World J Surg Oncol 2007;5:63)
Gross: well circumscribed, yellow-tan cut surface, fleshy or spongy with hemorrhage but no necrosis, up to 15 cm
Gross images: encapsulated omental tumor #1; #2; patient with 3 tumors - (a) greater omentum tumor (under forceps); (b) small jejunal tumor; (c) retroperitoneal tumor with portions of diaphragm and liver
Micro: uniformly cellular (similar to cellular areas of solitary fibrous tumor) with numerous, variably ectatic or compressed, thin walled branching vessels with staghorn configuration; tumor cells are spindled to round with small amounts of pale or eosinophilic cytoplasm, indistinct margins, bland vesicular nuclei; stromal hyalinization is not prominent; variable mitotic activity; no atypia
Cytology: cellular; single and tightly packed clusters of oval to spindle cells aggregated around branched capillaries; often basement membrane material present; nuclei are uniform, oval, with finely granular chromatin and indistinct nucleoli; no mitotic figures, no necrosis (Cancer 1999;87:190)
Hemangiopericytoma of soft tissue (continued)
Micro images: staghorn vessels are prominent; uniform cells around branched, thin-walled, staghorn vessels; various images (many from CNS); reticulin stain; hemangiopericytoma of CNS is CD34+ (figure 3) / CD31 neg (figure 4)
Cytology images: irregular fragments of tissue, loose cellular aggregates and single cells; uniform oval or spindled cells with indistinct borders, high N/C ratio, and capillary vessels with long and hyperchromatic nuclei Diff-Quik, ×400); metachromatic basement membrane material within the fragments separates tumor cells from endothelial cells; malignant cells radiating from vessels (also gross, Xray, H&E)
Virtual slides: hemangiopericytoma
Positive stains: CD34 (Hum Path 1998;29:636), CD99; reticulin surrounds individual cells
Negative stains: Factor VIII, CD31, CD34, usually actin and desmin (except in sinonasal hemangiopericytoma)
EM: no true pericytic differentiation; has fibroblastic or undifferentiated spindle cell features
DD: solitary fibrous tumor (more prominent collagen, less prominent vessels), monophasic synovial sarcoma, myopericytoma, deep fibrous histiocytoma, mesenchymal chondrosarcoma, endometrial stromal sarcoma (Mod Path 2005;18:40)
Lipomatous hemangiopericytoma
Definition: variant with mature adipose tissue
Also called adipocytic variant of solitary fibrous tumor
First described in 1995 (AJSP 1995;19:748)
Uncommon; 2/3 males, usually thigh, lower extremity and retroperitoneum
Only rarely recurs, does not metastasize
Case reports: Case of the Week #16, mediastinum (J Postgrad Med 2006;52:71), skull base and parapharyngeal space (Otol Neurotol 2006;27:560)
Gross: solid, tan-yellow
Micro: well circumscribed, patternless cellular areas, prominent hemangiopericytoma-like vessels, mature adipose tissue, variable collagen
Cytology: may resemble myxoid liposarcoma (Diagn Cytopathol 2003;29:287)
Micro images: retroperitoneal mass (Case of Week) - image #1; #2; #3; #4; #5; #6; #7; #8; #9; #10; mediastinal tumor #1; #2
Positive stains: vimentin, CD99, CD34 (75%), bcl2 (60%)
Negative stains: CD31, desmin, keratin, actins, S100, GFAP
EM: features of pericytes, no lipoblasts
DD: various lipomas, liposarcoma
References: Hum Path 2000;31:1108, AJSP 1999;23:1201
Inclusion body fibromatosis of soft tissue
Definition: dermal fibroblastic and myofibroblastic lesion with cytoplasmic eosinophilic inclusions, usually in digits of infants
Also called infantile digital fibromatosis, infantile digital fibroma (J Hand Surg [Am] 1995;20:1014)
Rare; lesions usually present at birth or in first 2 years; similar lesions in adults; often are multiple
Usually exterior surface of distal phalanges of fingers and toes, but not thumb or great toe, also oral cavity and breast
50% recur, do not metastasize
Similar inclusions reported in breast fibroadenoma (Archives 2007;131:1126), breast phyllodes tumor (AJSP 1994;18:506), cervical polyp (Pathology 1998;30:215), GI leiomyomas (Cesk Patol 2006;42:139)
Case reports: spontaneous regression (J Dermatol 1998;25:523)
Treatment: excision, but preserve function because recurrences are not destructive and tumors do not metastasize
Gross: nodules with stretched overlying skin, lesions are ill defined, white-tan, usually 2 cm or less; no hemorrhage or necrosis
Micro: nonencapsulated, dermal proliferation of hypocellular sheets or fascicles of fibroblasts and myofibroblasts with variable collagen; some spindle cells have peculiar eosinophilic (hyaline) cytoplasmic inclusions the size of a lymphocyte nucleus; usually mitotic figures; may infiltrate into adjacent tissue; no atypia
Micro images: proliferation extends from epidermis to deep dermis or subcutis; fibroblastic cells swirl around and engulf an eccrine duct; cells are bland and monomorphic; inclusions resemble red blood cells
Positive stains: inclusions - trichrome (stain red), PTAH, variable staining for actins; spindle cells - vimentin, muscle actins (tram track pattern)
Negative stains: inclusions - PAS
EM: spindle cells are myofibroblasts with rough endoplasmic reticulum and free lying inclusions composed of compact masses of actin granules and filaments without a limiting membrane (Am J Pathol 1979;94:19)
DD: infantile fibrosarcoma (not digits, usually > 2 cm, more cellular, chromatin is denser and more irregular, more mitotic figures, no inclusions), infantile desmoid fibromatosis (rare on hand, usually > 2 cm)
References: Stanford University
Inflammatory myofibroblastic tumor of soft tissue
Definition: tumor of myofibroblasts with plasma cells, lymphocytes and eosinophils
Also called inflammatory fibrosarcoma, inflammatory pseudotumor, plasma cell granuloma
See also discussions in these chapters: Bladder, Bone, Breast nonmalignant, CNS-tumor, Colon-tumor, Eye (orbit), Heart-tumor, Kidney-tumor, Liver-tumor, Lung-tumor, Lymph node-not lymphoma, Mediastinum, Pancreas, Salivary glands, Small bowel, Spleen, Thyroid gland
Retroperitoneum (omentum) and mesentery in children and young adults (mean age 10 years); also lung, GI, GU, other sites
1/3 have associated fever, growth failure, malaise, weight loss, anemia, thrombocytosis, polyclonal hyperglobulinemia, and elevated sedimentation rate; symptoms disappear after excision of mass (J Korean Med Sci 2002;17:699)
Poor prognostic factors: abdominal or pelvic sites, ALK negative (AJSP 2007;31:509)
Case reports: anterior abdominal wall (Surg Today 2007;37:352), mesenteric tumor (World J Gastroenterol 2007;13:3645), retroperitoneal tumor (World J Surg Oncol 2005;3:66), t(1;2)(q21; p23) with unusual features (Archives 2006;130:1042), bone marrow involvement (Archives 2003 Jul;127:865)
Treatment: excision (J Pediatr Surg 2005;40:1581), 25-35% recur, rare metastases (or may be evidence of multifocality)
Gross: circumscribed, not encapsulated; white tan mass with whorled fleshy or myxoid cut surface; may have focal hemorrhage, necrosis or calcification, mean 6 cm
Gross: 19 cm mesenteric tumor (fig 2-4)
Micro: myofibroblastic and fibroblastic spindle cells with inflammatory infiltrate of lymphocytes, plasma cells, eosinophils, histiocytes; background of abundant blood vessels; mixture of three patterns - (1) resembling nodular fasciitis with elongated myofibroblasts containing abundant eosinophilic cytoplasm and vesicular nuclei, loose myxoid stroma with neutrophils, lymphocytes and eosinophils, but few plasma cells; (2) cellular with spindled myofibroblasts and fibroblasts in more compact stroma, arranged as islands surrounded by fibromyxoid stroma with prominent plasma cells and mitotic figures; (3) densely hyalinized stroma with few spindle cells, few plasma cells or lymphocytes; may have ganglion-cell like myofibroblasts; all 3 patterns have no nuclear pleomorphism, no atypical mitotic figures
malignant behavior - associated with highly atypical polygonal cells with oval nuclei, prominent nucleoli, Reed-Sternberg like cells, atypical mitotic figures
Inflammatory myofibroblastic tumor of soft tissue
Micro images: typical appearance of spindled myofibroblastic cells and inflammatory infiltrate #1; #2; #3; #4; #5; #6; inflammation obscures the underlying myofibroblastic proliferation; spindle cells are evident at high power; tumor with more fibrous stroma; various images; retroperitoneal tumor #1; #2; #3; #4; peritoneal tumor with bone marrow involvement; H&E and ALK1; H&E, ALK1, p80; ALK1 and p80
Virtual slides: inflammatory myofibroblastic tumor
Positive stains: vimentin (diffuse, strong), usually alpha smooth muscle actin, muscle specific actin and calponin (Hum Path 2008 Apr 7 [Epub ahead of print]), ALK1 / p80 in 40%, but not specific (Mod Path 2002;15:931), keratin and desmin in 1/3
Negative stains: S100, CD117, HHV8 (Mod Path 2007;20:995), CD34, h-caldesmon
EM: myofibroblastic cells and activated fibroblasts
EM images: fig b: filamentous bundles, attachment densities, pinocytotic vesicles and basal laminae
Molecular/cytogenetics: clonal abnormalities of 2p23 (Cancer Res 1999;59:2776), including t(2;5)(p23;q35) involving ALK and NPM; also t(2;17)(p23;q23) involving ALK and CLTC (Am J Path 2001;159:411) and t(2;19)(p23;p13.1) involving ALK and TPM4 (Am J Path 2000;157:377); associated with ALK deregulation and younger patients; see Atlas of Genetics
Molecular images: t(2;5) schematic; t(2;5) karyotype; ALK translocation is indicated by separation of green and orange probes of ALK gene in inflammatory myofibroblastic tumor (a), but not leiomyosarcoma (b); ALK staining, FISH and karyotype; FISH for ALK
DD: calcifying fibrous pseudotumor (Mod Path 2001;14:784), nodular fasciitis (smaller size, older patients, less inflammation)
Ischemic fasciitis - Soft Tissue Tumor chapter
Definition: sarcoma-like fibroblastic proliferation, usually of soft tissue, overlying bony prominences
Also spelled ischaemic
First described in 1992 as atypical decubital fibroplasia (AJSP1992;16:708)
Occurs primarily in immobilized and elderly patients due to chronic pressure and impaired circulation
Most common sites are pressure points on shoulder, chest wall and sacrococcygeal region
Rarely occurs in young adults with physical disabilities: 25 year old man with melorheostosis (rare progressive disease of hyperostosis)- Path Int 1998;48:160, 20 year old with vulvovaginal lesion (Int J Gynecol Pathol 2004;23:65)
Case reports: Case of Week #64, Archives 2004;128:e139, 45 year old woman with post-mastectomy axillary mass (The Internet Journal of Pathology 2008;7:1)
Treatment: local excision is curative, although recurrences may occur due to continuation of underlying ischemia and injury
Gross: usually 1 to 8 cm, poorly circumscribed, often myxoid; usually involves deep subcutis, may extend into adjacent skeletal muscle; ulceration is uncommon (i.e. overlying skin is intact)
Micro: zones of fibrinoid necrosis with uneven borders staining deep red/violet and prominent myxoid areas surrounded by ectatic, thin walled vessels and proliferating fibroblasts; endothelial cells may be atypical; fibroblasts have degenerative features of abundant, basophilic cytoplasm, enlarged nuclei with smudged chromatin and prominent nucleoli (resembling proliferating fasciitis); may have frequent mitotic activity, but no atypical mitotic figures; fibrin thrombi are common within peripheral vessels, which may show fibrinoid necrosis and recanalization; may have multivacuolated macrophages, but no lipoblasts; no primary vasculitis or myositis
Micro images: cellular, fibrin-rich proliferation centered on subcutaneous fibrous septum and extending into adjacent fat; hyalinized focus with large ganglion-like cells, suggestive of proliferative fasciitis; fibrin is adjacent to foci of ganglion-like cells in collagenous stroma; central area of ischemic fasciitis filled with fibrin and surrounded by proliferating vascular fibrous tissue; fibrinoid necrosis with few viable cells; spindle cells with large nuclei with prominent nucleoli resembling proliferative fasciitis; capillaries lined by plump endothelial cells and surrounded by large fibroblasts/myofibroblasts enmeshed in a loose collagenous stroma (figure 5); central area of ischemic fasciitis filled with fibrin and surrounded by proliferating vascular fibrous tissue (figure 4); post-mastectomy axillary mass-various images
hip mass in 55 year old bedridden man - image #1; #2; #3; #4; #5; #6
Ischemic fasciitis - Soft Tissue Tumor chapter (continued)
Cytology: spindled and ovoid cells with ample cytoplasm and occasional nuclear atypia (Acta Cytol 1997;41:598)
Positive stains: vimentin, actin, CD68; variable CD34 in enlarged fibroblasts
Negative stains: keratin, desmin, S100
DD: epithelioid sarcoma (more cellular with central necrosis, but typically occurs in young adults on the distal extremities, composed of cells with prominent eosinophilic cytoplasm that are keratin positive, atypical mitotic figures), myxoid liposarcoma (prominent plexiform vasculature and lipoblasts), myxofibrosarcoma (marked atypia, but no smudgy chromatin or fibrin thrombi; lacks zonation), proliferative fasciitis (ganglion cells show less atypia)
References: Mod Path 1993;6:69, Stanford University
Juvenile hyaline fibromatosis of soft tissue
Definition: infantile disorder with extracellular hyaline material in skin, soft tissue and bone, due to aberrant fibroblasts
Also called fibromatosis hyalinica multiplex
Called infantile systemic hyalinosis if organ involvement, but some cases overlap (Pediatr Dermatol 2004;21:154)
Very rare, associated with consanguineous parents
Due to mutations in capillary morphogenesis protein 2 (Am J Hum Genet 2003;73:791, Am J Hum Genet 2003;73:957)
Cutaneous nodules (face and neck), gingival hypertrophy, flexure contractures (due to masses in periarticular soft tissue) and bone lesions (skull, long bones, phalanges)
Case reports: disease in 2 siblings of first-degree consanguineous marriage (Indian J Dermatol Venereol Leprol 2005;71:115), 14 year old girl without prominent hyaline changes (J Cutan Pathol 2005;32:235)
Clinical images: multiple subcutaneous nodules; nodules on pinna of ear; large ulcerated nodules on back; gingival hyperplasia
Gross: solid, white, waxy nodules
Micro: well circumscribed hypocellular nodules that obliterate normal tissue; nodules are composed of plump fibroblasts and uniform eosinophilic, non-fibrillar hyaline material; lesions are more cellular in young and early in disease; fibroblasts may have fascicular patterns or clear cytoplasm; no atypia, no necrosis
Cytology: benign spindle cells with background eosinophilic ground substance (Acta Cytol 2007;51:624)
Micro images: amorphous hyaline matrix in dermis with fibroblasts; fibrous dermis with homogenous eosinophilic matrix; eosinophilic hyaline matrix; chondroid-like cells due to cytoplasmic retraction
Positive stains: PAS (diastase resistant), vimentin
Negative stains: muscle actin, S100
EM: fibroblasts with fibril-filled balls (dilated ER with numerous cisternae containing filamentous material similar to extracellular ground substance)
DD: gingival fibromatosis (limited to gums, collagen-rich fibrous tissue)
References: OMIM #228600, Stanford University
Lipofibromatosis of soft tissue
Definition: fibroblastic cells in septa and skeletal muscle mixed with adipose tissue
Also called infantile fibromatosis of nondesmoid type
First described in 2000 (AJSP 2000;24:1491)
Rare childhood tumor (first surgery usually at age 1), 2/3 male, often of distal extremities
Associated with macrodactyly of foot (Foot Ankle 1991;12:40)
Recurs locally, no metastases
Case reports: forearm of 10 month old boy (Ups J Med Sci 2005;110:259), foot of male infant (Skeletal Radiol 2008 Feb 16 [Epub ahead of print])
Gross: white-tan or yellow, 1-3 cm
Micro: bland fibroblasts involving septa of adipose tissue mixed with adipose tissue, may have minute small vacuolated cells between fibroblasts and adipose; no atypia, no/rare mitotic figures
Micro images: various images (figure 5)
Positive stains: spindle cells - CD34, CD99, smooth muscle actin; variable bcl2, S100, EMA, muscle specific actin
Negative stains: desmin, keratin
Molecular/cytogenetics: three-way t(4;9;6) translocation in a 5-year-old boy (rare, Cancer Genet Cytogenet 2007;179:136)
DD: fibrous hamartoma of infancy (has primitive oval cell component), fibromatosis (solid fibrous growth, no fat)
References: Stanford University
Low grade fibromyxoid sarcoma of soft tissue
Definition: variant of fibrosarcoma with fibrous and myxoid areas, whorled growth pattern, low cellularity, bland fibroblastic cells and curvilinear vessels
Also called fibrosarcoma-low grade fibromyxoid type, Evan’s tumor, hyalinizing spindle cell tumor with giant rosettes
Rare, first described by Evans in 1987 (AJCP 1987;88:615)
Prolonged preclinical stage
In trunk and deep extremities of young to middle-aged adults (median age 34 years, range 3-78 years), also intrathoracic (Hum Path 2008;39:623)
Local recurrence (9%) and metastases (6%) are less common in prospective studies due to more aggressive surgery
Includes hyalinizing spindle cell tumor with giant rosettes (similar histology and translocation but with collagen-containing rosettes-AJSP 2003;27:1229); may be related to some cases of sclerosing epithelioid fibrosarcoma with same translocation (AJSP 2007;31:1387)
Presence of focal intermediate to high grade sarcoma does not affect prognosis (AJSP 2000;24:1353)
Superficial cases may be more common than previously recognized, and have a better prognosis (AJSP 2005;29:204)
Fibrosarcoma-low grade fibroblastic type-no myxoid component, a diagnosis of exclusion (Histopathology 2006;49:152)
Case reports: epicardial surface of heart (Hum Path 2008;39:623), falciform ligament (BMC Surg 2003;3:7)
Treatment: complete excision
Clinical images: swelling of lower left leg
Gross: often > 6 cm, well circumscribed, fibromyxoid cut surface, may be grossly infiltrative
Gross images:; tumor of falciform ligament #1; #2; #3; well circumscribed with myxoid cut surface and cystic change; well circumscribed tumor of leg; well circumscribed tumor with giant rosettes
Micro: low to moderately cellular, bland fusiform or spindled cells with focal to diffuse whirling in heavily collagenized stroma with abrupt transition to myxoid areas, 45% have epithelioid areas; 40% contain poorly formed but large collagen rosettes; often infiltrates adjacent skeletal muscle; occasionally has areas of increased cellularity, atypia, necrosis or mitotic activity characteristic of intermediate to high grade sarcoma
Cytology: cellular with spindle cells containing scant wispy cytoplasm, uniform elongated nuclei, small inconspicuous nucleoli; prominent myxoid background; no significant nuclear pleomorphism or mitoses (Acta Cytol 2006;50:208, Cancer 1999;87:75)
Low grade fibromyxoid sarcoma of soft tissue (continued)
Micro images: characteristic features include fibrous and myxoid areas, a swirling whorled growth pattern, low to moderate cellularity and bland cells with minimal nuclear pleomorphism #1; #2; the swirling growth pattern is storiform #1; #2; bland spindle cells in fibromyxoid stroma; there is a relatively linear cell arrangement in this area, but other areas have the characteristic swirling and whorled pattern; whirled fibroblastic cells in a myxoid background with prominent capillaries #1; #2; rosettes in spindled stroma; cells forming rosettes are PGP 9.5+, Factor XIII negative; various images #1; #2; lung metastasis is more cellular but still bland; vimentin+; staining of vessels but not tumor by CD34, smooth muscle actin
Cytology images: ovoid to spindle cells with tapered cytoplasm and bland nuclei in myxoid background; hypercellular three dimensional tissue fragment in myxoid background; bland spindle cells in myxoid background #1 (Diff-Quik); #2
Virtual slides: low grade fibromyxoid sarcoma
Positive stains: vimentin, CD99 (90%), bcl2 (90%)
Negative stains: S100, desmin, keratin, CD34, MDM2, smooth muscle actin, h-caldesmon, CD117, nuclear beta catenin
EM: fibroblastic differentiation
EM images: rosette forming cells have dense core granules; elongated irregular nucleus and prominent dilated rough endoplasmic reticulum are characteristic of fibroblasts
Molecular/cytogenetics: t(7;16)(q32-34;p11)-FUS-CREB3L2 in 90% or more, also t(11;16)(p11;p11)-FUS-CRE3L1 by RT-PCR (Lab Invest 2005;85:408, AJSP 2007;31:1387, Diagn Mol Pathol 2008 Mar 28 [Epub ahead of print]) or FISH (AJSP 2008;32:8)
Molecular/cytogenetic images: complex karyotype includes t(7;16)
DD: myxofibrosarcoma (more myxoid and less fibrous, more nuclear pleomorphism and hyperchromatism, more developed vascular network, Histopathology 2004;45:29), desmoid fibromatosis (fibrous cells are aligned straighter, cells appear more like reactive fibroblasts, distinct slit-like vessels present, diffuse or occasionally focal nuclear beta catenin staining, AJSP 2005;29:653), neurofibroma (wavy nuclei, background of thick collagen bundles, S100+)
References: Stanford University
Low grade myofibroblastic sarcoma of soft tissue
Definition: rare tumor of malignant myofibroblasts
Also called myofibrosarcoma
Deep intramuscular tumors of head and neck (tongue and oral cavity) and extremities, rarely abdominopelvic (J Clin Pathol 2008;61:301)
Commonly recurs, only rarely metastasizes
Diagnostic criteria: predominantly myofibroblasts, distinct from fibrosarcoma and MFH-pleomorphic
Gross: firm, pale, fibrous cut surface, ill defined margins
Micro: diffusely infiltrative pattern, with fascicles or storiform growth of spindled tumor cells; cells have ill defined pale eosinophilic cytoplasm, fusiform nuclei that are elongated or wavy with evenly distributed chromatin or round and vesicular with indentations and small nucleoli; at least focal moderate nuclear atypia with hyperchromasia and irregular nuclear membranes; collagenous matrix with prominent hyalinization; may have numerous thin walled capillaries, 1-6 MF/10 HPF; no histiocytic giant cells or prominent inflammation
Micro images: breast - H&E shows fascicular growth (fig 1A), alpha smooth muscle actin+ (fig 1B) and vimentin+ (insert), fibronectin+ matrix (fig 1C), type IV collagen negative (fig 1D)
Virtual slides: tumor of buttocks #1; #2
Positive stains: at least one myogenic marker (desmin, alpha smooth muscle actin, muscle specific actin, calponin)
Negative stains: S100, EMA, h-caldesmon, ALK
EM: myofibroblastic features of indented and clefted nuclei, variable rough endoplasmic reticulum, discontinuous basal lamina
DD: fibromatosis, myofibromatosis, nodular fasciitis (not infiltrative, not deep), leiomyosarcoma (alternating fascicular pattern), solitary fibrous tumor, fibrosarcoma, inflammatory myofibroblastic tumor (more heterogeneous, less cellular, less hyperchromasia, less infiltrative, Hum Path 2008 Apr 7 [Epub ahead of print])
References: AJSP 1998;22:1228
Mammary type myofibroblastoma of soft tissue
Definition: benign myofibroblastic lesion with mast cells in hyalinized collagenous stroma and adipose tissue, identical to breast lesion
See also Breast-nonmalignant, Lymph nodes-not lymphoma chapters
Median age 55 years, 80% men, usually incidental finding in hernia repair surgery
Usually inguinal / groin region or along milk line, also abdominal wall, buttock, back, vaginal wall
Usually subcutis, but may be deeper
May be related to hormonal status (gynecomastia or anti-androgen therapy in men)
Appears to differ from superficial cervicovaginal myofibroblastoma
Treatment: excision, does not appear to recur, but follow up has been short
Gross: median 6 cm, unencapsulated but well circumscribed, firm, white-pink-tan-brown, nodular or whirled cut surface
Micro: identical to breast lesion; fascicles of myofibroblastic spindle cells with eosinophilic to amphophilic cytoplasm with poorly defined borders, oval to tapered nuclei with fine chromatin and small nucleoli; stroma has haphazard bands of collagen; may have epithelioid features, focal nuclear atypia with enlarged nuclei or multinucleation, small vessels with perivascular lymphocytes, prominent adipose tissue, mitotic figures (but no atypical forms)
Cytology (breast): abundant random single and clustered benign spindle mesenchymal cells with scant cytoplasm and elongated or oval nuclei with finely granular chromatin and inconspicuous nucleoli (Diagn Cytopathol 2004;30:406)
Micro images (breast): circumscribed border; fascicles of spindle cells separated by dense collagen bundles #1; #2; #3; epithelioid type #1; #2; #3; CD34+; predominantly fatty variant #1; #2 (inset-desmin); fig 1: sharply circumscribed tumor with fibrous pseudocapsule, fig 2: composed of bland spindle cells in collagenous or myxoid stroma, fig 3A: CD34+, fig 3B: bcl2+, fig 4: desmin+ (focal)
Cytology images (breast): loose groups of cells with abundant eosinophilic granular cytoplasm and bland nuclei
Positive stains: desmin, CD34, variable smooth muscle actin
Molecular/cytogenetics: may have 13q and 16q changes (also spindle cell lipoma, Virchows Arch 2006;449:244)
DD: angiofibroma (thicker, hyalinized vessels), lipomatous hemangiopericytoma (larger ectatic vessels)
References: AJSP 2001;25:1022, Stanford University
Myofibroma / myofibromatosis of soft tissue
Definition: smooth muscle nodules that alternate with fibroblastic foci and hemangiopericytoma-like areas, usually before age 2 years
Formerly called infantile myofibromatosis, infantile hemangiopericytoma
Solitary (myofibroma) or multiple (myofibromatosis) nodules in skin (Mod Path 1989;2:603), soft tissues, bone or viscera
60% congenital, most before 2 years, but mean age 22 years in oral soft tissues (J Oral Pathol Med 2007;36:304)
Most common fibrous tumor of infancy
May regress spontaneously; orbital lesions may cause bony destruction (Ophthal Plast Reconstr Surg 2006;22:292); visceral lesions, especially lung, may cause morbidity and rarely death
Sites: 50% of myofibromas in head and neck, trunk, extremities; 15% of myofibromatosis in deep soft tissues and viscera
Case reports: large fetal neck tumor (J Med Assoc Thai 2007;90:376), newborn with mass compressing inferior vena cava (Adv Neonatal Care 2008;8:13), 5 month old girl with orbital tumor and death due to metastases (Ophthal Plast Reconstr Surg 2008;24:147), 63 year old man with cutaneous myofibroma of leg (Indian J Dermatol Venereol Leprol 2008;74:56)
Treatment: excision for solitary lesions (Arch Otolaryngol Head Neck Surg 1999;125:39); chemotherapy for multiple or visceral lesions (Cancer 2001;92:2692); also interferon (J Pediatr Hematol Oncol 2008;30:179)
Clinical: purple macules resemble a vascular neoplasm
Clinical images: multiple nodules of lower limb in 8 year old boy
Gross: mean 2.5 cm, firm, fibrous, gray-white-brown cut surface, often central necrosis / cystic spaces with cheesy material or hemorrhage, better defined in dermis than deep soft tissue or viscera
Micro: nodular or multinodular proliferation with zonal appearance; peripheral areas have short fascicles or whirls of plump myofibroblasts with pale pink cytoplasm and long, tapering nuclei with vesicular chromatin and 1-2 small nucleoli, but no atypia or pleomorphism; often associated with hyalinization; center of nodules has round, polygonal or spindle cells with scant cytoplasm, hyperchromatic nuclei, arranged around thin walled branching vessels resembling hemangiopericytoma; usually calcification, necrosis, hyalinization; often apparent intravascular growth (is actually subendothelial) but still benign; no/rare mitotic figures
Myofibroma / myofibromatosis of soft tissue (continued)
Micro images: solitary cutaneous lesion features zones of fibrous tissue with bundles of myofibroblasts and prominent thin-walled vessels; high power shows interface with normal collagen; biphasic with immature cells in hemangiopericytoma pattern and bundles of myofibroblastic cells; central hemangiopericytic area is rimmed by hyalinized myofibroblastic area;
