Soft Tissue Tumors Part 1
Introduction, Fibrous, Fibrohistiocytic and Adipose tumors
Last revised 7 August 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/round cell, 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, smooth muscle, blood vessels, lymphatics and peripheral nervous system
Usually mesodermal in origin; peripheral nerves derive from neuroectoderm
Soft tissue tumors - approach to diagnosis
Modified from Sternberg
1) Is lesion reactive or neoplastic?
2) Is lesion malignant? (necrosis favors malignancy)
3) Is malignant lesion a sarcoma? (may be melanoma, carcinoma, lymphoma)
4) What type of differentiation is present? - assign to phenotypic category or classify as round cell, spindle cell, epithelioid, other
5) If sarcoma, what is the grade?
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, core biopsy or incisional biopsy so appropriate treatment can be determined in advance
Congenital soft tissue tumors, even with high grade features, rarely have malignant behavior
Nodal involvement uncommon
Local recurrences show increased number of genetic changes, including loss at 9p, gains at 5p and 20q (Mod Path 2001;14:978)
Usually arise de novo, not from benign tumors (MPNST may be an exception); do not appear to arise from trauma
May be caused by radiation therapy (MFH, extraskeletal osteosarcoma), foreign bodies (MFH, angiosarcoma) or chemical carcinogens (angiosarcoma)
Poor prognostic factors: large size, deep seated versus superficial, retroperitoneum versus extremities, high grade, high stage, positive margins (associated with local recurrence)
Treatment: ideally wide local excision with 1-2 cm margin of normal tissue; but this is often impossible due to anatomic contraints (neurovascular bundle, bone) and thus a marginal excision (through pseudocapsule) or focally positive margin are sometimes acceptable; surgery should also remove site of prior incision; amputation is reserved for unresectable tumors; pre- or postoperative radiotherapy are routinely used; chemotherapy is frequently used for large, high-grade tumors or disseminated disease
Surgical resection of pulmonary metastases often has value
Fine needle aspiration: most specimens are recognized as sarcoma, and subtyping is most accurate in bone sarcomas and pediatric sarcomas; subtyping is often not possible in adult specimens, but this usually does not affect initial therapy (AJCP 2001;115:59)
Staging is discussed in Soft Tissue Tumors - Part 2 (click here)
Syndromes (molecular / genetic) associated with soft tissue tumors
Bannayan Zonana syndrome: OMIM #153480, multiple lipomas and hemangiomas
Beckwith-Wiedemann syndrome: OMIM #130650, congenital overgrowth syndrome associated with alveolar rhabdomyosarcoma (Pediatr Dev Pathol 2001;4:550)
Carney syndrome / complex: autosomal dominant multiple neoplasia syndrome with myxomas and pigmented lesions of skin and mucosa, due to mutation in PRKAR1A gene (OMIM #160980) or 2p16 abnormalities (OMIM #605244)
Carney triad: OMIM # 604287, gastric GIST, pulmonary chondroma and extra-adrenal paraganglioma (Mayo Clinic Proceedings 1999;74:543, Mayo Clinic Proceedings;1999;74:638)
Gardner syndrome: OMIM #175100, fibromatosis, familial adenomatous polyposis and osteomas
Kasabach-Merritt syndrome: OMIM #141000, microangiopathic hemolytic anemia associated with childhood hemangioma
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)
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, carcinoma (extension into soft tissue or metastases), clear cell sarcoma, epithelioid sarcoma, rhabdoid tumor, synovial sarcoma; epithelioid variants of leiomyosarcoma, MFH, MPNST, myxofibrosarcoma, schwannoma or vascular tumors
Pleomorphic: variants of leiomyosarcoma, liposarcoma, MFH, MPNST, myxofibrosarcoma, PHAT, pleomorphic lipoma or rhabdomyosarcoma; also melanoma and metastatic carcinoma
Round cell: desmoplastic small round cell sarcoma, Ewings/PNET, mesenchymal chondrosarcoma, MPNST, rhabdomyosarcoma, round cell liposarcoma, schwannoma with neuroblastoma-like features, synovial sarcoma; also carcinoma, lymphoma, melanoma, neuroblastoma
Spindle cell: benign nerve sheath tumor, DFSP, fibroma of tendon sheath (cellular), fibromatosis, fibrosarcoma, leiomyosarcoma and leiomyoma, MPNST, nodular fasciitis, spindle cell lipoma, spindle cell variant of embryonal rhabdomyosarcoma, solitary fibrous tumor, 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, synovial sarcoma
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)
Important to exclude a sarcoma with intratumoral hemorrhage
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
Micro: lobules of calcific material surrounded by histiocytic giant cells often containing small psammomatous calcifications
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 (