Soft Tissue Tumor Classification
The WHO introduced the classification of soft tissue and bone tumors (fifth edition) in 2020.
The new WHO classification of soft tissue and bone tumors, introduced in 2020 (fifth edition), has made significant improvements in classification and introduced many new diagnoses.
Histologic Subtypes of Soft Tissue Sarcomas
1. Undifferentiated Pleomorphic Sarcoma (UPS)
Previously Malignant Fibrous Histiocytoma (MFH).
High-grade pleomorphic tumor without identifiable line of differentiation.
Common sites: thigh, buttock, shoulder girdle, retroperitoneum.
Aggressive local behaviour; lung metastases common.
Treatment: wide excision ± radiotherapy; chemotherapy in selected cases.
2. Malignant Peripheral Nerve Sheath Tumor (MPNST)
Originates from peripheral nerves or pre-existing neurofibromas.
Strongly associated with Neurofibromatosis type 1 (NF1).
Rapidly enlarging deep-seated mass along nerve pathways.
S-100 and SOX10 positive in subset.
Prognosis: poor; 5-year survival <50%.
3. Synovial Sarcoma
Typically affects young adults (15–40 years), often around large joints (especially knee, ankle).
Despite name, does not arise from synovium.
t(X;18)(p11;q11) translocation → SYT-SSX fusion.
Histology: biphasic (epithelial + spindle cell) or monophasic.
Treatment: surgery + radiotherapy ± chemo (if high-grade or metastatic).
4. Liposarcoma
Most common soft tissue sarcoma in adults.
Occurs in thigh and retroperitoneum.
Subtypes:
Well-differentiated (low grade, local recurrence)
Myxoid/round cell (t(12;16), intermediate grade)
Pleomorphic (high grade, aggressive)Treatment: wide excision; radiotherapy for high-grade disease.
5. Rhabdomyosarcoma
Skeletal muscle–derived tumor; most common STS in children.
Subtypes: embryonal, alveolar, pleomorphic.
Markers: desmin, myogenin, MyoD1.
Treatment: multimodal — surgery + radiotherapy + chemotherapy.
6. Fibrosarcoma
Malignant spindle-cell tumor producing collagen.
Often arises in deep soft tissues of extremities or trunk.
Histology: herringbone pattern.
Management: wide excision ± radiotherapy.
Recurrence common; metastasis via hematogenous route.
7. Leiomyosarcoma
Originates from smooth muscle cells (vessels, uterus, GI tract, soft tissue).
Common in retroperitoneum and large veins.
Markers: SMA, desmin, h-caldesmon positive.
Prognosis: size and grade dependent.
8. Epithelioid Sarcoma
Occurs in young adults, often distal upper extremities (hand, forearm).
Mimics granulomatous or epithelial lesions.
Loss of INI1 (SMARCB1) expression diagnostic.
Tendency for local recurrence and lymphatic spread.
9. Angiosarcoma
Malignant endothelial tumor.
May arise spontaneously or post-radiation.
Common sites: skin (scalp/face of elderly), breast, liver.
CD31, CD34, ERG positive.
Highly aggressive, poor prognosis.
10. Dermatofibrosarcoma Protuberans (DFSP)
Low-grade, locally aggressive tumor of dermal fibroblastic origin.
t(17;22) → COL1A1–PDGFB fusion.
Slow-growing plaque or nodule on trunk or proximal extremities.
Treatment: wide local excision or Mohs surgery.
Recurrence common, metastasis rare.
References:
Coindre JM. Histologic classification of soft tissue sarcomas (update and perspectives). Histopathology. 2014;64(1):51–70.
Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. WHO Classification of Tumours of Soft Tissue and Bone, 5th Edition (2020).
Coindre JM, Terrier P, Guillou L, et al. Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas. Cancer. 2001;91(10):1914–1926.
Chibon F. The genetics of soft tissue sarcoma: from normal mesenchymal cells to malignant sarcomas. Nat Rev Cancer. 2013;13(8):545–558.
Jo VY, Fletcher CDM. WHO classification updates on soft tissue and bone tumours. Histopathology. 2014;64(1):38–49.
Widemann BC, Italiano A. Biology and management of malignant peripheral nerve sheath tumor. Neuro Oncol. 2018;20(6):763–773.
Helman LJ, Meltzer P. Mechanisms of sarcoma development. Nat Rev Cancer. 2003;3(9):685–694.
Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors. 7th ed. Philadelphia: Elsevier, 2020.
Thway K, Fisher C. Leiomyosarcoma: recent advances and diagnostic approach. Histopathology. 2015;67(5):701–711.
Sirvent N, Maire G, Pedeutour F. Chromosome translocations in dermatofibrosarcoma protuberans. Hum Pathol. 2003;34(12):1293–1301.
Soft Tissue Tumor Classification
Group | Benign | Intermediate (Local Agressive) | Malignant |
Adipocytic | Lipoma, Lipomatosis, Angiolipoma, Hibernoma vb. | Atypical lipomatous tumor | Well-diff. liposarcoma, Dediff. liposarcoma, Myxoid liposarcoma vb. |
Fibroblastic / Myofibroblastic | Nodular fasciitis, Elastofibroma, Fibroma of tendon sheath vb. | Palmar/Plantar fibromatosis, Desmoid-type fibromatosis, Dermatofibrosarcoma protuberans vb. | Fibrosarcoma NOS, Myxofibrosarcoma, Sclerosing epithelioid fibrosarcoma vb. |
Fibrohistiocytic | Tenosynovial giant cell tumor | Plexiform fibrohistiocytic tumor, Giant cell tumor of soft parts | Malignant tenosynovial giant cell tumor |
Vascular | Synovial hemangioma, Epithelioid hemangioma, Lymphangioma vb. | Kaposiform hemangioendothelioma, Retiform hemangioendothelioma, Kaposi sarcoma vb. | Epithelioid hemangioendothelioma, Angiosarcoma |
Pericytic | Glomus tumor NOS, Myopericytoma, Angioleiomyoma | — | Malignant glomus tumor |
Skeletal muscle | Rhabdomyoma | — | Rhabdomyosarcoma (Embryonal, Alveolar, Pleomorphic, Spindle cell vb.) |
Chondro-osseous | Chondroma | — | Extraskeletal osteosarcoma |
Peripheral nerve sheath | Schwannoma, Neurofibroma, Perineurioma, Granular cell tumor vb. | — | Malignant peripheral nerve sheath tumor, Melanotic variant vb. |
Uncertain differentiation | Myxoma, Angiomyolipoma vb. | Haemosiderotic fibrolipomatous tumor, Atypical fibroxanthoma vb. | Synovial sarcoma, Epithelioid sarcoma, Clear cell sarcoma, Undifferentiated sarcomas vb. |
Undifferentiated small round cell | — | — | Ewing sarcoma, CIC-rearranged sarcoma, Sarcoma with BCOR alterations |
