Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin arising from connective tissues including muscle, fat, fibrous tissue, blood vessels, peripheral nerves, and synovium. They comprise over 70 distinct histologic subtypes per WHO classification with widely varying biology, treatment response, and prognosis. STS are rare, accounting for less than 1% of all adult malignancies (incidence 4-5 per 100,000 annually).
Common adult subtypes include undifferentiated pleomorphic sarcoma (UPS — most common, mainly elderly extremities), liposarcoma (well-differentiated/dedifferentiated/myxoid/round cell/pleomorphic), leiomyosarcoma (uterus, retroperitoneum, vessels), synovial sarcoma (young adults, extremities, t(X;18) SS18-SSX fusion), malignant peripheral nerve sheath tumor (MPNST, often arising from plexiform neurofibroma in NF1), and angiosarcoma (skin of head/neck in elderly, post-radiation, breast). Pediatric STS are dominated by rhabdomyosarcoma (embryonal, alveolar). Risk factors include prior radiation therapy (5-30 year latency, secondary sarcoma), genetic syndromes (Li-Fraumeni p53, NF1, hereditary retinoblastoma, Gardner syndrome), chronic lymphedema (Stewart-Treves angiosarcoma), occupational exposures (vinyl chloride for hepatic angiosarcoma), and HIV (Kaposi sarcoma).
Diagnosis: clinical evaluation of painless enlarging deep mass over 5 cm warrants imaging (MRI of primary site with contrast as gold standard, showing heterogeneous T2 hyperintense mass with enhancement; CT for retroperitoneal/visceral). Biopsy planning is critical: core needle biopsy (preferred) or open incisional biopsy along future definitive surgical incision line to allow complete excision of biopsy tract; AVOID transverse incisions on extremities. Pathology requires expert sarcoma review with immunohistochemistry and FISH/molecular studies (synovial sarcoma t(X;18) SS18-SSX, alveolar rhabdomyosarcoma t(2;13) PAX3-FOXO1, myxoid liposarcoma t(12;16) FUS-DDIT3, Ewing-like sarcomas EWSR1 rearrangements, NTRK fusions for targeted therapy). Staging: AJCC 8th edition incorporates grade (FNCLCC G1-G3 based on differentiation, mitotic count, necrosis), tumor size and depth (T1 less than 5 cm, T2 5-10 cm, T3 10-15 cm, T4 over 15 cm), nodal involvement, and distant metastases. Chest CT for pulmonary metastases (most common site for STS metastases). Treatment is multidisciplinary at sarcoma referral centers: limb-sparing wide local excision (negative margins R0, ideally 1-2 cm or fascial plane); amputation reserved for unresectable extremity disease. Adjuvant external beam radiotherapy (50-66 Gy) for intermediate/high-grade tumors over 5 cm or close margins. Neoadjuvant radiotherapy may improve resectability. Adjuvant chemotherapy (doxorubicin + ifosfamide) considered for high-risk localized disease (large, high-grade, deep) — debated benefit. Targeted therapies for specific subtypes: imatinib for dermatofibrosarcoma protuberans (DFSP, COL1A1-PDGFB), pazopanib for non-adipocytic STS post-chemotherapy, NTRK inhibitors (larotrectinib) for NTRK fusion-positive tumors. Five-year overall survival is 50-65%, ranging from 80%+ for low-grade T1N0 to 20-30% for high-grade T2-T4 with metastases.