Soft Tissue Sarcomas

Soft Tissue Sarcomas

Prepared by Dr. Serdar DEMIROZ

A diverse group of malignant tumours arising from mesenchymal tissues, commonly affecting extremities.

Definition

Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin, representing about 1% of all malignancies. They may arise in any anatomical site, most commonly the extremities and trunk. The clinical presentation is often insidious, with slow-growing, painless masses that delay diagnosis.

Epidemiology

• Annual incidence: ~13,000 new cases in the U.S.
• Most occur in adults, with a slight male predominance.
• Deep-seated lesions are typical; superficial ones are less common.
• Etiology remains largely unknown, though some are linked to radiation, chronic lymphedema, or genetic syndromes (e.g., Li-Fraumeni, NF1).

Clinical Features

• Painless, enlarging mass is the most frequent symptom.
• May reach substantial size before detection, especially in pelvic or retroperitoneal sites.
• Usually does not invade bone or major neurovascular structures.

Imaging & Diagnosis,

• MRI: preferred for local staging, defining tumor margins, fascial plane involvement, and relation to vessels or bone.
• CT chest: screening for pulmonary metastases.
• Biopsy: core needle biopsy is the gold standard; excisional biopsy should only be done by the definitive surgical team.
• Molecular profiling increasingly aids subtype classification (>70 distinct subtypes).

Management

• Multidisciplinary approach essential (orthopaedic oncology, pathology, radiology, medical oncology, radiotherapy).
• Wide surgical excision with negative margins is the cornerstone.
• Radiotherapy: indicated for large, deep, or high-grade tumors—either pre- or postoperatively.
• Chemotherapy: limited role; used selectively in high-risk or metastatic disease.

Metastasis & Follow-Up

• Predominantly hematogenous spread to the lungs.
• Bone and liver metastases less frequent.
• Lymphatic spread rare but occurs in subtypes such as synovial sarcoma and epithelioid sarcoma.
• Postoperative surveillance:
  Clinical exam + chest imaging every 3–6 months (first 2 years), then annually.

Prognosis

• Local control: ~85–90% with adequate margins.
• Local recurrence: 10–15%.
• Poor prognostic factors:
  Large size > 5 cm
  Deep location
  High histologic grade
  Positive margins
  Lymphovascular invasion

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

1. WHO Classification of Soft Tissue and Bone Tumours, 5th Edition. IARC: Lyon, 2020.
2. Casali PG, Abecassis N, Bauer S, et al. Soft tissue and visceral sarcomas: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines. Ann Oncol. 2022;33(12):1348–1365.
3. NCCN Clinical Practice Guidelines in Oncology: Soft Tissue Sarcoma, Version 2.2025.
4. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. IARC, Lyon, 2013.
5. Burningham Z, Hashibe M, Spector L, Schiffman JD. The epidemiology of sarcoma. Clin Sarcoma Res. 2012;2(1):14.
6. Gronchi A, Miah AB, Dei Tos AP, et al. Soft tissue and visceral sarcomas: ESMO–EURACAN–GENTURIS guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(11):1348–1365.
7. Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas. J Clin Oncol. 1998;16(1):197–203.
8. Thway K, Jones RL, Noujaim J, Fisher C. Updates in the histopathology and classification of soft tissue sarcomas. Histopathology. 2014;64(1):51–70.
9. Stacchiotti S, Van Tine BA. Synovial sarcoma: current concepts and future perspectives. J Clin Oncol. 2018;36(2):180–187.

References – Undifferentiated Pleomorphic Sarcoma & Histologic Subtypes

1. Coindre JM. Histologic classification of soft tissue sarcomas (update and perspectives). Histopathology. 2014;64(1):51–70.
2. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. WHO Classification of Tumours of Soft Tissue and Bone, 5th Edition (2020).
3. 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.
4. Chibon F. The genetics of soft tissue sarcoma: from normal mesenchymal cells to malignant sarcomas. Nat Rev Cancer. 2013;13(8):545–558.
5. Jo VY, Fletcher CDM. WHO classification updates on soft tissue and bone tumours. Histopathology. 2014;64(1):38–49.
6. Widemann BC, Italiano A. Biology and management of malignant peripheral nerve sheath tumor. Neuro Oncol. 2018;20(6):763–773.
7. Helman LJ, Meltzer P. Mechanisms of sarcoma development. Nat Rev Cancer. 2003;3(9):685–694.
8. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors. 7th ed. Philadelphia: Elsevier, 2020.
9. Thway K, Fisher C. Leiomyosarcoma: recent advances and diagnostic approach. Histopathology. 2015;67(5):701–711.
10. Sirvent N, Maire G, Pedeutour F. Chromosome translocations in dermatofibrosarcoma protuberans. Hum Pathol. 2003;34(12):1293–1301.