Soft tissue sarcoma

• A soft tissue sarcoma is a malignant tumour of mesenchymal tissue (fat, muscle, nerve, vessel, connective tissue). It usually presents as a painless lump that grows.
• Red flags in a lump are size greater than 5 cm, a deep position, growth, firmness or pain. Any of these should make you think of sarcoma until proved otherwise.^[5]
• Do not excise a suspicious lump first. Complete imaging, usually MRI, and then a core needle biopsy, before any definitive operation.
• Stage every confirmed case: CT chest looks for the lung metastases that are common, and the tissue is graded (commonly with the FNCLCC system).^[4]
• Definitive treatment for a localised resectable tumour is wide excision with tumour-free margins, with radiotherapy for high-grade lesions; chemotherapy is added in selected high-risk or metastatic disease.^[2]

By the end of this page you should be able to:

1. Recognise the main adult soft tissue sarcoma subtypes and the ages or sites in which they typically occur.
2. List the clinical red flags of a soft tissue mass and explain why increasing size matters most.
3. Plan investigation of a suspected sarcoma so that imaging and biopsy precede excision.
4. Explain the roles of MRI, CT chest and core needle biopsy in diagnosis and staging.
5. Outline staging with the AJCC system and the FNCLCC grade, including pulmonary metastasis risk.
6. Describe the standard management of localised disease: multidisciplinary care, wide excision, radiotherapy and the situations in which chemotherapy is used.
7. Name the three guidelines that frame practice (ESMO-EURACAN-GENTURIS 2021, NICE NG12, NCCN Version 5.2026) and what each contributes.^[1][2][3]

True soft tissue sarcomas specifically exclude tumours of the skin's surface, solid organs, the central nervous system and lymphoreticular tissue. The term is also restricted here to adult-type disease: paediatric rhabdomyosarcoma and Ewing sarcoma are managed under their own protocols rather than under the adult sarcoma pathway.

Sarcomas are classified primarily by their line of differentiation, which is their presumed cell of origin. The common adult subtypes you will meet, with their usual settings, are:

The behaviour, rather than the name alone, is what drives management. The important cross-cutting split is between low-grade and high-grade disease, because that determines whether radiotherapy is added and whether chemotherapy is considered. Low-grade and high-grade disease carry very different metastatic potential, but current sources favour qualitative or grade-based estimates over a single 15% threshold: low-grade soft-tissue sarcoma has little metastatic potential, whereas high-grade disease has a substantially higher risk.^[5]

Soft tissue sarcoma is rare. It is roughly 1% of all adult malignancies.^[5] Tumours can occur at any age, but most present in middle-aged and older adults, and soft tissue sarcoma accounts for about 6% of childhood tumours in the NCI childhood PDQ series versus 7 to 10% of childhood cancers in the UK guideline, the difference reflecting which sarcomas and registries are counted.^[4][8] In the United Kingdom there are about 4,295 soft tissue sarcomas diagnosed annually in England, out of roughly 5,300 total sarcomas each year in the UK (including bone sarcoma and gastrointestinal stromal tumour).^[4]

About half (40% to 50%) of all lesions occur in the extremities, with 75% of those in the lower extremity; the site distribution varies between series (the NCI PDQ quotes 45% in adults), and the rest arise in the trunk wall, retroperitoneum or viscera, and head and neck.^[5][7] Each general practitioner will see very few such tumours in a career, whereas benign soft tissue masses are common. Both sexes are affected in most reports, although some studies suggest a slight male excess. Rhabdomyosarcoma makes up about half of all soft tissue sarcomas in children but is uncommon in adults.^[5]

Incidence and survival data in many countries still under-report these tumours because of the wide histological heterogeneity and historical coding.

In most cases no cause is identified. Established or proposed factors include:

• Previous radiotherapy to the involved field (radiation-associated sarcoma).
• Chronic lymphoedema.
• Certain inherited syndromes: Li-Fraumeni syndrome (TP53), neurofibromatosis type 1 (malignant peripheral nerve sheath tumour), familial adenomatous polyposis (desmoid-type fibromatosis), and Carney complex (myxoma syndromes).
• Specific genetic alterations, for example the t(X;18) translocation in synovial sarcoma and the COL1A1-PDGFB fusion in dermatofibrosarcoma protuberans.
• Exposure to vinyl chloride and to Thorotrast, which are each linked to specific subtypes.

There is no single identifiable underlying cause in the majority of patients, and no modifiable risk factor is known for sporadic disease.

Almost all clinical behaviour of soft tissue sarcoma follows from three facts: the tumour grows in a soft tissue compartment; it is contained at first by a pseudocapsule of compressed surrounding tissue; and it sheds cells late but, when it does, it spreads by the bloodstream.

• Local growth. The tumour expands and pushes rather than infiltrates at first, so it feels like a discrete lump. It can reach a large size in the thigh or retroperitoneum before causing symptoms, which is why presentation is often late.
• Pseudocapsule. The compressed rim gives the false impression of a benign, encapsulated lesion and invites "shelling out" (enucleation). Tumour cells sit beyond it, so this approach leaves disease behind and drives recurrence. Wide excision, not enucleation, is required.
• Metastasis. Blood-borne spread, usually to the lungs, is the life-threatening event. Lymph node spread is uncommon except in synovial sarcoma and epithelioid sarcoma, so regional nodes are examined but not treated routinely.
• Size and grade drive risk. The Memorial Sloan Kettering list of adverse prognosticators (tumour greater than 5 cm, deep location, high histological grade) is associated with rising metastatic risk within 5 years as the factors accumulate, and contemporary practice estimates individual risk with prognostic nomograms such as the Sarculator rather than with a single percentage.^[4][5]

Macroscopically the tumour is a solid, fleshy or myxoid mass, often grey-white, sometimes with haemorrhage or necrosis in high-grade lesions. It is usually pseudoencapsulated. Myxoid areas (gelatinous) are common in myxoid liposarcoma.

The appearance depends on the subtype: fat-forming cells in liposarcoma, fascicles of spindle smooth-muscle cells in leiomyosarcoma, sheets of pleomorphic cells in UPS, and so on. Necrosis and brisk mitotic activity mark high grade. The anatomic (FNCLCC) grade is assigned on three items: tumour differentiation, mitotic count and extent of necrosis. A core biopsy samples only part of the lesion and, because of tumour heterogeneity, may underestimate grade before the whole specimen is examined.^[4]

Most patients describe a lump that has been present for weeks or months and is growing. Pain is not typical, and a painless lump is not reassuring. Systemic symptoms such as fever, weight loss or malaise are uncommon. Late features reflect mass effect: swelling or oedema of a limb, paraesthesia from nerve compression, or abdominal or visceral symptoms for retroperitoneal disease. A lump that "suddenly appeared large" or grew after being stable for years is a red flag.

• Palpate the lump's site, size, shape, contour, consistency, tenderness, tethering, transillumination and fluctuance.
• Measure size. A dimension of 5 cm is an important threshold (roughly golf-ball size).^[5]
• Determine depth relative to the deep fascia: can the mass be moved independently of the underlying muscle, or is it fixed when the muscle is tensed? ^[5]
• Examine the regional lymph nodes (especially for synovial or epithelioid sarcoma).
• Look for stigmata of inherited syndromes (café-au-lait spots, neurofibromas).
• Note skin changes such as fungation.

Red flags that should make you assume malignancy until proved otherwise are:

The clinical mimics are benign (lipoma, ganglion, schwannoma, haematoma, muscle hernia, nodular fasciitis) and inflammatory or infective (abscess, myositis ossificans). The discriminating features are in the red-flag table above; the examination sequence (size, depth, tenderness, fixity) separates most sarcomas from lipomas. If imaging shows a well-defined homogeneous fat-density lesion that follows fat signal on MRI, the diagnosis is usually benign (lipoma or atypical lipomatous tumour); an indeterminate or suspicious mass always needs tissue.

The central rule: all imaging must be completed before any biopsy, and biopsy must be completed before any definitive excision. Biopsy-induced oedema and haematoma destroy the anatomical detail that imaging provides, and an unplanned biopsy site can force amputation rather than limb salvage.

• Ultrasound is the appropriate first test in primary care and gives size, cystic versus solid composition, and relationship to fascia. It is cost-effective and has a high negative predictive value for benign lesions, but it does not reliably predict pathology. In England an adult with an increasing unexplained lump should have an urgent direct-access ultrasound scan; in children and young people the scan is very urgent.^[1]
• MRI with contrast is the standard modality for local characterisation and staging. It defines extent, depth, relationship to neurovascular structures, biopsy tract and surgical planning. Features suggestive of malignancy include size greater than 5 cm, deep location, ill-defined margins, invasion, heterogeneous signal, necrosis and peritumoral oedema.^[5] MRI is repeated if biopsy changes the picture.
• CT (of chest at least) is used for staging; CT of the primary is reserved for patients unable to undergo MRI.
• PET-CT is not routine for the primary lesion.

• Core needle biopsy, preferably image-guided and performed by or in consultation with the surgeon who will perform definitive resection, is the usual diagnostic method.
• Incisional biopsy is used when core biopsy is non-diagnostic or more tissue is required.
• Excisional biopsy of an undiagnosed suspicious mass is unacceptable practice for a sarcoma: it violates compartments and seeds recurrence.
• Fine-needle aspiration is not useful for diagnosing sarcoma and is not recommended, because it gives neither tissue architecture nor enough material.
• Every biopsy tract is a contaminated route and must be resected en bloc with the tumour at definitive surgery. Place the incision in line with the longitudinal axis of the limb, mark it clearly, achieve strict haemostasis, and never go through neurovascular structures.
• Specimens go to a pathologist experienced in musculoskeletal tumours, with immunohistochemistry and molecular testing.

Staging separates local disease (stages I-III) from metastatic (stage IV).

• Local staging: MRI of the primary.
• Systemic staging: CT chest in all confirmed soft tissue sarcomas, or at least in intermediate- and high-grade tumours, to look for pulmonary metastases.^[4] Chest radiograph alone is accepted only for low-risk histotypes (for example atypical lipomatous tumour, small classic dermatofibrosarcoma protuberans) where metastasis is very unlikely, or where staging would change nothing.
• Regional nodes: clinical examination, with imaging and biopsy where suspicious in synovial or epithelioid sarcoma.

There is no blood test that diagnoses soft tissue sarcoma. Diagnosis rests on triple assessment: clinical examination, imaging and tissue. Histopathology supplies both type and grade.

The widely used European system is the FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) grade, which distinguishes three malignancy grades based on tumour differentiation, mitotic count and necrosis. Some subtypes (for example myxoid liposarcoma) cannot be graded this way and follow type-specific rules. A core biopsy may underestimate grade because of heterogeneity; imaging and the final resection specimen refine it. ^[4]

The most widely used system is the AJCC (American Joint Committee on Cancer) staging system, which uses tumour size, FNCLCC histological grade, and nodal and distant metastases. In its 8th edition the size (T) category was split into four groups rather than two, nodal disease became part of stage IV, and extra detail was added for anatomical site and for specific histotypes. Stages I to III are localised disease with incrementally greater metastatic risk; stage IV is metastatic disease.^[4]

Sarcoma nomograms (for example the Sarculator) give individualised predictions of disease-free and overall survival from tumour size, grade, histotype, patient age, anatomical site and completeness of resection; they supplement, rather than replace, AJCC staging.

Care should be delivered by a specialist sarcoma multidisciplinary team (surgical oncologist, medical and clinical oncologists, radiologist, pathologist, specialist nurse) in a recognised sarcoma service. Errors before referral (unplanned excision, inappropriate biopsy) worsen outcomes.

Soft tissue sarcoma is not usually an emergency. The first steps are referral to the sarcoma service and proper staging. Unplanned local complications include bleeding, pain and fungation; these are controlled with radiotherapy, analgesia and wound care while definitive treatment is planned. Rarely, urgent compartment decompression or haemorrhage control is needed.

• For all adult-type, localised, resectable tumours the standard treatment is en bloc wide excision with a rim of normal tissue and tumour-free margins, performed by a surgeon trained in sarcoma surgery. The minimal acceptable margin depends on histotype, prior or planned radiotherapy and resistant anatomical barriers (fascia, periosteum, epineurium).^[2]
• For superficial or small, deep tumours a true wide margin with R0 clearance can provide good local control alone. Most lesions, however, need adjuvant radiotherapy.
• Resection of limited, small, peripheral lung metastases can be curative in selected patients.

Radiotherapy improves local control in extremity and trunk wall disease. Preoperative radiotherapy is now preferred to postoperative: it treats a smaller volume and reduces late irreversible toxicity (fibrosis, stiffness, lymphoedema), at the cost of a higher rate of acute wound complications. The conventional regimen is 1.8 to 2.0 Gy per day over 5 to 6 weeks to 50 to 50.4 Gy.^[6] Postoperative radiotherapy uses a higher dose range and remains an option where surgery has already been performed.

Special notes:

• Myxoid liposarcoma is unusually radiosensitive; in the phase II DOREMY trial preoperative 36 Gy in 2 Gy fractions gave 100% local control at 25 months median follow-up.^[6]
• Retroperitoneal sarcoma: radiotherapy is not standard for the whole group after the STRASS trial; a benefit has been suggested in propensity-matched analysis for well-differentiated and grade I/II dedifferentiated liposarcoma, and the pros and cons should be discussed.^[6]
• Hypofractionated schedules are under trial and should be regarded as investigational outside prospective studies.

• First line in advanced or metastatic disease is between single-agent doxorubicin and combined doxorubicin plus ifosfamide. The combination gives a higher response rate but more toxicity (including cardiac toxicity from doxorubicin and renal toxicity from ifosfamide); single-agent doxorubicin is preferred when palliation or low toxicity is the priority.^[2][4]
• Ifosfamide is recommended at 9 to 10 g per square metre, given over two to three days, with dose-response seen; high-dose or continuous infusional regimens give higher responses.^[4]
• Anthracycline plus ifosfamide chemotherapy for at least three cycles is an option for patients at high risk of death with localised disease, or for limb preservation combined with radiotherapy, with benefit concentrated in chemosensitive subtypes (synovial sarcoma, pleomorphic sarcoma, liposarcoma, leiomyosarcoma).^[2]
• Histology-tailored agents matter: dermatofibrosarcoma protuberans responds to imatinib; NTRK-rearranged sarcomas to NTRK inhibitors; advanced liposarcomas may receive eribulin; trabectedin or pazopanib are options in later lines; gemcitabine-based combinations for selected subtypes.
• In uterine leiomyosarcoma, endometrial stromal sarcoma and undifferentiated endometrial sarcoma, adjuvant radiotherapy is not recommended.
• Neoadjuvant chemotherapy with regional hyperthermia is an individualised option.

• Wide local excision preserving limb function wherever possible.
• Split-thickness skin graft or vascularised flap for large wounds; rehabilitation with physiotherapy.
• Prehabilitation, nutritional support and psychosocial care through the sarcoma specialist nurse.
• Surveillance for recurrence as below.

• Positive margins predict recurrence. A microscopic positive margin at a deliberately preserved critical structure (planned R1) combined with radiotherapy carries a lower local recurrence risk than an unplanned positive margin; the latter should trigger re-excision or preoperative radiotherapy of the prior surgical bed.
• Follow-up: regular clinical examination and imaging of the primary site and chest. The exact schedule is not defined by ESMO and varies by institution; a pragmatic approach is clinical review with MRI of the primary site and CT chest at intervals for several years. Annual long-term review is often used because recurrence can appear late.
• Local recurrence is treated with a further wide excision plus radiotherapy if not previously given; metastatic disease is managed on the advanced disease pathway.

Any large, deep, growing or suspicious mass should be discussed with or referred to a sarcoma specialist service before biopsy or excision. Patients with a previously excised lesion that turns out to be sarcoma need immediate referral for re-staging and (usually preoperative) radiotherapy plus re-excision. Suspected recurrence always returns to the sarcoma service.

• Local recurrence from incomplete resection or unplanned excision.
• Metastatic disease, predominantly pulmonary.
• Lymph node spread (synovial, epithelioid subtypes).
• Complications of radiotherapy: acute wound dehiscence, late fibrosis, joint stiffness, lymphoedema.
• Complications of chemotherapy: neutropenia, cardiac toxicity (anthracyclines), renal toxicity and neurotoxicity (ifosfamide).

Prognosis depends on tumour size, depth, grade and histological subtype, surgical margin status, anatomical site (retroperitoneal and visceral sites fare worse) and the presence of metastases. Local control rates with wide excision plus radiotherapy are high for extremity disease. Metastatic disease carries a variable outlook depending on resectability and subtype.

There is no population screening for soft tissue sarcoma. Early recognition of red-flag lumps (size, depth, growth) and correct referral before excision are the achievable preventive measures. Where radiotherapy or chemotherapy has been used (for example lymphoma or childhood cancer), awareness of radiation-associated sarcoma in long-term survivors matters.

• Children and young people. Rhabdomyosarcoma and Ewing sarcoma dominate; they follow paediatric protocols (FaR-RMS and others). In children, an urgent referral within 48 hours after a very urgent ultrasound when findings are suspicious is the NICE rule.^[1]
• Pregnancy. Sarcomas in pregnancy are rare; multidisciplinary care with timing of surgery and delivery is individualised.
• Older adults. Toxicity limits intensive chemotherapy; hypofractionated or shorter courses of treatment may be considered.
• Immunocompromised. No special protocol; standard pathways apply.

• Ultrasound is the practical first test; MRI where funds allow, particularly for surgical planning.
• A defined referral pathway to a regional or national sarcoma service matters more than local technology.
• If sarcoma is suspected, do not excise before imaging; a simple ultrasound plus clinical assessment can prevent destructive surgery.
• Where radiotherapy or trained sarcoma surgeons are unavailable, early referral and staged care preserve outcomes.
• Send all resected soft tissue specimens for histology, with reporting by a pathologist experienced in sarcoma when possible.

• Soft tissue sarcomas are rare, mesenchymal malignancies; about half occur in the extremities.
• The basic nature of the disease is local growth contained by a pseudocapsule, with late blood-borne spread to the lungs.
• Red flags are size greater than 5 cm, depth, growth, firmness and pain; increasing size is the best single indicator.
• Do not excise first: MRI, then core needle biopsy, then planned wide excision.
• Fine-needle aspiration is not diagnostic; every biopsy tract is resected en bloc with the tumour.
• Stage with MRI of the primary and CT chest; FNCLCC grade and AJCC stage guide prognosis.
• Localised high-grade disease is treated with wide excision plus radiotherapy (preoperative preferred) in a sarcoma service.
• Low-grade tumours may be treated with wide excision alone where margins are adequate.
• Chemotherapy (doxorubicin, with or without ifosfamide) is used in advanced disease and selected high-risk local disease.
• Suspect and planned multidisciplinary care before any intervention produces the best outcomes.

Primary bone tumours in adults; metastatic bone disease; (planned or existing MedGrasp topics may be linked here with plain text only).