Soft tissue sarcoma

Soft tissue sarcomas are rare malignant tumors of connective tissue (e.g., fat and muscle). The most common histological subtypes are liposarcoma and leiomyosarcoma. Soft tissue sarcomas most commonly occur in the extremities (45% of cases) but can develop in any body site, such as the intra-abdominal region or the trunk. The clinical presentation varies by the anatomical location of the tumor and overlaps with the presentation of benign soft tissue masses (e.g., lipoma). Features that strongly suggest soft tissue sarcoma include mass size > 5 cm, pain, and/or a deep site (e.g., in musculature). Patients with concerning features should be urgently referred to a multidisciplinary sarcoma team. MRI is performed to assess the tumor area and invasion, with or without initial ultrasound assessment. Diagnosis is confirmed with imaging-guided core needle biopsy. Management combines surgical resection with radiation therapy. Factors associated with a poor prognosis include retroperitoneal location and high-grade tumors.

• Incidence: 2–5 cases per 100,000 per year ^[1]
• Age
  • Adults: most commonly occurs after 40 years of age ^[2]
  • Children: accounts for 7–10% of childhood cancers ^[2]

Epidemiological data refers to the US, unless otherwise specified.

• Individual risk factors ^[1][2]
  • History of radiation therapy
  • HIV infection in combination with human herpesvirus 8 infection (for Kaposi sarcoma)
• Hereditary risk factors ^[1][2]
  • Familial retinoblastoma
  • Li-Fraumeni syndrome
  • Neurofibromatosis type 1

The WHO 2020 classification includes approx. 70 histological subtypes of soft tissue sarcoma according to the likely tissue of origin, e.g.: ^[1][3]

• Adipocytic tumors: e.g., liposarcoma
• Smooth muscle tumors: e.g., leiomyosarcoma
• Undifferentiated sarcoma: e.g., undifferentiated pleomorphic sarcoma
• Vascular tumors: e.g., Kaposi sarcoma, angiosarcoma

The clinical presentation of soft tissue sarcoma varies by the anatomical location of the tumor and overlaps with the presentation of benign soft tissue masses (e.g., lipoma or leiomyoma).

• General features
  • Weight loss
  • Fever
• Site-specific features ^[1][4]
  • Extremities , trunk, head, or neck: palpable and visible mass ^[1]
    • Size is variable, > 5 cm is highly suggestive of soft tissue sarcoma
    • Often increasing size
    • Associated paresthesias and/or pain
  • Intra-abdominal , e.g., retroperitoneal sarcomas, uterine sarcomas ^[1]
    • Vaginal bleeding
    • Change in bowel habits
• Features of metastatic disease
  • Lung : dyspnea, cough ^[4]
  • Other organs: e.g., pathological fractures due to bone metastasis, jaundice due to liver metastasis

Refer urgently to a multidisciplinary sarcoma team if mass size is > 5 cm, there is associated pain, and/or a deep location. ^[2]

General principles ^[1][2][4]

• Initial studies (e.g., ultrasound, MRI) are performed for differential diagnosis and to evaluate the soft tissue mass.
• Refer patients with any of the following to a multidisciplinary sarcoma team:
  • Concerning mass features (i.e., mass > 5 cm and/or increasing in size, associated pain, and/or deep location)
  • Retroperitoneal tumor of any size
  • Ultrasound findings that suggest soft tissue sarcoma
• Additional studies (e.g., biopsy) to guide management are decided by the multidisciplinary sarcoma team.

The majority of soft tissue masses in the extremities and trunk are lipomas. ^[2]

Initial studies ^[1][2][4]

• Ultrasound: first-line for soft tissue masses with no features that strongly suggest sarcoma
• Cross-sectional imaging: to assess tumor and local invasion
  • MRI with contrast: preferred for soft tissue masses in the extremities, trunk, and pelvis
  • CT: preferred method for retroperitoneal and thoracic soft tissue masses
• X-ray: may be obtained to assess for bone involvement (e.g., fractures, areas of calcification) ^[5]
• Routine laboratory studies
  • CBC: may show anemia of chronic disease, leukocytosis
  • LDH: may be elevated
  • LFTs: transaminases may be elevated (e.g., due to liver metastases).

Additional studies ^[4][5]

• Biopsy
  • Percutaneous core needle biopsy with ultrasound guidance is typically performed. ^[2]
  • Liposarcoma and leiomyosarcoma are the most common histological subtypes.
• Imaging for tumor staging: CT chest, abdomen, and pelvis with IV contrast
• Specialized laboratory studies: may be used to guide targeted treatment (e.g., germline TP53 testing)

Involve a multidisciplinary sarcoma team before biopsy. Nonexpert biopsies on soft tissue masses are associated with residual disease and poor prognosis. ^[2][4]

• Benign soft tissue tumors ^[6]
  • Lipomas (most common soft tissue mass in the extremities and trunk) ^[2]
  • Leiomyomas (e.g., uterine leiomyoma)
• Malignant tumors ^[6]
  • Skin cancer (e.g., melanoma)
  • Metastatic disease
  • Lymphoma
  • Myeloid sarcoma

The differential diagnoses listed here are not exhaustive.

All patients should be managed by a multidisciplinary sarcoma team.

Surgical therapy ^[1][2]

• Complete tumor excision is first-line management for soft tissue sarcoma.
• Surgery should be performed by a surgeon specializing in sarcoma. ^[5]
• Limb reconstructive surgery may be considered.
• Resection of metastatic disease (e.g., pulmonary metastases) may be considered.

Sarcoma resection must be performed by a surgeon specializing in sarcoma. Suboptimal technique increases the risk of recurrence. ^[4][5]

Additional therapies ^[1][2][4]

• Radiotherapy
  • In combination with surgical therapy (preoperatively or postoperatively)
  • Reduces risk of local recurrence ^[7]
• Other therapies
  • Chemotherapy (e.g., anthracyclines) may be considered.
  • Targeted therapy (e.g., sunitinib) may be considered for certain soft tissue sarcoma histopathological subtypes.

• Overall 5-year survival rate: ∼ 55% ^[2]
• Disease progression
  • ∼ 25% of patients develop metastatic disease. ^[4]
  • Recurrent disease most often occurs in the first 5 years after diagnosis. ^[2][5]
• Factors associated with poor prognosis ^[1][4]
  • Retroperitoneal location
  • High-grade tumors
  • Certain histopathological subtypes (e.g., undifferentiated pleomorphic sarcoma)