Soft Tissue Sarcoma

Covering incidence, etiology, classification, natural history, and initial evaluation

  • Soft tissue sarcomas (STS) are heterogeneous rare malignancies
  • Vary extensively by anatomic location, histology, and biologic behavior
  • Can occur at any anatomic site
  • May arise from many soft tissues: connective tissues, fat, muscle, vascular tissue, peripheral neural tissue, visceral tissue
  • Approximately 12,400 new cases annually in the United States
  • Accounts for approximately 0.7% of all new cancer diagnoses
  • Median age at diagnosis: 65 years
  • Incidence varies by histologic subtype
  • Embryonal rhabdomyosarcoma: common in children
  • Synovial sarcoma: occurs mostly in young adults
  • Undifferentiated pleomorphic sarcoma, liposarcoma, and leiomyosarcoma: seen mostly in older adults
  • For the great majority of STS, there is no known etiology
  • A minority of cases can be attributed to environmental or genetic factors
  • Radiation exposure
  • Chemical exposures: vinyl chloride, dioxin, arsenical pesticides, phenoxy herbicides
  • Immunosuppression
  • Lymphedema (Stewart-Treves syndrome)
  • Viruses: human immunodeficiency virus, human herpesvirus type 8
  • Li-Fraumeni syndrome: associated with development of sarcoma
  • Werner syndrome: associated with development of sarcoma
  • Neurofibromatosis type 1: associated with malignant peripheral nerve sheath tumors
  • Familial adenomatous polyposis (Gardner syndrome): associated with abdominal desmoid tumors
  • World Health Organization divides soft tissue tumors into four categories
  • Benign tumors
  • Intermediate, locally aggressive tumors (e.g., desmoid fibromatosis)
  • Intermediate, rarely metastasizing tumors (e.g., plexiform fibrohistiocytic tumor)
  • Malignant tumors
  • More than 50 histologic subtypes of STS exist
  • Most common subtypes include:
    • Undifferentiated pleomorphic sarcoma
    • Liposarcoma
    • Leiomyosarcoma
    • Myxofibrosarcoma
    • Synovial sarcoma
    • Malignant peripheral nerve sheath tumor
  • These account for approximately 75% of STS cases
  • Determined largely by tumor cell morphology
  • Immunohistochemical staining helps refine diagnosis in many cases
  • Some subtypes have characteristic chromosome translocations and gene rearrangements
  • Two most widely used grading systems:
    • US National Cancer Institute (NCI) grading system
    • French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system
  • Both employ three-tiered system: low, intermediate, and high grade
  • Based on mitotic activity, necrosis, and differentiation
  • The College of American Pathologists prefers FNCLCC system (easier to use, more reproducible, better predictor of prognosis)
  • Certain STS subtypes have grading not applicable
  • Given the rarity of STS and numerous histologic subtypes, diagnostic variability exists
  • Agreement rates for histologic diagnosis or grade among pathologists: 24% to 68%
  • Among sarcoma specialists, concordance rates vary from 60% to 90%
  • Very important to submit diagnostic slides for review by experienced sarcoma pathologist prior to definitive treatment
  • STS can occur anywhere in the body
  • Most common site: extremity, specifically the thigh
  • Approximate distribution at presentation:
    • Extremity: 60% (lower extremity 45%, upper extremity 15%)
    • Trunk: 15% to 20%
    • Retroperitoneum: 10% to 15%
    • Head and neck: 9%
  • Certain histologic subtypes have predilections for specific sites
  • Angiosarcoma: commonly occurs in head and neck
  • Desmoid tumors: frequently occur in abdomen (associated with Gardner syndrome)
  • Epithelioid sarcoma: often occurs in distal extremities and forearm
  • Classic reports by Simon and Enneking describe local behavior of STS
  • STS tends to invade longitudinally along musculoaponeurotic planes
  • Tumors rarely transgress fascial boundaries or invade bone
  • As sarcoma grows, it compresses surrounding normal tissue to form pseudocapsule
  • Pseudocapsule contains compression zone, inflammatory cells, and tumor cells
  • Microscopic tumor cells perforate and extend beyond the pseudocapsule
  • STS rarely spreads to lymph nodes
  • Three series with >1,000 consecutive patients: only 1.8% to 3.7% had lymph node involvement at presentation
  • Notable exceptions with higher lymph node involvement rates:
    • Clear cell sarcoma: 10% to 18%
    • Cutaneous Angiosarcoma: 10% to 15%
    • Rhabdomyosarcoma: 20% to 25%
    • Epithelioid sarcoma: 20% to 35%
  • Mnemonic: "CARe" (Clear cell, Angiosarcoma, Rhabdomyosarcoma, Epithelioid)
  • American College of Surgeons Patterns of Care Study for adult STS
  • 23% of patients had metastatic disease at presentation
  • Single most frequent site of distant metastasis: lung (34%)
  • Bone, liver, and brain involvement: less common
  • Certain histologic subtypes exhibit distinct patterns of recurrence
  • Myxoid liposarcoma: predilection for spread to retroperitoneum, other extrapulmonary soft tissue sites, and bone
    • About 50% of recurrences occur in retroperitoneum
    • 20% in other extrapulmonary soft tissue
    • 15% to 17% in bone
  • Retroperitoneal STS: most common recurrence site is locally in retroperitoneum
  • Predilection for spread to liver as well as lung
  • Epithelioid sarcoma: can present with skip metastases (involving discontiguous locations in a limb) and lymph node involvement
  • Myxofibrosarcoma: exhibits infiltrative growth pattern
  • Associated with higher rates of positive resection margins and local recurrence compared to other STS histologic subtypes
  • Rate of distant recurrence to lung is lower than for other STS types
  • Most STS cases present as painless mass
  • History should include:
    • Duration of mass presence
    • Growth rate
    • Any associated local or systemic symptoms
  • Important to ask about potential risk factors for STS
  • Include history of radiation exposure or family history of malignancies
  • Physical examination should assess:
    • Mass characteristics: size, location, fixation to underlying structures, overlying skin changes
    • Potential evidence of neurovascular compromise
  • General examination should assess for lymphadenopathy or neurofibroma/café au lait spots
  • Association between neurofibromatosis type 1 and malignant peripheral nerve sheath tumors
  • Imaging workup should include:
    • Evaluation of primary site
    • Evaluation of sites of potential metastatic spread
  • For extremity, trunk, or head and neck STS:
    • Magnetic resonance imaging (MRI) scan generally preferred
    • T1-weighted MRI images provide excellent definition of anatomic relation between tumor and adjacent structures
    • T2-weighted images demonstrate tumor and any associated edema
  • Peritumoral edema can contain malignant cells
  • Important to identify for radiation and surgical planning
  • Demas et al. compared MRI and CT for STS lesions in extremities
  • Reported MRI scans showed tumor involvement in muscles in 23% of cases
  • Muscles appeared normal on CT scan
  • Panitch et al. found no significant difference between imaging modalities for preoperative evaluation
  • Most practitioners believe MRI is superior to CT for evaluation of soft tissue tumors
  • Chest imaging to rule out pulmonary metastases for all cases except:
    • Low-grade tumors
    • Small (<5 cm) high-grade lesions
  • Can be helpful to obtain baseline chest CT for diagnosis
  • PET scanning not recommended for routine use
  • May help distinguish peripheral nerve sheath tumors from benign neurofibromas in patients with neurofibromatosis
  • For prediction of spread to bone and soft tissue with MRI of spine and CT of abdomen and pelvis recommended for high-risk patients with this histologic subtype
  • CT-guided core biopsy is desired diagnostic approach (accurate, safe, expeditious)
  • Incisional biopsy is more invasive than core biopsy
  • If utilized, incisional biopsies should be performed carefully
  • Subsequent definitive resection should be performed in mind
  • Tumor cells can potentially seed an incision
  • Thereby necessitating removal of scar at time of surgical resection
  • Important that biopsy approach does not transgress an uninvolved tissue plane
  • Would create situation where much more radical resection needed
  • Consequence of inappropriately placed incisional biopsies can be significant
  • Include need to perform more complex operations with potential for subsequent loss of function, LR, and death
  • Fine needle aspirate (FNA) cytology is not appropriate for malignant soft tissue disease
  • Does not yield enough tissue to establish initial diagnosis