Leiomyosarcoma

DEFINITION AND PATHOGENESIS

  • A primary or secondary (metastatic) usually moderate grade tumor arising from smooth muscle origin

IMPORTANCE

  • Relatively rare, accounting for ~7% of all soft-tissue sarcomas

CLINICAL FEATURES

  • 9-80 years of age (mean = 52)
  • M:F = 1-2.4:1
  • 90% with pain averaging 11 months in duration (± pathologic fracture)
  • May have a history of a ‘benign’ uterine fibroid (malignant degeneration in up to 1%) resected previously—review the pathology slides (2-4 years previously)
  • Has been reported in a pt with a hx of retinoblastoma
  • Has been reported associated (probably incidentally) with the femoral interference screw after ACL reconstruction
    • (Biopsy of the lesion through the screw hole after screw removal)
  • GI sxs
    • Massive hematemesis reported in a gastric location

RADIOLOGIC FEATURES

  • Diaphyseal or metaphyseal
  • Average lesion is 7cm in size
  • Bones involved: distal femur, tibia, jaw, proximal humerus, fibula, pelvis, clavicle, ribs
  • Purely lytic lesion with geographic to moth eaten margins, without sclerotic margins
  • 10-15% with soft tissue mass
  • ± Codman’s triangle
  • MRI
    • T1-weighted images isointense with bone
    • T2-weighted images heterogeneous
    • May be nearly isointense to fat on T2, hypointense to fluid
  • ± soft tissue mass (esp pelvic lesions)

GROSS PATHOLOGY

  • Pink to yellow, firm, ± hemorrhage/necrosis
  • May arise directly from blood vessels in the extremities
    • 11/16 from the femoral vein
    • 3/16 from the popliteal vein
    • 2/16 from the posterior tibial vein
    • 3-33 cm (mean 10.4 cm)

HISTOLOGIC AND MOLECULAR FEATURES

  • Both primary and metastatic lesions have the same histologic appearance
  • Low power: eosinophilic cell bundles with smooth muscle appearance, tending to cross at right angles
  • Thin-walled vessels between thick bundles of spindle cells
  • Intracytoplasmic filaments seen at high power H&E stain, on EM, with immunostaining for actomyosin, with polarizing lenses, and PTAH staining (intracellular myofilaments)
  • + reticulin staining in lower grade lesions
  • + to desmin, laminin, vimentin, actin, and ?-SMA staining to myoglobin staining (for rhabdomyosarcoma)
  • + PAS with/without diastase
  • Trichrome staining: red cytoplasm
  • Saffron- or phloxine-tartrazine hematoxyin: muscle pink, collagen yellow
  • ± artifactual intracytoplasmic pseudovacuaoles caused by fixation
  • Cigar-shaped nuclei
  • ± hyalinized areas
  • Mitotic activity
    • 1-3/hpf = grade I
    • 3-20/hpf = grade 2
    • >20/hpf = grade 3
    • >20 with nuclear pleomorphism = grade 4
  • EM:
    • Spindle cells with basal lamina and thin filaments with dense bodies indicating smooth muscle differentiation
  • Cytogenetics
    • Similar 32K BAC array and gene expression profiling to undifferentiated pleomorphic sarcoma

DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS

  • Fibrosarcoma
  • MFH
  • Metastatic leiomyosarcoma
    • Has been reported with extramedullary spinal cord compression from a missed dx of uterine leiomyosarcoma

DISEASE COURSE AND TREATMENT

  • Women require work up for a primary uterine leiomyosarcoma (review of previous slides, pelvic exam, CT of the pelvis, hysterectomy if warranted)
  • All pts warrant evaluation for a silent primary in the retroperitoneum or GI tract
  • Inferior vena cava lesions txd with neoadjuvant external-beam XRT (45-50 Gy) and then en bloc resection
    • No reconstruction of the inferior vena cava was performed
      • LE edema in 50%
  • Chemotherapy
  • Survival
    • Lung and skeletal metastases with 50% 5 year survival warrants wide resection in solitary lesions with adjunctive chemotherapy
    • Overall survival at 5 yrs of pts whose tumors arise directly from blood vessels is 25%
    • Predictors of metastases
  • Other areas of metastases

SPECIAL CONSIDERATION

  • PRIMARY DURAL LEIOMYOSARCOMA

    • Reported without uterine primary

  • SUPERFICIAL LEIOMYOSARCOMA

REFERENCES

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