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
  • Higher risk of progression than synovial sarcoma on ifosfamide therapy
• 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
    • Loss of 4q31
      • (Encompasses the SMAD1 locus)
    • Loss of 18q22
    • Tumor necrosis
• Other areas of metastases
  • Liver
  • Kidney
  • Brain
  • Skin
  • Pancreas

SPECIAL CONSIDERATION

• PRIMARY DURAL LEIOMYOSARCOMA

• • Reported without uterine primary

• SUPERFICIAL LEIOMYOSARCOMA

• • A 20 cm neglected posterior shoulder location has been reported
  • One of the most common superficial sarcomas
  • Better outcome than deep locations

REFERENCES

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