Definition

• malignant tumor arising from peripheral nervous tissue or showing nerve sheath differenciation

Clinical setting

• sporadic :
  • peak onset in the fifth decade
• 30-50% associated with neurofibromatosis type 1 (NF1):
  • inactivating NF1 gene mutations, with increased ras signaling and subsequent increased risk of developing both benign and malignant tumors, especially peripheral nerve sheath tumors (2% lifetime risk of MPNST)
  • MPNST is difficult to detect clinically in NF1 patients
  • poor prognosis (high likelihood of local recurrence and distant metastasis)
• rarely arises from a benign schwannoma or a ganglioneuroma

Localisation

• buttock and thigh
• brachial plexus and upper arm
• paraspinal region

Gross findings

• classic form : large fusiform or eccentric mass in a major nerve
• fleshy white-tan surface, with areasof secondary hemorrhage and necrosis

Histology

• fasciculated growth pattern, with alternance of dense and hypodense fascicles
  • spindle cells, nuclei with tapered ends and wavy or buckled configuration
• perivascular accentuation and infiltration of vessel walls
• frequent mitoses
• possible heterologous differenciation (bone, cartilage etc.)
  • rhabdomyosarcomatous component : malignant Triton tumor

Variants

• epitheliod MPNST
• pigmented (melanotic) MPNST
• malignant Triton tumor

Immunohistochemistry

• 50% are S-100 protein positive (positivity in less than 20-30% of cells)
• EMA positivity if perineurial differenciation
• synchronous presence of p53, p16, and p27 alterations, decreased S-100 protein, Leu 7, and CD34 immunoreactivity patterns, and increased proliferation markers Mib-1 and TopoII[alpha] in high-grade MPNST

Differential diagnosis

 plexiform cellular schwannoma - multinodular cellular schwannoma (#14508393#)

Cytogenetics

 t(2;4)(q35;q31) (#12935926#)
 t(X;12)(q22;q24) (#12935926#)

References

• Am J Surg Pathol. 2003 Oct;27(10):1337-45 (#14508395#)