Malignant peripheral nerve sheet tumour

Clinical features

  • More frequent non rhabdomyosarcoma soft-tissue sarcoma in childhood
  • Deep seated tumour, arising from major nerves or pré existent neurofibroma
  • Median age of 10 years. Congenital cases have been reported
  • These tumours can recapitulate any or all elements of the nerve sheath (Schwann cells, perineural fibroblasts, fibroblasts)
  • Extremities (lower leg, buttock ), trunk and the head and neck,
  • 50% are associated with neurofibromatosis  Type I
  • 2% of patients with neurofibromatosis  Type I will develop one in their lifetime
  • Rarely arise from ganglioneuromas, pheochromocytomas and schwannomas

 

Fig 33a – Malignant peripheral nerve sheath tumor –Cohesive tissue fragment showing an epithelioid-like pattern area (H&E)
Fig 33b – Malignant peripheral nerve sheath tumor –high cellularity of rather monotonous malignant cells-feathering (H&E)
Fig 33c - Malignant peripheral nerve sheath tumor – High grade tumor with abundant necrosis and mitosis as well as obvious malignant nuclei (H&E)
Fig 33d - Malignant peripheral nerve sheath tumor- Isolated dispersed cells. This pattern is generally predominant in high grade tumors. Haemorrhage and necrosis in the background. (Giemsa)
Fig 33e - Malignant peripheral nerve sheath tumor - Rosettes and neuroepithelial pattern (Giemsa)

 

  • Smears with moderate to high cellularity
  • Large quantity of dissociated spindle cells
  • High nuclear/cytoplasmic ratio
  • Wavy nuclei
  • Prominent nucleoli
  • Low grade lesions are bland and monotonous-(differential diagnosis with benign lesions)
  • Multinucleate anaplastic cells are common
  • Myxoid or fibrillary background
  • Frequent mitosis
  • Pleomorphism can be present even though it is not per se a sigh of malignancy
  • Rosettes or an neuroepithelial pattern can be present

 

Immunocytochemistry

  • S100 protein: Positive (62%)
  • CD57 (leu7): Positive (55%)
  • CD99: Positive (86%)
  • Glial fibrillary acidic protein(GFAP): Positive (cases with perineurial differentiation)
  • Protein gene product 9.5 (PGP9.5): Positive (not specific)
  • P53 : Positive in high grade lesions
  • Desmin: Positive (Triton)
  • EMA: Negative (generally)
  • Keratins: Positivity is rarely described  (except for keratin 7 or 19) 

 

Electron microscopy

  • Cells with slender elongated apposed cell processes
  • Primitive cell junctions
  • Enfolding of cell membrane with lamellar configuration
  • Discontinuous basal lamina
  • Round to oval nucleus with smooth contours
  • Prominent nucleoli

 

Genetic studies

  • Translocation (17;22)
  • MDM2 amplification

 

Differential Diagnosis

  • Synovial sarcoma
    • Biphasic pattern
    • keratins( 7,or 19): Positive
  • Cellular schwannomas
    • Aggregates instead of loose cells
    • More monomorphic cellular population
    • Rare mitosis or necrosis
  • Fibrosarcoma
    • S-100 protein: positive (focal)

 

Main points

  • Poor prognosis
  • Metastases involve lungs, liver and bone
  • Propensity to spread along the nerve
  • Cases associated with Neurofibromatosis have worse prognosis
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