Localized Hypertrophic Neuropathy as a Neoplastic Manifestation of KRAS-Mediated RASopathy

M. Adelita Vizcaino, Allan Belzberg, Shivani Ahlawat, Sarra Belakhoua, Liam Chen, Verena Staedtke, Fausto J. Rodriguez

Research output: Contribution to journalArticlepeer-review

Abstract

Localized hypertrophic neuropathy is a rare Schwann cell proliferation that usually affects single nerves from the extremities, and it is of unclear etiology in its pure form. RASopathies are a defined group of genetic diseases with overlapping clinical features, usually secondary to germline mutations in genes encoding either components or regulators of the RAS/MAPK pathway. Herein, we report an 11-year-old boy presenting with café au lait spots and right leg length discrepancy. A fascicular nerve biopsy of the tibial nerve demonstrated a Schwann cell proliferation with prominent onion-bulb formation, satisfying criteria for localized hypertrophic neuropathy. Molecular genetic analysis demonstrated identical KRAS mutations (c38_40dupGCG) in the peripheral nerve lesion and melanocytes from café au lait spots, but not in blood, supporting a diagnosis of a KRAS-mediated rasopathy with mosaicism. Immunohistochemical staining in the peripheral nerve lesion demonstrated strong pERK staining consistent with downstream MAPK pathway activation. This report suggests that at least a subset of localized hypertrophic neuropathies are bonafide, well-differentiated Schwann cell neoplasms developing through oncogenic RAS signaling, which provides new insights into the controversial entity historically known as localized hypertrophic neuropathy.

Original languageEnglish (US)
Pages (from-to)647-651
Number of pages5
JournalJournal of neuropathology and experimental neurology
Volume79
Issue number6
DOIs
StatePublished - Jun 1 2020
Externally publishedYes

Keywords

  • KRAS
  • Localized hypertrophic neuropathy
  • Peripheral nerve
  • RASopathy
  • Schwann cell

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