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

1 Scopus citations

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 cafe 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, welldifferentiated 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 - 2020
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported in part by NIH grant P30 CA006973 to the Sidney Kimmel Comprehensive Cancer Center (PI: W. Nelson).

Publisher Copyright:
© 2020 American Association of Neuropathologists, Inc. All rights reserved.

Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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