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 language | English (US) |
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Pages (from-to) | 647-651 |
Number of pages | 5 |
Journal | Journal of neuropathology and experimental neurology |
Volume | 79 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1 2020 |
Externally published | Yes |
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
- Hypertrophy/genetics
- Humans
- Proto-Oncogene Proteins p21(ras)/genetics
- Male
- Schwann Cells/pathology
- Mutation
- Child
- Peripheral Nervous System Diseases/genetics
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural