More Than Just Multiple Melanomas: Insights from a Monoallelic Pot1 Mutation

Document Type

Conference Proceeding

Publication Date

7-1-2026

Publication Title

J Am Acad Dermatol

Keywords

Dermatology

Abstract

Germline Protection of Telomeres (POT1) mutations represent an emerging melanoma-predisposing syndrome, accounting for ∼4% of CDKN2A/CDK4-negative families, yet their clinical implications remain underrecognized. We report a 52-year-old woman with systemic lupus erythematosus, idiopathic thrombocytopenic purpura, and hypocomplementemic urticarial vasculitis who developed more than 25 primary cutaneous melanomas across both sun-exposed and covered sites. Genetic testing identified a germline monoallelic POT mutation (c.126T>G; p.D42E), with a brother carrying the same variant and additional family members affected by melanoma and hematologic malignancies. The patient's melanomas were histologically diverse, predominantly with superficial spreading subtype, and her surveillance course revealed extracutaneous neoplasms including thyroid nodules, a prepontine cistern meningioma, and a parotid MALT lymphoma. This case highlights the distinctive natural history of POT1 tumor predisposition syndrome, characterized by recurrent primary melanomas and heightened risk for systemic malignancies such as angiosarcoma, glioma, and chronic lymphocytic leukemia. Optimal management requires intensive dermatologic follow-up every 3-6 months with dermoscopy and photography, a low threshold for biopsy, rigorous photoprotection, and genetic counseling with cascade testing. Our report underscores the necessity of heightened awareness and multidisciplinary surveillance to mitigate morbidity in POT1 carriers and expands understanding of the phenotypic spectrum associated with this increasingly recognized hereditary melanoma syndrome.

Volume

95

Issue

1

First Page

AB304

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