Fatal GNAQ‐mutated CNS melanoma in an adolescent with nevus of Ota

Abstract

Nevus of Ota is an uncommon benign mesodermal melanosis that involves the first and second divisions of the trigeminal nerve. Primary non-cutaneous melanoma often involves distinct genetic mutations compared to cutaneous melanoma. In primary central nervous system (CNS) melanomas associated with nevus of Ota, somatic mutations most commonly occur at the Q209 and R183 residues of GNAQ and likely induce tumorigenesis through upregulation of the MAP kinase pathway. This case underscores the importance of elucidating neurologic symptoms early in patients with nevus of Ota, as a delayed presentation of CNS melanoma could portend a devastating outcome. slight female predominance, while Caucasian patients have a higher risk of malignant complications. 1 Development of CNS melanoma in patients with nevus of Ota is exceedingly rare, arising later in life for the few affected. 1 Nevus of Ota is known to harbor GNAQ mutations, 2 but more commonly, these mutations are associated with approximately 85% of uveal melanomas, and up to 75% of blue nevi. 3 GNAQ mutations can also be found in some port wine stains and in CNS tissue affected by Sturge-Weber syndrome. 4 Among melanomas, GNAQ and GNA11 mutations are infrequently present in non-uveal melanomas, when present, these mutations are essentially specific for melanoma. 5 Furthermore, GNAQ-and GNA11-mutated melanomas exhibit a mutually exclusive relationship with other common melanoma mutations (such as BRAF, NRAS, and KIT), and exhibit low mutational burden, potentially explaining the reduced response to targeted checkpoint blockade. 5 In sharing this tragic case, we hope to highlight the importance of regular follow-up and inquiry regarding neurologic symptoms in patients with nevus of Ota.

Comment on “Fatal GNAQ‐mutated CNS melanoma in an adolescent with nevus of Ota”

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We thank Blundell et al for their description of this illustrative and unfortunate case of fatal GNAQ-mutated primary CNS melanoma in an adolescent. 1 As the ophthalmologists who cared for this patient | 1609

Pediatric Dermatology

CORRESPONDENCEThis exquisitely rare case of CNS-derived melanoma in an ODM patient supplements a growing body of evidence that primary CNS and orbital tumors likely arise from abnormal melanocytes of similar developmental origin. In contrast to neoplasms derived from sunexposed epithelial melanocytes, which typically harbor characteristic BRAF, NRAS, or TERT promoter mutations, most uveal (83%) and CNS (40%) melanomas carry a distinct genetic signature including activating point mutations of the G a -protein-coupled receptor genes GNAQ and GNA11.

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“…We thank Blundell et al for their description of this illustrative and unfortunate case of fatal GNAQ-mutated primary CNS melanoma in an adolescent. 1 As the ophthalmologists who cared for this patient | 1609…”