An Unexpected Finding of a PTPN11 Germline Mutation in a Patient With a Melanocytic Lesion With a Somatic MAP2K1 Mutation. Coincidence or Not?

Melanocytic tumors are a diverse group of lesions and are traditionally classified based on a combination of clinical presentation as well as histological examination. More recently, molecular diagnostics has become an increasingly important part of differentiating different melanocytic lesions in the current WHO standards. This molecular testing, however, can result in unexpected findings. In this report, we describe that molecular testing of a clinical atypical melanocytic lesion showed a mutation in the MAP2K1 gene as well as an unexpected germline mutation in PTPN11, indicative of Noonan syndrome. Based on these findings we concluded that the patient had a MAP2K1 associated melanocytic lesion with Noonan syndrome as an incidental finding. Melanomas are classically not associated with Noonan syndrome. However, we hypothesized that the germline mutations of PTPN11 and the somatic second hit mutation in the MAP2K1 genes might be involved in the formation of the aforementioned lesion. As they are both part of the RAS-MAPK pathway. Furthermore, with the expansion of molecular diagnostics in melanomas, we expect to find an increase in unexpected (germline) mutations.
(© 2024 The Author(s). Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)