van der Woude Sven, Klein Wassink-Ruiter J S, Kluiver Joost, de Jonge Marthe, Diercks Gilles F H
Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Clinical Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Cutan Pathol. 2025 Jan;52(1):20-23. doi: 10.1111/cup.14730. Epub 2024 Oct 11.
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.
黑素细胞肿瘤是一组多样的病变，传统上根据临床表现和组织学检查相结合进行分类。最近，分子诊断在当前世界卫生组织标准中已成为区分不同黑素细胞病变的一个越来越重要的部分。然而，这种分子检测可能会产生意想不到的结果。在本报告中，我们描述了对一个临床非典型黑素细胞病变进行分子检测时发现，MAP2K1基因发生了突变，同时在PTPN11基因中出现了一个意外的种系突变，提示努南综合征。基于这些发现，我们得出结论，该患者患有与MAP2K1相关的黑素细胞病变，并伴有努南综合征这一偶然发现。黑色素瘤通常与努南综合征无关。然而，我们推测PTPN11的种系突变和MAP2K1基因中的体细胞二次打击突变可能参与了上述病变的形成。因为它们都是RAS-MAPK途径的一部分。此外，随着黑色素瘤分子诊断的扩展，我们预计会发现意外（种系）突变的增加。
