Molecular and immunohistochemical comparison between primary gastrointestinal mucosal melanomas and atypical gastrointestinal stromal tumors

Abstract

Background: It is sometimes challenging to differentiate between gastrointestinal (GI) mucosal melanoma and gastrointestinal stromal tumors (GISTs) because they share some similarities in histological and molecular features. In this study, we investigated their clinicopathological and molecular features.

Methods: Four primary GI mucosal melanomas and 4 atypical GISTs resected from 2017 to 2019 were included. Electronic medical records and histology slides were reviewed and, if needed, immunohistochemical stainings were additionally done. Somatic mutations were analyzed using whole exome sequencing (WES) with tumors and matched normal tissues.

Results: By immunohistochemistry, GISTs were positive for CD117 (4 of 4), DOG1 (4 of 4), and CD34 (2 of 4). In contrast, melanomas were positive for CD117 (2 of 4), HMB-45 (4 of 4), Melan-A (4 of 4), and S100 protein (3 of 4). Using WES, the KIT mutation was detected in 2 of 4 GISTs and 1 of 4 melanomas, all of which showed strong CD117 immunoreactivity. PDGFRA mutation was detected in 2 of 4 GISTs but 0 of 4 melanomas. TP53, NF1, RB1, TERT, and KMT2D mutations were detected in 1 of 4 melanomas but 0 of 4 GISTs. A patient with KIT-mutated melanoma was treated with Gleevec and has remained disease-free for 1 year.

Conclusions: GISTs and GI melanomas have a wide histopathological spectrum. Appropriate ancillary studies can be helpful for proper diagnosis and optimal treatment.

Keywords: Gastrointestinal Stromal Tumor; High-Throughput Nucleotide Sequencing; Immunohistochemistry; Melanoma; Mutation.