Mismatch repair protein deficiency (MMRd) and high microsatellite instability (MSI-H) in gastrointestinal stromal tumour (GIST) - a case report and review of the literature of this exceedingly rare phenotype.

内容摘要

We report a case of mismatch repair protein deficient (MMRd) and high microsatellite instability (MSI-H) GIST that is exceedingly rare. The patient is an elderly male who presented with abdominal discomfort and poor appetite. Investigations revealed a gastric GIST (CD117 and DOG1 positive, SDH expression retained), spindle cell type, 22 cm in size with 23 mitoses per 5mm2. Few small metastatic nodules were also present in the liver. Next generation sequencing (NGS) revealed a KIT exon 11 c.1668_1724del, p.(Trp557_Gln575del) variant, MSI-H phenotype and tumour mutational burden (TMB) of 15.7 mutations per megabase (Mb). MMR protein immunohistochemistry showed loss of MLH1 and PMS2 expression. The NGS also showed a MLH1 exon 17 c.1946del, p.(Pro649fs) variant. No germline testing was performed. MSI testing by MSI PCR, however, showed a microsatellite stable result. This highlights how MSI PCR may not be sufficiently sensitive in detecting MSI-H status in tumour types outside of colorectal carcinomas.