What question did this study set out to answer?

To report a rare case of KIT mutated GIST with high microsatellite instability and tumor mutational burden.

February 22, 2026

Case report of KIT mutated gastrointestinal stromal tumour (GIST) with high microsatellite instability (MSI-H) and high tumour mutational burden (TMB)

Key Points

To report a rare case of KIT mutated GIST with high microsatellite instability and tumor mutational burden.
Described a case of a 67-year-old male with a surgically resected gastric GIST.
Used next generation sequencing on the tumor to assess mutations and microsatellite instability.
Conducted immunohistochemistry to evaluate mismatch repair proteins.
Identified a KIT Exon 11 deletion mutation and high microsatellite instability status.
Elevated tumor mutational burden of 15.7 mutations/Mb was observed.
Loss of MLH1 and PMS2 expression noted in the tumor, indicating mismatch repair deficiency.

Abstract

Gastrointestinal stromal tumours (GIST) with microsatellite instability (MSI) and mismatch repair protein deficiency (MMRd) are exceedingly rare. We describe a case of a 67-year-old male with a resected 22 cm gastric GIST (CD117 and DOG1 positive, SDH expression retained), spindle cell type, with 23 mitoses per 5 mm 2 in keeping with high risk of progressive disease. Staging scans showed the presence of possible small metastatic nodules in the liver. Hybrid capture based next generation sequencing (NGS) of 523 genes performed on the gastric tumour revealed a KIT Exon 11 c. 1668₁724del, p. (Trp557Gln575del) variant as well as high microsatellite instability status (MSI-H) and elevated tumour mutational burden (TMB) of 15. 7 mutations/Mb. On immunohistochemistry, the tumour showed loss of MLH1 and PMS2 expression. The NGS result also showed the presence of MLH1 Exon 17 c. 1946del, p. (Pro649fs) variant. The patient did not undergo germline testing and did not have any significant family history of cancer. MSI testing by conventional PCR method showed a MSI stable result. However, only five microsatellite loci were evaluated in the PCR unlike 113 loci evaluated in the NGS. This highlights how MSI PCR may not be sufficiently sensitive in detecting MSI-H status outside of colorectal carcinomas.

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