Researchers presented the cases of 2 patients with gastrointestinal stromal tumors (GISTs) caused by novel germline variants in SDBH and KIT respectively, and published their findings in the Clinical Journal of Gastroenterology. 

Around 80% of GISTs are characterized by activating KIT mutations and around 7% to 8% have PDGFRA mutations. As for the remaining cases of GISTs, the most common variants involve SDH, ie, SDHA, SDHB, SDHC, or SDHD subunits. Most cases of GISTs arise sporadically, although a small percentage (around 5%) of patients have predisposing pathogenic germline variants.

The authors of the study presented 2 case reports. The first involved a 28-year-old female with 3 slowly growing cystic liver lesions that measured between 0.6 cm to 1.7 cm. She had a partial gastrectomy and distal pancreatectomy 2 years ago for a large multinodular tumor involving the pancreas, stomach, and surrounding lymph nodes. The diagnosis then was poorly differentiated pancreatic adenocarcinoma.

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This caused her physicians to suspect that the liver lesions were metastatic pancreatic adenocarcinoma. A needle core biopsy of the liver lesion revealed findings consistent with a metastatic GIST, raising questions about whether the patient’s initial diagnosis should have been a gastric GIST with pancreatic involvement.

Genomic profiling revealed a novel SDHB splice site mutation (c.286 + 2T>G, 67% variant allele fraction). Germline testing demonstrated the same SDHB variant. The patient was given imatinib, which was switched to sunitinib. Due to tumor progression, she was offered regorafenib but declined and stated her intention to pursue alternative herbal treatment. 

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A 64-year-old male presented with dysphagia. Endoscopy revealed a number of submucosal gastric masses and computed tomography imaging demonstrated at least 4 lesions up to 5.5 cm. Endoscopic ultrasound-guided aspiration revealed a GIST. Molecular profiling revealed a KIT exon 17 variant p.D820V (c.2459A > T) at a variant allele fraction of 51%.

His physicians started him on imatinib as other tyrosine kinase inhibitors were not immediately accessible (despite limited evidence of its effectiveness against the KIT D820V variant). Follow-up imaging 3 months later demonstrated no significant tumor response. The patient underwent a total gastrectomy. His surgeons noted innumerable spindle cell GISTs up to 6.1 cm.

“Molecular profiling was completed on 2 separate tumors, both of which showed KIT exon 17 variant p.D820V (c.2459A > T) at variant allele fractions of 49% and 50%, consistent with a germline variant,” the authors said. Imatinib was not restarted. Instead, the patient was closely followed up with regular imaging.


Rasmussen S, Stueck A, Colwell B, Gaston D, Carter M. Gastrointestinal stromal tumors caused by novel germline variants in SDHB and KIT: a report of two cases and literature reviewClin J Gastroenterol. Published online July 11, 2022. doi:10.1007/s12328-022-01672-y