Clinicopathological and mutational characteristics of primary double mutant gastrointestinal stromal tumor: a single center study with review of the literature

AIMS: Primary double KIT/PDGFRA mutations are very rare in gastrointestinal stromal tumours (GISTs) but have not been comprehensively studied to date. In the present study, we investigated the clinicopathologic and genetic features of eight cases of primary double-mutant GISTs, and we reviewed the literature. METHODS AND RESULTS: The tumours occurred in six males and two females (age range 57–83 years) and involved the small intestine (n = 4), stomach (n = 2), rectum (n = 1) and retroperitoneum (n = 1). Clinical manifestations were variable, ranging from indolent (no symptoms) to aggressive disease (tumour rupture and haemorrhage). All patients underwent surgical excision, and six of them were treated with imatinib. No one experienced recurrence or other complications during the follow-up time (10 to 61 months). Histologically, all the tumours exhibited mixed cell types, accompanied by variable interstitial changes. KIT mutations were detected in all cases, and the majority of them were present in different exons (n = 5). No PDGFRA exon 12, 14 or 18 mutations were found. All the mutations were validated by next-generation sequencing, and two additional variants with comparatively low allelic fractions were identified in one case. Two of the cases had available allele distribution data, one with an in cis compound mutation and the other with an in trans compound mutation. CONCLUSION: Primary double-mutant GISTs have distinctive clinicopathologic and mutational features. Studies of more cases are necessary for a better understanding of these tumours. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10684-x.