Cutaneous Hyperpigmentation and Familial Gastrointestinal Stromal Tumor Associated With Germline KIT Mutation Treated With Imatinib: A Chinese Case Report

Abstract BackgroundFamilial gastrointestinal stromal tumor (GIST) has been identified with multiple GISTs harboring the mutations in germline KIT and PDGFRA. There are only 35 kindreds with germline KIT and 6 with PDGFRA mutations have been reported to date. Familial GIST is often characterized by a series of manifestations, such as multiple lesions, hyperpigmentation, mastocytosis, and dysphagia. Only some kindreds have response to imatinib treatment.Materials and MethodsA 25-year-old Chinese woman presented to the hospital with abdominal pain, and computed tomography (CT) scan showed multiple tumors in the small intestine. Her father had a history of multifocal GISTs, and referred to the hospital with abdominal pain and tumor recurrences last year. Immuhistochemical analysis of CD117 and DOG-1 were performed on tumor samples from the two patients, while KIT mutational analysis was carried out by direct sequencing on DNA from paraffin-embedded specimens and saliva sample.ResultsMultiple GISTs associated with diffuse interstitial cells of Cajal (ICC) hyperplasia were illustrated in these two patients. These tumors were positive for CD117 and DOG-1. The germline mutation at codon 560 of exon 11 (p.V560G) of the KIT gene were found. Treatment with imatinib resulted in favorable responses in both tumor and cutaneous hyperpigmentation.ConclusionsIt is difficult to make a correct diagnosis of familial GIST at first time due to its rarity. This case was finally diagnosed as familial GIST depending on the combination of diffuse ICC hyperplasia, germline KIT mutation, hyperpigmentation and its family history.