Background: As with cases of sporadic gastrointestinal stromal tumor (GIST), familial GIST syndrome arises from mutations in KIT or PDGFRA. Only a few dozen such families have been described in the literature.
Methods: Cases of 2 individuals from 2 different newly described kindreds with familial GIST syndrome were retrospectively reviewed. Pertinent immunohistochemical stains, including CD117, CD34, DOG1, desmin, and S100, were performed. Samples from each case were sent to outside facilities for molecular analysis. A review of the relevant literature was performed and the number of familial GIST syndrome cases reported was updated through July 2014.
Results: In case 1, a woman 40 years of age with a family history of GIST presented with abdominal pain and gastrointestinal bleeding. Biopsy of a gastric mass revealed spindle-cell type GIST. Molecular analysis revealed a heterozygous mutation of p.Asp579del in exon 11 of KIT. The patient was placed on imatinib therapy and an initial positive response was demonstrated by imaging. Disease regression was seen on computed tomography, and several GIST tumors were surgically resected. The patient has had stable disease since surgery. In case 2, an asymptomatic woman 29 years of age presented for screening due to a family history of GIST. One small nodule was noted in her stomach and another was noted in the duodenum; both were surgically resected. The patient recovered well following surgery. The GIST in this patient was noted to have similar histological, immunohistochemical, and molecular findings as case 1.
Conclusions: Imatinib has often been shown to be an effective therapy in both the familial and sporadic forms of GIST. There is no standard protocol for addressing the surveillance of patients with spindle-cell type GIST seen in the setting of familial GIST syndrome and with a p.Asp579del mutation of exon 11 on KIT.