Background Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in gastrointestinal tract (GI), with striking features of morphology and immunohistochemistry. Pathogenic activating mutations of the proto-Oncogene Kit are detected in 80–85% GISTs, while 5–7% of cases harbor activating mutations of platelet derived growth factor receptor alpha (PDGFRA). There are still some rare mutation types, including succinate dehydrogenase (SDH)-x, BRAF, RAS and NF1 mutations, or ETV6-NTRK3 fusion. Herein, we reported the first case of GIST with ALK gene rearrangement and ALK (D5F3) overexpression. Case presentation In this study, we described a 33-year-old female patient who appeared a massive space occupying lesion (with the maximum diameter of 22 cm) in the stomach and was eventually diagnosed as Kit and PDGFRA wide type GIST. We unexpectedly found that GIST of this patient showed ALK (D5F3) overexpression and harbored a novel fusion CDC42BPB exon 24-ALK in exon 20. Conclusion This is the first case of GIST with both ALK rearrangement (CDC42BPB exon 24-ALK in exon 20) and ALK (D5F3) overexpression. This rare phenomenon might suggest that ALK (D5F3) immunohistochemistry could be a screening tool for ALK-rearranged GIST. In addition, ALK inhibitors could be a potential therapeutic target for patients (with ALK rearrangement), which should be confirmed further.
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.
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