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NTRK gene rearrangements occur in a wide spectrum of tumors and are actionable events predictive of response to TRK inhibitor. We report the first case of gastric carcinoma harboring a NTRK fusion in a 79-year-old man. The tumor was composed predominantly of poorly cohesive carcinoma with focal tubular differentiation. Solid sheet-like or nested pattern of large oxyphilic cells was also noted in 10% of tumor. Pan-Trk immunohistochemistry demonstrated Trk expression with a diffuse cytoplasmic and dot-like staining only in the solid component. Extensive lymphatic invasion and multiple nodal metastases were noted and were predominated by Trk-positive component. A novel ATP1B1-NTRK1 fusion was detected by RNA-seq using fresh frozen sample. The patient died of the disease, despite surgery and chemotherapy. Although extremely rare, NTRK rearrangement does occur in gastric carcinoma and might be associated with aggressive phenotype as well as histologic features like solid growth with extensive lymphatic invasion.

The first case of gastric carcinoma with NTRK rearrangement: identification of a novel ATP1B–NTRK1 fusion