In this issue of the Journal of Clinical Pathology, Pu and colleagues from the Nanjing University Medical School, China, report that NTRK gene alterations were enriched in gastric carcinoma with hepatoid or enteroblastic differentiation but not, as in the colon, dMMR-type gastric carcinomas.1 The study analysed 51 cases of EBV (Epstein-Barr virus)-associated gastric carcinomas, 94 cases of dMMR gastric carcinomas, 90 cases of gastric adenocarcinoma with hepatoid or enteroblastic differentiation and 256 cases of conventional gastric carcinomas. All four tumours with NTRK gene alterations were identified in gastric carcinoma with hepatoid or enteroblastic differentiation. Among these four cases, two were associated with fusion (NTRK2-SMCHD1 fusion and TPM3-NTRK1) and two with amplification (NTRK1 and NTRK3). The role of NTRK amplification is unclear, but emerging evidence suggests that these genetic alterations may also be targetable.2 The study adds to the growing literature that gastric carcinomas with enteroblastic differentiation (GAED) are biologically aggressive and genetically unique.

Adenocarcinoma with enteroblastic differentiation (AED) is a rare histologic variant first described by Kodama et al.3 It is defined by a tubulopapillary architecture composed of columnar cells with clear cytoplasm resembling the primitive embryonic intestine. These tumours have also been called clear cells (glycogen-rich carcinomas)4 and foetal-type adenocarcinomas.5

The incidence of AED ranges from 0.7% to 13% of gastric adenocarcinomas in the reported series. Notably, most data on GAED come from Asia, including Japan, China and Korea. Publications from the Americas and Europe are sparse. Although less common, these neoplasms are likely underrecognised in these …