Amphicrine (in Greek, on a urea breath test or history of intake of any proton pump inhibitors. abdomen. The tumor was within the corpus inside the square range highlighted with the blue range (A). Histopathological evaluation revealed a carcinoid-like tumor cell nest was situated in the center from the tumor, inside the reddish colored group, while signet-ring cell carcinoma cells had been distributed in the complete section of the tumor, inside the dark circle (B). In resected tissues specimens surgically, a poorly cohesive carcinoma harboring 2 unique phenotypes of signet-ring cell carcinoma cells were detectedcells with eosinophilic and somewhat granular cytoplasm (Physique 2A) or pale cytoplasm (Physique 2B). We also observed a carcinoid-like tumor cell nest round the signet-ring cells (Physique 2C). Open in a separate window Physique 2. Poorly cohesive carcinoma harboring 2 unique phenotypes of signet-ring cell carcinoma cellscells with eosinophilic and somewhat granular cytoplasm (A and B). Note the signet-ring cell carcinoma with eosinophilic granules indicated by black arrow. We also observed a carcinoid-like tumor cell nest (black arrowheads) round the signet-ring cells (C). Note the synaptophysin immunoreactivity in the carcinoid-like nested tumor cells (black arrowheads) and also in the signet-ring cell carcinoma cells (D). We confirmed the coexistence of synaptophysin immunoreactivity and Alcian blue (pH 2.5) staining in individual signet-ring cell carcinoma cells, which harbored eosin-stained abundant granular cytoplasm in a mirror image tissue section (E). Both chromogranin and CD56 Benserazide HCl (Serazide) immunoreactivity were found in malignancy cells (F and G, respectively). Interestingly, the CD44v9 immunoreactivity was found in the present gastric malignancy cells (H). Level bar: 100 m. White arrow indicates the same tubular structure to facilitate quick understanding of tissue location. Subsequently, we performed immunohistochemical staining using a Benserazide HCl (Serazide) specific antibody against synaptophysin, an integrated part of the neuroendocrine secretory granule membrane, which is usually broadly used as a protein marker for neuroendocrine cells. 6 Immunohistochemical staining was performed as previously reported.7 Notably, both carcinoid-like nested tumor cells and signet-ring cell carcinoma cells were stained by anti-synaptophysin antibody (Determine 2D). As expected, signet-ring cell carcinoma cells exhibited periodic acidCSchiff and/or Alcian blue (AB) (pH 2.5) positivity. We confirmed the coexistence of synaptophysin immunoreactivity and AB Benserazide HCl (Serazide) staining in individual signet-ring cell carcinoma cells, which harbored eosin-stained abundant granular cytoplasm (Physique 2E). In addition, we also found chromogranin and CD56 immunoreactivity in the present malignancy cells (Physique 2F and G). These findings indicated that this poorly cohesive carcinoma contained amphicrine signet-ring cell carcinoma cells with eosinophilic cytoplasm. CD44 variant 9 (CD44v9) marks a populace of malignancy stem cells, which are able to form tumors as well as regenerate the original tumor heterogeneity.8 Subsequently, immunohistochemical staining was performed using specific antibody to CD44v9 (Cat No. CAC-LKG-M001, Cosmo Bio, Tokyo, Japan). Interestingly, we found CD44v9 immunoreactivity in signet-ring cell carcinoma cells (Physique 2H). The presence of CD44v9-expressing cells might suggest Benserazide HCl (Serazide) HRMT1L3 that the present amphicrine cell would have a phenotype of progenitor cell. To our knowledge, this is also the first statement of amphicrine signet-ring cell carcinoma with eosinophilic cytoplasm. Acknowledgments The authors wish to thank Ms Reiko Shinoda for her technical assistance. Footnotes Funding:The author(s) received no financial support for the research, authorship, and/or publication of this article. Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Contributed by Author Contributions: All authors were involved in the diagnosis or treatment of the patient. YH, CS, and TT drafted the manuscript. ORCID iD: Chiemi Saigo https://orcid.org/0000-0002-1537-0093.