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Neuroendocrine neoplasms (NENs) of the esophagogastric junction (EGJ) are uncommon and the classification of these tumors has been revised several times. Since 2016, at the Department of Pathology, Rigshospitalet, Denmark, all adenocarcinomas and poorly differentiated carcinomas of the EGJ have been stained routinely with the neuroendocrine markers, synaptophysin and chromogranin A, to detect a possible neuroendocrine component. This study aimed to determine if routine immunohistochemical staining is necessary to detect neuroendocrine differentiation of the EGJ tumors by evaluating how often a neuroendocrine component of the tumors was correctly identified or missed on routine hematoxylin and eosin-stained slides, and by evaluating the interobserver agreement among several pathologists. Of 262 cases a NEN was identified in 24 (9.2%). Up to 22.7% of all EGJ NENs would have been missed without routinely performed neuroendocrine staining in all EGJ tumors. The interobserver agreement between 3 pathologists was slight to moderate. In conclusion, immunohistochemical staining with neuroendocrine markers is essential for the diagnosis of NENs, and to detect all NENs, we recommend to perform this routinely on all resected tumors of the EGJ.

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