The effect of the extent of neuroendocrine differentiation on cytopathological findings in primary neuroendocrine neoplasms of the breast

Objective: This study aimed to describe the cytological features of neuroendocrine breast tumors and to show the effect of the extent of neuroendocrine differentiation on cytological features. Methods: Breast tumor excision materials showing immunostaining with neuroendocrine markers (Synaptophysin or Chromogranin A) were determined and divided into two groups: cases with focal (10%–50% of tumor cells) staining and cases with diffuse (>50% of tumor cells) staining. A group of cases without neuroendocrine features/staining was used as control group. Fine needle aspiration biopsy specimens of the tumor mass or metastatic lymph nodes were examined and compared. Results: Twenty cases with neuroendocrine differentiation were included. Eleven cases were in the diffuse group, nine cases were in the focal group. Clean background, high cellularity, loosely cohesive cell groups with monotonous appearance, and naked nuclei were more common in the diffuse group. On the contrary, tight cohesive cell groups, the proportion of large cells, nuclear pleomorphism, and nucleolar prominence were higher in the group with focal staining. Plasmocytoid appearance, isolated cell groups, and binucleation were in similar distribution in both groups. Although round-oval nuclei were dominant in both groups, round nuclei were observed to be slightly more in the diffuse group. Only two cases in diffuse group showed cytoplasmic granularity and one case in focal group showed necrosis and mitosis. In the control group, tight cohesive groups, large cell size, pleomorphism, prominent nucleoli, and coarse chromatin were more commonly encountered. Conclusions: Clean background, hypercellularity, loss of cohesion, naked nuclei, monotonous cells with round nucleus, and granular cytoplasm were more prominent in cases showing diffuse staining with neuroendocrine markers. Suspecting neuroendocrine differentiation in tumors that show focal staining with neuroendocrine markers can be challenging in cytological preparations.