Neuroendocrine neoplasms of the breast: A review focused on the updated World Health Organization (WHO) 5th Edition morphologic classification

Neuroendocrine breast neoplasms are uncommon invasive carcinomas that have historically been poorly defined due to various definitions of what constitutes a neuroendocrine carcinoma. The 5th Edition of the World Health Organization (WHO) Classification of Breast Tumors has moved to a dichotomous classification of neuroendocrine neoplasms in the breast in order to become standardized with classifications of other organ systems. Neuroendocrine breast neoplasms in the new edition are classified as neuroendocrine tumor and neuroendocrine carcinoma. Key changes are exclusion of special histologic types (solid papillary carcinoma and hypercellular variant of mucinous carcinoma) and the inclusion of large cell neuroendocrine carcinoma. Neuroendocrine tumors are genetically heterogenous and harbor molecular alterations that differ from invasive carcinoma, no special type. Neuroendocrine carcinomas (high-grade) show some overlapping molecular alterations with their counterparts in other organ systems. Data regarding the prognostic significance of neuroendocrine differentiation are conflicting, and histologic grade and tumor stage remain the main prognostic parameters. Current management of neuroendocrine neoplasms is not different from other types of breast carcinoma. This review will provide an update to the current WHO classification of neuroendocrine breast neoplasms and describe pertinent clinical, histologic, and molecular features of these uncommon tumors.