Head to head: do neuroendocrine tumours in the breast truly exist?

Abstract

Breast cancer (BC) is a heterogeneous disease with a spectrum of morphological features. Concepts of histogenesis and differentiation in BC remain controversial. Recent evidence supports differentiation rather than histogenesis as the underlying mechanism for the myriad morphological appearances of BC. Prognosis and response to therapy are determined by a combination of factors, including tumour grade, stage and receptor status, whereas tumour histological types play an independent role in only limited examples. Neuroendocrine tumours (NETs) comprise one of the most debated entities in the breast since their first description. Apart from the rare small-cell NE carcinoma (NEC), which has well-characterized features similar to their counterparts in other organs, the true existence, diagnostic criteria and clinical significance of NE neoplasms (NENs) in the breast are shrouded in controversy. At the core of this discussion is whether normal NE cells exist in the breast, and if breast NETs have distinct morphology and clinical behaviour. When NETs are encountered in the breast, metastatic origin has to be excluded. The more frequent situation in which NE differentiation is observed in breast cancers is in the context of recognizable, morphologically well-described special-type neoplasms such as the hypercellular mucinous carcinoma and solid papillary carcinoma. In this review, arguments for and against maintaining the category of NENs in the breast are articulated in relation to existing literature on this group of unusual tumours.