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.

Neuroendocrine neoplasms of the breast: diagnostic agreement and impact on outcome

“…Intending to increase diagnostic reproducibility, WHO's latest edition of breast tumors classification [3] employs a uniform scheme for all human NE tumors across the different organ systems, as proposed by the International Agency for Research on Cancer [1]. However, when applied to the diagnostic practice, this classification has proven to be difficult to manage, and the existence of a pure Br-NEN is still controversial and widely debated in the literature, except for the extremely rare primary small cell carcinoma [12][13][14]. Indeed, in our experience, we can apply the category of pure Br-NENs in a small subset of cases, whereas mixed forms, in which NEN component co-exists with a NST or special type BC, are more common.…”

“…As recently discussed in several studies [ 4 , 13 , 14 ], fitting Br-NENs into the rigid two-tiered scheme of NEN classification (well-differentiated NETs vs. poorly differentiated NECs) poses various relevant diagnostic and conceptual challenges. In fact, the attempt to align the classification criteria of Br-NEN with those of other organs has been questioned, mainly due to the overlapping clinical behavior and treatment approach with that of non-NE conventional breast cancers.…”

An update on the pathological classification of breast cancer

“…20 Further refinement of the classification of these breast tumours is needed to improve their diagnostic reproducibility and consolidate the clinical significance of each diagnosis. 28 ILC is often considered to be a single tumour type characterized by loss of function of the cell adhesion protein, E-cadherin, with subsequent cell dyscohesion but comprises a spectrum of tumours with different histological features and clinical behaviour. The classical variant is the most common subtype, typically Nottingham grade 2, and shows a distinct clinical behaviour.…”

“…Breast NE neoplasms (NENs) are currently described either as NE tumours or NE carcinoma, although all represent carcinomas 20 . Further refinement of the classification of these breast tumours is needed to improve their diagnostic reproducibility and consolidate the clinical significance of each diagnosis 28 …”

“…20 Further refinement of the classification of these breast tumours is needed to improve their diagnostic reproducibility and consolidate the clinical significance of each diagnosis. 28 …”