A sneak peek into the diagnostic conundrum of neuroendocrine neoplasms of the breast: An updated review with a brief illustrative case series

Abstract

Listen

Translate article

Abstract Neuroendocrine neoplasms (NENs) of the breast are uncommon tumours that have been a hitherto poorly and variably defined entity. In the recent fifth Edition World Health Organisation (WHO) classification of breast tumour, NENs are dichotomously classified into neuroendocrine tumours (NETs) and neuroendocrine carcinomas (NECs), mirroring the classification of NENs in other organ systems. Both NETs and NECs are invasive tumours in the breast. However, the clinical significance of neuroendocrine differentiation (NED) in breast cancers, especially in NETs of the breast, is not yet fully understood, and a large overlap appears to exist between breast cancers showing NED and invasive breast carcinoma of no special type (IBC-NST). Although breast NECs show distinct clinical and morphological features and show overlapping molecular features with their counterpart in other organs, especially the high-grade component. Diagnosis of NETs based on the morphological characteristics alone can be challenging; one reason is that breast NETs do not necessarily have the same morphological characteristics as those of NENs arising in other organs and are genetically heterogeneous and harbour molecular alterations that differ from IBC, NST. The keynote changes in the current WHO are the exclusion of other histological subtypes that is, solid papillary carcinoma and a hypercellular variant of mucinous carcinoma which are strong immunohistochemical mimickers of NED and the inclusion of large cell neuroendocrine carcinoma (LCNEC). Thus, the heterogeneity of breast tumours with NED and the changes in their classifications over the years have left many open issues that still need to be resolved. Data regarding the prognostic significance of NED is conflicting and histologic grade and tumour stage remain the main prognostic parameters. Current management of NENs is similar to that of IBC of NST. In this review article, we will summarise the journey of NENs of the breast with an update on the recent WHO classification and discuss their differences from NENs arising in other organs by highlighting an interesting case series depicting their clinical, radiological, histological and molecular features.