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

Abstract

The classification of breast neuroendocrine neoplasms (Br-NENs) was modified many times over the years and is still a matter of discussion. In the present study, we aimed to evaluate the diagnostic reproducibility and impact on patient outcomes of the most recent WHO 2019 edition of breast tumor classification, namely, for neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). This multicentric observational study included 287 breast neoplasms with NE differentiation. The cases were blindly classified by three independent groups of dedicated breast and/or endocrine pathologists following the 2019 guidelines. Diagnostic concordance and clinical impact were assessed. We observed only a moderate overall diagnostic agreement across the three centers (Cohen’s kappa 0.4532) in distinguishing NET from solid papillary carcinomas (SPCs) and no special type carcinomas (NST) with NE differentiation. Br-NENs were diagnosed in 122/287 (42.5%) cases, subclassified as 11 NET G1 (3.8%), 84 NET G2 (29.3%), and 27 NEC (9.4%), the latter group consisting of 26 large-cell and 1 small-cell NECs. The remaining 165/287 (57.5%) cases were labeled as non-NEN, including SPC, mucinous, NST, and mixed NE carcinomas. While NET and non-NEN cases had a comparable outcome, the diagnosis of NECs showed negative impact on disease-free interval compared to NETs and non-NENs (p = 0.0109). In conclusion, the current diagnostic classification of Br-NENs needs further adjustments regarding morphological and immunohistochemical criteria to increase the diagnostic reproducibility among pathologists. Our data suggest that, apart from high-grade small- and large-cell NECs, Br-NENs behave like non-NEN breast carcinomas and should be managed similarly.

Predictors for axillary lymph node metastasis in primary neuroendocrine carcinomas of the breast and neuroendocrine differentiated breast cancers

“…Debates regarding the WHO classification of neuroendocrine neoplasms of the breast are still ongoing and it is emphasized that it needs further adjustments regarding morphological and immunohistochemical criteria. 25 In particular, welldifferentiated NECs of the breast are treated in the same way as invasive breast carcinoma. However, there is limited data on whether treatment modalities similar to this treatment for invasive breast carcinoma are effective for neuroendocrine neoplasm of the breast.…”

Neuroendocrine neoplasms in the breast oncology field: dilemmas of nature and morphology

“…In the breast oncology field, the assertion of NENs, as a cross-disciplinary disease concept in the WHO classification (5th ed.) updated in 2019, has given rise to various forms of confusion regarding diagnostic criteria as well as treatment on a global scale including in Japan (2,3). Specifically, the existence of an authentic mammary NEN is still controversial and widely debated in the literature, with the exception of the fairly uncommon primary small cell neuroendocrine carcinoma (4-7).…”