The classification of neuroendocrine neoplasms of the breast and its clinical relevance

Uccella, Silvia

doi:10.1007/s00428-021-03223-1

Cited by 6 publications

(7 citation statements)

References 27 publications

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“…Histogenetic existential crisis aside, the fact remains that tumours with NE features are encountered in the breast and pathologists have to grapple with their recognition, diagnosis and classification. There have been several insightful opinions and reviews that highlight current issues regarding NE breast tumours 23–26 . A pragmatic approach is to develop a reproducible algorithm for evaluating these tumours that can appropriately categorize them for clinical management, while awaiting more research that can direct refinement of their classification in the breast.…”

Section: Not Against (Puay Hoon Tan)mentioning

confidence: 99%

“…There have been several insightful opinions and reviews that highlight current issues regarding NE breast tumours. [23][24][25][26] A pragmatic approach is to develop a reproducible algorithm for evaluating these tumours that can appropriately categorize them for clinical management, while awaiting more research that can direct refinement of their classification in the breast. It is premature to sound the death knell for these tumours, which have been diligently described and discussed for decades.…”

Section: Not Against (Puay Hoon Tan)mentioning

confidence: 99%

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

Rakha

Tan

2022

Histopathology

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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.

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Section: Not Against (Puay Hoon Tan)mentioning

confidence: 99%

Section: Not Against (Puay Hoon Tan)mentioning

confidence: 99%

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

Rakha

Tan

2022

Histopathology

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“…It is important to differentiate between primary NENs and metastatic NE tumors from other organs to determine the optimal surgical approach. To diagnose the primary NENs, morphological findings, IHC markers including NE markers and hormone-receptors, intraductal lesion, clinical history, and clinical symptoms such as diarrhea and facial flushing should be considered [ 30 ]. There is little reported evidence for the optimal extent of resection for primary early Br-NENs [ 31 ].…”

Section: Managementmentioning

confidence: 99%

Neuroendocrine Neoplasms of the Breast: The Latest WHO Classification and Review of the Literature

Ozaki

Miura

Oki

et al. 2021

Cancers

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Breast tumors with neuroendocrine (NE) differentiation comprise an uncommon and heterogeneous group of tumors, including invasive breast cancer of no special type (IBC-NST) with NE features, neuroendocrine tumors (NETs), and neuroendocrine carcinoma (NEC). The most recent World Health Organization (WHO) classification in 2019 defined neuroendocrine neoplasms (NENs) of the breast (Br-NENs) as tumors in which >90% of cells show histological evidence of NE differentiation, including NETs (low-grade tumors) and NEC (high-grade). Due to the low prevalence of these tumors and successive changes in their diagnostic criteria over the years, only limited evidence of these tumors exists, derived mainly from case reports and retrospective case series. Breast tumors with NE differentiation are usually treated like the more commonly occurring IBC-NSTs. Immunohistochemistry (IHC) of breast tumors with NE differentiation usually shows a hormone receptor (HR)-positive and human epidermal growth factor type 2 (HER2)-negative profile, so that hormonal therapy with cyclin-dependent kinase (CDK)4/6 inhibitors or other targeted agents would be reasonable treatment options. Herein, we present a review of the literature on breast tumors with NE differentiation as defined in the latest WHO 2019 classification, and discuss the clinical management of these tumors.

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“…Although a uniform classification of all NENs from different organ systems may represent an ideal approach for both pathologists and clinicians, its application to breast neoplasms has raised several uncertainties [ 4 , 5 ]. Indeed, there is still a lack of clear-cut standards to differentiate real Br-NENs from solid BCs having some degree of neuroendocrine differentiation.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, there is still a lack of clear-cut standards to differentiate real Br-NENs from solid BCs having some degree of neuroendocrine differentiation. An effective differential diagnosis requires validated and reproducible morphological criteria, in addition to well-defined qualitative and quantitative thresholds for neuroendocrine marker assessment [ 4 ]. Regarding prognosis, only few studies described the impact of NE differentiation in BC, reporting contrasting results [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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The classification of neuroendocrine neoplasms of the breast and its clinical relevance

Cited by 6 publications

References 27 publications

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

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

Neuroendocrine Neoplasms of the Breast: The Latest WHO Classification and Review of the Literature

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

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