CASE REPORT article
Front. Med.
Sec. Pathology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1551309
Neuroendocrine carcinoma of the breast: A review of literature and illustration of 6 cases
Provisionally accepted
- 1University of California, San Francisco, San Francisco, United States
- 2Icahn School of Medicine at Mount Sinai, New York, New York, United States
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Primary neuroendocrine breast carcinoma (NEBC) is an underdiagnosed subtype of breast cancer, which includes small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Accurate diagnosis remains challenging given their low incidence; misclassification as IBC-NST, IDC, or a metastatic neuroendocrine carcinoma may occur.Cases with any component of adenocarcinoma and well-differentiated neuroendocrine tumors were excluded. A search of the pathology database (2012-2024) revealed six female patients (27-85 y.) with a final pathologic diagnosis of NEBC (stages IA-IV), including 4 LCNECs and 2 SCNECs. Even though most NEBC cases (5 of 6; 83%) were of the luminal subtype, 5 of 6 patients (83%) developed distant metastases within four years of the initial diagnosis. Molecular profiling of six cases revealed common alterations in FGF/FGFR and PI3K/AKT/mTOR pathways. In summary, primary neuroendocrine carcinomas of the breast display aggressive behavior. Yet, they are more likely to harbor certain alterations, such as activating PIK3CA mutations and FGFR1 amplification, which can be of therapeutic value. The Ki-67 index, unlike in the pancreas and gastrointestinal tract, is not suitable for grading neuroendocrine neoplasms (NEN) of the breast. However, it can still serve as a tool for risk stratification, similar to its use in luminal-type breast cancer.
Keywords: neuroendocrine carcinoma, Breast Neoplasms, Neuroendocrine Tumors, mTOR inhibitors, Synaptophysin
Received: 25 Dec 2024; Accepted: 08 Jul 2025.
Copyright: © 2025 Albayrak. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Nazire Albayrak, University of California, San Francisco, San Francisco, United States
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