Primary Neuroendocrine Neoplasms of the Breast: Clinicopathological Insights from Three Cases and Review of Literature

Abstract

Neuroendocrine neoplasms (NENs) of the breast are rare malignancies that constitute a small subset of breast cancers and often present diagnostic and therapeutic challenges due to their infrequency and lack of standardized management guidelines. This report describes the clinical, radiological, pathological, and therapeutic features of three cases of primary breast NENs occurring in postmenopausal women, with an emphasis on differential diagnosis and individualized treatment approaches. All patients presented with breast masses categorized as BI-RADS (Breast Imaging-Reporting and Data System) 5 on imaging. Histopathological examination revealed tumors with nested and trabecular architecture composed of cells with eosinophilic cytoplasm and finely stippled chromatin. Immunohistochemistry showed diffuse synaptophysin positivity in all cases, supporting neuroendocrine differentiation, while hormone receptor expression corresponded to luminal molecular subtypes. Comprehensive systemic imaging excluded the presence of extramammary primary tumors. All patients underwent modified radical mastectomy followed by adjuvant therapy according to standard breast cancer protocols, including four cycles of TC chemotherapy (docetaxel–cyclophosphamide) for invasive disease with recurrence risk warranting systemic therapy, endocrine therapy with letrozole for hormone receptor–positive disease, and bisphosphonates. One patient with bilateral disease additionally received adjuvant radiotherapy in view of synchronous bilateral disease and multidisciplinary assessment of increased locoregional recurrence risk. All three remained disease-free at 2-year follow-up. Primary breast NENs require a high index of suspicion for accurate diagnosis, which relies on characteristic morphology, confirmation of neuroendocrine marker expression, and exclusion of metastatic disease. Although management generally aligns with standard breast cancer treatment protocols, an individualized approach is necessary given the tumor's distinct biological behavior and uncertain prognosis. Greater awareness and further documentation of such cases are essential to improve understanding and inform future management strategies.