Primary Neuroendocrine Carcinoma of the Breast: A Diagnostic Challenge and Case Report

BACKGROUND: Primary neuroendocrine carcinoma of the breast (NECB) represents an exceedingly rare entity, comprising less than 0.5% of all breast carcinomas and approximately 1% of all neuroendocrine neoplasms. The 2019 WHO classification defines NECB as tumors expressing neuroendocrine markers in > 90% of tumor cells with morphological features resembling neuroendocrine tumors of other anatomical sites. CASE PRESENTATION: A 61-year-old postmenopausal female presented with a palpable left breast mass. Clinical examination revealed a 2 × 3 cm firm, poorly circumscribed mass at the 9 o'clock position with multiple satellite lesions and a solitary axillary lymph node measuring 1.5 × 1.5 cm with rubbery consistency. Sonographic evaluation demonstrated a hypoechoic mass with spiculated margins, heterogeneous echotexture, and posterior acoustic shadowing, classified as BI-RADS 6. Core needle biopsy yielded an initial diagnosis of infiltrative ductal carcinoma, grade III, with immunohistochemistry demonstrating ER+/PR+/HER2- status and a Ki-67 index of 22%. Following modified radical mastectomy, comprehensive histopathological examination revealed distinctive neuroendocrine morphology with diffuse positivity for synaptophysin and chromogranin A, confirming the diagnosis of primary neuroendocrine carcinoma of the breast, grade 2, T2N0M0. The patient underwent multimodal therapy comprising modified radical mastectomy with sentinel lymph node biopsy (all 17 nodes negative), adjuvant anthracycline-taxane chemotherapy, chest wall radiation (50 Gy in 25 fractions), and endocrine therapy with anastrozole. CONCLUSION: This case highlights the diagnostic challenges of NECB, which frequently mimics conventional breast carcinoma on initial assessment. The diagnostic discordance between core biopsy and final pathology underscores the imperative for comprehensive immunohistochemical evaluation in morphologically suggestive cases. Management strategies integrate established breast cancer protocols with neuroendocrine-specific considerations, though optimal treatment paradigms remain incompletely defined due to the paucity of dedicated clinical trials for this rare entity.