Contralateral Primary Small-Cell Neuroendocrine Carcinoma of the Breast With Focal Squamous Differentiation in a...

Primary neuroendocrine carcinoma of the breast is a rare malignancy. Tumors demonstrating predominant neuroendocrine differentiation with focal squamous features are exceptionally uncommon, and metachronous contralateral development following previously treated invasive ductal carcinoma (IDC) has been reported only rarely. We present the case of a 68-year-old woman with a history of estrogen receptor-positive, HER2-negative left breast IDC treated with neoadjuvant chemotherapy, mastectomy, adjuvant radiation therapy, and endocrine therapy who developed a distinct contralateral high-grade breast carcinoma seven years later. Following the discovery of right axillary lymphadenopathy, imaging revealed a right breast mass with progressive axillary adenopathy. Histopathologic examination demonstrated a primary small-cell neuroendocrine carcinoma of the breast with focal squamous differentiation. Immunohistochemistry showed diffuse positivity for INSM1, synaptophysin, and p63, with negativity for estrogen receptor, progesterone receptor, HER2, TTF-1, CDX2, SOX10, and GATA3, supporting a primary breast origin. This case highlights the diagnostic complexity and therapeutic uncertainty surrounding a metachronous contralateral neuroendocrine breast carcinoma following treatment of a separate primary breast malignancy. This exceptionally rare entity underscores the importance of continued case reporting to improve understanding of its clinicopathologic features and guide future management strategies.