Large cell neuroendocrine carcinoma of the breast – A case report with the diagnostic and therapeutic challenges and a review of selected cases

Large cell neuroendocrine carcinoma (LCNEC) of the breast (LCNECB) is exceedingly rare. We encountered a case of combined LCNEC, invasive breast carcinoma of no special type (IBC-NST), and squamous cell carcinoma (SCC) of the breast. The tumor was initially diagnosed on biopsy as high-grade triple-negative breast carcinoma (TNBC). The surgical specimen after neoadjuvant chemo-immunotherapy showed no residual TNBC but revealed ductal carcinoma in situ and luminal type A-like IBC-NST. Based on these findings, anti-estrogen therapy and radiotherapy were initiated. However, brain metastasis developed seven months after mastectomy. After morphological and immunohistochemical comparison among the biopsy, mastectomy, and brain specimens, the final diagnosis was combined LCNEC with IBC-NST and SCC. Although the diagnosis of LCNECB can often be challenging, accurate histologic identification is essential for selecting the optimal treatment strategy of breast carcinoma. No established therapeutic regimen exists for LCNECB because of its extreme rarity and overlapping histologic features with high-grade IBC-NST and neuroendocrine tumor (NET) of the breast. We discuss non-morphological diagnostic features of LCNECB that may aid in recognizing LCNECB, and review selected cases from the literature to summarize its clinicopathological characteristics and current treatment modalities for this rare tumor.