Abstract
Rectal large cell neuroendocrine carcinoma (LCNEC) is an exceedingly rare and aggressive neoplasm with a poor prognosis and median survival of 4-16 months. Diagnosis is challenging due to the clinical overlap with classical colorectal adenocarcinoma, and accurate diagnosis is reliant on histological examination via immunohistochemistry (IHC). For the diagnosis of LCNEC, neuroendocrine markers such as Synaptophysin, CD56, chromogranin A and Ki-67 are major determinants of the disease. We present a double case report of two individuals initially assumed diagnosed as rectal adenocarcinoma who were then re-diagnosed with rectal LCNEC via post-surgical IHC. Both patients received neo-adjuvant chemotherapy yet still developed metastatic disease. This report intends to appraise the role of routine early IHC as a critical tool for diagnosis and to guide management planning. Given the rarity and volatility of rectal LCNEC, further research is desperately needed to develop tailored treatment measures and improve patient outcomes.