Synchronous Hepatic Neuroendocrine Carcinoma and Rectal Adenocarcinoma With Pontine Metastasis: A Diagnostic Dilemma

We present a complex case of a 53-year-old male with stage IV large-cell neuroendocrine carcinoma (NEC) of unconfirmed primary origin, manifesting with a pontine brain mass, multiple hepatic lesions, lymphadenopathy, and a synchronous rectal adenocarcinoma. Imaging and pathology revealed distinct morphologic and immunohistochemical profiles: hepatic biopsy confirmed large-cell NEC positive for synaptophysin and CD56, whereas rectal biopsy showed adenocarcinoma with intestinal markers and no neuroendocrine differentiation. Differential diagnoses included two independent primary malignancies, mixed adenoneuroendocrine carcinoma (MANEC), or colorectal adenocarcinoma with neuroendocrine differentiation in the liver. Although molecular profiling or clonal comparison was considered to clarify the primary origin, it was not performed due to clinical constraints. This report underscores the diagnostic challenges in distinguishing synchronous multiple primaries from metastatic or mixed tumors, with significant implications for staging and treatment.