Unveiling the unexplored: shedding light on a novel aspect of colorectal carcinoma

Colorectal cancer (CRC) remains a prevalent malignancy worldwide, with a significant burden on public health despite advancements in screening and treatment modalities. While the majority of CRC cases are histologically classified as adenocarcinomas not otherwise specified (NOS), there exists a subset characterized by clear cell features or enteroblastic differentiation, which pose diagnostic and therapeutic challenges. This commentary explores the clinical and pathological aspects of these rare colorectal neoplasms, highlighting their distinct characteristics and aggressive behavior. Despite their rarity, clear cell adenocarcinomas or those with enteroblastic differentiation represent a notable proportion of CRC cases and are associated with adverse prognostic implications, including higher TNM stage and poorer survival outcomes. We advocate for a clearer recognition and classification of these entities within the framework of colorectal carcinoma, analogous to existing categorizations in other gastrointestinal malignancies, to facilitate optimal management strategies and further elucidate their underlying biology.