PHENOTYPIC SHIFT OF ADENOCARCINOMA TO SQUAMOUS CELL CARCINOMA OF RECTUM AFTER NEOADJUVANT CHEMORADIOTHERAPY WITH DETECTION OF HPV16: A CLINICAL CASE

Abstract

Adenosquamous carcinoma and pure squamous cell carcinoma (SCC) of the rectum are extremely rare malignancies, accounting for approximately 0.15% of all colorectal cancers. Increasing attention has been paid to tumor phenotypic plasticity in the context of intensive anticancer therapy. We report the case of a 45-year-old patient with locally advanced rectal adenocarcinoma (cT4bN2M0) who underwent total neoadjuvant therapy consisting of XELOX chemotherapy combined with pelvic radiotherapy. Baseline biopsy samples from multiple tumor areas showed moderately differentiated adenocarcinoma with an intestinal immunophenotype. After treatment, the resected tumor showed complete loss of intestinal differentiation markers (CK20, CDX2) and the emergence of a squamous immunophenotype with positive expression of p40 and p63. Histologically, the tumor was composed exclusively of poorly differentiated SCC. PCR analysis detected HPV16 DNA in the SCC component. Strong, diffuse p16INK4a expression was observed in both the primary adenocarcinoma and the post-treatment tumor. These findings indicate a marked therapy-associated phenotypic shift in tumor differentiation. However, the underlying biological mechanism remains uncertain. Possible explanations include therapy-associated tumor plasticity, clonal selection of a pre-existing squamous subclone, or an initially unrecognized mixed tumor phenotype. This case highlights the importance of careful pathological reassessment after neoadjuvant therapy in rectal cancer and illustrates the complexity of interpreting phenotypic changes in treated tumors. The potential role of HPV in such processes remains hypothetical and requires further investigation.