Case Report: Primary endometrioid adenocarcinoma of the cervix and secondary cervical involvement by endometrial carcinoma: diagnostic pitfalls and an integrated approach based on two cases.

BACKGROUND: Primary endometrioid adenocarcinoma of the cervix (PEAC) is a rare subtype of HPV-independent cervical adenocarcinoma. Due to overlapping clinical, histological, and immunophenotypic features, distinguishing PEAC from endometrioid adenocarcinoma of endometrial origin with cervical involvement remains challenging.

CASE PRESENTATION: We present two cases illustrating the diagnostic pitfalls in determining the primary site of endometrioid adenocarcinoma involving the cervix. The first case was ultimately diagnosed as PEAC based on comprehensive evaluation of the hysterectomy specimen, with no identifiable endometrial primary lesion. Molecular testing revealed microsatellite instability-high status and a pathogenic PMS2 germline variant associated with Lynch syndrome. The second case represented lower uterine segment endometrioid adenocarcinoma with secondary cervical involvement, which closely mimicked a cervical primary tumor. Careful assessment of tumor distribution and the relationship between uterine and cervical lesions supported an endometrial origin.

CONCLUSION: The primary site of endometrioid adenocarcinoma involving the cervix cannot be reliably determined by morphology or immunohistochemistry alone. Accurate diagnosis requires integrated evaluation of clinical, radiological, pathological, and molecular findings, with comprehensive examination of the hysterectomy specimen-particularly assessment of the tumor epicenter, lesion distribution, and the presence of precursor lesions-remaining crucial for definitive site assignment in operable cases. The suggestive framework presented here is intended to provide a systematic, teaching-oriented approach to this challenging differential diagnosis.