Mesonephric-like Adenocarcinoma of the Uterine Corpus in a 28-Year-Old with Down Syndrome and Hypothyroidism: A Case Series of Three Patients and Literature Review

Mesonephric-like adenocarcinoma is a rare uterine neoplasm recognized in the fifth edition of the World Health Organization Classification of Female Genital Tumors and poses diagnostic challenges due to its morphologic and immunophenotypic overlap with other endometrial carcinomas. We retrospectively reviewed three cases diagnosed at our institution, evaluating clinical presentation, histologic features, immunohistochemical profile, and available molecular findings, and performed a literature review of approximately 200 reported cases with emphasis on comorbidities and potential predisposing factors. All three patients presented with abnormal uterine bleeding and had hypothyroidism, and one patient had Down syndrome, representing the first reported case in this population. Tumors consistently expressed thyroid transcription factor 1, showed variable GATA3 expression, and demonstrated limited or absent hormone receptor expression. Literature review revealed frequent association with Müllerian-type lesions and recurrent KRAS mutations, while thyroid disease was not identified as a consistent comorbidity. These findings support a Müllerian origin for mesonephric-like adenocarcinoma and suggest that hypothyroidism is unlikely to represent a defining association. The occurrence in a patient with Down syndrome raises the possibility of an underlying genetic susceptibility that warrants further investigation.