| Summary: | When diagnosing endometrial carcinoma cases, we encountered histological features that strikingly resembled uterine mesonephric-like adenocarcinoma (MLA), but the differential diagnosis remained challenging after performing immunostaining. Considering the aggressive biological behavior and poor prognosis of uterine MLA, we believe that the accurate recognition of mesonephric-like differentiation (MLD) is important in the diagnosis of endometrial carcinoma. We aimed to investigate the clinicopathological and molecular characteristics of such cases and compared them with those of uterine MLAs. Five patients diagnosed with endometrioid carcinoma (EC) with MLD were included in this study. Histological evaluation, immunostaining, and targeted sequencing were performed. All five tumors showed typical morphological features of MLA, including densely aggregated tubular structures, deep basophilia under low-power magnification microscopy, eosinophilic intraluminal secretions, and diverse growth patterns. Immunostaining revealed moderate-to-strong nuclear immunoreactivity for estrogen and progesterone receptors in more than 50% tumor cells. The staining intensities and proportions of PAX2 and GATA3 were variable. None of the tumors harbored <i>KRAS</i> mutations. Considering the prognostic implications, ancillary tests, including immunostaining and targeted sequencing, should be performed to accurately differentiate between endometrial EC-MLD and uterine MLA.
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