Endometrioid adenocarcinoma is the most common histological subtype of endometrial carcinoma. The presence of mucinous differentiation may represent a diagnostic challenge, particularly in distinguishing it from primary mucinous carcinoma of the endometrium or mixed epithelial tumors, entities that may carry different prognostic and therapeutic implications.

We report the case of a 63-year-old woman who underwent total hysterectomy with bilateral salpingo-oophorectomy for endometrial carcinoma. Histopathological examination revealed a FIGO grade 2 endometrioid adenocarcinoma with deep myometrial invasion exceeding 50% of the myometrial thickness. The tumor displayed predominantly glandular and papillary architecture, with tumor cells showing abundant cytoplasm containing intracytoplasmic mucin. Mucinous differentiation was confirmed by Alcian blue staining, which highlighted both intracytoplasmic and luminal mucin deposits. No serous or clear cell component was identified.

Immunohistochemical analysis demonstrated a wild-type p53 staining pattern and a deficient mismatch repair (dMMR) phenotype, characterized by loss of PMS2 expression with weak and heterogeneous MLH1 staining, while MSH2 and MSH6 were retained. The tumor cells showed diffuse positivity for CK7 and progesterone receptors, supporting an endometrial origin and excluding a high-grade serous carcinoma.

This case highlights the morphological and immunohistochemical features of endometrioid adenocarcinoma with mucinous differentiation and emphasizes the importance of an integrated diagnostic approach. Accurate recognition of this variant is essential to avoid misclassification and to ensure appropriate prognostic stratification and therapeutic management in accordance with current FIGO and ESGO/ESTRO/ESP recommendations.