Undifferentiated/Dedifferentiated Carcinomas of the Endometrium: A Retrospective Clinicopathological Study of a Series of 11 Cases

Abstract Introduction Undifferentiated endometrial carcinomas (UDECs) are rare subtypes of endometrial carcinomas with aggressive clinical behavior. Histologically, UDEC exhibits a solid growth pattern and consists of monomorphic, discohesive, small to medium-sized round cells, with absent to minimal neuroendocrine differentiation. When UDEC is accompanied by a differentiated carcinoma component (usually International Federation of Gynecology and Obstetrics [FIGO] grade 1 or 2), it is termed dedifferentiated endometrial carcinoma (DDEC). The diagnosis of these tumors is challenging because of their close histological similarity to grade 3 endometrioid adenocarcinomas. Objectives This article aims to understand and elucidate the clinical presentation, pathological findings, treatment options, and outcomes of UDEC/DDEC. Materials and Methods Diagnosed/suspected cases of UDEC/DDEC, based on pathology reports between January 2018 and January 2023, were retrieved from the pathology database. Clinical, treatment, and follow-up details were retrieved from the electronic medical record database. Results Out of the 21 cases reviewed, 10 cases were reclassified as “grade 3 endometrioid adenocarcinoma” and 1 case as carcinosarcoma based on histomorphology and immunohistochemical findings. There were 11 cases of undifferentiated carcinoma, out of which 7 were reconfirmed and assigned a DDEC diagnosis. Lower uterine segment involvement was seen in 45% of cases. Out of the 11 patients, 6 patients were diagnosed with stage IIC disease, 4 patients with stage IIIC disease, and 1 patient with stage IV disease (FIGO 2023 staging). Mismatch repair (MMR) protein deficiency was seen in 50% of tested cases and loss of SMARCA4 (BRG1) was seen in one case. Four patients received adjuvant concurrent chemoradiation, one patient received adjuvant chemotherapy, and one patient received neoadjuvant chemotherapy. Six patients had no evidence of disease at follow-up ranging from 6 to 24 months. Two patients had disease progression and one patient died of disease. Conclusion UDECs and DDECs are rare endometrial tumors that show characteristic histomorphology, weak/absent immunohistochemistry staining for EMA/PAX8, and MMR protein deficiency in a subset of cases. It is important to have a high index of suspicion for these tumors due to close mimickers, their aggressive behavior, and the potential role of treatment with immunotherapy.