Underrecognized diagnostic discordance and delay in endometrial dedifferentiated and undifferentiated carcinoma

Aim: Dedifferentiated and undifferentiated endometrial carcinoma (DC/UC) is a rare subtype of endometrial cancer characterized by undifferentiated carcinoma components. This study aimed to investigate diagnostic discrepancies and delays in DC/UC and compare them with low-grade endometrioid carcinoma (LGEC). Methods: We retrospectively analyzed 20 DC/UC and 40 LGEC cases finally diagnosed at our hospital (2016-2024). We compared the data of the two groups, including clinicopathologic characteristics and diagnostic intervals defined as the time from the date of initial biopsy to the date of definitive diagnosis. We assessed diagnostic discordances between preoperative diagnoses, including radiological, clinical, and biopsy, and final diagnoses with immunohistochemical analyses. Results: DC/UC cases exhibited significantly longer diagnostic intervals (median 46 vs. 5 days, p = 0.037) and required more biopsy attempts (median two vs. 1, p = 0.002) and immunohistochemical tests (median 19 vs. 6, p = 0.001) than LGEC cases. In preoperative diagnoses, 60% of DC/UC cases showed diagnostic discrepancies. Radiological findings frequently suggested uterine sarcoma in DC/UC (30%, 6/20). Only 50% of DC/UC were suggested via initial biopsy. Immunohistochemistry revealed mismatch repair deficiency in 70% of DC/UC cases. Conclusions: Frequent diagnostic discrepancies and delays were observed in DC/UC, possibly due to its atypical imaging and histopathological features. Raising awareness of DC/UC's clinical and pathological characteristics is crucial to minimizing diagnostic delays. Given its frequency (at least 1% of endometrial cancers) and eligibility for emerging therapies, prioritizing DC/UC in differential diagnoses and improving diagnostic workflows through interdisciplinary collaboration are required for timely and effective treatment.