Most endometrial carcinomas metastasize by invading myometrial lymphatics and spreading to regional lymph nodes. However, uterine serous carcinomas (USCs) metastasize frequently to peritoneal surfaces even when only minimally invasive. This study examines the methods of spread and the role of retrograde transtubal spread. Eighty-seven USCs treated by hysterectomy were identified. Primary peritoneal cases and cases with significant ovarian involvement were excluded. Eighty (92%) cases were pure serous, and the remainder had at least 25% serous histology. Fifty-four of 87 (62%) had extrauterine spread at hysterectomy, most commonly to peritoneal surfaces and sometimes to the pelvic lymph nodes. Twenty-six of 54 (48%) cases had no lymphatic/vascular (LV) invasion and 18/54 (33%) had no myometrial invasion. Eleven of these 54 (20%) patients with metastases lacked both myometrial and LV invasion, and the metastases involved the peritoneal surface more often than the lymph nodes (p<0.001). Three of the 11 cases had tumor clusters in the fallopian tube lumen. Another 13 cases also had clusters of tumor within the fallopian tube lumen, and all 16 cases had peritoneal spread (p<0.001). Extrauterine spread correlated highly with LV invasion (p<0.001) but not with the presence or depth of myometrial invasion. Retrograde transtubal implantation as well LV invasion are two important mechanisms by which USC spreads; all cases with tumor clusters in the fallopian tube lumen had peritoneal spread. This explains the phenomenon whereby patients with serous carcinomas confined to the endometrium and lacking LV invasion have widespread metastases to the peritoneum.

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