Routes of Lymphatic Spread: A Study of 112 Consecutive Patients with Endometrial Cancer 1,2 Andrea Mariani, M.D.,* ,3 Maurice J. Webb, M.D.,* Gary L. Keeney, M.D.,² and Karl C. Podratz, M.D., Ph.D.* ,4 *Department of Obstetrics and Gynecology and ² Division of Anatomic Pathology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905 Received October 11, 2000; published online February 28, 2001 Objective. The goal of this work was to assess different patterns of lymphatic spread to pelvic and para-aortic lymph nodes (LNs) in endometrial cancer as a function of the location of tumor within the uterus. Methods. Between 1984 and 1999, 625 patients with endometrial cancer were managed with hysterectomy and node dissection at ourinstitution. The present study includes the 112 (18%) patients who had positive pelvic and/or para-aortic LNs;41 (37%) of them had cervical involvement. Results. The external iliac was the most commonly involved pelvic LN site both in patients with tumor limited to the corpus and in those with cervical invasion. Isolated pelvic LN metastases to a single site were more frequently observed in external iliac LNs and obturator LNs in patients with tumor confined to the uterine corpus, whereas they occurred more commonly in external iliac and common iliac LNs in patients with cervical involvement. Metastasis to the common iliac LNs was more frequent in patients with disease extension to the cervix. In fact, common iliac LNs were positive in 67%of patients with cervical invasion, compared with only 30%of those with tumor confined to the uterine corpus (P < 0.01). Para-aortic LN invasion was significantly associated with obturatorLN status. In fact, para-aortic LNs were positive in 64%of patients with positive obturator LNs compared with 23%of patients with negative obturator LNs (P  0.01). All patients with positive para-aortic LNs and tumor invading the cervix had pos- itive common iliac LNs. By contrast, when tumor was limited to the corpus, common iliac LNs were involved in only 27% of patients with positive para-aortic LNs. Conclusion. External iliac LNs are the most commonly involved LNs in endometrial cancer. Compared with carcinomas limited to the uterine corpus, endometrial cancers invading the cervix spread more readily to the common iliac LNs. Furthermore, these data suggest that para-aortic LN metastases spread via a route shared by the common iliac LNs when tumor involves the cervix but spread predominantly via a route common to the obturator LNs (and/or external iliac LNs) when the primary tumor site is the corpus only. © 2001 Academic Press Key Words: endometrial cancer; lymph nodes; lymphatic metastases. INTRODUCTION Adenocarcinoma of the endometrium is the most common malignancy of the female genital tract and the fourth most common cancer site, accounting for 6% of all neoplasms in women, exceeded only by breast, lung, and colon/rectum. In approximately 75% of cases, the tumor is clinically confined to the uterus at the time of diagnosis. For 2000, the estimated number of new cases of endometrial cancer and cancer deaths in the United States are 36,100 and 6500, respectively. The overall survival rate for endometrial cancer is 84% [1]. Since 1988, the disease of patients with positive pelvic or paraaortic nodes has been classified as stage IIIc [2]. The presence of retroperitoneal lymph node (LN) metastases is indicative of a poor prognosis, and patients with cervical invasion have a higher incidence of LN involvement [3]. The routes of lymphatic spread of different gynecologic tumors [4, 5] have been studied through the use of various techniques for lymphatic mapping. It is likely that cancers limited to the corpus uteri have different routes of lymphatic spread than those that invade the cervix [6, 7]. The objective of the present study was to assess the different patterns of lymphatic spread to pelvic LNs and para-aortic LNs in endometrial cancer as a function of the location of the tumor within the uterus. PATIENTS AND METHODS Between January 1984 and April 1999, 625 patients at our institution had endometrial cancer managed with hysterectomy and node dissection. Of these patients, we identified 112 (18%) who had positive pelvic LNs and/or para-aortic LNs and ana- lyzed their medical records. Staging was defined according to the International Federa- tion of Obstetricians and Gynecologists (FIGO) surgical stag- 1 Presented at the 31st Annual Meeting of the Society of Gynecologic Oncologists, San Diego, California, February 5–9, 2000. 2 Supported by the Mayo Cancer Center (P30CA15083) and the Rochester Research Committee, Mayo Foundation. 3 Present address: Department of Obstetrics and Gynecology, Osp. Sacra Famiglia, Erba (CO), Italy. 4 To whom reprint requests should be addressed. Gynecologic Oncology 81, 100 –104 (2001) doi:10.1006/gyno.2000.6111, available online at http://www.idealibrary.com on 100 0090-8258/01 $35.00 Copyright © 2001 by Academic Press All rights of reproduction in any form reserved.