Original ArticlesPrimary Female Urethral Carcinoma Proposed Staging Modifications Based on Assessment of Female Urethral Histology and Analysis of a Large Series of Female Urethral CarcinomasAron, Manju MD*; Park, Sanghui MD†; Lowenthal, Brett M. MD†; Gupta, Sounak MD‡; Sahoo, Debashis PhD§; Cheville, John C. MD‡; Hansel, Donna E. MD, PhD†Author Information *Department of Pathology, University of Southern California, Los Angeles Departments of †Pathology §Pediatrics and Computer Science, Moores Cancer Center, University of California at San Diego, La Jolla, CA ‡Department of Pathology, Mayo Clinic, Rochester, MN Present address: Donna E. Hansel, MD, PhD, Oregon Health and Science University, Portland, OR. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Donna E. Hansel, MD, PhD, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Pathology, L-113, Portland, OR 97239 (e-mail: [email protected]). The American Journal of Surgical Pathology: December 2020 - Volume 44 - Issue 12 - p 1591-1601 doi: 10.1097/PAS.0000000000001569 Buy Metrics Abstract Primary female urethral carcinoma is rare. Limited clinicopathologic information has hindered development of staging criteria in this disease. We analyzed 29 primary female urethral carcinoma resections from 3 academic medical centers to characterize histopathologic features, clinical outcomes, and applicability of current and a novel modified staging criteria. We complemented this analysis with review of fully embedded female autopsy urethras to detail anterior and posterior urethral wall histology. Primary female urethral carcinoma subtypes included urothelial carcinoma in situ (3/29, 10%), adenocarcinoma in situ (1/29; 3%), invasive urothelial carcinoma (13/29, 45%), clear cell carcinoma (5/29, 17%), adenocarcinoma not otherwise specified (4/29, 14%) and squamous cell carcinoma (3/29, 10%). Only 6/29 cases (21%) were originally assigned a stage at diagnosis. Using histologic landmarks specific to the female urethra, we modified existing eighth edition American Joint Committee on Cancer urethral staging to a histology-based female urethral carcinoma staging (UCS) system. UCS stages were defined as pTa/pTisUCS (noninvasive carcinoma), pT1UCS (subepithelial tissue invasion), pT2UCS (periurethral muscle invasion), pT3UCS (vaginal adventitia or surrounding fibrovascular tissue), and pT4UCS (anterior wall fibroadipose tissue or posterior vaginal wall). UCS staging was applicable to all cases and showed stepwise changes in disease recurrence with increasing stage and was statistically significant for disease-specific and overall survival in contrast to the American Joint Committee on Cancer staging system. This study of one of the largest cohort of primary female urethral carcinomas provides a modified histology-based staging system specific to female urethral anatomy that provides outcomes-related information, which may be further validated by larger multi-institutional studies. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.