Original ArticlesInvasive Stratified Mucinous Carcinoma (iSMC) of the Cervix Often Presents With High-risk Features That Are Determinants of Poor Outcome An International Multicenter StudyStolnicu, Simona MD*; Boros, Monica MD†; Segura, Sheila MD‡; Horn, Lars-Christian MD§; Parra-Herran, Carlos MD∥; Oliva, Esther MD¶; Abu-Rustum, Nadeem MD#; Soslow, Robert A. MD**; Park, Kay J. MD**Author Information *Department of Pathology, University of Medicine, Pharmacy, Science and Technology of Targu Mures, Targu Mures †Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania ‡Department of Pathology, Indiana University, Indianapolis, IN §University Hospital Leipzig, Leipzig, Germany ∥Sunnybrook Health Sciences Centre, Toronto, ON, Canada ¶Massachusetts General Hospital, Boston, MA Departments of #Surgery **Pathology, Memorial Sloan Kettering Cancer Center, New York, NY Conflicts of Interest and Source of Funding: Supported in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 (R.A.S., K.J.P.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Simona Stolnicu, MD, Department of Pathology, University of Medicine, Pharmacy, Science and Technology of Targu Mures, 38 Gheorghe Marinescu Street, Targu Mures 540139, Romania (e-mail: [email protected]). The American Journal of Surgical Pathology: October 2020 - Volume 44 - Issue 10 - p 1374-1380 doi: 10.1097/PAS.0000000000001485 Buy Metrics Abstract Invasive stratified mucinous carcinoma (iSMC) has been suggested to represent an aggressive subtype of endocervical adenocarcinoma. We sought to investigate the outcomes of iSMC and determine which clinical and pathologic parameters may influence the prognosis. Slides from 52 cases of iSMC were collected and classified as follows: pure iSMC (>90% of the entire tumor) and iSMC mixed with other human papillomavirus–associated adenocarcinoma components (miSMC) (>10%, but <90% of the entire tumor). Clinical and pathologic parameters were evaluated and compared with overall survival (OS) and recurrence-free survival (RFS). One third of patients with iSMC presented with lymph node metastases (LNM) and 25% developed local recurrences, whereas 4 (7.7%) developed distant recurrences. 29 cases (55.8%) were pure iSMC, whereas 23 cases (44.23%) were miSMC. OS was 74.7% in pure iSMC versus 85.2% in miSMC (P=0.287). RFS was 56.5% in pure iSMC and 72.9% in miSMC (P=0.185). At 5 years, OS in stage I was 88.9% versus stage II to IV 30% (P=0.004), whereas RFS in stage I was 73.9% versus stage II to IV 38.1% (P=0.02). OS was influenced by International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.013), tumor size (P=0.02), LNM (P=0.015), and local recurrence (P=0.022), whereas RFS was influenced by FIGO stage (P=0.031), tumor size (P=0.001), local recurrence (P=0.009), LNM (P=0.008), and type of surgical treatment (P=0.044). iSMC is an aggressive cervical tumor biologically different from other human papillomavirus–associated adenocarcinomas due to the propensity for LNM, local/distant recurrence. FIGO stage, tumor size, LNM, and presence of local/pelvic recurrences are determinants of outcome in iSMCs. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.