Original ArticlesClinicopathologic, Immunohistochemical, and Molecular Characteristics of Ovarian Serous Carcinoma With Mixed Morphologic Features of High-grade and Low-grade Serous CarcinomaZarei, Shabnam MD*; Wang, Yan MD†; Jenkins, Sarah M. MS‡; Voss, Jesse S. BS§; Kerr, Sarah E. MD∥; Bell, Debra A. MD§Author Information *Robert J Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH †Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China ‡Department of Health Sciences Research, Division of Biomedical Statistics and Informatics §Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester ∥Hospital Pathology Associates, Minneapolis, MN Conflicts of Interest and Source of Funding: Supported in part by NIH grant P50 CA136393. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Debra A. Bell, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic, Hilton 11-30A, 200 First Street SW, Rochester, MN 55905 (e-mail: [email protected]). The American Journal of Surgical Pathology: March 2020 - Volume 44 - Issue 3 - p 316-328 doi: 10.1097/PAS.0000000000001419 Buy Metrics Abstract Despite the current classification of high-grade serous carcinoma (HGSCA) and low-grade serous carcinoma (LGSCA) as mutually exclusive diseases based on morphology and molecular pathogenesis, cases with mixed morphologic features of HGSCA and LGSCA have been reported. Herein we assess the clinicopathologic, immunohistochemical (IHC), and molecular genetic characteristics of a group of these cases, which we termed indeterminate grade serous carcinoma (IGSCA) in comparison with groups of HGSCA and LGSCA. Using the World Health Organization (WHO) classification criteria, we selected 27 LGSCA and 19 IGSCA for detailed morphologic study. Thirteen classic HGSCA, 19 classic LGSCA, and 19 IGSCA were selected for p53 and BRAF V600E IHC and molecular genetic testing by next-generation sequencing. IGSCA showed the architectural patterns of invasion of LGSCA, but with higher grade nuclear features focally and a mitotic index intermediate between LGSCA and HGSCA. Few cases in the IGSCA group showed mutant TP53 by IHC or sequencing (4/18, 22.2%), 1 case had mutant BRAF non-V600E by sequencing, and 1 had an NRAS mutation. When present, the mutations were identical in the low-grade and high-grade areas. The IGSCA group had a long-term survival similar to the classic HGSCA group. IGSCA with mixed morphologic features of HGSCA and LGSCA is a rare and potentially clinically aggressive variant of serous carcinoma. Their distinct morphologic, but heterogenous molecular features, including low frequency of TP53 and BRAF mutations suggest that these rare tumors may have a different pathogenesis pathway compared with classic HGSCA and classic LGSCA. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.