Diagnosis of "cribriform" prostatic adenocarcinoma: an interobserver reproducibility study among urologic pathologists with recommendations.

• Type of Material: Article
• Authors: Rajal B Shah, Department of Pathology, The University of Texas Southwestern Medical Center Dallas, TX, USA.; Qi Cai, Department of Pathology, The University of Texas Southwestern Medical Center Dallas, TX, USA.; Manju Aron, Department of Pathology, University of Southern California Los Angeles, CA, USA.; Daniel M Berney, Department of Cellular Pathology, Bartshealth NHS Trust and Barts Cancer Institute, Queen Mary University of London United Kingdom.; John C Cheville, Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, USA.; Fang-Ming Deng, Department of Pathology, New York University Medical Center New York, NY, USA.; Jonathan Epstein, Department of Pathology, Urology, Oncology, The Johns Hopkins Medical Institutions Baltimore, MD, USA.; Samson W Fine, Department of Pathology, Memorial Sloan Kettering Cancer Center New York, NY, USA.; Elizabeth Genega, Emory University; Michelle S Hirsch, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA.; Peter A Humphrey, Department of Pathology, Yale School of Medicine New Haven, CT, USA.; Jennifer Gordetsky, Department of Pathology, Microbiology and Immunology, Urology, Vanderbilt University Medical Center Nashville, TN, USA.; Glen Kristiansen, Institute of Pathology of The University Hospital Bonn Bonn, Germany.; Lakshmi P Kunju, Department of Pathology at Michigan Medicine, University of Michigan Medical School Ann Arbor, MI, USA.; Cristina Magi-Galluzzi, Department of Pathology, University of Alabama at Birmingham Birmingham, AL, USA.; Nilesh Gupta, Department of Pathology, Henry Ford Health System Detroit, MI, USA.; George J Netto, Department of Pathology, University of Alabama at Birmingham Birmingham, AL, USA.; Adeboye Osunkoya, Emory University; Brian D Robinson, Department of Pathology, Weill Cornell Medicine New York, NY, USA.; Kiril Trpkov, Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary Calgary, AB, Canada.; Lawrence D True, Department of Laboratory Medicine and Pathology, University of Washington School of Medicine Seattle, Washington, USA.; Patricia Troncoso, Department of Pathology, The University of Texas MD Anderson Cancer Center Houston, TX, USA.; Murali Varma, Department of Cellular Pathology, University Hospital of Wales Cardiff, Wales, United Kingdom.; Thomas Wheeler, Department of Pathology & Immunology, Baylor College of Medicine Houston, TX, USA.; Sean R Williamson, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Cleveland, OH, USA.; Angela Wu, Department of Pathology at Michigan Medicine, University of Michigan Medical School Ann Arbor, MI, USA.; Ming Zhou, Department of Pathology, Tufts Medical Center Boston, MA, USA.
• Language: English
• Date: 2021
• Publisher: AJCR
• Publication Version: Final Published Version
• Copyright Statement: AJCR Copyright © 2021
• License: Creative Commons Attribution 4.0 International
• Title of Journal or Parent Work: Am J Cancer Res
• Volume: 11
• Issue: 8
• Start Page: 3990
• End Page: 4001
• Grant/Funding Information: Daniel M Berney is supported by Orchid.
• Keywords: reproducibility; consensus; gleason grade; grade group; Prostate adenocarcinoma; cribriform
• Research Categories: Health Sciences, Pathology

Abstract

Accurate diagnosis of cribriform Gleason pattern 4 (CrP4) prostate adenocarcinoma (PCa) is important due to its independent association with adverse clinical outcomes and as a growing body of evidence suggests that it impacts clinical decision making in PCa management. To identify reproducible features for diagnosis of CrP4, we assessed interobserver agreement among 27 experienced urologic pathologists of 60 digital images from 44 radical prostatectomies (RP) that represented a broad spectrum of potential CrP4. The following morphologic features were correlated with the consensus diagnosis (defined as 75% agreement) for each image: partial vs. transluminal glandular bridging, intraglandular stroma, <12 vs. ≥12 lumina, well vs. poorly formed lumina, mucin (mucinous fibroplasia, extravasation, or extracellular pool), size (compared to benign glands and number of lumina), number of attachments with gland border by tumor cells forming a "glomeruloid-like" pattern, a clear luminal space along the periphery of gland occupying <50% of glandular circumference, central nerve, dense (cell mass occupying >50% of luminal space) vs. loose, and regular vs. irregular contour. Interobserver reproducibility for the overall diagnostic agreement was fair (k=0.40). Large CrP4 had better agreement (k=0.49) compared to small CrP4 (k=0.40). Transluminal bridging, dense cellular proliferation, a clear luminal space along the periphery of gland occupying <50% of gland circumference, lack of intraglandular mucin, and lack of contact between the majority of intraglandular cells with stroma were significantly associated with consensus for CrP4. In contrast, partial bridging, majority of intraglandular cells in contact with stroma, mucinous fibroplasia, only one attachment to the gland border by tumor cells forming a "glomeruloid-like" pattern, and a clear luminal space along the periphery of gland accounting for >50% of the glandular circumference were associated with consensus against CrP4. In summary, we identified reproducible morphological features for and against CrP4 diagnosis, which could be used to refine and standardize the diagnostic criteria for CrP4.