Original ArticlesHistologic Classification and Molecular Signature of Polymorphous Adenocarcinoma (PAC) and Cribriform Adenocarcinoma of Salivary Gland (CASG) An International Interobserver StudyXu, Bin MD, PhD*; Barbieri, Andrea L. MD†; Bishop, Justin A. MD‡; Chiosea, Simon I. MD§; Dogan, Snjezana MD*; Di Palma, Silvana MD∥; Faquin, William C. MD, PhD¶; Ghossein, Ronald MD*; Hyrcza, Martin MD, PhD#; Jo, Vickie Y. MD**; Lewis, James S. Jr MD††; Lozada, John R.*; Michal, Michal MD‡‡; Pareja, Fresia G. MD, PhD*; Perez-Ordonez, Bayardo MD§§; Prasad, Manju L. MD**; Purgina, Bibianna MD∥∥; Reis-Filho, Jorge S. MD, PhD*; Scognamiglio, Theresa MD¶¶; Sebastiao, Ana P.M. MD*; Seethala, Raja R. MD§; Skálová, Alena MD, PhD‡‡; Smith, Stephen M. MD§§; Tekkeşin, Merva S. DDS, PhD##; Thompson, Lester D.R. MD***; Wasseman, Jason K. MD, PhD∥∥; Wenig, Bruce M. MD†††; Weinreb, Ilan MD§§; Katabi, Nora MD*Author Information *Department of Pathology, Memorial Sloan-Kettering Cancer Center ¶¶Department of Pathology, Cornell University, New York, NY †Department of Pathology, Yale University School of Medicine, New Haven, CT ‡Department of Pathology, UT Southwestern Medical Center, Dallas, TX §Department of Pathology, University of Pittsburgh Medical Center, Presbyterian Hospital, Pittsburgh, PA ∥Department of Histopathology, The Royal Surrey County Hospital, Guildford, UK ¶Department of Pathology, Massachusetts General Hospital **Department of Pathology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA #Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Centre, Calgary, AB §§Department of Pathology, University Health Network, University of Toronto, Toronto ∥∥Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada ††Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN ‡‡Department of Pathology, Charles University, Faculty of Medicine in Plzen, Plzen, Czech Republic ##Department of Tumour Pathology, Institute of Oncology, University of Istanbul, Istanbul, Turkey ***Department of Pathology, Southern California Permanente Medical Group, CA †††Department of Pathology, Moffitt Cancer Center, University of South Florida, Tampa, FL I.W. and N.K. are co-senior authors. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflicts of Interest and Source of Funding: Supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Nora Katabi, MD, Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (e-mail: [email protected]). The American Journal of Surgical Pathology: April 2020 - Volume 44 - Issue 4 - p 545-552 doi: 10.1097/PAS.0000000000001431 Buy Metrics Abstract Polymorphous adenocarcinoma (PAC) shows histologic diversity with streaming and targetoid features whereas cribriform adenocarcinoma of salivary gland (CASG) demonstrates predominantly cribriform and solid patterns with glomeruloid structures and optically clear nuclei. Opinions diverge on whether CASG represents a separate entity or a variant of PAC. We aimed to assess the level of agreement among 25 expert Head and Neck pathologists in classifying these tumors. Digital slides of 48 cases were reviewed and classified as: PAC, CASG, tumors with ≥50% of papillary architecture (PAP), and tumors with indeterminate features (IND). The consensus diagnoses were correlated with a previously reported molecular alteration. The consensus diagnoses were PAC in 18/48, CASG in16/48, PAP in 3/48, and IND in 11/48. There was a fair interobserver agreement in classifying the tumors (κ=0.370). The full consensus was achieved in 3 (6%) cases, all of which were classified as PAC. A moderate agreement was reached for PAC (κ=0.504) and PAP (κ=0.561), and a fair agreement was reached for CASG (κ=0.390). IND had only slight diagnostic concordance (κ=0.091). PAC predominantly harbored PRKD1 hotspot mutation, whereas CASG was associated with fusion involving PRKD1, PRKD2, or PRKD3. However, such molecular events were not exclusive as 7% of PAC had fusion and 13% of CASG had mutation. In conclusion, a fair to moderate interobserver agreement can be achieved in classifying PAC and CASG. However, a subset (23%) showed indeterminate features and was difficult to place along the morphologic spectrum of PAC/CASG among expert pathologists. This may explain the controversy in classifying these tumors. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.