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.

Department of Histopathology The Royal Surrey County Hospital Guildford UK

Department of Pathology and Laboratory Medicine The Ottawa Hospital University of Ottawa Ottawa ON Canada

Department of Pathology and Laboratory Medicine University of Calgary Foothills Medical Centre Calgary AB

Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston MA

Department of Pathology Charles University Faculty of Medicine in Plzen Plzen Czech Republic

Department of Pathology Cornell University New York NY

Department of Pathology Massachusetts General Hospital

Department of Pathology Memorial Sloan Kettering Cancer Center

Department of Pathology Microbiology and Immunology Vanderbilt University Medical Center Nashville TN

Department of Pathology Moffitt Cancer Center University of South Florida Tampa FL

Department of Pathology Southern California Permanente Medical Group CA

Department of Pathology University Health Network University of Toronto Toronto

Department of Pathology University of Pittsburgh Medical Center Presbyterian Hospital Pittsburgh PA

Department of Pathology UT Southwestern Medical Center Dallas TX

Department of Pathology Yale University School of Medicine New Haven CT

Department of Tumour Pathology Institute of Oncology University of Istanbul Istanbul Turkey

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