Histologic Classification and Molecular Signature of Polymorphous Adenocarcinoma (PAC) and Cribriform Adenocarcinoma of Salivary Gland (CASG): An International Interobserver Study

Bin Xu, Andrea L. Barbieri, Justin A. Bishop, Simon I. Chiosea, Snjezana Dogan, Silvana Di Palma, William C. Faquin, Ronald Ghossein, Martin Hyrcza, Vickie Y. Jo, James S. Lewis, John R. Lozada, Michal Michal, Fresia G. Pareja, Bayardo Perez-Ordonez, Manju L. Prasad, Bibianna Purgina, Jorge S. Reis-Filho, Theresa Scognamiglio, Ana P.M. SebastiaoRaja R. Seethala, Alena Skálová, Stephen M. Smith, Merva S. Tekkeşin, Lester D.R. Thompson, Jason K. Wasseman, Bruce M. Wenig, Ilan Weinreb, Nora Katabi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number0000143
JournalAmerican Journal of Surgical Pathology
DOIs
StateAccepted/In press - 2019

Keywords

  • cribriform adenocarcinoma of salivary gland
  • polymorphous adenocarcinoma
  • salivary gland neoplasm

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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    Xu, B., Barbieri, A. L., Bishop, J. A., Chiosea, S. I., Dogan, S., Di Palma, S., Faquin, W. C., Ghossein, R., Hyrcza, M., Jo, V. Y., Lewis, J. S., Lozada, J. R., Michal, M., Pareja, F. G., Perez-Ordonez, B., Prasad, M. L., Purgina, B., Reis-Filho, J. S., Scognamiglio, T., ... Katabi, N. (Accepted/In press). Histologic Classification and Molecular Signature of Polymorphous Adenocarcinoma (PAC) and Cribriform Adenocarcinoma of Salivary Gland (CASG): An International Interobserver Study. American Journal of Surgical Pathology, [0000143]. https://doi.org/10.1097/PAS.0000000000001431