Histologic classification and molecular signature of polymorphous adenocarcinoma (PAC) and cribriform adenocarcinoma of salivary gland (CASG): An international interobserver study Journal Article


Authors: 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. Jr; Lozada, J. R.; Michal, M.; Pareja, F. G.; Perez-Ordonez, B.; Prasad, M. L.; Purgina, B.; Reis-Filho, J. S.; Scognamiglio, T.; Sebastiao, A. P. M.; Seethala, R. R.; Skálová, A.; Smith, S. M.; Tekkeşin, M. S.; Thompson, L. D. R.; Wasseman, J. K.; Wenig, B. M.; Weinreb, I.; Katabi, N.
Article Title: Histologic classification and molecular signature of polymorphous adenocarcinoma (PAC) and cribriform adenocarcinoma of salivary gland (CASG): An international interobserver study
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 (kappa=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 (kappa=0.504) and PAP (kappa=0.561), and a fair agreement was reached for CASG (kappa=0.390). IND had only slight diagnostic concordance (kappa=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.
Keywords: tongue; variant; gland; papillary adenocarcinoma; oral-cavity; low-grade adenocarcinoma; polymorphous adenocarcinoma; salivary gland neoplasm; cribriform adenocarcinoma of salivary; terminal duct
Journal Title: American Journal of Surgical Pathology
Volume: 44
Issue: 4
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2020-04-01
Start Page: 545
End Page: 552
Language: English
ACCESSION: WOS:000524995100013
DOI: 10.1097/pas.0000000000001431
PROVIDER: wos
PUBMED: 31917707
PMCID: PMC7437128
Notes: Article -- Source: Wos
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MSK Authors
  1. Ronald A Ghossein
    425 Ghossein
  2. Nora Katabi
    265 Katabi
  3. Snjezana Dogan
    163 Dogan
  4. Bin   Xu
    172 Xu
  5. John Roy Lozada
    20 Lozada