Comprehensive clinicopathologic, morphologic, and molecular evaluation and outcomes in polymorphous adenocarcinoma tumors with applicability of a 2-tiered grading system Journal Article


Authors: Viswanathan, K.; Steward-Tharp, S.; Lubin, D.; Saeed, F.; Magliocca, K.; Delfin, L.; Bilodeau, E.; Ilyas, G.; Ghossein, R.; Xu, B.; Katabi, N.
Article Title: Comprehensive clinicopathologic, morphologic, and molecular evaluation and outcomes in polymorphous adenocarcinoma tumors with applicability of a 2-tiered grading system
Abstract: Polymorphous adenocarcinoma (PAC) is an uncommon salivary gland tumor demonstrating morphologic diversity, including conventional trabecular/tubular/reticular/single filing, cribriform/solid (cribriform adenocarcinoma of minor salivary gland [CASG]), and papillary (tumor with papillary growth pattern [TPAP]) patterns, with differing molecular alterations and biologic behavior. However, similar to other salivary gland tumors, whether a grading system incorporating mitotic count and necrosis could be applied to PACs is unclear. Retrospective histologic evaluation was performed on a bi-institutional cohort of 154 PACs, and a 2-tiered low-grade/high-g1rade (HG) system, incorporating mitoses ≥ 5 per 2 mm2 and/or necrosis, was applied. Molecular data, when available, and outcome status were collected. Statistical analyses, including univariate analysis and multivariable analysis, were performed. The most common site was palate (62.1%) followed by oral cavity (20.9%). Conventional PACs, CASG, and TPAP represented 56.6%, 39.5%, and 3.9% of cases, respectively. In the cohort, 12.3% demonstrated necrosis and 19.5% had mitosis ≥ 5 per 2 mm2; HG criteria were met in 24.7% of cases. Follow-up data were available in 89.6% of cases. On univariate analysis, as per the 8th edition of the American Joint Committee on Cancer, T category, lymphovascular invasion, bone invasion, mitosis ≥ 5 per 2 mm2, HG, necrosis, and CASG/TPAP morphologic subclassification had worse disease-specific survival and disease-free survival (DFS). PRKD fusion-positive cases affected only DFS, and 61.8% of the cases were of HG. On limited multivariable analysis, HG tumors had worse DFS. With the grading system, the 3-year, 5-year, and 10-year DFS rates were 97%, 91%, and 81% for low-grade tumors and 71%, 65%, and 46% for HG tumors. Although death from disease was limited (3.6%), the majority (80%) were of HG. PAC tumors generally have good outcomes; however, a 2-tiered grading system may identify a subset with worse clinical outcomes, independent of morphology and staging. Consideration should be given to evaluating not only the morphologic pattern but also for the presence of mitotic activity and necrosis in PACs. © 2025 United States & Canadian Academy of Pathology
Keywords: salivary gland; histomorphology; grading system; polymorphous adenocarcinoma
Journal Title: Modern Pathology
Volume: 38
Issue: 9
ISSN: 0893-3952
Publisher: Nature Research  
Date Published: 2025-09-01
Start Page: 100803
Language: English
DOI: 10.1016/j.modpat.2025.100803
PUBMED: 40447138
PROVIDER: scopus
DOI/URL:
Notes: Source: Scopus
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  1. Ronald A Ghossein
    487 Ghossein
  2. Nora Katabi
    307 Katabi
  3. Bin   Xu
    231 Xu