Polymorphous Adenocarcinoma and Cribriform Adenocarcinoma of Salivary Glands (Cribriform Subtype of PAC ): PRKD Mutation, Diagnosis, and Prognosis‐A Systematic Review

Purpose This systematic review summarizes the data on Polymorphous Adenocarcinoma (PAC) and its contentious salivary gland subtype, Cribriform Adenocarcinoma of Salivary Gland (CASG), focusing on the molecular and clinicopathological characteristics of PRKD1/2/3. Methods This PROSPERO‐registered study followed PRISMA 2020 standards. The review includes case studies, case reports, and cohort studies of polymorphous adenocarcinoma with PRKD1/2/3 fusion from PubMed, Google Scholar, Web of Science, Embase, World Health Organization (WHO), Ovid database, Wiley library, and Clinical Key databases from inception to February 2025. Results PRKD1/2/3 expression is exclusive to PAC and CASG salivary gland cancers. Several unique rearrangements and fusions may aid focused therapy. PRKD expression is linked to improved prognosis and survival. Clinicopathological findings show that the tumor is most common in women and on the palate. CK7 and S100 IHC markers consistently test positive. The peak incidence occurs between the fourth and seventh decades. Resection and adjuvant radiotherapy are the conventional and effective treatments, with no documented tumor‐related deaths. Conclusion CASG is more aggressive and more likely to metastasize distantly than PAC. Beyond histomorphological similarities, molecular changes are essential for accurate diagnosis and prognosis. PRKD alterations serve primarily as diagnostic markers, and their prognostic significance remains inconclusive. Our study indicates that salivary gland cancers should be diagnosed and treated through molecular analysis. PAC and CASG exhibit distinct molecular profiles, which enable clinicians to develop personalized treatments that enhance patient outcomes.