Highly Recurrent IDH1 Mutations in Prostate Cancer With Psammomatous Calcification

Prostate cancer is a heterogeneous disease with several well-recognized morphologic subtypes and histologic variants-subsets of which are enriched for or associated with specific genomic alter-ations. Herein, we report a cohort of 4 unique prostate cancers characterized by intratumoral psammomatous calcification-which we have termed prostate cancer with psammomatous calci-fication (PCWPC). Clinicopathologic review demonstrates that PCWPCs are high-grade (grade group >= 3) tumors that involve the anterior prostate, and integrative targeted next-generation sequencing reveals recurrent hotspot IDH1 mutations. This morphology-molecular correlation is independently confirmed in The Cancer Genome Atlas prostatic adenocarcinoma cohort, with 3 of the 5 IDH1- mutant prostate cancers showing psammomatous calcification (rf = 0.67; Fisher exact test, P < .0001). Overall, these findings suggest that PCWPC represents a novel subtype of prostate cancer enriched for an anterior location and the presence of hotspot IDH1 mutations. Recognition of these unique morphologic features could help identify IDH1-mutant prostate cancer cases retrospectively and prospectively-facilitating future large research studies and enabling clinical trial enrollment and precision medicine approaches for patients with advanced and/or aggressive disease.(c) 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.

Automated summary

This study reports a subtype of prostate cancer with psammomatous calcification (PCWPC) that is enriched for specific genetic alterations. These tumors are high-grade and commonly located in the anterior prostate, and are associated with recurrent hotspot IDH1 mutations. Recognition of this unique subtype could aid in identifying IDH1-mutant prostate cancer cases and facilitating further research and precision medicine approaches.