Highly Recurrent IDH1 Mutations in Prostate Cancer With Psammomatous Calcification

Abstract

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 alterations. Herein, we report a cohort of 4 unique prostate cancers characterized by intratumoral psammomatous calcification—which we have termed prostate cancer with psammomatous calcification (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 (rφ = 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.