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 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.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2023 Feb 22 [Epub ahead of print]

Rohit Mehra, Tanmay Shah, Chia-Jen Liu, Komal R Plouffe, Xiaoming Wang, Rahul Mannan, Xuhong Cao, Arul M Chinnaiyan, Scott A Tomlins, Aaron M Udager

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; University of Michigan Rogel Cancer Center, Ann Arbor, Michigan; Michigan Center for Translational Pathology, Ann Arbor, Michigan., Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan., Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; Michigan Center for Translational Pathology, Ann Arbor, Michigan., Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; University of Michigan Rogel Cancer Center, Ann Arbor, Michigan; Michigan Center for Translational Pathology, Ann Arbor, Michigan; Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan; Howard Hughes Medical Institute, Ann Arbor, Michigan., Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; University of Michigan Rogel Cancer Center, Ann Arbor, Michigan; Michigan Center for Translational Pathology, Ann Arbor, Michigan. Electronic address: .