Re-evaluating tumors of purported specialized prostatic stromal origin reveals molecular heterogeneity, including non-recurring gene fusions characteristic of uterine and soft tissue sarcoma subtypes

• Published in: Modern pathology 2021-09, Vol.34 (9), p.1763-1779
• Main Authors: Acosta, Andres M., Sholl, Lynette M., Dickson, Brendan C., McKenney, Jesse K., Gordetsky, Jennifer B., Pins, Michael R., Marino-Enriquez, Adrian, Dong, Fei, Dubuc, Adrian M., Cin, Paola Dal, Fletcher, Christopher D.M.
• Format: Article
• Language: English
• Subjects: 45/23; 45/91; 692/420/755; 692/699/2768/589/466; Adolescent; Adult; Aged; Copy number; Deoxyribonucleic acid; DNA; DNA sequencing; Growth patterns; Humans; Laboratory Medicine; Male; Medicine; Medicine & Public Health; Mesenchyme; Middle Aged; Neoplasia; Oncogene Fusion; p53 Protein; Pathology; Prostate; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Reclassification; Ribonucleic acid; RNA; Soft Tissue Neoplasms - genetics; Soft Tissue Neoplasms - pathology; Soft tissue sarcoma; Stat6 protein; Tumors; Uterus; Young Adult
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/s41379-021-00818-6

Tumors of purported specialized prostatic stromal origin comprise prostatic stromal sarcomas (PSS) and stromal tumors of uncertain malignant potential (STUMP). Prior studies have described their clinicopathologic characteristics, but the molecular features remain incompletely understood. Moreover, these neoplasms are morphologically heterogeneous and the lack of specific adjunctive markers of prostatic stromal lineage make precise definition more difficult, leading some to question whether they represent a specific tumor type. In this study, we used next-generation DNA and RNA sequencing to profile 25 primary prostatic mesenchymal neoplasms of possible specialized prostatic stromal origin, including cases originally diagnosed as PSS (11) and STUMP (14). Morphologically, the series comprised 20 cases with solid architecture (11 PSS and 9 STUMP) and 5 cases with phyllodes-like growth pattern (all STUMP). Combined DNA and RNA sequencing results demonstrated that 19/22 (86%) cases that underwent successful sequencing (either DNA or RNA) harbored pathogenic somatic variants. Except for TP53 alterations (6 cases), ATRX mutations (2 cases), and a few copy number variants (−13q, −14q, −16q and +8/8p), the findings were largely nonrecurrent. Eight gene rearrangements were found, and 4 (NAB2-STAT6, JAZF1-SUZ12, TPM3-NTRK1 and BCOR-MAML3) were useful for reclassification of the cases as specific entities. The present study shows that mesenchymal neoplasms of the prostate are morphologically and molecularly heterogeneous and include neoplasms that harbor genetic aberrations seen in specific mesenchymal tumors arising in other anatomic sites, including soft tissue and the uterus. These data suggest that tumors of purported specialized prostatic stromal origin may perhaps not represent a single diagnostic entity or specific disease group and that alternative diagnoses should be carefully considered.