Association of tertiary lymphoid structures and benign lymphoepithelial lesions in NIH-category IV prostatitis: pathophysiological correlations

Dorian Dikov¹, Maria Koleva^2,*, Kiril Simitchiev³, Anelia Bivolarska⁴, Albena Fakirova⁵, Victoria Sarafian^6,7
1 Department of Pathology, Jossigny Hospital, Jossigny, 75000, France
2 Department of General and Clinical Pathology, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, 4000, Bulgaria
3 Department of Analytical Chemistry and Computer Chemistry, University of Plovdiv “Paisii Hilendarski”, Plovdiv, 4000, Bulgaria
4 Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd., Plovdiv, 4002, Bulgaria
5 Department of Pathology, Military Medical Academy, Sofia, 1606, Bulgaria
6 Department of Medical Biology, Medical University of Plovdiv, Plovdiv, 4000, Bulgaria
7 Technological Center for Emergency Medicine, Plovdiv, 4000, Bulgaria
* Corresponding Author: Maria Koleva. Email: email
(This article belongs to the Special Issue: Prostate Cancer: Biomarkers, Diagnosis and Treatment)

Canadian Journal of Urology https://doi.org/10.32604/cju.2025.068575

Received 01 June 2025; Accepted 12 November 2025; Published online 08 December 2025

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Abstract

Background: Chronic inflammation is closely associated with the most common and socially significant prostate conditions, including benign prostatic hyperplasia (BPH), prostate cancer (PCa), and prostatitis syndromes. NIH-category IV prostatitis (histologic prostatitis, HP) is defined as asymptomatic chronic inflammation of the prostate. The presence of lymphoid follicles, referred to as tertiary lymphoid structures (TLSs), along with benign lympho-epithelial lesions (BLELs), is among the key histological indicators of immune inflammation and can be assessed relatively easily. This study aimed to quantitatively assess TLSs and BLELs, as well as their relationship with the severity of HP. Methods: We investigated TLSs and BLELs in 110 prostatic specimens, including inflammatory and normal tissues, within the context of common prostate pathologies such as BPH and PCa. HP was graded as low-grade (LG) or high-grade (HG) based on the severity of inflammation. Results: TLSs were observed in 51 out of 110 cases (46.4%), while BLELs were identified in 78 cases (70.44%). Both TLSs and BLELs co-occurred in 45 cases (40.9%). Statistical analysis revealed a significant correlation between the presence of TLSs, BLELs (individually or combined), and HG-HP (p < 0.001). Conclusions: This study is the first to quantitatively evaluate the immunopathologic patterns in the inflamed human prostate by analyzing the presence and co-occurrence of TLSs and BLELs. Their formation, likely triggered by antigenic stimuli and external factors, indicates a chronic inflammatory microenvironment. The strong association between TLSs, BLELs, and HG-HP underscores their potential role in HP aggressiveness. These findings suggest that TLSs and BLELs may be crucial contributors to the pathophysiology and morphogenesis of NIH-category IV prostatitis. Furthermore, TLS/BLEL formation may represent a hallmark of tissue autoimmunity, reflecting the immune or autoimmune phase of this prostatitis subtype.