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PA28.3-5 | Prostate: BPH, Carcinoma & Prostatitis — SDL Guide (Part 2)

Chronic Pelvic Pain Syndrome and Granulomatous Prostatitis

Chronic Pelvic Pain Syndrome (CPPS — NIH Category III)

The commonest and most diagnostically challenging form of prostatitis. By definition, cultures are negative.

Pathogenesis: Multifactorial — proposed mechanisms include sterile autoimmune inflammation (molecular mimicry with bacterial antigens), pelvic floor muscle spasm and myofascial trigger points, neurogenic inflammation (substance P, mast cell activation), and psychosocial amplification.

Subtypes:
• IIIa (inflammatory CPPS): WBCs >10/hpf in EPS or post-massage urine — histology shows lymphocytic infiltrate; likely represents residual immune activation.
• IIIb (non-inflammatory CPPS): No excess WBCs — pelvic floor dysfunction predominates.

Clinical features: Pelvic pain for ≥3 of the past 6 months; variable dysuria, frequency; ejaculatory pain; normal or near-normal PSA; DRE often normal or mildly tender. Diagnosis is one of exclusion.

Treatment: Alpha-blockers (relax bladder neck and prostate smooth muscle), NSAIDs, 5α-reductase inhibitors, pelvic floor physiotherapy, psychosocial support.

Granulomatous Prostatitis

Types and causes:
1. Infectious granulomatous prostatitis — Mycobacterium tuberculosis (most important in India; part of urogenital TB); also Histoplasma, Blastomyces in endemic areas.
2. Non-specific granulomatous prostatitis — most common type; thought to be a reaction to extravasated prostatic secretions; caseous-free epithelioid granulomas mixed with lipid-laden macrophages.
3. BCG-induced granulomatous prostatitis — iatrogenic, after intravesical BCG therapy for bladder cancer; non-caseating granulomas throughout prostate.

Pathology: Epithelioid macrophages ± Langhans giant cells, lymphocytes; in TB — caseating granulomas with Ziehl-Neelsen-positive bacilli.

Clinical trap: Granulomatous prostatitis can produce a hard, irregular prostate on DRE and elevated PSA — mimicking carcinoma. Biopsy is diagnostic.

Medical illustration of granulomatous prostatitis showing an epithelioid macrophage granuloma with Langhans giant cells, lymphocytes, prostatic acini, and a PSA clinical correlation. — **Panel A:** Medium-power H&E view showing epithelioid macrophage granuloma, Langhans giant cell, surrounding lymphocytes, prostatic stroma, and prostatic acinus.. **Panel B:** High-power detail of Langhans giant cell with peripheral horseshoe-arranged nuclei, surrounded by epithelioid macrophages and lymphocytes.. **Panel C:** Clinical pearl schematic showing disrupted prostatic epithelium releasing PSA into circulation, with reminders about prostatitis, recent manipulation, and delayed PSA testing..

CLINICAL PEARL

PSA is prostate-specific, NOT cancer-specific. Any disruption of the prostate epithelial architecture releases PSA into the circulation — acute prostatitis can push PSA to >100 ng/mL, BPH causes a moderate steady rise (roughly 0.3 ng/mL per gram of tissue), and prostate biopsy causes a sharp spike lasting up to 3 weeks. Always ask: 'When was the DRE? Any recent biopsy? Any UTI or prostatitis?' before interpreting a PSA result. The clinical rule: never order PSA during active prostatitis — wait at least 4–6 weeks after treatment before testing.

Benign Prostatic Hyperplasia: Hormonal Pathogenesis

Benign prostatic hyperplasia (BPH) is a non-neoplastic, non-inflammatory enlargement of the prostate due to nodular hyperplasia of glandular epithelium and fibromuscular stroma in the transition zone.

Epidemiology: Virtually universal with advancing age — histological BPH in ~20% at age 40, ~70% by age 60, >90% by age 80. Symptomatic disease affects ~50% of men over 60. Requires: (1) functioning testes (eunuchs do not develop BPH) and (2) advancing age.

Hormonal pathogenesis — the DHT hypothesis:

Testosterone (from Leydig cells) enters prostatic stromal cells and is converted to dihydrotestosterone (DHT) by 5α-reductase type 2 (expressed in prostatic stroma).
DHT binds the androgen receptor with ~5× greater affinity than testosterone and dissociates more slowly → more potent and sustained nuclear signal.
DHT activates growth factor signalling (IGF-1, FGF-7/KGF, EGF) → promotes epithelial and stromal cell proliferation AND inhibits apoptosis → net tissue accumulation.
Disequilibrium between proliferation and apoptosis, rather than de-novo oncogenesis, is the mechanism → BPH is hyperplasia, not neoplasia.

Diagram showing testosterone conversion to DHT in a prostatic stromal cell, androgen receptor nuclear activation of growth factors, and epithelial plus stromal proliferation in BPH. — **Panel A:** Prostatic stromal cell, cell membrane, cytoplasm, nucleus, testosterone entry, 5α-reductase type 2, conversion of testosterone to DHT, cytoplasmic androgen receptor, DHT-androgen receptor complex, clinical evidence inset including 5α-reductase type 2 deficiency, finasteride, and castration.. **Panel B:** Nuclear pore, nuclear translocation of DHT-androgen receptor complex, androgen receptor, androgen response elements on DNA, transcriptional activation of growth factor genes.. **Panel C:** FGF-7, IGF-1, paracrine signaling arrows, prostatic epithelial gland, proliferating epithelial cells, proliferating stromal cells, nodular benign prostatic hyperplasia..

Supporting evidence for DHT hypothesis:
• Men with 5α-reductase type 2 deficiency (pseudohermaphroditism) have absent prostatic tissue and never develop BPH.
• Finasteride (5α-reductase type 2 inhibitor) reduces prostate volume by 20–30% and relieves LUTS — direct therapeutic proof of the DHT mechanism.
• Castration causes prostate involution.

BPH: Morphology — Gross and Microscopic

Gross appearance:
The enlarged prostate in BPH typically weighs 20–100+ grams (normal ~20 g). The transition zone expands concentrically, producing a pale grey, firm, multinodular mass that compresses the peripheral zone and distorts the urethra into a narrow slit or crescentic channel. The cut surface shows well-defined nodules with a honeycomb-like appearance due to cystically dilated glands oozing milky fluid. The outer (surgical) capsule is formed by compressed peripheral zone tissue — important for TURP (the surgeon resects within this capsule).

Microscopic components — two main types of nodules:

1. Glandular (epithelial) nodules — composed of hyperplastic, back-to-back glands lined by two layers:
• Inner layer: tall columnar secretory cells (pale cytoplasm) often forming papillary projections into the lumen.
• Outer layer: flattened basal cells (small, dark nuclei) — this intact basal cell layer is the key microscopic feature that distinguishes BPH from carcinoma.
• Lumina contain corpora amylacea (pink, laminated concentric structures from condensed secretions — normal finding, increases with age).

Stromal nodules — predominantly composed of smooth muscle and fibrous tissue with sparse glands; feel firmer and are less responsive to 5α-reductase inhibitors (which primarily shrink glandular tissue).

Three-panel histology diagram of benign prostatic hyperplasia showing crowded papillary glands, intact basal layer, corpora amylacea, stromal smooth muscle, and key differences from carcinoma. — **Panel A:** Medium-power BPH showing back-to-back hyperplastic glands, papillary infoldings, luminal corpora amylacea, and stromal smooth muscle.. **Panel B:** High-power gland lining showing columnar secretory cells, intact basal layer, papillary projection, gland lumen, and corpora amylacea.. **Panel C:** Microscopic differential between BPH and carcinoma: gland architecture, basal cell layer, nuclear features, growth pattern, and perineural invasion..

Key microscopic differential (BPH vs Carcinoma):

Feature	BPH	Carcinoma
Gland architecture	Large, papillary, back-to-back	Small, crowded, infiltrative
Basal cell layer	Present (two cell layers)	Absent
Nuclei	Bland, uniform	Enlarged, prominent nucleoli
Pattern	Nodular, zonal	Haphazard infiltration
Perineural invasion	Absent	Present