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

Learning Objectives

Classify prostatitis into its four clinical categories and describe the distinct pathogenesis, causative organisms, pathology, and clinical features of each
Explain the hormonal basis of BPH, focusing on the role of DHT and 5α-reductase in the transition zone
Describe the nodular hyperplasia morphology of BPH — glandular versus stromal — and correlate with lower urinary tract symptoms (LUTS)
Enumerate the urological complications of BPH: acute urinary retention, hydronephrosis, UTI, and chronic kidney disease
Interpret PSA in the context of BPH versus carcinoma, recognising the limits of PSA specificity
Outline medical management (α-blockers, 5α-reductase inhibitors) and surgical management (TURP) of BPH
Describe the peripheral zone origin of prostatic adenocarcinoma and explain its androgen-dependent pathogenesis, including the TMPRSS2-ETS fusion
Apply the Gleason grading system and ISUP grade groups to predict behaviour and guide treatment
Describe the gross and microscopic features of prostatic adenocarcinoma — small crowded glands, prominent nucleoli, absent basal layer, perineural invasion
Explain the routes of spread of prostate cancer, with emphasis on osteoblastic bone metastases
Outline PSA screening, staging, and the principles of androgen deprivation therapy

INSTRUCTIONS

Prostate disease is among the most common cause of morbidity in aging men worldwide — BPH affects more than half of men over 60, and prostate cancer is the second most common cancer in men globally. In India, an ageing population and rising screening awareness are pushing these diseases into the clinical spotlight. This module builds your mechanistic framework — from DHT signalling in the transition zone to Gleason grade groups in the peripheral zone — so that you can confidently interpret a PSA report, describe a biopsy finding, and counsel a patient on treatment choices. Year-1 foundations you will use here: anatomy of the prostate zones (McNeal), androgen physiology (testosterone → DHT via 5α-reductase), and basic concepts of tumour grading.

References

Robbins & Cotran Pathologic Basis of Disease, 10th ed., Ch. 21 (Male Genital System) (textbook)
Harsh Mohan — Textbook of Pathology, 8th ed., Ch. 22 (Male Reproductive System) (textbook)
Underwood's Pathology, 7th ed., Ch. 19 (Urinary and Male Genital Systems) (textbook)

Version 2.0 | NMC CBUC 2024

CLINICAL SCENARIO

A 68-year-old retired schoolteacher visits his GP with a six-month history of getting up three times every night to pass urine — small amounts each time — followed by a weak, hesitant stream and a persistent feeling that his bladder never fully empties. His PSA is 5.2 ng/mL. His GP performs a digital rectal examination and feels a smooth, symmetrically enlarged, rubbery prostate. He is reassured: 'It's probably just BPH.'

Six months later he returns. He has had two urinary tract infections. His PSA is now 8.7 ng/mL. A transrectal ultrasound-guided biopsy is performed. The histology report reads: Gleason 4+3=7, ISUP Grade Group 3, perineural invasion present, two of twelve cores positive, right peripheral zone.

Same gland, same patient, two completely different diseases — occurring simultaneously. The prostate is unique in that it harbours three major pathological processes — prostatitis, BPH, and carcinoma — that can mimic, mask, or coexist with each other. Getting them right is one of the most clinically impactful things you will learn in Pathology this year.

WHY THIS MATTERS

PA28.3 (BPH) is a guaranteed long-answer or structured question in university exams; it is also the number-one urological presentation in general medicine wards.
PA28.4 (carcinoma) is a high-yield integrated question crossing Pathology, Surgery, and Oncology; PSA interpretation and Gleason grading appear repeatedly in NBE/NExT papers.
PA28.5 (prostatitis) is shorter but tested as a short note and in differential-diagnosis MCQs; chronic pelvic pain syndrome is one of the most under-recognised clinical entities.
Clinico-pathological pearls: BPH → central zone (transition zone), never premalignant; carcinoma → peripheral zone, androgen-dependent, osteoblastic metastases to spine/pelvis.
Year-1 bridge: testosterone → DHT (5α-reductase, Type 2 in prostate); McNeal zones of the prostate (transition, central, peripheral).

RECALL

Before proceeding, briefly recall:
1. McNeal zones of the prostate — which zone surrounds the urethra (transition zone), which zone is palpated on DRE (peripheral zone), and roughly what percentage of the normal gland each occupies.
2. Testosterone → DHT conversion — which enzyme catalyses this, where is it expressed in the prostate, and what is DHT's role in prostatic growth?
3. PSA (prostate-specific antigen) — is it specific for cancer? What is the normal range? What else can raise it?
4. Basic tumour grading concepts — what does it mean to grade a tumour, and why does grade predict prognosis better than size alone in adenocarcinomas?

If any of these feel uncertain, pause and revisit your Year-1 Anatomy and Physiology notes — this module builds directly on all four concepts.

Normal Prostate Anatomy: The Zone Framework

Understanding prostate pathology requires the McNeal zonal anatomy, because each disease preferentially targets a specific zone:

Zone	Location	% of Gland	Disease
Transition zone	Periurethral, flanks proximal urethra	~5–10% (normal)	BPH — can expand to 90% of gland
Central zone	Surrounds ejaculatory ducts, base	~20–25%	Rarely involved in disease
Peripheral zone	Posterior and posterolateral, palpable on DRE	~70–75%	Carcinoma (~70%); Prostatitis
Anterior fibromuscular stroma	Anterior surface	—	Smooth muscle, no glands

A three-panel medical diagram showing sagittal and axial prostate anatomy with McNeal zones and clinical correlations for BPH and carcinoma. — **Panel A:** Midsagittal prostate showing bladder neck, prostatic urethra, ejaculatory ducts, rectum, transition zone — BPH, central zone, peripheral zone — carcinoma, and anterior fibromuscular stroma.. **Panel B:** Axial cross-section showing anterior fibromuscular stroma, periurethral transition zone, central zone around ejaculatory ducts, posterior peripheral zone, prostatic urethra, and orientation markers.. **Panel C:** Clinical correlation inset showing BPH expanding inward to compress the urethra causing LUTS, and peripheral-zone carcinoma as a posterior nodule palpable on DRE; includes note that BPH does not predispose to carcinoma..

Clinical correlation: BPH expands inward and compresses the urethra (hence LUTS); carcinoma arises posteriorly and is palpable on DRE as a hard nodule before it becomes symptomatic. This anatomical separation explains why BPH does not predispose to carcinoma — they are independent diseases arising in different zones with different molecular mechanisms.

Prostatitis: Classification and Overview

Prostatitis encompasses four clinical syndromes classified by the National Institutes of Health (NIH) into Categories I–IV:

NIH Category	Name	WBC in EPS	Culture	Key Feature
I	Acute bacterial prostatitis	+++	Positive	Systemic sepsis possible
II	Chronic bacterial prostatitis	+	Positive	Recurrent UTI, same organism
III	Chronic pelvic pain syndrome (CPPS)	IIIa: +; IIIb: −	Negative	Commonest form (~90–95%)
IV	Asymptomatic inflammatory prostatitis	+	Variable	Incidental biopsy finding

EPS = expressed prostatic secretions

The majority of clinical prostatitis (90–95%) is Category III (CPPS), which has no proven bacterial cause and is thought to involve neurogenic inflammation, pelvic floor dysfunction, and immune dysregulation.

Medium-power histology diagram of acute bacterial prostatitis showing prostatic ducts and acini filled with neutrophils, with stromal oedema and hyperaemic vessels. — **Panel A:** Medium-power H&E-style histology showing prostatic ducts and acini, ductal lumen, acute inflammatory infiltrate of neutrophils, stromal oedema, and hyperaemia.. **Panel B:** Simplified enlarged duct/acinar unit highlighting neutrophils filling the lumen, oedematous stroma, and congested hyperaemic blood vessel with a color-coded legend..

Acute and Chronic Bacterial Prostatitis

Acute Bacterial Prostatitis (NIH Category I)

Aetiology: Most commonly caused by gram-negative enteric organisms — Escherichia coli (most frequent), Klebsiella, Proteus, Pseudomonas. Organisms reach the prostate via ascending urethral infection (most common), reflux of infected urine, haematogenous spread, or iatrogenic (post-TRUS biopsy).

Pathology: Acute suppurative inflammation — ducts and acini packed with neutrophils, stromal oedema, hyperaemia. Microabscesses may form; coalescence produces a prostatic abscess (requires surgical drainage).

Clinical features: Sudden onset fever, chills, rigors; severe perineal/low back pain; exquisitely tender, boggy prostate on DRE (do NOT vigorously massage — risk of bacteraemia); dysuria, frequency, acute urinary retention. PSA is markedly elevated (can exceed 100 ng/mL — do not order or interpret PSA in acute prostatitis).

Treatment: IV fluoroquinolones or aminoglycosides; total duration 4–6 weeks (long course because the blood-prostate barrier limits antibiotic penetration in chronic disease).

Chronic Bacterial Prostatitis (NIH Category II)

Aetiology: Same organisms as acute; persistence due to bacterial biofilm formation in prostatic calculi or poor antibiotic penetration.

Pathology: Lymphocytes, plasma cells, macrophages, and occasional neutrophils within and around acini and in periductal stroma. Chronic inflammation → fibrosis.

Clinical features: The hallmark is recurrent UTI with the same organism in an otherwise well man; perineal discomfort, post-ejaculatory pain; DRE may be mildly tender or normal; PSA mildly elevated.

Diagnosis: Meares-Stamey 4-glass test (or simpler 2-glass pre/post-massage test) — bacterial counts significantly higher in expressed prostatic secretions (EPS) than in the initial urethral voided urine localises infection to the prostate.