Content

The prostate is a retroperitoneal organ around the neck of the bladder and the urethra, without a distinct capsule, about 20 g, 4 x 3 x 2 cm in young men. Zones - Peripheral zone (about 70 percent of the volume): loosely arranged stroma; site of more than 80 percent of prostate cancers. - Central zone (about 25 percent): surrounds the ejaculatory ducts; about 5 percent of cancers. - Transition zone (about 5 percent, expanding after age 50): surrounds the proximal urethra; site of nodular hyperplasia and about 10 percent of cancers. - Periurethral zone. The seminal vesicles lie behind; Denonvilliers fascia separates the prostate from the rectum. Histology: glands with two cell layers: secretory columnar cells inside and a layer of basal cells (stem cells) outside, embedded in a fibromuscular stroma. The presence of basal cells indicates a benign gland; their absence is a key feature of adenocarcinoma.

Acute bacterial prostatitis: usually from organisms that cause urinary tract infection (E. coli), reaching the prostate by reflux of infected urine; fever, chills, dysuria and a tender boggy prostate on rectal examination (avoid massage); neutrophils in the glands. Chronic bacterial prostatitis: recurrent urinary infections. Chronic prostatitis/chronic pelvic pain syndrome (non-bacterial) is common and its cause is uncertain. Granulomatous prostatitis can follow BCG therapy or infections.

Very common in men over 50 (about 90 percent at age 80). Mechanism: androgens (dihydrotestosterone, made from testosterone by 5-alpha reductase) and stromal-epithelial interaction. Morphology: nodules of hyperplastic glands (often cystically dilated) and fibromuscular stroma in the transition zone, compressing the urethra. Clinical: lower urinary tract symptoms (hesitancy, weak stream, nocturia, incomplete emptying), urinary retention, infection, bladder hypertrophy and hydronephrosis. BPH is not a precursor of cancer. Treatment: alpha-blockers, 5-alpha reductase inhibitors, and surgery (transurethral resection).

Epidemiology: the commonest cancer in men; risk increases with age, family history, race and BRCA mutations. Precursor: high-grade prostatic intraepithelial neoplasia (PIN). Morphology: small crowded glands infiltrating the stroma, single layer of cells without basal cells, prominent nucleoli, perineural invasion. Diagnostic tests: PSA, digital rectal examination, MRI and biopsy. Immunohistochemistry: loss of basal cell markers (p63, high molecular weight keratin), positive AMACR. Grading: Gleason score (sum of the two most common architectural patterns, each from 3 to 5) is converted to ISUP grade groups 1-5: grade group 1 (score 6), 2 (3+4=7), 3 (4+3=7), 4 (score 8), 5 (scores 9-10). Prognosis depends on grade group, stage and PSA. Metastases go to pelvic lymph nodes and bone (osteoblastic lesions).

1. In which zone do most prostate cancers arise and in which zone does BPH occur? 2. What distinguishes benign glands from adenocarcinoma? 3. Which hormone drives BPH? 4. How is a Gleason score obtained and what is ISUP grade group 2?

1. Cancer: peripheral zone. BPH: transition zone. 2. Basal cells are present in benign glands and absent in adenocarcinoma. 3. Dihydrotestosterone (from testosterone by 5-alpha reductase). 4. The sum of the two most common patterns (3-5 each); grade group 2 is Gleason 3+4=7.

Bladder cancer is more common in men (about 3:1) with a peak at 60-70 years. Risk factors: cigarette smoking (most important), occupational aromatic amines (dye and rubber industries), chronic irritation (schistosomiasis: squamous cell carcinoma; long-term catheters), drugs (cyclophosphamide, pioglitazone), pelvic radiotherapy, and genetics (FGFR3 mutations in low-grade tumours, TP53 in high-grade). More than 95 percent are epithelial and about 90 percent of these are urothelial carcinomas; others are squamous cell carcinoma, adenocarcinoma and small cell carcinoma. Tumours are often multifocal. Presentation: painless haematuria. Diagnosis: cystoscopy with transurethral resection (TURBT), urine cytology, imaging.

Non-invasive papillary lesions (graded by biological behaviour): - Papilloma: small, single, stalked, normal-looking urothelium; rare recurrence. - Inverted papilloma: benign, cords of bland urothelium in the lamina propria. - Papillary urothelial neoplasm of low malignant potential (PUNLMP): thicker urothelium, rare progression. - Low-grade papillary carcinoma: orderly architecture, mild atypia; may recur and rarely invade. - High-grade papillary carcinoma: disorder, pleomorphic hyperchromatic nuclei, mitoses, high risk of progression. Carcinoma in situ (flat, high-grade, non-invasive): full-thickness atypia, dyscohesive cells; high risk of invasive disease; treated with intravesical BCG.

Invasive carcinoma penetrates the lamina propria (T1) and the muscularis propria (T2 and beyond), then perivesical fat (T3) and adjacent organs (T4). Histological variants: squamous, glandular, micropapillary, nested, sarcomatoid, plasmacytoid. Non-muscle-invasive disease (Ta, T1, Tis) is treated with TURBT and intravesical BCG or chemotherapy with frequent cystoscopic follow-up because of recurrence; muscle-invasive disease needs radical cystectomy (with neoadjuvant chemotherapy) or bladder-preserving chemoradiation, and metastatic disease systemic therapy including immunotherapy.

1. Name the main risk factors for bladder cancer. 2. List the non-invasive papillary lesions in order of increasing risk. 3. What is the treatment of carcinoma in situ? 4. What determines treatment of invasive bladder cancer?

1. Smoking, aromatic amines, schistosomiasis and chronic irritation, cyclophosphamide, pelvic radiation. 2. Papilloma, PUNLMP, low-grade papillary carcinoma, high-grade papillary carcinoma. 3. Intravesical BCG after TURBT. 4. Invasion of the muscularis propria: muscle-invasive disease needs cystectomy or chemoradiation.