Prostate & Testicular Pathology
Pathology · Neoplasia · lean revision notes
Prostate & Testicular Pathology
Male genital tract pathology is a compact but heavily-tested slice of NEET PG uro-oncology. The recurring high-yield axes are zonal anatomy of the prostate, the BPH-versus-carcinoma contrast, Gleason grading, the osteoblastic bone metastasis of prostate cancer, and the seminoma-versus-NSGCT marker dichotomy. Master the tables here and most one-liners answer themselves.
Prostate: Zonal Anatomy (the key to two diseases)
The prostate is divided into zones, and where a lesion arises tells you what it is. This single concept drives multiple MCQs.
| Zone | Proportion | Disease arising here |
|---|---|---|
| Peripheral zone | ~70% of glandular tissue | Adenocarcinoma (most cancers; palpable on DRE) |
| Central zone | ~25% | Relatively resistant to both |
| Transitional/periurethral zone | ~5% | Benign Prostatic Hyperplasia (BPH) |
High-yield: BPH arises in the transitional/periurethral zone (causes obstruction because it surrounds the urethra). Prostate carcinoma arises in the peripheral zone (posterior — hence palpable on digital rectal examination, but causes obstruction late).
Mnemonic: "BPH is in the Back-up-around-urethra (transitional); Cancer is in the Circumference (peripheral)." A simpler aide: Cancer hugs the rectum (peripheral/posterior) so DRE detects it.
Benign Prostatic Hyperplasia (BPH)
Definition & Pathogenesis
BPH is nodular hyperplasia of both glandular and stromal elements in the transitional zone. It is not premalignant — BPH does not progress to carcinoma. The driver is dihydrotestosterone (DHT), formed from testosterone by 5-alpha-reductase (type 2) within stromal cells. DHT binds androgen receptors and upregulates growth factors, producing hyperplasia of glands and stroma.
High-yield: BPH is hyperplasia, NOT hypertrophy histologically, and is NOT a precursor of cancer. The hormone responsible is DHT (via 5α-reductase type 2).
Morphology
- Well-circumscribed nodules; enlargement is predominantly of the inner (transitional) zone, compressing the urethra into a slit.
- Microscopy: two cell layers retained (inner luminal/secretory + outer basal layer) — the intact basal cell layer is the single most important feature distinguishing benign glands from carcinoma. Corpora amylacea (laminated proteinaceous concretions) are common in benign glands.
Clinical Features (LUTS)
- Obstructive (voiding): hesitancy, weak stream, intermittency, terminal dribbling, incomplete emptying.
- Irritative (storage): frequency, urgency, nocturia.
- Severity quantified by IPSS (International Prostate Symptom Score).
Complications
Acute urinary retention → recurrent UTI → bladder diverticula/trabeculation → bilateral hydronephrosis → post-renal (obstructive) azotaemia/renal failure; bladder stones; overflow incontinence.
Diagnosis
- DRE: smooth, symmetrically enlarged, rubbery gland.
- PSA may be mildly elevated (large benign glands make more PSA).
- Uroflowmetry, post-void residual volume by USG.
Management — Drug of Choice
- Alpha-1 blockers (tamsulosin, alfuzosin, silodosin) → relax smooth muscle of prostate/bladder neck → rapid symptom relief. First-line for symptoms.
- 5-alpha-reductase inhibitors (finasteride, dutasteride) → shrink the gland, useful for large glands (>40 g); take months to work; also lower PSA by ~50%.
- Surgery: TURP (transurethral resection) is the gold-standard surgical treatment for refractory/complicated BPH.
Stepwise approach: Mild LUTS → watchful waiting + lifestyle → moderate → alpha-blocker ± 5-ARI (if large gland) → refractory/complications (retention, stones, renal impairment) → TURP.
Prostatic Adenocarcinoma
Epidemiology
Most common visceral cancer in men (Western data); incidence rises sharply after age 50. Risk factors: age, ethnicity (highest in Afro-Caribbean men), family history, BRCA2 (aggressive disease).
Origin & Morphology
- Arises in the peripheral zone (posterior) — hence palpable as a hard nodule on DRE.
- Almost all are acinar adenocarcinomas.
- Microscopy: small, crowded glands with loss of the basal cell layer, prominent nucleoli, and amphophilic cytoplasm. The diagnostic hallmark is absence of the basal layer (confirmed by negative basal markers — see below).
High-yield: The basal cell layer is present in benign glands and BPH but ABSENT in carcinoma. Immunostains for basal cells (p63, high-molecular-weight cytokeratin/34βE12) are negative in cancer; AMACR (P504S / racemase) is positive in cancer.
Gleason Grading & Grade Groups
Gleason grading is based purely on architecture (glandular pattern), not nuclear features. Each pattern is scored 1–5 (well to poorly differentiated). The score = (most predominant pattern) + (second most prevalent / highest on biopsy), giving a sum from 2 to 10. Modern practice rarely assigns scores below 6.
| Gleason Score | ISUP Grade Group | Differentiation / Prognosis |
|---|---|---|
| ≤ 6 (3+3) | Group 1 | Well differentiated, best prognosis |
| 7 (3+4) | Group 2 | Favourable intermediate |
| 7 (4+3) | Group 3 | Unfavourable intermediate |
| 8 (4+4 / 3+5 / 5+3) | Group 4 | Poor |
| 9–10 | Group 5 | Worst prognosis |
High-yield: Gleason 7 = 3+4 is better than 4+3 — the first number (primary/predominant pattern) carries more prognostic weight. Higher Gleason → worse outcome.
High-yield: Gleason grading uses architectural pattern only, not cytology/nuclear pleomorphism — a classic distractor.
Spread & Metastasis
- Local: seminal vesicles, bladder base.
- Lymphatic: obturator nodes first.
- Haematogenous → BONE. Prostate cancer characteristically causes OSTEOBLASTIC (sclerotic, dense) bone metastases, especially in the axial skeleton (lumbar spine via Batson's vertebral venous plexus).
High-yield: Prostate cancer = osteoBLASTIC bone mets (raised alkaline phosphatase on bone scan/blood). Contrast: most other cancers (lung, kidney, thyroid, multiple myeloma) are osteolytic. *Memory: Prostate = Plastic = blastic.*
Tumour Markers / Diagnosis
- PSA (prostate-specific antigen): organ-specific, not cancer-specific. Cut-off traditionally >4 ng/mL prompts evaluation.
- PSA velocity (rate of rise), PSA density, free:total PSA ratio (a low free:total ratio favours cancer) refine specificity.
- PSA is the best marker for monitoring treatment response/recurrence.
- Investigation of choice for diagnosis: TRUS-guided needle biopsy (increasingly MRI-targeted/fusion biopsy). MRI (multiparametric) for local staging; bone scan / PSMA-PET for metastatic work-up.
Management
- Localised: radical prostatectomy or radiotherapy; active surveillance for low-risk (Grade Group 1) disease.
- Metastatic (drug of choice concept): Androgen-deprivation therapy (ADT) — the cornerstone, since the tumour is androgen-dependent.
- GnRH agonists (leuprolide/goserelin) — cause an initial testosterone flare (cover with an anti-androgen first).
- GnRH antagonists (degarelix) — no flare.
- Anti-androgens: bicalutamide, enzalutamide; abiraterone (blocks CYP17/androgen synthesis).
- Orchidectomy = surgical castration.
Testicular Tumours — Overview
- 95% are germ cell tumours (GCTs); the rest are sex-cord/stromal (Leydig, Sertoli) and lymphoma.
- Cryptorchidism (undescended testis) is the major risk factor — increases risk in both testes; the most common tumour in a cryptorchid testis is seminoma.
- Most present as a painless, firm testicular mass that does not transilluminate.
High-yield: Investigation of choice = scrotal ultrasound. NEVER do a trans-scrotal biopsy/FNAC (seeds tumour along scrotal lymphatics) — definitive procedure is radical inguinal (high) orchidectomy.
Precursor lesion
Germ Cell Neoplasia In Situ (GCNIS) — formerly intratubular germ cell neoplasia (IGCN/ITGCN) — is the common precursor of nearly all invasive GCTs.
Seminoma vs Non-Seminomatous GCT (NSGCT) — THE table
| Feature | Seminoma | Non-Seminomatous GCT (NSGCT) |
|---|---|---|
| Frequency | Most common testicular tumour (single type) | Group includes embryonal, yolk sac, choriocarcinoma, teratoma |
| Peak age | 30s–40s (later) | 20s (younger) |
| Gross | Homogeneous, bulky, fleshy, grey-white, no necrosis/haemorrhage | Variegated, haemorrhage & necrosis |
| Microscopy | Sheets of uniform cells, clear cytoplasm (glycogen), fibrous septa with lymphocytes ± granulomas; "fried-egg" cells | Pleomorphic, primitive |
| AFP | Normal (never raised) | Raised (yolk sac, embryonal) |
| β-hCG | Normal or mildly ↑ (syncytiotrophoblasts) | Markedly ↑ (choriocarcinoma) |
| PLAP | Positive | Variable |
| Radiosensitivity | Very radiosensitive | Radioresistant |
| Prognosis | Excellent | Worse than seminoma but chemo-responsive |
| Spread | Lymphatic (para-aortic nodes) | Earlier haematogenous |
High-yield: Seminoma NEVER raises AFP. If AFP is elevated, the tumour is NOT a pure seminoma — treat as NSGCT (a yolk sac/embryonal component is present). This is a perennial exam favourite.
High-yield: Seminoma is exquisitely RADIOSENSITIVE (and chemosensitive to platinum). NSGCTs are managed with chemotherapy (BEP — Bleomycin, Etoposide, cisPlatin) ± RPLND.
Marker quick-map (essential)
- AFP → Yolk sac tumour (most common testicular tumour in young children/infants; Schiller-Duval bodies are pathognomonic) and embryonal carcinoma.
- β-hCG → Choriocarcinoma (markedly raised; aggressive, haematogenous, "burnt-out" primary); also raised in some seminomas.
- PLAP → Seminoma.
- LDH → marker of tumour bulk/burden, used for staging/monitoring.
Mnemonic for yolk sac: "Yolk → AFP → infant → Schiller-Duval bodies (glomerulus-like)."
Key individual NSGCTs
- Embryonal carcinoma: aggressive, primitive epithelial cells; ↑AFP and/or ↑hCG.
- Yolk sac tumour: commonest in <3 years; ↑AFP; Schiller-Duval bodies.
- Choriocarcinoma: syncytio- + cytotrophoblast; very high hCG → may cause gynaecomastia/thyrotoxicosis (hCG mimics LH/TSH); spreads early via blood.
- Teratoma: in adults, teratoma is malignant (behaves aggressively); in prepubertal children/infants, mature teratoma is benign.
High-yield: Adult testicular teratoma is malignant; the same histology in an infant is benign — age changes the answer.
Other Testicular Lesions (don't ignore)
| Tumour | Key fact |
|---|---|
| Leydig cell tumour | Sex-cord; produces androgens/oestrogens → precocious puberty (boys) or gynaecomastia; Reinke crystals are pathognomonic; usually benign |
| Sertoli cell tumour | Usually hormonally silent, mostly benign |
| Testicular lymphoma | Most common testicular tumour in men >60 yrs; usually DLBCL; often bilateral; not a GCT |
| Spermatocytic tumour | Older men; excellent prognosis, does NOT metastasise; unrelated to GCNIS |
High-yield: In a man over 60 with a testicular mass, think LYMPHOMA (DLBCL), not GCT. It is the commonest testicular tumour of the elderly and may be bilateral.
Key Differentials
- Testicular mass: GCT vs lymphoma (age!) vs epididymo-orchitis (painful, tender) vs hydrocele (transilluminates) vs varicocele ("bag of worms", left-sided).
- Prostate enlargement: BPH (smooth, symmetric, transitional zone) vs carcinoma (hard nodule, peripheral, ↑PSA, osteoblastic mets) vs prostatitis (tender, fever).
- Raised PSA: carcinoma vs BPH vs prostatitis vs recent DRE/catheterisation/ejaculation (transient).
- Sclerotic bone lesions: prostate cancer vs breast cancer (mixed) vs osteoblastic metastasis differentials.
Recently asked / exam angle
- Zone of origin: BPH = transitional, carcinoma = peripheral — asked repeatedly, often as image/diagram.
- Basal cell layer present in benign, absent in malignant; IHC: AMACR positive, p63/HMWCK negative in cancer.
- Gleason: based on architecture only; 3+4 better than 4+3; ISUP grade groups 1–5.
- Osteoblastic metastasis with raised ALP = prostate cancer (P = blastic).
- Seminoma never raises AFP; raised AFP ⇒ non-seminomatous element.
- Seminoma is radiosensitive; NSGCT treated with BEP chemotherapy.
- Yolk sac tumour → AFP, infants, Schiller-Duval bodies; Reinke crystals → Leydig cell tumour.
- Testicular lymphoma in the elderly (>60), often bilateral DLBCL.
- No trans-scrotal biopsy — radical inguinal orchidectomy; first investigation = USG.
- DHT and 5α-reductase type 2 drive BPH; finasteride halves PSA.
- Adult teratoma malignant; infantile mature teratoma benign.
Rapid revision
- BPH → transitional zone; prostate cancer → peripheral zone (palpable on DRE).
- BPH is hyperplasia driven by DHT (5α-reductase type 2) and is NOT premalignant.
- Intact basal cell layer = benign; loss of basal layer = carcinoma. Cancer: AMACR+, p63/HMWCK−.
- Gleason = architecture only; sum 2–10; 3+4 < 4+3 in aggressiveness; ISUP grade groups 1–5.
- Prostate cancer = osteoblastic mets to axial spine (Batson plexus) with raised ALP.
- PSA is organ- (not cancer-) specific; low free:total ratio favours cancer; best for monitoring.
- Metastatic prostate cancer → androgen-deprivation therapy (GnRH agonist/antagonist, abiraterone, enzalutamide); watch the testosterone flare.
- Cryptorchidism raises tumour risk bilaterally; commonest tumour = seminoma.
- Seminoma: commonest, radiosensitive, PLAP+, AFP never raised, hCG ± mild ↑.
- NSGCT: younger, AFP/hCG raised, treat with BEP chemo; yolk sac → AFP + Schiller-Duval bodies (infant); choriocarcinoma → very high hCG.
- Reinke crystals → Leydig cell tumour; testicular tumour in >60 yrs → lymphoma (DLBCL, often bilateral).
- USG first; radical inguinal orchidectomy for diagnosis/treatment — never trans-scrotal biopsy.