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Male Genitourinary Pathology

Male Genitourinary Pathology. Prostate Benign prostatic hyperplasia Carcinoma of the prostate Testis Germ cell tumours Penis Condyloma accuminatum Carcinoma. EG Feb 3rd 2009. Prostate. Surrounds bladder neck and urethra Normal weight = 20gm

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Male Genitourinary Pathology

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  1. Male Genitourinary Pathology • Prostate • Benign prostatic hyperplasia • Carcinoma of the prostate • Testis • Germ cell tumours • Penis • Condyloma accuminatum • Carcinoma EG Feb 3rd 2009

  2. Prostate • Surrounds bladder neck and urethra • Normal weight = 20gm • Enlarged prostate palpable on rectal examination • CZ = Central zone • PZ = Peripheral zone

  3. Benign prostatic hyperplasia • Nodules around prostatic urethra • 70% men over 60 yrs • Growth requires dihydrotestosterone (Leydig cells), its metabolite 3-alpha-androstanediol & estrogens, which increase DHT receptor expression in prostatic tissue • DHT converted from testosterone by 5-alpha-reductase • BPH not precancerous • Clinical: • (None in most) • Obstruction - compression of urethra -> frequency, nocturia, etc • Dysuria because of UTI; acute retention

  4. Benign prostatic hyperplasia • Prostate = 40 - 200 gm • Nodules vary in size, colour and texture • Nodules consist of glands and / or fibromuscular stroma NODULE

  5. Benign prostatic hyperplasia • Treatment • None • Transurethral resection (TURP) • (Open prostatectomy for very enlarged prostates) • Medical treatment • 5 alpha-reductase inhibitor, or • Alpha adrenergic blockade

  6. Carcinoma of the prostate • Commonest cancer in males • Second leading cause of cancer deaths in men >50 • Incidence increases with age 70 >60 >50 yrs • Afro-Americans at earlier age >US whites >Asians • Endocrine, genetic & environmental factors • Androgens • Susceptibility loci on chromosomes 1 and 10 (near PTEN) • Incidence in Scandinavians > Japanese • Animal fat in diet? • Prostatic Intraepithelial Neoplasia (PIN) • in situ precursor of prostatic carcinoma

  7. Clinical presentation • Latent carcinoma - asymptomatic. Screening - PSA, PR +/- Transrectal Ultrasound, prostatic biopsies • PSA is a serine protease secreted by prostatic acinar cells, that liquifies the ejaculate. A single serum PSA test is not fully sensitive or specific. • Advanced carcinoma- obstruction or symptoms due to local extension or metastases e.g. bone pain.

  8. PSA in prostatic acini

  9. Preferential sites for prostatic lesions • Transverse section • BPH around prostatic urethra * • 70% of carcinomas are peripheral, and often posterior *

  10. Pathology • Peripheral in 70%, mostly posterior, palpable on PR • Often not easily recognised on gross examination • Invasion outside capsule; seminal vesicles, bladder • Lymphatics; bloodstream, osteoblastic mets late • Micro: Adenocarcinoma (different patterns = diff grades) • Grading: Gleason grade 1 ( virtually normal glands -> Gleason grade 5 (poorly differentiated). • Gleason score: add two predominant grades • Score 2-6 predicts a good prognosis; 8-10 a poor prognosis • Immunostaining: PSA+, loss of HMW keratin stain

  11. Prostatic carcinoma - microscopic Gleason G 5 Gleason Grade 3

  12. Capsular & perineural invasion (L) and bone metastasis (R) Nerve

  13. Prostatic carcinoma stage, prognosis • Staging: clinical, PR, U/S, CT/MRI, bone scan, pathological stage in prostatectomy • T1, T2 - both treated by radical prostatectomy or radiotherapy • T3 locally invasive - radiotherapy • T4 metastatic - hormonal therapy • Prognosis: • Slow growing cancers • Stage and Grade (Gleason score) • 90% 10 yr survival for T1, T2 • 10-40% for T4

  14. Testis • Cryptorchidism (“hidden testis) • testis in lower abdomen to inguinal canal • mostly unilateral • Infertility; risk of malignancy 4 X gen population • Germ cell tumours • Commonest malignant tumour in males 15-34 yrs • Pathogenesis: Cryptorchidism; testicular dysgenesis • (Whites, familial). Isochromosome 12p • A. Seminoma • B. Non-seminomatous germ cell tumours

  15. Seminoma • Peak incidence 30-40 yrs • Painless enlargement of testis • Grey-white lobulated tumour • Clear cytoplasm, prominent nucleoli • Lymphocytes in stroma • 70% stage 1, spreads to iliac, paraaortic nodes • 90% cure for patients with stage 1 seminoma

  16. Seminoma • Circumscribed grey white tumour • No haemorrhage

  17. Seminoma - microscopic • Seminoma cells have nucleoli and clear cytoplasm • 10% have HCG+ syncytiotrophoblast giant cells* *

  18. Non-seminomatous germ cell tumours • Peak incidence 20-30 yrs • Painless, small tumours; 60% metastases at presentation • 50% of NSGCT contain mixed subtypes • Embryonal carcinoma, yolk sac ca, choriocarcinoma • All of the above are “primitive carcinomas” • Necrosis, haemorrhage; vascular invasion • Alpha-FP and beta-HCG useful for diagnosis; also as tumour markers in serum for monitoring recurrence • NSGCT microscopic appearance may be altered after treatment e.g. embryonal ca may transform to teratoma follow chemotherapy • 80% remissions on chemotherapy

  19. Non-seminomatous GCT • Embryonal carcinoma • Alpha-fetoprotein in embryonal ca

  20. Combined germ cell tumour • Combined germ cell tumour of testis - seminoma and embryonal carcinoma • Venous invasion by NSGCT component Vein wall

  21. Non-seminomatous germ cell tumours - micro • Choriocarcinoma • beta-HCG in synctiotrophoblast giant cells

  22. NSGCT - Yolk sac carcinoma • Schiller-Duval bodies like primitive glomeruli • AFP +

  23. Mature Teratoma • Differentiation of tumour cells into structures resembling mature adult tissues - bronchi, skin, cartilage, glia etc • “Abortive organs” • Often combinedwith embryonal ca etc • (Immature teratoma)

  24. Intrtubular germ cell neoplasia • Large seminoma-like cells, clear cytoplasm • In cryptorchid testes • Adjacent to majority of germ cell tumours • Precursor lesion of germ cell tumours

  25. Penis • Condyloma accuminatum • Irregular warty lesions on muco-cutaneous surfaces. Also anus, vulva • Sexually transmitted: HPV 6 and 11. • Benign. • Verrucous carcinoma • Large warty tumour; also HPV 6 and 11 • Locally invasive carcinoma - does not metastasise

  26. Verrucous carcinoma *

  27. Carcinoma of Penis • Uncommon in West, 40-70 yrs; but 10% of all cancers in Africa • Hygiene; phimosis; HPV 16, 18. Circumcision protective if as babies or as children, but not as adults; PUVA for psoriasis - risk X 280 • Carcinoma in situ (Bowen’s disease) a precursor • Ulcerated or exophytic squamous cell carcinoma; lymphadenopathy • Slow growing, 45% have mets in inguinal nodes (stage 3) at Dx • Distant metastases are uncommon • 5 yr survival 25-70% *

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