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 = 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) Germ cell tumours
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 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 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 combined with 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 Verrucous carcinoma
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, 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% *