Transcript Male Genitourinary Pathology • Prostate • Testis • Penis

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
• Enlarged prostate
palpable on rectal
examination
• CZ = Central zone
• PZ = Peripheral zone
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
Benign prostatic hyperplasia
NODULE
• Prostate = 40 - 200 gm
• Nodules vary in size,
colour and texture
• Nodules consist of
glands and / or
fibromuscular stroma
Benign prostatic hyperplasia
• Treatment
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None
Transurethral resection (TURP)
(Open prostatectomy for very enlarged prostates)
Medical treatment
• 5 alpha-reductase inhibitor, or
• Alpha adrenergic blockade
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
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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
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.
PSA in prostatic acini
Preferential sites for prostatic lesions
• Transverse section
• BPH around prostatic
urethra *
• 70% of carcinomas are
peripheral, and often
posterior
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Pathology
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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
Prostatic carcinoma - microscopic
Gleason G 5
Gleason Grade 3
Capsular & perineural invasion (L) and
bone metastasis (R)
Nerve
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:
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Slow growing cancers
Stage and Grade (Gleason score)
90% 10 yr survival for T1, T2
10-40% for T4
Testis
• Cryptorchidism (“hidden testis)
– testis in lower abdomen to inguinal canal
– mostly unilateral
– Infertility; risk of malignancy 4 X gen population
• Germ cell tumours
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Commonest malignant tumour in males 15-34 yrs
Pathogenesis: Cryptorchidism; testicular dysgenesis
(Whites, familial). Isochromosome 12p
A. Seminoma
B. Non-seminomatous germ cell tumours
Seminoma
• Peak incidence 30-40 yrs
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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
Seminoma
• Circumscribed grey
white tumour
• No haemorrhage
Seminoma - microscopic
• Seminoma cells have
nucleoli and clear
cytoplasm
• 10% have HCG+
syncytiotrophoblast
giant cells*
*
Non-seminomatous germ cell tumours
• Peak incidence 20-30 yrs
• Painless, small tumours; 60% metastases at presentation
• 50% of NSGCT contain mixed subtypes
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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
Non-seminomatous GCT
• Embryonal carcinoma
• Alpha-fetoprotein in
embryonal ca
Combined germ cell tumour
• Combined germ cell
tumour of testis seminoma and
embryonal carcinoma
• Venous invasion by
NSGCT component
Vein wall
Non-seminomatous germ cell tumours - micro
• Choriocarcinoma
• beta-HCG in
synctiotrophoblast
giant cells
NSGCT - Yolk sac carcinoma
• Schiller-Duval
bodies like
primitive
glomeruli
• AFP +
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)
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
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
Verrucous carcinoma
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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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