Male Genitourinary Pathology

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Male Genitourinary Pathology

• Prostate
• Benign prostatic hyperplasia
• Carcinoma of the prostate
• Testis
• Germ cell tumours
• Penis
• Condyloma accuminatum
• Carcinoma

EG Feb 3rd 2009
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Prostate

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

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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 -gt
  frequency, nocturia, etc
• Dysuria because of UTI acute retention

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Benign prostatic hyperplasia

• Prostate 40 - 200 gm
• Nodules vary in size, colour and texture
• Nodules consist of glands and / or fibromuscular
  stroma

NODULE
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Benign prostatic hyperplasia

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

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Carcinoma of the prostate

• Commonest cancer in males
• Second leading cause of cancer deaths in men gt50
• Incidence increases with age 70 gt60 gt50 yrs
• Afro-Americans at earlier age gtUS whites gtAsians
• Endocrine, genetic environmental factors
• Androgens
• Susceptibility loci on chromosomes 1 and 10 (near
  PTEN)
• Incidence in Scandinavians gt Japanese
• Animal fat in diet?
• Prostatic Intraepithelial Neoplasia (PIN)
• in situ precursor of prostatic carcinoma

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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.

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PSA in prostatic acini
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Preferential sites for prostatic lesions

• Transverse section
• BPH around prostatic urethra
• 70 of carcinomas are peripheral, and often
  posterior

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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 -gt 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

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Prostatic carcinoma - microscopic
Gleason G 5
Gleason Grade 3
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Capsular perineural invasion (L) and bone
metastasis (R)
Nerve
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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

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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

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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

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Seminoma

• Circumscribed grey white tumour
• No haemorrhage

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Seminoma - microscopic

• Seminoma cells have nucleoli and clear cytoplasm
• 10 have HCG syncytiotrophoblast giant cells

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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

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Non-seminomatous GCT

• Embryonal carcinoma
• Alpha-fetoprotein in embryonal ca

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Combined germ cell tumour

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

Vein wall
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Non-seminomatous germ cell tumours - micro

• Choriocarcinoma
• beta-HCG in synctiotrophoblast giant cells

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NSGCT - Yolk sac carcinoma

• Schiller-Duval bodies like primitive glomeruli
• AFP

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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)

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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

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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

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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 (Bowens 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