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The Male Genital System pathology

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The Male Genital System Penis scrotum and testes prostate

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Malformations Inflammatory conditions & STDs Neoplasms Disease Categories

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Penis Malformations Hypospadias epispadias

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Hypospadias more common (1 in 250 live male births) urethral opening along ventral aspect urinary tract obstruction risk of infections other anomalies: Inguinal hernias UDTs

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Epispadias Orifice on dorsal aspect of penis Lower urinary tract obstruction Urinary incontinence Commonly associated with bladder extrophy..

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balanitis : glans penis balanoposthitis : glans penis & prepuce by smegma Phimosis paraphimosis congestion, swelling & pain Urinary retention Candidiasis Penis Inflammatory Lesions

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Neoplasms of the Penis >95% originate from squamous epithelium Higher rates in developing countries Most cases are uncircumcised & older than 40 Pathogenesis: Poor hygiene (smegma) Smoking HPV 16 and 18

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Intraepithelial neoplasia (carcinoma in situ) Three clinical variants : 1-Bowen disease Older uncircumcised males Solitary, plaquelike lesion on shaft Malignant cells throughout epidermis No invasion of stroma Invasive SCC in 33%..

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Bowen disease (carcinoma in situ) Hyperchromatic Dysplastic Dyskeratotic epithelial cells scattered mitoses

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Intraepithelial neoplasia (carcinoma in situ) 2-Erythroplasia of Queyrat Erythematous patch on glans

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Intraepithelial neoplasia (carcinoma in situ) 3-Bowenoid papulosis young, sexually active males multiple reddish brown papules on glans most often transient rare progression to carcinoma in immunocompetent patients

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Squamous cell carcinoma of penis gray, crusted, papular lesion on glans penis or prepuce infiltrates underlying tissue indurated, ulcerated lesion irregular margins keratinizing SCC with infiltrating margins

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Glans penis deformed by a firm, ulcerated, infiltrative mass

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Gray, crusted, papule on glans or prepuce that infiltrates underlying tissue

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Most case are indolent locally infiltrative Regional metastases in inguinal lymph nodes (25% ) Distant metastases relatively uncommon Overall 5-year survival rate averages 70%

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Verrucous carcinoma a variant of SCC papillary architecture less striking cytologic atypia rounded, pushing deep margins

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SCROTUM SCC: Sir Percival Pott observed a high incidence in chimney sweeps

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SCROTUM Hydrocele: most common cause of scrotal enlargement serous fluid within tunica vaginalis causes: infections tumors idiopathic

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SCROTUM blood : Hematoceles Lymphatic fluid :chyloceles

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SCROTUM Elephantiasis lymphatic obstruction (filariasis) Scrotum & lower extremities

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The Testes Cryptorchidism & Testicular Atrophy Inflammatory Lesions Testicular Neoplasms

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Cryptorchidism failure of testicular descent into scrotum Descent from coelomic cavity into pelvis by the third month of gestation Through inguinal canals into scrotum during the last 2 months of intrauterine life Diagnosis difficult to establish before 1 yr

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Cryptorchidism By 1 yr seen in 1% of the male population 10% are bilateral Causes: hormonal intrinsic testicular abnormalities mechanical (inguinal canal obstruction) congenital syndromes (Prader-Willi) unknown

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Cryptorchidism Sterility Risk of testicular malignancy x3-5 times unilateral cryptorchidism : 1- cancer risk in contralateral, descended testis 2- atrophy of contralateral gonad and sterility

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Orchiopexy Surgical placement of UDT into scrotum before puberty decreases likelihood of atrophy,cancer and infertility

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Cryptorchidism Right >left 10% bilateral normal size early in life at 5 to 6 yrs: tubular atrophy at puberty: hyalinization hyperplasia of Leydig cells intratubular neoplasia

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Atrophic changes Cryptorchidism chronic ischemia Trauma Radiation antineoplastic chemotherapy chronic elevation in estrogen levels (cirrhosis)

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Inflammatory Lesions epididymis > testis Acute gonococcal epididymitis (abscess)

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Inflammatory Lesions Nonspecific epididymorchitis : begins as a primary UTI secondary ascending infection of testis testis is swollen and tender with PMNs

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Inflammatory Lesions mumps orchitis 20% of infected adults rarely in children testis is edematous and congested lymphoplasmacytic infiltrate tubular atrophy, fibrosis & sterility

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Inflammatory Lesions Testicular TB: most common cause of testicular granulomas epididymitis testis granulomas & caseous necrosis

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Testicular Neoplasms Firm, painless enlargement 5 /100,000 males peak 20 - 34 yrs

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Testicular Neoplasms cause unknown Cryptorchidism (10%): X3-5 in both sides syndromes: androgen insensitivity gonadal dysgenesis isochromosome 12p risk in siblings of patients risk in contralateral testis whites >blacks Caucasians

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Heterogeneous group: 1-germ cell tumors (95%,all are malignant) 2-sex cord/stromal tumors (uncommon,usually benign)

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Classification of Germ Cell Tumors One Histologic Pattern ( 60% ) Seminoma nonseminoma Embryonal carcinoma Yolk sac tumor Choriocarcinoma Teratomas Mature Immature malignant transformation More Than One Histologic Pattern

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Intratubular germ cell neoplasia most tumors arise from in situ lesions in situ foci are adjacent to germ cell tumors in almost all cases

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Seminoma 1- classic : 50% of germ cell neoplasms identical to dysgerminomas & CNS germinomas

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Large Soft well-demarcated Homogeneous gray-white bulge from cut surface confined to testis intact tunica albuginea foci of coagulation necrosis usually without hemorrhage

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Large,uniform cells distinct cell borders Clear,glycogen-rich cytoplasm round nuclei conspicuous nucleoli small lobules intervening fibrous septa lymphocytic infiltrate granulomatous reaction

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cells staining positively for hCG in 25 % similar to syncytiotrophoblasts elevated serum hCG concentrations

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Seminoma 2- spermatocytic occur in older patients medium-sized cells large uninucleate or multinucleate cells small cells with round nuclei no association with intratubular germ cell neoplasia metastases are exceedingly rare

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Embryonal carcinomas Ill-defined,invasive masses Hemorrhage & necrosis primary lesions may be small,even in cases with metastases may invade epididymis & spermatic cord

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Embryonal carcinomas Large,primitive cells basophilic cytoplasm indistinct cell borders large nuclei prominent nucleoli

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Embryonal carcinomas undifferentiated, solid sheets glandular structures & irregular papillae other patterns are admixed with embryonal areas

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Embryonal carcinomas Pure forms 2% to 3% of all testicular germ cell tumors foci of intratubular germ cell neoplasia frequently present in adjacent tubules

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Yolk sac tumors (endodermal sinus tumors) the most common primary testicular tumor in children

Morphology periurethral glands of prostate prostate is enlarged even >300 gm cut surface well-circumscribed nodules solid or with cystic spaces urethra is usually compressed (slit-like orifice) may project into bladder lumen

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Well-defined nodules compress urethra into a slitlike lumen

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Microscopical appearance Glands tall columnar epithelial cells flattened basal cells crowding of epithelium (papillary projections) corpora amylacea Infarction (advanced cases) squamous metaplasia in adjacent glands

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Microscopical appearance fibromuscular stroma surround glands Spindle cells & connective tissue nodules

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basal cell and secretory cell layers

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Clinical Features in only about 10% of patients lower urinary tract obstruction & infections Hesitancy intermittent interruption of urinary stream painful distention of bladder hydronephrosis bladder irritation ( frequency, nocturia & urgency)

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Carcinoma of the Prostate the most common visceral cancer in males 2nd cancer-related death cause in men >50 peak incidence between 65 and 75 years overall frequency >50% in men above 80

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Pathogenesis Hormones: not seen in males castrated before puberty androgens probably contribute growth inhibited by orchiectomy or DES Genes: Higher risk among 1st-degree relatives Environment: American blacks >whites, Asians or Hispanics A high animal fat diet is suggested as a risk factor

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prostatic intraepithelial neoplasia (PIN) frequent coexistence with infiltrating carcinoma probable precursor to carcinoma high-grade and low-grade patterns degrees of atypia vary an intermediate between normal & malignant tissue

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Gross pathology 70-80 % in periphery irregular hard nodules less likely to cause urethral obstruction ill-defined masses firm, gray-white to yellow Infiltrative margins

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Microscopy adenocarcinoma small glands lie "back to back" single layer of cuboidal cells basal cell layer absent conspicuous nucleoli

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perineural invasion by malignant glands

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Low-grade (Gleason score 2) back to back uniformly sized glands

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Anaplasia irregular, ragged glands papillary or cribriform structures sheets of poorly differentiated cells

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(Gleason score 6) variably sized widely dispersed Moderately differentiated (Gleason score 10) Poorly differentiated sheets of malignant cells

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Clinical Features often clinically silent during early stages may be discovered by routine rectal exam 10% found in histologic examination of tissue removed for nodular hyperplasia autopsy studies,30% in men 30 to 40 years Prostatism when more extensive : local discomfort lower urinary tract obstruction

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More aggressive cases come to attention because of metastases regional pelvic LN seminal vesicles periurethral zones bladder wall Invasion of rectum less common Clinical Features

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Bone metastases axial skeleton common: osteolytic (destructive) osteoblastic (bone-producing) osteoblastic metastases in an older male strongly suggests advanced carcinoma

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Metastatic osteoblastic prostatic carcinoma within vertebral bodies

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prostate-specific antigen (PSA) proteolytic enzyme secreted into prostatic acini and seminal fluid increases sperm motility serum level 4.0 ng/L is the upper limit of normal Cancer cells produce more PSA also elevated in : nodular hyperplasia prostatitis

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prostate-specific antigen limited value when used as an isolated screening test for cancer diagnostic value enhanced when used with digital rectal examination transrectal sonography needle biopsy

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prostate-specific antigen great value in monitoring patients after treatment for cancer rising levels indicate recurrence and/or metastases

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prostate-specific antigen useful refinements PSA (4 to 10) gray zone: PSA velocity PSA density free vs bound forms of PSA Free PSA level >25% indicate a lower risk level