The Male Genital System pathology

The Male Genital System Penis scrotum and testes prostate

Disease Categories Malformations Inflammatory conditions & STDs Neoplasms

Penis Malformations Hypospadias epispadias

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

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

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

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

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% .

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

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

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

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

Glans penis deformed by a firm, ulcerated, infiltrative mass

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

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

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

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

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

SCROTUM blood : Hematoceles Lymphatic fluid :chyloceles

SCROTUM Elephantiasis lymphatic obstruction (filariasis) Scrotum & lower extremities

The Testes Cryptorchidism & Testicular Atrophy Inflammatory Lesions Testicular Neoplasms

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

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

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

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

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

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

Inflammatory Lesions epididymis > testis Acute gonococcal epididymitis (abscess)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Yolk sac tumors (endodermal sinus tumors) the most common primary testicular tumor in children <3 In adults,often admixed with embryonal carcinoma

Yolk sac tumors often large and well demarcated low cuboidal to columnar epithelial cells microcysts, sheets, glands, and papillae

structures resembling primitive glomeruli, Schiller-Duvall bodies Eosinophilic hyaline globules (AFP)

Choriocarcinomas Trophoblastic differentiation primary tumors often small & nonpalpable May have extensive systemic metastases small cuboidal cytotrophoblastic cells large, eosinophilic syncytiotrophoblastic cells (multiple dark & pleomorphic nuclei) hCG within cytoplasm of syncytiotrophoblasts Well-formed placental villi not seen

Choriocarcinomas Hemorrhage necrosis c s

Teratomas Differentiation along somatic cell lines in prepubertal boys : usually benign Pure forms In adults: metastases in 37% of cases often contain other malignant elements

Teratoma: variegated cut surface with cysts

1-Mature teratomas one or more germ cell layers neural, cartilage, adipose, bone & epithelial haphazard array

neural glandular cartilaginous squamous

2- Immature teratomas immature somatic elements reminiscent of those in developing fetal tissue

Teratoma disorganized collection of glands, cartilage, smooth muscle & immature stroma

3-Teratomas with somatic-type malignancies frank malignancy in preexisting teratomatous elements usually scc or adenocarcinoma

Mixed germ cell tumors 40% of all testicular germ cell neoplasms Combinations of any of described patterns teratoma, embryonal carcinoma & yolk sac tumors

Clinical Features Seminomas often remain confined to testis may reach considerable size Metastases to iliac and para-aortic nodes Hematogenous metastases occur later

Clinical Features non-seminomatous widespread metastases at diagnosis with no palpable testicular lesion metastasize earlier lymphatic & hematogenous (liver & lungs)

Testicular germ cell neoplasms staging Stage I: confined to testis Stage II: Regional LN only Stage III: Nonregional and/or distant metastases

Assay of tumor markers role in primary diagnosis & staging Serially measured to monitor patients

hCG syncytiotrophoblastic cells always elevated in choriocarcinoma Seminoma: 10-25%

AFP Glycoprotein fetal yolk sac & other fetal tissues reliable indicator of a nonseminomatous component (yolk sac) most nonseminomatous tumors have elevations of both hCG and AFP also elevated in hepatocellular carcinoma.

treatment Seminomas Radiosensitive respond well to chemotherapy nonseminomatous germ cell tumors platinum-based chemotherapy

PROSTATE Prostatitis nodular hyperplasia carcinoma

Acute bacterial prostatitis E.coli & other gram-negative rods Most patients have acute urethrocystitis direct extension from urethra or bladder vascular channels from more distant sites

Chronic prostatitis bacterial episodes of acute prostatitis may also develop insidiously abacterial account for most cases nonbacterial agents: Chlamydia trachomatis Ureaplasma urealyticum,

Granulomatous prostatitis not a single disease a reaction to a variety of different insults disseminated TB Sarcoidosis fungal infections Wegener granulomatosis reaction to inspissated prostatic secretions Following TURP

Morphology Acute prostatitis: neutrophilic inflammatory infiltrate Congestion stromal edema glandular epithelium may be destroyed Microabscesses Gross abscesses uncommon (in diabetics).

Morphology chronic prostatitis nonspecific in most cases lymphoid infiltrate glandular injury concomitant acute inflammation tissue destruction fibroblastic proliferation

Morphology granulomatous prostatitis multinucleate giant cells foamy histiocytes sometimes eosinophils Caseous necrosis only in TB prostatitis

Clinical Features of Prostatitis acute: Dysuria urinary frequency lower back pain suprapubic or pelvic pain fever and leukocytosis chronic: recurrent UTI in men silent

normal prostate: glandular stromal parenchyma: 1-Peripheral 2-Central 3-Transitional 4-periurethral

most hyperplastic lesions arise in inner transitional & central zones most carcinomas (70-80%) arise in peripheral zones

Nodular Hyperplasia of the Prostate glandular & stromal hyperplasia extremely common abnormality a significant number of men by age 40 its frequency rises progressively with age (90% by the 8th decade)

"Benign prostatic hypertrophy" (BPH) a synonym for nodular hyperplasia redundant and a misnomer the lesion is a hyperplasia rather than a hypertrophy

Cause remains incompletely understood androgens have a central role not seen in males castrated before puberty Not in men with genetic diseases (blocked androgen activity)

pathogenesis of nodular hyperplasia local, intraprostatic concentrations of androgens and their receptors increases in estrogens may increase expression of DHT receptors on prostatic parenchymal cells ( age-related )

currently 5α-reductase inhibitors are used to treat symptomatic nodular hyperplasia

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

Well-defined nodules compress urethra into a slitlike lumen

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

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

basal cell and secretory cell layers

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)

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

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

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

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

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

perineural invasion by malignant glands

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

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

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

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

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

Metastatic osteoblastic prostatic carcinoma within vertebral bodies

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

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

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

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 <10% are worrisome

staging

Treatment combinations: Surgery Radiation Hormonal ( advanced carcinomas)

Quiz

1-In Bowen disease which statement is true A)it is seen in young uncircumcised males B)it is a solitary, plaquelike lesion. C)it has invasion of stroma D)invasive SCC never develops in such patients

2-in Epispadias which sentence is false? A) The orifice is on ventral aspect of penis. B) Lower urinary tract obstruction is seen C) Urinary incontinence may occur D) Bladder extrophy is commonly noted

3-AFP is A)A Glycoprotein B)Produced by fetal yolk sac & other tissues C)A reliable indicator of yolk sac tumor D)All of the above.

4-in acute prostatitis which change is not present? A) neutrophilic inflammatory infiltrate B) Congestion & stromal edema C) glandular epithelium destruction D) granulomas.

5-prostate cancer is associated with : A)irregular soft nodules B)well-defined masses C)High serum PSA level. D)All of the above

The End