MALE REPRODUCTIVE SYSTEM PATHOLOGY --- PENIS Malformations Hypospadias - Urethral opening on the ventral (underside) of penis - Occurs in 1 in 300 male births -
MALE REPRODUCTIVE SYSTEM PATHOLOGY --- PENIS Malformations Hypospadias - Urethral opening on the ventral (underside) of penis - Occurs in 1 in 300 male births - Can cause urinary obstruction and increased UTI risk - Associated with inguinal hernia and undescended testis - Epispadias - Urethral opening on the dorsal (top) side of penis - Less common than hypospadias - --- Inflammatory Lesions Balanitis — inflammation of the glans penis Balanoposthitis — inflammation of the glans AND prepuce (foreskin) - Caused by: Candida albicans, anaerobic bacteria, Gardnerella, pyogenic bacteria - Most common in uncircumcised males with poor hygiene - Smegma (dead skin, sweat, debris buildup) acts as the irritant - Phimosis — foreskin cannot retract over the glans - Can be congenital - Most cases are acquired from scarring after balanoposthitis - --- Neoplasms Risk Factors for Squamous Cell Carcinoma (SCC) - Uncircumcised males over 40 - Poor hygiene (smegma exposure) - Smoking - HPV infection, especially types 16 and 18 - More common in developing countries - Bowen Disease (SCC in situ) - Solitary plaque on the shaft of the penis - Malignant cells throughout epidermis but NO stromal invasion - Progresses to invasive SCC in about 10% of cases - Invasive SCC - Gray, crusted, papular lesion — most commonly on glans or prepuce - Becomes indurated and ulcerated with irregular margins - Histology: keratinizing squamous cell carcinoma - Prognosis depends on stage - Verrucous Carcinoma - Variant of SCC with papillary architecture - No cytologic atypia, pushing (not infiltrating) margins - Locally invasive but does NOT metastasize - --- SCROTUM, TESTIS, AND EPIDIDYMIS Cryptorchidism (Undescended Testis)- Incomplete descent of testis from abdomen to scrotum - Present in about 1% of 1-year-old males - Leads to tubular atrophy and sterility (bilateral or unilateral) - 3 to 5 times higher risk of testicular cancer - Microscopic atrophy starts by age 5-6; hyalinization by puberty - Treatment: Orchiopexy (surgical fixation) reduces risk of sterility and cancer - --- Inflammatory Lesions Nonspecific Epididymitis and Orchitis - Usually spreads from a urinary tract infection via vas deferens or lymphatics - Testis is swollen and tender - Histology: neutrophilic inflammatory infiltrate - Mumps Orchitis - Complicates mumps in about 20% of adult males (rare in children) - Testes are edematous and congested - Lymphoplasmacytic infiltrate - Severe cases: necrosis, tubular atrophy, fibrosis, sterility - Testicular Tuberculosis - Most common cause of granulomatous orchitis - Begins as epididymitis, then spreads to testis - Histology: granulomatous inflammation with caseous necrosis - --- Vascular Disturbances — Testicular TorsionTwisting of the spermatic cord obstructs venous drainage while arteries remain open, causing venous infarction. Two types: Type When Key Feature --- --- --- Neonatal In utero or shortly after birth No anatomic defect Adult Adolescence Bell clapper abnormality — testis has increased mobility - Adult torsion: sudden onset of testicular pain, may wake patient from sleep - UROLOGIC EMERGENCY — must untwist within 6 hours to save the testis - Contralateral testis is surgically fixed (orchiopexy) to prevent same occurrence - --- Testicular Neoplasms Epidemiology - 6 per 100,000 males; more common in whites - Brothers of affected males have 8 to 10 times higher risk - Cryptorchidism increases risk 3 to 5 fold - Virtually all germ cell tumors carry isochromosome i(12p) - In post-pubertal males: 95% of testicular tumors are germ cell tumors and ALL are malignant - Sex cord-stromal tumors (Sertoli/Leydig) are uncommon and usually benign - --- Tumor Summary Table Tumor Peak Age Key Morphology Marker --- --- --- --- Seminoma 40-50 Sheets of uniform cells, clear cytoplasm, lymphocytes in stroma hCG elevated in 10% Embryonal Carcinoma 20-30 Poorly differentiated, pleomorphic, cords/sheets/papillary Negative (pure) Yolk Sac Tumor 3 years Endothelium-like cuboidal/columnar cells AFP elevated in 90% Choriocarcinoma 20-30 Cytotrophoblast + syncytiotrophoblast, no villi hCG elevated in 100% Teratoma All ages All 3 germ layers, variable differentiation Negative (pure) Mixed Tumor 15-30 Variable; commonly teratoma + embryonal carcinoma hCG + AFP in 90% --- Tumor Markers - hCG — always elevated in choriocarcinoma; mildly elevated in others with syncytiotrophoblastic cells - AFP — elevated indicates yolk sac tumor component - LDH — correlates with tumor burden - Clinical Features - Present as painless, non-translucent testicular mass - Standard treatment: radical orchiectomy (no biopsy — risk of tumor spillage) - Seminomas: spread late, mainly to iliac and para-aortic lymph nodes - Nonseminomatous: spread earlier, liver and lungs via hematogenous route - --- PROSTATE Prostatitis — 4 Categories Type Frequency Cause --- --- --- Acute bacterial 2-5% Common UTI organisms Chronic bacterial 2-5% Common uropathogens Chronic nonbacterial (pelvic pain syndrome) 90-95% No pathogen identified Asymptomatic inflammatory Unknown Leukocytes in secretions, no symptoms Granulomatous Prostatitis - Most common cause: BCG instillation for bladder cancer treatment - BCG is an attenuated TB strain — looks identical to TB histologically - Fungal granulomatous prostatitis: only in immunocompromised patients - Clinical Features - Acute: fever, chills, dysuria; prostate is tender and boggy on rectal exam - Chronic bacterial: recurrent UTIs, low back pain, dysuria, perineal discomfort - Chronic pelvic pain syndrome: no proven treatment; diagnosed by sequential urine and prostatic fluid collection - --- Benign Prostatic Hyperplasia (BPH) Key Facts - Extremely common — present in 90% of men by the 8th decade - Occurs in the inner transitional zone of the prostate - Proliferation of both stromal and epithelial elements - Pathogenesis - Driven by dihydrotestosterone (DHT) - DHT is formed from testosterone by the enzyme 5-alpha reductase type 2 - DHT is 10 times more potent than testosterone - Does NOT occur in castrated males or those with androgen insensitivity - Morphology - Prostate weighs 60-100 g (normal ~20 g) - Well-circumscribed nodules, may be solid or cystic - Urethra compressed to a narrow slit - Hyperplastic glands: tall columnar cells + peripheral basal cells + corpora amylacea (inspissated secretions) - Symptoms - Hesitancy, intermittent urinary stream - Urgency, frequency, nocturia - Risk of UTIs from residual urine - Can progress to complete obstruction and hydronephrosis - Treatment - Finasteride — inhibits DHT formation (5-alpha reductase inhibitor) - Flomax (Tamsulosin) — relaxes smooth muscle via alpha-1 adrenergic blockade - Surgery for severe cases unresponsive to medication - --- Carcinoma of the Prostate Epidemiology - Most common cancer in men; typically age 65-75 - More aggressive in American Black men than whites - Many men die WITH prostate cancer, not OF it - Pathogenesis - Most common mutations: TMPRSS2-ETS fusion genes; PI3K/AKT pathway activation - Arises in the outer peripheral zone — may be palpable on rectal exam - Morphology - Adenocarcinoma — neoplastic glands lined by a single layer of cells (no basal layer) - Graded by the Gleason system — correlates with stage and prognosis - Spread - Bone metastases — characteristically osteoblastic - PSA levels used for screening and monitoring recurrence - PSA - Useful but imperfect screening tool - Has significant false-positive and false-negative rates - Most valuable for monitoring treatment response and detecting recurrence