Male Reproductive Pathology

Cryptorchidism and the testicular mass

Cryptorchidism. An undescended testis is the most common congenital male genitourinary anomaly and is more frequent in premature infants. The warmer location impairs spermatogenesis (infertility), while Leydig cells are relatively spared, so testosterone is often normal. Germ cell tumor risk rises in both testes. Orchiopexy at 6 to 12 months (by 18 months at the latest) reduces, but does not eliminate, the cancer risk.

A painless solid mass is cancer until proven otherwise. About 95% of testicular tumors are germ cell tumors (GCTs), and they are malignant. They present as a painless, firm mass that does not transilluminate; risk factors are cryptorchidism and Klinefelter syndrome. Reflecting its abdominal origin, the testis drains to para-aortic (retroperitoneal) nodes, whereas scrotal skin drains to inguinal nodes, so the tumor is removed by radical inguinal orchiectomy and never biopsied through the scrotum.

Germ cell tumors, markers and other testicular tumors

Seminoma. The most common GCT (men in their 30s–40s) shows sheets of "fried-egg" cells with clear cytoplasm separated by lymphocyte-rich septa. It metastasizes late, is radiosensitive, and has an excellent prognosis. Placental alkaline phosphatase (PLAP) may be elevated; AFP is normal. Seminoma is the male counterpart of ovarian dysgerminoma.

Nonseminomatous GCTs are more aggressive, present younger, and are often mixed. Choriocarcinoma's hCG has a β subunit homologous to those of LH and TSH, so very high levels drive gynecomastia and hyperthyroidism; teratoma, benign in the ovary, is malignant in adult males.

Tumor markers. AFP is elevated in yolk sac tumor and embryonal carcinoma but is NEVER elevated in pure seminoma, so a raised AFP proves a nonseminomatous component and the tumor is managed as a nonseminoma. β-hCG is highest in choriocarcinoma and is mildly raised in some seminomas (syncytiotrophoblastic giant cells). LDH reflects tumor burden. Markers are followed after orchiectomy to detect recurrence.

Non-germ-cell tumors. A Leydig cell tumor contains Reinke crystals and secretes androgens (precocious puberty) or estrogens (gynecomastia); a Sertoli cell tumor is usually hormonally silent. In men over 60, lymphoma (usually diffuse large B-cell) is the most common testicular tumor and cancer and is often bilateral.

Prostate

Benign prostatic hyperplasia (BPH). With age, dihydrotestosterone (DHT, made by 5α-reductase) drives nodular hyperplasia of the transition (periurethral) zone, compressing the urethra: nocturia, weak stream, hesitancy and incomplete emptying. PSA may be mildly raised, but BPH is NOT premalignant. Complications include urinary retention, bladder wall hypertrophy and diverticula, UTI and hydronephrosis. α₁-Blockers (-osin, e.g., tamsulosin) relax prostatic smooth muscle for rapid relief (watch for orthostatic hypotension); 5α-reductase inhibitors (finasteride) shrink the gland over months and roughly halve the PSA value.

Prostate adenocarcinoma. The most common cancer in men (excluding skin) arises in the peripheral (posterior) zone, the largest zone and the one felt on digital rectal exam (DRE), so it presents as a hard nodule, often before urinary symptoms. PSA is elevated with a decreased percent-free PSA, and the Gleason score grades glandular architecture. Spread to the lumbar spine and pelvis through the vertebral (Batson) venous plexus produces osteoblastic metastases with back pain and elevated alkaline phosphatase. Advanced disease is treated with androgen deprivation.

Prostatitis. Acute bacterial prostatitis causes fever, dysuria and a tender, boggy, warm prostate; Escherichia coli predominates in older men and Chlamydia/Neisseria gonorrhoeae in younger men. Avoid vigorous prostate massage in acute disease (bacteremia risk). Chronic prostatitis is more indolent: the bacterial form causes recurrent UTIs, while the more common nonbacterial form (chronic pelvic pain syndrome) has negative cultures.

Penile pathology

Squamous cell carcinoma. Penile SCC is linked to HPV 16/18, lack of circumcision, and phimosis. Its in situ precursors are Bowen disease (plaque on the shaft or scrotum), erythroplasia of Queyrat (red velvety plaques on the glans), and bowenoid papulosis (multiple papules in younger men).

Structural and vascular disorders. Hypospadias (ventral opening; urethral folds fail to fuse) is more common than epispadias (dorsal opening; malpositioned genital tubercle, associated with bladder exstrophy). Peyronie disease is a fibrous plaque of the tunica albuginea causing curvature. Priapism is a prolonged (>4 hours) painful erection from sickle cell disease or drugs (e.g., trazodone, PDE-5 inhibitors); the ischemic form is an emergency.

Scrotal masses and the acute scrotum

Painless masses. A hydrocele is serous fluid in the tunica vaginalis that transilluminates (congenital forms reflect a patent processus vaginalis). A varicocele is dilated pampiniform plexus veins ("bag of worms") that does NOT transilluminate and enlarges on standing. It is usually left-sided because the left gonadal vein drains into the left renal vein (the right drains into the IVC), and it causes subfertility by warming the testis. A sudden left varicocele can signal left renal vein obstruction by renal cell carcinoma, and a new right-sided or non-reducing varicocele likewise warrants evaluation for renal cell carcinoma.

Torsion vs epididymitis. Torsion, usually in adolescents with a "bell-clapper" deformity, causes sudden severe pain with vomiting, a high-riding testis with a horizontal lie, an absent cremasteric reflex, and no relief on elevation (negative Prehn sign). Detorse surgically within 6 hours to save the testis, fixing both sides. Epididymitis is more gradual, with fever, a tender epididymis and relief on elevation (positive Prehn sign); it is caused by Chlamydia/gonorrhea (young men) or E. coli (older men) and treated with antibiotics.

Absent cremasteric reflex plus a negative Prehn sign means torsion, a surgical emergency; imaging must not delay detorsion.