Testicular Disorders and Germ Cell Tumors

Diseases of Male Genital Organs - Overview

• Presentation of the topic, listing author

Diseases of the Penis

• Common Congenital Anomalies:

  • Hypospadias: Urethral opening on the ventral surface of the penis.
  • Epispadias: Urethral opening on the dorsal surface of the penis.
  • Phymosis: Narrowing of the prepuce opening, potentially congenital or acquired due to infection.

• Inflammations:

  • Non-specific inflammation
  • Specific inflammations: syphilis, gonorrhea, herpes, and granuloma inguinale.

• Tumors:

  • Benign: Condyloma acuminatum
  • Malignant: Carcinoma in situ (Bowen disease), squamous cell carcinoma

Condyloma Acuminatum (Anal Wart)

• Benign papillomatous squamous tumor with a fibrovascular core.
• Caused by human papillomavirus (HPV) infection (STD).
• Affects both sexes equally, appearing mainly in the third decade of life.
• In females, it may involve the vulva, vagina, or uterine cervix, but the anal canal and perianal skin are the most common sites in both sexes.
• Giant condyloma acuminatum can show deep growth, local destruction, and may become malignant.
• Gross appearance: sessile or pedunculated masses, usually multiple, pink, potentially painful.
• Primarily involving the coronal sulcus (penis).
• Microscopic features: stromal papillae, stratified squamous epithelium with prominent hyperkeratosis, common vacuolation of surface epithelial cells.

Carcinoma in Situ (Bowen Disease)

• Very early form of skin cancer affecting squamous cells in the outer skin layer.
• Red, scaly patch on the skin is the primary symptom.
• May occur in genital regions of both males and females, predominantly after age 35.
• In males, it presents as solitary or multiple plaques on the penile shaft.
• Microscopically shows marked epithelial atypia with loss of surface maturation.

Squamous Cell Carcinoma

• Accounts for more than 95% of all penile cancers.
• Occurs between ages 40-70, with a median age of 58.
• Potential causes (risk factors):
  • Smegma accumulation under the prepuce in non-circumcised individuals.
  • HPV infection.
• Gross appearance: ulcer or exophytic growth.
• Microscopic features: range from well-differentiated to poorly differentiated.

Diseases of Testes & Epididymis

• Cryptorchidism: Failure of the testicle to descend into the scrotum.

  • Occurs in 1% of boys.
  • Testicle is present along the normal path of descent from the abdominal cavity to the inguinal canal.
  • Mostly unilateral.
  • Microscopic: atrophic changes may develop in the testes early at 2 years.
  • Clinical significance: prevalence of inguinal hernia, sterility (due to atrophy), and neoplasms.
  • Treatment: surgical orchidopexy before age 2.

• Testicular atrophy: Secondary to:

  • Cryptorchidism
  • Klinefelter syndrome (47 XXY chromosome)
  • Vascular disease
  • Inflammation
  • Hypopituitarism
  • Elevated serum female sex hormones
  • Radiation

• Morphology of testicular atrophy:

  • Sertoli cell only lining of seminiferous tubules.
  • Decreased germ cell production (germ cell aplasia).
  • Thickening and hyalinization of tubular basement membrane.
  • Interstitial fibrosis.
  • Bilateral testicular atrophy leads to infertility (azoospermia).

Inflammations of Testes

• Non-specific epididymo-orchitis:

  • Causative organisms:
    • Gram-negative organisms (pediatric patients)
    • Chlamydia and goncocci (men < 35)
    • E. coli and pseudomonas (older men)
  • Symptoms: congestion, edema, neutrophilic infiltration.

• Specific inflammations:

  • Gonorrhea: Retrograde inflammation from the urethra, congestion, edema, neutrophilic infiltration, and suppuration.
  • Mumps: Common in children, may occur in adults, occurs about a week after the onset of parotitis, may cause sterility if fibrosis occurs in both testes.
  • Tuberculosis: Inflammation begins in the epididymis, granulomatous inflammation associated with caseous necrosis.
  • Syphilis: Inflammation begins as orchitis, occurs in congenital and acquired syphilis, may produce diffuse or gummatous nodules.
  • Granulomatous noninfectious orchitis: Uncommon cause of unilateral testicular enlargement, occurs in middle-aged men, possibly auto-immune origin, sudden onset mass (with or without pain), microscopically resembles tuberculosis but without caseous necrosis.

Vascular Disturbances of Testes (Torsion)

• Occurs due to twisting of the spermatic cord.
• Typically seen in adolescence, but neonatal torsion is known and can occur in utero or shortly after birth.
• Presents as sudden onset of testicular pain.
• Due to increased mobility of the testis.
• Requires untwisting within 6 hours to prevent necrosis.

Cystic or Semi-Cystic Disorders of Tunica and Spermatic Cord

• Hydrocele: Abnormal accumulation of serous fluid in the tunica vaginalis due to local injury (inflammation, tumors), or idiopathic.
• Spermatocele: Presence of serous fluid and sperms in the tunica vaginalis due to dilatation of epididymal tubules.
• Hematocele: Blood in the tunica vaginalis, due to trauma, tumor, torsion, or blood disease.
• Varicocele: Dilatation of veins of pampiniform plexus, potentially idiopathic or due to venous drainage obstruction.

Testicular Tumors

• A) Germ cell tumors:
  • Seminoma (classic type), Spermatocytic seminoma (non-classical type), Embryonal carcinoma, Yolk-sac (endodermal sinus) tumor, Choriocarcinoma, Teratoma.
• B) Sex-cord stromal tumor: Leydig cell tumor, Sertoli cell tumour.
• Predisposing factors for germ cell tumors: Cryptorchidism, Genetic factors, Testicular dysgenesis (e.g., Klinefelter syndrome), Cytogenetic abnormalities involving chromosome 12.
• Germ cell neoplasia in situ (GCNIS) tumors: Seminoma and non-seminoma (NSGCT). NSGCT includes teratoma (post-pubertal), embryonal carcinoma, choriocarcinoma, yolk sac tumors (YST).
• non-GCNIS tumors: Spermatocytic tumors, YST (prepubertal type), teratoma (prepubertal type). Neoplasia in situ means dysplastic changes beyond the basement membrane.

Seminoma

• Classic type (95%): Most common testicular tumor, peak incidence in the 30s, may metastasize.

• Gross appearance: Round, firm, homogeneous, lobulated, tunica albuginea usually intact.

• Microscopic appearance: Large polyhedral cells, abundant clear cytoplasm, large nuclei with prominent nucleoli, fibrous stroma infiltrated by lymphocytes.

• Spermatocytic type (5%): Occurs in older patients, no tendency to metastasize, neoplastic cells resemble secondary spermatocytes, better prognosis than classic type.

Embryonal Carcinoma

• Peak incidence between 20-30 years.
• More aggressive than seminoma.
• Morphology: Primitive cells forming irregular sheets, tubules, alveoli, and papillary structures.
• 90% of cases have elevated alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in the blood.

Yolk Sac Tumor

• Primarily in children under 4 years, but may occur in adults.
• Composed of cuboidal cells arranged in a reticular pattern.
• Structures resembling primitive glomeruli in 50% of cases.
• Patients have elevated AFP levels.

Choriocarcinoma

• Rare as a pure form (<5%).
• Can form special elements in some testicular teratomas.
• Occurs in the 2nd and 3rd decades.
• Morphology: Composed of large syncytiotrophoblastic and cytotrophoblastic cells.
• Elevated HCG levels in all patients.

Testicular Teratomas

• Peak incidence in the 2nd and 3rd decades, but also in pediatrics (second most common germ cell type, after yolk sac).
• Morphology: Formed from the three embryonic layers:
  • Ectoderm (squamous epithelium, renal tissue)
  • Mesoderm (cartilage, smooth muscle, bone)
  • Endoderm (GIT & respiratory epithelium)

Types of Teratomas

• Prepubertal: Benign, not associated with GCNIS, normal spermatogenesis, no metastatic potential.
• Postpubertal: GCNIS-derived, metastatic potential (22-37% of cases).

Sertoli Cell Tumor & Leydig Cell Tumor

• Sertoli cell: Rare, usually benign, structures resembling testicular tubules, secretes estrogen leading to gynecomastia.
• Leydig cell: 1-2% of testicular tumors in adults and 3-6% in prepubertal males. Small minority (<10%) are clinically malignant. In children, secretes androgen; in adults, secretes estrogen.