Patho(reproduction)

• Major categories of testicular tumors

  • Germ cell tumors (95%)
  • Sex-cord stromal tumors
• Types of germ cell tumors

  • Seminoma (classical, anaplastic, spermatocytic)
  • Non-seminomatous germ cell tumor (NSGCT) (Embryonal carcinoma, Yolk sac tumor, Polyembryoma, Choriocarcinoma, Teratomas)
• Types of sex cord-stromal tumors

  • Well-differentiated forms (Leydig cell tumors, Sertoli cell tumors, Granulosa cell tumors)
  • Tumors in the fibroma-thecoma group
  • Mixed form
  • Incompletely differentiated (unclassified) forms
• Germ cell tumors are aggressive cancers capable of rapid, wide dissemination
• Sex-cord stromal tumors are generally benign
• Seminoma


  The most common type of germ cell tumor (50%)
• Seminoma


  Age-peak incidence in 4th decade; almost never occur in infants
• Dysgerminoma


  Identical tumor that arises in the ovary
• Environmental risk factors for testicular germ cell tumors

  • Testicular dysgenesis syndrome (cryptorchidism, hypospadias, poor sperm quality)
  • In utero exposures to pesticides and nonsteroidal estrogen
  • Cryptorchidism (10% of GCT, higher location = greater risk)
• Genetic risk factors for testicular germ cell tumors

  • 4 times higher risk in fathers and sons of affected patients
  • 8-10 times higher risk in brothers
  • Reduplication of the short arm of chromosome 12 (isochromosome 12p) found in invasive GCTs
  • Defects in the genes encoding the ligand for receptor tyrosine kinase KIT and BAK
• Seminoma


  • Sheets of uniform cells divided into poorly demarcated lobules by delicate fibrous septa
  • Large, round to polyhedral cells with distinct cell membrane, clear or watery-appearing cytoplasm, and a large, central nucleus with 1 or 2 prominent nucleoli
  • Infrequent mitoses
  • Tumor giant cells and syncytial giant cells may be present
  • 15% contain syncytiotrophoblasts and have elevated serum hCG levels
  • 80% have lymphocytic infiltration of septa, 20% have granulomatous reaction
• Anaplastic seminoma


  • Greater cellularity and nuclear irregularity
  • Foci of hemorrhage and necrosis
  • Frequent tumor giant cells
  • Many mitoses (3 or more/HPF)
  • Lymphocytes and granulomatous reactions are infrequent
  • Extends to tunica albuginea
  • Poor prognosis and aggressive clinical course
• Spermatocytic seminoma


  • Uncommon, occurring in older men (>65 years)
  • Slow growing, rarely metastasizes, excellent prognosis
  • Larger than classical seminoma, soft, pale gray and mucoid cysts
  • No lymphocytes in stroma, more common mitoses
  • Three distinct cell populations: medium-sized, smaller, and scattered giant cells
• Embryonal carcinoma


  Less radiosensitive and more aggressive than seminoma
• Embryonal carcinoma


  • Smaller than seminoma, variegated appearance with foci of hemorrhage and necrosis
  • Penetrate tunica albuginea very early
  • Very primitive highly undifferentiated polygonal cells arranged in solid sheet and papillae
  • Extreme polymorphism and mitotic activity
  • No lymphoplasmacytic stroma
• Yolk sac (endodermal sinus) tumor


  • Differentiation towards embryonal yolk sac structure
  • Microcystic or papillary or glandular pattern
  • Lining cells are small, primitive cuboidal cells with clear cytoplasm
  • 50% have endodermal sinus resembling primitive glomeruli (Schiller-Duval bodies)
  • Eosinophilic, hyaline-like globules present, positive for AFP and α1-antitrypsin
• Polyembryoma


  • Variant of yolk sac tumor
  • Characterized by formation of embryoid bodies and disc or tubules lined by primitive epithelial cells
• Choriocarcinoma


  • Highly malignant, rapidly metastasizing tumor
  • Biphasic population of syncytio- and cytotrophoblast arranged in solid sheets
  • Not effective by radiation or methotrexate
  • More aggressive than female counterpart
  • Tumor marker is β-hCG
• Teratoma


  • Large (5-10 cm), heterogenous appearance with solid, cartilaginous and cystic areas
  • Haphazard array of differentiated mesodermal, ectodermal and endodermal elements
  • Tissues can be mature or immature
  • Teratoma with malignant transformation signifies non-germ cell malignancy developing within teratoma
• Leydig cell tumors


  • Can produce androgens, estrogens and even corticosteroids
  • Most are benign, 10% are invasive and produce metastases
• Leydig cell tumors


  • Circumscribed nodules with distinctive golden-brown homogeneous cut surface
  • Large, round or polygonal cells with abundant granular eosinophilic cytoplasm and a round central nucleus
  • Cytoplasm frequently contains lipid droplets, vacuoles, or lipofuscin pigment
• Sertoli cell tumors


  Most are benign, 10% are malignant
• Sertoli cell tumors


  • Firm, small nodules with homogeneous gray-white to yellow cut surface
  • Tumor cells arranged in trabeculae that tend to form cordlike structures and tubules
• Testicular lymphoma


  • Aggressive non-Hodgkin lymphomas (5% of testicular tumors)
  • The most common form of testicular tumor in patients > 60 years
  • Most are diffuse large B-cell lymphomas
  • Higher propensity for CNS involvement
• Any solid testicular mass should be considered neoplastic unless proved otherwise
• Seminoma remain localized to testis for a long time and 70% present in clinical stage I
• Seminoma are treated with surgery and radiotherapy (radiosensitive)
• Differences between seminoma and NSGCT

  • Stage (I vs II, III)
  • Spread (lymphatic vs hematogenous)
  • Response to therapy (radiosensitive vs radioresistant)
  • Prognosis (good vs poor)
  • Tumor markers (PLAP vs AFP, hCG)
• Embryonal carcinoma is less radiosensitive and more aggressive than seminoma
• Yolk sac tumor in children and infants has a good prognosis, while the mixed form in adults is more malignant
• Choriocarcinoma is not effective by radiation or methotrexate and is more aggressive than the female counterpart
• Teratoma with malignant transformation signifies non-germ cell malignancy developing within teratoma
• Leydig cell tumors and Sertoli cell tumors are mostly benign, with 10% being malignant
• Testicular lymphoma is the most common form of testicular tumor in patients > 60 years and has a higher propensity for CNS involvement
• Cryptorchidism


  Complete or partial failure of the intra-abdominal testes to descend into the scrotal sac
• Cryptorchidism


  • Associated with testicular dysfunction and an increased risk of testicular cancer
  • Found in approximately 1% of 1-year-old boys
  • Usually occurs as an isolated anomaly but may be accompanied by other malformations of the genitourinary tract, such as hypospadias
• Testicular descent


  1. Transabdominal phase - testis comes to lie within the lower abdomen or brim of the pelvis (controlled by müllerian-inhibiting substance)

  2. Inguinoscrotal phase - testes descend through the inguinal canal into the scrotal sac (androgen-dependent, mediated by androgen-induced release of calcitonin gene-related peptide from the genitofemoral nerve)
• The testes may arrest anywhere along their pathway of descent, with the most common site being the inguinal canal
• Cryptorchidism is only rarely associated with a well-defined hormonal disorder
• Cryptorchid testes


  • Small and firm
  • Histologic changes begin as early as 2 years of age, including thickening of the basement membrane of the spermatic tubules, loss of spermatogonia, and scarring of the tubules