B94, tumors of the testis and epididymis

Question 1

General characteristics of these tumors

Answer 1

Are the main cause of firm, painless testicular enlargement.

Occur in 1% of males.

Peak is 15-34 years. (except for yolk sac tumors, at age 3)

Are very curable

They are solid masses, and cannot be transilluminated like hydrocele

They are usually not biopsied this presents a risk for disruption and seeding of the cells into the scrotum.

Germ cell tumors all have the i12p isochromosome.

Question 2

Germ cell tumors, prognosis, metastases, and treatment.

Answer 2

h) Clinical Features
i. Present with painless enlargement of the testis.

ii. Some tumors (especially nonseminomatous germ cell neoplasms) have widespread metastases at diagnosis. Usually without palpable testicular lesion.
1. Metastases usually to the iliac and para‐aortic lymph nodes, particularly in the upper lumbar region (hematogenous metastases occur later)
a. Usually do not spread to inguinal lymph nodes.
2. Nonseminomatous germ cell neoplasms tend to metastasize earlier, by both lymphatic and hematogenous routes.
3. Hematogenous metastases go to the: Liver and Lungs, and also Brain and Bones.

Treatment and prognosis

j) Treatment
i. The treatment of testicular germ cell neoplasms is considered a success story of chemotherapy.
ii. ~ 8000 new cases of testicular cancer occur in the US per year. < 400 men are expected to die of the disease.
iii. The treatment is determined by both the histologic pattern of the tumor and the stage of disease at the time of diagnosis.
iv. Seminomas are very radiosensitive and they also respond well to chemotherapy.

95% with early stage seminoma are totally cured

90% of all the non-seminiomatous germ cell tumors are cured/complete remission. (pure choriocarcinoma is the exception)

If they do recur, it occurs within 2 years and at distant sites.

Staging:

i. Stage I: Tumor confined to the testis
ii. Stage II: Regional lymph node metastases only
iii. Stage III: Nonregional lymph node and/or distant organ metastases

hCG, AFP are tumor markers for the germ cell tumors

LDH is used to assess tumor burden. Its levels correlate with tumor mass.

Question 3

Types of testicular, epididymis tumros

Answer 3

Germ cell tumors - 95%, all are malignant

• seminomas
• nonseminomatous germ cell tumors
  
  • Embryonal carcinoma
  • Yolk sac tumor
  • Choriocarcinoma
  • Teratoma
  • Mixed germ cell tumor

Sex cord - stromal tumors, Sertoli and Leydig cell tumors. 5%, are usually benign

Question 4

Risk factors for testis/epid cancers

Answer 4

• Cryptorchidism
• Intersex syndroms,
  
  • androgen insensitivity synd
  • gonadal dysgenesis
• Family history, mrothres have high associated risk
• Previous cancer in contralateral teste
• Isochromosome of the short arm of chromosome 12 is found in all germ cell tumors.
• Precursor lesion is intratubular germ cell neoplasia, seen as precursor and in tissue adjacent to the cancer in all cases.

Question 5

Seminomas, morphology, histology

Answer 5

Morphology

• Soft, well demarcated white/pale tumor.
• Bulge from the cut surface, and lobulated.
• May have foci of coagulative necrosis, not hemorrhage

Histology:

• Large, polygonal neoplastic cells
• large nuclei and large clear glycogen filled cytoplasm.
• There is prominent lymphocytic infiltration, that may even outnumber the neoplastic cells and create islands of noeplastic cells.
• Lobules and fibrous septa
• May also infvolve some granulomatous reaction sites
• 15% have syncytiotrophoblasts present, which elevate hCG concentrations. this does not affect prognosis

Question 6

Seminomas, presentation and prognosis

Answer 6

In ages 40-50 years.

Are highly radiosensitive and usually curable

Question 7

Embryonal carcinoma morphology, histology

Answer 7

Morphology:

• irregular border, ill defined, invasive
• many foci of hemorrhage and necrosis
• softer, non uniform lesions

Histology:

• Large, anaplastic looking cells
• Large, pale basophilic cytoplasm.
• According to text, they have ‘indistinct borders’
• Arranged in clusters and form small, primitive gland structures
• It is usually mixed with some other types of germ cell tumors, only 2-3% of embryonal carcinomas are pure.
• Often also has syncytial cells producing HCG

Question 8

Embryonal carcinoma presentation, prognosis

Answer 8

Peaks in ages 20-30 years.

Mostly resistant to radiotherapy

Still very susceptible to chemotherapy.

Question 9

Yollk sac tumors, morphology, histology

Answer 9

Morphology:

• large and often well demarcated
• Secretes AFP serum tumor marker.

Histology:

• Low cuboidal or columnar epithelial cells forming microcysts, sheets, glands, and papillae.
• Glomeruloid formations, Schiller-Duval bodies.
• often is mixed with embryonal carcinoma, indicated by serum AFP.
• Eosinophilic hyaline depositions of AFP and alpha 1 antitrypsin seen by immunostain.
  *

Question 10

Yolk sac tumors, presentation, prognosis, treatment

Answer 10

Peaks in children at age 3

Has a very good prognosis in children, in adults it is usually mixed with embryonal carcinoma and has a slightly worse prognosis.

Treated with chemotherapy.

Question 11

Choriocarcinomas, morphology, histology

Answer 11

Morphology:

• Present as small testicular tumors, because they aggressively metastasize, and present in other sites very early.
• Grow so rapidly that they often outgrow their blood supply and die off, with the primary tumor leaving behing only a small site of hemorrhagic necrosis and then a small scar. “disappearing primary tumor,” while the metastases continue to grow. (LungLiver, BoneBrain)
• The trophoblast cells, syncytiotophos and cytotrophos secrete hCG, used as serum marker.
• Often are mixed with embryonal carcinoma and teratocarcinomas.
• Rarely present alone.

Histology

• Sheets of small cuboidal cells - cytotrophoblastic cells
• mixed with large, eosinophilic syncytial cells with multiple dark pleomorphic nuclei. - syncytiotrophoblastic cells.
• Areas of hemorrhage and necrosis are prominent.

Question 12

Choriocarcinoma presentation, prognosis

Answer 12

Peaks in ages 20-30

Often presents first as a lung or liver tumor, all of these tumors express hCG seen in serum.

Pure choriocarcinoma has a horrible prognosis

But if it presents as part of a mixed tumor, it is still responsive to chemo.

Question 13

Teratomas, morphology, histology

Answer 13

Morphology:

• firm masses
• cysts,
• notable cartilage
• pure teratomas are common in children and infants.
• Pure teratomas are rare in adults. and are usually in mixed tumors.
• Prepuberty, they are benign
• Post puberty they are malignant.

Histology

• all cell types
• Cells are both mature and immature
  *

Question 14

Teratoma presentation, prognosis

Answer 14

Second most common testicular tumor of children

Pure teratomas are common in hcildren, rare in adults

Good prognosis with resection.

In rare cases they may give rise to non-germ cell tumors such as squamous cell carcinoma, sarcoma, or adenocarcinomas.

This is called”teratoma with malignant transformation” and significantly worsens prognosis. These non-germ cell tumors are not responsive to chemo, and have a very bad prognosis if they ahve metastasized.

Question 15

Mixed germ cell tumor presentation, morphology

Answer 15

Most common mix is teratoma plus embryonal carcinoma

but can be any combination.

90% have elevated hCG and AFP.

Question 18

Non germ cell tumors

Answer 18

Leydig and sertoli cell tumors

Are benign and generally incosequential. Usually less than 1cm in size.

Often seen as incidentalomas

If they produce symptoms, they are related to expressing androgens, or more often estrogens, producing gynecomastia.

Rarely can produce glucocorticoids.