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Germ Cell Tumors

Clinical Presentation
Germ cell tumors arise in the ovaries (in girls), the testes (in boys), and in several other locations, including the lower back (common in infancy), the abdomen, the chest, and within the brain. Germ cell tumors starting within the brain are discussed further under Brain Tumors.
  
Germ cell tumors in the testes of an adolescent male commonly present as an enlarging, solid mass, which may be painful. Within the ovaries, germ cell tumors can usually be distinguished from ovarian cysts, which are much more common, using ultrasound. Germ cell tumors can spread to lymph nodes, lung, liver, and brain. Some germ cell tumors secrete hormones that can lead to changes resembling puberty. Germ cell tumors are more common, but still rare, in undescended testes that were not corrected. Abnormal ovaries or testes due to genetic syndromes (such as Turner’s or Klinefelter’s) are also at higher risk.

Signs or symptoms concerning for a Germ cell tumor include:

- a solid testicular mass, with or without associated testicular pain
- a solid ovarian mass discovered on ultrasound done for abdominal pain
- a mass visible in the lower back, near the anus, often in an infant
- respiratory distress associated with a mass inside the chest
- development of pubic hair, breast enlargement, or vaginal bleeding at a very young age

Diagnostic Testing and Surgery
After a careful history and physical examination, we typically obtain:

- CT scan of chest, abdomen, and pelvis, with oral and intravenous contrast
- Ultrasound of the testes (if testes tumor) or abdomen (if ovarian)
- blood tests for AFP and bHCG (elevated in some Germ cell tumors)
- blood tests to measure blood counts and liver and kidney function
- a baseline hearing evaluation
- pulmonary function tests, as a baseline lung evaluation
- a nuclear medicine GFR test, as a baseline kidney evaluation

After completing the diagnostic evaluation, a surgical resection is planned.  A testicular or ovarian malignancy will be removed along with the involved normal testes or ovary. Abdominal lymph nodes may be biopsied.  Tumors arising in the lower back, the chest, or elsewhere will also be removed surgically if possible – otherwise they will be biopsied. A central line will be placed to allow chemotherapy.

Pathology
Based on the pathology, Germ cell tumors are classified into several subtypes:

- Benign Teratoma, requires no chemotherapy
- Malignant Teratoma, may require chemotherapy, depending upon Stage
- Yolk sac tumor, has a high AFP blood test, which can be used to follow for recurrence
- Choriocarcinoma, has a high bHCG blood test, which can be used to follow for recurrence
- Embryonal carcinoma, common in the testes of adolescent boys
- Germinoma (also called seminoma in boys or dysgerminoma in girls)

Staging
Based on the results of the imaging studies and surgery, a clinical stage will be assigned:
 
- Stage I tumor completed resected
- Stage II tumor resected, but a small number of cells were left behind
- Stage III tumor has spread to lymph nodes
- Stage IV tumor spread to the lung or liver or other locations

Therapy and Prognosis
Chemotherapy is based on tumor stage and location. Patients are given the opportunity to enroll on Children’s Oncology Group therapy protocols or may choose to be treated off protocol with standard of care therapy as summarized below:

-Stage I testes/ovary  
no chemotherapy unless recurs

- Stage II-IV testes, Stage II-III ovary, Stage I-II non-testes or ovary
           Cisplatin, Etoposide, Bleomycin intravenously every 3 weeks for 3 cycles

- Stage IV ovary, Stage III or IV non-testes or ovary
           Cisplatin, Etoposide, Bleomycin intravenously every 3 weeks for 4 cycles

Radiation therapy is not routinely used for initial therapy, except in some instances instead of chemotherapy for germinoma.

If there is a residual tumor present after chemotherapy, surgical resection may be recommended, and additional chemotherapy may be needed.

The cure rates are approximately 90% for Stage I, 90% for Stage II, 87% for Stage III, and 82% for Stage IV.

Therapy for Relapse
Stage I patients who relapse after surgery alone are treated with 3-4 cycles of Cisplatin, Etoposide, Bleomycin chemotherapy.  Patients who relapse after receiving chemotherapy can still be cured, with use of additional chemotherapy (such as Paclitaxel, Ifosfamide and Carboplatin) followed by autologous stem cell transplantation (this involves harvesting the patient’s blood or marrow stem cells, followed by very high dose chemotherapy with Carboplatin and Etoposide, and finally re-infusion of the patient’s own stem cells to rescue the blood counts). Tandem transplantation, in which this procedure is done twice, is our current practice.

Long-term Evaluation
Once therapy is complete, patients are followed for recurrence, by physical examination, with blood tests for AFP or bHCG (if they were abnormal initially), with CT scans of the chest and abdomen, and after several years with chest X-rays instead. Blood counts, kidney function, hearing, and lung function are also followed for signs of chemotherapy toxicities.  The large majority of patients have few long-term side effects from their therapy.

 

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