Childhood Germ-Cell Tumors

A germ cell is a type of cell that forms as a fetus develops. These cells later become sperm in the testicles or eggs in the ovaries.

Early in development, germ cells travel through the body to reach the gonads. Sometimes they stop along the way. That is why a germ cell tumor can appear at the tailbone, in the chest, in the abdomen, or in the head and neck, and not only in an ovary or testicle.

Extracranial germ cell tumors, meaning those outside the brain, form in the:

• Testicles.
• Ovaries.
• Sacrum and coccyx, the tailbone area.
• Retroperitoneum, the area at the back of the abdomen.
• Mediastinum, the space between the lungs.
• Head and neck.

The pattern differs by age. Young children tend to develop sacrococcygeal tumors, at the tailbone. Adolescents tend to develop tumors in the mediastinum and the gonads.

Germ cell tumors can also form inside the brain. Those are handled as childhood CNS germ cell tumors and are treated differently.

In children younger than 15, germ cell tumors make up about 3% of cancers. The picture changes sharply at puberty. Among males aged 15 to 19, they account for about 15% of cancers. Among females of the same age, about 4%.

Rates per million children, from 2014 to 2018, show the same split. For gonadal tumors, the rate in males aged 15 to 19 was 36.1 per million, the highest of any group. For females of the same age it was 8.3 per million. For tumors outside the gonads, the highest rates were in infants: 17.7 per million in females under 1 year, and 8.8 per million in males under 1 year.

Teratomas. These contain tissues from more than one germ layer, and may include hair, muscle, or bone. They may be mature or immature. Mature teratomas are usually treated with surgery and then observation.

Malignant germ cell tumors. These are divided into seminomatous and nonseminomatous types. Named types include yolk sac tumors, dysgerminomas, germinomas, choriocarcinomas, embryonal carcinomas, and gonadoblastomas.

Mixed germ cell tumors. These contain more than one type in the same tumor. They are common, and they are treated according to the most aggressive part present.

Yolk sac tumors make alpha-fetoprotein (AFP). This single fact drives much of how these tumors are followed.

Reported signs include:

• A lump in the neck, abdomen, or lower back.
• A painless lump in a testicle.
• Pain in the abdomen or back.
• Trouble breathing.
• Fever.
• Constipation.
• Trouble passing urine.
• Early puberty.
• Missed or irregular periods in girls.

A painless testicular lump in a teenager is easy to ignore out of embarrassment. It should be checked the same week, not eventually.

• Trouble breathing, or fast, laboured breathing, in a child with a known or suspected chest mass.
• Inability to pass urine.
• New weakness in the legs, or loss of bowel or bladder control, in a child with a tumor near the spine or tailbone.
• Severe, sudden pain in a testicle.
• A fever during chemotherapy. Follow your center's fever rules exactly. Do not wait until morning.

Most children with germ cell tumors have no known risk factor. Some genetic conditions do raise risk:

• Klinefelter syndrome may increase the risk of germ cell tumors in the mediastinum.
• Swyer syndrome may increase the risk of gonadoblastoma and seminoma.
• Turner syndrome may increase the risk of gonadoblastoma and dysgerminoma.

An undescended testicle and gonadal dysgenesis, meaning abnormal formation of the gonads, also raise risk. Ask whether a genetics referral or a chromosome test is appropriate for your child.

Two blood tests do a great deal of work in this disease.

Alpha-fetoprotein (AFP) is a protein made by yolk sac tumors and by some other germ cell tumors. Newborns normally have high AFP that falls over the first months of life, so infant results must be read against age-adjusted values.

Beta human chorionic gonadotropin (beta-hCG) is a hormone made by choriocarcinomas and some other types.

The half-life matters. AFP falls with a half-life of 5 to 7 days. Beta-hCG falls with a half-life of 1 to 2 days. So the team can predict what your child's numbers should look like after surgery or a chemotherapy cycle, and can spot it when they do not fall as expected.

That prediction carries real weight. In one analysis, children whose AFP fell satisfactorily had an 11% risk of relapse. Those whose AFP fell unsatisfactorily had a 38% risk.

Ask for the actual marker numbers at each visit, and ask whether the fall is on track.

Blood tumor marker tests come first, along with ultrasound, CT, MRI, and a chest x-ray. A biopsy confirms the diagnosis, though in some cases the tumor is removed whole and diagnosed then.

Staging depends on site and age. Testicular tumors in children under 11 use a four-stage system, while adolescents are grouped as stage I or metastatic. Ovarian tumors use either the Children's Oncology Group system or FIGO staging, stages I to IV. Tumors outside the gonads follow a similar four-stage pattern.

Surgery. Surgery to completely remove the tumor is done whenever possible. For a mature teratoma, surgery plus careful observation is often all that is needed.

Chemotherapy. Standard treatment uses etoposide, bleomycin, and cisplatin, either at high dose or standard dose. Carboplatin-based combinations are also used. These regimens are known as PEB and JEB.

Surveillance. Some children with early-stage disease can be watched closely after surgery, with chemotherapy held in reserve. This spares many children the side effects of cisplatin. Ask whether your child qualifies.

Tumor markers are checked monthly for 6 months, then every 3 months, for a total of 2 years. For sacrococcygeal teratoma, follow-up runs for 3 years.

Most tumors do not come back after treatment. When recurrence does happen, it usually happens within 3 years.

The prognosis for childhood extracranial germ cell tumors is good, and ovarian germ cell tumors do particularly well.

Age makes a difference. In one multicenter study, the 5-year event-free survival rate was 90% for children (95% confidence interval, 81% to 95%) and 72% for adolescents (95% confidence interval, 62% to 79%).

Ask your child's oncologist for the numbers that apply to your child's site, stage, and age. Broad figures cover a wide range of situations.

Cisplatin causes permanent hearing loss in up to 75% of children who receive it. Sodium thiosulfate is approved by the FDA to reduce this risk in patients aged 1 month through 18 years with localized tumors that have not spread. It is given as a 15-minute infusion after cisplatin. In a Children's Oncology Group trial, 44% of children who received it had hearing loss, compared with 58% who did not.

Ask three questions before the first cisplatin dose: Is my child eligible for sodium thiosulfate? When will hearing be tested? What is the plan for fertility preservation?

• Childhood Extracranial Germ Cell Tumors Treatment (PDQ) Patient Version — National Cancer Institute
• Childhood Extracranial Germ Cell Tumors Treatment (PDQ) Health Professional Version — National Cancer Institute
• Sodium Thiosulfate Reduces Hearing Loss in Kids with Cancer — National Cancer Institute
• Cisplatin Injection — MedlinePlus, National Library of Medicine
• Childhood Brain and Spinal Cord Tumors Treatment Overview — National Cancer Institute