CNS nongerminomatous germ cell tumor (NGGCT)

Germ cells are cells in an unborn baby that later become sperm or eggs. Most germ cell tumors grow in the testicles or ovaries. When one forms in the brain or spinal cord, doctors call it a central nervous system (CNS) germ cell tumor. These tumors are split into germinomas and nongerminomatous germ cell tumors (NGGCTs). NGGCT means any CNS germ cell tumor that is not a pure germinoma.

The main NGGCT types are yolk sac tumor, embryonal carcinoma, choriocarcinoma and mixed germ cell tumor. A mixed tumor contains more than one germ cell type, and it may include germinoma or teratoma. Yolk sac tumors and embryonal carcinomas make a marker called alpha-fetoprotein (AFP). Choriocarcinomas make beta-human chorionic gonadotropin (beta-hCG). The Children’s Oncology Group includes immature teratoma with the NGGCTs. A mature teratoma is treated mainly with surgery.

Like other CNS germ cell tumors, NGGCTs most often start near the pineal gland, deep in the middle of the brain, or just above the pituitary gland. CNS germ cell tumors are found most often between ages 10 and 19 and more often in boys and men. In U.S. cancer registry data from 1973 to 2004, for people up to age 29, there were more germinomas than NGGCTs. Germinomas peak in the teen years, while NGGCTs occur at a fairly steady rate through childhood and young adulthood.

The cause of most CNS germ cell tumors is not known. One idea is that, while a baby grows in the womb, some early germ cells travel to the wrong place and later turn into a tumor. Another idea is that the tumor starts from an early embryo cell that escaped the normal signals that control growth.

Lab studies have found changes in the tumor cells, for example in a gene called KIT and in genes that pass growth signals inside the cell. An extra copy of part of chromosome 12 (called 12p gain) is found more often in NGGCTs than in germinomas. In one study it was linked with lower survival.

Some patterns are known. Boys and men are affected more often. Rates also differ by background. In U.S. cancer registry data from 1992 to 2010, people aged 10 to 29 of Asian or Pacific Islander descent had two to three times the rate of white people. Germ cell tumors are the most common kind of brain tumor reported in people with Down syndrome. Case reports also link Klinefelter syndrome, in which a male has an extra X chromosome, with germ cell tumors outside the testicles, including some in the brain.

Symptoms depend on where the tumor is. A tumor in the pineal region can block the flow of the fluid around the brain (cerebrospinal fluid). The fluid builds up, a problem called hydrocephalus, and raises the pressure inside the head. This causes headaches, nausea, vomiting and tiredness. Pineal tumors can also cause trouble looking up and double vision.

A tumor above the pituitary often affects hormones. It can cause diabetes insipidus: great thirst and passing large amounts of clear urine. This is not sugar diabetes. It can also cause slow growth, early or late puberty and loss of vision as the tumor presses on the nerves to the eyes. Loss of appetite, weight loss and trouble with schoolwork can also happen.

NGGCTs can spread through the fluid to other parts of the brain and spine, and they can come back there after treatment. They rarely spread outside the brain and spinal cord. Most relapses happen within 3 years of diagnosis.

Treatment is long. It usually means four to six rounds of chemotherapy, sometimes a second surgery, and then radiation. In the current Children’s Oncology Group trial, radiation is given once a day, five days a week, for about six weeks. Scans, blood tests and spinal fluid tests are repeated to see how well treatment is working. Care is usually led by a pediatric oncologist or a radiation oncologist. The team may also include a neurosurgeon, an endocrinologist (hormone doctor), an eye doctor, a psychologist, a social worker and a fertility specialist.

After treatment, people whose tumor markers were high at diagnosis usually have their blood markers checked. A rising level can be a sign that the tumor has come back.

Many people have lasting effects. Hormone problems such as diabetes insipidus are often permanent and need replacement medicines. Radiation to the brain can affect thinking, learning, memory and vision, and in rare cases leads to a stroke or a second tumor years later. These effects can happen in teens and young adults as well as children. Follow-up often includes hormone checks, school support and testing of thinking and learning skills (neuropsychology testing).

No donor is involved in the usual treatment of a CNS NGGCT. Most people are treated with chemotherapy, radiation and sometimes surgery.

Some people have high-dose chemotherapy, either because the tumor responded poorly to first chemotherapy or because it came back. That treatment also destroys the blood-forming cells in the bone marrow. Before it starts, stem cells are collected from the patient’s own blood or bone marrow and frozen. Afterward they are thawed and given back through a vein, where they rebuild the blood cells. This is called stem cell rescue, or an autologous transplant. It uses the patient’s own cells, so no registry match is needed.

U.S. transplant guidelines from NMDP and ASTCT say this own-cell treatment may be considered for an NGGCT that did not go away with first chemotherapy, or one that came back. This applies when the tumor still responds to chemotherapy and no large tumor is left. A donor (allogeneic) transplant is not a standard treatment. European transplant experts (EBMT, 2025) say donor transplants for children with solid tumors should be explored only in clinical trials. Joining a registry helps people with many other conditions who do need a donor.