What is an Intracranial Germ Cell Tumor?
Germ cell tumors (GCTs) arise from primordial germ cells that did not migrate appropriately during embryonic development. Residual primordial germ cells deposited in the brain give rise to intracranial germ cell tumors. These residual primordial germ cells tend to be located in the midline of the body; therefore intracranial germ cell tumors typically originate in the suprasellar or pineal region. Rarely GCTs originate in other midline intracranial locations including the basal ganglia, thalamus, and ventricles. Intracranial germ cell tumors are twice as likely to be located in the pineal region compared to the suprasellar region. Approximately 5-10% of cases have “bi-focal” disease, defined as simultaneous involvement of the suprasellar and pineal region. Intracranial germ cell tumors mainly occur in adolescents and young adults (peak incidence is 10-12 years of age) and are more commonly seen in boys. These tumors have the capacity to spread (metastasize) through the spinal fluid (leptomeningeal spread).
There are two distinct histological groups of intracranial germ cell tumors: germinomas and non-germinomatous germ cell tumors (NGGCT).
Germinomas make up two thirds of all intracranial germ cell tumors. Germinomas are malignant tumors. They are more commonly seen in boys compared to girls. The preferred location for germinomas is the pineal region. Germinomas are mainly seen in adolescents and young adults.
Non-germinomatous germ cell tumors (NGGCT) make up one third of intracranial germ cell tumor and consist of several different subtypes (endodermal sinus tumor (yolk sac tumor), embryonal carcinoma,choriocarcinoma, teratoma and germ cell tumors of mixed origin termed mixed germ cell tumors). All NGGCTs are malignant tumors, except for mature and immature teratomas. NGGCTs have a more equal distribution between boys and girls and are seen in all pediatric age groups.
Intracranial germ cell tumors account for less than 4% of pediatric brain tumors in North America. For unknown reasons the incidence of GCTs is higher in Japan and Taiwan where they account for up to 11% of pediatric brain tumors. There are no known risk factors for the development of intracranial GCTs other than living in Japan and Taiwan and being of male gender.
What are the symptoms of an Intracranial Germ Cell Tumor?
The symptoms of GCTs depend on the location of the tumor. Pineal region tumors usually present with eye movement abnormalities (difficulty looking up) or increased intracranial pressure (headache, vomiting, poor balance and lethargy) due to obstructive hydrocephalus. Tumors located in the suprasellar region may present with pituitary dysfunction including excessive urination and thirst due to diabetes insipidus (DI), growth failure, and precocious or delayed puberty.
How is an Intracranial Germ Cell Tumor diagnosed?
All patients with symptoms concerning for a brain tumor will undergo an MRI of the brain and spine to further define the location of the tumor and to assess if there is any metastatic (spread) disease. Some germ cell tumors secrete proteins termed “tumor markers” which aid in the diagnosis. Endodermal sinus tumors and embryonal tumors secrete alpha-feto protein (AFP). Choriocarcinomas and embryonal carcinomas secrete beta-human chorionic gonadotropin (BHCG). Mixed germ cell tumors and malignant teratoma may secrete AFP and/or BHCG.
Germinomas may secrete BHCG in low quantities. All patients should have blood and spinal fluid analyzed for AFP and BHCG. Depending on the AFP and BHCG values, the diagnosis of NGGCT (any AFP secreting tumor) vs. germinoma (low level of BHCG with normal AFP) might be possible without needing to biopsy the tumor. In cases where the diagnosis cannot be made by tumor markers, a biopsy of the tumor is required to make the final diagnosis. All patients require a spinal tap (lumbar puncture) to assess for microscopic spread of the tumor in the spinal fluid.
How is an Intracranial Germ Cell Tumor treated?
Germinomas that are diagnosed off tumor markers (low BHCG and normal AFP) require no surgery, because chemotherapy and radiation are curative, and surgical removal does not improve outcome but adds risk. In cases where a diagnosis cannot be made off markers, a surgery is required to biopsy the tumor to make the diagnosis. Cases where the tumor is causing obstructive hydrocephalus may require a 3rd floor ventriculostomy or placment of a VP shunt.
Chemotherapy and radiation therapy are both required to give the best outcome and the least long term side effects. Although radiation therapy alone is curative for germinomas, chemotherapy is usually recommended for children because it allows for reduction in the dose and volume of radiation. Following chemotherapy, radiation is given to provide the best outcome, but the dose and volume of radiation delivered depends on the response of the tumor to the chemotherapy and the presence of bifocal and/or metastatic disease at diagnosis.
Non-germinomatous germ cell tumors that are diagnosed off tumor markers (elevated AFP and normal or elevated BHCG or very high levels of BHCG) require no surgery initially. In cases where a diagnosis cannot be made off markers, a surgery is required to biopsy the tumor to make the diagnosis. Depending on the location of the tumor and ease of surgical removal, an attempt at complete surgical removal might be attempted at the initial surgery. Cases where the tumor is causing obstructive hydrocephalus may require a 3rd floor ventriculostomy or placment of a VP shunt. All NGGCTs require chemotherapy initially to shrink the tumor. If residual tumor remains after chemotherapy, a surgery is required to remove any residual tumor if possible. Radiation is then given to kill any remaining tumor cells. The dose and volume of radiation delivered is dependent on the response of the tumor to the chemotherapy, if residual tumor remains, and the presence of metastatic disease at diagnosis.
About treatment for Intracranial Germ Cell Tumor at Children’s Hospitals and Clinics of Minnesota
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