General Information About Childhood Central Nervous System (CNS) Germ Cell Tumors
The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization classification of nervous system tumors.[1,2] For a full description of the classification of nervous system tumors and a link to the corresponding treatment summary for each type of brain tumor, refer to the PDQ summary on Childhood Brain and Spinal Cord Tumors Treatment Overview.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2002, childhood cancer mortality has decreased by more than 50%. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification.Anatomy
Central nervous system (CNS) germ cell tumors (GCTs) may arise from the pineal and/or suprasellar regions as solitary or multiple lesions. Pineal region tumors are twice as frequent as suprasellar tumors, but approximately 5% to 10% of patients have both suprasellar and pineal gland involvement at the time of diagnosis. Involvement of both sites is most commonly seen in pure germinomas. Males have a higher incidence of GCT than females, with males having a preponderance of pineal region primaries. Other areas that may be involved, though rare, include the basal ganglia, ventricles, thalamus, cerebral hemispheres, and the medulla.[5,6]Diagnosis
Radiographic characteristics of CNS GCTs cannot reliably differentiate germinomas from nongerminomatous germ cell tumors (NGGCTs) or from other CNS tumors. The diagnosis of GCTs is based on clinical symptoms and signs, tumor markers, neuroimaging, and cytological cerebrospinal fluid (CSF) and histological confirmation. Patients with intracranial GCTs often present with pituitary dysfunction including diabetes insipidus (DI), with an increased presence in patients with tumors involving the suprasellar region. Two-thirds to 90% of patients with a GCT of the suprasellar region present with DI.[7,8] Patients with tumors in the pineal region may also present with DI without imaging evidence of third ventricular and suprasellar involvement. Visual loss, growth hormone deficiency, precocious puberty (suprasellar tumors), and Parinaud syndrome (pineal tumors) are also common. Nonspecific symptoms such as enuresis, anorexia, and psychiatric complaints can lead to delays in diagnosis, whereas signs of increased intracranial pressure or visual changes tend to result in earlier diagnosis.
Appropriate staging is crucial since patients with metastatic disease should receive different total radiation doses and more extended radiation fields. All patients with a suspected CNS GCT should have the following tests:
- Magnetic resonance imaging (MRI) of brain and spine with gadolinium.
- Alpha-fetoprotein (AFP) and beta subunit human chorionic gonadotropin (beta-HCG) in both serum and CSF. If pre-operative lumbar CSF can be obtained safely and tumor markers are elevated, this may obviate the need for upfront surgery. Lumbar CSF is preferred and is more sensitive than serum markers for beta-HCG. In cases where the patient presents with hydrocephalus requiring CSF diversion, CSF tumor markers can be obtained by ventricular CSF sampling at the time of surgery.
- CSF cytology.
- Evaluation of pituitary/hypothalamic function.
- Visual field examinations for suprasellar or hypothalamic tumors.
- Baseline neuropsychologic examination.
Diagnosis of GCTs often requires a tumor biopsy, except in cases with characteristic increased tumor markers in the serum and/or CSF. When the tumor markers are negative or mildly elevated but below diagnostic criteria, or if there is any noncharacteristic finding, a tumor biopsy should be done.References
- Louis DN, Ohgaki H, Wiestler OD, et al., eds.: WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon, France: IARC Press, 2007.
- Louis DN, Ohgaki H, Wiestler OD, et al.: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 (2): 97-109, 2007. [PUBMED Abstract]
- Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
- Weksberg DC, Shibamoto Y, Paulino AC: Bifocal intracranial germinoma: a retrospective analysis of treatment outcomes in 20 patients and review of the literature. Int J Radiat Oncol Biol Phys 82 (4): 1341-51, 2012. [PUBMED Abstract]
- Goodwin TL, Sainani K, Fisher PG: Incidence patterns of central nervous system germ cell tumors: a SEER Study. J Pediatr Hematol Oncol 31 (8): 541-4, 2009. [PUBMED Abstract]
- Villano JL, Propp JM, Porter KR, et al.: Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries. Neuro Oncol 10 (2): 121-30, 2008. [PUBMED Abstract]
- Afzal S, Wherrett D, Bartels U, et al.: Challenges in management of patients with intracranial germ cell tumor and diabetes insipidus treated with cisplatin and/or ifosfamide based chemotherapy. J Neurooncol 97 (3): 393-9, 2010. [PUBMED Abstract]
- Hoffman HJ, Otsubo H, Hendrick EB, et al.: Intracranial germ-cell tumors in children. J Neurosurg 74 (4): 545-51, 1991. [PUBMED Abstract]
- Crawford JR, Santi MR, Vezina G, et al.: CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. Neurology 68 (20): 1668-73, 2007. [PUBMED Abstract]
- Allen J, Chacko J, Donahue B, et al.: Diagnostic sensitivity of serum and lumbar CSF bHCG in newly diagnosed CNS germinoma. Pediatr Blood Cancer 59 (7): 1180-2, 2012. [PUBMED Abstract]