eMedicine Specialties > Oncology > Carcinomas of the Central and Peripheral Nervous System

Germinoma, Central Nervous System

Author: Daniel D Mais, MD, Medical Director of Hematopathology, Surgical Pathologist, St Joseph's Mercy Hospital and Warde Medical Laboratory
Coauthor(s): Timothy J Murphy, MD, Consulting Staff, Cancer Center of Colorado Springs; Thomas B Repine, MD, Fellow, Department of Hematology/Oncology, Brooke Army Medical Center
Contributor Information and Disclosures

Updated: Nov 21, 2006

Introduction

Background

The central nervous system is the second most common site of extragonadal germ cell tumors, after the mediastinum. Germ cell tumors are broadly divided into germinomas and nongerminomatous germ cell tumors. Germinomas originate from a primordial germ cell, demonstrate no histologic differentiation, and with treatment have a relatively favorable overall prognosis. Nongerminomatous germ cell tumors (yolk sac tumors, choriocarcinomas, embryonal carcinomas, and teratomas) display various forms of differentiation and are more refractory to treatment. Most intracranial germ cell tumors arise in the midline, and they account for about 50% of all pineal region tumors. A slight majority of these (60%) are germinomas.

Pathophysiology

Germ cell tumors arise in midline locations, including the gonads, mediastinum, retroperitoneum, and CNS from neoplastic transformation of embryonic germ cells that inappropriately migrated into or failed to migrate out of these locations during development.

While the underlying etiology remains unknown, approximately 90% of germ cell tumors are associated with structural chromosomal anomalies, especially an isochromosome on chromosome arm 12p known as i(12p). The i(12p) is often seen in germ cell tumors of adults (male or female) and male adolescents. The i(12p) has also been found in germ cell tumors associated with hematolymphoid neoplasms. Central nervous system germinomas in particular often display sex chromosome abnormalities, usually an increased number of copies of chromosome X.

Several lines of evidence lead to the belief that that germ cell tumors are gonadotropin-driven. Klinefelter syndrome (XXY genotype), for example, in which gonadotropin levels are chronically elevated, is associated with an increased risk of germ cell tumors. However, this association may have more to do with chromosomal anomalies.

From several lines of evidence, it is thought that germ cell tumors are gonadotropin-driven. Klinefelter syndrome (XXY genotype), for example, in which gonadotropin levels are chronically elevated, is associated with an increased risk of germ cell tumors. However, this association may have more to do with chromosomal anomalies.

Lastly, it is now recognized that most germinomas contain c-kit mutations. C-kit is a tyrosine kinase whose mutations may result in constitutive activation and which has been implicated in chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST).

Frequency

United States

Primary intracranial germ cell tumors account for only 2-5% of all CNS malignancies, and just over half of these are germinomas.

International

Primary intracranial germ cell tumors are more common in Asia, especially Japan, where they account for up to 10% of all CNS malignancies.

Mortality/Morbidity

For germinomas, the estimated survival rate is 75-95% at both 5 and 10 years.

  • Significant morbidity is most often due to treatment rather than the tumor itself, but direct tumor effects can be significant.
  • Spinal cord metastasis is observed in up to 10-15% of patients, but extraneural metastasis is very uncommon.
  • The survival rate is remarkably better than that for the nongerminomatous CNS germ cell tumors.

Race

Prevalence rates vary worldwide, with the highest frequency in Japan and Taiwan.

Sex

Males are affected more commonly than females, with an estimated male-to-female ratio of 2.5:1.

  • Among pineal germinomas, males outnumber females by about 3:1.
  • Among suprasellar germinomas, females slightly outnumber males.

Age

Intracranial germ cell tumors are seen primarily in children and adolescents.

  • Ninety percent of patients present when younger than 20 years, and 98% when younger than 30 years.
  • The incidence peaks in children aged 10-12 years.
  • Sixty-five percent or tumors arise in the second decade of life (age 11-20 years).

Clinical

History

As with intracranial tumors generally, the clinical presentation depends upon the tumor location and rate of growth.

  • The pineal region is the most common site for an intracranial germinoma, and 50-60% of cases present in this location. These tumors manifest with symptoms and signs of increased intracranial pressure, obstructive hydrocephalus, or both. Common nonspecific complaints include headache, nausea, vomiting, and Parinaud syndrome.
    • Compression of the quadrigeminal plate causes Parinaud syndrome.
    • Parinaud syndrome is characterized by an upward gaze palsy, loss of convergence, pupillary dilation with poor reactiveness to light, and nystagmus.
  • Germinomas arising in the suprasellar region are observed more often in females than in males and are the site of approximately 30% of intracranial germ cell tumors. These may present with visual field defects due to impingement upon the optic chiasm or with endocrine manifestations due to effects upon the hypothalamic-pituitary axis.
    • Common endocrine manifestations include diabetes insipidus, retarded growth, precocious puberty, secondary amenorrhea, and panhypopituitarism.
    • The spectrum of visual symptoms includes deficits in visual acuity (84% of patients), failure of pupillary contraction to light, diplopia, and bitemporal hemianopsia.
  • Case reports describe involvement of the ventricles, basal ganglia, cerebellum, brain stem, and spinal subarachnoid spaces. These tumors can also be involved in the production of site-specific features based on direct tumor effects at their location. Multifocal germ cell tumors are not uncommon, are usually bifocal, and most often involve the pineal and suprasellar compartments simultaneously.

Physical

Focus the physical examination on identification of cranial nerve deficits, visual-field cuts, and visual acuity. Be aware of the physical manifestations of endocrinopathies such as hypothyroidism, precocious puberty, and hypogonadism.

Causes

Specific causes of germ cell tumors have not been identified.

More on Germinoma, Central Nervous System

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References
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Further Reading

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Keywords

intracranial germinoma, pinealoma, ectopic pinealoma, atypical teratoma, germ cell tumor, germ-cell tumor, GCT, CNS germ cell tumor, CNS germinoma, atypical teratomas, pinealomas, ectopic pinealomas, CNS malignancy, malignant CNS tumor, central nervous system germinoma

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Contributor Information and Disclosures

Author

Daniel D Mais, MD, Medical Director of Hematopathology, Surgical Pathologist, St Joseph's Mercy Hospital and Warde Medical Laboratory
Daniel D Mais, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Pathologists, and College of American Pathologists
Disclosure: Nothing to disclose.

Coauthor(s)

Timothy J Murphy, MD, Consulting Staff, Cancer Center of Colorado Springs
Timothy J Murphy, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, and American Society of Hematology
Disclosure: Nothing to disclose.

Thomas B Repine, MD, Fellow, Department of Hematology/Oncology, Brooke Army Medical Center
Thomas B Repine, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Benjamin Movsas, MD, Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Therapeutic Radiology and Oncology, and American Society of Clinical Oncology
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

John S Macdonald, MD, Professor of Medicine, New York Medical College; Chief, Division of Medical Oncology, St Vincent's Hospital and Medical Center; Medical Director, Saint Vincent's Comprehensive Cancer Center
Disclosure: Nothing to disclose.

 
 
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