Central Nervous System Germinoma Clinical Presentation

  • Author: Amani Al-Kofide, MBBS; Chief Editor: Jules E Harris, MD   more...
 
Updated: Aug 17, 2011
 

History

Clinical presentation varies, depending on age of patient and site of tumor.[7] [27]

  • Prenatal/neonate – Congenital teratomas produce polyhydramnios and hydrocephalus; ultrasound will show a heterogeneous echogenic mass with cystic and solid components.
  • Young infants -  The teratoma and choriocarcinoma subtypes of nongerminoma germ cell tumor are most common in this age group.[26] These patients may present with irritability, listlessness, failure to thrive, macrocephaly, and bulging fontanelle.
  • Beyond Infancy – Presentation depends on tumor location.

Pineal region tumors

Parinaud syndrome is one of the most common presentation in CNS GCTs, seen in for 34-50 % of cases. It is due to compression on the tectum. The syndrome comprises paralysis of upward gaze, loss of light perception and accommodation, nystagmus, and failure of convergence.

Features of increased intracranial pressure may supervene. These include headache, nausea and vomiting, and papilledema. Somnolence, ataxia, seizures, and behavioral abnormalities may develop.

Precocious puberty may develop in a pre-pubertal child.

Diabetes insipidus and anterior hypopituitarism are rare occurrences and may indicate involvement of floor of the fourth ventricle and suprasellar area.[10]

Suprasellar region tumors

Patients with suprasellar GCTs usually present with endocrine deficits. These include the following:

  • Anterior hypopituitarism and Diabetes insipidus (DI)
  • Thyroid and/or cortisol deficiency
  • Growth failure from growth hormone deficiency
  • Delayed puberty from gonadotrophin deficiency
  • Regression of sexual development or sexual dysfunction
  • Posterior pituitary dysfunction (vasopressin deficiency)
  • Precocious puberty may develop in a pre-pubertal child (due to tumor-induced hypothalamic injury or secretion of human chorionic gonadotrophin by the tumor).

Visual disturbances may include diplopia, blurred vision, and diminished vision. Enuresis and psychiatric abnormalities may develop.[7, 5, 28] In general, patients with symptoms of increased intracranial pressure and visual changes tend to present earlier in the disease course than patients with endocrine dysfunction.

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Physical

The clinical evaluation should include the following:

  • General physical examination
  • Check of growth parameters
  • Careful neurological evaluation, with assessment for neurocutaneous stigmata
  • Assessment of primary and secondary sexual characteristics
  • Ophthalmological exam.
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Causes

The exact cause of CNS GCTs is unknown. GCTs appear to arise from primordial germ cells that migrate to the germinal ridges in the developing embryo.[5, 27, 15, 16] This process appears to be under the control of complex molecular events. Aberration in any of these molecular pathways may potentially give rise to GCTs.

Important factors in cell migration include the extracellular matrix, which affects cell adherence and migration. Other factors, such as chemotropic factors, may also be involved in cell migration.[29] In vitro studies have shown that tumor growth factor beta 1 may initiate the migration of primordial germ cells.[30]

Some primordial germ cells that have left the yolk sac endoderm migrate aberrantly cranially towards the diencephalic midline structures rather than laterally to genital ridges.

Maturation of the fetal hypothalamus coincides with the migration of primordial germ cells. The fetal hypothalamus may secrete chemotrophic factors that attract primordial germ cells to the diencephalon.[31]

The vacular theory may be an alternative event in which the primodial germ cells migrate into the mesenchyme of the mesentery and stimulate blood vessel formation and may reach intracranial locations via the circulation.

Once the primordial germ cells have reached their intracranial location through abnormal pathways, congenital or acquired aberrant molecular events occur in the primordial germ cell itself or in the surrounding microenvironment, leading to the formation of CNS GCTs.

The surge of the neuroendocrine functions of reproduction in the diencephalon may also be a cause or contributing factor to the development of CNS GCTs, as demonstrated by the location of these tumors and their predominance in the pubertal age group ref Jennings et al, Intracranial germ cell tumors natural history and pathogenesis.

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Contributor Information and Disclosures
Author

Amani Al-Kofide, MBBS  Assistant Professor, Alfaisal University College of Medicine; Consultant, Department of Pediatric Hematology and Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh

Amani Al-Kofide, MBBS, is a member of the following medical societies: American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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, and American Society for Therapeutic Radiology and Oncology

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, 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

Jules E Harris, MD  Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

Additional Contributors

Hindi N Al-Hindi, MD, FCAP

Consultant Anatomic Pathologist and Neuropathologist

Coordinator, Anatomic Pathology Residency Training Program

Director of Electron Microscopy Services

Department of Pathology and Laboratory Medicine

King Faisal Specialist Hospital & Research Center

P O Box 3354

Riyadh 11211

Kingdom of Saudi Arabia

Tel 966 1 442 4207

Fax 966 1 442 4280

email: hal-hindi@kfshrc.edu.sa

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MRI of the brain - T1 weighted-image- coronal view- showing a heterogeneously enhancing, multicystic mass in the suprasellar region
MRI of the brain - axial view- heterogeneous mass lesion measuring approximately 3.2 x 2.9 x 4.0 cm.
MRI of the brain - T1-weighted image - post-gadolinium sagittal view- A suprasellar lesion that severely compresses the optic chiasm encases the posterior aspect of the optic nerves bilaterally and causes superior displacement of the third ventricle, with significant compression of the brain stem.
Biopsy specimen from an intracranial germ cell tumor - Large tumor cells with large nuclei; prominent nucleoli; and abundant, clear cytoplasm (rich in glycogen) are noted among reactive inflammatory cells--lymphocytes and histiocytes. Elsewhere there are well-formed granulomas, a well-known phenomenon in germinomas, especially of the pineal region.
Table1: Immunohistochemical findings of CNS GCTs[6, 16, 25]
Tumor typeβ- HCGAFPPLAPc-Kit
Germinoma-Pure--+/-+
Germinoma with STGC+-+/-+
Endodermal sinus tumor-++/--
Choriocarcinoma+-+/--
Embryonal Carcinoma--+-
Mixed Teratoma+/-+/-+/-+/-
Mature Teratoma----
Immature teratoma+/-+/--+/-
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