Central Nervous System Germinoma Clinical Presentation

Updated: May 04, 2015
  • Author: Amani A Al Kofide, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Presentation

History

The clinical presentation in central nervous system (CNS) germ cell tumors (GCTs) varies, depending on the age of patient, the site of the tumor, and the duration of the disease. [7, 33, 34, 35] Typical presentations by age are as follows:

  • 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 [32] ; 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 34-50% of cases. It is due to compression of the tectum. The syndrome includes the following ophthalmic manifestations:

  • Paralysis of upward gaze
  • Loss of light perception and accommodation
  • Nystagmus
  • 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, 36] 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.

Rare presentations

Rare presentations of CNS GCTs include the following:

  • Multiple lesions - GCTs in the pineal, sellar region, corpus callosum, and ventricles was reported in an 18-year-old man who presented with psychosis [37]
  • Wide skull base extension - This was reported in a 15-year-old girl with radiologic evidence of central skull base and suprasellar tumor extending into the cavernous sinus, intraorbital region, ethmoid sinus, sphenoid sinus, and pituitary fossa [38]
  • Optic pathway - Intracranial germ cell tumors may occur primarily in the optic nerve and/or optic chiasma with progressive, painless visual loss [39, 40, 41] ; therefore, biopsy for definitive diagnosis may be required in patients with imaging studies suggestive of optic gliomas who have visual loss with hypothalamic-pituitary-adrenal dysfunction [42]
  • Midbrain outflow tremor (Holmes tremor) - Holmes tremor is a hyperkinetic movement disorder that presents as mild to severe tremors, dystonia, and cerebellar deficits; it has been reported in patients with germinoma [43, 44]
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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, 33, 16, 17] 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. [45] In vitro studies have shown that tumor growth factor beta 1 may initiate the migration of primordial germ cells. [46]

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. [47]

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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