Intracranial germ-cell tumors: natural history and pathogenesis

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✓ The natural history of primary intracranial germ-cell tumors (GCT's) is defined from 389 previously published cases, of which 65% were germinomas, 18% teratomas, 5% embryonal carcinomas, 7% endodermal sinus tumors, and 5% choriocarcinomas. Intracranial GCT's display specificity in site of origin. Ninety-five percent arise along the midline from the suprasellar cistern (37%) to the pineal gland (48%), and an additional 6% involve both sites. The majority of germinomas (57%) arise in the suprasellar cistern, while most nongerminomatous GCT's (68%) preferentially involve the pineal gland (p < 0.0001). The age distribution of afflicted patients is unimodal, centering with an abrupt surge in frequency in the early pubertal years; 68% of patients are diagnosed between 10 and 21 years of age. Nongerminomatous GCT's demonstrate an earlier age of onset than do germinomas (p < 0.0001). Prolonged symptomatic intervals prior to diagnosis are common in germinomas (p = 0.0007), in suprasellar GCT's (p = 0.001), and among females (p = 0.02). Parasellar germinomas commonly present with diabetes insipidus, visual field defects, and hypothalamic-pituitary failure. Nongerminomatous GCT's present as posterior third ventricular masses with hydrocephalus and midbrain compression. Germ-cell tumors may infiltrate the hypothalamus (11%), or disseminate to involve the third ventricle (22%) and spinal cord (10%). Among a subpopulation of 263 conventionally treated patients, two factors were of prognostic significance: 1) histological diagnosis; germinomas were associated with significantly longer survival than nongerminomatous GCT's (p < 0.0001); and 2) staging of the extent of disease; this emphasizes the ominous character of involvement of the hypothalamus (p = 0.0002), third ventricle (p = 0.02), or spinal cord (p = 0.01). Specific recommendations regarding the necessity of histological diagnosis and staging of the extent of disease are made in light of modern chemotherapeutic advances.

The pathogenesis of GCT's may be revealed by their specificity of origin within the positive (suprasellar cistern-suprachiasmatic nucleus) and negative (pineal) regulatory centers for gonadotropin secretion within the diencephalon. The abrupt rise in age distribution at 10 to 12 years suggests that the neuroendocrine events of puberty are an “activating” influence in the malignant expression of these embryonal tumors.

Article Information

Address reprint requests to: Mark T. Jennings, M.D., Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021.

© AANS, except where prohibited by US copyright law.

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Figures

  • View in gallery

    Distribution by age at diagnosis for all patients with intracranial germ-cell tumors. (Reproduced with permission from Jennings MT, Gelman R, Hochberg F: Intracranial germ cell tumors: natural history and pathogenesis, in Neuwelt EA (ed): Diagnosis and Treatment of Pineal Region Tumors. Baltimore: Williams & Wilkins, 1984, pp 116–138.)

  • View in gallery

    Distribution by age at diagnosis for patients with intracranial teratoma (upper left), embryonal carcinoma (upper right), endodermal sinus tumor (lower left), and choriocarcinoma (lower right). Cong'l = congenital. (Reproduced with permission from Jennings MT, Gelman R, Hochberg F: Intracranial germ cell tumors: natural history and pathogenesis, in Neuwelt EA (ed): Diagnosis and Treatment of Pineal Region Tumors. Baltimore: Williams & Wilkins, 1984, pp 116–138.)

  • View in gallery

    Distribution by age at diagnosis for patients with intracranial germinoma. (Reproduced with permission from Jennings MT, Gelman R, Hochberg F: Intracranial germ cell tumors: natural history and pathogenesis, in Neuwelt EA (ed): Diagnosis and Treatment of Pineal Region Tumors. Baltimore: Williams & Wilkins, 1984, pp 116–138.)

  • View in gallery

    Left: Kaplan-Meier survival curves and quartile survival periods for primary intracranial germinomas and nongerminomatous germ-cell tumors (GCT's). Right: Kaplan-Meier survival curves and quartile survival periods for each histological category of primary intracranial GCT. Abbreviations: G = germinoma; T = teratoma; EC = embryonal carcinoma; EST = endodermal sinus tumor; and CC = choriocarcinoma. (Reproduced with permission from Jennings MT, Gelman R, Hochberg F: Intracranial germ cell tumors: natural history and pathogenesis, in Neuwelt EA (ed): Diagnosis and Treatment of Pineal Region Tumors. Baltimore: Williams & Wilkins, 1984, pp 116–138.)

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