Intracranial germ-cell tumors: natural history and pathogenesis

Abstract

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 less than 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 less than 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 less than 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.

Pre‐radiation chemotherapy with response‐based radiation therapy in children with central nervous system germ cell tumors: A report from the Children's Oncology Group

“…Germ cell tumors of the brain include pure germinomas, which may be successfully treated in 85-100% of patients with radiation therapy, and the more diverse nongerminomatous germ cell tumors, which tend to recur after standard radiation (20-45% reported 5-year survivals) [1][2][3][4][5]. The biologic disparity between pure germinomas and nongerminomatous tumors is also supported by the difference in mean age at diagnosis (adolescent versus middle school years), with nongerminomatous tumors having a more heterogeneous appearance with spread to distant structures [1][2][3][4][5].…”

“…The biologic disparity between pure germinomas and nongerminomatous tumors is also supported by the difference in mean age at diagnosis (adolescent versus middle school years), with nongerminomatous tumors having a more heterogeneous appearance with spread to distant structures [1][2][3][4][5]. With the goal of reducing potential late sequelae of cranial radiation [6][7][8][9][10][11], platinum-based regimens have sought to decrease radiation dose by administering chemotherapy before reduced radiation [12][13][14][15][16].…”

Effects of Therapy on Anterior Pituitary Functions in Patients with Primary Intracranial Germ Cell Tumor.

“…INTRACRANIAL germ cell tumors mainly occur in adolescents and young adults, and their incidence is relatively high in Japan, being calculated to be 2.1 to 9.4% of all intracranial neoplasms occurring in adolescents and young adults [1,2]. According to cells of origin, germ cell tumors can be divided into germinoma and non-germinomatous germ cell tumor (teratoma, embryonal cell carcinoma, choriocarcinoma, endodermal sinus carcinoma and mixed germ cell tumors) [3].…”

Germinoma localizado nos núcleos da base e tálamo com invasão do tronco cerebral: relato de caso

“…Os germinomas se originam de estruturas medianas, tais como o mediastino anterior, retroperitônio, gônadas, região sacrococcígea, raramente nasofaringe e órbitas, ou do sistema nervoso central (SNC), onde se localizam preferencialmente nas regiões pineal e supra-selar, também chamadas de "localizações típicas" 1,2 . Os germinomas localizados nos núcleos da base e tálamo são raros, correspondendo a cerca de 5 a 10% dos germinomas intra-cranianos [1][2][3][4] .…”

“…Os germinomas localizados nos núcleos da base e tálamo são raros, correspondendo a cerca de 5 a 10% dos germinomas intra-cranianos [1][2][3][4] . As imagens de tomografia computadorizada (TC) e ressonância magnética (RM) dos germinomas localizados nos núcleos da base e tálamo diferem daqueles observados nas regiões pineal e supra-selar 2,[4][5][6] .…”