Intracranial germ-cell tumors: natural history and pathogenesis

1985 ◽  
Vol 63 (2) ◽  
pp. 155-167 ◽  
Author(s):  
Mark T. Jennings ◽  
Rebecca Gelman ◽  
Fred Hochberg
Keyword(s):  
Spinal Cord ◽  
Germ Cell ◽  
Third Ventricle ◽  
Age Distribution ◽  
Germ Cell Tumors ◽  
Content Type ◽  
Intracranial Germ Cell Tumors ◽  
Suprasellar Cistern ◽  
Extent Of Disease ◽  
Fine Print

✓ 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.

Pathogenesis of intracranial germ cell tumors reconsidered

1999 ◽  
Vol 90 (2) ◽  
pp. 258-264 ◽  
Author(s):  
Keiji Sano
Keyword(s):  
Survival Rate ◽  
Germ Cell ◽  
Survival Rates ◽  
Germ Cell Tumors ◽  
Yolk Sac ◽  
Endodermal Sinus Tumor ◽  
Content Type ◽  
Intracranial Germ Cell Tumors ◽  
Sinus Tumor ◽  
Fine Print

Object. To determine the pathogenesis of intracranial germ cell tumors (GCTs), the author studied 153 cases of these tumors encountered through 1994, 62.7% of which showed monotypic histological patterns and 37.3% of which were shown to be mixed tumors.Methods. Six patients died soon after admission and underwent autopsy; the other patients underwent surgery followed by radio- and/or chemotherapy. One hundred thirty-four cases were followed through the end of 1997. All patients with a choriocarcinoma died within 1 year. Patients with a yolk sac tumor (endodermal sinus tumor) or an embryonal carcinoma also had poor outcomes. Patients with a mature teratoma had 5- and 10-year survival rates of 93% each. Patients with an immature teratoma had 5- and 10-year survival rates of 86% each, whereas patients who had a teratoma with malignant transformation had a 3-year survival rate of 50%. Patients with a germinoma had a 5-year survival rate of 96% and a 10-year survival rate of 93%. These results may bring into question the validity of the germ cell theory because germinoma, which should be the most undifferentiated tumor according to the theory, was the most benign and choriocarcinoma and yolk sac tumor (endodermal sinus tumor), which should be the most differentiated tumors, were the most malignant according to results obtained during the follow-up study.Conclusions. Germ cell tumors other than germinomas may not originate from one single type of cell (primordial germ cells). The embryonic cells of various stages of embryogenesis may perhaps be misplaced in the bilaminar embryonic disc at the time of the primitive streak formation, becoming involved in the stream of lateral mesoderm and carried to the neural plate area to become incorrectly enfolded into the brain at the time of neural tube formation. The author propounds the following hypothesis: tumors composed of cells resembling the cells that appear in the earlier stages of embryogenesis (ontogenesis) are more malignant than those composed of cells resembling the cells that appear in the later stages of embryogenesis.

Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases

1997 ◽  
Vol 86 (3) ◽  
pp. 446-455 ◽  
Author(s):  
Masao Matsutani ◽  
Keiji Sano ◽  
Kintomo Takakura ◽  
Takamitsu Fujimaki ◽  
Osamu Nakamura ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Germ Cell ◽  
Malignant Tumors ◽  
Survival Rates ◽  
Germ Cell Tumors ◽  
Surgical Removal ◽  
Content Type ◽  
Intracranial Germ Cell Tumors ◽  
Mixed Tumors ◽  
Fine Print

✓ The authors analyzed 153 cases of histologically verified intracranial germ cell tumors. The histological diagnosis was germinoma in 63 patients (41.2%), teratoma in 30 (19.6%), and other types of tumors in 60 patients (39.2%). The patients were treated by a consistent policy of surgical removal with histological verification followed by radiation therapy with or without chemotherapy. The 10- and 20-year survival rates of patients with pure germinoma were 92.7% and 80.6%, respectively. The 10-year survival rates of patients with mature teratoma and malignant teratoma were 92.9% and 70.7%, respectively. Patients with pure malignant germ cell tumors (embryonal carcinoma, yolk sac tumor, or choriocarcinoma) had a 3-year survival rate of 27.3%. The mixed tumors were divided into three subgroups: 1) mixed germinoma and teratoma; 2) mixed tumors whose predominant characteristics were germinoma or teratoma combined with some elements of pure malignant tumors; and 3) mixed tumors with predominantly pure malignant elements. The 3-year survival rates were 94.1% for the first group, 70% for the second group, and 9.3% for the third group, and the differences were statistically significant. Twenty-six patients with malignant tumors received chemotherapy that consisted of cisplatin and carboplatin combinations with or without radiation therapy. However, chemotherapy was not significantly more effective than radiation therapy alone. From these treatment results, the authors classified tumors into three groups with different prognoses and proposed a treatment guideline appropriate for the subgroups.

Immunohistochemical study of placental alkaline phosphatase in primary intracranial germ-cell tumors

1985 ◽  
Vol 63 (5) ◽  
pp. 733-739 ◽  
Author(s):  
Jun Shinoda ◽  
Yoshiaki Miwa ◽  
Noboru Sakai ◽  
Hiromu Yamada ◽  
Hiroto Shima ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Germ Cell ◽  
Tumor Cells ◽  
Embryonal Carcinoma ◽  
Germ Cell Tumors ◽  
Positive Staining ◽  
Placental Alkaline Phosphatase ◽  
Content Type ◽  
Intracranial Germ Cell Tumors ◽  
Fine Print

✓ Indirect immunoperoxidase staining by the peroxidase-antiperoxidase (PAP) technique was carried out on 23 human primary intracranial germ-cell tumors (17 germinomas, one embryonal carcinoma, one yolk-sac tumor, three teratomas, and one teratoma with embryonal carcinoma) and on six human primary pineal nongerm-cell tumors (one pineocytoma, two pineoblastomas, two astrocytomas, and one glioblastoma multiforme). The technique used specific rabbit antisera against placental alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), and human chorionic gonadotropin (HCG). Thirteen of 17 intracranial germinomas (76.5%) showed positive staining for PLAP mainly on the tumor cell membrane. In six primary intracranial non-seminomatous germ-cell tumors, there was weak positive staining indicating the presence of PLAP in only a few cells of one embryonal carcinoma, and in some glandular epithelial cells of one teratoma; this staining was limited to the cytoplasm. None of the other six primary pineal non-germ-cell tumors showed any positive PLAP reaction. From these results, PLAP was shown to be very useful in histopathology as a diagnostic tumor marker of intracranial germinoma. Positive AFP staining was seen in several yolk-sac tumor cells and a few embryonal carcinoma cells. However, no intracranial germinomas and non-germ-cell tumors of the pineal region showed positive reaction. As for HCG, only one suprasellar germinoma and one pineal embryonal carcinoma among 29 specimens contained a few positive-staining tumor cells.

Precocious puberty in a girl with an hCG-secreting suprasellar immature teratoma

1994 ◽  
Vol 81 (4) ◽  
pp. 601-604 ◽  
Author(s):  
Chifumi Kitanaka ◽  
Masao Matsutani ◽  
Shigeo Sora ◽  
Sachiko Kitanaka ◽  
Ayako Tanae ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Precocious Puberty ◽  
Germ Cell Tumors ◽  
Immature Teratoma ◽  
Content Type ◽  
Intracranial Germ Cell Tumors ◽  
Hcg Secretion ◽  
High Level ◽  
Very High ◽  
Fine Print

✓ Although precocious puberty is common in boys with human chorionic gonadotropin (hCG)-secreting brain tumors, it is extremely rare in girls. The authors describe a 6-year-old girl with an hCG-secreting suprasellar immature teratoma who presented with diabetes insipidus, increased intracranial pressure, and precocious puberty. On admission, breast budding was observed. The serum hCG level was 1230 mIU/ml. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) remained below detectable levels, even after gonadotropin-releasing hormone stimulation. Serum estrogen and androgen were moderately elevated. After chemotherapy, breast budding disappeared with normalization of serum hCG. It has been believed that hCG does not produce precocious puberty in girls in the absence of FSH, and this has been used as an explanation for the rarity of precocious puberty in girls with hCG-secreting brain tumors. However, it has also been reported that hCG has not only LH activity but also intrinsic, although weak, FSH-like activity. In the present case, this FSH-like activity was considered to have played a role in the development of precocious puberty. It is speculated that a very high level of serum hCG can produce precocious puberty in girls. The rarity of intracranial germ-cell tumors with a high potential of hCG secretion may be one of the reasons why hCG-induced precocious puberty is uncommon in girls.

Combination chemotherapy with cisplatin and etoposide for malignant intracranial germ-cell tumors

1989 ◽  
Vol 70 (5) ◽  
pp. 676-681 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Jun Yoshida ◽  
Junzo Ishiyama ◽  
Satoshi Noda ◽  
Akira Kito ◽  
...  
Keyword(s):  
Germ Cell ◽  
Combination Chemotherapy ◽  
Germ Cell Tumors ◽  
Intracranial Germ Cell Tumor ◽  
Content Type ◽  
Total Response Rate ◽  
Intracranial Germ Cell Tumors ◽  
Dna Histograms

✓ Antitumor activity against intracranial malignant teratoma by combination chemotherapy with cisplatin and etoposide was evaluated in experimental and clinical studies. A human teratoma cell line (Tera 2) was exposed in vitro to cisplatin and/or etoposide, after which cell growth inhibition and alterations of deoxyribonucleic acid (DNA) histograms were observed. The results indicated that a synergistic cytotoxic effect was achieved by use of both agents in combination. Four cases of recurrent intracranial germ-cell tumor (three malignant teratomas and one germinoma) were treated with cisplatin and etoposide. With this combinationtherapy, regression of the tumor was observed in all four cases (three complete and one partial), for a total response rate of 100%. During a follow-up period of 9 to 22 months, no recurrence or progression has been noted in three of these cases.

Primary embryonal-cell carcinoma of the parietal lobe

1991 ◽  
Vol 75 (3) ◽  
pp. 468-471 ◽  
Author(s):  
Robin F. Koeleveld ◽  
Alan R. Cohen
Keyword(s):  
Cell Carcinoma ◽  
Parietal Lobe ◽  
Germ Cell Tumors ◽  
Review Of The Literature ◽  
Resonance Imaging ◽  
Content Type ◽  
Imaging Characteristics ◽  
Intracranial Germ Cell Tumors ◽  
Embryonal Cell Carcinoma ◽  
Fine Print

✓ A case of primary embryonal-cell carcinoma of the parietal lobe is reported. The unusually chronic presentation of such a malignant tumor is described. The atypical computerized tomography and magnetic resonance imaging characteristics of this lesion are presented. Review of the literature yielded no previous reports of a lobar embryonal-cell carcinoma. The rarity of intracranial germ-cell tumors presenting off the midline is discussed.

Intracranial germ-cell tumors in children

1991 ◽  
Vol 74 (4) ◽  
pp. 545-551 ◽  
Author(s):  
Harold J. Hoffman ◽  
Hiroshi Otsubo ◽  
E. Bruce Hendrick ◽  
Robin P. Humphreys ◽  
James M. Drake ◽  
...  
Keyword(s):  
Survival Rate ◽  
Adjuvant Therapy ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Pineal Region ◽  
Pineal Tumors ◽  
Content Type ◽  
Suprasellar Region ◽  
Intracranial Germ Cell Tumors ◽  
Sick Children

✓ All patients with confirmed intracranial germ-cell tumors treated at the Hospital of Sick Children during the period January, 1952, to December, 1989, were reviewed. Of the 51 tumors reviewed, 16 were located in the suprasellar region, 32 in the pineal region, and three in both the pineal and the suprasellar regions. Forty-nine patients underwent surgical resection which was total in seven and partial in 20, and consisted of a biopsy in 22. Two patients were managed on the basis of serum and cerebrospinal fluid markers. Surgical tools such as the operating microscope, the ultrasonic surgical aspirator, and the laser beam allowed safe debulking and removal of the deep-seated tumors in the pineal region. There were no operative deaths in the 36 patients treated since 1972, who included 23 with pineal tumors. Twenty-five patients with germinomas received radiotherapy and had a 5-year survival rate of 85.1%. Thirteen patients with non-germinoma germ-cell tumors received radiotherapy and had a 5-year survival rate of 45.5%. On the basis of this review, the authors recommend resection of pineal and suprasellar germ-cell tumors in order to firmly establish an accurate histological diagnosis to guide the extent of adjuvant therapy. In the case of a pure germinoma without evidence of dissemination, adjuvant therapy consists only of local radiotherapy. On the other hand, for malignant non-germinoma germ-cell tumors, adjuvant therapy must include chemotherapy as well as craniospinal axis radiotherapy.

Third ventricle germinoma after total removal of intrasellar teratoma

1992 ◽  
Vol 77 (4) ◽  
pp. 643-647 ◽  
Author(s):  
Sándor Czirják ◽  
Emil Pásztor ◽  
Felicia Slowik ◽  
György Szeifert
Keyword(s):  
Germ Cells ◽  
Third Ventricle ◽  
Relevant Literature ◽  
Germ Cell Tumors ◽  
Total Removal ◽  
Unique Case ◽  
Content Type ◽  
The Third ◽  
The Brain ◽  
Fine Print

✓ A unique case is presented of a third ventricle germinoma developing 3 years after total removal of an intrasellar teratoma. The third ventricle germinoma was not considered to be a recurrence or dissemination of the mature intrasellar teratoma but to have been transformed from multicenter germ cells present in the midline of the brain with different temporal development. The relevant literature is reviewed and the problems of management of patients with germ-cell tumors are discussed.

Diagnostic significance of soluble c-kit in the cerebrospinal fluid of patients with germ cell tumors

2002 ◽  
Vol 97 (1) ◽  
pp. 177-183 ◽  
Author(s):  
Osamu Miyanohara ◽  
Hideo Takeshima ◽  
Masatomo Kaji ◽  
Hirofumi Hirano ◽  
Yutaka Sawamura ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Cell Types ◽  
Giant Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diagnostic Significance ◽  
Content Type ◽  
Tumor Dissemination ◽  
Fine Print

Object. Overexpression of the protooncogene c-kit has been suggested in a gonadal germ cell tumor (GCT). Recently, the soluble isoform of c-kit (s-kit) has been expressed in a variety of cell types. The goal of this study was to investigate the expression of c-kit and the clinical significance of s-kit in patients with GCTs. Methods. The authors first conducted an immunohistochemical investigation of the expression of the c-kit protein in 27 surgical specimens. In all 18 specimens that contained germinomas, c-kit was diffusely expressed on the cell surface of the germinoma cells, but was not found on lymphocytes or interstitial cells. In seven of eight immature teratomas, only some mature components, such as cartilage and glands, were immunoreactive for c-kit. Syncytiotrophoblastic giant cells (STGCs) demonstrated negative findings as well, suggesting that primarily germinoma cells express c-kit. Next, 47 cerebrospinal fluid (CSF) samples collected from 32 patients with GCTs (15 samples from patients with pure germinomas, 16 from patients with STGC germinomas, 14 from patients with teratomas, and two from a patient with a choriocarcinoma) were analyzed using a sandwich enzyme-linked immunosorbent assay. The level of s-kit was significantly higher in CSF collected from patients with germinomas and STGC germinomas than in CSF collected from patients with teratomas or non—germ cell brain tumors, or in CSF collected from controls. The concentration of s-kit in CSF was correlated with the patient's clinical course; it was significantly higher in pretreatment samples obtained before and in samples obtained at the time of tumor recurrence than in samples collected from patients in whom the tumor was in remission. The level of s-kit was remarkably high in CSF collected from patients with subarachnoid tumor dissemination. Conclusions. These results indicate that the concentration of s-kit in CSF may be a useful clinical marker for germinomas, especially for detecting recurrence or subarachnoid dissemination of these lesions.

Control of extraneural metastasis of a primary intracranial nongerminomatous germ-cell tumor

1989 ◽  
Vol 71 (4) ◽  
pp. 601-604 ◽  
Author(s):  
Jan Watterson ◽  
John R. Priest
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Germ Cell Tumors ◽  
Whole Brain Radiotherapy ◽  
Pineal Region ◽  
Cell Tumor ◽  
High Dose ◽  
Content Type ◽  
Extraneural Metastasis ◽  
Fine Print

✓ Primary intracranial germ-cell tumors are infrequently occurring neoplasms which most often arise in the pineal or sellar regions. Germinomas are seen more frequently than nongerminomatous germ-cell tumors; they are often curable with radiotherapeutic approaches, or with chemotherapy in the rare instance of extraneural metastasis. Nongerminomatous germ-cell tumors are relatively radioresistant and when extraneural metastasis has occurred, they have been fatal in all of the 32 previously reported cases. The case of a 14-year-old girl with a mixed malignant germ-cell tumor arising in the pineal region is reported. Extraneural metastasis to the lung developed 12 months after whole-brain radiotherapy was completed. She was treated with etoposide (VP-16), high-dose cisplatin, vinblastine, and bleomycin and is currently without evidence of disease 46 months postmetastasis.

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