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.

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.

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.

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.

Characterization of a model of hydrocephalus in transgenic mice

1999 ◽  
Vol 91 (6) ◽  
pp. 978-988 ◽  
Author(s):  
Alan R. Cohen ◽  
David W. Leifer ◽  
Marc Zechel ◽  
Daniel P. Flaningan ◽  
Jonathan S. Lewin ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Transgenic Mice ◽  
Clinical Manifestations ◽  
Congenital Hydrocephalus ◽  
Immunofluorescent Staining ◽  
Pcr Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Fine Print

Object. The purpose of this study was to elucidate the pathophysiological characteristics of hydrocephalus in a new transgenic model of mice created to overproduce the cytokine transforming growth factor—β1 (TGFβ1) in the central nervous system (CNS).Methods. Galbreath and colleagues generated transgenic mice that overexpressed TGFβ1 in the CNS in an effort to examine the role of this cytokine in the response of astrocytes to injury. Unexpectedly, the animals developed severe hydrocephalus and died. The authors have perpetuated this transgenic colony to serve as a model of congenital hydrocephalus, breeding asymptomatic carrier males that are heterozygous for the transgene with wild-type females.One hundred twelve (49.6%) of 226 mice developed clinical manifestations of hydrocephalus, characterized by dorsal doming of the calvaria, spasticity, limb tremors, ataxia, and, ultimately, death. The presence of the TGFβ1 transgene was determined by performing polymerase chain reaction (PCR) analysis of sample tail slices. Animals with the hydrocephalic phenotype consistently carried the transgene, although some animals with the transgene did not develop hydrocephalus. Animals without the transgene did not develop hydrocephalus.Alterations in brain structure were characterized using magnetic resonance (MR) imaging, gross and light microscopic analysis, and immunocytochemical studies. Magnetic resonance imaging readily distinguished hydrocephalic animals from nonhydrocephalic controls and demonstrated an obstruction at the outlets of the fourth ventricle. Gross and light microscopic examination confirmed the MR findings. The results of immunofluorescent staining of brain tissue slices revealed the presence of the TGFβ1 cytokine and its receptor preferentially in the meninges and subarachnoid space in both hydrocephalic and control mice. Reverse transcriptase—PCR analysis demonstrated tissue-specific expression of the TGFβ1 gene in the brains of transgenic mice, and enzyme-linked immunosorbent assay confirmed overexpression of the TGFβ1 cytokine in brain, cerebrospinal fluid, and plasma.Conclusions. The transgenic murine model provides a reproducible representation of congenital hydrocephalus. The authors hypothesize that overexpression of TGFβ1 in the CNS causes hydrocephalus by altering the environment of the extracellular matrix and interfering with the circulation of cerebrospinal fluid. A model of hydrocephalus in which the genetic basis is known should be useful for evaluating hypotheses regarding the pathogenesis of this disorder and should also help in the search for new treatment strategies.

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.

Successful treatment of intracranial nongerminomatous malignant germ cell tumors by administering neoadjuvant chemotherapy and radiotherapy before excision of residual tumors

2003 ◽  
Vol 99 (1) ◽  
pp. 106-114 ◽  
Author(s):  
Masato Kochi ◽  
Youichi Itoyama ◽  
Shoji Shiraishi ◽  
Isao Kitamura ◽  
Toru Marubayashi ◽  
...  
Keyword(s):  
Germ Cell ◽  
Neoadjuvant Therapy ◽  
Germ Cell Tumors ◽  
Residual Tumor ◽  
Complete Response ◽  
Complete Excision ◽  
Content Type ◽  
Platinum Based Chemotherapy ◽  
Malignant Germ Cell Tumors ◽  
Fine Print

Object. The goal of this study was to confirm the effectiveness of our novel treatment strategy, neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy, which are performed before complete excision of residual tumor in patients with intracranial nongerminomatous malignant germ cell tumors (NGMGCTs). Methods. The authors treated 11 consecutive patients with NGMGCTs by applying NAT consisting of combined platinum-based chemotherapy and radiotherapy, followed by complete excision of residual tumors. The pretreatment diagnosis, based on tumor markers with or without biopsy, was yolk sac tumor in five patients, embryonal carcinoma in one patient, immature teratoma in one patient, and mixed germ cell tumor containing malignant tumor components in four patients. Among the 11 patients, NAT achieved a complete response in two and a partial response in six patients; two patients manifested no change and one suffered disease progression. Residual tumors that occurred post-NAT were surgically removed in nine patients. Of the 11 patients, 10 are currently alive without recurrence of their disease, 30 to 177 months (mean 96 months) after diagnosis. In one patient a leptomeningeal tumor recurred and he died of the disease 21 months after diagnosis. Conclusions. Neoadjuvant therapy, consisting of combined chemo- and radiotherapy, followed by complete excision of residual tumors is highly effective in patients with intracranial NGMGCTs.

Ventricular entry during resection of malignant gliomas: effect on intracranial cerebrospinal fluid tumor dissemination

1994 ◽  
Vol 80 (5) ◽  
pp. 834-839 ◽  
Author(s):  
J. Paul Elliott ◽  
G. Evren Keles ◽  
Michael Waite ◽  
Nancy Temkin ◽  
Mitchel S. Berger
Keyword(s):  
Cerebrospinal Fluid ◽  
Survival Rate ◽  
Ventricular System ◽  
University Of Washington ◽  
Content Type ◽  
Index Operation ◽  
System P ◽  
Tumor Dissemination ◽  
The University ◽  
Fine Print

✓ The ventricular system is not infrequently entered during the course of maximum cytoreductive surgery for high-grade supratentorial gliomas. It is unclear if ventricular entry during surgery and/or proximity of the tumor to the ventricular system affects cerebrospinal fluid (CSF) tumor dissemination or the patients' overall survival rate. The authors retrospectively reviewed hospital records and neuroradiological studies of 51 patients operated on at the University of Washington between 1987 and 1991. Inclusion in this study necessitated a pathological diagnosis of malignant glioma and the availability of preoperative and postoperative computerized tomography scans or magnetic resonance images. Patients were excluded from the study if they had radiographic evidence of ventricular entry or CSF tumor dissemination prior to referral to the authors' institution. The index operation was defined as the first operation at the University of Washington or (in those patients with ventricular entry) the operation in which the ventricle was entered. Patients were followed until time of death or, in the case of survivors, until February, 1992. The effect of both ventricular entry and the proximity of the tumor to the ventricular system on CSF tumor dissemination and survival rate was assessed using statistical survival methodology. There was no significant difference in time from diagnosis to the index operation between groups compared (Mann-Whitney U-test, p > 0.40). Cerebrospinal fluid dissemination was radiographically documented in 18 patients (35%) following the index operation. This occurrence was not significantly influenced by either ventricular entry during surgery (Mantel-Cox test, p = 0.13), the proximity of the tumor to the ventricular system (p = 0.63), or these two variables combined (p = 0.28). Survival rate following the index operation was not significantly affected by ventricular entry (p = 0.66), proximity of the tumor to the ventricular system (p = 0.61), or these two variable considered in combination (p = 0.44). However, survival rate was significantly decreased once CSF tumor dissemination had occurred (Cox model, p = 0.03).

Pituitary adenoma producing growth hormone and adrenocorticotropin: a histological, immunocytochemical, electron microscopic, and in situ hybridization study

1998 ◽  
Vol 88 (6) ◽  
pp. 1111-1115 ◽  
Author(s):  
Kalman Kovacs ◽  
Eva Horvath ◽  
Lucia Stefaneanu ◽  
Juan Bilbao ◽  
William Singer ◽  
...  
Keyword(s):  
Growth Hormone ◽  
In Situ Hybridization ◽  
Pituitary Adenoma ◽  
Immunoelectron Microscopy ◽  
Secretory Granules ◽  
Cell Types ◽  
Content Type ◽  
Separate Cell ◽  
Fine Print

✓ The authors report on the morphological features of a pituitary adenoma that produced growth hormone (GH) and adrenocorticotropic hormone (ACTH). This hormone combination produced by a single adenoma is extremely rare; a review of the available literature showed that only one previous case has been published. The tumor, which was removed from a 62-year-old man with acromegaly, was studied by histological and immunocytochemical analyses, transmission electron microscopy, immunoelectron microscopy, and in situ hybridization. When the authors used light microscopy, the tumor appeared to be a bimorphous mixed pituitary adenoma composed of two separate cell types: one cell population synthesized GH and the other ACTH. The cytogenesis of pituitary adenomas that produce more than one hormone is obscure. It may be that two separate cells—one somatotroph and one corticotroph—transformed into neoplastic cells, or that the adenoma arose in a common stem cell that differentiated into two separate cell types. In this case immunoelectron microscopy conclusively demonstrated ACTH in the secretory granules of several somatotrophs. This was associated with a change in the morphological characteristics of secretory granules. Thus it is possible that the tumor was originally a somatotropic adenoma that began to produce ACTH as a result of mutations that occurred during tumor progression.

Recurrent intracranial solitary fibrous tumor with cerebrospinal fluid dissemination

2004 ◽  
Vol 101 (6) ◽  
pp. 1045-1048 ◽  
Author(s):  
Katsuyoshi Miyashita ◽  
Yutaka Hayashi ◽  
Hironori Fujisawa ◽  
Mitsuhiro Hasegawa ◽  
Junkoh Yamashita
Keyword(s):  
Cerebrospinal Fluid ◽  
Malignant Transformation ◽  
Solitary Fibrous Tumor ◽  
S100 Protein ◽  
Spinal Tumors ◽  
Content Type ◽  
Csf Dissemination ◽  
Fibrous Tumor ◽  
Fine Print ◽  
Mib 1

✓ Solitary fibrous tumor (SFT) is a benign and rare neoplasm. To date, only 37 patients with intracranial SFTs have been reported. Although a number of the tumors were recurrent and some later underwent malignant transformation, none of these lesions progressed to cerebrospinal fluid (CSF) dissemination. In this paper the authors report a case of SFT in which the lesion recurred several times and ultimately was disseminated by the CSF. The patient was a 63-year-old woman with multiple intracranial and spinal tumors. Fifteen years before this presentation, at the age of 48 she had been hospitalized for resection of a falcotentorial tumor. During the ensuing 15 years she underwent multiple surgeries and sessions of radiation therapy for recurrent lesions. The exclusive location of her tumors in the subarachnoid space at the end of this 15-year period indicate CSF dissemination of the tumor. The tumor that was resected when the patient was 48 years old and the latest resected lesion were analyzed by performing immunohistological CD34, epithelial membrane antigen, vimentin, S100 protein, and reticulin staining, and determining the MIB-1 labeling index (LI). Most of the results were identical, and both tumors were diagnosed as SFT according to a staining pattern that showed a strong and diffuse positive reaction for CD34. Nevertheless, the authors noted that the MIB-1 LI increased from less than 1% in the original tumor to 13% in the latest tumor. The increased proliferation of MIB-1 indicates that the malignant transformation could have occurred during tumor recurrence with CSF dissemination.

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