Chromosomal translocation, t(1;11)(q12;p15), in an extragonadal immature teratoma.

A case of immature teratoma arising from the base of the skull is reported. The cytogenetic analysis revealed t(1;11)(q12;p15) as a sole chromosomal abnormality, suggesting that the breakpoint on chromosome 11 plays an important role in the early oncogenesis of human germ cell tumors (GCTs).

[Intracranial fibrous xanthoma (xanthofibroma) in an infant: a case report].

A case of intracranial fibrous xanthoma (xanthofibroma) is reported. Intracranial fibrous xanthoma in infancy under the age of 1 year is extremely rare. This patient was a 8-month-old boy with a history of convulsive seizure. He had a previously known chest wall tumor which was diagnosed as fibrous xanthoma of the skin. Plain CT scan revealed a well defined high density area in the left temporal lobe. The area was well enhanced with contrast media. At operation, it was found that the tumor did not attach to dura mater and was almost well demarcated. Total removal of the tumor was performed. The patient has been doing well for these 6 months following craniotomy, with no sings of recurrence and no neurological deficits. Histologically, the tumor was composed of fibroblastic cells and foamy phagocytic cells in storiform pattern. Some multinucleated giant cells were found. Immunohistochemistry technique revealed that the tumor cells were negative for GFAP, positive for Vimentin, positive for S-100 protein and negative for EMA. Our studies support the diagnosis of intracranial fibrous xanthoma coexistent with the same tumor found in the subcutaneous space of the chest wall of a boy under 1 year of age. We regard it as a rare incidence. Differential diagnosis and the characteristics of fibrous xanthoma were discussed.

Relationship of invasiveness to proliferating activity and to cytoskeletal protein production in human neuroepithelial tumors maintained in an organ culture system: use of human cortex and dura as supporting matrices.

The proliferation and invasiveness of cultured human neuroepithelial tumors were studied. A human malignant astrocytic glioma cell line (U-251 MG) and a medulloblastoma cell line (D283 Med) were maintained for 3 weeks in an organ culture system using adult human brain cortex, dura mater, or Gelfoam sponge as growth matrices. The cells were labeled with bromodeoxyuridine (BrdU) at different time points, and immunohistochemistry was performed for BrdU, glial fibrillary acidic (GFA) protein (in U-251 MG), and neurofilament (NF) protein (in D283 Med). In the U-251 MG line, the cells grew successfully in each matrix, forming a fibrillated solid area and a peripheral zone of invasion. The labeling index (LI) expressed as the percentage of BrdU-labeled cells and the percentage of GFA protein-positive cells in the two zones of the explants were analyzed. The LIs in all cultures were significantly higher in the peripheral than in the central zones. On the other hand, the percentage of GFA protein-positive cells in each matrix was greater in the central zone than in the periphery. The LI was inversely correlated with the percentage of GFA protein-positive cells over the areas counted in each growth matrix. GFA protein production in cells grown on cortex and on dura mater was significantly higher than that in cells grown on Gelfoam. In the D283 Med line, the cells formed an aggregated zone, with peripheral cells infiltrating the Gelfoam. This line showed poor growth on human cortex. Cells grown on the dura demonstrated an LI similar to that on Gelfoam, and cells often infiltrated the dura.(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetics and glial fibrillary acidic (GFA) protein production in a transplantable human giant cell glioblastoma (D-212 MG) of near haploid karyotype maintained in an organ culture system. An immunohistochemistry study.

A transplantable subcutaneous tumour (designated D-212 MG), sequentially passaged in athymic nude mice and originally derived from a human giant cell glioblastoma, was maintained in an organ culture (matrix) system and studied immunohistochemically after in vitro pulse-labelling with bromodeoxyuridine (BrdU) and for the presence of glial fibrillary acidic (GFA) protein, after 1, 2 and 3 weeks in culture. The histological characteristics of the tumour, showing two cell populations of giant multinucleated cells and small cells, were preserved in the explants. An increased percentage of multinucleated giant cells was found after 3 weeks in vitro. A small but constant fraction (4-6%) of these cells continued to synthesize DNA. The labelling index of the small cells was somewhat higher, but decreased slightly although significantly over the 3-week period in vitro (from approximately 10.5 to 8%). The percentage of small cells that were positive for GFA protein was in the region of 75% and that of the giant multinucleated cells was in the region of 45%; it did not change significantly during the 3 weeks in vitro. The in vitro results confirm the astrocytic nature of both the small cells and the giant multinucleated cells in this tumour, the capacity of both cell populations to synthesize DNA in culture and to demonstrate invasiveness, and suggest the possibility that some of the giant multinucleated cells may have originated from the conversion of a number of small tumour cells.

Relationship of the demonstration of intermediate filament protein to kinetics of three human neuroepithelial tumor cell lines. Lack of neural-related proteins in most cells in S phase: a double-labeled immunohistochemical study on matrix cultures.

The immunocytochemical demonstration of intermediate filament proteins in three human neuroepithelial tumor cell lines maintained in vitro on a three-dimensional matrix was correlated with the proportion of cells in S phase. The cell lines of a medulloblastoma (D283 Med), a retinoblastoma (WERI-Rb1), and an astrocytic glioma (U-251 MG) were cultured in an organ culture system, pulse-fed with bromodeoxyuridine, and double-labeled by immunoperoxidase and by the avidin-biotin peroxidase complex method for bromodeoxyuridine and for intermediate filament proteins [each triplet of neurofilament proteins, as well as vimentin and glial fibrillary acidic (GFA) protein] using eight different antibodies. The average percentages of bromodeoxyuridine-labeled cells for the D283 Med, WERI-Rb1, and U-251 MG lines were respectively, 25, 32, and 12% 30 minutes after pulse labeling. In the D283 Med line, 15- greater than 95% of the cells were positive for each neurofilament protein, and 80% of the cells were positive for vimentin; less than 10% of the cells in S phase were positive with each of the five antineurofilament protein monoclonal antibodies (Mabs), but 20% of the vimentin-positive cells were in S phase. In the WERI-Rb1 line, 44 and greater than 96% of the cells were positive for the high-molecular-weight neurofilament subunit and high- and middle-molecular-weight neurofilament subunits proteins, respectively, but only 5% of the high-molecular-weight neurofilament positive cells were in S phase. In the U-251 MG line, 37 and 98% of the cells were positive for GFA protein and vimentin, respectively; only 3% of the GFA protein-positive cells, but 13% of the vimentin-positive cells, were in S phase. The results indicate that, when maintained in a matrix culture system, most cells in S phase in these lines lack markers of neural differentiation.

[Immunohistochemical study of S-phase cells in human gliomas].

Intermediate filament proteins are cytoskeletal components in most vertebrate eukaryotic cells and some of these proteins are recognized markers of cell differentiation. To investigate the expression of intermediate filament proteins of the S-phase cells in human glial tumors, we have examined fourteen patients with benign and malignant gliomas by immunohistochemical study using in vivo labeling with bromodeoxyuridine (BrdU). Five glioblastoma multiforme, five anaplastic astrocytoma, three fibrillary astrocytoma and one gemistocytic astrocytoma were studied. All patients were given intravenous infusion of BrdU (10 mg/kg) one hour before craniotomy for labeling the S-phase cells of the tumors. Surgical specimens were immersed in 70% ethanol, and embedded in paraffin. Four micron sections were immunostained with anti-BrdU monoclonal antibody (Mab) and anti-vimentin Mab by avidin-biotin complex (ABC) method, and anti-glial fibrillary acidic protein (GFAP) serum by peroxidase-antiperoxidase (PAP) method. All sections (except for case 4) were double-labeled with anti-BrdU Mab and anti-GFAP serum, or with anti-BrdU Mab and anti-vimentin Mab. The population of BrdU-labeled cells (i.e. S-phase cells), and double-labeled cells were analyzed. The proportions of BrdU-labeled cells ranged from 6.1% to 17.0% (average 11.1%) in glioblastoma multiforme, from 3.5% to 15.6% (average 8.8%) in anaplastic astrocytoma, and from 2.0% to 2.8% (average 2.5%) in fibrillary astrocytomas. One gemistocytic astrocytoma showed S-phase fraction of 1.7%. Two recurrent cases of anaplastic astrocytoma showed higher S-phase fractions than other non-recurrent cases of anaplastic astrocytoma.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of cerebellar neuroblastoma].

A three-year-old boy with a progressive history of headache, vomiting and ataxia in the course of 2 months, was admitted on August 1983, when he was lethargic. Neurological examination revealed dysphagia, scanning speech and tremor in the bilateral hand. CT scan showed a very large enhanced mass in the center of posterior fossa with central necrosis in it and the dilatation of whole ventricular system. Suboccipital craniectomy was immediately performed and the tumor that occupied the vermis and invaded into both cerebellar hemisphere was subtotally removed. Postoperative irradiation was well performed: 4140 rads to the whole brain and 3162 rads to the spinal cord. However, 5 months later, facial palsy in the left side and progressive ataxia became prominent. CT scan showed multiple enhanced masses in the left trigonum and right anterior horn of the lateral ventricles and in the left cerebellopontine angle. In spite of chemotherapy, the patient had a down-hill course, especially after the ventricular hemorrhage, and died on June 9th, 1984. Histologically, the tumor had a lobulated appearance with an aggregation of tumor cells encircled by vascular septae. The cells within lobules generally had vesicular nuclei, which were arranged in parallel row. Occasionally smaller hyperchromatic cells with scant cytoplasm were present along the vascular septae. Reticulin was present within the septa, but was not observed within the lobules. Scattered astrocytic cells and processes were identified within the lobules by the immunoperoxidase technique for GFAP. The fibrillary cytoplasmic processes within the lobules were stained by immunoperoxidase technique for neurofilament (68K).(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of pleomorphic xanthoastrocytoma].

A case of pleomorphic xanthoastrocytoma (Kepes) is reported. This patient was a 12-year-old boy with a history of convulsive seizure. Neurological examination on admission showed no abnormality. Plain CT scan revealed a well defined low density area with calcification in the right frontal lobe. A part of peripheral portion of low density area were well enhanced with contrast media. At operation, there was a cyst containing xanthochromic fluid in the right frontal lobe. A part of cyst well near the cerebral surface was reddish hard. Total removal of nodular tumor and subtotal removal of the cyst wall were performed. He has been doing well for these 3 years following craniotomy and has no deficit without CT evidence of recurrent tumor. Histologically the tumor cells displayed marked pleomorohism. However either necrosis or mitosis were not seen. Frequently these cells had vacuolated or foamy cytoplasm. There were many of the giant cells and multinucleated cells. In some area, these tumor cells were surrounded by a fine network of reticulin fibers. Electron microscopically the tumor cells were occasionally filled with glial filament and lipid granules were seen. Immunoperoxidase technique revealed GFAP in the cytoplasm of the tumor cells. This case was considered to be pleomorphic xanthoastrocytoma first proposed by Kepes.

[Photoradiation therapy of experimental brain tumor].

Malignant tumors retain hematoporphyrin to a much greater extent than do normal tissues and can be destroyed by exposure to light. To utilize this mechanism in the treatment of malignant brain tumor, we investigated the antitumor effect of photoradiation on rat and mouse glioma, utilizing hematoporphyrin administration and cold light irradiation. In vitro study of rat glioma (EA285), the tumor cells which were exposed to hematoporphyrin and light irradiation showed marked degeneration in a short time, though no change was found in the control groups of hematoporphyrin administration alone and of light irradiation alone. The subcutaneously transplanted gliomas of rat and mouse also showed the growth inhibition after treatment of hematoporphyrin and light irradiation, though they grew up again. Histological degeneration by this treatment reached about 7 mm depth in the tumor. It was made clear that the effect on gliomas was induced by photosensitization and not by heat. From these results it is concluded that photoradiation therapy would be a great means for adjuvant therapy for malignant brain tumor.

[A case of cervical intramedullary neurenteric cyst].

A case of cervical intramedullary neurenteric cyst was reported. A 12-year-old girl was admitted with severe pain over the nape and shoulders, and weakness of all extremities. At the age of 4 years, she had suffered from the nape pain and paraparesis which, however, cleared later spontaneously. Neurological examination revealed evidences of presumptive cervical intramedullary lesion, and myelography showed a complete block at the third cervical level accordingly. Surgical exploration through C3-C5 laminectomy disclosed an intramedullary cyst situated within the right half of the cord. The cyst was removed except for its upper and lower apices. Excellent clinical results followed the operation. The cyst was composed of collagen fibers with an inner epithelial lining, which consisted of single or pseudostratified layer of columnar, cuboidal or squamous cells. Cells were ciliated at some parts. The base of the epithelial cells rested upon the basement membrane. Nuclei were positioned near the base of the cells, to present a row. The cytoplasm in the majority of cells contained abundant mucin positive to PAS staining. Pathological diagnosis of neurenteric cyst was made on the basis of these histological findings. Usually intraspinal neurenteric cyst is located in the subarachnoid space and ventrally to the spinal cord. Neurenteric cyst appears histologically similar to ependymal cyst, though, in the latter the epithelial cells seldom contain mucin, and only in scanty amount, if any present. Embryogenesis during the third week of embryonic life was discussed in relation to the development of neurenteric cyst.

Multivariate analysis of factors affecting postoperative survival in malignant astrocytoma. Importance of DNA quantification.

Fifty-eight patients with supratentorial malignant astrocytoma were analyzed statistically to evaluate the factors most important for predicting postoperative survival. Clinical information such as age, sex, duration of preoperative symptom, Karnofsky score at admission and at discharge, location of tumor, amount of tumor removal, number of operations, and postoperative survival in months, together with data on radiation and chemotherapy were analyzed by chi square test, t-test, and multivariate analysis. Cytofluorometric DNA quantification using paraffin embedded specimens was also performed in 20 cases and these data were also evaluated. Multiple correlation coefficient, and therefore the total statistical accuracy, increased to 0.824 when data of DNA quantification, percentages of S phase cells and of polyploid cells, were included. Multivariate analysis revealed that 6 items were the major factors for predicting postoperative survival, i.e. the location of tumor, the Karnofsky score at discharge, the percentage of S phase cells, the number of operations, the percentage of polyploid cells, and the amount of tumor removed. Based on this analysis, the estimated survival time could be expressed as a formula.

[Effect of interferon on mouse glioma].

Mouse interferon (IFN) induced in L 929 cells by Newcastle disease virus was examined for its effect on the growth of mouse brain tumor cell line. In this study, we used subcutaneously transplanted 203 Glioma model, which had been originally induced by methylcholanthrene in C 57 BL mice. After subcutaneous transplantation, intraperitoneal administration of IFN was started by following schedule; 5 X 10(3) IU twice a week, 5 X 10(4) IU twice a week, 2.5 X 10(5) IU twice a week, 5 X 10(3) IU every day and 2.5 X 10(4) IU every day. In all groups treated by IFN intraperitoneally, no inhibition of the tumor growth was seen. On the other hand, natural killer (NK) activity was augmented by IFN treatment. Therefore, we considered that augmentation of NK activity was not directly correlated with the antitumor effect of IFN. Then, local administration was examined. After subcutaneous tumor was recognized, 2.5 X 10(4) IU of IFN was injected intratumorally every day. About 20 days later, the tumor decreased its size less than that treated by local injection of saline. It was suggested that the local administration of IFN might be better than the systemic administration.

[Interferon therapy for brain tumor patients (author's transl)].

Nine cases of recurrent and metastatic brain tumors were treated by Hu-IFN-alpha. It was given intramuscularly and singly to those who finished the usual treatments of surgical removal and 60Co irradiation more than 6 months before, to exclude their effects on tumors. They were divided into 2 groups of small dosage (fifty thousands units weekly) and large dosage (3 million units every other day). The total dosage of IFN varied from about 2 million units for the small dosage group to 264 million units for the large dosage group. No side effects were noted. In two cases of six which were followed up over 4 months, the tumors regressed about 50% on serial CT. However, IFN was not effective on the tumors which had already showed a rapid growth before IFN administration. Almost all the patients showed improvements in their general condition, PPD and PHA skin test, peripheral lymphocyte counts and natural killer cell activities.