Multifocal dysembryoplastic neuroepithelial tumour in a male with the XYY syndrome.
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Biomedical subjects
Publications and source records attributed to S J Mørk.
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The present study examined the extent and distribution of lymphocyte infiltration in demyelinated lesions in the cerebral cortex of multiple sclerosis (MS) patients. Tissue sections from the brain of 10 MS patients and five patients without neurological disease were double labeled for myelin basic protein and the lymphocyte markers CD3, CD4, CD8, CD45RO, and CD20. The highest density of CD3-positive T cells was found in MS white matter lesions (40.4/10 high power fields (hpf)). Fewer T cells were detected in cortical lesions that extended through both white and gray matter (12.1/10 hpf; P < 0.001). The lowest number of T cells was detected in intracortical demyelinated lesions (1.1/10 hpf). This was equal to the lymphocyte density in nondemyelinated cerebral cortex within the same tissue block (1.1/10 hpf) or cerebral cortex in control brains (1.8/10 hpf). A similar distribution was found using the CD4, CD8, and CD45RO markers. CD20-positive B cells were scarce in all specimens examined. These data indicate that areas of intracortical demyelination in chronic MS are not associated with an increased number of lymphocytes, or an altered distribution of lymphocyte subsets, when compared with control areas in MS and control patients. This finding indicates that the extent of lymphocyte infiltration in MS lesions is dependent on lesion location.
Invasion of spheroids from 20 human primary glioblastomas into precultured fetal rat brain tissue in culture has been studied and quantified. Between 30 and 98 percent of the normal brain tissue was destroyed by invading glioma cells within 4 days. The degree of invasion did not correlate with patient survival. A slightly higher invasiveness and shorter survival was seen in tumors with EGF receptor overexpression, and the opposite pattern was found for tumors with a TP53 mutation. The degree of invasiveness in vitro was far higher than would be expected from the dynamics of clinically observed tumor spread. This suggests that mechanisms suppressing invasion may be operative in the normal brain; alternatively the differences may be due to a higher permissiveness of the fetal brain tissue for invasion in vitro.
BACKGROUND: Primary brain tumors are characterized by an extensive infiltrative growth into the surrounding brain tissue. This process is confined to the central nervous system, and tumor cell metastasis to other organs is rare. However, other tumors of non-neural origin may frequently metastasize to the central nervous system. PURPOSE: The purpose of the present study was to examine the invasive behavior of different glioma cells into tissues of neural (brain aggregates) as well as non-neural origin (leptomeningeal tissue). Using the same target tissues, the invasive characteristics of two neural metastatic tumors (one malignant melanoma and one small-cell lung carcinoma) were also studied. This direct comparison of the invasive behavior between tumors of neural and non-neural origin provides valuable information regarding the mechanisms of glioma cell dissemination in the central nervous system. METHODS: The in vitro invasive behavior of human tumors of the central nervous system into human leptomeningeal tissue as well as into normal rat brain tissue was studied. For this purpose, a co-culture system consisting of tumor biopsy specimens, human leptomeningeal cell aggregates, and brain cell aggregates was established. Three glioblastomas, one oligodendroglioma, one meningioma, one small-cell lung carcinoma, and one malignant melanoma were studied. RESULTS: In co-cultures of gliomas and leptomeningeal cell aggregates, a well-defined border between the two tissues was observed. The brain cell aggregates, in contrast, were consistently invaded by the glioma cells. The brain metastases showed a different invasion pattern. The metastatic cells invaded and progressively destroyed leptomeningeal cell aggregates, whereas they did not invade the brain cell aggregates. Upon confrontation of the leptomeningeal tissue with the meningioma, a fusion of the two tissues was observed. Immunostaining of the leptomeningeal tissue showed a strong expression of the basement membrane components fibronectin, collagen type IV, and laminin with no expression of glial fibrillary acidic protein, neuron-specific enolase, or S-100 protein. CONCLUSIONS: The present study indicates that there may be important biologic differences between the invasive behavior of gliomas and non-neuroepithelial tumors. Our co-culture experiments suggest that leptomeningeal cells and associated acellular components may constitute a barrier against glioma cell invasion. However, this barrier may not be functional for metastatic tumors to the brain. The presence of glioma cells within the leptomeninges should not necessarily be taken as evidence of aggressive growth or as an indicator of malignancy.
To clarify the influence of diving activity on the central nervous system, we studied 10 amateur and 10 professional deceased divers with emphasis on the presence of subacute or chronic pathologic changes in the spinal cord. Of the 10 professional divers (median age 38 yr; range 29-52; median experience in excess of 13 yr), 7 were experienced saturation divers. Five had dived to a maximum depth of 150 meters of seawater, the 2 others to 300 and 500 msw, respectively. Five of the professional divers had experienced decompression sickness. The experience of the amateur divers (median age 29 yr; range 17-51) varied from a few dives to many years of recreational diving. The spinal cords were formalin-fixated and routinely processed for neuropathologic examination, which included light microscopy after immunostaining for glial fibrillary acidic protein and monocyte-macrophage-microglial markers. The microscopic examination did not reveal previous spinal cord damage. Thus, diving activity, saturation diving to extreme depths included, does not in itself seem to lead to necrosis, degeneration, or scar formation in the human spinal cord.
Interference with the dynamics of cerebrospinal fluid may lead to loss of ependymal lining in the ventricles of the brain. The ependymal loss of the lateral ventricles under the corpus callosum at the level of the commisura anterior was measured in 21 diver brains and in a control material of 15 neurologic and non-neurologic brains. The divers were sport divers and professional divers with and without saturation exposure. The different groups were compared with respect to the mean loss of ependymal cells (in percentage). A statistically significant higher loss of ependyma was found in the total number of divers than in the controls. There was no significant difference between the group of sport divers and the control group. The largest loss of ependymal cells was found in the professional divers without saturation experience. Statistically, this loss was significantly larger than the loss of ependymal cells in the controls.
A consecutive series of 34 meningiomas were re-examined as to subtype and presence of nuclear atypia, mitotic figures, areas of high cellularity and necrosis. Meningioma cells were epithelial membrane antigen (EMA) positive in 31 out of the 34 tumours. The presence of mononuclear cells and macrophages was assessed by immunohistochemistry using the monoclonal antibodies L26 (CD20, B cell marker), DF-T1 (CD43, T cell marker), KP1 (CD68, macrophage marker) and MAC387 (monocytes). L26 positive B cells were observed infrequently. CD43 positive mononuclear cells were infiltrating the parenchyma as individual cells and as groups of cells in 29 (87% of the tumours). CD68 positive macrophages were seen in 19 (59% of the tumours), as scattered single cells or groups of cells. There was a statistically significant association between the number of CD68 positive cells (necrotic areas excluded) and microscopic features of aggressiveness, i.e. high cellularity as well as the combination of nuclear atypia and frequent mitotic figures. MAC387 stained only a few cells; the immunopositive cells were present mainly within and around vessels. Meningioma cells displayed a diffuse immunopositivity for L26 (CD20) in 29 out of 34 meningiomas, but did not stain with macrophage markers. Mast cells were found in 9 out of 32 tumours; when present they were significantly more prevalent in the syncytial subtype. Thus, mononuclear cell infiltrates in meningiomas are mainly composed of T cells and macrophages, indicating an immune system surveillance and response to the tumour cells. The functional and prognostic significance of the presence of CD68 positive cells, macrophages, deserve further study in the search for more reliable histological criteria to predict recurrence and biological aggressiveness in meningiomas.
Two patients, in whom visual disturbance (Case 1) and sudden hemiparalysis due to a hemorrhagic lesion (Case 2) had led to craniotomy and histological diagnosis of giant cell glioblastoma, each had an unexpectedly long survival period of 7 and 9 years, respectively. Radiologically, the tumours were well demarcated, but without any distinguishing features, by comparison with glioblastomas in general. The tumours, to a great extent, consisted of cells with large, bizarre multiple nuclei. The highly pleomorphic cells displayed strong cytoplasmic GFAP immunopositivity, which suggested an astroglial origin. Thus, these tumours were considered a variant of glioblastoma ("giant cell glioblastoma") with a more favourable prognosis than experienced by most patients with glioblastoma.
All 1632 cases of meningioma reported to the Norwegian Cancer Registry from 1955 to 1986 have been studied: a) 96% appeared in patients over 30 years of age, b) 95% were histologically benign, c) 88% were located intracranially, and d) 66% occurred in females. The female predominance manifested itself in the middle age period. Eighty-seven percent of the intraspinal meningiomas presented in females, but the ratio between intracranial and intraspinal meningiomas was significantly lower in females (5.4) than in males (20.4). Increased incidence rates of meningioma in females are revealed for the birth-cohorts after 1930. The reason for this change is unclear so both environmental and hormonal factors should be explored. Based upon the epidemiological data, it appears that female sex hormone(s) could act as a growth stimulus in the development of meningiomas, but are neither sufficient nor necessary for tumourigenesis.
A 63-year-old man died of a brain tumor 29 years after onset of multiple sclerosis (MS). The MS diagnosis was based upon clinical evidence of two brain stem lesions, separate in time, retinal periphlebitis, a fluctuating course of the disease, and supported by the observation of definite cognitive impairment at the age of 41 years, and an increased number of lymphocytes in the cerebrospinal fluid which normalized during gradual recovery. The MS diagnosis was confirmed at autopsy, which also revealed a glioblastoma developing adjacent to typical MS plaques.
A survey of all patients (173 males and 294 females) registered with primary intraspinal neoplasms in the Norwegian Cancer Registry from 1955 through 1986 is presented. Annual age-adjusted incidence rates of new tumors per one million population were three for males and five for females. Altogether, 89% of the tumors were verified histologically. Meningioma was the most common tumor type, followed by ependymoma and neurilemoma. Intraspinal ependymomas accounted for 34.5% of all 223 ependymomas of the central nervous system, whereas only 0.2% of the 3046 glioblastomas were found intraspinally. Patients with intraspinal meningioma had a better life expectancy than those with intracranial meningioma. The 5-year relative survival rate for patients with intraspinal ependymoma was 88.9% in contrast to 24.4% for patients with intracranial ependymoma.
Data were analysed from 4859 patients with different histological types of intracranial glioma registered by the Norwegian Cancer Registry between 1955 and 1984. Glioblastoma comprised 57.9% of all cases. The second most common primary brain tumour was astrocytoma (19.0%), then mixed glioma (9.2%), oligodendroglioma (7.9%), medulloblastoma (3.1%) and ependymoma (2.9%). A primary brain tumour in a child is approximately twice as likely to be an astrocytoma as a medulloblastoma. The age-specific incidence for glioblastoma increases with age, whereas the incidence of astrocytoma and oligodendroglioma peaks at middle age. Both glioblastoma and astrocytoma showed increased incidence rates over the study period and this was most pronounced in the age-group above 60 years. The prognosis for gliomas varied with age at time of diagnosis, generally being better the younger the patient. For oligodendroglioma patients, survival prospects were independent of age at time of diagnosis. The best prognosis was seen in patients up to 30 years with astrocytoma. Applied in epidemiology, the data indicate that astrocytoma, oligodendroglioma, mixed glioma and ependymoma may be treated as a group which should be separated from both glioblastoma and medulloblastoma.
The association between meningioma and a primary malignant neoplasm at another site was studied. The data from the population-based Norwegian Cancer Registry were analysed according to whether the meningioma occurred before or after the malignant neoplasm. Male patients with meningioma showed a raised risk for developing a subsequent renal cancer. A significant association was found between meningioma and subsequent breast cancer in females 50-64 years old at time of meningioma diagnosis and between breast cancer and subsequent occurrence of meningioma. Breast cancer patients with symptoms of an intracranial neoplasm may therefore have a potentially curable meningioma and female meningioma patients over 50 years should be considered for breast cancer screening programmes.
Adenoid-like formations resembling ducts and glands or forming a cribriform pattern have previously been described in malignant gliomas, resulting in some cases in a confusion with metastatic adenocarcinoma. The interpretation of these structures as being composed of anaplastic glial cells rests partly on the presence of transitions to more differentiated neoplastic astrocytes and partly on the positivity of some of these cells for glial fibrillary acidic protein. In this report two cases are presented in which the adenoid pattern was associated with papillary formations mimicking the arrangement of a medulloepithelioma. These structures represent a form of aberrant neoplastic differentiation in a malignant glioma rather than the expression of an embryonal neuroepithelial neoplasm.
Six cases are reported (four gliosarcomas and two glioblastomas) in which the epithelial-like areas of glial anaplasia showed focal squamous cell differentiation, characterized by the development of epithelial whorls, keratin pearls and immunopositivity for cytokeratin. The expression of glial fibrillary acidic protein and the development of squamous metaplasia usually were mutually exclusive. Autopsy findings in two patients and clinical work-up in five failed to disclose a primary extraneural malignancy. It is suggested that squamous differentiation may represent an extreme form of epithelial metaplasia in a malignant glioma. This possibility should be kept in mind in the diagnostic evaluation of such cases, especially in view of the current emphasis on the immunomorphologic demonstration of intermediate filament tumor markers.
The Norwegian Cancer registry includes reports on 8,933 cases of primary central nervous system neoplasms diagnosed in the period 1955-1984. Before submitting this data set to epidemiological analysis, errors were searched out and subsequently corrected, and a quality control was performed. First, seven categories of neoplasm records likely to be faulty were defined. In this way 109 cases (1.2% of the total) were identified for extensive study. Minor or major errors were found and corrected in 86 cases. The main source of error was misinterpretation of data by cancer registry staff (67 out of 109 cases). The second approach was to evaluate the quality of the corrected data set by a random draw of 300 cases. Errors concerning total incidence rates and rates for main groups of gliomas, meningiomas and neurilemmomas represented 0.3% of the total, and altogether 9.3% of errors of varying severity were revealed. The series is discussed with regard to prerequisites for serving as reliable data on CNS neoplasm epidemiology. The results indicate that the data from the Norwegian Cancer Registry is sufficiently valid for a thorough study of CNS neoplasms.
A population-based study of 8480 patients - 4508 (53%) males and 3972 females - with primary intracranial neoplasms reported to the Norwegian Cancer Registry during the period 1955-84, is presented. 81% of the cases were histologically verified. The peak age-specific incidence rate in the total series occurred in the age-group 55-64 years. Gliomas constituted the largest histological group with an age-adjusted incidence rate of 5.0 cases per 100,000 population per year for males and 3.5 for females. Case ascertainment of primary intracranial neoplasms is reduced above the age of 60 in Norway, mostly due to a a low autopsy rate. The major impact of the introduction of computer tomography (CT) in the case ascertainment of intracranial neoplasms has been a raised incidence, in patients over the age of 60, of neoplasms which are not histologically verified.
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