Prospects of research in neurooncology.
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Animals↗
Biomedical subjects
L J Rubinstein
Publications and source records attributed to L J Rubinstein.
Cerebral medulloepithelioma. Report of a case with multiple divergent neuroepithelial differentiation.
A cerebral medulloepithelioma, a rare embryonal multipotential central neuroepithelial neoplasm of childhood, is described, bringing to 16 the total number of cases reported in the literature. It is the first example recorded to date which displayed the entire range of differentiation from embryonal to mature cells, of both glial and neuronal lineage (i.e., primitive medullary epithelium, spongioblasts, astrocytes, oligodendroglia, ependymal cells, neuroblasts, and mature ganglion cells). The significance of this tumor as a paradigm of multipotential divergent neuroepithelial differentiation is discussed.
Adolescent↗
Meningeal mesenchymal chondrosarcoma: report of 8 cases with review of the literature.
This paper reviews 8 personally examined cases of primary meningeal mesenchymal chondrosarcoma and 4 similar cases previously reported by others. The clinicopathologic features of these extraosseous intracranial and intraspinal examples are similar to those of other extraskeletal mesenchymal chondrosarcomas. The tumor occurred most often in the second and third decades, showed a moderate tendency to local recurrence (5 of 12 cases) and occasionally metastasized to the lungs (1 case). Both intracranial and intraspinal tumors occurred with equal frequency, but the former, probably due to the later onset of symptoms, had the worse prognosis. Microscopically, they are composed of primitive undifferentiated mesenchymal cells and frequently well-defined islands of hyaline cartilage. There is an apparent correlation between the frequency of mitotic figures and the likelihood of recurrence and metastasis. Electron microscopic study of one example revealed morphologic features similar to those previously described by others and supports the conclusion that the neoplastic cells represent primitive precartilaginous mesenchyme displaying focal cartilaginous differentiation.
Adolescent↗
Contribution of immunohistochemistry to diagnostic problems of human cerebral tumors.
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Astrocytes↗
Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: use of virus-containing cells in the urine to assess response to therapy.
Two patients with biopsy-proved progressive multifocal leukoencephalopathy (PML) were treated with near-maximal doses of adenine arabinoside (Ara-A), 18.6 and 20 mg per kilogram of body weight per day for 14 days. In both patients, clinical progression of the disease was correlated with an increase in the size of low-density lesions seen by computerized tomography. One of the patients was observed to excrete abnormal epithelial cells into the urine. These cells contained papovaviruslike particles, and JC virus was cultured from the urine sediment. The relative number of these abnormal cells declined during Ara-A treatment. Both patients died shortly after the conclusion of therapy without a change in the progression of the central nervous system disease. Systemic administration of Ara-A did not offer significant clinical benefit in the treatment of these 2 advanced cases of PML.
Aged↗
The angioblastic meningioma: a reappraisal of the nosological problem. Light-, electron-microscopic, tissue, and organ culture observations.
The validity of the concept of the angioblastic meningioma, now in dispute, was reexamined by reviewing 79 meningeal and angioblastic tumors of the central nervous system and by comparing the fine structural characteristics and in vitro evolution of 2 typical meningiomas and 1 intracranial hemangiopericytoma. While most tumors show the consistent features of either hemangiopericytoma or hemangioblastoma, there exist transitional forms between these tumors and typical meningioma. There is also a greater degree of morphological overlap at the electron microscopic level than has been recognized up till now. In view of these findings the concept of the angioblastic meningioma deserves to be retained as a generic term to include craniospinal hemangiopericytomas and transitional forms between hemangiopericytoma, hemangioblastoma and classic meningioma. It is postulated that all these tumors share a common origin from polyblastic mesenchymal cells originating in or derived from the meninges.
Brain Neoplasms↗
Correlation of animal brain tumor models with human neuro-oncology.
The paper reviews the histopathology and cytopathology of a number of experimental animal brain tumor models to determine their relevance to human neuro-oncology. The models discussed include brain tumors produced by local implants of carcinogenic hydrocarbons and by the administration of resorptive N-nitroso compounds, some of the cell lines derived from the latter, tumors resulting from the intracerebral inoculation of oncogenic viruses, and the differentiating neuroepithelial component of a transplantable mouse teratoma. The structural and biochemical criteria that can be applied for the identification of the various stages of neuronal and glial cell maturation are highly precise. They reveal a wide diversity of tumor cell types that are now available in experimental neuro-oncogenesis.
Animals↗
Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. III. Melanin pigment and melanogenesis in experimental neurogenic tumors: a reappraisal of the histogenesis of pigmented nerve sheath tumors.
Four melanin pigment-containing intracranial tumors were found in three Long-Evans rats in the course of experimental oncogenesis by transplacental ethylnitrosourea (ENU). One of them was a leptomeningeal melanoma. Aside from the presence of scattered melanin-pigmented cells, the other three had the typical histological features of ENU-induced malignant nerve sheath tumors. Two of the three tumors were studied by electron microscopy and in tissue and organ culture systems. One of them demonstrated progressive melanogenesis in vitro; the other failed to produce more melanin and showed increasing differentiation, with a Schwannoma-like pattern by light microscopy. Melanosomes and premelanosomes were identified in both tumors by electron microscopy; the other fine structural features were those of malignant Schwannomas. These observations are relevant to the controversy on the histogenesis of pigmented nerve sheath tumors occasionally encountered in man and on the relationship of these tumors to pigmented nevi. The findings in the present study support the view of Masson that neoplastic nerve sheath cells are capable of melanogenesis.
Animals↗
Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. I. Light microscopy observations.
Explants from seven nerve sheath tumors (four cranial and three spinal) induced in rats by transplacental ethylnitrosourea were grown on collagen-coated coverslips and in organ culture systems, using sponge foam matrices and Millipore filter platforms. Their sequential morphological features in vitro were compared to those of a human acoustic Schwannoma maintained in similar culture systems. The original experimental tumors were either undifferentiated or poorly malignant Schwannomas. In cultures on collagen-coated coverslips the explants demonstrated cellular features that were considerably more anaplastic than those of the human acoustic Schwannoma. On the other hand, in organ culture systems, in which viable cultures were maintained up to 82 days, many of the experimental tumor explants exhibited progressive differentiaiton, with nuclear palisading, increasing whorl formation and abundant reticulin fibers, and their pattern of histological organization came therefore closely to resemble that of the cultured acoustic Schwannoma. Unlike the latter, however, the cultured experimental tumors infiltrated the sponge foam matrices, a feature that mimicked the invasive character of the original tumors in vivo. Included normal ganglion cells remained demonstrable in the cultures up to 69 in vitro.
Animals↗
Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. II. Electron microscopy observations.
The sequential electron microscopic features of six malignant nerve sheath tumors (three cranial and three spinal) induced in rats by transplacental ethylnitrosourea and maintained in organ culture systems were compared with those of a human acoustic Schwannoma similarly cultured. After 4 weeks in vitro, the malignant tumor cells often showed progressive elongation of their processes, with the development of an interdigitating pattern resembling that seen in well-differentiated Schwannomas. This was accompanied by an increase of microtubules. Basal lamina formation, less well-developed and less complete than in the benign Schwannoma in this study, was maintained in culture. Some explants demonstrated an increase in number and width of collagen fibrils, accompanied by a relative concomitant decrease of inter-cellular basement membrane material. The malignant tumor cells also showed numerous micropinocytotic vesicles and various junctional complexes, which are characteristic of perineurial cells. Since the origin of the experimental tumors from adult Schwann cells seems well established, this apparent contradiction is best resolved by the concept that Schwann cells and perineurial fibroblasts are functional variants of the same cell type.
Animals↗
Primary cerebral neuroblastoma. A clinicopathological study of 35 cases.
A series of 35 primary cerebral neuroblastoma is reported. These rare tumours occur most often in children in the first half of the first decade. Grossly the tumors are often massive, discrete, lobular, firm and cystic. Histologically three variants, largely determined by the extent and distribution of the fibrous connective tissue stroma, are recognized: (1) a classical variant, which most resembles the peripheral neuroblastoma and is characterized by a high frequency of Homer Wright rosettes and a relatively high frequency of ganglionic differentiation; (2) a desmoplastic variant, which is characterized by an intense connective tissue stroma; and (3) a transitional variant, in which both the classical and the desmoplastic features may be present within the same case, either concurrently or consecutively. Both the desmoplastic and the transitional forms are less likely to exhibit differentiation to mature ganglion cells, but the importance of identifying the primitive cell elements as neuroblasts is emphasized. With rare exceptions, this can be established only by specific silver impregnations on frozen material. Occasionally the direction of growth may be largely leptomeningeal. Seven illustrative clinical histories with pathological correlations are described. The over-all clinical behaviour of these tumours is that of malignant neuroepithelial neoplasms, characterized by a high recurrence rate. Recurrence may, however, be a late development, in some cases occurring five or seven years after apparently successful surgical removal. The tumour shows shows a high incidence of metastatic spread, almost 40 per cent of the cases examined at autopsy having disseminated in the cerebrospinal pathways. Exceptionally, extraneural metastases may also develop. However, long post-operative survival occasionally occurs, and the subsequent clinical course is not always predictable in the individual case. The differential diagnosis is briefly discussed. The cellular nature of the tumour and its biological behaviour recall those of the cerebellar medulloblastoma. Post-operative radiation to the entire neuraxis should be considered for these neoplasms.
Adult↗
Current concepts in neuro-oncology.
Recent years have witnessed a significant resurgence of interest in neuro-oncology. This has largely been due to the use of new, potent neuro-oncogenic agents that have provided researchers with a growing body of data. New tools are being devised for the experimental study of brain tumors utilizing radiotherapeutic, chemotherapeutic, and immunological methods. In this chapter, selected observations on naturally occurring and experimentally induced nervous system tumors are discussed in relation to the following current areas of interest in oncology: (a) the somatic mutation theory of cancer and the additive mutagenic action of radiation and alkylating carcinogens; (b) the viral theory of cancer and the production of tumors by oncogenic viruses; (c) disturbances of immunological mechanisms concerned with tumor surveillance involving the central nervous system; and (d) the operation of epigenetic mechanisms in neoplastic systems, the applicability of these mechanisms to embryonal tumors of the central nervous system, and the development of suitable neural neoplastic models for the study of altered patterns of gene expression. Neural neoplasms are particularly suitable for the study of epigenetic phenomena because precise morphological, biochemical and antigenic markers exist which permit the various stages of divergent differentiation in neurocytogenesis to be clearly defined.
Animals↗
Histogenetic and morphological in vivo and in vitro data concerning androgen-estrogen-induced scent gland tumor in the Syrian hamster.
The scent gland tumor of the Syrian hamster is induced by exogenous androgen and estrogen. Microscopic nodules are induced normally in old males by endogenous androgen. The histogenesis of the scent gland tumor is complex and not completely understood. In this study microscopic preneoplastic nodules and macroscopic tumors were studied by light and electron microscopy, and the macroscopic tumors were grown in tissue culture on collagen-coated coverslips and on sponge foam matrices by the organ culture method. The cultures were fed with an unfiltered fetal calf serum-bovine serum ultrafiltrate medium, which contained endogenous androgen-estrogen, 110-100 pg and could maintain growth without additional androgen-estrogen. Exogenous androgen-estrogen was also added to some cultures. Scent gland tumors grown in organ culture contained cells of two shapes, spindle and ovoid arranged in cords. Cultures on coverslips showed radiating outgrowths of spindle cells suggesting either mesenchymal or Schwann cells. By electron microscopy, both in vivo and in vitro preneoplastic and tumor samples contained cells with segments of basal lamina, micropinocytotic vesicles, and junctional complexes. These features were similar to those of poorly differentiated experimental malignant rat schwannomas maintained in similar in vitro systems. Tumors grown in vivo and in vitro were associated with collagen fibrils with a periodicity ranging from 400 to 1075 A. The evidence reported in this paper suggests that one component of the scent gland tumor is an androgen-estrogen-induced poorly differentiated schwannoma.
Animals↗
Disseminated necrotizing leukoencephalopathy: a complication of treated central nervous system leukemia and lymphoma.
This report describes a form of disseminated necrotizing leukoencephalopathy that has been observed in four children with acute lymphoblastic leukemia, and one child with Burkitt's lymphoma terminating in a leukemic phase. In addition to systemic vincristine, cytosine arabinoside, cyclophosphamide, and steroids, these patients received courses of intrathecal methotrexate, cytosine arabinoside, and hydrocortisone, because of meningeal tumor cell infiltration. Whole brain radiation was also given either before or during intrathecal therapy. Three of the children had a progressive irreversible neurologic illness, which developed either at or shortly after the completion of combined triple intrathecal therapy, death ensuing approximately 2 months later. The neuropathologic lesions consisted of discrete multifocal necroses of coagulative type, apparently extending by confluence, and disseminated in the cerebral white matter in a random manner. In one case, extensive symmetrical demyelinating and necrotizing lesions involved the centrum ovale bilaterally. There was a remarkable absence of inflammatory cellular response and a relative paucity of macrophage reaction, with usually little or no tissue breakdown. In addition to demyelination and glial cell loss, there was striking axonal damage, with conspicuous axonal swelling both within and around the necrotizing lesions. The surrounding white matter showed focal status spongiosus and a moderate astrocytic response. Vascular fibrinoid necrosis was inconstant and, except in one case, rarely observed. The possible causal relationship of these lesions to combined triple intrathecal antimetabolite therapy and brain radiation is discussed.
Antineoplastic Agents↗
Cerebellar capillary hemangioblastoma: its histogenesis studied by organ culture and electron microscopy.
A capillary hemangioblastoma from the vermis of a 21-year-old man with von Hippel-Lindau's disease was successfully maintained in organ culture systems on Millipore filter platforms and gelatin sponge foam matrices up to 48 days. Three cell types--endothelial cells, pericytes, and stromal cells--identified by their fine structural features and their architectural relationships to vascular lumens and to the extracellular space were recognized in the original tumor. By light microscopy the explants showed, in the late stages, increased lipid droplets in the stromal cells and perivascular hyaline thickening. By electron microscopy, endothelial cells, pericytes, and stromal cells remained distinguishable as cell types. However, the stromal cells demonstrated, in addition to an increase of their normal complement of microfilaments and lipid droplets, features that were more characteristic of the two other cell types, i.e. micropinocytotic vesicles and the formation of zonula occludens junctions and hemidesmosomes. Basement membranes also became more apparent around the stromal cells. With increasing time in vitro, there was a striking increase in mature collagen fibers in the extracellular space. The roles of the different cell types in capillary hemangioblastoma and the histogenesis of the stromal cells are discussed in light of these observations. It is concluded that the capillary hemangioblastoma consists of multiple cell lines--endothelial cells, pericytes, stromal cells and, occasionally, hematopoietic cells--all of which are neoplastic and replicate in parallel with one another. Stromal cells may be regarded as an aberrant monopotential cell type which shares with the endothelial cell and pericyte a common mesenchymal, presumably angiogenic, ancestry, and may, on occasion, display morphological features, such as increased basement membrane formation and the formation of zonula occludens junctions, which recall its angiogenic lineage. However, interconvertibility between endothelial cells and stromal cells does not appear to occur in vivo or in vitro.
Adult↗
Papillary meningioma: a malignant variant of meningioma.
A series of 17 meningiomas histologically characterized by a papillary pattern is reported. This pattern was invariably associated with other histologic features of malignancy. The tumors often displayed aggressive clinical behavior marked by a high rate of local recurrence or the development of distant metastases. A relatively large proportion occurred in children. It is suggested that this variant of meningioma is sufficiently characteristic to justify its separation as a distinct clinicopathologic entity.
Adult↗
Megavoltage irradiation in the treatment of gliomas of the brain and spinal cord.
Curative radiotherapy was attempted in treating 256 patients with unresected or partially excised gliomas of the brain and spinal cord. Survival decreased with increasing age, reflecting the different incidences of tumor types in various age groups. Actuarial 5-year survival ranged from 85% for cerebellar astrocytomas, to 47% for medulloblastomas, to 41% for cerebral hemispheric astrocytomas, and 0% for glioblastoma multiforme. Further improvements in survival utilizing radiotherapy are unlikely until new adjuncts are developed, for higher radiation doses may lead to a disproportionate increase in radiation complications.
Age Factors↗
The striatonigral degenerations. Putaminal pigments and nosology.
Three new cases of striato-nigral degeneration (SND) are presented with particular reference to the identification of putaminal pigments. These were studied by histochemical methods, electron microscopy and elemental analysis. Three interrelated parenchymal perikaryal pigments were identified in the putaminal lesions of all 3 patients: a "haematin" pigment, neuromelanin and lipofuscin. The presence of neuromelanin in the putamen may be due to accumulation of dopamine in the synaptic terminals of the nigro-striatal pathway and its polymerization into pigment. This suggests that the putaminal atrophy is the primary lesion in SND which is a true supranigral form of parkinsonism. Clinically this manifests itself in predominance of rigidity over other parkinsonian symptoms and in a poor, or absent, response to treatment with L-dopa and anticholinergic drugs.
Corpus Striatum↗