Morphological markers in neuro-oncology.
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Astrocytoma↗
Biomedical subjects
R C Janzer
Publications and source records attributed to R C Janzer.
In vivo metabolism and reaction with DNA of the cytostatic agent, 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC).
The cytostatic drug dacarbazine [DTIC, 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide] is strongly carcinogenic in rats. Bioactivation of DTIC yields a methylating intermediate but the extent of interaction with cellular macromolecules has not previously been reported. Following a single i.p. injection of [14C-methyl]DTIC, exhalation of 14CO2 occurred with a t1/2 max of approximately 2 hr (0.95 mg/kg) and 2.5 hr (95 mg/kg). Of the total radioactivity administered, 8.5% was exhaled as 14CO2; 54% was excreted via the urine, predominantly as unchanged DTIC. In liver, kidney and lung, formation of 7-[14C]methylguanine in DNA and RNA was directly proportional with dose. DNA methylation by a single dose of DTIC (9.8 mg/kg; 5 hr survival time) was highest in liver (35 mumoles 7-methylguanine/mole guanine), followed by kidney (25 mumoles) and lung (20 mumoles). The remainder tissues showed 7-methylguanine concentrations approximately 50% of those in liver DNA, with the exception of the brain which had a very low extent of DNA modification (approximately 1 mumole/mole guanine). At the specific radioactivity used (48 mCi/mmole), the promutagenic base O6-methylguanine was only detectable in liver, kidney, lung, and stomach DNA (0.6-0.8 mumoles/mole guanine). Autoradiographic studies revealed a diffuse distribution of reaction products in rat liver. In contrast, N-nitrosodimethylamine and related carcinogens known to be bioactivated by the hepatic cytochrome P-450 system show a predominantly centrilobular distribution. This difference may be due to the greater stability of proximate carcinogens generated by alpha-C hydroxylation at one of the methyl groups of DTIC.
Animals↗
Progressive myoclonic epilepsy (Unverricht type) with atypical Lafora bodies. Case report.
A patient with advanced progressive myoclonic epilepsy (Unverricht type) with Lafora bodies is presented. Although the clinical history and symptoms were classical, the regional distribution of the cerebral involvement differed from the classical picture: the corpora mamillaria, the nucleus subthalamicus, and the nucleus ruber, which are normally reported to be spared, contained multiple Lafora bodies, whereas the lateral geniculate body, which is usually involved, was intact. The number of inclusions per cell, up to 25, was extremely high and correlated with the marked cortical atrophy and the prolonged clinical course. Using electron microscopy, type I and type II Lafora bodies were found, but the latter lacked the typical filamentous ultrastructure in the peripheral zone. The lack of visceral Lafora bodies in this case suggests that liver, muscle, and skin biopsies, which are widely used for the diagnosis, may lead to false negative results and cannot always replace a stereotactic brain biopsy. The differential diagnosis on polyglucosan bodies is emphasized.
Adult↗
Early and late effects on the normal dog brain of permanent interstitial iridium-192 irradiation.
To investigate the effects of a permanent interstitial source of gamma-irradiation on normal brain tissue, single iridium-192 (Ir-192) wires (1.05 mCi) were stereotactically implanted into the left centrum semiovale of adult dogs (survival times, 25, 46, 74, 230 and 362 days). Within 25 days, a coagulation necrosis developed in the immediate vicinity of the radioactive source. In later stages, the necrosis increased in size and became progressively mineralized. Staining for extravascular immunoreactive serum proteins revealed the presence of a chronic perifocal vasogenic edema, which extended into the white matter of the entire ipsilateral hemisphere. This edema persisted through all stages and showed a significant decrease only in the animal with a 1-year survival. A reactive gliosis with formation of a dense network of glial fibrillary acidic protein-positive astrocytes developed around the central necrosis in the adjacent white matter and, at later stages, in the contralateral hemisphere. Demyelination was restricted to the ipsilateral centrum semiovale without affecting the internal capsule or the contralateral hemisphere. It was present as early as 25 days and showed no tendency to increase at later stages. Analysis of the sequential morphological changes following Ir-192 implantation suggests that the central coagulation necrosis represents a direct radiation effect, the sharp focal delineation of which can be explained by the physical characteristics of the radiation source, i.e., rapid fall-off of the dose at short distances. Due to the continuous emission of radiation energy, there is a perifocal zone with overlapping of progressive radiation damage and tissue organization. This focus becomes the source of a chronic vasogenic edema, which in turn is most likely to be responsible for the partial demyelination of the adjacent centrum semiovale. The widespread reactive gliosis observed at all stages may also, in part, be a consequence of chronic vasogenic edema, but its distribution suggests that direct radiation effects may also be involved.
Animals↗
Elevated concentration of IGF II in brain tissue from an infant with macrencephaly.
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Abnormalities, Multiple↗
Severe neonatal centronuclear (myotubular) myopathy: an X-linked recessive disorder.
Prenatal onset and rapidly fatal course of centronuclear myopathy are described in four male newborns including two brothers. Diagnosis was established by muscle biopsy within the first week of life in two and at autopsy in the two other patients: Central nuclei, central aggregation of oxydative enzyme activity in the majority of muscle fibers and type 1 fibre hypotrophy were demonstrated. Prenatal manifestation included polyhydramnios, reduced fetal movements and breech presentation. All four newborns developed respiratory insufficiency requiring artificial ventilation immediately after birth. Severe muscular weakness and hypotonia as well as hardly elicitable grasping, deep tendon reflexes and Moro response were noticed. Additional findings included high arched palate, joint contractures, thin ribs, lung hypoplasia, abundant skin and cryptorchidism. In two families, the pedigree contains other affected males, suggesting X-linked inheritance. Seven female carriers were clinically healthy and one of them showed normal muscle histology. Fourteen previously published neonatal cases of centronuclear myopathy are reviewed and compared with our findings. This severe perinatal form of centronuclear myopathy has to be considered in male fetuses and newborns with polyhydramnios and respiratory failure due to muscular weakness or in infants who died of unexplained postnatal asphyxia. Diagnosis should be established by muscle biopsy.
Genetic Carrier Screening↗
The capillary bed in the choroid plexus of the lateral ventricles: a study of luminal casts.
Micro-angioarchitecture of the choroid plexus of the lateral ventricles is investigated in microcorrosion casts of animal and human preparations studied with the scanning electron microscope. The capillary bed in the diverse regions of the tissue belongs to one of three patterns: (1)-a network of capillary meshes that envelop the larger arteries and veins predominates in the central segment. (2)-in the villous regions a "leaf-like" organization of sinusoids is found together with (3)-fronds of "glomerular" formations. "Glomeruli" are formed when arterial afferents and venous efferents converge in a quasi hilar structure before branching in arterio-venous loops. Nodular thickenings are observed on glomerular capillaries. The preparations studied (rat, dog, human) are remarkably similar and differ mostly in degree of occurrence of common architectural patterns. Arterio-venous communications are found at the hilus of human glomerular formations.
Adult↗
An unusual association of dentato-rubral degeneration with spinal ataxia, ophthalmoplegia and multiple cranial nerve palsies.
Clinical and neuropathological data of a 50-year-old woman with an unusual multisystem degeneration are presented. Clinically the illness was characterized by progressive ataxia with ophthalmoplegia and multiple cranial nerve palsies. Neuropathological investigation showed a severe and selective degeneration of the dentato-rubral system, of the posterior columns and of several cranial nerve nuclei. The problems of differential diagnosis and classification are discussed.
Ataxia↗
Primary intracranial germ-cell tumors. A clinicopathological study of 14 cases.
Fourteen cases of primary intracranial germ-cell tumors are presented. Histologically, there were eight germinomas, three teratomas, and three germ-cell tumors of more than one histological type. Immunohistochemical studies revealed alpha-fetoprotein in yolk-sac tumor components in two cases and beta human choriogonadotropin in syncytiotrophoblastic giant cells in one case. One teratoma contained an unusual pleomorphic sarcomatous portion with features of early myoblastic differentiation. Comparison of intracranial with gonadal germ-cell tumors shows that the same subtypes are found in both locations with comparable incidence and similar biological behavior. The detailed World Health Organization classification of testicular germ-cell tumors should be applied to the histopathological classification of intracranial germ-cell tumors. Despite the critical location of intracranial germ-cell tumors, a good outcome can be achieved by optimal surgical excision. A primary microsurgical approach provides a histopathological diagnosis, which is indispensable for the proper choice of postoperative management.
Adolescent↗
Intraoral malignant melanotic schwannoma. Ultrastructural evidence for melanogenesis by Schwann's cells.
Clinical and light and electron microscopic findings of one case of malignant melanotic schwannoma of the oral cavity are presented. The tumor recurred four times and developed submandibular metastasis. At autopsy, 24 months after manifestation of the initial symptoms, a hematogenous metastatic nodule was present in the liver. Peripheral melanotic schwannomas show a more malignant behavior than intraspinal examples. The Schwann's cell character of the individual tumor cells is demonstrated ultrastructurally by the presence of a prominent basal lamina, desmosomelike junctions between interdigitated elongated cell processes, and melanosomes in all stages of formation. These findings support the concept that neoplastic human Schwann's cells are capable of melanogenesis.
Female↗
Infantile small cell gliomas.
Fourteen juvenile patients with small cell gliomas were studied at two institutes. These tumors are believed to form a distinct entity. They arise mostly in the diencephalon or the brain stem and are composed of a poorly differentiated small cell component having a pronounced tendency to differentiate into a glioma. Signs of neuroblastic differentiation were also found with the electron microscope. Small cell gliomas disseminate early and profusely throughout the ventricular walls and the subarachnoid spaces including the spinal meninges. Prognosis is grave, most patients dying within 1 year of diagnosis or surgical intervention. The designation "infantile small cell glioma" overlaps with both the "metastasising gliomas in young subjects" of Eade and Urich (1971) and with the primitive neuroectodermal tumor of infancy of Hart and Earle (1973).
Adolescent↗
Dandy-Walker syndrome with atresia of the fourth ventricle and multiple rhombencephalic malformations.
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Brain Stem↗
Do Rosenthal fibers contain glial fibrillary acid protein?
Sixteen cases of pilocytic astrocytomas with excessive Rosenthal fiber (RF) formation were examined by the indirect immunoperoxidase method for the localization of glial fibrillary acid protein (GFAP). RF never contained GFAP but they were often enclosed in plump and thickened GFAP-positive astrocytic processes. The border between the negative RF and the surrounding positive rim of cytoplasm was always sharp and without gradual transitions. The antigenic difference between RFs and glial filaments imply that glial filaments undergo a profound change in their chemical composition during their transformation into RFs. The possibility that RFs are not degradation products of glial filaments but consist of some chemically unknown substance produced by metabolically activated astrocytes cannot be excluded.
Astrocytes↗
Hypotensive brain stem necrosis or cardiac arrest encephalopathy?
Selective symmetrical necroses of many tegmental brain stem nuclei including motor cranial nerve nuclei, superior and inferior colliculi, cuneate and gracilis nuclei, and others are known as hypotensive brain stem necrosis (Gilles 1969). We found such lesions in eight infants and seven adults. Examination of their clinical records revealed a well documented episode of cardiac arrest in each case. Cardiac output was restored in all but one patient 5 min to 4 h after the beginning of resuscitation. All patients remained comatose in a decerebrate state up to their death 17 h to 4 weeks after admission. Our findings and a review of the literature indicate that this type of lesion relates specifically to cardiac arrest. The term "hypotensive brain stem necrosis"is a misnomer and should be replaced by the term "cardiac arrest encephalopathy".
Adolescent↗
The relation between solid cell nests and C cells of the thyroid gland: an immunohistochemical and morphometric investigation.
Thyroid tissue of 300 routine autopsies was processed in a standardized manner. So-called solid cell nests (SCN) were found in 21 patients (7%). These cases were investigated carefully by serial step sectioning. In order to explore the correlation of SCN to the C-cell system, the sections were stained by silver impregnation and the immunoperoxidase method. Morphometric analyses revealed a significant increase in the density of C cells in the proximity of the SCN. With progressive distance from the SCN, the C-cell density decreased and reached normal values. In 30% of the cases argyrophilic and calcitonin-positive cells were found lying within the SCN. Occasionally, mixed follicles could be discerned: These were lined on the one side by a multilayered squamous epithelium, on the other side by normal monolayered cubic follicular epithelium, and contained a peculiar granular material. In one case, SCN were associated with intrathyroid portions of the parathyroids and adult adipose tissue, in a second case with adipose tissue only. Most probably SCN are vestiges of the ultimobranchial body and should be interpreted as such, despite the fact that other authors have expressed different views. The lack of disturbances in the calcium metabolism of the patients and the absence of medullary carcinoma in their family histories led us to interpret locally confined C-cell hyperplasia not as reactive nor premalignant, but rather as normal.
Adipose Tissue↗
Perisulcal infarcts: lesions caused by hypotension during increased intracranial pressure.
A pattern of cortical necrosis surrounding the cerebral sulci and similar to ulegyria was found in 5 patients. The lesions were widely disseminated in all parts of the hemispheric cortex, affecting mostly the deep cortex of several adjacent sulci. They were hemorrhagic in 3 patients, ischemic in the others. Each patient had suffered a severe brain injury and became comatose thereafter. Increased intracranial pressure was evident from clinical findings, necropsy changes, or both. While in coma, each patient had at lease one episode of hypotension. The data suggest that perisulcal infarcts are a manifestation of diminished vascular perfusion during a period of increased intracranial pressure.
Adult↗
[C-cells of the thyroid gland].
In the human thyroid gland, the C-cell system reacts in physiologic and pathologic conditions as an entity and represents an independent endocrine organ. Its special features are its embryology, which relates it to other derivatives of the neural crest, the special histologic methods needed to demonstrate its disseminated C cells, and the obscure physiologic role of its hormone, calcitonin. Although there exist many histopathologic findings, the only C-cell disease of clinical interest is medullary carcinoma, which in its familial form is usually associated with pluriglandular syndromes.
Calcitonin↗
The influence of chronically hypoxemic states on human carotid body structure and cardiac hypertrophy.
Quantitative and qualitative changes in the human carotid body morphology, and their relationship to changes in the weight of right and left ventricles were investigated in 10 patients with a history of chronic hypoxemia. 5 patients without a history of cardiac, pulmonary or cerebral respiratory failure served as the control group. In the chronically hypoxemic group, a 2.67-fold increase in the total specific glomus cell volume was found. Up to a critical volume this increase is due to hypertrophy, beyond that it is due to hyperplasia. The course of the morphologic changes under the influence of slowly progressive chronic hypoxemia is discussed in a frame work of three stages (stage I - hypertrophy, stage II = nodular hyperplasia, stage III = atrophy). Plasmacellular infiltrates are constant though sometimes sparse. They are mostly perineural in location, less often intralobular and if so almost exclusively periglomoidal. In one case, we found an increase of Schwann cells in the interstitial and periglomoidal space without demonstrable degeneration of the nerve fibres themselves. Our hypothesis suggests that degeneration of special nerve terminals of the reciprocal type occurs in afferent nerve fibers. The increase of right ventricular weight (by a factor of 2.05) is significant, in contrast to that of the left. A linear correlation between the increase of right ventricular weight and the increased total glomus cell volume was not established. In 4 cases, however, we found pulmonary hypertensive vascular changes, which might be responsible for the disparity in the linear relationship.
Aged↗