p53 gene mutations in human astrocytic brain tumors including pilocytic astrocytomas.

Recent molecular biological studies have shown evidence for a distinct pathogenesis of pilocytic astrocytomas based on alterations other than mutations of the tumor suppressor gene p53. To prove these data, the authors screened a series of 42 astrocytic human brain tumors with a relatively high proportion (16.6%) of the pilocytic variant for the presence of p53 mutations, using the polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis, followed by DNA sequencing. Mutations were found in one of seven (14.3%) pilocytic astrocytomas, in one of 18 (5.6%) low grade astrocytomas, and in one of four (25%) anaplastic astrocytomas, but in none of 13 glioblastomas. Sites of missense mutations were in exon 8 (codons 281 and 282), and exon 5 (codon 151). Silent mutation was found in exon 9 (codon 324), which was related to pilocytic astrocytoma. This is, to the authors' knowledge, the first report that shows a p53 mutation in pilocytic astrocytomas. However, the p53 mutation was only found in one of seven tumors of this entity and was a silent mutation, which does not lead to change of amino acids. Thus, the significance of this alteration for the development of this special tumor type seems to be low. Nevertheless, it may be a sign of genetic instability and is thus suggested to be of certain pathogenetic relevance. The p53 findings concerning the other tumors are in accordance with the view of p53 gene mutations to be early events in astrocytoma formation.

Involvement of chromosome 22 in ependymomas.

We have karyotyped a total of twelve ependymomas using GTG-banding including seven for which preliminary results have already been published. One case showing hyperdiploid main line with two marker chromosomes was further analyzed by nonisotopic chromosome in situ suppression hybridization. It was shown that the marker chromosomes consisted of 1q, 14q and 1q, and 22q. The possible role of chromosome 22 in ependymomas and the usefulness of fluorescence in situ hybridization for cytogenetic analysis in tumor investigation are discussed.

How to run a "brain bank"? Clinical and institutional requirements for "brain banking".

"Brain Banking" or prospective sampling of tissues relevant to the study of neurological disease is a complex task which needs organization at various levels of operation such as the establishment of a donor system, recruitment of clinical assessment centres, establishment of standardized assessment protocols, the inauguration of logistic structures for brain removal and transport to the bank, proper storage of patient data and tissues, histological verification of the disease and availability of tissue and clinical data to researchers. This effort certainly promises to bear fruit since there is a striking lack of precise prospective studies into etiology and pathogenesis in most neurological diseases especially in the field of the neurodegenerative diseases.

Epidemiologic data on meningiomas in East Germany 1961-1986: incidence, localization, age and sex distribution.

From 1961 to 1986, 8119 new cases of meningioma were reported to the National Cancer Register of East Germany (former German Democratic Republic) with an average population of 16.9 million. The crude annual incidence was 1.85 per 100,000 population. The crude rates were 1.16 for males, and 2.44 per 100,000 for women; after age adjustment ("world" population) these rates were 0.90 and 1.92 per 100,000, respectively. Thus meningioma occurred 2.1 times more frequently in women than men. Independent of sex, the incidence rose continuously with increasing age. At the same time, there appeared to be an increase in meningioma frequency in the course of the 26-year reporting period. The overwhelming majority of cases, 7375, (90.8%) were intracranial in location but 711 (8.8%) were intraspinal. Some 50% of all cases were first discovered at autopsy, with the proportion of such cases being markedly higher in the older age groups.

[Cell proliferation and glial fibrillary acidic protein in brain tumors]. / Zellproliferation und Expression des sauren Gliafaserproteins (GFAP) in Hirntumoren.

The results of histoautoradiographic and immunohistochemical studies of biopsy specimens of 15 brain tumours are reported. The specimens were labeled with 3H-thymidine using an in vitro technique. Meningiomas, oligodendrogliomas and well differentiated astrocytomas showed a median S-phase fraction of about 1%. In contrast, the labeling indices of 4 from 7 anaplastic astrocytomas were higher (2.1, 3.0, 3.5, 11.4). With increasing degree of malignancy the proliferative heterogeneity of the tumours increases. In every glioma varying amounts of glial fibrillary acidic protein (GFAP) were detected immunohistochemically (PAP technique). In 3 high-grade gliomas (2 glioblastomas, 1 anaplastic astrocytoma) an inverse relation of the investigated parameters (high S-phase fraction, low GFAP expression) was found. An exact prediction on biological behaviour of an individual tumour by GFAP detection immunohistochemically is not possible, because a high GFAP content can be detected also in some malignant tumours. However, the 3H-thymidine labeling indices of viable parts of the tumours, probably reflecting the growth fraction seem to be clinically important parameters, especially in respect to the prognosis.

Isolation of a SV40-like virus from a patient with progressive multifocal leukoencephalopathy.

A SV40-like virus was isolated from the brain of a patient with progressive multifocal leukoencephalopathy. The virus was antigenically and serologically indistinguishable from SV40 wild type. A unique difference from SV40 was its ability to grow on human glial and CV-I monkey cells. The molecular weight of the viral DNA was very similar to that of SV40 DNA and the DNA cleavage patterns obtained after digestion with Hind II and Hind III restriction endonucleases were indistinguishable from those of SV40.

[Epidemiology of primary tumors of the central nervous system in the 1st year of life]. / Zur Epidemiologie der primären Geschwülste des Zentralnervensystems im ersten Lebensjahr.

148 children under the age of 5 have been identified from the files of the National Cancer Registry of the GDR. They all had primary tumors of the central nervous system (CNS), which were histopathologically diagnosed in the period 1975 to 1980. Additional information concerning their health status and diseases was collected from birth history, postnatal care-unit files, out- and in-patient medical records and other sources. Based on these materials the time of clinical onset of the disease has been elucidated. In 12 of the 148 patients the onset was in the perinatal period and in another 36 during the first year of life. 1,322,450 births took place in the GDR in the index period. The incidence of primary tumors of the CNS with onset of signs and symptoms prior to the end of the first year of life was 3.6 per 100,000 births. The most common type of tumor was astrocytoma, with an incidence of 0.9/100,000. It is followed in frequency by other neuroectodermal tumors and by intracranial teratomas. No meningiomas or pituitary adenomas had their onset in infancy. The conclusion is drawn that the incidence of neuroectodermal tumors is almost the same in newborns and infants as it is in older age groups. The findings contradict the genera view, that CNS tumors in infants are very rare.

[The 10th revision of the International Classification of Diseases]. / Uber die 10. Revision der Internationalen Klassifikation der Krankheiten.

The 43rd World Health Assembly approved the 10th Revision of the International Classification of Diseases (ICD-10) in May 1990 and recommended its implementation by January 1, 1993. The ICD-10 uses a new alpha-numeric code, which provides sufficient code-numbers for all new entities, included in ICD-10 and for further amendments in the future. The extended tabular list of ICD-10 contains HIV-disease (AIDS) and permits separate coding of HIV-disease resulting in various infections, neoplastic and other diseases, such as HIV-dementia complex. Extensions and rearrangements have been made in other groups of diseases, for instance in the chapter on diseases of the genitourinary system. ICD-10 now permits a clear distinction between glomerular and renal tubulointerstitial diseases. The different groups of glomerular diseases can be further characterized by a fourth-digit subdivision of the code-number according to the histopathological findings. Thus, ICD-10 reflects recent developments in medial science. The scientific and practical impact of ICD-coding on mortality statistics, however, largely depends on the use of precise diagnosis and their proper arrangement on the death certificate by the physician, certifying the death. This permits the underlying cause of death to be clearly identified by the coder. The role of the pathologist in this process is stressed. Exact and internationally unified formulation of the diagnosis will be supported in the future by the on-going project developing an International Nomenclature of Diseases (IND). A few volumes of the IND have already been published in English, others are in preparation.

[Epidemiology of tumors of the central nervous system--influence of the autopsy rate on the incidence rate]. / Epidemiologie der Tumoren des Zentralnervensystems--Einfluss der Obduktionsquote auf die Inzidenzrate.

Using the records of the population-based National Cancer Registry (NCR) of the German Democratic Republic from 1968-1983 it was assessed that 5608 (28.9%) out of 19,413 registered primary CNS-tumors were diagnosed at autopsy only. This rate was especially high in meningiomas (53.8%), choroid plexus papillomas (40%) and melanomas (37.9%). 20.7% of the primary malignant melanomas of the CNS were clinically diagnosed as metastases to the CNS. The results show a considerable influence of the autopsy rate on the incidence-values of brain tumors. The autopsy rate should be taken into consideration when comparing incidence rates of CNS-tumors obtained in various regions.

[100 years "Zentralblatt für allgemeine Pathologie und pathologische Anatomie." Origin and growth of the journal]. / 100 Jahre "Zentralblatt für allgemeine Pathologie und pathologische Anatomie". Entstehung und Werdegang der Zeitschrift.

An account is given of the historic background against which the journal was founded in 1890 by publisher GUSTAV FISCHER, Jena, and Prof. Dr. ERNST ZIEGLER, Freiburg/Br. The developments that have ever since taken place through a hundred years under different publishers and editors provide enlightening insights into changing concepts of the journal and variable external conditions for its publications. It came under extremely negative influence during national-socialist rule in Germany. So far unpublished documents are evaluated to describe the reprisals to which the long-standing co-editor Prof. Dr. WALTHER BERBLINGER, University of Jena, had been exposed by the national-socialist rulers for the Jewish origin of his wife. "Zentralblatt für allgemeine Pathologie und pathologische Anatomie", after the end of World War Two, succeeded in gradually regaining an international standing reflected in its community of authors and readers.

[Expression of immunohistochemical differentiation markers in normal and transformed neoplastic neuroectodermal stem cells]. / Expression von immunhistochemischen Differenzierungsmarkern in normalen und neoplastisch transformierten neuroektodermalen Stammzellen.

The cells of primitive neuroectodermal tumours may undergo differentiation and, eventually, may be transformed to neurons, glial cells, and ependymal cells. Early stages of neuroectodermal differentiation may primarily be determined by means of immunohistochemical methods. Immunohistochemical investigations were performed on brains of human foetuses obtained from the 18th to 36th weeks of pregnancy, with a view to elucidating the process of maturation during foetal development and to determining the antigens identifiable in cells in the course of differentiation, following fixation in formalin and embedding in paraffin. Gliafibrillar acid protein (GFAP) and vimentin proved to be of particularly high stability and, consequently, were easily detectable from paraffin material. The same antigens were focally recordable also from eight of 17 primitive neuroectodermal tumours. Clues were rare in these tumours as to neuronal differentiation. This was attributed to instability of neurofilament proteins under conditions of formalin fixation and paraffin embedding.

[Tumour induction by methylnitrosourea in clawed frogs (Xenopus laevis) (author's transl)]. / Tumorinduktion beim Krallenfrosch (Xenopus laevis) durch Methylnitrosoharnstoff.

15 clawed frogs were bathed 12 to 17 times in solutions of 2 mg methylnitrosourea, dissolved in 1000 ml destilled water. 7 frogs developed tumours 8 to 22 months after starting the experiments. Another frog died of polycystic kidneys. The tumours were adenocarcinomas of the kidneys, sarcomas and a benign papilloma of the pelvis of the left kidney. A sarcoma of the soft tissues of the head showed an excessive granular storage of acid mucopolysaccharides in the cytoplasma of many tumour cells. Tumours of the nervous system did not occur.

[Chemicals and cancer risk (author's transl)]. / Chemische Verbindungen und Krebsrisiko.

Environmental factors are considered to be the main causes creating human cancer risks. Some of the topical problems involved, resulting from the existence of defined or discrete carcinogens and so called carcinogenic risk factors, are discussed. Up to now it has been rather difficult to analyse them exactly. Qualitative and quantitative aspects of the assessment of carcinogens and the relevance of short-term tests, long-term bioassays and epidemiological studies are discussed. It is estimated that the possibilities to assess cancer risks have improved during the last few years.

[Autopsy report of the corpse of the composer Robert Schumann-- publication and interpretation of a rediscovered document]. / Der Obduktionsbefund der Leiche des Komponisten Robert Schumann--Veröffentlichung und Wertung eines wiederentdeckten Dokuments.

The report, previously regarded as lost, of the post mortem examination performed on Robert Schumann was found in 1973 by G. Nauhaus in the Archive of the "Robert Schumann House" in Zwickau. The original version is published here for the first time. Dr. med. Richarz, director of the private psychiatric institution in which Schumann had been hospitalized, conducted the autopsy together with his assistant Dr. med. Peters. Fragments of the autopsy findings, published by Richarz are known through his letters, provided, until now, the only available facts. The prosector's diagnosis of brain atrophy is not supported by the brain weight of 1,336 g, which is near the average brain weight for men of the corresponding age, nor by the volume of the cranium. 1,510 cm3, as reported by Schaaffhausen. The indentations and protuberances of the cranial bones in the region of the middle cranial fossa were regarded as reflecting prominent indentations of the gyri and were attributed no pathological significance. A small osteophyte in the region was not regarded as clinically important. The thickenings and scattered adhesions of the arachnoid membrane described in the report, cannot be pathologically interpreted. Moreover such findings are so uncharacteristic as to provide no compelling evidence for a resolved or on-going chronic inflammatory process. The available information permits no further interpretation of a mass in the hypophyseal region, described as gelatinous and partly of cartilagenous consistency. The cardiac findings do not suggest hypertension. The condition of the kidneys is not mentioned. The rediscovered document contains no information which persuasively supports any of the hypotheses about Robert Schumann's underlying illness which have appeared in the literature.

[Epidemiology of primary tumors of the central nervous system in children and adolescents. A population-based study]. / Epidemiologie der primären Tumoren des Zentralnervensystems bei Kindern und Jugendlichen. Eine bevölkererungsbezogene Studie.

The incidence of primary CNS tumours in children and adolescents (0-20 years of age) was investigated for the time period 1970-1989 using the records of the East German National Cancer Registry. 2906 such tumors were registered. 93.2% of them were histopathologically confirmed. The incidence was 31.0/1,000,000 for the male and 25.9 for the female population. 2719 (93.6% of all tumours) were intracranially and only 187 (6.4%) intraspinally situated. The incidence of the CNS tumours increased during the time period of the investigation. This increase was more pronounced in the male and less in the female population. The most common tumour types were gliomas (38.7% of all registered CNS tumours), medulloblastomas (14.0%) and ependymomas (10.9%). 130 primary CNS tumours occurred in infants (less than 1 year of age). Among these tumours were 21 ependymomas and 21 choroid plexus tumours.

[Primary tumors of the choroid plexus. Frequency, localization and age]. / Primärgeschwülste des Plexus choroideus. Häufigkeit, Lokalisation und Lebensalter.

In 30 years, from 1956 through 1985, 155 primary tumours of the choroid plexus were first reported for entry into the National Cancer Registry of the GDR, with 125 of them having been identified as plexus papillomas and 30 as plexus carcinomas. A total of 30.4 per cent of all plexus papillomas was diagnosed in patients in the first decade of life, half of them during the first year of life. A lateral ventricle was the site from which 78.9 per cent of the plexus papillomas in the first decade were recorded. Among all plexus tumours 39.4 per cent were detected only on postmortem investigation. The number of plexus tumours reported for entry into the National Cancer Registry had continuously grown in the period under review, which, however, did not necessarily suggest increasing incidence of such tumours in the general population. Possible factors of influence are discussed in some detail, for example, completeness of recording. The number of plexus tumours reported in children up to three years of age rose with significance, between 1981 and 1985. This is assumed to have possibly been the consequence of an aetiological factor. The average annual incidence (crude rate) of plexus tumours at GDR level was found to be 0.3 to one million (0.36 among males and 0.25 among females). Reasons are given that might support the assumption that real incidence has been above these values.