Notwithstanding the pleasure we feel about the steadily advancing develop- ment of our technology and improvements to our instrumentarium, we should never forget the eminent accomplishments of our great masters. Their activities of that time constitute the foundation of our present-day knowledge and skills, and just as our hypothesis of today already harbour the errors of tomorrow, we should judge the.
With 200 Figures and 86 Tables
Here in Germany neurosurgery has advanced to the stage where it has become an established, acknowledged constituent of medical science as a whole. More than that, it has succeeded in re-establishing the contact with its international counterparts lost during the Second World War, and can present itself today as ranking equal to them.
It combines the good of the past with the better of present-day advances, and is paving a path for itself into the future that is full of hope. Could a tradition that has grown up on the basis of long and fruitful experience present a better image of itself than by retaining that which has proved to be good and jettisoning that which has not been found to be meaningful, or even wrong?
The public at large, but especially the sick, those requiring help, sho'uld be grateful to the majority of doctors for not having complied with the frequently expressed wish for change also in this direction. A good conservative attitude is of greater value than any form of doubtful experimenting with its uncertain outcome, in particular when this relates to the sick person.
As is to be expected, these ideas, which in part have their origin in pure ideologies, come almost entirely from healthy people. They know neither the world of the sick, nor are they able to put themselves into their position. How rapidly these frequently totally practiceremote notions collapse is usually shown whenever the loaded question is asked: "Who would you like to operate on you, if necessary"? The intern, the surgeon who has already carried out several similar operations, the head surgeon, or perhaps the senior medical officer, who has in the meantime become the whipping-boy of a whole horde of papers, but who has nevertheless the most experience at his disposal, or perhaps, if one asks "Who is to decide about your illness, your treatment, a team of doctors or one responsible doctor"?
After all responsibility is not divisible. But it is out of this that a mission arises, which generations of medical practitioners have taken very seriously. For them, apart from the illness to be treated there was also the patient that wanted to be cared for. And since the one and same illness of years ago does not differ one iota from the one of today, the anxiety of the sufferers has always remained and will always remain the same, the treatment can only be directed towards two things: 1.
These are facts that no one can pass over without seing them. The demand for full mechanisation of hospitals is justifiable for organisational reasons. It promotes the flow of the work processes. The steady reduction in the working hours, on the other hand, encourages personnel to watch the clock; the 5-day week, from the viewpoint of the hospital, by comparison with other professions that can afford it, induces staff to press for an ever-longer week-end off.
In the hospital it is just one of those things that special tasks are in the foreground, these having very much to do with ethics, humanity and personal help, but very little to do with politics, ideologies or even empty verbosity, which can neither help the sick nor give them hope. The patient, with his understandable hypersensitivity, most certainly notices the shift or sliding duty arrangements or whatever other term might be used.
It is only with difficulty that he gets used to the changing number of staff nursing and attending to him. Those who are in a position to critically judge the case of the sick in former times and today will come to the conclusion that the work in the wards has become a nec- essary service branch and is no longer a genuine nursing of the sick that comes from the heart.
Perhaps I may express this in slightly different words. No two-way communications system, no control desk with individual parameter monitoring, no optic or acoustic information on the condition of the patient can replace the friendly chat with him, the touching of his hand to re-assure him. The personal ties of the patient with the doctor treating him and vice versa are the best foundation for his recovery. A patient who has trust in his doctor is well off, one who believes in him is even better off. These are facts that every experienced doctor is familiar with.
What do those healthy people, who are able to avail themselves of medical help at any time, know of the inner self of a doctor? Of his decisions that very often have to be taken alone, and which many a time involve life or death, and which no one can lift from his shoulders? What do they know of his worries and cares about a patient, his frequently nocturnal deliberations when it is a question of the pros and cons regarding a high-risk operation?
What do they know of his involvement in the experience and suffering of a patient whom he has come to have a feeling for, also in human terms, but whom he is no longer able to help? What do they know of his feelings when he has to break the news to parents that their only child can no longer be saved, that the life of the young mother can no longer be preserved? And then there are also those intellectual critics who, against their better knowledge and belief, perhaps only because they have had some negative personal experience with a rather unsympathetic doctor, whom we too know, by making generalisations about a whole profession, would like to imprint upon all the stamp of amoral conduct.
In doing so, they contribute not only to the discrimination of a whole professional group, but above all to undermining the patient-doctor relationship.
The fact that at the same time, however, also the confidence relationship between the two partners suffers in consequence, and accordingly the decisive and most important pre-requisite for every successful treatment is destroyed, appears to have escaped their attention. How many members of that professional group, which again and again demand from us a full clarification, ask neither for the exact diagnosis nor for the prognosis when they themselves are the persons involved.
A large number of patients would with certainty refuse an operation, which despite all risks could prove successful, if they were given information in advance about every detail of diagnostic or therapeutic methods. All too frequently in the past hopes have been raised in the population by distorting reports that simply could not be realised, if only for the reason that they were factually incorrect.
How often are collections made even these days for sick people and big sacrifices made for them on the assumption that their salvation lies only on the other side of the ocean, whereas any well-read layman knows that this help could be had just as well in a nearby German town. In all these questions meaningful cooperation between the mass media and doctors would be better than working against one another and thus be a true help for the sick, whom in the final instance is involved.
Let us hope that the discussion of the problems to be dealt with will proceed in the same spirit: as a valuable answer to critical questions for the benefit of the patients entrusted to our care! Koos, G. BAuER, H. GAAB, and T. WILD, H. KAHL, and W. TzoNOS and F. BOCK, R. POLL, P. MOCK, and H. WILD, F. B6cKEM, and K. ERBS, H. SINN, and P. FEIGl, and H. PALM, and K. BARZ, andH. J urgenstr. BARZ, D. GAAB, M. KAHL, R. Meningiomas are commonly thought to be derived from a meningo- thelial 5 matrix, i. The term of dural endo- thelioma has become obsolete, all the more so because most text- books mention a subdural capillary space between the inner surface of the dura and the outer aspect of the pia-arachnoid, and deny the existence of a cellular layer on the inner surface of the dura.
Electron-microscopic observations, however, indicate a 'neurothel- ial' cell layer between dura proper and pia-arachnoid 1. These cells appear to be very easily damaged by mechanical tear and autolytic changes. This cell layer can be identified on prepara- tions from human leptomeningeal tissue removed during operation 7. Therefore, the question of histogenetic derivation of menin- gioma tissue should be re-evaluated. In some instances, meningioma cells of apparently fusiform shape can be identified as sections through flattened cell bodies ar- ranged in stacks.
Vacuolated cell bodies, sometimes with hyaline inclusions, might correspond to neurothelial cells. Highly vascular meningiomas should not be lumped together with hemangioblastomas of the CNS 4 and hemangiopericytomas of the meninges 3, 6. Concerning pathogenesis of meningiomas, the discovery of abnormal chromosomal pattern with loss of one G 22 chromosome 8, 10 might be connected with the presence of a virus belonging to the papova group The unique observation of a sarcoma in the mouse induced by human spinal meningioma implant 2 might be another hint at a possibly viral origin of some meningiomas.
Grading appears to be a useful tool for differentiating between meningiomas of different prognostic value. Thus, meningioma grade does not exceed usual degrees of insinuation between other tissue structures. Meningioma grade 3 reveals definite infiltrative and destructive growth.
The aspect of meningioma grade 4 conforms to sarcoma with a recognizable de- rivation from meningioma. Meningioma grade 4 has also been called meningosarcoma 9. Grading should be applied within a single tumor species only, not to a hodgepodge of different tumor species. BEGG, Ch. Cancer 2, - Acta neuropath. Their source and favoured seats of origin. Brain li, - Neurology Minn.
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ZANG, K. Nature , 85 A critical evaluation of malignancy in meningiomas presupposes the definition of malignancy. Malignancy has some significance in our current daily work; its meaning, however, is not always clear, espe- cially if we deal with tumors of the nervous system. Historical Evolution In the field of neurological sciences LEBERT 11 was the first to state, in , that fibroblastic and sarcomatous tumors of the intra- cranial cavity have different survival times.
Fibroblastic tumors appeared to be more benign. This was the first correlation of histo- logical classification and prognosis. Their observations form the basis of our present day knowledge 21, This case illustrated that a very long history does not contra- dict the eventual malignant transformation of a tumor of this group.
We were able to report a very similar case from our own collection, in which a metastasis in the lungs weighting more than 1 kg was found 22 years after the first operation. This case was considered as not benign from the beginning because of the angiographic findings and because of the in vitro growth of tumor cells in tissue culture However, metastases from meningiomas to remote sites have always been considered rarities 5, 6, 7, 19, Malignancy in Neurooncology In neurooncology there is no particular histological feature decisive for the diagnosis of malignancy for all tumors in question.
On the contrary, malignancy has to be defined for each tumor entity by a cor- related clinico-pathological investigation. By this procedure histo- logical criteria may be found for each tumor group, which allow a de- finition of its biological behaviour. Yet this procedure is compli- cated by the fact that the pure clinical malignancy, derived from the peculiarities of the central nervous system, has to be ruled out, and that growth properties have to be judged somewhat theoretically In the attempts of the World Health Organization to establish a new classification, this point of view was taken to define the biological behaviour of the different groups.
A group of experts is working out. This work is in progress and all major problems seem to be solved to date. In the preliminary draft a malignant variant for all groups of tumors is foreseen Table 1. In the work of the WHO "anaplasia" or "malig- nancy" is defined as including all morphological pecularities which, according to our clinical experience, presumably lead to malignant growth. These features are: pleomorphism, increased cellularity, growth by invasion, numerous mitotic figures, particularly atypical forms, poor differentiation, giant cells, abnormous stroma reactions, especially vascular proliferations, pseudopalisades, necroses and, in some cases, metastases through the cerebralspinal pathways and even outside the central nervous system.
Table 1. Anaplasia or malignancy according to the preliminary draft of the WHO classification of tumors of the central nervous system Pleomorphism increased cellularity numerous mitotic figures, particularly atypical forms poor differentiation Abnormous stroma reaction, especially vascular proliferation giant cells pseudopalisades necroses Growth by invasion metastasis through the spinal pathway outside the central nervous system. They are, then, considered to be the histological equiv- alent of malignant growth. One difficulty consists in the synonymous use of the terms anaplasia and malignancy, which, however, may be con- sidered preliminary.
Concept of Malignancy Applied to Meningiomas According to our clinical experience, these general peculiarities are the signs of rapid, anaplastic and malignant growth. These signs may be more or less prominent in the different entities, but it is nor re- quired for all of them to be present. Therefore, a combination of sev- eral of these features may be decisive for malignant growth in each tumor group. In the case of the meningiomas Table 2 the most impor- tant indicator of anaplasia apparently is an increasing number of mitoses, i. Another rather important point consists in the infiltrative growth into the surrounding brain tissue.
However, infiltrative growth has to be demonstrated histologically; fingerlike extensions into the surroundings, as often seen in tumors of the Sylvian area or the temporal base, are not considered to be an invasion, neither is the not unusual growth within mesenchymal tissue, e. On the other hand, cellular pleomorphism in meningiomas alone does not indicate higher malignancy. Table 2. Anaplasia or malignancy in meningiomas; only few of the gen- erally adopted criteria are valuable High number of mitoses, especially atypical low differentiation cellular pleomorphism combined with numerous mitoses infiltrative growth metastases.
Cellular pleomorphism is a malignant sign in the meningioma group on- ly if combined with other indications of rapid growth. The pattern of histological features associated with malignancy in meningiomas is therefore the following: 1. Grading of Malignancy in Meningiomas Grading schemes have proved to be helpful in diagnostic work during the last 25 years. For in- stance, we may have only two grades for most gliomas, e. In this scheme meningiomas are generally considered to be benign.
Malignant or anaplastic meningiomas belong to the groups II semi- benign or even III semimalignant of our scale. Group IV malignant is reserved for the true primary fibrosarcomas of the meninges. Some, probably secondary very malignant meningiomas, mostly recurrent tumors of former benign meningiomas, have to be classified as sarcomatous meningiomas and belong to this group; they grew infiltrating and eventually metastasized. Using this grading scheme, we adopt a rough subgrouping of benign and anaplastic meningiomas.
We used this grading as the basis of a statistical analysis dealt with later on. This subgrouping contains Fig. The benign meningiomas including the benign! Polymitotic meningiomas with transitional forms from benign to semibenign and semimalignant. The metastasizing and infiltrative meningiomas which in general have to be considered as at least semimalignant. The primary fibrosarcoma of the meninges. This, however, has been con- tested by several authors 3, The splitting-up of the group of socalled angioblastic meningiomas into angiomatous meningiomas, heman- gioblastic meningiomas and hemangiopericytic meningiomas may prove useful in solving this question The preliminary draft of the WHO-nomenclature has introduced these three types as meningioma sub- groups Table 3.
It has been reported by some authorities that only the hemangiopericytic type of meningioma is more prone to recur 9. This statement has to be reviewed after additional work on the basis of the WHO-classification. No general conclusions may be drawn from the participation of the stroma in this tumor group. Table 3. Subclassification of meningiomas according to the preliminary classification scheme of the WHO Meningiomas 1. Primary fibrosarcomas of the meninges may be considered to be the truly malignant counterparts of the benign meningiomas.
They have been introduced as the primary meningeal sarcomatosis into the WHO classification. Their growth is invasive and infiltrating, their vas- culature is not very prominent, necroses are generally not associated with stroma reaction. This is quite different from the features seen in glioblastoma, where all sorts of vascular hyperplasia up to the formation of glomerula are found. However, the isomorphic monotony of cellular growth in fibrosarcomas may be interrupted by the occur- rence of chromatin-dense multinucleated giant cells.
The number of mitoses, on the other hand, is the same in other tumors of this group in the body. Inbetween the benign tumors on one side, and the malignant sarcomas on the other, we find the different forms of polymitotic, rapidly growing, partly invasive meningiomas which exhibit the malignant char- acter in different expressions. Both these groups, in our grading scheme II semibenign and III semimalignant , are the main subject of the following statistical evaluation. Statistical Data In our collection of tumors of the nervous system, are meningiomas, i.
Statistical analysis was only possible in the cases collected from on. In the time between and we classified cases as meningiomas, 57 of which, i. Some- times these tumors showed a prominent intercellular fiber production, as usually seen in reticulum cell sarcomas. Only 5 tumors were thought to be of grade IV. These are some of the recurrences of former benign meningiomas which became sarcomas as mentioned above.
The sex distribution of meningiomas in our collection shows the well known female preponderance. For this group of tumors we have found a rate of approximately 2 : 1. Interestingly enough, in the malignant form there is a preference for the male sex; the relation is about 3 : 2.
This is apparently consistent with a general trend in neuro- oncology Fig. Malignant forms occur predominantly in males, the benign in females In contrast, the age incidence of the benign and 57 malignant tu- mors is almost identical. This shows quite clearly that malignant meningiomas are by no means sarcomas, which have no age peak when oc- curring in the central nervous system. The length of preoperative history could be evaluated only in a part of our material. There were no major differences in benign and less benign forms.
However, in the malignant form short preoperative his- tories prevail. One explanation of this fact may be seen in the high frequency of benign psammomatous meningiomas in the spinal region, which almost exclusively occur in women in the age between 50 and 65 10, Malignant meningiomas are, in contrast, more frequent in the intracranial cavity, especially with a frontal site. Malignancy of Meningiomas in General Neurooncology General neurooncology has been broadly influenced by the experimental result of tumor induction with resorptive carcinogens. Peculiar facts of these experiments are, for instance, the occurrence of multiple tu- mors in these animals and the higher malignancy of induced tumors.
These results, therefore, have stressed once more the discussion of malignancy in neurooncology as well as the discussion of multiplicity of tumor growth. One example of this higher malignancy is the fact that in the experi- ments with resorptive carcinogenes almost no true benign meningiomas. If tumors occurred in the meninges, they were almost exclusively malignant meningeal sarcomas, which, however, were not very numerous in these experiments. In contrast, they were regularly induced by topic application of carcinogenic carbohydrates as well as in viral carcinogenesis in the central nervous system.
Meningeal sarcomas, found sporadically in rats treated with resorptive carcinogens, were constituted by spindle cells and had a strong parti- cipation of collagen and reticulin fibers. Cells explanted in vitro behaved like fibroblasts without, however, showing contact inhibition. In vitro production of reticulin fibers was observed at the beginning of in vitro growth.
Tumors could be transplanted successfully. They grew subcutaneously as well as in the cranial cavity. In this latter site they grew only within the meninges and infiltrated the brain through the perivascular space. Neurooncogenic viruses, on the other hand, almost regularly produce very malignant tumors of the meninges. One of the last results is that of OGAWA 15 , who employed adenovirus 12, which induces tumors starting from the meninges and growing into the brain not unlike the human fibrosarcomas.
These tumors exhibit the highest cellular pleo- morphism. One chromosome of the G-group is lacking. MARK 13, 14 has identified this chromosome as being number BENEDICT and coworkers 2 , and MARK 13, 14 , showed tumors which had more chromosome aberrations than this mentioned pattern; both authors tried to correlate this karyotype to recurrence and malignancy. General Conclusions We think we can state the following points as a general conclusion for the malignancy of meningiomas:.
The risk of recurrence apparently correlates better with the total- ity of removal than with the histological subgroups or histologi- cally observed anaplasias. Our criteria of malignancy in meningiomas are pragmatic. We took over the preliminary definition of anaplasia of the WHO. In menin- giomas, however, this definition is only of value if the tumor is totally removed.
Up to now, the significance of different subgroups of meningiomas as to the prognosis does not seem to be established with sufficient certainty. Comparable follow-up studies are only reasonable on the base of a commonly accepted classification. Yet these studies are urgently needed to clarify the different points not solved up to now.
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Philadelphia: I. Lippincott Co. Lan- cet 1, - Springfield, Ill. Thomas Sistema Nervoso 20, - Neuro- surg. KALM, H. Staff Meet. Mayo Clin. Neurology 11, - A comparison between studies with G- and Q-banding techniques.
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Hereditas 75, - MARK, J. Acta path. Acta Neuropath. In: Handbuch der Neurochirurgie, Bd. Berlin-Gottingen-Heidelberg: Springer In: Handbook of Clinical Neurology, Vol. BRUYN pp. Amsterdam: North-Holland Publ. Compo North-Holland publ. Marked variation in cell size and shape is not considered as sign of malignancy unless other indications of rapid growth are present.
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Numerous mitoses are the most important indicator of in- creasing malignancy in meningiomas. In anaplastic meningiomas a dense reticulin network may be present. Case E , Tibor Pap, x. In the sarcomas of the meninges, necroses are - in contrast to glioblastomas - not followed by major stromal reactions. Case , cresyl violet, x. A number of meningiomas which showed histological signs of malignancy, while retaining their primary structures, were diagnosed as "malig- nant meningiomas". While many of the cases described in the literature as "meningosarcomas" correspond to the malignant meningiomas, there is a number of sarcomas of the meninges which display no primary menin- gioma-like structures under light microscopic examination, and can thus be distinguished from malignant meningiomas.
They are also called fibrosarcomas 24, 27, 6 or fibrosarcomas of the dura 14, 32, 10,2. The purpose of the electron microscopic examination of malignant me- ningiomas was to determine ultrastructural criteria of malignancy in these tumors and to establish their relationship to the sarcomas of the meninges. Material and Methods Four tumors diagnDsed under the light microscope as malignant menin- giomas, and one diagnosed as a meningosarcoma, were examined.
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Table 1 gives a summary of the duration of illness, localization, and histological findings. Electron Microscopic Results The malignant meningiomas, which, in spite of a certain variability, can be classified as a single group under the light microscope, can be divided into two groups with the electron microscope. Group 1 cases 1 and 2 The cells are elongated, nearly parallel, and closely packed Fig. The nuclei have both elliptic-roundish and irregular pOinted profiles.
Most of them lie directly on the nuclear membrane Fig. The cytoplasm is arranged as a fringe around the nucleus, extending processes in all directions, but above all toward the pole. They ex-. The mitochondria display a distinct poly- morphy. Monstrous mitochondria appear which attain, in the second case, a size of 5 ]. I Fig. Golgi zones are seldomly encountered. The endoplasmatic reticulum is sparsely developed and almost exclusively of the granular type. Glyc- ogen granules are ubiquitous, frequently in dense accumulations Fig.
Solitary lysosomes are found. The cytofilaments are loosely aligned or run in narrow trains. In a few areas of case 2, they are more developed and clustered in some regions of the cytoplasm. Here the cells display a more developed Golgi apparatus and an increase in the number and size of nuclear bodies. The plasma membranes frequent- ly show pinocytotic bubbles. Desmosomes between neighbouring plasma membranes are numerous, but mostly only 50 - nm long Fig. In case 3 one observes areas with closely fitting, elongated cells, most- ly lying parallel, with a tendency to spiral Fig.
In case 4 there are also areas in which the cells lie close to each other in groups. They are, however, not elongated, but polygonal, and the short ex- tensions have no tendency to form whorls Fig. The principle of the enclosure of a tumor cell by processes from neighbouring cells is distinctly noticeable. In both cases the connective tissue has so greatly increased that the tumor cells have been pushed apart and lie isolated between the connective tissue processes. The nuclei display an irregular, usually poligonal in case 3 also elongated profile with occasional indentations.
The most obvious finding in the cytoplasm of the tumor cells is the abundance of cytofilaments, which run through the cytoplasm frequent- ly in whorls, and pushed the other organelles to the periphery Fig. The latter consist mostly of granulated endoplasmatic reticulum.
Its cisterns contain a homogenous, slightly adielectric substance. Free ribosomes, arranged in rosettes, are numerous in some areas. The mitochondria have, as a rule, a regular structure. Extensive Golgi zones are frequent, partly in the immediate neighbourhood of the nu- cleus, but also between the structures surrounding the cytofilaments. In the areas rich in connective tissue, the cells are solitary or lie in small groups.
In many of the cell sections, there were regressive changes. These consisting of a change of the endoplasmic reticulum, whose ribosomes are lost and whose narrowed cisterns, without adielectric content, display circular or elliptical patterns. The cytoplasm has few or- ganelles, and few or no filaments Fig. Glycogen clumps may appear. Lysosomes and occasional fat vacuoles are also present. Some- times there are pyknotic nuclei, which are surrounded by a very dark, narrow cytoplasmic border. Between the group of tumor cells is a broad intercellular.
In a few places a spiral pattern of the tumor cells occurs. This always involves a central cell, which is more or less completely surrounded by a few other cells Fig. The nuclei have irregular, mostly polygonal sometimes lobulated profiles. The chromatin is homogenously distrib- uted. Nucleoli are mostly small and appear in only a few nuclear sec- tions Fig. The cytoplasm represents only a thin layer around the cell nucleus, but can also display broad spreading. The mitochondria appear regular- ly, but not in clumps. They are mostly small and have regularly formed cristae.
But there are some monstrous mitochondria with scarcely any peripheral cristae. Golgi zones appear broadly spread. The granular endoplasmic reticulum is sparsely present. Free ribosomes are also present only in small numbers. In a few places, one sees greatly de- generated cells, in which there are many lysosomes. The plasma mem- branes lie close together, and very small desmosomes may sometimes be recognized.
They form short finger-like extensions into the broad intercellular space. The endothelial cells of the vessels are large and plump and contain ample endoplasmic reticulum and mitochondria. The basal membrane around the vessels is frequently multilayered. The ultrastructural architectonic principles in the cases of group I correspond to those which we described for endotheliomatous and fibro- blastic meningiomas 5. The cytological differences are simply a matter of the number and size of the nucleoli, as well as of the number and polymorphy of the mitochondria.
An increase in the size of the nucleoli was found in the second remov- al of a meningioma, compared with the material from the first 1. For a number of tumors, the size of the nucleolus was seen as a criterion for malignancy 19 or simply as an expression of active protein syn- thesis Differential evaluation of the ultrastructures of nucle- oli 26, 29 show that the results from one type of cells and its tu- mors cannot be extrapolated to other cells. Within one type of cells, the increase in the nucleolus is an expression of rapid growth. Preuve de la faute technique. Dommages; douleurs et souffrance.
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