Journal of Medical Research.



No. i.


F. B. MIALLORY, M.D. (Fr-om tile Sears Patholqogical L-aboroator-y of tAie'Ifr-vazrd Unziversity Mledical School.)

In i890,2 in announcing his discovery of a specific stain for neuroglia fibers, Weigert called attention to certain dots or granules (Kornchen) in the protoplasm of ependymal cells, which stain by the same differential methods that are used for neuroglia fibers. In his monograph " Die Neuroglia" 3 he states that these granules are present not only in the ependymal cells lining the ventricles and the neural canal, but also, in adult cords, in certain cells and groups of cells which have been cut off from the neural canal by the neuroglia fibers and lie imbedded in them. So far as known these granules do not occur in any other kind of cell; they afford, therefore, a very characteristic marking by which to distinguish ependymal cells from all other cells. Their significance is entirely unknown. Weigert speaks of them as " K6rnchen " and " Punktierung," but does not describe them further. He has, however, proved definitely that they are not cilia. Careful examination of these characteristic markings of ependymal cells shows that they vary considerably in size, shape, and nuLmber in different cells. They may be round, oval, or rod slhaped; as the markings appear in the cells they stronigly suggest minute cocci or delicate bacilli. The
I Read March 29, I902, at the Second Annual Meeting of the American Association of Pathologists and Bacteriologists, at Cleveland, Olio. 2 Weigert. Centralbl. f. allg. Path. u. Path. Anat., I890, p. 736. 3Weigert. Die Neuroglia. I895.

but on the whole the cells predominate. As a rule it is not distributed equally around the nucleus which in consequence often lies eccentric. as a rule the ends are square. round to oval in shape. and occasionally quite large.2 MALLORY. while of the round form twenty to thirty are sometimes present. They vary from two to about ten in a clump in a single cell. and of large blood vessels. often shows them lying in a lighter staining area. The cells show a marked tendency to form small clumps with fusion of their protoplasm. measuring four by five by three centimeters. They do not always adjoin the inner edge of an ependymal cell. of cells which form a fairly coarse meshwork. When this occurs the . The relative proportions of cells and of blood vessels vary considerably in different parts. The phosphotungstic acid hematein method. The cells are distinguished by two peculiarities: most of them contain in their protoplasm the markings characteristic of ependymal cells. They contain numerous fine chromatin granules. Microscopically the tumor consists of two very different structures. reddish gray in color. although some of the cells possess little or apparently none. and very vascular. The protoplasm of the cells is fairly abundant in amount. The first occurred in an adult and was pendent from the roof of the fourth ventricle. surrounded by connective tissue. soft in consistence. The cells are epithelial in type. The limits of the protoplasm are not well defined: it fades otut at the periphery. The nuclei are of fair size. It was irregularly spherical in shape. but are irregularly clumped together. rod forms may be from two to four times as long as broad. it seems advisable to put them on record. although sometimes irregular. The rod forms do not run in any one direction. but may lie at any point between it and the nucleus. but as a rule no distinct nucleoli. which lie in the spaces in the meshwork. As the following three gliomata present peculiarities which have not hitherto been described. which colors the protoplasm slightly. and they have running between them and touching their protoplasm numerous delicate neuroglia fibers.

The characteristic markings of the ependymal cells are found not only in the cells lining the gland cavities. 3 nuclei are usually arranged at the periphery. In this mass of protoplasm there is often found a very small. In the cell clumps there may be one large group of these peculiar bodies or as many small clumps as there are nuclei. Besides these apparent attempts at gland formation. but in no very definite order: the long axes of the nuclei may run in any direction. They show a tendency to arrange themselves around the periphery of this lighter area. When a minute gland-like cavity is present the markings are grouped in the protoplasm adjoining it. irregular. round or irregular. that is. Like them they also contain the characteristic markings in the protoplasm on the side adjoining the lumen. usually rather large blood vessels surrounded by a compara- . they run in all directions between the cells and cell clumps. They vary in number from about ten to thirty. Occasionally as many as four of these cavities are present. In sections stained by the phosphotungstic acid hematein method. the markings are found to be almost invariably in a lighter staining area in the protoplasm. as already mentioned. but also in the protoplasm of the clumps of cells and in many but not all of the single cells. Within some of the larger gland cavities a process similar to that seen in chronic ependymitis has occurred. the larger. which are from two to four times as long as broad. In shape the markings vary from round and oval bodies to definite rods with square ends. The neuroglia fibers are not in any way remarkable. they are quite numerous. the ependymal cells are lacking in places and a mass of naked neuroglia fibers projects into the lumen. although occasionally coarse. These cavities are lined by cells exactly like the ependymal cells. many perfectly definite gland cavities are present in the tumor.THREE GLIOMATA OF EPENDYMAL ORIGIN. Only occasionally does one of these cell masses suggest the appearance of a giant cell. and fairly fine for the most part. the smaller ones are usually round. sharply defined cavity like the lumen of a small gland. The stroma of the tumor consists of very numerous.

On section it presented the same grayish translucent appearance as the outer surface. As a rule they are round or oval. which it completely filled. It was attached to the floor of the ventricle and the smaller conical end projected beneath the pia over the posterior surface of the pons and the beginning of the medulla. It formed a semitranslucent. lateral ventricles much dilated. The walls of many of the blood vessels are hyaline. but vary from two to about ten in ntumber in a cell. but tend to fuse together. One was found within the nucleus of a large neuroglia cell. interpeduncular space bulging. In some parts of the tumor numerous corpora amylacea are present. in1I am indebted for this case to Dr. and the cerebellar tissue adjoining the new growth considerable sclerosis. The cellular areas closely resemble the appearance of the first tumor described. . The cells tend to arrange themselves in clumps. tively small amount of connective tissue. symptoms for over two years. a boy aged seventeen years. They are not so numerous as in the first case. They are present in most of the cells in the cellular areas. occasionally there occur welldefined gland cavities lined with a definite epithelium. The remains of old hemorrhages are shown by areas of connective tissue containing numerous large pigmented cells. weight of brain after escape of fluid one thousand five hundred and forty grammes. E. always among the neuroglia cells from which in this case they seem to arisb. The two forms of tissue are not very sharply marked off from each other. Microscopically the tumor is composed of areas consisting chiefly of neuroglia fibers and of other areas about equal in extent which are very cellular. Brain: convolutions flattened. The floor of the fourth ventricle shows well-nmarked chronic ependymitis. somewhat pear-shaped mass measuring five by six and five-tenths by three ceintimeters. grayish. M. The remains of old hemorrhages and the absence of mitotic figures would seem to indicate that the tumor grew slowly. Holmes.4 MALLORY. Patient. The second tumor 1 likewise occurred in the fourth ventricle. but occasionally rod-shaped. In this tumor as in the other small groups of the characteristic ependymal cell markings are present in the protoplasm of the cells.

It lay almost exactly in the median line over the coccyx and lower part of the sacrum. The third tumor is much the most interesting of the series. The following case. 5 cluding the cells lining the gland-like cavities. Joseph M. and no markings can be found. It has always been taught that gliomata -develop only in the central nervous system and in the eye. but where the neuroglia fibers are most abundant. and of enucleation with the finger. The blood vessels are not nearly so numerous as in the first case. The operation was simple. consisting of an incision half around the base of the growth. the cells are few in number. Inow that attention is called to such a possibility. and are rather more numerous in the cellular parts. and it is probable. Sheahan. Mass. when it rapidly increased in size. It was not attached to the underlying bony structures. are thin-walled.. The enlargement was particularly marked during the three months preceding the operation. The finding of several mitotic figures is evidence that the tumor was growing rapidly. Even in the cellular parts of the growth they are fairly abundant and run in all directions between the single cells and cell-clumps. to whom I am indebted for the following clinical history. have practically no protoplasm around them. and in many of the cells in the denser areas. The wound closed by first intention. that other gliomata not directly connected with the central nervous system will be found. of Quincy. because when first noticed it was a nodule the size of a hickory nut situated in the median line of the back over the coccyx.THREE GLIOMATA OF EPENDYMAL ORIGIN. Throughout the tumor the neuroglia fibers are all fine. At that time it had reached the size of a base-ball. The tumor in question was sent to me for diagnosis by Dr. no coarse ones occur. shows that they may occur elsewhere. The tumor had been present for twenty-five years to the patient's knowledge and was probably congenital. and the skin covering it was freely movable. . The patient was a woman forty-four years old who had always enjoyed good health. however. It kept that form and size until about one year before removal.

the masses of cells large. On section the surface was gray. translucent. of comparatively coarse. The growth was dense. and rather granular. Only fair results were obtained from this material. although a low temperature has the property of preserving the peculiar chemical properties of neuroglia fibers remarkably well. and definitely encapsulated. A small piece of the tissue was preserved in Zenker's fluid. In places the stroma is slight. slightly lobulated. had been carried off by an assistant at the operation and been by him preserved in formaldehyde. The structure of the growth on microscopic examination suggested a glioma.6 MALLORY. in other places the stroma is very abundant and the tumor cells occur in small groups or in rows of single cells: in other words. and this diagnosis was confirmed later by differential stains. between the cells in the alveoli. refractive fibers which vary greatly in different parts of the growth. When the nature of the tumor was suspected the tissue preserved on ice was immediately brought out and sections of it put into formaldehyde. opaque areas of necrosis scattered throughout it. but in places are very abundant. It consists of a connective tissue stroma in the meshes of which lie masses of epithelial-like cells. the growth presents a very peculiar appearance due to the presence. homogeneous. partly scirrhous in type. On careful examination. with numerous irregular. Fortunately that part of the tumor which had not originally been sent to me. As this was ten days after the operation. and the rest was put on ice. Histologically the tumor closely resembles at first sight a carcinoma. It consisted of a hemispherical mass partly covered with skin. the growth is partly medullary. For the most part the fibers in the alveoli tend to run in the same general direc- . A little over half the tumor was sent to me for examination. In its gross appearance the tumor suggested a fibro-sarcoma. however. This tissue was later kindly placed at my disposal and from it a perfectly satisfactory differential staining of the neuroglia fibers was obtained. and of several smaller pieces. not much in the way of the usual differential stains of neuroglia fibers could be hoped for.

This latter appearance may. but occasionally are wavy or even corkscrew-like. but no distinct nucleolus. although the fibers often touch the protoplasm in passing a cell. however. Some of them are very fine. but many of them are extremely coarse. containing numerous fine chromatin granules. it does not branch. The nuclei are vesicular. and here its structure can be more readily studied. as though confined within too narrow quarters. So far as can be made out they swell slightly. the limits of the cells are not sharply defined. running in the same direction as the neuroglia fibers. and are usually oval in shape. The swollen ends unite laterally and thus form. In places the limiting surface thus formed has been stripped away from the stroma by the shrinkage due to the fixing reagent. 7 tion. A given fiber always preserves a uniform size. The protoplasm around the nucleus is finely granular and usually fairly abundant. be an artifact. the other end probably terminates in the same way. but many of them certainly are long.THREE GLIOMATA OF EPENDYMAL ORIGIN. The fact that the tumor is growing rapidly is shown by the presence of comparatively numerous mitotic figures which occur even in cells surrounded by numerous neuroglia fibers. at least in places. forming a sort of foot which ends squarely and stains less intensely than the rest of the fiber. a fairly definite surface which is closely applied to the connective tissue stroma. With the analin blue connective tissue stain the neuroglia fibers stain intensely red in marked contrast to the blue of the connective tissue fibrillk. It . The neuroglia cells in the alveoli are epithelial in type. and does not begin or end in the protoplasm of a cell. They are usually straight or a little curved. One end of them seems always to start from the wall of an alveolus. as a rule a process of protoplasm extends out on each side of the nucleus. The connective tissue of the stroma is not remarkable. The neuroglia fibers vary much in size. It is impossible to determine the length of the fibers. occasionally quite large nuclei occur. Just how the fibers end is difficult to decide.

They have no definite arrangement within the cell. of course. or into ependymal cells and their derivatives. p. the potential possibilities of differentiating either into cells like the epidermis (as seen in the dermoid sinuses and cysts found in this region).' published in I892. I03. They stain by the differential methods for neuroglia fibers. By the phosphotungstic acid hematein method the markings are often seen to lie in a lighter staining area in the protoplasm. I stated that examination of the tissues over the coccyx and sacrum of seven embryos showed in each of six of them one or more gland-like structures lined with epithelium. Sciences. Twice they were found in cells in mitosis. although when the cell is elongated and the marking is single. J. These I believed to be the remains of the lower end of the neural canal which closes very irregularly. its long axis usually coincides with that of the cell. and three to six times as long as broad. Med. These cells unquestionably have.8 MALLORY. Sinuses. in this case neuroglia tissue. It would be interesting to study the fetal remains of the neural canal in embryos by means of the new differential stains to see if neuroglia fibers or the protoplasmic markings characteristic of ependymal cells are ever present. in consequence of their origin. In a paper on Sacro-Coccygeal Dimples. . varies considerably in amount in different places. it seems to me. The latter. 263. Vol. and Cysts. from one to five minute rod-shaped bodies with square ends. admits of a simple explanation. It seems to me that the explanation of the tumor described in this paper is connected with these same embryonic remains. this I 'Mallory. I892. and occasionally sends small bundles of fibrille in between the neuroglia cells and fibers. are present in the protoplasm of at least most of the cells. They may lie near the nucleus or at some distance from it in the cell process. This view is strengthened by the fact that in the more cellular parts of the tumor and to a less extent in the denser portions. but cannot be demonstrated in any other way. in its situation and in its histogenesis. but it may lie crosswise or oblique. Amer. The interest in this tumor lies.

consisting of masses of epithelioid cells embedded in the meshes of a connective tissue stroma. but also in the cell clumps and in many of the single cells. differentially staining markings characteristic of ependymal cells are present not only in the cells lining the gland-like cavities. The third tumor is interesting from its location. in a two-weeks-old infant. its structure. namely. Situated subcutaneously over the coccyx. Delicate neuroglia fibers are quite abundant throughout the tumor. I may add in this connection. The second tumor. is much less vascular. fine and coarse fibers which stain by the differential methods for neuroglia fibers. however. They vary from two to about ten in a cell. 9 have not had an opportunity to do. The cells tend to fuse together into cell-clumps. They vary from about ten to thirty in a group and are usually situated in the periphery of a lighter staining area in the protoplasm. likewise from the fourth ventricle. some of which contain minute lumina.THREE GLIOMATA OF EPENDYMAL ORIGIN. and is composed of cellular and dense areas of neuroglia tissue. The markings peculiar to ependymal cells are present in the cells of this tumor also. but between the epithelioid cells occurs a second intercellular substance. and rod-shaped. and definite gland-like cavities occur. Definite gland cavities of various sizes are also present. but in smaller numbers than in the first. Unfortunately the tissue had not been fixed in such a way that it could be stained for the markings characteristic of ependymal cells. in which the lesion was due to an adenocystoma. The first tumor is a very vascular slowly growing glioma of the fourth ventricle. and its histogenesis. Moreover many of the cells contain from . In the cellular areas the cells tend to fuse together. it resembles in its structure a carcinoma. oval. of which the cells were lined with ciliated epithelium as are the cells lining the neural canal in early embryonic life. Summnary and Conclusionzs. The peculiar round. that I have recently studied a case of spina bifida of the lower lutmbar vertebrx below the termination of the cord.

-A single cell. (Figs. 5. . One is on end. DESCRIPTION OF PLATE. and 6 are from the glioma over the coccyx. one to five minute rod-shaped markings which stain by the same methods. .A fused clump of cells. PLATE I. . 4. FIG. FIG. the other four are lying flat. 4.Cells in the wall of the bottomn of a gland cavity.Straight and corkscrew-like neuroglia fibers. and 3 are from the first tumor described. it seems reasonable to infer that the tumors are of ependymal origin. In consequence of the presence of characteristic. 2. . 3.) FIG. . 5. differentially-staining markings in the cells of these gliomata. FIG.IO MALLORY. I. 6.Shows the neuroglia fibers terminating in swollen ends which unite laterally to form a sort of membrane which is applied to the connective tissue stroma.) FIG. and show the markings characteristic of ependymal cells. FIG. I. 2. Possibly all gliomata of ependymal origin are definitely characterized in the same manner. -Cells showing single rod-shaped markings in the protoplasm. (Figs.


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