Granule is the name applied to such spheroidal or elliptical bodies as do not present any internal cavity when viewed under the microscope. They are present in vast numbers in some albuminous tumors. Often, too, in different specimens of carcinoma, the germinal cells were found to contain, in addition to the formative globules and young cellules, a number of small granules perfectly distinct from both. In carcinoma fasciculatum, many round granules are situated between the fibres.

The Cell is by far the most frequent element of morbid growths. Thus, it exists in sarcoma cellulare, in enchondroma, in carcinoma simplex, reticulare, and alveolare. In many growths this cellular texture is so coarse as to be evident by a very low magnifying power, or even to be distinguishable by the naked eye; but, generally, the cells, unless magnified 400 to 500 times, look like granules.

"Cells sometimes form the only tissue of morbid growths, as in the case of cholesteatoma, of carcinoma alveolare, of cellular sarcoma, and of osteo-sarcoma. In these instances, cells cohering by their walls form the important parts of the structure, while fibres of cellular tissue serve only to form membranes uniting together its several lobuli.

In other cases, where microscopic cells still form the basis of the growth, these cells do not cohere, though in close apposition; but, on the contrary, are free, may be separated from each other, and, when looked at under the microscope, present the appearance of globules. It is only by employing high magnifying powers that their real structure becomes evident: then they are seen to be spheroidal cells, the presence of a small cellule, or of several corpuscules in their interior, serving to mark their cavity. These minute globular cells, which form the real seminium morbi in several forms of carcinoma, as in carcinoma simplex, reticulare, and alveolare, are deposited in extraordinary number in the meshes of a fibrous texture." 16.

Nuclei. The presence or absence of a nucleus in the walls of the cell constitutes a structural difference between morbid growths. The nucleus, when present, is situated in the substance of the wall of the cell, and from it the cell has been developed. Sometimes also a cell contains within its cavity nuclei, which serve as the germs of new cellules. This is the case in enchondroma, and in carcinoma alveolare. In most cases, as in enchondroma, in several forms of carcinoma, in cellular sarcoma, and in osteosarcoma, the parietal nucleus, at least, of each cell is evident, and may be recognized by its flat or roundish form, and generally by its darker tint. In other instances, however, the cells have no nuclei; of this, cholesteatoma affords an example.

Some normal cellular structures, cartilage for instance, yield gelatine-so does the cellular pathological structure, enchondroma. The cellular textures, the chorda dorsalis, and decidua, yield no gelatine-nor do the parallel pathological products-gelatiniform tumors and cellular sarcoma.

Young Cellules." Some cells do not contain young cellules, while within others a series of younger ones are encased one within another, and this furnishes us with a new means for distinguishing between different morbid growths. Laminated cholesteatoma affords an example of the former kind, for it consists of a polyedrous cellular tissue, resembling vegetable parenchyma, in which the author has never detected smaller cellules. In other cases the cells are encased,

one within the other. A cell, when viewed under the microscope, appears to contain corpuscules in its interior; but careful examination shews, in accordance with Schwann's discoveries as to the primitive formation of healthy tissues, that these corpuscules are either young cells, one contained within the other; or nuclei, from which young cellules are developed. This holds good of many of the cells in sarcoma cellulare, in carcinoma alveolare, and in enchondroma, as also of some formative globules in carcinoma simplex and reticulare. The finest cells can be recognised only by the most powerful magnifying-glasses, and often are not larger than 0.00015 to 0.00021 of an English inch: the average size of the cells in growths with a cellular base is 0.00054 of an English inch." 17.

Caudate Bodies.-Another frequent element of morbid growths. They are elliptical pouches, or cells, terminating at one or both extremities in a fine caudiform fibril of uncertain length. Sometimes the interior of these bodies is granulated, and filled with a greater or less number of granules. The interior of their cavities is, however, seldom distinctly visible, though occasionally a nucleus, of a somewhat darker tint than the surrounding substance, may be observed, together with one or more nucleoli. Schwann observed the same structure in primitive cellular and in other tissues undergoing the transformation from cellular to fibrous structure. Elongated cells become fibres, and thus do most fibres in the animal body seem to be formed: but in those structures which consist of caudate corpuscules, it would appear as though the development of the fibres had been arrested while they were in the half cellular state in which they exist in the embryo. Frequently, one end only of the corpuscules is prolonged into a fibril, while the other remains obtuse. There is a great difference, too, in the length of the fibril: sometimes it is no longer than the corpuscule, or even does not equal it in length, while at other times it greatly exceeds it. The diameter of each fibril is generally from to only of that of the corpuscule. In no case has the author observed several corpuscules connected with one fibril. In some instances, however, not only does each end of the corpuscule give origin to a fibril, but a third springs from its side, and sometimes the fibril which proceeds from the end of the corpuscule becomes bifurcated at its extremity.

The arrangement of the caudate corpuscules often presents great varieties, sometimes a few only being found in fungus medullaris, at others there being so many as to constitute the main bulk of the tumor.

The caudate corpuscules are by no means peculiar to fungus medullaris ; they may, indeed, often be observed in its substance, but often they do not exist in it, while they are as frequently met with in non-carcinomatous as in medullary growths. They occur in the substance of aneurism by anastomosis, and in one instance the author saw them in an albuminous osteo-sarcoma of the lower jaw, which was extirpated with success. On another occasion a large benignant fungus of the conjunctiva, of the nature of albuminous sarcoma, was made up almost entirely of these corpuscules. In no instance has the author met with them in large number, in those tumors which become converted into gelatine by boiling. Nevertheless, it is possible that, even in these latter growths, they may be found at certain periods in considerable number, for they probably depend only on the transformation of cells into fibres, and consequently are merely fibres in an early stage of development.

4. Development of Morbid Growths.

:

"Differences in the structure of the microscopic forms of morbid growths depend on the way in which their development proceeds. Cellular growths are those in which the process of development can be most easily traced, now that Schwann has laid the foundation for such investigations by his discoveries with regard to the development of healthy tisues. According to Schwann's observations, nearly all animal tissues are, in their primitive form, composed of cells, which have precisely the same structure as those of vegetables, and their formation and growth are regulated by laws exactly resembling those to which Schleiden discovered the cells of plants to be subject. In the wall of each young cellule is a nucleus from which it is developed. New cells are formed either within the interior or on the surface of old cells in the former case they are developed from a nucleus loose within the cavity of the parent cell, and unconnected with its parietes. Schwann has demonstrated the former process as it occurs in cartilage, and in the chorda dorsalis: the latter appears to take place in the case of many other textures, for Schwann has shewn that all tissues in the embryo consist of cells with parietal nuclei, though it is not possible in all to prove the formation of new cells in the interior of old ones. An instance of the constant formation of new cells with parietal nuclei, external to the old cells, is afforded in the adult by the cells of the epithelium, which do not display any approach to an endogenous mode of growth. The formation of young cells can, however, be best observed in those cases in which they are developed internal to the old ones, or, in other words, in which the nuclei of new cells are situated within the cavity of old cells. In these cases the process of development 'as observed by Schleiden in vegetable tissues, and by Schwann in those of animals, is as follows:

The nuclei protrude young cellules, which project from their surface as the watch-glass from the watch. As growth proceeds, the young cell increases in size, while the nucleus remains imbedded in its wall. If several young cells should be formed from several nuclei seated within the parent cell, they progress in growth so as to fill up its cavity, and then their walls usually become confounded with those of the parent cell. Fresh nuclei form within the cavity of these young cells, and from a repetition of this process result successive generations of cells. The walls of the young cells are perfectly transparent, but those of the older cells become thickened, and, in animal tissues, often converted more or less into a fibrous structure. In this way the cells of cartilage and of the chorda dorsalis, probably also those of the decidua, become developed." 32.

It would be natural, observes our author, to expect a similar process in the formation of many pathological structures. The young cells in enchondroma and in cancer alveolaris are formed in a precisely similar way; and the author's observations render it probable that the same process also obtains in the development of many forms of carcinoma, and of cellular sarcoma. Albumino-cellular sarcoma and osteo-sarcoma, and gelatiniform sarcoma, appear to be developed in this way, as is also collonema. In many of the parent cells the young cellules with their parietal nuclei, were very distinctly seen. Successive series of cells, encased the one within the other, are seen to make up the structure of carcinoma alveolare. The large cells, which are visible to the naked eye, contain in their cavities a second generation and so forth, till we arrive at the smallest cells of all, in which are nuclei of a darkish yellow tint, generally somewhat elongated, and presenting a minutely granular structure. Here and there these nuclei may be seen lying free in the cavity of the cells; in other parts they have already evolved a germinal cell, and may be seen imbedded in the substance of its

parietes. The walls of the large cells, when greatly developed, appear to assume a fibrous structure, and at last to burst.

The formative globules of simple and of reticular cancer of the breast are not merely cells containing granules, but sometimes in the interior of each are one or more roundish or elongated germinal cells, with a darkish nucleus in their parietes, from which they have probably been developed.

How similar soever, adds our author, the most different morbid growths may be at their first origin, still they present great diversities in their subsequent development—a fact which he illustrates by what takes place in carcinoma alveolare, and in carcinoma simplex and reticulare.

5. Development of Caudate Corpuscules.

"It results from Schwann's observations on the tissues of the embryo, that these bodies are cells which have undergone a metamorphosis. In proof of this may be adduced the fact, that not only has the author seen caudate corpuscules in carcinoma medullare scattered among cells; but likewise in a specimen of sarcoma with causate corpuscules in the midst of the fasciculi of these bodies were cells, some elongated, and others round, containing a germinal cellule with its parietal nucleus. In this instance the greater part of the morbid growth presented a fibrous appearance, owing to its being formed of caudate corpuscules arranged in fasciculi; but towards the surface the fibrous part seemed to assume a granular structure, and examination with the microscope shewed that there cellular globules existed in place of the caudate corpuscules. In melanosis some of the cells containing pigment were seen by the author to be round or oval, while others had a caudate foam. Lastly, caudate corpuscules are sometimes seen in which there is a distinct cavity. The external skin of the foetus is, according to Schwann's observations, entirely formed of caudate corpuscules which terminate in long fibres, and constitute the fibres of the skin. In many other situations, too, Schwann saw caudate corpuscules in cellular tissue. These facts satisfactorily account for the presence of caudate corpuscules in innocent as well as in malignant growths. They are, like the germinal cells, an embryonic formation; and embryonic formations are found to be repeated in a remarkable manner in morbid growths." 24.

The consequence of these observations would seem to be highly important -for they upset the division of pathological structures into homologous and heterologous-a division, says M. Müller, founded on "gratuitous hypothesis." Some other pathognomonic characters of carcinomatous growths must be sought. The distinction between the carcinomatous and the innocent forms of albuminous growths presents the greatest difficulties. Here, neither the minute structure nor the chemical characters of the growth can be our guide, for carcinomatous tumors belong to that class the main constituent of which is a substance yielding albumen; consequently there are malignant albuminous growths. On the other hand, the diagnosis between carcinomatous structures and such as yield gelatine is very simple.

"Whether the carcinomatous diathesis be peculiar and distinct from all others, or whether, under certain circumstances, any other structure may pass into the state of carcinoma, still the same question presents itself;-is there any other characteristic of carcinomatous growths than such as are derived from their minute structure, or from the process of their development? The solution of this question must always be the grand problem in the anatomy of morbid growths. The examination of numerous specimens of carcinoma has taught the

author that they are, indeed, possessed of certain peculiar anatomical characters, which may serve to identify them; and, further, that these characters are distinguishable, on making a section of the growth, either by the naked eye, or at any rate by the aid of a common magnifying glass.

Although the structures which belong to this class are extremely various, still one may take the place of another. After the extirpation of carcinoma simplex, for example, carcinoma alveolare or fasciculatum may succeed, and often the several forms are coexistent. But, although transitions of the different forms into each other may occur, yet their extremes are very dissimilar, and no sort of resemblance can be traced between carcinoma simplex, or scirrhus, and carcinoma fasciculatum. In order, therefore, to be able to recognise carcinoma, a person must make himself acquainted with the individual peculiarities of every form of morbid structure, both innocent and malignant: in short, he must proceed as the botanist does who busies himself with the study of poisonous plants." 26.

M. Müller is convinced that a tolerable degree of accuracy and certainty may be attained, in diagnosis, but he admits that there are some forms of disease, which, being destitute of any well-marked external peculiarities, may be readily confounded with others.

The principles, he winds up this introductory chapter by remarking, in accordance with which morbid structures must be classified, cannot be exclusively derived either from their minute structure, or from their chemical composition. For growths widely differing in their physiological characters and in their susceptibility of cure may present a perfect indentity in their minute structure: similarity of structure may coexist with differences in their chemical constituents, or the same chemical characters, may be found in growths, between which the greatest diversity exists with regard to their structure, physiological characters or curableness. In determining the different genera, therefore, the subject must be regarded in all these points of view.

M. Müller passes to the particular consideration of the several morbid growths. He first treats of the minute structure of carcinomatous growths -and then examines those morbid growths which may be confounded with carcinoma. The present publication is only the first Part of the entire work; the second is to appear hereafter. The importance of the subject, and the commensurate importance of the manner in which it is handled, furnish ample reasons for our noticing it in the fullest manner.

ON THE MINUTE STRUCTURE OF CARCINOMATOUS GROWTHS.

M. Müller opens this section with some observations on carcinomatous growths in general-and then takes up successively-scirrhus, or carcinoma simplex-carcinoma reticulare-carcinoma alveolare-carcinoma melanodes -carcinoma medullare-carcinoma fasciculatum, and winds up by an ac count of the development and softening of carcinoma-the chemical properties of carcinoma-and the nature of it. To each of these subjects we shall now advert.

1. On Carcinomatous Growths in General.

M. Müller defines those growths as cancerous, which destroy the natural No. LXV.

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