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PATHOLOGICAL AND EMBRYONIC NEW-FORMATION. 399

like constituents, in which at certain points other things, such as muscles and nerves, are imbedded. Now it is in this more or less connected framework, that, according to my investigations, genuine new-formation goes on, and that in accordance with the same law, which regulates embryonic development.

This law of the correspondence between embryonic and pathological development was, as you know, laid down by Johannes Müller, who continued the investigations commenced by Schwann. But at that time the contents of an ovum were placed on a level with blastema; it occurred to no one that the whole process of development in the ovum took place within the limits of a cell, but it was concluded simply, that there was a certain quantity of organizable material in the ovum, which-in virtue of a peculiar power innate in it, by means of some organizing force, or, as those would have it who regard the matter from a "higher" point of view, impelled by an organizing idea-transformed itself into this or that particular shape. But here too the conviction has been gradually acquired, that the matter in question is a cellular substance, and if what has been most rigidly maintained by Remak is correct, namely, that the cleavage of the yolk also is due to a visible division of cells, to the growing in of membranous partitions into the interior of the ovum, and their coalescence, we have not here to deal with a free organizing impulse taking place within the yolk, but with progressive acts of division on the part of the originally single cell. But long before this simple view of the process of the cleavage in the yolk had been arrived at, it had been very distinctly perceptible that in pathological processes a comparison between plastic exudations, or blastema, with the matters contained in the ovum was obviously inadmissible, and that, where really formed parts were found, they had proceeded from a pre-existing part, a cell.

The mode of origin of new formations is, as it seems, a double one. We have, namely, either to do with a simple division, such as we discussed when treating of irritation (p. 307). We then see the whole series of changes from the division of the nucleolus to the final division of the cell. If an epithelial cell acquires two nuclei, divides and this process is repeated, a long series of developmental changes may, by means of a continual repetition, be produced. If the skin becomes irritated in consequence of continued friction, and the irritation is increased to a certain point, the epithelium will thicken, and

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Fig. 124. Proliferation of the growing cartilage of the diaphysis of the tibia of a child. Longitudinal section. a. The cartilage-cells on the border of the epiphysis, some of them simple, some of them in a state of commencing proliferation. b. Groups of cells that have arisen from the repeated division of simple cells. c. Groups of cells lying near the calcifying border of the diaphysis, and considerably developed through the growth and enlargement of the individual cells; the intercellular substance growing continually more and more scanty. d. Section of a blood-vessel. 150 diameters.

ENDOGENOUS CELL-FORMATION.

BROOD-CAVITIES. 401

if the proliferation is very energetic, it may lead to the production of tolerably large tumour-like formations. The same mode of development which is presented by layers of epithelium, we meet with also in the interior of organs. In cartilage, for example, where the individual cellular elements are enclosed in an intercellular substance, the place of each of them is at last occupied by an accumulation of numerous cells, the whole group, like the cell from which it proceeded, being shut off from its neighbours by the intercellular substance. This mode of development, therefore, is one which, though very simple in itself, may, since it originates in dissimilar parts, produce very different results.

But we have besides another class of new-formations in the body which are indeed much less well known, and of which the special peculiarities cannot as yet be seized with such great precision. These are processes, where we see endogenous changes set in in the interior of pre-existing cells. In a simple cell a vesicular cavity forms, which, contrasted with the somewhat cloudy and generally slightly granular contents of the cell, presents a very clear, bright, homogeneous

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Fig. 125. Endogenous new formation; cells containing vesicles (physaliphores). 4. From the thymus gland of a new-born infant together with epithelioid cells: in the interior of a vesicle which has a double contour (more distinctly marked in C), and is besides surrounded by a cell-like border, lies a perfect nucleated cell. B. C. Cancer-cells (Cf. Archiv für pathol. Anatomie, Vol. I, Pl. II, and Vol. III, Pl. II). B, one with two nuclei; C, one with a physalid which nearly fills the whole cell and another, where the physalid (brood-cavity) again encloses a perfect nucleated cell. 300 diameters.

appearance. In what manner cavities of this first kind, which I class together under the name of physalides, arise, is not yet altogether certain. The greatest probabilities are in favour of the nuclei being, in certain forms, likewise the starting-point of these formations. For, besides these cells, others are seen with two nuclei, one of which, in several of them, has become somewhat larger and brighter than usual, though still preserving the character of a nucleus. Subsequently, this vesicle becomes so large, that the cell is gradually almost entirely filled with it, and its former contents with the nucleus only look like a little appendage to the vesicle. So far the process is tolerably simple. But besides these vesicles, thus growing and filling the cells, others are met with, in the interior of which elements of a cellular nature are enclosed. This is of pretty frequent occurrence in cancerous tumours, but also in normal parts, for example in the thymus gland. This form seems to indicate, that in fact by means of a process which cannot be directly traced to any division of pre-existing cells, and indeed in peculiar vesicular cavities (which I have named brood-cavities (or -vesicles-Bruträume), ) in the interior of cellular elements, new elements of a similar kind may be developed. However, this is at all events a condition which plays but a subordinate part in the whole history of new-formations; the regular form is the one first described. There are only a few pathological new-formations, in the history of which this endogenous development plays any distinct part, whilst in nearly all forms cell-division is met with to a great extent.

The essential points of difference between the several modes of the development of cells are therefore these: in one class of formations the divisions proceed with a certain regularity, so that the ultimate products from their very beginning exhibit a complete correspondence with the parent structures, and the young structures at no time

HOMOLOGOUS AND HETEROLOGOUS DEVELOPMENT. 403

deviate in any remarkable degree from the parent-cells. Such processes are in ordinary life mostly designated as hypertrophies, but I have, in order to express the nature of the change more accurately, proposed the name of hyperplasia, inasmuch it is not an increase in the nutrition of existing parts that takes place, but a real formation of new elements (p. 65).

In another class the development proceeds in such a way, that divisions certainly also do take place, but make very rapid progress and produce cells which gradually decrease in size, and ultimately in some instances become so small, that they can scarcely be distinguished to be cells. The proliferation may cease at this point, and then the cells severally begin to grow, and to become larger; and under certain circumstances a structure may in this case again also be produced analogous to that in which the development originated. This, however, is not usually the case; generally, the young, small cells pursue a somewhat different course of development, and a heterologous structure begins to form.

The mode of development, which I here describe to you, may also run its course in such a way, that the cells do not at once begin to divide, but the nuclei first greatly multiply, becoming continually more numerous and at the same time smaller. We find something similar to this in pus, in which a division of the nuclei very rapidly takes place, and generally in such a way, that the originally single nuclei at once divide into a considerable number of smaller ones, which at first remain coherent. But in pus it is not certain whether the division of the nucleus is succeeded by a real division in the cell, whilst in other new-formations this is certainly the case-only the complete division, or if you will, the cleavage, of the cells is delayed for a long time, and this intermediate stage of the mere division of the nuclei continues for a dispro

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