PATHOLOGY 381 remote from the physiological glandular surface, namely, the connective tissue of the serous or external coat (fig. 49). It is impossible to trace a continuous growth of these subscrous gland- like groups of cells from the actual glands of the mucous surface ; they are separated from the latter by nearly a quarter of an inch of mus cular and other tissue, in which the " infiltration " occurs only here and there. The wide extension of the cancerous process is not mere overgrowth or protrusion of the secreting structure, nor is it even an infiltration, in the literal sense, of the cast-off secreting cells ; it is an infection of the cells of the sub- FIG. 49. Diffused cancer of stomach ; jacent tissue to become epithelial tubular- gland grouping of cells in cells and gland - like cell - groups, sub-peritoneal tissue. And therein lies the essence of cancer. acer- Extension of Cancer from the Surface to the Depth. Whereas, i pro- under commoner circumstances, the catarrhal by-products of the s. process of secretion find their way to the underlying textures and there give occasion to an " inflammatory " reaction, to hardness and coarseness of the connective tissue, under other circumstances the less nuclear or more epithelial by-products of the glandular activity have the power to induce the remarkable formative process in the neighbouring tissues which we know as cancer. The cancerous pro cess implies, accordingly, such a condition of the secreting structure and function, or of its individual cells, as can excite this formative reaction, and it involves also the changing of the surrounding tissue (or of its cells) into epithelial forms of cells, either in rows or groups or in gland-like systems. As regards the former, there is no lack of evidence that cellular by-products of secretion are often the ante cedent or concomitant of cancer in an epithelial organ or part ; they may be seen sometimes in the stomach heaped up between the glandular tubules, or in the mammary gland (especially of the bitch) infiltrated into the sur rounding stroma. The cut (fig. 50) is an illustration from the mamma ; the rows of cells which lie in the spaces of the connect ive tissue are the cellular products of the secretory function characteristic of an immature or low-pow ered intensity of secretion, and they are easily iden tified in all phases of the mammary secretion in the dog, whether regular or irregular, by their yellow ish-brown pigmentation. It is not to be expected that such an infiltration of by-products of secretion can be proved for every case of cancer, nor is there reason to suppose that there is always such an infiltration. The elements of the secreting structure may serve in situ to excite or infect the neighbour- Flo 50 ._ infiltration of pigmented^epithelial ing tissue, and this they cells into the stroma of the mamma in a usually do for the con- case of tumour (dog), nective tissue on which they immediately rest. But we have to take due account of the much more important fact that the in fection also manifests itself at a number of remote and isolated centres, within each of which the new growth arranges itself as if implicitly according to a design, the pattern being the more or less regular epithelial type proper to the organ or part. Thus in fig. 49, from a diffuse cancer of the whole stomach, the glandular tube-like structures have arisen at a number of points in the con nective tissue of the outer coat. The pattern of tubular glands is often more complex than in that figure, both in other stomach cases and in cancers of the great intestine and rectum. This remarkable breaking out, as it were, of very perfect epithelial tubules, disconnected from the physiological tubules and often in the midst of dense tracts of plain muscular fibre, appeared to Johannes Mailer to be so extraordinary that he ascribed them to an invisible seminium dispersed through the tissues ; according to him, the seminium was a literal seed whose particles themselves grew to be the new epithelial cells. We do not now admit the possibility of cells so arising by gcneratio equivoca ; every cell must be the descendant of some pre-existing cell. And, although it is neces sary to retain the doctrine of the seminium, the part played by that hypothetical element is not formative within its own particles ; but it is a fertilizing or infecting influence upon the pre-existing cells of the neighbourhood. In most cases the cells so fertilized are the corpuscular elements of the common binding-tissue of the body, or the connective-tissue cells. Cancerous Infection of the Connective-tissue Cells. The cut (fig. Cancer - 51) is an exact drawing of a piece of cancerous tumour where the ous in- connective-tissue cells can be seen in the act of transforming into fectiou. epithelial cells, or in various stages of that transformation-process. The process carries us once more back to that embryonic activity
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-^uea ,. -zg^jgf^ ^ - -;- ^ <^ ^S^-ffSmsSsSS^&^^SES^^SKf^ i^z~39Ms**a FIG. 51. Cancerous infection of connective tissue in a case of tumour of skin-glands of the dog. of cells in mature life which we have had frequently occasion to discover in other elementary processes of disease. The cells of the connective tissue are ordinarily quiescent in the form of plates more or less compressed laterally, the cell-plates of tendon being extreme examples. Just as, in the process of repair, they become plump and granular, developing in the third dimension as well, and ultimately becoming granulation-cells, so in cancerous infection they start from their obscurity among the bundles of fibres, passing by rapid trans itions into the form and semblance of the epithelial cells proper to the occasion ; and they may even go on to assume a glandular grouping round the wall of a space, acting as if harmoniously or according to an implicit design. There is no fact in pathology more noteworthy than this ; if it has any analogy among the facts of normal biological processes, we shall probably have to go to the very lowest groups of animals or to the earliest stages of evolution to find it. Whatever the infective influence may have been, it touches all the quiescent cells over a certain area simultaneously ; a " terri tory " of tissue, larger or smaller as the case may be, but always involving a number of cells, assumes the embryonic life throughout its whole extent, and goes through all the steps of the transformation towards the epithelial type and grouping, as if its cells had received one common impact. States of the Connective Tissue predisposing to Infection. There are, indeed, reasons for thinking that the special factor in the production of cancer, and of the production of it at particular spots in a large area of choice, is not so much the presence of cellular by-products of the secretion as a particular disposition of the connective tissue of the particular spot to be easily acted on by them. Catarrhal products are often present without any infection following ; but the two favourite seats of repeated or chronic catarrh, namely the stomach and the uterus, may at length become the seats of cancer. Cancer is hardly ever a disease of the first half of life ; it is very distinctively a disease apt to occur after the meridian is passed. In those who are liable to uterine and gastric catarrhs the mucosa and the submucosa at length become thick and succulent. This happens at particular spots, notably just within the pylorus of the stomach ; the epithelial surface may not be appreciably different from the surface elsewhere, but the under lying tissues are thickened and, it may be, contracted to a stricture. It is in such dense new formations of connective tissue that cancer is most apt to form ; what is called cicatricial tissue is proverbially liable to cancer, and a tissue may be to all intents and purposes " cicatricial " (and apt to shrink) even if it underlie an unbroken surface. Some cancers of the stomach form entirely below the surface, in the thickened floor of a healed nicer, or even in the not unfrequent dense adhesions between the serous membrane of the back of the stomach and the piece of peritoneum which is drawn over the anterior surface of the pancreas. A cancerous stricture of the intestine or rectum is not unlikely to have been to some extent a stricture before it became a cancer. The condition of the con nective tissue in all such circumstances is not easy to define ; it is often spoken of as young connective tissue or "embryonic," and there is probably in it a smaller preponderance of the fibrous element over the cellular than is usual in mature life. A general change in the connective tissue of the body has been asserted to take place as age advances, a senile change which has been described by Thiersch, for the corium, as a relaxed state. The epitheliated localities subject to persistent functional disturbance do at least seem to undergo a change in their inderlying or surrounding con nective tissue, whereby that tissue becomes predisposed to cancerous infection. The infection emanates from the secreting structure proper, for it carries with it the likeness of such structure (in its more or less irregular or morbid state). The cellular waste or by products of the secretion would appear to acquire something of the property of sperm-cells ; and, inasmuch as the infected or impreg nated connective tissue produces not merely individual epithelial
