cells tissue infection disease epithelial stomach breast structure process tumour
PATHOLOGY CANCER - the popular estimate of the nature of cancer is so well founded that a definition is superfluous. Cancer in patho-logical anatomy differs from cancer as commonly under-stood in being restricted to the malignant tumour-diseases of secreting structures and epitheliated surfaces generally, to the exclusion of a. certain number of equally- malignant tumours which grow from the periostenm or the marrow of bone, or from other mesoblastic tissues. The great majority of all the cases which have the fatal progressiveness of cancer are diseases of the stomach, the uterus, the breast, the intestine, and the skin ; this group makes so large a,n element in the sum-total of tumour-disease, and is so homo-geneous within itself, that it may justly- appropriate the name of cancer, leaving the other cases of tumour-malig-nancy to be described by. more technical names. At the same time it should be clearly understood that the smaller detached group does contain cases where the particular man-ner of fatal progression is not different from the progressive-ness of the epithelial tumour-disorder, such, for example, as the c.a.ses of periosteal tumours becoming parosteal.
Chief S'cats of Cancer. - The absolute and relative frequency of cancer in the various seats of secretion has been ascertained by D'Espine, from the mortality returns of the canton of Geneva, for both hospital patients and the well-to-do treated at home, to be as follows over the period front 1838 to 1855 : - :•itemach 399 cases, or 45 per cent.
'Uterus 139 „ Liver 93 „ 10*5 „ Breast „ 8*5 „ Small and large intestine „ 3'3 „ Rectum „ 3 „ being 762 or 85-3 per cent in a total of 88 eases of malignant tumours of all sorts. Most cases of cancer of the liver are really secondary to cancers in the stomach or elsewhere-, so that the leading position of the stomach, and after it of the uterus, the breast, and the intestine, becomes more marked. According to the facts collected by Virehow from the mortality returns of the town of Wiirzburg front 1852 to 1855, the deaths front malignant tumours were 5.3 per cent. of the total mortality, and the percentages among malignant tumours were as follows : - stomach 34.9 per cent.
Uterus, &e 13'5 „ Int(*stine S•1 „ Liver, &e. 7.5 „ nye and 4'9 „ Breast 4-3 It may be accepted, then, that the digestive tract is the seat in about one-half of the cases of malignant tumour-disease, and the, female sexual organs (excluding the ovaries, but including the breasts) in about one•fourth, while the reinaining fourth has to be apportioned among other epithelial organs or parts and the bones and other inesoldastic tissues. It must not be supposed that these ratios hold good equally for all localities ; the breast sometimes appears to usurp a larger share, and sometimes the rectum. Again it is a noteworthy fact that cancer is a comparatively rare disease among the vast populations within the tropics.
The beginnings of cancer have to be sought for in disturbances of the apparatus and proce-ss of secretion. Even in the cases where hereditary or c.ongenital predisposition plays a part there must have been local irregularities of structure and function to deter-mine the seat of the disease ; thus, of four sisters of W110111 1.11.1'ud were married and had. families, one died of cancer of the breast, another of cancer of the stomach, a third of cancer of the rectum, and the fourth of cancer of the uterus, - the ineidence of the disease in them all happening about the age of fifty to sixty. Cancer in secreting strnetures is essentially one process ; but each of the favourite seats of c.ancer has its own special liability, as well as points of structure special to itself. The liability of the female breast is tut entirely different thing from the liability of the stomach ; and the liability of the uterus lA more closely allied to that of the stomach than to that of the breast, although the breast and the uterus have a closer systemic relationship. There is, however, something in the cellular law of secretion common to them all, and it is that common feature of the secretory process which first engages the attention.
liclatio)1 of Cancer to Secretory I'rocess. - The product of secretion is not, under all circumstances, a fluid; in the simpler forms of animal life, and in more recent or le.ss elaborated glands of the higher forms, it may be thrown olf in cellular shape, just as it is always cellular in its origin. We have already seen that in the catarrhal state the cellular admixture is considerable, and there can be hardly any question that the cells of a catarrhal discharge are derivatives of the epithelial cells, being indeed little other than their nuclei. 'We have also seen reason to believe that the infiltration of nuclear cells in the thickened mucous membrane of chronic catarrh had been a real infiltration of the catarrhal cells beneath the surface. Now the favourite seats of chronic catarrh, the stomach and the uterus, are also the favourite seats of cancer. What, then, is the relation between these two very different diseases, both of them primarily disorders of the apparatus and process of secretion ?
A particular case will bring out the points of resemblance and the points of difference. In a fatal case of cancer of the stomach the whole organ is found to be uniformly thickened, the mucous mem-brane being much ridged. and furrowed ; but its epithelium is un-broken, The interval of submucous tissue, ordinarily a loose layer between the mucosa and the muscular coats, is occupied through-mit the whole extent of the organ by a nearly uniform stratum of firm whitish tissue. This is an exceptional case of cancer of the stomach, but it is a very instructive one ; the morbid condition is as uniformly diffused over the organ as if it had been the thickening of chronic ca-tarrh, and it wan ts the usual tumour - char-acter of cancer. The micro-scopic exami-nation proves, what the white-ness and almost gristly fi tallness of the subinu-cons interval had suggested, that the disease is hard cancer. The white stra-thin under the • mucosa has the structure shown in the cut (fig. 48), and it is an average example of the infiltration of seirrhous cancer. Epithelial -like cells, with a disproportionately large nucleus, are as if packed in rows in the spaces of a very dense fibrous tissue, which contains a large number of elastic fibres. 'Besides the. linear processions of cells, there are elsewhere groups of them arranged round the walls of spaces like the epithelium of a gland. 'I hroughout the whole thickness of the coats of the stomach in this case such collections of cells are found ; in the muscular coats they are met with chiefly where there are fibrous septa ; and it is noteworthy that the gland-like collections are by far the most numerous in the tissue most impossible to trace a continuous growth of these subserous gland-like groups of cells from the actual glands of the liltleOUS 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 secretin, structure, nor is it even infilgation, in the literal sense, of the cast-off secretin, cells ; it is an infection. of the eelfs of the sub-jacent tissue to become epithelial cells and gland -like cell-groups.
And therein lies the essence of cancer.
Extension of Cancer from the Surface to the Depth. - Whereas, under commoner circumstances, the catarrhal by-products of the process of secretion find their way- to thc 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 IWO-eeS6 hllpileS, accordingly, sueli 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 concoinitant of cancer in an epithelial organ or part ; they inay be seen sometimes in the stoinach heaped up between the glandular tubules, or in the mammary gland (especially of the bitch) infiltrated into the sur-rounding stroina. The cut (fig. 50) is aii 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-ercd 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-, isli--brown pigmentation. I It is not to be expected , that such an infiltration of by -products of secretion can be proved for every \ ease 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-ing tissue, and this they usually do for the connective 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 11eW 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 eases and in cancers of the great intestine and rectum. This remarkable breaking out, as it were, of very perfect epithelial tubilles, disconnected from the physiological tnbules and often in the midst of dense tracts of plain muscular fibre, appeared to Johannes to be so extraordinary that he ascribed them to an invisible senzinium dispersed through the tissues ; according to him, the 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 gencratio eguivoea ; every cell must be the descendant of some pre-existing cell. And, although it is neeessary to retain the doctrine of the 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 eases the cells so fertilized are the corpuscular elements of the coinmon binding-tissue of the body, or the connective-tissue cells.
Cancerous Infection of the aninective-tissue Cells. - The cut (fig. 1 51) is an exact drawing of a piece of cancerous tumour where the connective-tissue cells can be seen in the act of transforming into ; epithelial cells, or in various stages of that transformation-process. The process carries us once more back to that embryonic activity 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 yery 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 riSSile 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 larg,e 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 scats 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 ineridian is passed. In those who are liable to uterine and gastric catarrhs the mucosa and the submueosa 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 tissne 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, beloy; the surface, in the thickened floor of a healed ulcer, or even in the not unfrcquent 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 snch 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 aote 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 underlying or surrounding con-nective tissue, whereby that tissue becomes predisposed to cancerous infection. The infection emanates from the secretin, structure proper, for it carries with it the likeness of such struaure (in its more or less irregular or morbid state). The cellular waste or by-products of the secretion would. appear to acquire soinething of the property of sperm-cells ; and, inasameli as the infected or impreg-nated connective tissue produces not merely individual epithelial cells of the appropriate type but also the appropriate grouping of such cells, the sperm-cells must be held to carry more than the influence of cell-nnits, and in fact to be representative of the whole structural and functional process in whieli they had played a part.
Varieties of Cancer. - The two main varieties of cancerous texture are the hard and the soft, Or the scirrhous and the medullary. Seirrhous cancer is very often the "infiltrating " kind, with the epithelial cells lying in scattered groups or in single tile within the spaces of a peculiarly dense and elastic connective tissue. lt is common in the breast and not rare in the stomach. The medullary cancer consists of very much larger and closer groups of cells, which may be in nondescript heaps or in the more regular arrangement of glandular structure. When the glandular type is very distinct the tumour is sometimes called a, "de-structive adenoma." Colloid can-cer is a very peculiar variety, apt to occur in the stomach but not unknown in the breast ; most of the structure is changed into a. brownish jelly - like substance which forms more or less definite spherical or alveolar masses sepa-rated by narrow bands of stroma. Under the microscope (fig. 52) little of cellular structure of any kind is found remaining, but in place of it there are an immense number of spherical pearl - like bodies, each of which consists of several delicate concentric lamitile arranged round a more dense nuclear point.
)f Cancer of the-skin, and of the lips and tongue, is generally termed epithelionta ; it is not a disorder of secretion in the same sense as i- other cancers are, but it is a disorder incidental to the constant waste and repair of the epithelium of the skin. It is characterized by the encroachment of processes of the rcte mucosum upon the corium and subcutaneous tissues, or, in the lips, tongue, 'upper part of the (esophagus, &e., of epithelial columns of cells upon the subepithelial region. The type of this encroachment is the papillary arrangement of the normal rete raucosum, where the appearance of regular columns of epithelium reaching down into the corium is equally due to the reciprocal protrusion of loops of blood -vessels upwards. The interlocking of epithelial eolumns and connective-tissue tracts in epithelioma is much more extensive and ir-regular than in the normal skin, and it is always difficult to de-cide, from the super-ficial microscopic ap-pearances, whether the encroachment of the epithelium is merely a displacing or a trans-forming encroach went (fig. 53). In some cases, such as destructive epi-thelioinas of the tom-me, or of chinmey - sweep's cancer, it is possible to find reliable evidence in the microscopic sections that the progressiveness of the disease is really an infection, like that of cancer elsewhere - connective-tissue cells, are infected so that they assume the epi-thelial type proper to the locality - and that infection tends to spread without But the doctrine of continuous growth from the rete mucosum downwards, by mere subdivision of pre-existing epithelimn, appears to be justified as a part, at least, of the patho-logy of cancer of the skin. As in cancers of the stomach aud uterus, the regions liable to skin-cancer are especially those subject to re-peated irritation or to prolonged functional disturbance. One of the most striking instances of this law used to be the cancer of the skin of the scrotum and groins in cliiinney-sweeps, a form of disease which has become much less common of late. Again, it is nearly always the lower of the two lips that suffers, and the rare cases of epithelioina of the lip that occur in women are among those of the sex who smoke pipes. Like other cancers, the cancer of the skin, lips, and tongue, ke., is a disease of later life ; according to Thiersch, it is due to a " disturbance. of the histogenetie equilibrium between epithelium and stroina, to the disadvantage of the stroma." The perfect balance of tissues would be exemplified by that regular interloeking of vascular papilke from below and epithelial processes front above which the skin ordinarily shows ; as age advances the downward force of the epithelial growth prevails, owing to a certain decreased " turgor vitalis," or to loss of resistance on the part of the tissue carrying the blood-vessels, so that, when long-standing irritation of a particular spot is added, we should have the two great determining causes of cancer of the skin. But the question tvill always remain, whether the essence of the disease is not really an infective transformation of the quieseent cells of the connective tissue into the type and pattern of the irritated epithelial structure.
The female breast is peculiar among the glands of the body in its great liability to cancer ; the disease is of essentially the same nature as that which we find in the stomach and other epitheliated organs, but the occasion of it is quite different. It will therefore be convenient to reserve further remarks on cancer of the female breast until the next section - that on the "liabilities of obsolescence."
Extension of Cancer to Lymphatic (Rands and Other DiSCOnii)171011S Tarts. - If the beginnings of cancer are to be sought for in some t disorder of the apparatus and process of secretion, the disease very soon passes the limits of the primarily disordered organ or part. The cancerous property of a tumour, as we have concluded, is from the first an affair of infection of the neighbouring tissues by epithelial products ; the infected neighbourhood is the seat of the primary tumour, the progressiveness or infiltrating character of which may soon cause a large arca to be involved and a large growth to result. Sooner or later there is discontinuous infection, or the infection of more or less remote centres, whereby secondary tumours arise. This phase of cancerous infectiveness is by no means dependent on the extent of the primary infection or the infection of the original neighbourhood. That which distinguishes secondary can-cerous nodules, wherever they are found, is the very close inimieiy of the pattern of structure in the indigenous scat of disease, a pattern which is itself determined by the structural and func-tional characters of the secreting organ or part concerned. In the majority of cases the nearest lymphatic glands become the subject of this miinetic process first ; the liver also is very liable to discontinuous infection, not only in cancers of the stomach and intestine, but even in eases of cancer of the breast, sub-maxillary glands, &c. There is always an interval of time before this secondary infection is set up ; and, although the cellular process is not different in kind front the infection of the neigh-bourhood of the indigenous disease, it is necessary to regard the latter as, in a, sense, the parent of the former. 'This parental I relationship is made all the more probable by the fact that sar- I comatous tumours, which depend in many cases npon a reversion to or survival of embryonic characters in the mesoblastic cells of a particular locality, are also apt to be followed by tumours in distant ( parts, particularly in the lungs. LI cancers, accordingly, we should distinguish three factors, and in sarcomas only two : in the former We have first the accumulation of cellular by-products of the secre-tion, next the infection of the predisposed connective fissile by these epithelial products, and lastly the parental influence of the whole primary seat of infection ; in the latter we have the embryonic reversion of cells over a particular region, together with their increase or growth, and then the parental influence of tlic tumour which had so arisen. In both eases the primary tumour acquires a kind of individuality and a power to reproduce itself ; but it is only in some eases of sarcoma, especially those soft tumours of periosteal origin which become parosteal, that there is infection of the neighbourhood, whereas a cancer is not a cancer at all until the tissues adjoining or supporting the epithelial secreting structure are epithelially infected. This difference between sarcoma and cancer corresponds to the familiar fact that the former are only occasionally " infiltrating" tumours, being in most cases marked off from the neighbouring tissues by a definite capsule.
The simplest case of discontinuous cancerous infection is in the lymphatic glands near the original seat of disease, It is only ex-ceptionally that the lymphatic glands are infected in sarcomatous tumours, and those cases appear to be mostly the infiltrating sarcomas which have the distinctively cancerous property of in-fecting the neighbourhood. Infection of the axillary lymphatic glands is the common sequel of cancer of the breast, while the epi-gastric, portal, mesenteric, and other abdominal lymph-glands receive the infection in calmer of the stomach and intestine. In epithelioma of the lip and tongue the infection of lymph-glands is much slower, and is often so slight as to be undetected during life ; it specially affects the lymph-glands under the chin. In all cases the tendency is to reproduce the exact pattern of the primary tumour. In some, including those sarcomatous cases where this kind of infection does take place, the lymph-gland seems to have been transformed en masso, ve.ry rapidly and directly, so that steps in the process arc hardly to be detected. But in other cases it is possible to find, either within the same gland or among the various glands of a cluster, a certain amount of instructive histogenetic detail as to the mode of infection. The lymphoid cells become affected, not cer-tainly in the way of atrophy, but in the way of' transformation. There is indeed nothing more wonderful in the whole range of biological phenomena than to observe the adaptation of the cells and tissues of a lytnph-gland to assume the cancerous structure already established in the organ to which they are related, an adaptation always close in its iniinic.ry, involving the co-operation of large groups of cells and fibres, and directed as if by a presiding intelligence. In many instances the infecting substance may- even want the perfect cellular character ; it may be no more than the detritus or the juices of cells and tissues. The most obvious form of infection, although probably the rarest, is where the new growth extends continuously' along the sides or in the interior of lymphatic vessels from the secreting structure to the lymph-gland; Int even this continuous extension has been shown to be, not a protrusion of the primary ttunour by increase or subdivision of its elements, but a succession of infective transformations along the line of cells constituting the lymph-vessel or investing it. Under all circum-stances the lymph-gland becomes changed -ultimately into a texture which reproduces with astonishing fidelity the particular pattern of the priinary cancer, a pattern which is never quite the same in any two cases of tumonr-disease even of the same organ. In some cases it is not always uniform throughout the same tumour ; thus pre-parations might be described from a cluster of infected lymph-glands under the cancerous mamma of the bitch wherein two kinds of structure in the extensive strip of primary disease are severally reproduced in different lymph-glands.
The infeetion of the liner is a very common sequel of cancer of the digestive tract, as well as of other cancers, and even of sarcomas (especially the melanotic) and lymphomas. Opinions differ as to the share which the liver-cells take in the building up of the new texture ; but there is hardly any room for doubting that it is from the pre-existing cells of each infected area, even if it be exclu-sively froin the cells of the supporting tissue and the capillary walls, that the elements of the secondary- tumours are derived by infective transformation. The infection breaks out and proceeds part passu at a number of areas throughout the liver-substance, affecting the whole of an area as if at one blow ; there is an absolute lack of evidence in favour of the .assertion often made, that the secondary tumours are due to the mere increase, by division, of cells detached from the primary mass and lodged here and there in the liver. There is a certain amount of evidence in favour of some such embolic theory for the secondary tumours of the hangs, which are usually a sequel of sarcomatous growth in some bone or in other mesoblastic tissue. Sarcomatous tumours are apt to grow through the walls of neighbouring veins, and pieces of them doubtless get detached and carried into the pulmonary circulation ; but it is more than doubtful whether even these emboli give rise to the secondary tumours of the lungs merely by continnous proliferation of their cells, and not rather by the infective action of their presence.
Another seat of secondary tumour-formation, both epi-thelial and melanotic sarco-matous, is the ;serous mem-branes. The accompanying figure (fig. 51), from a nodule on the diaphragm in a ease of cancer of the colon in the horse, may be set beside fig. 51 as showing the substan-tial identity of the infective process in the secondary and primary seats of disease ; in both eases the cells of the connective tissue are seen in the stages of transformation towards the epithelial form and g,rouping. The infection of the neighbourhood is the essence of the cancerous process. But the discontinuous infection of distant parts is not different from it in kind. It is merely "Wirkung in der Perim," and it is more mysterious only because it is more remote.
The disorder of secretion thus eventually assumes a cancerous character in which traces of its origin may be hard to find. As the disease persists or extends the patient's colour becomes sallow or dull grey, the colourless cells are increased in the blood, the bones may become fragile, and general wasting (curiously associated some-times with local production of fat at the seat of disease) puts an end to a life of suffering. In abdominal cancers death may be hastened by dropsy of the peritoneum ; in various forms of the disease there may be fatal bleeding from au eroded vessel. It has often been remarked that an appearance of exceptionally blooming health goes with the liability to cancer ; and the blooming appearance of the face and plump condition of the tissues will sometimes persist when the local ravages of the disease have made consider-able progress.' § 9. - THE LIABILITIES OF OBSOLESCENCE.
We have seen in the foregoing sections that various liabilities to error underlie the embryological tissuc-de-velopments, the process of blood-making, the process of bone-making, and the process of secretion. But there are functions of the body, of its tissues and organs, in which the morbid liability is something special. The most striking instance of this is in the reproductive organs, particularly those of the female ; the obsolescence of the function, and in part of the structure, in the ovaries, uterus, and breasts of women long before the natural term of life creates a peculiar liability- to disease. There are two other organs, the thyroid and the suprarenal, which hold a some-what special position ; it cannot be doubted that each of these organs plays an important part in the economy, but there are suggestions in their morphology- of survivalship from a former state of things, and their diseased conditic,is are not only peculiar in their occasion but also peculiarly important in their consequences. Lastly, there are two ininute bodies situated at the bifurcation of great arterial trunks, the coccygeal gland and the intercarotid body, which are clearly- marked as survivals; and the former, at least, of these carries a, peculiar liability to tumour-disease during the period of intra-uterine life. These instances do not include the so-called "involution-diseases" or the liabilities of old age. The self-limitation of life may be said to be too large a, problem for the present purpose ; but sexual involution is a part of this problem which comes directly into pa,thology.
Cancer of the Breast in connexion with Obsolescence of Structure and Function. - The diseases of the climacteric period in women make an important chapter in the special pathology of the sex ; together with the disorders incidental to inaturation, they stand for the larger part of the special ill health of women. It will not be possible in this article to give more than a single illustration of the morbid effects of this peculiar periodicity, namely, the obsolescence of the mammary function. The statistics collected by Paget clearly show that cancer of the breast in women is peculiarly a disease of the climacteric and post-climacteric period ; throughout the whole period from the age of about fifteen to about forty-five, during which the breast is capable of lactation, the cancerous disorder is rare in it, the tumour-disorders to which the organ is then liable being comparatively tractable. A few words about the physiology will serve to indicate the pathology of the simpler as well as of the more formidable malady.
The reproductive functions in the female are not only peculiar among other functions of the organism in their maturation and obsolescence, but they are further remarkable for their periodicity within the period of vigour itself. In the lower species of the vegetable and animal kingdoms seasonal periodicity is in every-thing, in the higher it is only in the sexual and secondary sexual characters, and in the human species it is practically confined to the reproductive system. The consequences, as regards the breast, are that its structure and function unfold during the term of gestation, continue in full vigour for a longer or shorter period (which may be arbitrarily limited), and then go through definite stages of subsidence and npfolding to the resting state. This periodical reduction of structure in an orderly way is a peculiar and unique thing ; it is "as though a rose should shut and be a bud again." The upfolding and unfolding of structure have corresponding functional aspects ; there are crude secretory pro-ducts formed and discharged, and hence it is that the hreast is a peculiarly suitable organ in which to investigate the question of cellular by-products or waste of secretion, and their disposal by the lymphatic system. Compared with other secreting organs and parts the breast is not peculiarly liable to catarrh, but it has a physiological liability of its own which puts it on the same footing, as regards tumour-disease, with the great seats of catarrhal dis-order, the stomach and the cervix uteri. Like these organs, it is not generally subject to cancer until after middle life ; but, where-as in them the predisposition appears to depend on long-eontinned functional irregularities, the liability of the breast arises out of its normal ob.solescence. Its secreting ineehanisin becomes finally broken up, so that one may find little HI besides traces of the larger ducts in the midst Of wide areas of fibrillar tissue and fat. Traces of the glandular structure persist to a very various extent in dilfemiff women, aud even in different parts of the same breast. It is obvious that the process is one which offers numerous oppor-tunities for a devious course ; it may be retarded, or advance un-equally, or be the end inconidete. That which in all cases must be held to create the peculiar liability to cancerous infection is the readiness of the preponderant connective tissue to be acted on by epithelial cells dispersed throughout it or otherwise in direct contact with its corpuscles.