Chapter VI: Part II: , Showing Predominance of Malarial Element . . . . 617 (5)

The actual inheritance of tuberculosis is very unlikely, although this disease is frequently found in successive generations of a single family. The various members of the family are rather to be regarded as furnishing a suitable soil for the growth of the tubercular bacillus, and their exposure to its seed is favored by the existence of tuberculosis in one or more members of the household. The scrofulous condition is still to be regarded as hereditary as well as acquired, and the scrofulous remain as the class to be especially protected from the reception and effects of the bacilli of tuberculosis.

{102} It is obviously a matter of importance to determine in any given case of phthisis whether bacilli are present or absent. A ready means of ascertaining this fact is offered by the examination of the sputum in cases of pulmonary phthisis, the feces in intestinal phthisis, the urine in renal phthisis, and the aspirated pus in cases of supposed tuberculosis of the joints. Koch has found in examining the sputa from numerous cases of phthisis that the bacilli were present in one-half the number, and that they were absent from the sputa of individuals who were not phthisical. Balmer and Fraentzel[71] have found bacilli in the sputum from one hundred and twenty cases of phthisis, and concluded that the progress of a case of pulmonary tuberculosis might be readily determined from the number and degree of development of the typical bacilli present in the sputum. The more numerous and well-developed bacilli, with distinct and constant spores, were found in the graver cases, which advanced more rapidly. The sputum of the protracted cases contained few, small, and thin bacilli with scanty spores. The presence of fever was associated with numerous bacilli, while its absence was noted in those cases where but few were present.

[Footnote 71: _Berliner klinische Wochenschrift_, 1882, xlv. 679.]

The bacilli are readily detected by means of the staining method devised by Koch. Various modifications have been presented from time to time, of which that of Ehrlich[72] has proved the most satisfactory. The essential features are to obtain a dry, thin layer of a selected portion of the suspected sputum, which is then to be deeply stained with fuchsin or methyl-violet; the excess of color is to be removed with nitric acid, and the preparation is then ready for examination with the microscope. A power of four or five hundred diameters is sufficient for the recognition, and the object should be illuminated with a flood of light through a large diaphragm or an achromatic condenser. The bacillus retains the color notwithstanding its exposure to the acid, and the violet colors are more strongly presented if the preparation is tinted yellow after the action of the acid. If the bacilli are stained red with fuchsin, the background should be made blue. It is important that the reagents should be freshly prepared and filtered, that other bacteria may not obscure the picture, and that all the apparatus employed should be thoroughly clean.

[Footnote 72: _Allg. med. Centr. Zeitung_, 1882, xxxvii. 458.]

A fragment of thick, opaque sputum is to be taken in forceps, placed on a cover-glass, and spread into a thin layer by means of a second cover-glass. The prepared slide is then to be passed slowly through an alcoholic flame, or that of a Bunsen burner, till the layer of sputum is dried. A saturated alcoholic solution of methyl-violet or fuchsin is made and filtered, and added, drop by drop, to a filtered, saturated solution of aniline oil shaken in water. The color is to be added with stirring till an opalescent film forms on the surface of the mixture. The slide containing the dried sputum is to be placed in or on this staining fluid, and allowed to remain for half an hour or less, the application of warmth hastening the process, when it is removed, and the specimen is decolorized in a solution of one part of nitric acid and two parts of water. The preparation is then washed in water, and may be examined directly in water, glycerin, or, after dehydration in alcohol, in oil of cloves. The tinted bacilli are made more prominent by a secondary staining, for a minute or two, of the red (fuchsin) preparation {103} in a concentrated solution of methyl-blue, the violet preparation being secondarily stained in a like solution of aniline-brown. If the preparation is to be permanently preserved, it should be dehydrated in strong alcohol after washing with water, and it may then be treated with oil of cloves and mounted in Canada balsam.

After the observer has become thoroughly familiar with the tubercle bacilli by means of the method of Ehrlich, much time may be saved by following that of Baumgarten.[73] The cover-glass bearing the dried sputum is placed in a very dilute solution of caustic potash (two drops of a 33 per cent. solution in a watch-glass of distilled water) till the layer of sputum becomes transparent. The cover is then placed on a slide moistened with a drop of water, tapped slightly, and examined with the microscope. The bacilli are readily seen, and may be differentiated from other varieties of bacteria, if necessary, by again drying the object and examining it in a drop of a dilute watery solution of aniline-violet or of other preparations of aniline used for staining nuclei. The tubercle bacilli remain unstained, while putrefactive bacteria are tinted.

[Footnote 73: _Centralblatt für die med. Wissenschaften_, 1882, xxv. 433.]

The tubercular products of the invasion of the body by the bacillus tuberculosis are regarded as primary or secondary, according as they are present at that part of the body which directly receives the organisms or as they are dependent upon the transfer of the latter to parts remote from the region of their admission and immediate effects. This differing relation is also expressed by the terms local and general tuberculosis. In the former the bacilli excite the growth of tubercle only at a given part of the body. Their apparent effects may be wholly limited to this region, and it not rarely happens that the same is quite distant from the channels through which the bacilli are admitted. A general tuberculosis occurs when the latter are disseminated over the body, and their effects, especially the production of numerous tubercles, are found at various parts. The dissemination may take place at the time of entrance, or, as is more commonly the case, apparently occurs at some subsequent period, the immediate disturbances being localized at a given portion of the body. The necessary conditions being here offered for the propagation of the bacilli, their sudden distribution in great numbers is afterward permitted when favorable opportunities arise for their absorption. Such conditions are present when the local tubercular growths extend into lymphatics or blood-vessels. The frequency with which scrofulous glands are tuberculous--that is, contain miliary tubercles--is already fully recognized, and a tuberculosis of the lymphatic glands is essentially regional. These glands become affected in consequence of disturbances, the local effects of which may have wholly disappeared, in the region from which they receive their lymph. The cervical glands become permanently enlarged, perhaps tuberculous, in connection with persistent or recurrent inflammatory processes in the tonsils and pharynx, the bronchial glands from similar bronchial or pulmonary affections, and the mesenteric glands from like intestinal disturbances. In such instances, the direct reception of the bacilli into the lymph-current is assumed rather than demonstrated from a knowledge of the possibilities of absorption and an appreciation of the conditions in the glands.

That an actual growth of tubercles from the wall of the intestinal {104} lymphatics may take place has long been known, and Ponfick has recently discovered that tubercles may be found growing from the wall of the thoracic duct. The possibility of the direct admission into the lymph-current of the infective element in tuberculosis is thus apparent, and its indirect entrance into the blood-current is equally obvious. That the bacillus of tubercle may be directly received into the blood-current is likewise evident from the observations of Weigert, who found tubercles growing from the walls of the pulmonary blood-vessels, venous as well as arterial. This discovery of a tuberculosis of the blood-vessels was confirmed by Klebs, who had found a tuberculosis of the azygos veins. The occurrence of multiple miliary tubercles of the pulmonary veins, especially near the place of entrance of smaller branches, has been asserted by Mügge,[74] although appearances similar to those described by him may be met with, due simply to the agglomeration of white blood-corpuscles and their necrosis. Such a condition simulates very closely the miliary tubercle, but is usually analogous to the appearances figured by Virchow,[75] and described by him as one of the phenomena of coagulation. In his observation the white bodies were adherent to the red clots, and were with them drawn from the pulmonary artery.

[Footnote 74: _Virchow's Archiv_, 1879, lxxvi. 243.]

[Footnote 75: _Die Cellular Pathologie_, 4te Auflage, 1871, 184.]

With the admission into the body, and the colonization of the tubercular bacilli, their effects may either be progressive until the death of the individual is occasioned, or, with the cessation of the growth of the bacilli or a possible modification of their noxious properties, recovery may ensue. The history of scrofulous glands, as well as that of circumscribed pulmonary inflammation in scrofulous persons, both presumably of a tuberculous nature, show that the effects of an invasion of the parasites may be overcome.

The regions of the body which are usually the seat of a primary tuberculosis are unquestionably the respiratory and intestinal tracts. With regard to the first of these regions, the one most frequently affected, there can be no doubt that in most instances the inhaled air carries the bacilli or their spores, or both. Their constant presence in the sputum of the frequent cases of tuberculous phthisis suggests a ready means for their escape into the atmosphere. The well recognized infective qualities of the sputum, as demonstrated by the various experiments before the bacillus was discovered, demand the thorough disinfection of phthisical sputa, since these are in all probability the chief source of the dissemination of the disease.

The tuberculosis of the intestine in like manner is to be regarded in the main as the result of an absorption from its surface of the specific agent. An obvious direct means of the approach of the bacilli is offered in the sputum, which, when swallowed, is likely to retain its virulent properties. The frequent coexistence of chronic pulmonary and intestinal tuberculosis is thus most readily explained. To what extent the presence of the bacilli in the pearly distemper of cattle and in the tuberculosis of other edible domesticated animals, as fowls and swine, may lead to an infection of the intestinal wall, still remains an unsolved problem. It is not yet determined at what temperatures the bacilli are destroyed, although their growth takes place only between 30° C. (86° F.) and {105} 41° C. (105.8° F.). The inoculation of pearly masses produces tuberculosis in certain animals, yet the effect of cooking in destroying the bacilli and their spores is likely to prove of great importance. Aufrecht's[76] attempts at inoculating rabbits with cooked pearly masses proved unsuccessful. Schottelius[77] publishes an interesting series of observations relating to the prolonged use of meat from cattle affected with the pearly distemper, and shows that after a period of years no disease of the nature of tuberculosis occurred among the one hundred and thirty individuals included in the families concerned. Whatever may be the value of this negative testimony, there is, as yet, no evidence on the other side which satisfactorily determines the point in question--viz. that the flesh of animals affected with pearly distemper produces tuberculosis in the human consumer.

[Footnote 76: _Op. cit._, 51.]

[Footnote 77: _Virchow's Archiv_, 1883, xci. 129.]

The milk from cows thus diseased has likewise been regarded with suspicion, and the frequency of intestinal tuberculosis among children has been attributed to this source. Although the theoretical possibility of the escape of the bacilli into the milk of cows affected with pearly distemper is obvious, their presence in such milk is first to be demonstrated under conditions which necessitate their origin from the animal. If boiling the infective material for three minutes destroys its virulence, as claimed by Aufrecht, a ready means is offered of destroying the tubercle bacilli which may be present, not only in the milk from animals affected with pearly distemper, but in all milk which has been exposed for a certain time to an atmosphere which may contain the bacilli of tuberculosis. In the light of our present knowledge extreme hygienic precautions are only demanded in those cases where such a congenital or acquired basis (constitution) is present as facilitates the development of tuberculosis.

Morbid Growths.

In a system of practical medicine it is obviously important to include under the head of Morbid Growths not only what is spoken of by the surgeon as a tumor, but also those new formations of tissue which, in virtue of their nature, seat, manner of growth, and retrograde changes, produce an important series of disturbances in the physiological processes of the individual. The surgeon deals essentially with the swelling, which, producing irregularities in the outline of the accessible surfaces of the body, is regarded as an excrescence or outgrowth. It is important for him to realize the nature of this swelling, that he may follow a different treatment for the abscess, the wen, the watery accumulation, or the fleshy mass. The last is the tumor in the limited sense; it is the growth which, though called morbid, becomes so only in consequence of its presence being associated with symptoms whose existence and persistence interfere with the well-being of the possessor.

The physician, on the contrary, is more concerned with the tumor as a growth than as a swelling. The latter element in deeply-seated portions of the body may not be brought to his attention. The growth takes place in such a manner as to be productive of certain symptoms more or less serious, among which swelling is least obvious. The morbid {106} growth to him becomes prominent as it displaces or replaces normal tissues by those newly formed, which may or may not be normal to the part in which the growth is situated. His tumor is therefore a morbid growth, a new formation, a neoplasm or pseudoplasm, rather than a swelling, a bunch, or an excrescence.

In a consideration of the general pathology of morbid growths the first question which suggests itself relates to the method of origin of the tumor. The tendency of the present seeks for a local cause, and the most recent theory, that of Cohnheim, demands an accumulation of dormant embryonal cells as such a cause. Cohnheim supports this view by the experiments of Zahn and Leopold, which show that foetal cartilage transplanted into the tissues of a mature animal may grow so rapidly as to present the characteristics of a cartilaginous tumor, while tissues transferred from the animal after birth do not increase in size, but are usually absorbed.

As the active elements of the growth are cells, and all cells admissibly arise from pre-existing cells, it follows that the primitive cells of a tumor are derived from those resulting from the segmentation of the ovum or are introduced from without. Numerous experiments have been made with a view to the inoculation of tumors, the transplantation of living fragments of the latter to the living tissues of a healthy individual, for the sake of producing a tumor, but hitherto almost invariably without success. The alternative remains that the embryonal cells are those whose derivatives are present in, and form the essential element of, the morbid growth. All tumors may thus be said to have an embryonal origin. As the segmentation of the ovum eventually results in the production of normal tissues and groups of tissues whose structure and function are wholly different, so the possibility of the production of abnormal groupings of tissue with corresponding irregular manifestations of function is obvious.

The cells of the part from which a tumor arises may be regarded as indifferent, those whose limitations of growth, like the early embryonal cells, are only determined by the changes they undergo, or their limits of growth may be already defined in kind, and their like be produced in the formation of the tumor. The origin of a tumor thus presupposes the existence of such indifferent cells, or the presence of those whose limit of transformation has already been reached. The leucocytes of the body, whether found as white blood-corpuscles or lymph-corpuscles, or as the wandering cells of connective tissue, are, as Virchow has indicated, such indifferent cells. Always present and apparently transitory, what they are to become can only be determined from their condition and surroundings at the time of observation. Although their actual transformation into the various cells of a more permanent type is merely a matter of inference in the growth of tumors, the evidence presented by Ziegler[78] leads directly to the conclusion that their presence is necessary to the new formation of tissues whose growth is the result of an inflammatory process. These tissues may occur under such restrictions as permit them to be classified as tumors, and the granulomata, or tumors whose tissue resembles that of the granulations upon the surface of a wound, represent a well defined group in structure as well as method of origin.

[Footnote 78: _Op. cit._, 150.]

{107} The production of the cells of a tumor from indifferent cells is at present an assumption, based upon the frequent presence of the latter within tumors and in their vicinity; and the obvious objection arises that even if the presence of these cells is admitted as indispensable, it by no means follows that they are directly transformed into the more characteristic cells of the tumor. That they may serve for the nourishment of the amoeboid cells of certain tumors is suggested by the existence of both in morbid growths, and the well-known property of amoeboid corpuscles to take in formed material, even cells, from without.

The origin of tumors from cells whose limits of growth are already defined is rendered probable from the absence, entire or in great part, of indifferent cells from certain tumors, and the direct continuity of the latter with a similar normal tissue of the body. Various tumors show such an intimate relation, and there is no sharply defined border-line between the normal tissue and that which represents the tumor. The occasional presence of islets of well characterized tissue at points more or less remote from the normal position of such tissue at the time of their discovery suggests a feasible source for an eventual tumor. Virchow long ago called attention to isolated nodules of cartilage within bones in the vicinity of epiphyseal cartilages, probably detached from the latter, which might serve as the origin of a cartilaginous tumor in this region. This inclusion of tissue is also suggested by the frequency of certain tumors in certain regions where the developmental conditions are favorable. Lücke[79] mentions the frequency of dermoid cysts near the median line of the head, the vicinity of the eye, and the side of the neck. Such regions are those where fissures exist during foetal life, with normal involutions of the outer germinal layer; which involutions may become irregular, and eventually included or shut in, as the fissures become closed. A similar explanation is offered for the frequent occurrence of cartilaginous tumors at the angle of the jaw, it being thought probable that bits of embryonal cartilage, during the formation of the ear, become included in the salivary glands.

[Footnote 79: _Volkmann's Sammlung klinischer Vorträge_, xcvii. 819.]

In like manner, Cohnheim explains the frequent occurrence of certain epithelial tumors at the orifices of the body--the cervix uteri and the vicinity of the tracheal bifurcation--not through the exposure of these parts to injury, but because they are regions in which embryonal irregularities of development are likely to arise.

That congenital, local peculiarities are an important element in the origin of tumors has already been strongly advocated by Virchow. Not only are children born with tumors, but instances of growths eventually arising from birth-marks, and the occurrence of certain tumors in the same locality in successive generations of the same family, are sufficiently familiar.

Although certain tumors are admitted to be due to congenital peculiarities of tissue, and even to represent atypical growths from embryonal tissue, the theory of such an embryonal origin for all tumors seems unnecessary. The resemblance in symptoms as well as in appearance, and even in structure, of certain tumors to inflammatory products, and their frequent association with these, has led to the suggestion of an irritant as an exciting cause for the tumor, even in the absence of local peculiarities of tissue. {108} It is obvious that were the embryonal theory of origin, as extended by Cohnheim, universally applicable, the growth demands something more than a focus of embryonal cells. An immediate cause for their growth after a dormant period, extending even into old age, is required. Cohnheim finds such in a sufficient supply of blood. He attributes the development or rapid growth of the tumor to this feature, and supports his view by the usual appearance of exostoses when the skeleton is at its period of most vigorous growth, and of dermoid cysts at a time when the formation of the beard indicates active developmental conditions in the outer germinal layer.

The growth of ovarian cystomata at and after puberty, and of these and mammary tumors during pregnancy, are also explained on the ground of a more abundant supply of blood at such periods. He and others find in physiological conditions a source for the abundant blood-supply--that is, the efficient nutrition for the growth of a tumor. The necessity of sufficient nutrition in the development of tumors is universally admitted, and its source may be looked for in pathological as well as physiological conditions.

The existence of an irritant of some sort often seems probable, and, although its absence is more frequently determined than its presence, it is obvious that when present it may be overlooked. Although traumatic irritants of considerable mechanical severity exist in but a small percentage of tumors, their occasional influence in the production of morbid growths is not to be denied. Their action may be explained as producing a congestion or as enfeebling the opposition of physiological tissues to pathological growths. The importance of an irritant as the exciting cause, however its action may take place, is supported not only by the sequence of injuries and tumors, but also by the frequent occurrence of tumors in parts exposed to injury and irritation. Such exposure may result from position, structure, or function. The orifices and prominences of the body, the retained testis in the inguinal canal, are notoriously liable seats of tumors. Soft, friable, and slightly resistant structures, like mucous membranes, are not only the frequent place of origin of tumors, but the most exposed parts of such structures are oftenest affected. The exposure resulting from function is manifest by the relation presented by the periods of greatest functional activity of the growth of tumors in such organs as the mammary gland, uterus, and ovaries.

The importance of an irritant is still further suggested by the association of tumors with inflammation. The growth of tubercles and cancer from serous membranes is frequently accompanied by an acute inflammation of the latter; fibrous tumors and chronic interstitial inflammations often coexist, while elephantiasis is usually preceded by recurrent, erysipelatous inflammation of the skin.

The recent discovery of infective organisms as an exciting cause for many of the members of an entire group of tumors, the granulomata, has resulted in making prominent the etiological rather than the structural features of the tumors concerned.

Local peculiarities of tissue, whether congenital or acquired, are thus regarded as representing the beginnings of the growth. With the multiplication of the cells their transformation may take place or a change in their grouping may arise. The essential condition in the production {109} of the morbid growth is that the formation of the cells should take place at an abnormal time or place and should progress in a normal or abnormal manner.

The growth takes place with greater or less rapidity in one or another direction according to the nature of the tumor and its seat. The more closely the tumor resembles the normal structures of the body, the slower is its growth; the more it differs in composition, the more rapid is its progress. This difference may arise from a predominance of cells over intercellular substance, as in the case of the sarcoma, or it may result from an atypical combination of tissues, as seen in the development of epithelium and connective tissue in cancer.

The seat of the tumor is of importance mainly on account of the vascular supply of a part and the more spongy or yielding nature of certain regions. That the more abundant the nutrition of certain regions of the body, the more favorable the opportunities for growth, may be admitted without question. The spongy nature of tissues implies a predominance of cavities over solid constituents. These cavities are lined by surfaces which represent, on the one hand, the walls of lymph-spaces, on the other the free surfaces of the body exposed to the air, as the mucous or cutaneous surfaces and the pulmonary surface. The rapidity of growth in the direction of the least resistance is amply shown in the projection of tumors above the surface of serous membranes and the frequent presence of fungoid excrescences in various parts of the body.

The growth of tumors extends in all directions, but a distinction has long been drawn between the concentric or interstitial manner of growth and the excentric or infiltrating form. This distinction is based upon the presence of a sharply defined limitation of pathological and normal tissues or upon the absence of such a limitation. Such a distinction is merely of relative importance, as certain tumors may grow in both ways. This is best observed in those bulging superficial tumors whose base is irregularly extended into the continuous healthy tissues.

The concentric variety of growth includes those tumors which have commonly been described as encapsulated, and which are capable of ready enucleation from their surroundings in virtue of a thin layer of loose connective tissue lying between the tumor and the contiguous tissue. Such a capsule represents the matrix, the pia mater, in which lie the blood-vessels going to and coming from the tumor, and is often nothing else than the distended and hyperplastic fibrous tissue remaining after the absorption of the muscular fibres or gland-cells from the tissues surrounding the morbid growth.

The excentric, peripheral, or infiltrating extension of the tumor takes place when the surrounding parts are invaded by the active elements of which the tumor is composed. The amoeboid property of the cells of certain tumors is well known, and the possibility is admissible that the indifferent cells of the body, so often accumulated at the periphery of the growth, become impregnated with a formative function by the constituents of the tumor. Such amoeboid and wandering cells represent a means through which the growth of the tumor may become extended in its vicinity as well as in more remote parts of the body.

The extension in the vicinity may be continuous or the reverse, the latter through the formation of secondary nodules, which may {110} eventually become fused with the primary mass. The continuous growth takes place, as has been more particularly shown by Köster, along the lymph-channels surrounding the tumor, which may become filled, distended, and eventually obliterated by projections from the neoplasm. Both methods of peripheral growth, by secondary nodules and continuous extension, represent an infection of the surrounding tissues, especially if it be admitted that the cells through which the increase is accomplished are direct descendants of the pre-existing cells of the part. Not only does the extension take place through the lymphatic vessels about the tumor, but blood-spaces as well as lymph-spaces may be invaded. Thrombi are then found whose structure is frequently that of the tumor, and whose connection with the same is direct through the perforated wall of the vessel. These features in the growth of tumors lead directly to the consideration of the means by which multiple tumors appear in remote parts of the body after a single tumor has appeared in a given locality, and after the removal of such a primitive growth.

The distinction between primary and secondary tumors is now so obvious that one is inclined to forget that the presence of numerous tumors at various parts of the body was at one time regarded as evidence of the constitutional or dyscrasic nature of the morbid growth. Such a multiplicity seemed to indicate that the blood was charged with the constituents of the tumor, which were deposited at various parts of the body.

Although certain multiple tumors may be present in different localities without an apparent relation between an antecedent and a subsequent growth, such tumors are usually limited to certain systems of the body. Multiple bony tumors are found growing from bones, fibrous and warty tumors from the skin, and fibro-myomata from the uterus. Cohnheim's theory of the embryonal origin of tumors may seem applicable in such cases, but the frequent association of the osteomata with chronic inflammatory conditions, of cutaneous warts and fibrous tumors with local irritative processes, makes such a hypothesis unnecessary.

Those tumors whose multiplicity is of the greatest clinical importance are the rapidly growing forms terminating fatally. Such are those which reappear in the scar after the removal of a cancer, or in the adjoining chain of lymphatic glands or at remote parts of the body. The most satisfactory explanation of their presence, and of the generalization, recurrence, or metastasis of tumors, is derived from what has already been stated with reference to the manner of the growth of the latter.

It is well known from experiments on animals that various living, normal tissues when transplanted to remote parts of the same individual or to other individuals may continue to grow. Cohnheim claims, as has been previously stated, that a distinction is to be drawn in this respect between the tissues of the adult and the foetus, where the genesis of tumors is concerned. This observer, in connection with Maas,[80] has found that the transplanted material (periosteum), although growing for a while, disappears at the end of five weeks, and it is asserted that fragments of tumors, when transferred, suffer a similar fate. Wile,[81] on the contrary, {111} who has experimented with reference to the fate of transplanted tissues and portions of tumors, reports that one hundred days after the transfer of periosteum the lung was found to contain several centres of ossification. He regards the latter as proceeding from the fragments of periosteum introduced into the jugular vein, and his results thus widely differ from those of Cohnheim.

[Footnote 80: _Virchow's Archiv_, 1877, lxx. 161.]

[Footnote 81: _The Pathogenesis of Secondary Tumors_, reprint from _Philadelphia Med. Times_, July, Aug., and Sept., 1882.]

Notwithstanding the numerous experiments which have been made in various parts of the world to excite the growth of transplanted bits from tumors, most of them have terminated unsuccessfully. Although a temporary growth of fragments of tumors has taken place after transplantation, their eventual disappearance has usually occurred. Cohnheim lays stress upon this fact in connection with his theory of the origin of tumors. He considers that the fragments of tissue and tumors disappear in consequence of the inability of the foreign particles to withstand the metamorphosis of physiological tissues. If this opposition is neutralized, the existing germs of tumors become capable of development. Wile, however, found that eight weeks after the introduction of a bit of cancer into the lung of an animal the fragment had increased nearly twice in size. He also refers to the positive experiments of Newinsky,[82] who transplanted a bit of cancer from a dog to the subcutaneous tissue of another, young dog, and found, after five months, not only an ulcerating cutaneous cancer at the place of inoculation, but also a metastatic nodule of the size of a hazel-nut in an axillary lymphatic gland.

[Footnote 82: _Allgem. medicinische Central-Zeitung_, 1876, lxxi. 875.]

For the present consideration it may be borne in mind that fragments of normal (foetal) tissues, as shown by the experiments of Zahn and Leopold, when introduced into the organs of animals, may become enlarged. It is also certain that bits of tumors, after their introduction into the tissues and organs of animals, have become increased in size. What their eventual fate might have been does not appear; and herein lies the weak point of the experiments with reference to the production of secondary tumors. For such experiments to be regarded as crucial it is necessary that a large number of previously healthy animals, after inoculation with fragments of morbid growths, should present in various parts of the body well characterized tumors whose structure should be like that of the particles introduced.

The experiments above referred to are of value in confirming the views concerning the generalization of tumors which have been generally admitted since Virchow's discoveries with regard to the phenomena of embolism.

Tumors are said to become generalized when they appear not only in various systems of the body, but in various organs and tissues. They are found usually in considerable numbers, and with such differences in size, shape, and appearance as to indicate different ages. Such tumors are regarded as arising directly or indirectly from a common source. This source is called the primitive or primary tumor, and its derivatives the secondary tumors. The latter are usually considered as the direct descendants of the former, although their relation may be that of several successive generations.

The primitive tumor in its growth may extend into lymphatics and blood-vessels, as has already been suggested. Such an extension may be {112} so little obvious when the tumor is removed by the surgeon that all diseased tissues are apparently separated from the body. A recurrence of the tumor is said to take place when the growth returns in the cicatrix, frequently in a multiple form. The explanation of such a recurrence is based upon the probable presence, at the time of the operation, of fragments of the tumor within the tissues forming the base and edges of the wound. During and after the healing of the wound their growth is supposed to continue till they become apparent as small tumors. The progress of these recurrent tumors is at times extremely rapid, and they may attain a considerable size in the course of a few weeks. Such nodules are secondary in point of time, although they were actually a part of the primary growth.

Secondary nodules in descent as well as time are those which appear at distant parts, often after the discovery of the primary tumor. Such nodules are regarded as resulting from the transfer of particles of various size from the primitive growth, either through the lymph-vessels or blood-vessels. If the invasion of the body takes place through the former, the fragments may be floated along to the nearest lymphatic gland, where it remains when too large to pass through. If it retains the capacity of growth or of stimulating a like growth, there results a more or less complete transformation of the gland into a morbid tissue like that from which the fragments came. Adjoining lymph-glands may become infected from the first, until eventually an entire series becomes more or less completely transformed into morbid growths. A like invasion of the lymphatic glands may take place through a continuous extension along the lymph-vessels; and it is not rare to find the sub-pleural or sub-peritoneal lymphatics as an elevated meshwork in consequence of the neoplastic growth within them. Such a method of extension may take place when a cancer of the stomach or liver is associated with a cancer of the pleura, the intervening lymphatics of the diaphragm offering a direct and continuous communication.

With the outcropping of a tumor upon a serous surface the possibility of the detachment of particles is at hand. These may become transplanted to the opposed serous surface or may be transferred to the most dependent parts, and there serve as seed for subsequent growth.

The probability of the embolic nature of many secondary tumors was early suggested in the history of embolism. Rapidly growing tumors were known to be capable of perforating the walls of adjacent blood-vessels, especially veins, and to continue growing along the course of such vessels. The possibility of the detachment of portions of these tumors and their transfer along the course of the circulation was an inevitable inference from the results of experimentation with foreign bodies. Cancerous emboli were thus recognized as a possible variety, and their distribution was subject to the same laws as those governing emboli otherwise constituted. Multiple nodules were frequently found in the lungs in connection with tumors growing into the inferior vena cava, while multiple nodules in the liver were usually associated with tumors of the gastro-intestinal canal or other regions whose vessels formed a part of the portal circulation. The readiness with which portions may be detached after death from the soft masses projecting into the interior of veins suggests the ease with which particles may be {113} separated during life. The experiments already referred to show that isolated fragments of tissue serving as emboli may grow in the place of their reception, and it is presumable that the resulting growth takes place under the same conditions as those prevailing at the place from which the embolus started. The question whether the secondary tumor arises from the reproduction of elements transferred from the primitive disease, or whether these excite a characteristic, specific growth of the cells in the place of their retention, may still be regarded as open. The experiments favor the former view, and they alone are capable of satisfactorily determining the point in question.

The secondary nodules, whatever may be their method of origin, present the peculiarities of the primitive growth. If the cells of the latter are pigmented, those of the former show the same peculiarity. If the structure of the primitive tumor contains bone, cartilage, or squamous epithelium, the secondary growths show like characters, though they may be present in the heart or other organs where such tissues are not present as normal constituents. So constant and characteristic is this feature that the structure of the tumor is usually as well displayed in the examination of the secondary as of the primitive nodule. Indeed, the structural peculiarities of the growth may be more characteristically shown in the former in those instances where the primitive tumor has undergone degenerative changes obscuring its histological features.

The tissues of the tumor are subject to the various changes which take place in the normal tissues of the body. Their growth is attended with a multiplication of cells and a formation of intercellular substance. Tumors whose growth is the most rapid are those whose blood-vessels are the most numerous and whose relation to the cells is most intimate. The slower the advance of the tumor, the more permanent is it likely to become, while the more rapid the progress, the more transitory are its elements. The growth may continue, and yet the actual size of the tumor may diminish through the absorption of its degenerated parts. The cells of the neoplasm may undergo fatty degeneration, or they may become cornified. They may undergo the mucous metamorphosis or the amyloid and colloid degenerations. They may take up pigment or they may produce the same. The intercellular substance varies in its character as does that of normal tissues. It may be slimy, homogeneous, or fibrillated. It may contain mucin, chondrin, or gelatin, and may be infiltrated with calcareous salts. Limited necroses with characteristic cheesy appearances are of frequent occurrence.

Tumors may become the seat of inflammatory processes, indicated by suppuration and fever, which may result in abscess or gangrene, or their progress may terminate in the production of scars. Ulceration may occur in consequence of the extension of an inflammatory process to the surface, or it may result in the course of the degenerative softening of a tumor. In both cases the cutaneous or mucous surface is involved and destroyed, and the interior of the tumor being exposed putrefactive processes, with fistulæ and sinuses, arise, the latter favoring the retention of the product and the persistence of the inflammatory process.

Tumors are always pathological, but the resulting disturbances vary within wide limits and are often of a complex character. The familiar distinction between benignant and malignant tumors is based chiefly {114} upon this variance in the nature of the disturbances. Those are benignant which closely resemble the normal structures of the body, increase but slowly, and, if they attain a large size, produce mainly mechanical disturbances. They may prove serious, even fatal, if so seated as to interfere with the function of important parts of the body. Very large and heavy tumors may prove burdensome solely on account of their weight, while others of similar character, elsewhere seated, may interfere with respiration or circulation, and eventually with nutrition. Tumors in exposed situations may become important only in virtue of their liability to injury, while others impede the function of a part or an organ by pressure upon its nerves and vessels or by obstructing its ducts.

The malignant tumors, on the contrary, differ in their structure from the normal tissues of the body. Their growth is rapid and infiltrating rather than slow and concentric. Such tumors usually have a predominance of cells and thin walled blood-vessels. The former may be little else than nuclei enveloped in an easily destructible protoplasm, or they may be composed of multi-nucleated masses of protoplasm, and are then known as giant-cells. The most malignant tumors are those which tend to become generalized as well as to spread locally. They recur locally, and appear in the nearest lymph-glands and at remote parts of the body. The disturbances produced by the malignant tumors depend less upon their mechanical relations than upon their tendency to destroy tissues and disturb functions. With their presence and progress in vital organs there is associated, from their manner of growth, a destruction of the cells of such organs, as the kidneys and liver, the lungs and heart. When they are seated in the spleen and lymphatic glands, a disturbance in the blood-making process must be associated. Their occurrence in the alimentary canal opposes the admission, digestion, and expulsion of its contents, and produces disturbances varying as to the seat and peculiarities of the tumor. The progress of the malignant tumor is often associated with ulceration, watery discharges, and hemorrhage. The frequent coexistence of emaciation, weakness, anæmia, and a yellowish discoloration of the skin forms a group of disturbances which, included under the name "cachexia," have long been prominent as significant of malignant tumors. At the present day this cachexia is regarded rather as the result than the cause of the tumor, whereas formerly the reverse was the case.

The modern classification of tumors is based chiefly on their structure, in part upon their method of origin, and in part upon their cause.

With the observation of the similarity of appearances in the flesh of which the external and internal neoplasms are composed, the suggestion readily presented itself to regard the external tumors and the internal growths as similar in character. External forms, physical characteristics, clinical peculiarities, all proved insufficient as a means of identifying the two, and the step was a short one which led to the minute study of the flesh of the tumor and a comparison of its resemblances and differences. This comparison obviously included a knowledge of the structure and peculiarities of normal tissues. As histological studies advanced, so did the pursuit of pathological histology, and the tumors which were once designated as encephaloid, mastoid, pancreatoid, or nephroid, from real {115} or fancied resemblances to certain organs of the body, became analyzed into their microscopic rather than macroscopic characteristics.

It is unnecessary to say that the modern classification of morbid growths owes its foundation and a large part of its superstructure to Virchow, whose classic work, _Die Krankhaften Geschwülste_, showed the direction which future investigators were to pursue and the nature of the discoveries likely to result.

The tumor represents the result of the growth of a tissue or tissues which are like or resemble those which form the normal constituents of the body. Although a new formation is present, it is composed of tissues lying within the possibilities of the individual. A new formation of feathers, as Virchow suggests, is beyond the productive powers of human tissues, though within those of feathered animals. A goose can produce a tumor containing feathers, not one in which hairs are found; in the human species tumors containing hairs may occur, not those, however, in which feathers are present. Although the cells of the tumors of man may deviate in their appearances from the cells of normal tissues, this deviation is never so extreme that their analogue cannot be met with in some part of the body.

As the normal tissues originate from pre-existing tissues, so the pathological tissues of the tumor grow only from the antecedent tissues. The matrix from which the tumor arises is a normal tissue. There is produced from it, as a neoplasm, either a tissue which follows the type of the maternal tissue, a homologous tumor, or one which deviates in type from that of the matrix, a heterologous growth. Although the latter differs in its composition from that of the matrix, it does not vary essentially from a like tissue to be found elsewhere in the body. It occurs where it does not belong either in place, time, or quantity. The homologous tumor appears rather as a hypertrophy of the tissue from which it arises, and the line between this variety of growth and a simple hypertrophy is often purely arbitrary.

Although tumors, in the more limited sense, are solid, fleshy masses, the new formation of tissues may result in the presence of a tumor within which is a cavity with various contents. Such a cavity is not a mere hole, but has a distinct wall of connective tissue lined with epithelium or endothelium. A distinction is thus drawn between cysts and growths--one which is of daily importance in the practice of medicine--and Virchow's oncology includes the consideration of the two varieties of tumors.

Cystic tumors are subdivided according to the nature of their contents and the method of their origin. One group is composed of clotted blood within cavities resulting from the laceration of tissues or in preformed spaces. If the cyst primarily is merely a rent, the wall becomes thickened in time from a growth of the limiting tissues, and the blood-clot, of which the tumor was chiefly composed, may remain or become absorbed. If the latter event occurs, its place of deposit may become obliterated by a fusion of the walls of the cyst, or may persist from the subsequent addition of serum.

The cystic tumor whose contents are extravasated blood is the hæmatoma, familiar instances of which are met with in the hæmatoma of the dura mater, of muscle, of the vulva, and the polypoid hæmatoma of {116} the uterus. The latter is the long retained and constantly enlarging blood-clot, due to the adherence of portions of the placenta after childbirth.

The second group of cystic tumors has for its contents a more watery fluid, and to this the term hygroma is applied. This watery fluid lies, for the most part, within preformed cavities, and its accumulation is connected with a dilatation of these cavities. Instances are met with in the tumors resulting from the accumulation of fluid in the membranes of the brain or spinal cord, and in the ventricles of the former or in the central canal of the latter. These lead to the congenital cystic tumors of the cranium or spine, with watery contents. The ganglion, the house-maid's knee, as also the hydrocele of the tunica vaginalis, are regarded as hygromata. The hydrocele of the neck and elsewhere in the subcutaneous or intermuscular connective tissue is now removed from the hygromata to the tumors which arise from lymph-vessels. A like transfer of other hygromata might be made in accordance with the prevailing views concerning the cavities in which the watery fluid is accumulated.

A third group of cysts contains material which represents essentially a production from the wall, with a difference of composition dependent upon the nature of the wall. Such cysts give rise to tumors through the retention of their contents, and they are called retention-cysts or retention-tumors. In the wall of the cysts is a gland-tissue, which may line the surface or lie beneath. The glandular structures may be cutaneous, mucous, or represent a part of the great glands of the body, as the liver and kidneys. The atheromatous cyst of the skin, the mucous cysts of the gastro-intestinal mucous membrane, and the ovula Nabothi of the uterus are examples of the retention of secretion within glands. The dropsical dilatations of the antrum, the vermiform appendage, the uterus, the biliary and renal canals furnish instances of tumors resulting from the retention of secretion on a large scale. In the subsequent history of these retention-cysts the secretion may be modified chemically and physically; the cells upon the walls may be transformed from columnar forms into flattened and scale-like varieties. In time, the original secretion frequently becomes a watery fluid, resembling the contents of the hygroma previously mentioned.

This grouping of cysts in contradistinction to fleshy tumors omits the consideration of a series of cystic tumors of enormous size, the multilocular tumors of the ovary. This class represents a more complex form of cystic growth--one whose tendency is toward the reproduction of cysts, to which the term cystoma is applied. The cystoma is the result of an active new formation of epithelium and connective tissue, and is classified as a variety of the epithelial group of tumors.

Morbid growths, as distinguished from cysts, are divided by Virchow into the simple and complex forms. The former consist of a single tissue, the histoid tumors; the latter of several tissues suggesting an organ, the organoid tumors; while still others, in which the number and grouping of tissues is so complex as to simulate systems of the body, even monstrosities, have received the term systematoid or teratoid tumors.

Virchow claimed that the growth of most tumors took place from the connective tissues, and that most of the organoid tumors, especially cancer, arose from the formative action of the connective tissue in the part where {117} it first made its appearance. The structure of cancer suggested an organ, as it consisted of collections of cells resembling epithelium, within spaces or alveoli whose walls were formed of connective tissue. The epithelioid cells of the cancer, as well as the connective-tissue corpuscles, were considered to arise from pre-existing cells of connective tissue.

The first, most important, modification of Virchow's views, which has led to a more rational appreciation of the relation of the various tumors, especially of the epithelial group, to each other, arose in consequence of the investigations of Thiersch and others with regard to the origin of certain cancers. This observer[83] claimed that the epithelioid element of cutaneous cancers arose in all instances from pre-existing epithelium, either of the rete mucosum or cutaneous glands. Similar views were suggested, with various degrees of precision, by other authors concerning certain cancerous tumors elsewhere, but were first applied to all cancers with a more exact formulation by Waldeyer,[84] to whom the prevailing views with regard to the histogenesis of morbid growths are due. According to him, the essential (epithelioid) element of all primitive cancers arises from pre-existing epithelium; consequently, no cancer-cell can arise except in organs where epithelium is normally present.

[Footnote 83: _Der Epithelial Krebs, namentlich der Haut, etc._, 1865.]

[Footnote 84: _Virchow's Archiv_, 1867, xli. 470; 1872, lv. 67; _Volkmann's Sammlung klinischer Vorträge_, 1871, xxxiii.]

This comprehensive statement was rendered possible by the embryological researches of Remak at the outset, and afterward by those of His and Waldeyer. Remak showed that after differentiation of the cells of the ovum into the several germinal layers, those from one layer could not serve to originate the cells belonging to another layer. The development of normal tissues takes place within the limits defined by this differentiation. Epithelium thus is not derived from connective tissue, nerves, or muscles, nor was the reverse known to occur. To His is due the exact appreciation of the superficial cells of serous membranes, which had been previously called epithelium, and had thus been confounded with the epithelial cells of mucous or cutaneous membranes and of secretory glands. He showed that these cells had a wholly different origin from epithelium, and were simply scale-like cells of fibrous tissue, to which he applied the name endothelium. The latter is now used as the term for the thin, squamous cells of fibrous tissue, whether they are found lining the walls of the great serous cavities or the smaller lymph-spaces, the endocardium, or the inner coat of blood-vessels and lymphatics.