Part 18

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 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.

{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 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.

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, 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, 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.

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, 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.

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.