Part 19

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 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, 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.

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.

The importance of this distinction is obvious when the occurrence of tumors, called cancers, is observed in parts which contain no epithelium. Aside from the vagueness of the term cancer, as applied clinically, tumors are sometimes met with, even in parts where epithelium normally does not exist, whose structure resembles more or less closely that of cancer as usually recognized. Such tumors are to be regarded as of an endothelial rather than epithelial character, and as such their histogenesis falls under the general laws of the development of tissues.

Waldeyer has suggested that the primitive basis for the development of the genito-urinary tract contains cells which are equivalent in their possibilities of ultimate development to the epithelium of the limiting germinal layers--a suggestion which is of importance in permitting the {118} epithelial tumors of the ovary to be brought under the general embryological laws of development.

As the growth of embryonal tissues is so defined that descendants are like their ancestors in all respects, so the development of tissues in the adult is regarded as defined with equal precision. Eberth and Wadsworth have shown that the regeneration of corneal epithelium takes place from pre-existing epithelium. E. Neumann and others claim in like manner the development of muscular tissue from antecedent muscular cells.

The relation of cancer to epithelial tumors is regarded as similar to that borne by sarcoma to tumors composed of connective tissues. The growth of the epithelial elements into the neighboring parts is through paths determined by pre-existing or new-formed connective tissue. The active element of the cancer lies more especially in its epithelioid cells, and its growth takes place in an atypical rather than a typical manner. Of the various epithelial tumors, there are those like the cutaneous horn or corn, the adenoma or cystoma, whose epithelial growth takes place in accordance with normal methods of production. The epithelioid constituent of the cancer, on the contrary, grows often with great luxuriance and with but little tendency to carry out the normal mutual relations of the epithelium and connective tissue of the part from which it proceeds. The epithelioid masses or sprouts are composed of cells whose relation to each other resembles that of normal epithelium in the absence of an intercellular substance, while the shapes of the cells correspond more or less closely with that of the epithelium in the region from which the tumor arises. The epithelioid cells of cutaneous cancers resemble those of the surface, the rete, or the glands of the skin. Cancers of the stomach or uterus contain epithelioid cells whose shape simulates the varieties in the stomach and uterus. Such resemblances are carried out in the degenerations which the cells of cancer undergo. The horn-like, keratoid, transformation of epidermoid cells in cutaneous cancers, the mucous degeneration of the epithelioid cells of cancers of mucous membranes, are sufficiently familiar. Notwithstanding these resemblances, which are also present in secondary tumors at remote parts of the body, the epithelioid growth advances without limit and without reproducing the normal type. Cancer is therefore defined as an atypical, epithelial new formation.

Sarcoma, on the other hand, whose clinical features correspond so closely with those of cancer, simulates, as shown by Virchow, the connective tissues. It is composed of cells and intercellular substance, both of which may be as varied as are those of the connective tissues. The shape of the cells is as diverse and their contents as various, while their possibilities of degeneration are alike. The cells of the sarcoma are not simply cemented together, as are epithelial cells, but they are separated from each other by an intercellular substance, which corresponds in its appearance and chemical properties with that of mucous, fibrous, cartilaginous, or osseous tissue. The structure of the sarcoma differs from that of these tissues in presenting a predominance of cells over intercellular substance, while the reverse is the characteristic of most varieties of connective tissue. In this predominant cell-formation lies its absence of type, {119} whereas the atypical character of the cancerous growth is manifested rather by the irregular grouping of the cellular masses than by an abundance of cells.