THE

PATHOLOGY AND SURGICAL TREATMENT

OF

TUMORS.

I. ORIGIN AND NATURE OF TUMORS.

THE subject of tumors is one of the much-neglected departments of surgical pathology. Laboratory investigation, experimental research, and clinical observations have revolutionized the etiology and pathology of inflammatory diseases during the last decade. During that time the attention of pathologists has been occupied largely in the etiological and pathological elucidation of infective diseases, while surgeons have expended their energies in enlarging the scope of operative surgery by an increased knowledge thus gained, and by the diminution of the immediate and remote risks to life of operative procedures attending the general adoption of antiseptic and aseptic precautions. The benefit to humanity in the saving of life and the lessening of suffering derived from these investigations and from improved practice is incalculable. The great work initiated by Pasteur, Lister, and Koch has inaugurated a new era in the study and treatment of disease, and must serve as a permanent foundation for all future investigations. When we realize the amount of suffering and the number of deaths resulting from tumors, it appears somewhat strange that this vast department of pathology has received so little attention on the part of modern investigators. It is true that recently a great deal of work has been done to establish the microbic origin of malignant tumors, but no positive results have been obtained so far, and we must confess that but little additional light has been shed on the etiology and pathology of tumors since the epoch-making labors of Virchow and Cohnheim.

History. The old authors regarded tumors as something entirely foreign grafted upon the organism. John Hunter taught that a drop of blood, being accidentally extravasated, became organized and assumed a growth independent of the adjacent tissues, and continued to grow till it was limited by some obstacle opposed to it. Effusion of

lymph has been considered as a possible cause. It was suggested that in the development of the tumors the lymph played the same rôle claimed by Hunter for the extra-vascular blood. Chronic inflammation was regarded for a long time as the essential etiological factor. These and many other vague theories advanced in regard to the origin and nature of tumors prior to the time they were recognized as a part of the body they inhabited, the result of proliferation of pre-existing cells, do not merit an extended discussion in a modern text-book. Schleiden established the cell theory which inaugurated the science of biology; Schwann showed from a cellular basis the analogy of the structure of plants and of animals.

The study of tumors in plants and in the lower animals has done much in adding to our knowledge of the etiology and pathology of tumors. Pathological processes in plants are much simpler than in animals, owing to the absence in the former of many complicating factors, such as nerves and blood-vessels; at the same time, the plants are constructed upon a much simpler embryological plan. Both animal and vegetable cells have in common the nitrogenous carbon compound called "protoplasm." Johannes Müller applied the cell theory to the study of tumors. Virchow elaborated this doctrine in establishing by his immortal researches the motto of his great work on cellular pathology, Omnis cellula e cellula. Cohnheim imparted a new stimulus to the study of tumors by advancing a novel theory in reference to their origin. It appears recently that Durante of Rome was the real originator of the theory of the embryonic origin of tumors, as his publication on this subject antedates that of Cohnheim by one year. Virchow taught that an epithelial tumor could develop from connective tissue. Cohnheim referred every tumor to its proper embryonic layer, and claimed that a tumor never had its origin from mature tissue, but always developed from a matrix of embryonic tissue. This essential tumor-matrix he traced back to its embryological source. He believed that during the process of cell-differentiation in the embryo groups of cells not utilized in the growth of the embryo, or displaced, were arrested in their further development, and remained in a latent condition until their activity was awakened later, when the product of their proliferation resulted in the formation of a tumor. This theory found many supporters, but at the present time only a few authors uphold it in its entirety. As we shall see further on, it has much to recommend it, but it does not satisfactorily explain the origin of all tumors. In the absence of better proof of the origin of tumors, the writer will adhere to the doctrine advanced by Cohnheim, and in addition to it will claim that the essential tumor-matrix may be composed

of embryonic cells, the offspring of mature cells which for some reason have failed to undergo transformation into tissue of a higher type, and which may remain in a latent, immature state for an indefinite period of time, to become, under the influence of either hereditary or acquired exciting causes, the essential starting-point of a tumor.

It has been the good fortune of Roux to discover isolated colonies of cells in the middle, more rarely in the inner embryonal layer of frog embryos, sometimes in large numbers-once as many as thirteenscattered among the other cells. Barfurth, in his experiments in the regeneration of the embryonal layers, observed that by puncturing and turning inward the ectoderm of the gastrula that a growth of cells very like a dermoid took place. Grawitz traced some of the tumors of the kidney to islets of separated and displaced suprarenal tissue. These experiments and observations have a very important bearing upon the development of tumors from displaced embryonal cells.

Definition. So long as our ideas in reference to the origin and nature of tumors rest exclusively on a theoretical basis, it is evident that no satisfactory definition can be given. The definition of each author must necessarily vary according to his views on the subject. A few definitions will be given to corroborate the correctness of this statement. John Hunter thus defines a tumor: "A tumor is a circumscribed substance produced by disease, and different in its nature and consistence from the surrounding parts." "Neoplasm is a new growth characterized by histological diversity from the matrix in which it grows," is the description of a tumor given by J. Bland Sutton. Bär regards the characteristic feature of a tumor as an "active multiplication of cells which takes place independently of inflammatory processes." The process which leads to the formation of tumors he calls "a monstrosity in the development of cells." Lücke wrote on the subject of tumors from the standpoint that a tumor is "an increase of volume by the production of new tissue without a corresponding physiological function." Cohnheim, in consonance with his definite ideas concerning the origin of tumors from embryonic tissue, and the difference between the character of the tissues of which they are composed and the structure of the tissues in their immediate vicinity, describes a tumor as "a circumscribed, atypical production of tissue from a matrix of superabundant or erratic deposit of embryonic elements." From these definitions it becomes apparent how difficult it is to give even an approximately correct definition of a tumor. "Many pathologists have regarded tumors as a localized form of hypertrophy, but upon making a closer comparison we find that, to whatever extent the adapted hypertrophy may develop, the overgrown part maintains itself in the normal.

type of shape and structure, while a tumor is essentially a deviation from the normal type of the body in which it grows, and, as a rule, the longer it exists the more marked becomes the deviation" (Williams). One of the greatest difficulties in the way of a proper appreciation of what is meant by a tumor is a failure on the part of authors and teachers to draw a dividing-line between tumors and inflammatory swellings. That tumors should have been confounded with inflammatory swellings before the essential causes of the latter were discovered and understood is not strange, but that these entirely different pathological processes should not be separated sharply at the present time is inexcusable.

It has been the writer's custom for ten years, in his lectures, didactic and clinical, to make a sharp distinction between a tumor, an inflammatory swelling, and retention-cysts. In writing this book this distinction will be maintained by eliminating from discussion all affections. of which the microbic origin has been established, as well as swellings caused by retention of a physiological secretion, the latter of which will be discussed in a separate part of the book, and the definition of a tumor will therefore be framed upon a more limited basis. The definition of a tumor should explain its origin, its histological characteristics, and its behavior toward its immediate environment. A tumor is a localized increase of tissue, the product of tissue-proliferation of embryonic cells of congenital or post-natal origin, produced independently of microbic causes. This definition refers all tumors histogenetically to embryonic cells, which, according to Cohnheim, may be of congenital origin, or which, according to the writer's views, may also be of post-natal origin, being derived from pre-existing mature tissue in consequence of injury or disease, and, failing to undergo the normal transformation, may give rise to tumor-formation in the same manner as embryonic cells of fetal origin. This definition also excludes mature tissue and pathogenic microbes as etiological factors in the production of tumors, thus establishing a well-defined line between a true tumor and an inflammatory swelling. It is not necessary to include absence of function in the definition, as this applies equally, if not more forcibly, to swellings of an inflammatory origin. The writer does not claim that this definition is above criticism, but it will convey to the student what is so essential in teaching-a correct idea concerning the histogenesis and the essential pathological features of tumors, which knowledge will enable him, later, at the bedside to make a correct differential diagnosis between a true tumor and an infective swelling.

Histological and Clinical Differences between a Tumor and an Inflammatory Swelling.-According to our definition, the most important histological difference between a tumor and a swelling caused

by infection consists in the fact that in the former the localized increase of tissue is the result of proliferation of embryonic cells (of pre- or postnatal origin) which are not utilized in the growth and development of the body or in the repair of injured or diseased parts, constituting thus a process entirely distinct and independent of the tissues in its immediate vicinity; while an inflammatory swelling results from tissueproliferation provoked by the action of pathogenic microbes or their toxines upon pre-existing mature tissue-cells. The incipient pathological product is therefore always more localized and better defined in tumorformation than in inflammatory affections. A benign tumor always remains local, tissue-growth being limited to the fixed primary matrix. A malignant tumor has a similar local origin, but it gives rise to dissemination by migration of cells into the adjacent tissues or by their transportation to distant parts through the lymphatic or general circulation. In the production of an inflammatory swelling the fixed tissue-cells which have been exposed to pathogenic microbes or to their toxines participate; the new cells produced mingle with the corpuscular elements of the blood, reaching the inflamed area through damaged capillary walls caused by the same agents, and constituting with the transudation the inflammatory product. Inflammatory affections lack from the very beginning the localized character of a true tumor. Progressive and often very speedy extension by continuity and contiguity of structure is one of the most conspicuous clinical features of inflammatory diseases as compared with tumor-formation, and the existence or absence of such manifestations is often of great importance to the surgeon in making a correct differential diagnosis between a tumor and an inflammatory swelling. Another important point in the early differentiation between a tumor and a swelling of infective origin is the durability of the new tissue-product. The tissue of which a tumor is composed is permanent. While in cases of progressive marasmus the subcutaneous fat disappears ultimately almost completely, a fatty tumor in such an individual remains unaffected, showing its independence from the general laws of nutrition and waste that govern the body. A tumor never disappears except by removal or destruction. There is no authenticated record of spontaneous disappearance of a tumor or of disappearance of a tumor under any kind of internal medication. In all cases in which such a termination is said to have taken place we have instances in which an infective swelling was mistaken for a tumor. The growth of a tumor is usually progressive. Some of the benign tumors, such as neuroma and osteoma, reach a certain size, when further growth is spontaneously arrested. The nearer the tumor-elements resemble normal tissue, the greater the probability of spontaneous cessation of