XXVIII. SARCOMA.

It is less than fifty years since all malignant tumors were included under the one term "carcinoma." Johannes Mueller found and described in some malignant tumors spindle-shaped cells, but he regarded them as a variety of carcinoma-cells. A description of similar cells was later given by Valentin. Lebert in 1845 made these cells the basis for his fibroplastic tumor. In 1847, Virchow introduced the term sarcoma," and upon a histological basis separated from carcinoma a large group of malignant tumors. He asserted that the spindle-cells were not characteristic of sarcoma, and he called attention to the different forms of sarcoma-cells. He relied upon the relation of cells to the reticulum in making a differential diagnosis between carcinoma and sarcoma. He placed special stress upon the absence of a well-marked stroma and alveolar grouping of the cells. Follin called sarcoma plasmôme. Rindfleisch called attention to the histological resemblance of sarcoma to granuloma. By degrees pathologists were brought to admit that under the term "sarcoma" must be included all malignant tumors originating from tissue of mesoblastic origin. Carcinoma represents the malignant tumors of the tissues of epiblastic and hypoblastic origin. Sarcoma represents the malignant tumors of the tissues of mesoblastic origin. As the typical tumor-element of the former the embryonal epithelial cell is recognized; of the latter, the embryonal connective-tissue cell is the prototype.

Definition.-Sarcoma is an atypical proliferation of connective-tissue cells from a matrix of fibroblasts of congenital or post-natal origin. This definition acknowledges the connective tissue as the sole origin of sarcoma. Histological investigations have shown that sarcoma originating in the different parts and organs always begins in the connective tissue primarily, and that the other tissues are involved secondarily that is, by extension. Sarcoma springs from the subcutaneous or intermuscular connective tissue, fascia, submucous and subserous connective tissue, the neuroglia of the central nervous system, the lymphoid tissue, the periosteum, the marrow of bone, and the stroma of other tumors. Only the cartilage is exempt as a primary starting-point of sarcoma. The atypical proliferation of the connectivetissue cells is evidenced from the fact that the sarcoma-cells do not

reach maturity, and that they invade the adjacent tissues and very frequently give rise to metastasis. We have already shown, in connection with carcinoma, that mature normal cells never take an active part in the formation of a malignant tumor. The same remarks apply to the essential cause of sarcoma. The mature connective tissue is acted upon by microbic causes, and if these causes are not sufficiently intense in their action to destroy the tissue, it proliferates and forms granulation-tissue, of which the different infective swellings, the granulomata, are composed.

It is impossible to explain satisfactorily the origin of a tumor from pre-existing normal connective tissue without assuming the presence of a localized specific microbic cause. It is true that the different forms of sarcoma resemble more closely chronic inflammatory processes than does carcinoma, but we are not yet, and probably never will be, in possession of demonstrative proof of the microbic origin of sarcoma. We are therefore forced to conclude that sarcoma-tissue is produced from a matrix of embryonic connective-tissue cells of congenital or post-natal origin.

Of all tumors, sarcoma probably develops more frequently from a matrix of embryonic connective-tissue cells or fibroblasts than any other tumor. The matrix is composed of the same kind of cells as the matrix of fibroma, except that the cell-development was arrested at an earlier stage. The cells of a sarcoma as compared with those of a fibroma possess greater reproductive power, but do not reach the same degree of development, owing to a more imperfect specialization of the cells of which the matrix is composed. Every surgeon knows that trauma plays a more important rôle in the etiology of sarcoma than in that of carcinoma. The trauma in sarcoma not only acts as an exciting cause in stimulating a latent matrix to active proliferation, but it frequently produces at the same time the essential cause, a postnatal matrix of granulation-tissue. It would be difficult to explain satisfactorily in any other manner the frequent origin of sarcoma in inflammatory products and at the seat of a fracture. As the endothelial cells are only a modified form of connective-tissue cells, malignant endothelial tumors will be included among the sarcomata.

Histology and Histogenesis.-The presence of a reticulum in sarcoma was formerly denied. Ackermann and others have shown that a reticulum is always present. In some specimens the stroma is well marked; in others it is so fine that it is almost hidden by the tumorcells. Teasing preparations of hardened specimens shows the fibrillated structure best. Ackermann claims that the reticulum of sarcoma is the product of sarcoma-cells. Schwann asserted that embryonal

connective-tissue cells elongate and break up into fibrillæ until the cells are lost. His views were supported by Virchow, Danders, and Kölliker. Virchow denied that fibrillæ are produced by the breaking up of cells. Lücke and Rindfleisch were of the same opinion. The origin of normal connective tissue from a blastema was asserted by Bizzozero, Kollmann, Valentin, M. Schulze, and Bruecke. Ackermann studied fibrillation in spindle-celled sarcoma, and observed that fibrillæ were produced by splitting up of the protoplasm of the cells. The fibrillæ in sarcoma resemble the same structures in connective tissue. The reticular arrangement of the fibrillæ has been explained by union occurring between projections of different cells. The meshes of this reticulum become apparent when filled with fluid or cells. If the meshes are empty, they collapse. A jelly-like substance is always present in embryonal connective tissue, and is always found in the connective-tissue spaces. This substance, which is a mucin-serum, can be seen best around transverse sections of fibrillæ. In old portions of the tumor this material is scanty, as the fibrillæ become more compact by contraction. Cicatricial contraction does not occur from loss of substance, but from the disappearance of the intercellular substance. Many authors consider this substance, with the fibrillæ, as one body which constitutes the cement-substance. Bizzozero says the stroma of a sarcoma is either soft, amorphous, mucoid, or jelly-like, at times more compact and fibrillated.

The intercellular substance holds a relation to the question of the origin of fibrillæ. If the fibrillæ originate from the blastema, they form a part of the cement-substance; if they are a product of cells, they are derivatives of these structures, which would leave the mucinserum only as the proper cement-substance.

In sarcoma cell-proliferation takes place in the immediate vicinity of blood-vessels, and is controlled and influenced by them. Spindlecells are formed in the adventitia; these cells either cannot be distinguished from the cells of this part of the vessel-wall or they differ only in size. The cells either come in direct contact with the vessel-wall or are separated from it only by a gelatinous layer. The latter contains the sarcoma-cells, few in number, imbedded in a fine net-like groundsubstance, the wide meshes of which contain the mucin-serum. There grow into the tumor young buds of capillary vessels which have imperfect walls; the cells arrange themselves into minute cylinders, the centres of which correspond with new blood-vessels.

The intimate relations of the walls of new blood-vessels with the parenchyma of the tumor is the characteristic feature of sarcoma. As sarcoma, starting from a central point, extends almost equally in all directions,

the resulting tumor usually approaches a globular shape, unless at some points obstacles to its growth are presented. In organs where the structure is uniform throughout, as in the brain, tumors grow in a globular shape, while in organs presenting parallel arrangement of

FIG. 369. Sarcoma of skull, showing capillary vessels, the walls of which are composed in part of sarcoma-cells (Surgical Clinic, Rush Medical College, Chicago): a, delicate stroma of connective tissue; b, groups of small round cells; c, new capillary vessels.

the structures the tumor assumes an oblong shape, as is the case in muscles and long bones. In bone the tumor either destroys the bonetissue or pushes the compact layer before it. All these properties of the tumor indicate the presence of great tension, which can be referred to increased blood-pressure. This increased pressure can be explained readily in the case of sarcoma from the presence of numerous and dilated blood-vessels. In many cases the tumor is composed largely of new blood-vessels with the characteristic cells interposed between them. In the vascular variety of sarcoma the tumor differs from an angioma in the greater amount of tissue which exists between the vessels and in the greater firmness of this tissue. In fibro-sarcoma the vessels are scanty, but are gradually increased in size. The vessels in sarcoma remain patent in the cut surface, as in cases of papilloma.

The spindle-cells with a scanty intercellular substance constitute the walls of the new capillary blood-vessels, as was first shown by Waldeyer. In all capillary vessels the endothelial cells are preserved. In a new sarcomatous growth the vessels increase in size and are later pushed apart by the cellular elements. The walls are thin and remain thin, so that finally the lumina of the vessels appear to be surrounded by only a single layer of endothelial cells (Fig. 369, c). The circulation in the capillaries is active and the blood-pressure is considerable, and, as the walls are weak, the blood-pressure is communicated to the tissues of the tumor, in which event the tumor pulsates.

In all histological varieties of sarcoma the cells are characterized by the existence of a large nucleus, which in young tumors almost obscures the cell-protoplasm. In the spindle-cells the nucleus is centrally located (Fig. 370). The giant-cells are multinuclear (Fig.

FIG. 370.-Spindle-cells from sarcoma (after Lücke).

371). The cells vary greatly in size and shape, but a certain uniformity is observed in each tumor. The shape of the cell is not only greatly influenced by the structure of the mesoblastic tissue in which the tumor originates, but also by the cell-environments. The cells are often moulded into different shapes by pressure. The shape of the nucleus is determined by the shape of the cell. The nucleus is always clear, well-defined, and surrounded by a proper nuclear membrane. The contents of the nucleus vary according to the age of the cell. In young and rapid-growing sarcoma the contents are rich in chromatin; later the chromatin is diminished and there appears a beautiful network of chromatin threads that do not readily absorb staining material. One or two nucleoli which are deeply stained are always present. In young