MYXOSARCOMATA WITHA REPORTON 51 CASESSTUDIED AT THE STATEINSTITUTE FOR THE STUDYOF MALIGNANTDISEASE, BUFFALO, NEW YORK A. A. THIBAUDEAU, M.B., AND L. C. KRESS, M.D., F.A.C.S. A perusal of modern texts on pathological anatomy gives us but little information on the subject of the myxosarcoma. A few sentences, or at most a short paragraph, usually suffice for description of this type of neoplasm, and the statements made are often misleading or more than usually vague. Yet during the past century a voluminous literature has been published on, and a vast amount of research devoted to, the myxomatous tumors. Early to attract the attention of pioneers in pathological anatomy, these neoplasms have, through succeeding generations, presented for solution problems which still remain un- solved. The fact that myxomatous or pseudomyxomatous tissue at times appears in many different types of tumor further complicates the study. Maximow makes the definite statement that mucous connec- tive tissue is not present in adult mammals, and continues: “It is found during the development of the embryo in many places of its body, as under the skin, and is a form of the common, loose, irregular con- nective tissue.” Early investigators made intensive studies of this type of tissue in the gelatinous matrix of the umbilical cord, Wharton’s jelly. Frey and others thought that they could demonstrate that the cord is composed of a cellular reservoir with anastomosing tubes on which could condense, in surrounding them, a system of channels, resulting from the condensation of the mucous substance. Thus each cell or branch would occupy the axis of a young connective tissue fiber which would completely enclose it. The interior of these channels would be filled with mucus, containing here and there some embryonic cells, destined later to form fat cells. This conception was valiantly contested by Renaut, who brought evidence to show that the mucin of the cord is not confined in canals or lymphatics, but that it is found in cords or strands of varying size, on which the connective-tissue cells are placed as plaques. He also showed that these connective-tissue cells, fibroblastic in type, did not form a complete sac for the mucin or jelly. It is quite probable that tLe apparent canalization of Wharton’s jelly, and the formation of strands in it, may have been due to the ireparation of tissue for microscopic study and did not represent actual conditions found during life. “The intercellular substance [of the cord] is soft, jelly-like, and homogeneous in fresh condition ; when fixed, it contains granules and fibrillar precipitates. It gives the reac- tion for mucin” (Maximow p. 94). 267 268 A. A. THIBAUDEAU AND L. C. KRESS While these observations are of interest from historical and histo- logical standpoints, they throw no light on the source of the myxomatous tissue itseIf. When we come to a consideration of the myxomatous tumors in adult tissues, this question still remains unanswered. Tho majority of writers on the subject have been content to attribute the myxomatous tissue to a mucoid or myxomatous degeneration of some form of connective tissue. Cruveilhier, one of the early writers on this subject, referred in this connection to “dQgQnQrescencesareo- laires.” Virchow, who in 1857 gave the first clear description of these tumors and of the lipomyxosarcoma, and who suggested the terms “Tumor mucosus-myxoma” and “Myxoma lipomatodes” to describe them, was rather noncommittal on this point, though he believed that fat developed from the mucus. More modern writers quite generally speak of the mucoid or myxomatous degeneration found in these tumors. This conception, however, does not take cognizance of important facts observed in a careful study of such neoplasms. The myxornatous portions are quite characteristically seen at the growing edge of the tumors, while the central portions tend to become more cellular. In most of the malignant growths, the infiltrating, advancing edge is the most cellular part of the tumor, while the deeper areas show the greatest evidence of cell degeneration. Furthermore, the myxosarcomas are usually sufficiently vascular to assure an adequate blood supply to all parts of the tumor, so that rapidity of growth in advance of blood supply cannot be used as an argument in favor of degeneration at the advanced edge. In the myxomatous tissue, small blood vessels and capillaries usually appear in great profusion, and because of the paucity of cells in these locations are readily demonstrable. In the second place, necrosis, when found, is observed in the more cellular parts of these tumors, in which areas vascularity is less. Ne- crotic and degenerated areas usually fail to show myxomatous tissue. Should myxomatous change represent a degeneration, we should nat- urally expect to find it most pronounced where other degenerative processes are prominent. But these tumors rarely show any consid- erable amount of necrosis, and this change never appears in the ad- vancing edge of the growth. In the necrotic portions, occurring in cellular areas, the histological architecture is usually maintained ; cell contours persist and nuclear outlines can be seen, but characteristic staining properties have been lost; blood vessels and capillaries are absent or obliterated. In myxomatous areas, blood vessels are promi- nent and capillaries numerous, while existing cells readily take char- acteristic stains. In the neoplasms studied, it has been rather universally observed that where metastasis or recurrence has occurred, the secondary or recurring growth has been more cellular than the original tumor and has shown much less myxomatous tissue. In many instances these metastases and recurrences showed practically no trace of the myxom- atous character of the parent growth. The more definite the estab- lishment of the tumor as a malignant neoplasm, the more cellular it MYXOSARCOMATA 269 tends to become. The clinical observation of the rapid recurrence of myxomatous tumors af tcr apparently complete removal of the primary growth also merits attention. The primary growth is often a well encapsulated tumor which can be removed irz foto with comparative ease. Prompt recurrence locally is the rule. If the myxomatous tissue represents a degeneration and if, as is usually observed, the myxom- atous portion is more definitely located just inside the capsule, we should not expect as regular nor as prompt a recurrence. But if myxomatous tissue be not a product of the degeneration of some type of pre-existing connective tissue, what is its source? Various explanations have been advanced. Of these, the two most commonly entertained are (1) derivation from embryonal rests of mucous tissue, and (2) metaplasia of existing connective tissue. (1) While the theory that tumors arise on the basis of embryonal rests must remain an intriguing one, few actual facts have been ad- duced to support it, if we make a possible exception of the mesoblastic tumors of the kidney. In embryonic life myxomatous tissue is particu- larly abundant just beneath the surface epithelium. Myxomatous tu- mors in adult life rarely are found in this exact location. They usually arise in the deeper layers of the connective tissue and in the fascia1 planes. The myxoliposarcomas are found in many locations where myxomatous tissue is not common even in embryonic life. Further- more, we have not been able to find reference to a single case of this type of tumor arising in the adult in the region of the umbilicus-a region where, because of the pure myxomatous character of Wharton’s jelly in the umbilical cord, we might reasonably expect such an oc- currence. A few cases of congenital myxoma and myxosarcoma in the umbilical cord are reported in the literature. Ewing, in a discussion of this subject, states that where a tumor develops directly from embryonal mucous tissue it may be called a primary myxoma, and that such tumors must be rare. For such tumors in this group as may develop from a metaplasia of other tissues he reserves the term “secondary myxomas. ” (2) Metaplasia has been suggested as a ’source of myxomatous tissue by a host of observers. It has been noted that pure myxomas are exceedingly rare in the adult. On the other hand, myxomatous tissue appears at times in practically every type of tumor arising in tissues developed from the mesoderm. We find it in different neo- plasms, intimately associated with fat, cartilage, bone, muscle, and other well differentiated connective-tissue derivatives. If the theory of metaplasia be accepted, we must agree that practically every type of differentiated adult connective tissue has the faculty of producing embryonic mucous connective tissue by metaplastic processes. The close association of fatty and myxomatous tissues in many of these neoplasms has been the cause of much speculation. Virchow, though he primarily held that fat developed from the mucous tissue, later partially reversed this decision, stating that the myxoma may occa- sionally arise from embryonal fat tissue. If Virchow is right in both 270 A. A. THIBAUDEAU AND L. C. KRESS ’ contentions, then the metaplastic process must be a reversible one, and if applicable in the case of fat tissue, should also hold in the cases of the other connective-tissue derivatives. Robertson, writing in 19-16 on the subject of “lipoma myxomatodes” made this statement: “Con- siderable controversy has arisen over whether the lipomatous portions [of these tumors] represent a fatty degeneration of the myxomatous or vice versa.” He himself regarded them as independent develop- ments of mesoblastic cells. Maximow believes that the fat cell is derived from the fibroblast. Forster, also, as far back as 1857, took issue with Virchow and insisted that fat cells were derived from con- nective-tissue cells. In a group of 51 patients with myxomatous tumors treated at the Institute, 8 only showed appreciable fat in the neoplasms.