Myxosarcomata at the State Institute Study Of

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 connective 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 connective 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 histological 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 considerable amount of necrosis, and this change never appears in the advancing 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 prominent and capillaries numerous, while existing cells readily take characteristic 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 myxomatous 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 myxomatous 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 tumors 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 occurrence. 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 neoplasms, 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 occasionally 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 connective-tissue cells. In a group of 51 patients with myxomatous tumors treated at the Institute, 8 only showed appreciable fat in the neoplasms.

FIG. 1. ADVANCINGEDQE OF A ~YXOSARCOMA,SHOWING MYXOMATOUS CHARACTER

Of these 8 neoplasms, 3 showed sufficient numbers of both adult and embryonic fat cells to be classed with the lipomyxosarcomas. The remaining 5 growths showed adult fat cells in comparatively small, number. If the myxomatous tissue were derived solely from fat cells, either embryonic or adult in type, it would seem that this derivation should be apparent in a much larger percentage of the tumors studied. While many pathologists have in the past insisted on so-called es- sential differences in the production of mucus in the myxoma and in the colloid or mucoid carcinoma, others have, rather guardedly at times, pointed to an analogy between these tumors of different type. Ewing in discussing the myxoma in his text on Neoplastic Diseases (p. 184) says: “Myxoma is to be sharply distinguished from epithelial tumora undergoing mucous degeneration. Here the mucus is a form of hyper- secretion, while in myxoma it is an integral part of the living tissue.” However in his discussion of the mucoid carcinoma of the breast (p. MYXOSARCOMATA 27 1

554) he states : “Much discussion has occurred regarding the source of the mucus. Its usual position outside of and surrounding compact groups of well preserved cells is not in accordance with an epithelial origin and has not been satisfactorily explained by those who maintain this orikin.” While it is true that in some cases of mucoid carcinoma one can see the production of mucus from the epithelial cells either in the form of secretion or as droplets of mucus in the protoplasm of the cell, it may be safely stated that in the majority of these tumors the presence of the mucus cannot be adequately explained on this basis. In these tumors the mucus is usually present in relatively large quantity and is apt to be most abundant at the periphery of the tumor, while the epithelial tumor cells themselves, if found at all, are situated in the

FIG.2. MYXOSARCOMA,SHOWING VASCULARITY OF THESE TUMORS central portions of the gelatinous mass. Furthermore, these epithelial ‘cells are usually not of the mucus-secreting type. Mucoid carcinomata are usually slow of development and produce large bulky tumors locally, involving surrounding structures by exten- sion. When removed surgically, they tend to recur promptly. Metas- tases are late, as a rule, and are frequently much more cellular than the parent growth. In fact, in the metastases the mucoid or gelatinous property may be entirely lost. In all of these respects the mucoid carcinoma exhibits a behavior clinically and developmentally analogous to the myxosarcoma. We are all familiar with the frequency of myxomatous tissue in the supporting stroma of the fibro-adenoma of the breast. In these tumors it is quite possible to make accurate histological study of the epithelial tissues entering into the structure of the neoplasm. Long tubular glands, often surrounding islands of con- 272 A. A. THIBAUDEAU AND L. 0. KRESS nective tissue, are lined with a single row of columnar epithelial cells placed in orderly array on an intact basement membrane. While these cells are of the secretory type, rarely does one find any evidence of mucus secretion within the lumen of the gland. The stroma, however,, often does contain a considerable amount of myxomatous tissue. It would seem, therefore, that the production of mucus in epithelial malignant neoplasms is not always dependent on the activities of epithelial cells. Moreover, the presence of mucus in a malignant neoplasm would seem to have definite effects on the growth, development, metastasis, and recurrence of the tumor. These effects are apparent in both epithelial and connective-tissue tumors and are in many respects analogous for both types of neoplasm.

FIG.3. GIANT-CELL FORMATIONIN A MYXOSARCOMA

According to some authorities, mucus is produced by fibroblastic cells; others insist that fat cells can produce mucus. Perhaps both are correct in their contention. If we assume that myxomatous tissue can be derived from different types of connective tissue, the various histological pictures presented are less difficult of explanation. Just what factors induce the production of mucus from normal tissues has not been definitely determined. In a serics of 51 patients presenting themselves at the Institute with myxomatous tumors, a surprisingly large percentage gave a history of injury, often severe, at the site of the subsequent appearance of the tumor. The injury frequently resulted in a small fibrous swelling which, after a period of months or years, suddenly took on rapid growth. In other patients the growth of the tumor started shortly after the accident and showed steady progress. Two theories might, therefore, be presented to account for the production of mucus: (1) a blocking, through injury, of normal drainage MYXOSARCOMATA 273 channels, lymph, and blood vessels, and a subsequent retention in the connective-tissue cells of waste products, and eventually the production of mucus; (2) direct injury to a group of connective-tissue cells with the immediate production of mucus. Neither, however, adequately explains the continued production of mucus in a large myxomatous tumor. We must, therefore, assume a fundamental and permanent change in the growth characteristics of some type of connective-tissue cell. This, in turn, can be explained oiily by (1) a basic instability in the cell, which allow~sit, on the proper stimulation, to revert to embryonic type, or (2) a special combination of circumstances under which a normal cell can produce mucus which, in turn, acts as a matrix in which the surrounding cells of mesoblastic origin may proliferate.

FIG.4. BONEFORMATION IN MYXOSARCOMA

Under. normal conditions, when the stimulation leading to the production of mucus ceases these cells should revert again to type. Rut certain cells of some individuals are apparently unable successfully to accomplish this reverse action and we may have the production of tumors ; the character of cell proliferation in this event determines the degree of malignancy. In a review of 51 myxomatous tumors in patients treated at the Institute, three distinct groups were identified. The histological find- ings in each group were as follows : (1) Mylr;ofibroma: This group, comprising 9 patients, included tumors of the jaw, pterygoid fossa, vocal cord, cheek, shoulder, scapula, forearm, and thigh. The histological picture showed moderate or small amounts of myxomatous tissue in which were p1aced;in rather orderly arrangement, connective-tissue cells of fibroblastic type. In all these 274 A. A. THIBAUDEAU AND L. C. KRESS cases the myxomatous areas carried numerous blood vessels and branch- ing capillaries. The more cellular portions of these tumors were made up of spindle-shaped cells laid down in orderly manner with an occa- sional regular mitotic figure. A few fat cells of adult type were observed in but one of these tumors. The invasive property of this group of tumors was rated as low or moderate in all but one. This tumor showed marked invasion of surrounding tissues, was more cellular than the others in the group, and also showed some giant cells. This patient, treated by radiation alone, is well for four years and a half. Necrosis was not found in any of the tumors in this group. All nine of the patients with tumors in this classification are well, for periods of from nine months to ten years and ten months.

FIG. 5. TYPICALMYXOSARCOMA, SHOWING VASCULARITY

(2) il4yzoZigosarcoma: Tumors falling in this classification are those carrying an appreciable number of adult or embryonal fat cells. Typi- cally, embryonal and adult fat cells are intimately associated with the myxomatous tissue and usually constitute the major portion of the cellular elements in this group. Their invasive property is usually moderate. Necrosis is not a prominent feature of this tumor, and giant cells are rarely seen. Mitoses are infrequent, but are observed in both embryonic fat cells and in fibroblasts. We have but 3 patients with tumors in this histological group. (3) My~osarcoma:The histological picture presented by this group of tumors shows many variations. Some of the tumors show a large proportion of mysomatous tissue ; others only small rnyxomatous areas. Spindle-shaped cells of various sizes are found in a majority of these neoplasms, though some tumors show only round cells in the cellular areas. Mitotic figures, some of which are irregular, are seen MYXOSARCOMATA 275 in appreciable numbers, while in some tumors they are very numerous. Giant cells of varying size with multiple nuclei are a prominent feature in many cases. As a group, these tumors exhibit marked invasive properties, while a few show necrosis in the cellular areas. Thirty- nine patients with tumors in this histological group were treated at the Jnstitute. An attempt was made to correlate the histological appearance of the growth with the clinical course of the disease, but we were unable to determine that any histological feature observed in our sec- tions could aid us in determining the degree of clinical malignancy. We did observe, however, that those tumors in which mitosis was most marked were as a rule most rapidly fatal. CLINICALOBSERVATIONS A careful clinical study was made of 51 patients afflicted with myxomatous tumors and treated at the Institute, including 42 myxosarcomata and 9 myxofibromata. For purposes of this clinical study the 3 cases of lipomyxosarcomata are included with the myxosarcomata, as they differed from them in no respect in their clinical course and in their response to treatment.

2Myx;osarcomata In this group we find a total of 42 patients, including the three patients having a large percentage of fat in myxomatous tissue. These tumors occur almost as frequently in the female as in the male, being found 20 times in the former and 22 times in the latter in this series. Nineteen patients, or 45.2 per cent, were between the ages of forty and sixty years when the tumor developed. Of the remainder, 15, or 35.7 per cent, showed tumor growth between the ages of one and forty years ; while in 8 the neoplasm appeared between the ages of sixty and eighty-three. It is apparent, therefore, that this disease is more prev- alent between the ages of forty and sixty, although the range of occurrence is wide, extending from one to eighty-three years. Duration of Lesion. before Treatment was Sought: While the history obtained from patients is often misleading, a consideration of the length of time the tumors had existed before application for treatment soon led to the conclusion that this factor had an important bearing on the clinical outcome. Thus in 17 patients, 40.47 per cent of all cases, the growth appeared within the year prior to admission. Of this group, 6 patients, approximately 35 per cent, are clinically well, without tumor, while 11, or 65 per cent, have died. A second group of 17 patients reported tumor present for from one to twelve years before seeking treatment. Of these patients only 3 are clinically well, 17.6 per cent, without tumors, while 11 are dead, and 3 are still alive but with tumor which does not respond to treatment. The third and last group con- sists of 8 patients whose tumors had existed for from twelve to forty- eight years before admission. Only one patient in this last group is clinically well, 12.5 per cent; 4, or 50 per cent, are dead; 2, or 25 276 A. A. THIBAUDEAU AND L. C. MRESS per cent, are still alive but with tumor active in spite of treatment; while one has been lost trace of. If we assume that the last mentioned patient is now dead, as seems likely, the percentage of fatal termina- tions in this group is approximately the same as in Groups l and 2. The history in 6 of the 8 cases in this third group stated that a qui- escent growth, existing for from fifteen to forty-eight years, had suddenly taken on active growth from six months to five years before the patient reported for treatment. No definite reason for this sudden activity could be determined in any case. It would seem, then, that the earlier these tumors are discovered and treated, the higher will be the percentage of clinical cures. Experience shows that it is likely that the patients who are alive with tumor will eventually succumb to

FIQ. 6. LIPOMYXOSARCOMA,SHOWING BOTH ADULT AND EMBRYONICPAT CELLS the disease ; it is improbable that any of them will obtain a clinical cure. The end-results for those patients who are clinically well will be discussed further under the results of therapy. Locatiort of Tumors: Myxosarcoma can occur in almost any part of the body. In this series the head and the lower extremities were the most common sites, with 12 tumors occurring in each of these locations. The upper extremities and buttocks were next, with 5 and 3 tumors respectively, while a tumor in the breast was found on 2 occasions. One patient had a tumor in the thigh and a second in the parotid region, the parotid tumor first appearing twelve years before admission and the tumor in the thigh five years later, or seven years prior to admission. In the remaining patients, the tumor was found once in each of the following regions : neck, chest wall, abdomen, uterus, kidney region, sacral region, and ovary. MYXOSARCOMATA 277 Previous Treatment: Most of the patients presenting themselves at the clinic have had previous treatment elsewhere. Only 9 of the 42 patients under consideration came to the Institute untreated. Treat- ment was varied, consisting of surgery, x-rays, Christian Science, chiro- practic, salves, and poultices. For the most part surgery had been the method of choice, 24 patients having been so treated in various parts of New York State, in both large and small cities. Single removal of the tumor had been previously performed on 15 patients, removal of the lesion and one recurrence was performed on 6 patients, primary removal and two recurrences on 2 patients, while one patient had seven kecurrences removed over a period of five years. Four patients received incomplete surgery, in which biopsy only was performed or in which the entire tumor was not removed. Only 2 of the 24 patients had received x-ray irradiation before admission, a rather surprising observation, since some of the cities in which these patients resided have excellent facilities for this type of treatment. The 3 remaining cases had received no adequate treatment. The fact that 9 patients had recurrences after surgery in hospitals other than our own bears out the point that these tumors do recur with this type of treatment, and that the results in other hospitals are the same as those experienced at this clinic. Recurrences: After surgical removal these tumors are prone to recur and, as was stated under previous treatment, the recurrence is sometimes multiple. Twenty-one patients suffered recurrences, 14 before admission and 7 after admission. The time elapsing between the recurrence and admission ranged from three weeks to thirteen years. Seven patients were admitted without demonstrable recurrence and later, during the course of the disease, had a recurrence. The time elapsing from admission to the discovery of the recurrence varied from eight months to three years and eleven months. Of the patients who developed recurrences, none have been well for a five-year period. Three are clinically well, two for three years and one for two years and four months, and another patient is alive but has tumor. It would seem that the chances for recovery after recurrence are not good. Recur- rence took place in 21 or exactly one-half of the 42 cases, one patient having had seven recurrences in five years, as previously stated. Metastuses: Metastases in myxosarcoma are quite common. It is probable that this report does not show as many cases of metastases as actually occurred, since the capacity of the clinic does not permit hospitalization until termination of the disease. An endeavor was made to follow up metastatic lesions by sending questionnaires to the patients and attending physicians, but replies were for the most part vague and the results of the enquiry unsatisfactory. However, of the 42 patients, 15 were definitely known to have metastases. Six of these had metastases before or upon admission, while in 9 they developed after admission and during treatment. In one of these patients there was some doubt as to whether or not metastasis was present. At .the time of death the attending physician reported a large mass in the 278 A. A. THIBAUDEAU AND L. C. KRESS pelvis; the primary tumor of the breast had been clinically cured for four years. The metastases in this group occurred in the abdomen (3), lurigs (Fj), liver (2), chest (3), spine (2), kidney (2), regional nodes (2), and scalp (1). Four patients upon death had a general sarcomatosis. All of the patients with metastases are dead with the exception of one who is alive three years since the metastatic growth was discovered and still has tumor. Therapy: Surgery and irradiation have been used in the attempted eradication of myxosarcoma and have been successful in several cases. Surgery followed by x-radiation is most frequently used. Of 22 patients who received this therapy, 9 are living and 13 are dead. x- radiation was given with the high-voltage 200 kv. machine. The dosage was fractional, being given for the most part on alternating days and over alternating areas, the tumor on each occasion receiving from 100 to 130 per cent of an erythema dose. An erythema being considered 100 per cent or 1200 r (tissue scattering), this dosage would be from 1200 to 1560 r. The x-radiation was given with 200 kv., at 8 or 30 ma., filter of 0.5 mm. Cu and 1. mm. A1 (effective wave length 0.16 A), dis- tance from 50 to 80 em., size of field from 8 x 10 to 27 X 27 em. Four patients were treated with surgery and radium packs, 3 with the 4-gram pack, the totals for each lesion being 5000, 3200 and 3440 r. The distances varied from 10 to 25 em.; the filter used was 1 mm. Pt and 1.5 mm. steel. The other patient was treated years ago with a radon pack, at a time when the output was measured not in roentgens but in millicurie hours. The average used in these cases was 11,000 to 23,630 me. hrs., depending on the number of fields. All of the patients thus treated died. X-ray alone was used three times, with the result that 2 patients died and one is still alive with the tumor. The combination of surgery, x-rays (as described above), and a radium tube (with 0.5 mm. brass and 0.5 mm. gold filtration, for a total of 150 me. hrs.) was given to 3 patients, who died. One patient was treated by surgery for a small lesion and later a tube of radon was applied for 150 me. hrs., resnlting in a clinical cure to date, a year and nine months after admission. Interstitial radiation by means of gold seeds and sheath needles containing radium was used, the dosage depending on the size of the growth. This type of radiation used alone on a small lesion on the cheek resulted in a clinical cure for over five years. Again it was used with radium tubes and surgery, resulting in a clinical cure for thirteen years. Interstitial radiation and 200 kv. x-rays were used on two patients, of whom one is alive with tumor and the other has been clinically well for six years. One patient received all of these types of therapy-surgery, radium packs, interstitial radiation and x-rays-but died in spite of this exten- sive treatment. Efind-results: Forty-one of the 42 patients received treatment, one refusing treatment and further observation. Ten, or 23.8 per cent, MYXOSARCOMATA 279 are clinically well: 1for less than a year, 3 for a year, 1for two years, 2 for three years, 1 for five years, 1 for six years, and 1 for thirteen years. Only 3, or 7 per cent, are clinically well for a five-year period or longer. While this type of tumor has not been considered very malignant, the end-results are not good, and it would seem, from its poor response to various combinations of therapy, that we must revise our opinions as to its degree of malignancy. This series has received adequate surgery by our own staff and by the surgeons who cared for the cases before we saw them, and the varied radiation has been sufficient for the period in which it was given. It is true, however, that radiation technic is constantly improving, and results in the future may be more encouraging. The lesions which remained well over five years were located in the nose, mouth, and cheek, and were small when discovered and treated. The locations of the tumors in the patients who are clinically well for less than five years, are mouth (3), buttocks (a),orbit (l), abdomen (l),arm (l), chest (l),and nose (1). None of those with tumors in the lower extremity is clinically well. The myxosarcomata about the head and face would thus seem to respond more favorably to treatment than tumors in other locations. There were 26 deaths, 61.9 per cent, and of these 16 occurred within one year after admission, the length of life being from ten days to ten months. Two patients succumbed at one to two years, 5 died after two years, 2 after four years, and one at seven years and five months. The majority of deaths, therefore, occurred during the first year, while only 3 of these patients lived more than two years and nine months. When this tumor does not respond to treatment, the length of life is short. Five patients are alive with tumor reduced but still present two to seven years after onset. Mycofib romata We present only a small group of patients with benign myxomatous tumor, 9 as compared to 42 in the malignant group. Again the number of males and females is almost equal, with 4 of the former and 5 of the latter. The age incidence shows a fairly even distribution between the decades from ten to seventy years. Two of the patients were between ten and twenty years of age, 3 were between thirty and forty, 1between forty and fifty, 2 between fifty and sixty, and 1 between sixty and seventy. The age of the lesions on admission were as follows: 6 under one year (from one week to ten months), one four years, one five years and one nineteen years. The majority of lesions were thus of short duration before treatment was sought. Only 3 patients received treatment before admission, consisting in each case in complete surgical removal. The remaining 6 received no treatment other than that rendered at the clinic. Five lesions occurred in the head (mouth 2, face 2, vocal cord 1); there were 3 in the upper extremities, and one in the thigh. To date none of these lesions has recurred nor have they metastasized. 280 A. A. THIBAUDEAU AND L. C. KRESS

Treatment: The treatment given at the clinic was less varied than it was for the malignant growths. Five patients received surgical treatment only, surgery and x-ray were given to 3 patients, and one received x-ray radiation alone. The x-ray dosage was slightly more than an erythema to the tumor or the tumor site, with factors as described earlier. Results: The results iii this group were very gratifying, in that all of these patients are alive and free from tumor: 2 less than one year, 1 over one year, 2 over three years, 1 over four years, and 1 each over seven, eight, and ten years, giving 3 five-year cures, or 33.3 per cent as compared to 7 per cent for the malignant group. Though this group is small when compared to the malignant group, the tumors were diag- nosed histologically before treatment, the histological diagnoses being taken from the files without correction or reclassification.

CONCLUSIONS 1. The occurrence of myxomatous tissue in a tumor is not an evidence of degeneration. 2. Myxomatous tissue is a derivative of connective tissue and can probably originate from the metaplasia of different types of connective tiasue. 3. The more malignant a myxomatous tumor, the more cellular it becomes. 4. Myxosarcoma is clinically a highly malignant tumor, responding only occasionally to recognized forms of therapy. 5. As a group the myxosarcomata are resistant to radiation therapy; some tumors, however, have responded admirably to this type of treatment. 6. Myxosarcoma is most apt to arise between the ages of forty and sixty years; it shows no special predilection for either sex. 7, The shorter the clinical duration of the tumor before treatment, the more satisfactory is the response to therapy. 8. Cases of myxosarcoma in which recurrences have occurred do not respond to treatment. 9. Widely disseminated metastasis occurs late in myxosarcoma. 10. Myxofibrorna is readily eradicated by appropriate therapy.

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