«rALTH'lc\'E^N"clf|^SSi' HX64171167 RC646 .C67 Pri^iafy neoplasms ot RECAP .!^- PRIMARY NEOPLASMS OF THE LYMPHATIC GLANDS INCLUDING HODGKIN'S DISEASE By WILLIAM B. COLEY, M.D. NEW YORK RCfc^fe ^Lil CoUegc of ^^psiciang anb ^urgcong ILitirarp Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/primaryneoplasmsOOcole PRIMARY NEOPLASMS OF THE LYMPHATIC GLANDS INCLUDING HODGKIN'S DISEASE BY WILLIAM B. COLEY, M.D. NEW YORK Reprinted from The Transactions oj the American Surgical Association 1915 CONTENTS Diagnosis 4 Treatment 6 Hodgkin's Disease 8 Sarcoma of the Neck 15 Sarcoma of Tonsil and Neck 31 Sarcoma of Axillary Glands 46 Sarcoma of Inguinal Glands 53 Sarcoma of Retroperitoneal and Mesenteric Glands ... 56 Sarcoma of Mediastinal Glands 62 Borderline Cases with Clinical Diagnosis of Hodgkin's Disease, Microscopic Diagnosis of Sarcoma, or Vice Versa ... 63 Rare Types of Malignant Disease of the Lymphatic Glands: (a) Melanoma; (&) Carcinoma 82 Cases of Sarcoma of Lymphatic Glands Successfully Treated by other Surgeons with the Mixed Toxins (Coley) .... 112 Summary of Results 116 -118 Recurrence after Apparent Cure 119 Tables ■ 122-146 PRIMARY NEOPLASMS OF THE LYMPHATIC GLANDS INCLUDING HODGKIN'S DISEASE By WILLIAM B. COLEY, M.D. NEW YORK This paper is an attempt to add some further clinical data bearing upon primary tumors of the lymphatic glands, on the basis of a study of i68 cases personally observed. I scarcely need state that this group of neoplasms gives the most hopeless prognosis of any in the entire field of malignant tumors — hopeless not only from the stand-point of surgery, but also as regards x-ray and radium treatment. I should like to discuss the clinical diagnosis of neoplasms of the lymphatic glands if time and space permitted. I can merely say that while in many cases it is possible to make a correct diagnosis from clinical signs alone, together with the history of the case, rapidity of growth, and blood examinations; in most cases a positive early diagnosis cannot be made without a micro- scropic examination, and not always then. I do not believe there is much risk in an exploratory operation for the removal of enough tissue for a microscopic examination. In many of these cases the tumor is made up of a considerable number of more or less discrete glands, and one small gland can be taken out with little risk of producing generalization of the disease. The almost hopeless prognosis of the disease has been empha- sized by the paper of Fabian^ based upon the results of treat- ment in a large series of cases collected by him. "Operation," he emphatically declares, "can come into consideration only 1 Miinchener med. Wochenschr. , August 26, 1913, No. 34, p. 1876. 2 COLEY: NEOPLASMS OF THE LYMPHATIC GLANDS in such cases in which the site of the disease is isolated, a thing which it is often difficult to prove. It is furthermore necessary to exclude leukemia and pseudoleukemia by quantitative and and qualitative blood analysis, tuberculosis by Pirquet's and lues by a Wassermann reaction." He further holds that, in ^'iew of the extreme difficulty in making an early definite diagno- sis, it is essential to do an exploratory incision for the purpose of microscopic examination which in the majority of cases enables one to differentiate between lymphosarcoma and Hodg- kin's disease. "Clinically," he states, "these two conditions ma}' be deceptively similar, a circumstance which would not be of great importance were the treatment of the two lesions the same. This, however, is not the case. Operation, according to .our present knowledge, is contra-indicated in cases of malignant lymphoma even if localized in character. Numerous observa- tions ha\dng shown that in these cases, as in leukemia and pseudoleukemia, the most thorough excision often does not check the progress of the disease, but, on the contrary, causes more rapid proliferation." "On the basis of the collected experience up to the present time," Fabian states, "we must admit that surgical treatment in general has been most discouraging." He cites the exhaustive compilation of Dufhus. in 1895, comprising 22 cases of lympho- sarcoma of the neck and axilla observed at the Greifswald Clinic. Of these 3 were inoperable; 3 of the remaining 19 were operated upon by exploratory incision only; 6 of the cases treated by radical operation had a speedy recurrence; g left the cKnic well but in 4 of these a recurrence was soon observed; i patient was operated upon four times. No permanent cures are mentioned. The number of cases in which the appearance of the sar- coma in the cer^dcal glands is preceded by an attack of tonsillitis or sore throat, points very strongly to an infectious origin. One of the cases in my series, which I have given in some detail, also points very strongly toward an extrinsic and infec- " tious origin other than through the tonsil. In this case the patient cut her finger on a vase; a swelling in the axillary gland on the coley: neoplasms of the lymphatic glands 3 same side almost immediately appeared and developed into a rapidly growing sarcoma. Of course, in this case it is not pos- sible to prove tbe causative connection between the prick of the finger and the sarcoma; the latter may have been merely a coincidence, still in connection with the cervical cases following an infection in the tonsil it is certainly suggestive. There is much evidence pointing to a very close relationship between the groups of tumors at present designated as mahg- FiG. I. — Hodgkin's disease. nant tumors — sarcoma and carcinoma — and the group regarded as Hodgkin's disease. Indirect evidence of this close relationship is suggested by the recently published experimental work of Dr. Maude Slye, of Chicago, covering a period of ten years. She found that cancer was apparently hereditary in mice, and was able to produce a breed of mice in which practically every member of the family died of cancer. Aside from the question of heredity — -which is irrelevant to 4 coley: neoplasms of the lymphatic glands the topic under discussion — she found that all the different types of malignant disease were produced in these cancer families, one having carcinoma, another sarcoma, another epithelioma, I and still others Hodgkin's disease and lymphatic leukemia. Furthermore, these latter conditions she has never observed except in cancer families. To turn for the moment to the histological features in these different tumors of the lymphatic glands, we find there is great difference of opinion in characterizing the histological structures. In one of my cases, a tumor of the axillary glands was pro- nounced, in the original report, lymphosarcoma, and the same pathologist two years later described it as an endothehoma. Other specimens were pronounced round-celled sarcoma by one pathologist and Hodgkin's disease by another. This is a com- mon observation. Not infrequently have I received the following opinion : ''The tumor is certainly malignant, but whether sarcoma, or carcinoma, I am uncertain." The term "embryonal carci- noma," much used of late, is being more and more frequently employed to describe some of these border-line cases. Herein lies the great significance of the study of primary neoplasms of the lymphatic glands. This study leads one to pay less and less heed to the finer histological distinctions, the ''judicial niceties" of the microscopic examination in these cases — the interpretation of which is by no means clear — but rather to group the cases according to certain well-defined clinical fea- tures. Thus we have a group of the so-called Hodgkin's type of tumors, or neoplasms of the lymphatic glands, with fairly distinct clinical features, sufficiently characteristic in the ordi- nary case to make the diagnosis comparatively easy, namely: I. Enlarged glands, usually beginning (in the cervical region) on the one side, and soon involving those on the other side; freely movable; more or less discrete, skin not attached; mod- erately firm in consistence but not fluctuating, gradually followed by involvement of the axillary a^d inguinal glands, and not infrequently the spleen and liver; a blood picture which Bunt- coley: neoplasms of the lymphatic glands 5 ing and Yates believe to be peculiarly characteristic : a more or less rapid deterioration in general health, uniformly endingin death. 2. The ordinary type of round-celled sarcoma of the cervical glands, beginning as a single nodule, softer in consistence and more apt to infiltrate the surrounding tissue than in the Hodg- kin's type; may extend to the glands on the opposite side, but this is not usual in the early stages; more rapid increase in size; Fig. 2. — Lymphosarcoma. more frequently associated with pain; running a much more rapid course than the ordinary Hodgkin's and only infrequently causing general metastasis. It resembles Hodgkin's in the fatal prognosis. The differential diagnosis of this type of tumor from tuberculosis is not usually difficult, owing to its very rapid progress without any tendency to become caseous. Then we have a third group of cases designated ordinarily as lymphatic leukemia, which differs from the Hodgkin's very httle except in the blood picture. I beheve it is possible to regard 6 coley: neoplasms of the lymphatic glands this group of cases as closely allied to Hodgkin's, and perhaps a different stage of the same disease. A uniformly hopeless prog- nosis is common to each of these different groups. the treatment of primary sarcoma of the lymphatic GLANDS If the disease is discovered before more than a single gland has become involved it should be removed by surgical operation Fig. 3. — Lymphosarcoma of tonsil. and the patient put upon a prolonged course of treatment with the mixed toxins of erysipelas and Bacillus prodigiosus, in the hope of preventing a recurrence. If the disease is primary in the tonsil, and is discovered before the surrounding tissues have become markedly infiltrated, and before metastases have taken place in the glands of the neck, ■ the tonsil should be removed, and if the diagnosis is confirmed by microscopic examination, similar prophylactic toxin treatment should be instituted. coley: neoplasms of the lymphatic glands 7 One of the most remarkable cases of an. apparent cure is that in which a large tumor, a round-celled sarcoma, of the tonsil and cervical glands disappeared under seven weeks' treatment with the mixed toxins of erysipelas and Bacillus prodigiosus and the patient remained well for nearly seven years, when a similar trouble developed in the opposite tonsil and neck, and rapidly recurred after two operations. Following the recur- rence after the second operation the mixed toxins were used for Fig. 4. — Hodgkin's disease; rapid course. a short time with apparently little effect. The patient died two months later. Here it is fair to believe that the original tumor was completely cured and that the one in the opposite side was an entirely new development, not a recurrence of the original tumor. In many cases it is almost certain that operation, particularly incomplete operation, greatly increases the malignancy of the tumor and causes it to grow more rapidly than before. Hence^ 8 coley: neoplasms or the lymphatic glands I believe that "palliative operations," or partial operations, in this class of cases are contra-indicated. In view of the importance of establishing the correctness of the diagnosis, beyond question, I believe that a portion of tissue, preferably a- small isolated gland, sufficiently large to permit of microscopic examination, should be removed; this can be done in most cases without any material risk in the way of caus- ing metastasis or increasing the malignancy of the growth. The prognosis after x-ray treatment in these cases is not infrequently good as regards immediate result; but as Fabian states, and my own experience confirms, there have been no permanent cures from the x-rays in this group of cases. The same is true of radium. hodgkin's disease Assuming the correctness of the view which I have long held that Hodgkin's disease is a type of sarcoma, closely related, etiologically, I believe the same treatment should be applied to Hodgkin's disease as to sarcoma of the lymphatic glands. If the disease is discovered in the early stages, when only one or a few glands are involved, most extensive and radical removal, if possible, should be employed, always accompanied by enucleation of the tonsils, if enlarged, as they are the most probable source of primary infection. Inasmuch as operation alone is practically always followed by a recurrence of the disease, any hope of a cure must depend upon postoperative treatment. Yates and Bunting believe that long-continued x-ray treat- ment together with enucleation of the tonsil has apparently effected a cure in two cases, the patients having remained well upward of five years. It should be noted that in both of these cases the disease was attacked while in the very early stages, both having been sons of physicians, and the disease was recognized comparatively early. coley: neoplasms of the lymphatic glands 9 In one case, first treated in November, 1908, diagnosis con- firmed by microscopic diagnosis, tonsillectomy was followed by x-ray treatment and hygienic measures. In this case there were only a few enlarged bilateral cervical and axillary glands, with no involvement of abdominal glands, spleen, or liver. In December, 191 2, a few glands, smaller than peas, could be felt in the posterior triangle of the neck, but none in the groin. Fig. 5. — Clinical diagnosis was sarcoma of neck. Microscopic diagnosis was Hodgkin's disease. In January, 1914, six years after the beginning of the treatment, the patient was in excellent health; the blood picture was negative. In the other case of Yates and Bunting, ten years of age, there was slight enlargement of the glands in the axillae and groins; abdomen negative; blood picture positive Hodgkin's; axillary gland removed for diagnosis; pronounced Hodgkin's. In this case the disease was first noticed in December, 1909; 1910. lo coley: neoplasms of the lymphatic glands tonsillectomy, followed by x-yslj and hygienic treatment. Sep- tember, 1913: glandular condition about the same; a few slightly enlarged glands palpable. January 6, 1914: blood picture normal; glands quiescent. This patient was well at the last observation, made four years after the beginning of the treatment. Nearly everyone has observed very marked beneficial effects following the use of the x-rays in Hodgkin's disease in almost all Fig. 6. — Lymphosarcoma. its stages; but aside from the cases observed by Bunting and Yates, I believe there is not a single case on record of a cure by this agent; nor do I consider it proper to regard the two cases cited in their series as positive cures. It should be noted that in both of these cases they were dealing with in an early stage of the disease, and there was no evidence of involvement of the spleen or liver, such as was present in my cases treated with the toxins. coley: neoplasms of the lymphatic glands II My reasons for advocating the toxins in Hodgkin's disease are based upon the remarkable effects that I have observed in a number of such cases, particularly the two in which entire disappearance of the lesions occurred. The following two cases of Hodgkin's disease have been reported somewhat fully in my earlier papers: Fig. 7.— Case I. Hodgkin's disease. Entire disappearance of tumors in neck, oxilla, and groin. Return of liver and spleen to normal size. Under six weeks mixed toxins alone. Recurred in six months. Death in one year. Case I.^ — Hodgkin's disease: Clinical diagnosis confirmed by microscopic examination; entire disappearance of lymphatic and splenic enlargement under two months'' treatment with mixed toxins of erysipelas and Bacillus prodigiosus, without other treatment. G. K., aged twenty- four years; family history negative. This patient felt so entirely well that he refused any further 1 Further Evidence in Support of the Theory that Hodgkin's Disease is a Type of Sarcoma, Transactions of the American Surg. Assn., 1908. 12 coley: neoplasms of the lymphatic glands treatment, and left the hospital. He gained forty pounds in weight and remained in good condition for about seven months. Shortly after, all of his former symptoms returned, and the disease progressed rapidly, causing death in about six months; this proves the correctness of the diagnosis. The second case^ I believe to be so remarkable that I have decided to reproduce it in full. Fig. 8. — Hodgkin's disease. Fig. 9. — Lymphosarcoma of the neck. About thirty x-ray exposures before entering the hospital; no effect. Few treatments were given in hospital. Case II. — Advanced Hodgkin's disease successfully treated with the mixed toxins of erysipelas and Bacillus prodigiosus. The patient was treated, under my direction, by Dr. C. E. Preston, of Ottawa, Canada, one of my former house surgeons. G. M., aged nineteen years, was admitted to the Ottawa Hos- pital May 4, 1908, with a history of glandular sweUing beginning on one side of the neck and later involving both sides, of about one year's duration. There was gradual loss of weight and increasing anemia. The glands of the neck were greatly enlarged; 1 A Report of Recent Cases of Inoperable Sarcoma Treated with Mixed Toxins of Erysipelas and Bacillus Prodigiosus, Cancer Research Society, Buffalo, April 12, 1922, and Surgery, Gynecology and Obstetrics, August, 1911. coley: neoplasms of the lymphatic glands 13 the spleen was enlarged and palpable three-fourths of an inch below the margin of the ribs; the liver extended three inches below the border of the ribs; inguinal glands were moderately enlarged. Weight, 122 pounds. The diagnosis of Hodgkin's disease was made by all of the attending physicians and surgeons of the hospital and a hopeless prognosis was given. The mixed toxins were begun June i, the initial dose being one-fourth minim. This was gradually increased until July July 10, the maximum dose of twelve minims was reached. This caused a temperature of 103° and a rather severe chill. Fig. 10. — -Round- celled sarcoma of neck. Decreased three-quarters in one week, but later increased. Patient died four months later. Fig. II.— Round-celled sarcoma. The treatment was continued for three months, partly by the family physician. Examination on January i, 1909, showed the patient quite well, weight 145 pounds, with only a small gland in the right side of the neck. He had returned to his usual work. The toxins were discontinued. Reexamination on September 10, 1909, by the family physi- cian shows the patient in fine condition, all the glands have dis- appeared and he continues his hard work. Under date of April 6, 191 1, Dr. Preston stated that he had just examined the patient and found him in perfect condition. 14 coley: neoplasms of the lymphatic glands Under date of September i, 1915, Dr. R. E. Webster, of the County Carleton Genera] Hospital (Ottawa, Canada), writes that the patient at present is in perfect health seven years later. Glandular system is apparently normal. He further adds that, while no glands were removed, the case was a typical one of Hodgkin's disease; all the glandular symptoms were present. The patient was treated from June i to July 30 at the Ottowa Hospital, after, 1908, which the toxin treatment was carried on by the family physician at home. Fig. 12. — Pathological diagnosis was sarcoma, but clinical course was that of Hodgkin's disease. In spite of the absence of a microscopic examination there can be little doubt that the diagnosis of Hodgkin's disease was correct. All evidence of the disease disappeared under no other treat- ment than the toxins, and the patient has remained well for more than seven years after treatment. I believe this case comes nearer to being a permanent cure than any case thus far recorded. The more important cases of my series are given in consider- able detail, the entire number being reported in tabular form at the end of this paper. Some of the cases have been previously coley: neoplasms of the lymphatic glands 15 reported in the Transactions of the Third International Cancer Research Conference (Brussels, 1913), but inasmuch as this volume is likely to be found only in the larger Hbraries, and in order to make the paper complete, I have thought it wise to re- produce the histories of these cases either in full or in abstract, the most important feature being the addition of full data as to the subsequent progress in the cases that are still living. Fig. 13. — Hodgkin's disease I. SARCOMA OF THE NECK Case III. — Round-celled lymphosarcoma of the neck and supra- clavicular glands recurrent; inoperable. A. P., female, aged two years and ten months. Referred to me by Dr. E. J. McKnight, of Hartford, Conn., in March, 1902. Pri- mary tumor removed by Dr. McKnight at the Hartford Hospital on January 27, 1902. No examination of the specimen was made, but the tumor rapidly recurred and a second operation was done in March, 1902. The specimen removed at this time was exam- ined by Dr. W. R. Steiner, pathologist at the Hartford Hospital, who made the diagnosis of smaH round-celled sarcoma. The disease was considered too extensive for removal. The patient was first seen by me on March 8, 191 2, when I found a series of tumors extending from the clavicle to the mastoid bone on the right side; the submaxillary and axillary glands on the right side were also involved; the cKnical appearance of the disease i6 coley: neoplasms oe the lymphatic glands was typically sarcomatous. I advised the toxin treatment which was carried out by Dr. McKnight for about three months. Immediate improvement, followed by complete disappearance. Fig. 14. — Round-celled sarcoma of neck / Fig. 15. — Hodgkin's disease. Fig. 16. — Round-celled sarcoma of neck. In a letter dated June 9, 191 5, the patient states that she is well at present, over thirteen years afterward. This patient was also shown before the Congress of Clinical Surgeons of North America on November 12, 191 2, and before the Internationa] Congress of Surgery, April 12, 19 14. coley: neoplasms of the lymphatic glands 17 Case IV. — Round-celled sarcoma of the neck. F. W., male, aged fifty-eight years of age, referred to me by G. H. Gray, of Lynn, Massachusetts, December 21, 1908. Family history negative. Personal history: Two years before patient noticed a small painless tumor in the right cervical region. This grew slowly at first, but more rapidly later, and at the time of the first operation, November 24, 1908, by Dr. Gray, the tumor had reached the size of a small egg. It was found impossible to make a complete removal. At the time the patient came to me (December 21, 1908, there was a well- FiG. 17. -Round-celled sarcoma of neck. Fig. 18. — Round-celled sarcoma of the neck after one-third disappearance. marked recurrence, and the condition was inoperable. The patient was admitted to the general Memorial Hospital on the 25th of December, 1908, and received eleven treatments under my care. He was then advised to return to his home, and the treatments were continued by Dr. Gray. He had 82 injections altogether, the highest dose being 5 and 4.5 minims; the tem- perature ranging between 99.5° and 100°. At the end of six months the toxins were given but once a week. The treatment was continued for nearly a year altogether. Examination, November 11, 1909, nearly a year after the treatment was i8 coley: neoplasms or the lymphatic glands begun, showed a three-inch cicatrix over the interior sterno mastoid region, soft, pHable, with no evidence of a tumor remain- ing. General health was perfect. In a letter received from Dr. Gray (dated April 9, 191 1) he states that the patient is well at present and in perfect general health, nearly two and one-half years later. October 9, 1913, Dr. Gray writes: "M. W. is alive and we]]." He remains well June, 1915, six and a half years later. Fig. 19. — Case IV. Inoperable recurrent sarcoma of neck. Entire dis- appearance under toxin treatment. Patient well at present, over three years later. Case V. — Small round-celled sarcoma of the neck. Entire dis- appearance under three months^ treatment with the mixed toxin. Patient well at present, six years later. P. K., male, aged forty-one years, heavy smoker. First noticed a lump in the submaxillary region in April, 1909. This grew rapidly, and by June had reached the size of a hen's egg. coley: neoplasms of the lymphatic glands 19 On June 11, 1909, the patient was admitted to the Roosevelt Hospital to the service of Dr. Charles H. Peck, who stated that he found a very vascular tumor which had invaded the periosteum of the lower jaw. There was also marked infiltration of the muscles and skin. Dr. Peck could not make a complete removal, and gave a hope- less prognosis. A microscopic examination was made by Dr. Fig. 20. — Melanotic sarcoma of neck (apparently primary in glands). Hodenpyl, the pathologist to the hospital, and he pronounced it a small, round-celled sarcoma, highly malignant. The patient was referred to me by Dr. Peck a few weeks after operation, for the toxin treatment, which was carried oiit under my direction by Dr. Lipset, the family physician. Shortly after the treatment was begun, the infiltrated area in the region of the cicatrix began to soften and recede, and at the end of three months it had entirely disappeared. The toxin was kept up in small doses, with intervals of rest, for one year. 20 coley: neoplasms of the lymphatic glands The patient was shown before the Congress of the Inter- national Surgical Association, New York, April, 1914, also before the Clinical conference at the General Memorial Hospital in March, 1915. He remains in good health without any trace of the disease, in July, 191 5, six years afterward. Fig. 21. — Hodgkin's disease. Case VI. — Sarcoma of neck. E. M., female, aged sixty years, referred to me by Dr. R. P. Sullivan, of Brooklyn, on May 13, 191 5, with the following history : Six months ago she first noticed a 4ump in the right side of the neck just behind the angle of the jaw. This slowly increased in size and by the end of April apparently involved the lower portion of the parotid. The glandular tumor below the jaw was removed on May i at St. Mary's Hospital; Brooklyn, and microscopic examination by the pathologist of the hospital showed it to be a spindle-celled sarcoma. Physical examination on May 13, 1915, showed a recent cicatrix, two inches long, just below the ear, and running along the margin of the jaw. There is some fulness or induration in the region of the cicatrix, as also a mass in the region of the right parotid gland, extending down into the neck itself. The tumor is firmly fixed. The patient entered the General Memo- rial Hospital and was immediately put upon the mixed toxins of erysipelas and Bacillus prodigiosus, without other treatment. COLEY: neoplasms of the lymphatic glands 21 She remained at the Hospital for three weeks receiving the toxins in gradually increasing doses from 0.5 to 6 minims; dur- ing this time she had five chills. The tumor slowly decreased in size and at the end of three weeks had apparently entirely disappeared. The toxins have been continued up to the present time, two to three times a week. August 20, 1915. There is no evidence of any return of the disease. Fig. 22, Case VII. — Recurrent sarcoma of glands of the neck; inoperable. Disappeared after use of toxins; well two and a half years (April, 1915). Clinical diagnosis: microscopic doubtful (very poor section). Case VII. — Round-celled sarcoma of the neck. Dr. P. V. In the early part of 1913, patient noticed a swelling in the neck, starting midway between the chin and thyroid; considered at first an inflammatory process by one, phlegmon by another physician. Operation by Dr. Russell S. Fowler, of Brooklyn, and after microscopic examination the disease was 22 coley: neoplasms of the lymphatic glands pronounced infective granuloma. Later it was pronounced round-celled sarcoma. Three sections were also submitted to Dr. William H. Welch, of Johns Hopkins, who stated that they were extremely unsatisfactory for study, the material having been allowed to dry and being poorly preserved, and that therefore he could not make a positive diagnosis; he added that round-celled sarcoma could not be excluded. Four weeks after the operation, a recurrence set in which grew rapidly, soon reaching the size of a fist, and extending from the mastoid to the clavicle. The case was considered inoperable by Dr. Fowler, who then started the toxin treatment, April lo, 1913. After five or six injections the tumor began to soften, and it opened sponta- neously, discharging necrotic material and gradually decreasing in size so that in the early part of May, Dr. Fowler regarded the trouble as practically cured, and he diminished the size of the dose of toxins. When he had gone back from 14.5 minims to 8.5 minims, the tumor began to increase again very rapidly, where- upon the doses were again increased. I first saw the patient on the 15th of May, and on physical examination found an old cicatrix two inches long, about an inch below the angle of the jaw, extending over to the chin. There were two recent cica- trices at the site of the old healed sinuses. In the anterior portion of the neck, beginning a little to the left of the median line and extending downward to the angle of the jaw, was a mass about two and a half inches in diameter laterally, very firm in consistence and much harder than ordinary sarcoma, more like carcinoma. There were several other smaller and discrete tumors in the cervical and supraclavicular regions. Skin adherent only in the region of the cicatrix, and not reddened. Tumor not attached to the trachea or thyroid cartilage. General condition good, but the patient had lost fifteen pounds in weight. I urged pushing the toxins to the limits of safety, and after in- creased doses his condition quickly showed signs of improve- ment. The improvement, continued, and when seen on July 17, 1913, the tumors in the cervical and submental regions had coley: neoplasms of the lymphatic glands 23 almost completely disappeared, and his general condition was good. The dose of the toxins had been carried up to 20 minims given in the pectoral region. Physical examination January 20, 1914, shows the neck entirely normal. There is no suspicion of any enlarged glands. The patient's weight has increased from 212 to 222 pounds. The patient has continued in good health up to the present time, December, 191 5. Fig. 23. — Case VIII. Angiopapillary endothelioma of neck. Specimen from exploratory operation. Case VIII. — Round-celled angiosarcoma of neck or adenocar- cinoma. Mr. K., aged forty- three years, was referred to me by Dr. J. A. Bodine, of the New York Polyclinic Hospital, on March 14, 191 1, with the following history: Fifteen months before, he first noticed a tumor in the left cervical region which increased in size and finally involved a num- 24 coley: neoplasms of the lymphatic glands ber of the glands in the cervical and supraclavicular regions. An attempt to remove the tumor had been made by Dr. Bodine at the Polyclinic Hospital two weeks previously, but the growth was found too extensive, and it was impossible to make a com- plete removal. The. patient was referred to me for treatment with the mixed toxins. At the time of his admission to the General Memorial Hospital he showed a recent cicatrix three inches long, just above the clavicle, extending up to the cervical Fig. 24. — Same case as Fig. 23. Papillary adenocarcinoma of neck (thyroid ?). Specimen from removal of most of tumor. Third operation. region, only partly healed; there was an irregular tumor, about two and a half inches in diameter, ulcerated in the centre, and several outlying tumors, more or less intimately connected with the main mass extending down to and beneath the clavicle. The tumor had every appearance of sarcoma. Dr. Bodine stated that the microscopic examination had shown the growth to be a round-celled sarcoma. Dr. Jeffries, stated it was an adenosarcoma. The patient was put upon the mixed toxins, the coley: neoplasms of the lymphatic glands 25 injections being made chiefly in the pectoral region, four to five times a week. At the end of one week there was decided improvement, the sluggish ulcerating surface had become nearly healed, the tumor had decreased in size and was more freely movable. The improvement continued steadily until in June all that remained was a small fibrous-feeling mass, about the size of a hazel-nut, just above the clavicle, anterior to the sternomastoid muscle. This was freely movable and could have been easily removed by operation. The patient has been steadily gaining in weight during the last four weeks. The highest dose of toxins given in this case was 7 minims, which usually was followed by a good reaction Physical examination, July 15, 191 1, showed only a small movable mass about three-fourths inch in diamete r, just above the clavicle, which felt more like fibrous tissue than a tumor. His general condition was excellent. The patient then left the hospital and I lost sight of him until June 21, 19 14, when he returned to me with the following history: He stated that he had remained well until about two months before, when a local recurrence was noticed above the left clavicle; the tumor grew very rapidly with occasional hemorrhages and some ulceration. Physical examination showed a large tumor in the left cervi- cal and supraclavicular region, the size of a hen's egg, made up of nodules or less fused together. It is soft in consistence, with an ulcerating area in the centre which bleeds freely. General health fair. The tumor measured two and a half inches by four inches in diameter. There is some dulness over the midsternum, which would indicate involvement of the midsternal glands as well. The toxins were again started, most of the injections being made in the buttocks, although a few doses were given into the tumor itself. Growth continued, though not as rapidly as before; the tumor seemed fairly movable and it was decided to remove as much as possible by operation, which was done on At this time the tumor was the size of half an orange, and occu- pied the whole left supraclavicular region extending from the 26 coley: neoplasms of the lymphatic glands inner end of the clavicle nearly to the outer. It proved to be extremely vascular and extended down behind the clavicle and was found in intimate relationship with the pneumogastric nerve, common carotid artery and subclavian vein. It was dissected off from the carotid with difficulty. On separating the base of the tumor from the attachment below, the subclavian vein was apparently wounded and a hemorrhage ensued which it was difficult to control. One of the smaller nodules above the clavicle was removed for microscopic examination, and Dr. Ewing pronounced it a lymphangioma. The specimen was evidently too small to show the true nature of the tumor. The tumor extended beneath the clavicle and no attempt was made to remove it completely. The wound healed kindly and no^ further hemorrhage occurred. After he had recovered sufficiently, he was again put upon the mixed toxins, plus :r-rays. Up to the present time there is no apparent recurrence of the growth. The report of the microscopic examination of the large tumor, by Dr. Ewing, was adenocarcinoma.^ (Fig. 25.) Case IX. — Round-celled sarcoma of the glands of the neck. Successfully treated with the mixed toxins of erysipelas and Bacillus prodigiosus; well two years. H. W., male, aged fifty-five years. Patient had been in good health until the early part of May, 1913, when he noticed a small painless lump appear just under the jaw on the right side, in the region of the submaxillary glands. The nodule grew rapidly in size and was operated upon by Dr. Frederick B. Sweet, of Springfield, Mass., who found a tumor about the size of a pecan nut, which shelled out of its capsule like a pea from its pod. There was no infiltration of the surrounding tissues nor was the tumor attached to the bone. Microscopic examination proved the growth to be round-celled sarcoma. Shortly after the operation another gland developed beneath the right 1 November 15, 19 15. Examination' shows no local recurrence but during the past three weeks he has developed marked hoarseness, which is probably- due to mediastinal involvement. December 25, growing rapidly worse. Died January i, 1916. coley: neoplasms of the lymphatic glands 27 sternomastoid muscle. This was removed by operation, and found lying between the carotid and interna] jugular vein, about the size of a small cherry. A portion was removed and sent to Dr. Ewing, whose report reads: "June 12, 1 9 13. "The material shows a process which I should call lymphosarcoma. It is somewhat peculiar in that the cell type is not very typical, but mitotic figures are abundant and the structure of glands is obliterated. I assume that there is no leukemia." Fig. 25. — Case IX. Lymphosarcoma of neck; recurrence after three opera- tions; condition then inoperable. Entire disappearance and patient well for two and one-half years. Within a week of this operation a rather diffused swelling developed at the site of the incision. No attempt at removal was made for fear of injuring the facial nerve. Patient entered the General Memorial Hospital, June 5, 1913, for the mixed toxin treatment. The toxins were given in gradually increasing doses but no reactions were obtained until 8 minims had been 28 coley: neoplasms oe the lymphatic glands reached. There was no temperature from the smaller doses, although they caused considerable depression. During the earlier period of the treatment two to three very small glands appeared at the site of the second operation over the carotid vessels. These grew slowly until they reached the size of a hazel-nut. After the first reaction was obtained there seemed to be no further increase in the size of these growths. Patient re- turned home July 26, and the toxins were continued by his family physician, Dr. Shores, three times a week in doses ranging from 7 to 9 minims. On my return from Europe, the end of August, patient came to me for examination and advice. I found that the glands in the neck had not increased any in size during my absence and that there was no return of the tumor in the sub- maxillary region, which had disappeared under the toxins. In order to lessen the severity of the treatment, and also in the hope of increasing the chances of controlling the disease, I decided to again operate and remove the tumors in the carotid region, for which purpose, patient reentered the hospital on Septem- ber 4, 1913. I found tumors very deeply placed about the caro- tid vessels, and removed three growths ranging from the size of a pecan to that of a hazel-nut. Microscopic examination showed them to be round-celled sarcoma. There were undoubtedly a few smaller growths situated higher up, which were not removed the wound was fulgurated for five minutes. The toxins were immediately resumed and the dose pushed to- 9 minims which gave a good reaction. On September 11, the patient left the hospital and returned home where the treatment was continued three times a week for two months, after which he received one week's respite. He came to see me on December 2, 1913, at which time I found his weight to have increased considerably, and the condition of his neck revealed no trace of the former tumor. The toxins were continued for upward of one year; total number of doses, 150; highest dose, 9 minims. Last examina- tion, November i, 191 5, shows no trace of recurrence; patient's general health excellent; weight normal. Well two and a half years. coley: neoplasms of the lymphatic glands 29 Case X. — Small round-celled sarcoma of neck. A. W., aged forty-nine years; admitted to my service at the New York Cancer Hospital in 1894; family history good. The patient had first noticed a small tumor just beneath the arigle of the jaw on the right side of the neck six months before; this grew very rapidly but was accompanied by little or no pain; it was associated with repeated attacks of quinsy. At the time when he entered the hospital, the tumor was the size of an orange, fixed to the deeper structures; the skin was not adherent. Under cocaine a portion of the tumor was removed for microscopic examination which showed it to be a small round celled sarcoma. The patient was put upon the mixed toxins of erysipelas and Bacillus prodigiosus, which caused very severe reactions. Very remarkable improvement followed the treat- ment; within one week the tumor was reduced from the size of an orange to a hen's egg and became freely movable; there was no sign of breaking down of the tumor. The injections were continued and pushed to the limit of tolerance. No further decrease in size followed however, and very shortly the tumor began to increase again and grew as rapidly as before, later involving the pharynx and tonsil. Whether or not the tumor was primary in the tonsil is not clear. The tumor in the neck was noticed before any increase in the size of the tonsil was noted. The patient died two weeks later. The entire duration of the disease in this case was only about eight months. Case XL — Small spindle-celled sarcoma of the cervical and supraclavicular glands and mediastinal glands held under control for nearly three years with the toxins. Final result, death. J. M., male, aged twenty-seven years, was referred to me by Dr. Edgerton in October, 191 1, with the following history: Four years ago he had glands removed from the neck at the Polyclinic Hospital, which were thought to be tubercular. The disease recurred and increased steadily in size and six months ago a second operation was performed by Dr. Edgerton at the New York Hospital. Microscopic examination of the glands removed from the neck and supraclavicular region showed the disease to be spindle-celled sarcoma. 30 coley: neoplasms of the lymphatic glands When the patient came to me in October, 191 1, he was put upon the mixed toxins in gradually increasing doses up to 8 minims, which were followed by rather severe reactions and con- siderable decrease in the size of the tumor. He left the hospital, and when I saw him again in March, 191 2, physical examina- tion showed him in good general health, except that he had a severe cough. There was marked fulness just above the supra sternal and supraclavicular region, especially on the left side. No distinct tumor could be felt, but a general infiltration of the tissues had taken place. There were several old cicatrices in the left supraclavicular region. He was also examined by Dr. W. L. Culbert, who found the left side of the larynx considerably encroached upon by the tumor. The toxines were given at irregular intervals, as the patient would not give up his work, and had to be treated as well as was possible as an out-patient, which made it impossible to give him doses large enough to produce good reactions. On January 13, 19 13, he was readmitted to my service at the General Memorial Hospital, where he was treated with subcutaneous and intravenous injections of the toxins, under which treatment the tumor showed some retrogres- sion. He received in all sixteen treatments, the highest dose being 7 minims, which was followed by a chill and temperature of 100.° He again left the hospital on February 8, 1913, after which the treatment was continued rather irregularly. In the spring of 19 14 he was taking the toxins only once or twice a week in small doses, as he did not wish the treatment to interfere with his occupation. During the summer the tumor showed slight increase in size and when the treatment was discontinued entirely during August and September, the increase became very pronounced. He was urged to return to the hos- pital for more systematic treatment, but failed to do so until November 18, when the tumor had reached considerable size and he had developed a hacking cough, due to pressure of the growth upon his trachea and mediastinum. Under two to three weeks' treatment the tumor above the clavicle, which was the size of a goose-egg, became softer and under ether an coley: neoplasms of the lymphatic glands 31 incision was made and a large amount of partially necrotic tumor tissue removed. The disease apparently extended beneath the clavicle and mediastinum and no radical operation was possible. Microscopic examination of the tissue was made by Dr. Ewing, whose report read: small spindle-celled sarcoma. The disease progressed with extreme rapidity, involving pleura and lungs and causing death one month later. II. — malignant tumors of tonsil and neck Case XII. — Inoperable spindle-celled sarcoma of the tonsil and nasopharynx {for full report see Medical Record, November 17, 1894). Male, aged thirteen years, had a rapidly growing tumor, starting apparently in the tonsil and extending up into the nasopharynx, seriously interfering with the patient's breathing. A portion of the tumor was removed and examined by a compe- tent pathologist, who pronounced it spindle-celled sarcoma. I saw the patient in consultation with Dr. Walter B. Johnson (Paterson, N. J.), in October, 1893, at which time the clinical appearance was that of an inoperable malignant tumor. The toxin treatment was started by me and later carried out under my direction, by Dr. Johnson. Under three months' treatment (local and systemic injections) the tumor entirely disappeared. He was examined by Dr. Johnson, June, 191 5, and found to be in good health twenty- two years after treatment. Case XIII. — Inoperable round-celled sarcoma of the tonsil and neck successfully treated with the mixed toxins. A. L., female, aged eleven years. Hartford, Conn. The patient was referred to me by Dr. William R. Porter, of Hartford, on November 8, 1906. The patient had always been in good health, except that she had frequent attacks of tonsillitis. A year ago she had a small swelling in one of the glands on the right side of the neck. The mother does not know whether it entirely subsided or not. Two months ago she noticed considerable enlargement in this region, which increased rather rapidly. When examined 32 coley: neoplasms of the lymphatic glands by Dr. Porter in the latter part of October he discovered a large tumor, apparently originating in the right tonsil and nearly blocking up the pharynx. She was examined by Dr. McKnight and a number of other physicians in Hartford, and all considered the tumor inoperable. The patient was referred to me by Dr. Porter on November 8, 1906. Physical examination at this time showed a growth the size of half a hen's egg, 0I1 the right side of the neck, involving the pharynx wall and tonsil, nearly blocking up the passage. On the opposite side of the neck, just below the angle of the jaw, there is a tumor about the size of a small hen's egg, fairly movable, smooth in outline, fairly firm in con- sistence, skin not adherent. Diagnosis: round-celled sarcoma of tonsil and neck. The toxins were begun November 9, 1906, and continued with two or three intervals to rest, one of three weeks in duration, up to the middle of May, 1907, the patient receiving in all between eighty and ninety injections, nearly all of which were given in the pectoral region ; a few were given into the tumor of the neck, but none into the tonsil. After two or three weeks' treatment there was a marked softening of both neck and tonsil tumor. Examination in consultation with Dr. W. L. Culbert; the latter removed a portion of the tumor of the tonsil, and it was found that the central portion of the same had become entirely necrotic, and several drams of broken-down tumor tissue were curetted out. I also removed some tissues from the tumor of the neck, which also proved softened and necrotic in the centre. Both specimens were examined at the Loomis Laboratory by Drs. Tracy and Buxton, and both proved to be round-celled sarcoma. This patient was rather susceptible to the toxins, and was rarely able to stand more than 2 or 3 minims without a severe chill followed by a temperature of 103° to 105°. The highest temperature was 106°. In two months the tumor of the tonsil and the neck had entirely disappeared. Shortly afterward a new swelling devel- oped in the neck, about one inch higher up. This swelling per- sisted for a long time in spite of continued and severe treatment. coley: neoplasms of the lymphatic glands 33 She also developed a small glandular tumor on the other side of the neck beneath the sternomastoid muscle. In February, while taking the treament, she had a severe attack of herpes, involving the right pectoral region and entire right arm. This was extremely painful, and she was unable to take the treatment for about three weeks. In the early part of May there still remained some swelling in both sides of the neck, rather deeply seated, underneath the sternomastoid muscle, and I decided to explore under ether. I found the swelling consisted entirely of broken-down necrotic material which had not found an easy exit. Some of the tissues from both sides were sent to Dr. Tracy of the Loomis Laboratory, and microscopic examina- tion showed no evidence of sarcoma remaining. The wound quickly healed. The patient was shown before the Hartford Medical Society on May 27, 1907, apparently perfectly cured, and again before the Clinical Congress of Surgeons of North America, in November, 191 2, in good health. My last report was received in January, 1916. She is still well, eight and a half years later. Case XIV. — Small round-celled sarcoma of the tonsil and neck. Entire disappearance in seven weeks under treatment with the mixed toxins of erysipelas and Bacillus prodigiosus; recurrence in other tonsil and other side of neck seven years later. Very rapid growth; death in four months. H. M., male, aged thirty- two years. The patient was referred to me on October 17, 1905, by Dr. Arpad G. Gerster, of New York, as a case of inoperable sarcoma for toxin treatment, with a history of having noticed a swelling on the left side of the neck, just behind the sternomastoid muscle, in about the middle of August, 1905. At about the same time he also noticed an en- largement of his left tonsil; there was no pain at first, but as both tumors increased rapidly in size, they soon became painful . In the latter part of August, 1905, the patient was operated upon at St. Mark's Hospital by Dr. Carl Beck, who made an attempt to remove the tonsil tumor, as well as that of the neck; he found it impossible, however, to make a complete excision. X-ray as 34 coley: neoplasms of the lymphatic glands well as radium treatment was tried with little or no effect. On October 13, while under the care of Dr. Goldwater, at the New York Polyclinic, a portion of the tonsil tumor was removed and examined by Dr. F. M. Jeffries, director of the pathological laboratory of the New York Polyclinic, and also by the patho- logist of the Practitioners' Laboratory, both of whom reported the tumor to be a small round-celled sarcoma (see pathological reports below). I first saw the patient October 17, 1905, and found the left side of the neck occupied by a soft globular tumor, about the size of half an orange; it extended from the angle of Fig. 26. — Case XIV. Sarcoma of neck. the jaw in front to the mastoid process behind and downward nearly to the clavicle. Examination of the left tonsil showed it enlarged to two or three times its normal size. The patient's general health had been but little affected. He was admitted to the General Memorial Hospital in October 17, 1906, and immediately put upon the mixed toxins of erysipelas and Bacillus prodigiosus without any other treatment. Daily injections were given, alternately into the neck tumor direct, and into the pectoral region. The highest dose given was 7 minims; his temperature ranged between 99.5° and 103°. In less than a week there was decided decrease in the size of the tumors and coley: neoplasms of the lymphatic glands 35 increase in mobility. The diminution continued steadily until, at the end of six weeks, both the cervical and tonsil tumor had apparently entirely disappeared. The patient left the hospital at the end of seven weeks. The toxins were, however, continued twice a week for some time, as a prophylactic against recurrence. He remained in good health up to the fall of 191 1, and had been shown before various medical society meetings. At this time Fig. 27. — Case XIV. (Third operation, April, 1912.) there was a recurrence in the tonsil and neck, which was removed by Dr. Erdman, December, 191 1. Unfortunately the specimen was lost. The growth returned very rapidly, and in less than three weeks had becom^e larger than at the time of the last operation. In January 15, 191 2, the patient entered my service at the General Memorial Hospital where a very extensive opera- tion was performed by Dr. William A. Downes and myself. A mass about the size of an orange and several smaller masses above 36 coley: neoplasms of the lymphatic glands the clavicle were removed as well as the entire sternomastoid muscle. These tumors were carefully examined by Dr. Ewing, who pronounced them round-celled sarcoma. The patient made a good recovery, but refused to remain at the hospital for the toxin treatment, as I had advised. The latter was, therefore, carried out for a few weeks by his family physician, when the patient lost hope, and declined further treatment. The tumor grew with marked rapidity causing death within less than two months after the last operation. Pathological Reports, October 17, 1905: (i) "The neoplasm submitted has the character of round-celled sarcoma. The cells are a mixture of small and large. The tumor appears decidedly malignant, and has probably extended beyond local limits. Examination shows that the cells have invaded the bloodvessels, and could easily have been swept into the current. "(Signed) Peactitioners' Laboratory." (2) December 21, 1911: "Specimen consists of a mass of tissue removed from the tonsil. "Microscopic examination shows the following changes: "The tissue is irregularly covered externally by stratified squamous epithlium. The main volume of the tissue is made up of round cells, the nuclei of which show mitotic figures. These cells are closely packed together and show no attempt to reproduce the lymphoid follicles normally encountered in the tonsil. The cellular foci are definitely surrounded by connective tissue. "The diagnosis in this case rests between a sarcoma of the tonsil and a granuloma. From the histological appearance it is quite impossible to decide. "Blood from this patient fails to give a Wasserman reaction." "(Signed) Douglas Symmers, "Acting Pathologist to New York Hospital." coley: neoplasms of the lymphatic glands 37 Dr. James Ewing's report on the tumor removed by me on January 15, 1912, showed it to be undoubtedly a "round-celled sarcoma." (3) Pathological Report, dated April, 1912: "Sections show a diffuse growth of medium-sized round cells. Nuclei are moderately hyperchromatic ; mitoses are occasionally seen. No reticular stroma is visible but the tumor is infiltrating the muscular and fat tissues after the manner of a malignant growth. Diagnosis: Lymphosarcoma. "(Signed) James Ewing." Case XV. — Small round-celled sarcoma of the tonsil with exten- sive metastases on both sides of neck. Entire disappearance under toxin treatment. Recurrence one year later. Mr. C, aged forty- two years. Marked loss of weight; referred to me by Dr. T. J. Reardon, of Boston, May 29, 1906. Physical examination at this time showed a large tumor in the right tonsil nearly blocking up the pharynx; it had the typical clinical appearance of sarcoma ; metastases occupied both cervical regions extending down nearly to the clavicle; general condition mark- edly deteriorated. The prognosis seemed so hopeless, that no microscopic examination was made. The toxins were given into the pectoral region and pushed to extremely high doses, as much as 20 minims of the uniiltered preparation being given which were followed by severe reactions, the temperature rising to 104° to 105°. There was considerable decrease in the size of the tumors while he was in the hospital, but his general con- dition was bad and he continued to lose weight under the treat- ment, so that it was not considered wise to continue and after he had thirty-one injections he was sent home for an interval of rest. The improvement continued steadily after he left the hospital and at the end of four months the tumors of the tonsil and neck had entirely disappeared. The patient stated that he had taken some patent medicine for a time after he left the hospital. In June, 1907, a little over a year later, there was a recurrence in the right side of the neck, and he again returned 38 coley: neoplasms of the lymphatic glands to me. At this time there was a smooth globular swelling in the submaxillary region about the size of a small hen's egg, mod- erately soft in consistence and not very firmly attached. It had the typical clinical appearance of a sarcoma. I removed the tumor, and microscopic examination by Drs. B. H. Buxton and E. K. Dunham showed it to be a small round-celled sarcoma. The patient's general health was good. I advised resumption of the toxin treatment, but the patient refused and returned home. Other tumors quickly developed in the neck and grew with great rapidity, causing death within a year. This case, I believe, is of extreme importance, inasmuch as it shows that a tumor of high malignancy, the diagnosis of which was confirmed by the fatal issue, entirely disappeared together with the metastases under three months' treatment with the tox- ins. The subsequent recurrence with the diagnosis this time confirmed by microscopic examination removes all doubt of the nature of the primary tumor. Case XVI. — Lymphosarcoma of the tonsil with extensive metas- tases in the glands of the neck; complete disappearance under the toxins; later recurrence no longer controlled by the toxins; death; autopsy. Mr.W-, male, aged thirty-five years, a patient of Drs. McMullen and Stanton, Schenectady, N. Y., noticed a swelling of left tonsil late in November, 1909. A few weeks later he noticed an enlargement of the glands of the neck on the left side. The tumors grew with great rapidity, and in February, 1910, had become so extensive that the patient was sent to Dr. George W. Crile for operation, if he considered it feasible. Dr. Crile found a tumor nearly blocking up the pharynx, and the neck tumor so large that he did not beHeve it possible to do a radical operation, and at once put the patient upon the mixed toxins (Coley), prepared by Dr. Tracy, of the Huntington Cancer Research Fund. The patient was emaciated and in very bad general condition at the time the treatment was begun. At the end of two weeks there was a marked decrease in the size of the tumors. The patient's general condition has become worse. At coley: neoplasms of the lymphatic glands 39 the end of five weeks tbe tumors had nearly disappeared. In September the tonsil again enlarged to about twice its normal size. Sections examined by this showed the same histological picture as at the previous examination. Lymphosarcoma. He entered the Ellis Hospital on September 7, remaining until Sep- tember 28, during which time he received fifteen injections of the toxins, with a complete disappearance of the growth. In Sep- tember, 1 910, I examined him and there was no evidence of any tumor. During October he received eight injections; November, seven injections; December, seven injections; January, six in- jections. About January 18 the growth again appeared, involv- ing the tonsil and extending along the anterior pillar and along the palate anteriorly. The tonsil was about three times its normal size, no glandular involvement. During February he received nine injections; March, seven injections. While nearly all of the injections were made in the pectoral region, a few were made into the neck tumor itself, and one directly into the tonsil, causing a very decided local reaction, swelling of pharynx and cervical glands. A large slough of the upper part of the growth took place. Dr. McMullen stated the patient was getting the injections just as rapidly and in as large doses as his general condition permitted and that he "hoped to have the growth again cleared up in a short time." The ultimate result is still in doubt. In February, 191 1, the patient was referred to me for personal treatment by Drs. McMullen and Stanton; he remained under my care for four weeks, during which time the toxins, both filtered and unfiltered, were given intravenously, and caused severe reactions. Temporary improvement occurred, but later the toxins seemed to have little effect upon the tumor which gradually increased in size. The patient's general condition slowly deteriorated and he 'died on February 7, 191 2. I am indebted to Drs. McMullen and Stanton for the follow- ing very complete postmortem examination report, made by Dr. Kellert: "The right side of the neck is greatly enlarged by two tumor 40 coley: neoplasms or the lymphatic glands masses, the smaller one of which is approximately 5 cm. in diameter and is intimately associated with the inferior maxilla. The larger mass, approximately 10 cm. in diameter and of oval shape, is situated beneath and behind the above mass. From the smaller mass there extends two minute openings through the skin and from which there exudes a small amount of puri- form material. In the medium line beneath the larynx is an incision 4 cm. in length, at the lower end of which is a round opening i cm. in diameter which extends into the trachea. Over the sacral region are two small areas of ulceration. Edema of extremities is absent. Median incision made. "The organs of the neck were removed en masse and the tumor masses above described are seen to consist of a grayish- white, soft friable tissue involving the glands, which extend downward toward the clavicle. The glands are matted together and form one continuous mass. On cut section the tumor presents numerous irregular, yellowish white softened areas. The upper mass has a centre which is of a dark greenish color and communicates with the gland. The tissues surrounding the larynx are slightly edematous. The mucous membrane of the trachea, below the larynx, presents a reddened injected appear- ance. The tongue is negative." Dr. McMuUen adds: "The remarkable fact about the autopsy was that not a single metastasis was discovered anywhere outside of the chain of cervical glands which drained the tonsil. In spite of the long continued use of such large doses of the toxins there were no remarkable changes in either the heart, muscle, or kidneys." A microscopic examination was made by four pathologists, including Dr. Crile. Dr. Swing's report, dated January 22, 1913, reads as follows: "The material consists of a section of small portion of sub- cutaneous or submucous tumor nodule. The structure is that of lymphosarcoma. The proliferating cell is large, mononuclear with vesicular nucleus, granular acidophilic cell body. These are found diffusely scattered throughout the section. No giant coley: neoplasms of the lymphatic glands 41 cells; few traces of lymphocytes, some focal necrosis and some traces of reticular tissue. The cells are loosely packed and tlie general appearance recalls that of an infectious granuloma with excess of large round cells. The true neoplastic nature of the process, as of most lymphosarcomas, appears doubtful." This together with the autopsy report render the case par- ticularly complete and full of interest. Case XVII. — Round-celled sarcoma of tonsil with metastases in neck. Entire disappearance under toxin treatment; no recur- rence five years later. C. W., male, aged thirty-six years. Family history: Uncle died of cancer of leg. Patient's general health always good. Referred to me by Dr. Skeels, of St. Albans, Vermont, on May 26, 1910. He had smoked a great deal, but stopped smoking six weeks ago. He first noticed a swelling in the right tonsil two months ago; two weeks ago noticed an enlargement of the gland in the right side of the neck. He was treated by a throat specialist for some time, but the tumor increased steadily and rapidly. It had been pronounced an inoperable malignant tumor by four prominent surgeons of Montreal. Physical examination by me on May 26, 1910, showed the right tonsil enlarged to the size of an almond, ulcerated on its posterior surface. The tumor was very hard on palpation, resembling carcinoma rather than sarcoma; there was a hard, movable gland the size of an English walnut in the right cervical region, anteriorly to the sternomastoid muscle. The patient was admitted to the General Memorial Hospital and remained in the hospital for about six weeks. A portion of the tonsil was removed for microscopic examination, and pronounced round-celled sarcoma, by Dr. W. C. Clark, Pathol- ogist to the Hospital. The injections were practically all made into the pectoral region and doses ranged from 0.5 minim to 5 minims, with fairly severe reactions from the larger doses. The tumor in the neck first became softer and more movable; at the end of a week it began to decrease in size with final disappear- ance under four weeks' of further treatment. The tumor of the tonsil diminished more slowly but at the end of two or three 42 coley: neoplasms of the lymphatic glands months this, too, entirely disappeared. A letter from the patient's physician, dated March 19, 191 1, stated: "He is at present perfectly well; there is absolutely no sign of any growth in his tonsil; his recovery here is considered as almost miracu- lous." Later Notes: A letter received from the attending physician, Dr. E. J. Melville, under date of July 10, 1913, states: " There is no return of the tumor in Mr. W.'s case and no parti- cular change in his condition from what I reported to you six months ago. The tumor has not returned. In fact the tonsil and peritonsillar tissue is normal. His only ailment is a pro- gressive dementia^ probably caused by ischemia of the brain. ''This case is a complete cure, with no return to date." Under date of January 14, 1914, Dr. Melville writes: "There has been no return of the sarcoma of the tonsil, which disappeared under the toxin treatment four years ago. " Mr. W. is about the same as when I wrote you last, suffering from ischemia of certain areas of the brain, which causes a form of brain softening, and progressive dementia, of a mild idiotic type. This condition is probably due to arteriosclerosis, from which disease he has suffered for ten years. "His appetite and general physical condition have not mate- rially changed in the past two years." Last note, August 2, 1915, five years after treatment Dr. Melville writes Mr. W. has had no return of his sarcoma of tonsil, but his mind is still degenerating. Case XVIII. — Lymphosarcoma of tonsil and pharynx with metastases in the neck. Mr. C, aged forty-three years. Family history good; Wassermann negative. About a year ago he noticed enlarge- ment of the right tonsil, which increased in size from time to tinie for about six months. Removal of tonsils by Dr. Leonard at the St. Bartholomew Clinic. A local recurrence took place and grew rapidly until November, 19 14, when the growth filled nearly the entire pharynx. In December, 1914, a section of the original specimen removed was examined by Dr. Dickson, the coley: neoplasms of the lymphatic glands 43 pathologist of the Eye and Ear Infirmary, who pronounced it small round-celled sarcoma, which diagnosis was subsequently confirmed by Dr. James Ewing. On January 31, 191 5, the patient was admitted to the General Memorial Hospital. Physical examination at this time showed a tumor of the right tonsil, extending nearly over to the opposite pillar and blocking up Fig. 28. — Case XVIII. Inoperable lymphosarcoma of tonsil and neck. Nearly disappeared after two months' toxin treatment, but then increased slightly. Removed by operation and toxin treatment again given. Recurred ; marked improvement. Under radium and x-rays. Temporary; still under treatment, but getting worse. the whole pharynx and reaching up behind the soft palate, pushing the latter forward into the buccal cavity. The toxins were started at once, the injections being made in the pectoral region; the initial dose was 0.5 minim which was increased by 0.5 minim daily until 5 minims were reached, which produced a chill and moderate reaction. After three or four injections, marked diminution in the size of the tumor was noticed and 44 coley: neoplasms of the lymphatic glands there was less distress in swallowing. The tumor continued to decrease in size rapidly and two and a half weeks after the treatment was started, it was only about one-third its original size. He received from three to five injections a week, practic- ally all systemic and the highest dose given was 9 minims; he usually had one or two reactions a week. During Aprilthe tumor showed little change in size, but was considerably paler than before and much harder in consistence; it felt like fibrous tissue. Fig. 29. — Case XVIII. Lymphosarcoma of tonsil and neck; after toxins. There is increase in fibrous tissue. Dr. Welch's report on the slides sent him reads as follows: " March, 15 191 5. "The sections show along one edge lamin- ated, flat epithelium with many wandering cells. Beneath the epithelium is a thin ayer of rather dense fibrous tissue, here and there penetrated by the cells of the underlying neoplasm. There appears to be no ulceration. The rest of the sections is composed of a densely packed mass of cells belonging to the lymphocytic coley: neoplasms of the lymphatic glands 45 group. Many of these cells are ordinary lymphocytes, but the prevailing cells are larger with round and oval nuclei presenting a nuclear membrane and one or more nucleolar particles of chromatin. These latter cells have a fair amount of cytoplasm, but cellular outlines are indistinct. These larger cells I regard as of lympho cytic nature, rather than fibroblastic. There are no evidences of follicles or other architectural features of the tonsil. There are occasional strands or septa of connective tissue, but in general there is very little basement substance or tissue between the cells. Bloodvessels are recognizable, but do not appear to be abundant. Nuclear figures are numerous. "Diagnosis: lymphoblastoma. The tumor may also be called a round-celled sarcoma, although I consider its origin to be from lymphatic tissue. Remark: The tumor is histologically to be regarded as malignant." The toxins were continued four or five times a week until the middle of May, 191 5. There seemed to be no further decrease in the size of the tumor. Under ether an incision was made through the soft, palate, and a mass about the size of an English walnut was enucleated with the finger. Microscopic examina- tion made by Dr. Ewing showed it to be lymphosarcoma. A small gland, about the size of an olive was removed at the same time, and proved to be lymphosarcoma (see illustration of slides). The toxins were resumed after operation and continued until the middle of July. Examination at this time showed the general condition to be about the same. There was some thick- ening at the site of the incision, which was apparently only scar tissue. There has been no increase during the last month The patient left the hospital for a two weeks' vacation. On his return the small indurated area at the site where the tumor had been removed, had increased markedly in size, so that at this time there was a tumor about one inch in diameter, firm in consistence. The patient was again put upon the mixed toxins and at the end of two weeks the growth was apparently checked but had not noticeably decreased in size. He then had an application of 80 mg. of radium for eight hours. 46 coley: neoplasms of the lymphatic glands Under the combined treatment the tumor rapidly diminished in size, and soon there was scarcely more than an indurated edge at the site of the growth. Later Notes (October 12, 191 5). The improvement which followed the use of radium proved very temporary, and in spite of x-ray, radium, and toxin treatment, the primary tumor not only began to increase in size, but more and more of the cervical glands became involved; these were at first held in check by the ir-rays, but the disease gradually progressed, and at present there is little hope of further control. November 18, 191 5. Patient returned to the General Mem- orial Hospital this morning, and was shown at the cKnical conference. Four and one-half weeks previous he developed a severe attack of pneumonia; his temperature ranged to 104° and fell as low as 95° at the crisis. During this period, the glands on both sides of the neck which were remarkably enlarged entirely disappeared. Examinations this morning shows no evi- dence of a tumor in the tonsil or pharynx; no enlarged glands are palpable in the cervical region. It should be stated that he had radium treatment in the pharynx a few days before he developed pneumonia. Inasmuch as the enlarged glands devel- oped while he was receiving the radium treatment, and the disease had been only temporarily held in check by the a;-rays, it would seem a reasonable inference thatthe pneumonia infection was responsible in part at least for the disappearance of the glands. A week later, November 25, 1915, small recur- rence in tonsil again visible. January i, 1916, disease slowly progressing. III. — SARCOMA or axillary glands Case XIX. — Lymphosarcoma of axilla. Mrs. J. G., aged forty-five years. Family history good. In December, 1905, first noticed a lump in the left arm, which slowly increased in size until March, 1906, when it was removed by operation. The operation was regarded as incomplete. coley: neoplasms of the lymphatic glands 47 Microscopic examination was made by the pathologist of the West Pennsylvania Hospital, whose report reads: "The tumor is composed of small round cells of about the size and appearance of mononuclear leucocytes (sarcoma cells) with a moderate amount of intercellular substance and shows the reticulum and stroma formed by branching stellate forms, which is characteristic of lymphosarcoma." The patient was referred to me March 25, 1906, by Dr. K. I. Sanes, of Pittsburgh, Pa., who stated that the glandular tumor was adherent to the axillary vein; but it was impossible to state from examination whether or not the axillary vein itself was involved; I advised the use of the mixed toxins, which were started immediately and continued for a number of weeks by the family physician. Two years later (March 23, 1908) I received a letter from the patient's husband, which stated: "Mrs. G. is quite well. Has been troubled recently with some rheumatism and during summer had severe attack of bronchitis followed by intercostal neuralgia brought on by the coughing. On conval- escing partly, she went to Cape May for six weeks, and a specialist there, who treated her with electricity, stated that her condi- tion had nothing to do with her old trouble." In a letter received from the patient's husband, dated Jan- uary 20, 1914, he states: "Mrs. G. has never had a return of the trouble for which the toxin treatment was administered, and is now well after eight years." Case XX. — Lymphosarcoma of the axillary region. Mr. C. R., male, aged twenty-nine years. In the spring of 1910, the patient was operated upon by Dr. Samuel Robinson, of Bos- ton, for a tumor situated in the right axillary region. Microscopic examination showed the growth to be round-celled sarcoma. A second operation was performed by Dr. Robinson, on August 8, 191 1, for what was supposed to be a recurrent or metastatic tumor involving the right axillary glands. The portion removed was examined by Dr. Homer Wright, pathologist of the Massa- chusetts General Hospital, and pronounced lymphosarcoma. Two weeks later the patient was referred to me for toxin treat- 48 coley: neoplasms of the lymphatic glands ment. The injections were started by my associate, Dr. J. P. Hoguet, and later continued by the family physician until January, 191 2, at which time there was no trace of the tumor left. I made a careful examination of the patient in October, 1913, over two years after treatment was begun, and found him in good health, with no sign of a recurrence. The patient remains well at present, four years later. Case XXI. — Sarcoma of the axillary and cervical glands {Pos- sible Hodgkin's). E. F., male, aged thirty-five years. Family history negative. In August, 191 1, first noticed a swelHng in the right axillary region which continued to grow until at the end of eight months it had reached the size of a fetal head. First operation was performed by Dr. V. Gaudiani, of New York, in April, 191 2, at which time there were no traces of inflammatory trouble, the skin was movable and not adherent, and the tumor was not attached to the chest-wall. There were a few glands in the supraclavicular region; spleen not enlarged; no dulness in the mediastinum. Patient's general condition good. A few supra- clavicular nodules were left behind at the time the axillary tumor was removed. Anatomical examination showed glands of various sizes, easily detached one from the other, almost uni- form in arrangement, and markedly soft in consistence. Microscopic examination: Lymph cells seem to be a little enlarged in size with a prevalent type of eosinophiles cells, occasionally giant cells (not typical Langhans's cells); connec- tive-tissue hyperplastic with spaces of hyaline degeneration. The diagnosis of Hodgkin's disease was made by Dr. Ewing. It was regarded as sarcoma by Dr. Elser, and a third patholo- gist inclined to believe it tuberculous. After a few months (July, 191 2) Dr. Gaudiani removed the other few nodules, which meanwhile had become enlarged and painful. He found the anatomical condition a little changed, as a few glands were included in a periglandular inflammation and one of the nodules had a necrotic focus as large as a bean. Shortly after a few nodules appeared again in the neck and pec- toral region, which rapidly diminished under x-ray treatment. coley: neoplasms of the lymphatic glands 49 I first saw the patient in July, 19 13, at which time there was a mass about the size of a fist beneath the pectoral muscle; supraclavicular and cervical glands markedly enlarged. The toxins were then started by me at the Italian Hospital, and carried out by Dr. Guadiani under my direction. After a few weeks' treatment, on account of the marked local reactions which followed, the patient refused further treatment. He took a trip to Italy where he remained four months. On his return to New York he was examined by Dr. Gaudiani, who stated that he found the mass in the subclavicular and pectoral region as well as the gland in the supraclavicular region, to have entirely disappeared. This was on the side of the first operation. At the time of the last operation, Dr. Gaudiani states that he left a large mass behind. In the right carotid and left axillary regions, where no operation had been performed the glands showed some slight increase in size. He was then put upon aresenic treatment, which is still being used at the present time. On March 31, 191 5, Dr. Gaudiani writes that the patient's general health remains good. The tumors in the right axillary, sub- and supraclavicular regions where the disease started, disappeared under the toxin treatment, and there has been no sign of a recurrence since. The left axilla is now occupied by a tumor the size of a fist, connected with the lymph glands. Other lymph glands the size of an apple, occupy the right carotid region. Patient had several treatments with salvarsan, although he had a negative Wassermann reaction. The glands have all disappeared and he is now well, January 7, 1916. Case XXII. — Round-celled sarcoma of axilla. P. W., female, aged twenty-seven years, cut her hand on a flower vase in 1893, and wore a bandage for two weeks. During this time a small lump appeared in the axilla of the same side. This lump never disappeared and slowly increased in size. Two other lumps appeared later and finally the three lumps became fused into one. In May, 1895, the tumor had reached the size of a hen's egg. It continued to increase in size and in January, 1896, Dr. A. J. McCosh, of the Presbyterian Hospital found 50 coley: neoplasms of the lymphatic glands it impossible to remove the entire growth. The portion remain- ing increased rapidly in size and gradually the entire arm became swollen. The patient was referred to me in August, 1896. Physical examination at this time showed a tumor the size of a fist, occupying the right axillary region and extending backward, apparently involving the clavicle and a portion of the scapula. Anteriorly it reached to the border of the sternum; it was firmly adherent to the chest wall. The skin was a bluish-purple in color, and there was an area of ulceration three-fourths inch in diameter. Her general condition was fair. A few injections of the mixed toxins were given, but it was not considered wise to continue them. The case went on to a rapidly fatal termination. Case XXIII. — Lymphosarcoma or endothelioma of axilla recur- rent in groin. P. J. B., male, aged sixty-seven years, referred to me in January, 191 1, by Dr. Ferbert, of Los Angeles. Family history good; no tubercular history. Three years before had first noticed a small enlarged gland in the left axilla; this slowly increased in size. Four to five weeks before his admission to the hospital it began to grow very rapidly, doubling in size within a month. Physical examination on January 31, 191 1, showed a tumor in the left axilla two and a half by three incjies in diam- eter, made up of a number of more or less discrete, enlarged glands varying in size from a hazel-nut to a walnut, partially fused together, making one tumor mass. Operation was done on February i, under ether anesthesia. The tumor mass extended up to and beneath the clavicle, and removal was regarded as incomplete. Immediately after the operation the patient was put upon regular treatment with the mixed toxins of erysipelas and Bacillus prodigiosus which was kept up for three weeks at the hospital and later continued by Dr. Ferbert at Los Angeles. Microscopic examination of the tumor was made by Dr. James Ewing, whose report stated: "The tumor is a sarcoma of the lymph nodes." In a later report Dr. Ewing pronounced it ■endothelioma. Dr. W. C. Clarke, the pathologist at the General Memorial Hospital reported : "round-celled sarcoma." coley: neoplasms of the lymphatic glands 51 In a letter dated November 11, 191 2, Dr. Ferbert stated that the patient was still well. In September, 1913, he returned to to Dr. Ferbert with a recurrence underneath the pectoralis minor muscle, attached to the subclavian vein. This was removed and the toxins were resumed as a prophylactic. Most of the tumor was sent to me, and examination made by Dr. Ewing on January 29, 1914, proved it to be a true lymphosarcoma. The report adds: "It is composed of rather large cells quite different from the spurious lymphosarcomas which resemble Hodgkin's disease." In his last report, dated April 17, 191 5, Dr. Ferbert states: "On examination today I found no recurrence whatever." Case XXIV. — Fibrosarcoma or neurosarcoma primary in the right axilla. Mrs. W. D., aged thirty-three years, was referred to me by Dr. Fredericks. Downs, of Bridgeport, Conn., in September, 19 13, with the following history. Family history good. Ten years ago she noticed a small lump in the posterior portion of the right axilla, following slijortly after a blow received by striking the axilla against a door. The tumor was removed by Dr. Hy. Blodget, of Bridgeport, Conn. There was apparently no micro- scopic examination made at this time. Two years later there was a local recurrence just behind the original tumor involving the lower portion of the scapula. The patient consulted Dr. Downs who removed a portion of the scapula together with the tumor. Microscopic examination proved the disease sarcoma. She remained well for nearly two and a half years, when a second recurrence took place in the pectoral region on the same side just below the clavicle. A third operation was done by Dr. Downs who removed a portion of the fifth and sixth rib together with the tumor. There also was a hard, shghtly protuberant tumor mass above the clavicle which was not operated upon. A small sinus persisted after the operation. The patient then received a month's treatment with the mixed toxins, and a little later a second course of two months' duration, during which time the tumor above the clavicle entirely disappeared. In 52 coley: neoplasms oe the lymphatic glands November, 1910, she had an attack of pneumonia. Shortly afterward a tumor developed at the inner portion of the cica- trix in the pectoral region and grew rather rapidly until it had reached the size of a grapefruit, being quite five inches pro- tuberant. The patient states that this for a time diminished apparently spontaneously to about half its former size, accom- panied by marked falling-off in general health. Physical examination at the time of admission to the General Memorial Hospital on September 22, 19 13, showed in the middle of the right pectoral region, between the nipple and clavicle, a tumor markedly protuberant, the size of an orange, partly pedunculated with an attachment to the chest wall of not more than one-half the diameter of the tumor itself. The tumor was not covered by skin, reddish in color, of fungoid appearance, but there was very little exudate; it was appar- ently not highly vascular. There was also a hard tumor above the clavicle very firmly fixed. An ic-ray of the chest showed a large intrathoracic mass, apparently as large or larger than the extrathoracic tumor. In addition there was a tumor the size of a goose egg in the axillary region. Under ether anesthesia I removed the mass in the pectoral region flush with the chest wall, but no attempt was made to follow it into the thoracic cavity. There was some hemorrhage which was controlled by gauze dressing. The patient made a good recovery and was then put upon the mixed toxins of erysipelas and Bacillus pro- digiosus which were given up to the time she left the hospital in October, 191 3, and later continued at home by her local physician. When she returned to the hospital in May, 1914, she had gained twelve pounds in weight and there was no sign of a local recurrence. The axillary tumor which showed a tendency to infiltrate the surrounding tissues had become more movable and, under ether, I removed a mass the size of a hen's egg from the axillary region. The patient was again put upon the mixed toxins and returned to her home on June 18, 1914. Microscopic examination of the second tumor was made by Dr. Ewing, whose diagnosis was neurosarcoma. coley: neoplasms of the lymphatic glands 53 Physical examination of the patient on August i, 191 5, shows no return of the tumor of the chest wall, but a slight falling off in weight. The tumor above the clavicle is slightly larger. The toxins were resumed. IV. — SARCOMA OF INGUINAL GLANDS Case XXV. — Sarcoma of groin {clinical diagnosis). H. P., male, age seven years, was referred to me by Dr. E. P. Swasey, of New Britain, Conn., on November 8, 1910. No his- tory of tuberculosis or malignancy in the family. The patient received a kick in the right groin by another boy three months ago. A few days later a swelling appeared, which gradually increased in size until one month later it had reached the size of an egg. This was removed by Dr. Swasey. The specimen was not examined microscopically. The wound did not heal promptly and a gradual thickening of the surrounding tissues with involve- ment of the pelvic glands followed. Physical examination on November 8, 19 10, showed the patient apparently in good general health. Examination showed considerable swelling of the whole upper portion of the right thigh and inguinal region. Just above Poupart's ligament there were two incisions, one two inches the other two and a half inches long, showing no tendency to heal, filled with slug- gish, grayish granulations. Palpation above Poupart's liga- ment showed a hard mass, the size of an English walnut. The toxins were advised and the patient was admitted to my service at the Hospital for Ruptured and Crippled. The toxins were given for about one month by which time the tumor mass had become much smaller and softer and under ether curettement was carried out. The swelling of the leg gradually disappeared, and the wound promptly healed. On January 17, 1914, Dr. Swasey writes: "I saw the patient and take pleasure in reporting that he is in excellent health, over three years afterward." 54 coley: neoplasms oe the lymphatic glakds Case XXVI. — Sarcoma of the inguinal glands. E. C. B., male, aged twenty-one years, always well until January, 1908, when he was struck in the left groin by a lever. One week later he noticed a swelling at the point of injury. This increased steadily in size and in February 2, three weeks after the injury, was removed by Dr. Dudley Carlton, of Springfield, Mass. The microscopic examination was made by Dr. J. F. Butler, of Springfield, Mass., who pronounced it small, round-celled sarcoma. A recurrence took place shortly after- ward in the inguinal and iliac glands and the patient was referred to me for the toxin treatment. Physical examination, March 26, 1908, showed his general condition good. Examination of the left groin revealed enlargement of the inguinal and super- ficial ihac glands; skin was not adherent and there was no tenderness; the tumor was of moderately firm consistence. The patient entered my service at the General Memorial Hospital, where the toxin treatment was at once begun. The injections were made in the buttocks and continued for two weeks in doses ranging from 0.5 to 5 minims followed by well- marked reactions a temperature up to 104°. At the end of this time the tumors had almost completely disappeared and he was allowed to go home with the advice to have the toxins continued by his family physician. The treatment was carried out rather irregularly during the summer and in October of the same year, he returned to my service with evidence of a recurrence. The toxins were again administered for a period of three and a half weeks, partly into the tumor, and partly into the buttocks, with good reactions. He received nineteen injec- tions during this time. He was then sent home and urged to have the treatment continued for another three or four months. When last heard from (January, 19 14), six years after operation, he was in good health and free from recurrence. Case XXVII. — Lymphosarcoma primary in the inguinal region. Mrs. L. S., aged forty-seven years. Family history: one brother died of tuberculosis. On admission to the General Memorial Hospital, March, 1915, physical examination showed coley: neoplasms of the lymphatic glands 55 a multiple glandular enlargement. Microscopic diagnosis : lym- phosarcoma. Previous personal history negative ; patient had had diphtheria and measles when a child. Patient had always been in good healthy until two years ago, when she first noticed a movable glandular swelhng in both inguinal regions, which appeared apparently simultaneously. Shortly after she noticed several small nodules in the anterior aspect of both thighs, also of simultaneous appearance. One year later a nodule was excised and examined microscopically, pro- nounced sarcoma. She was then operated upon at the Fordham Hospital by Dr. Kenyon, one week later, at which time several glands the size of a fist were removed from the left cervical region. A few days later Dr. Kenyon again operated, removing several nodules from the right thigh. The patient returned home, and shortly after had an attack of vomiting, which lasted for two months. On November 19, 1914, x-ray treatment was begun and con- tinued once a week for about two months. Physical examination, upon admission to the General Mem- orial Hospital, March, 191 5, showed a mass in the left cervical region, consisting of two nodules (2 cm. in diameter), slightly tender and freely movable. No glands could be felt in the abdomen. The largest tumor, situated in the right inguinal region, measured 6 cm. in diameter; was flat on the surface and more deeply fixed than the other tumors. Three small nodules the size of a hickory nut were situated in the left thigh and four more in the right thigh. Knee-jerks exaggerated. The patient stated that she had had for some time what she char- acterized as "rheumatic or grip attacks" twice a week, accom- panied by muscular pains and general malaise. She had noticed that almost immediately after each one of these so-called "at- tacks of grip" a new nodule appeared. Blood test made showed: White-blood cells, 7500; polynuclears, 71 per cent.; eosino- philes, 4 per cent.; transitionals, 11 per cent.; lymphocytes, 3 per cent. A large amount of nuclears, 11 per cent. Wassermann negative. 56 coley: neoplasms of the lymphatic glands The toxins were begun April 10, in 0.5 minim doses and gradually increased up to 12 minims; she received in all twenty four injections while in the hospital. During the treatment the nodules became much smaller, and after leaving the hospital some of them entirely disappeared. The patient was again admitted to the General Memorial Hospital on October 9, 191 5, and stated that in the meantime nearly all of the nodules had entirely disappeared, but that a few weeks ago she began to have great pain in the back, and throughout the right iliac region. Physical examination at this time shows tenderness in the region between the scapula and the vertebral hne on the left side. An enlarged gland can be seen in the axilla, and there is dulness in the retroperitoneal region, over an area of two and a half inches. The inguinal glands are not enlarged, and no enlargement can be felt in the abdomen. In the right thigh there is some pain and tenderness, also in the sacral region; pelvic examination negative. The tumors that were present at the time of her first admission to the hospital have practically all disappeared. November 18. The patient's general condition has become worse, and there is evidence of spinal involvement. V. — sarcoma op retroperitoneal and mesenteric glands Case XXVIII. — Intra-abdominal lymphosarcoma, involving mesentery, mesenteric glands and portion of small intestine. Mrs. W., aged twenty-five years, was operated upon in Novem- ber, 1 9 13, by Dr. Wilham M. Conant, of the Massachusetts General Hospital, for an abdominal tumor. Exploratory opera- tion showed a tumor the size of a closed fist, occupying the posterior parietal part of the mesentery and a portion of the small intestine. It was so extensive that no attempt was made to remove it. A portion was excised for microscopic examina- tion, which was made by Dr. W. F. Whitney and Dr. A. C. Potter the former the pathologist of the Massachusetts General coley: neoplasms of the lymphatic glands 57 Hospital, the latter of the Harvard Medical School — who pro- nounced it round-celled sarcoma. In December, 1903 the patient was referred to me by Dr. Conant and I immediately put her upon the mixed toxins, giving five to six injections a week, also adding the number of :r-ray treatments. The tumor immediately began to decrease in size and at the end of four months it had entirely disappeared. At this time the patient developed a high temperature and acute abdominal symptom, pointing to a local peritonitis, due — as it proved — to a necrosed portion of the small intestine involved in the tumor. She was desperately ill and hope of life was abandoned for more than a week. Thereupon a fecal fistula developed and she slowly recovered her health. She ran irregular temperatures until the latter part of July, when the temperature fell to normal. The toxins were given for a considerable time after recovery by her family physician. Dr. William Wilson, of Pawtucket, R. I. In a letter received from Dr. Wilson, dated February 13, 1906, he stated that evidence of a return had appeared in the spring of 1905, as shown by accumulation of fluid in the peritoneal cavity. Dr. Conant was called in and estabhshed permanent drainage; at which time he discovered several retroperitoneal growths. The condition gradually became worse and the patient died a few months later. Case XXIX. — Round-celled sarcoma of mesentery and small intestine. J. B., physician, aged fifty-six years; noticed a rapidly growing tumor in the lower portion of the abdomen just above the bladder in the summer of 1904. Operation by Dr. J. S. Mixter in September, 1904, when the growth had reached the size of two fists. The disease was pronounced to be round-celled sarcoma, probably originating in the mesenteric glands. As all of the tumor could not be removed, the ic-rays plus mixed toxins of erysipelas and Bacillus prodigiosus were begun ten days after operation and continued for two months. The induration disappeared and the patient remained well until the spring of 1907, two and a half years, when a local recur- 58 coley: neoplasms of the lymphatic glands rence occurred in the lower portion of the abdomen. A central mass the size of two fists and several outlying smaller ones could be made out on palpation. The mixed toxins were again given by Dr. Mixter and the tumors diminished rapidly in size. During the month of May the size of the dose was reduced with the result that the tumor again began to increase. The patient was then placed under my care for six weeks but, on account of the severe local reactions following the injections, was unable to take more than 4 to 5 minims at a dose; he was further- more suffering from indigestion and had very little appetite, so that the treatment could not be pushed as far as desirable. Nevertheless, the disease was held in check until November, 1907, when a second operation was performed by Dr. Mixter, which, however, was a partial one only, although a portion of tumor weighing four and a half po\mds was removed. The patient made a good recovery and after two weeks the toxin treatment was resumed. His appetite improved greatly and on December 7 his general condition seemed better than for a year, he having gained twelve pounds since the operation. In view of the good condition Dr. Mixter believed it possible to remove the remaining portion of the tumor and performed a third operation which proved fatal, the patient dying from shock. Case XXX. — Sarcoma intra-abdominal involving omentum, mesentery of small intestine, and gall bladder. E. J., female, aged twenty-three years. In 1894 she began to have attacks of pain in the right hypochondriac region, which gradually became more frequent and severe, with depreciation of general health until finally she was confined to bed. August 16, 1894, exploratory operation by Dr. Willy Meyer of New York. A solid tumor was found apparently springing from the mesentery of the intestine and attached to omentum and gall- bladder. It was clearly inoperable and no attempt was made to remove it; a portion was excised for microscopic examina- tion and the abdomen closed. The examination of the piece removed was made by the pathologist of the German Hospital, Dr. F. Schwyzer, who pronounced it round-celled sarcoma. coley: neoplasms of the lymphatic glands 59 Early in 1894, as soon as the patient recovered from the operation. Dr. Meyer referred her to me for the toxin treatment. Palpation at this time showed and intra-abdominal mass beneath the cicatrix in the right hypochondrium, about four inches in diameter; the tumor was hard and fLxed. General condition good. Systemic treatment with the mixed toxins was begun, the injections being given alternately in the abdominal wall and buttocks. They were kept up, with occasional intervals of rest, until February 7, 1895, five months, with the result that the tumor gradually disappeared. The patient was in good health and free from recurrence, twelve years later since, which time I have lost sight of her. Case XXXI. — Inoperable spindle-celled sarcoma of the retro- peritoneal region and iliac fossa clinical diagnosis. Disappear- ance under the toxins. Well three and a half years later. J. G. K., male, aged twenty-five years. In December, 191 1, first noticed swelhng just above the crest of the ilium on the right side. This gradually increased in size but there was no pain; no swelling in leg ; slight loss of weight. The patient was referred to me, March 26, 191 2, by Dr. E. W. Hedges, of Plainfield, N. J., and Dr. John L. Erdman later pronounced the disease sar- coma and inoperable. Physical examination at this time showed a tumor behind the right inguinal and iliac region, extending down over the crest of the ilium, but not into Scarpa's triangle, and upward about three inches. It apparently had its origin in the retroperitoneal region or anterior surface of the ilium; the skin was not involved. The tumor was soft and semi- fluctuating with small areas almost nodular in character. Aspira- tion at various times showed only bloody serum. The patient had been examined by Dr. John L. Erdman, New York City, who believed the trouble to be of malignant nature and inoperable. He was admitted to Dr. Bull's Private Hospital where the treatment with the mixed toxins was started and continued for two months. At the end of four weeks the tumor became distinctly fluctuating, and under ether I made incision just above the upper part of the ilium, and evacuated 6o coley: neoplasms of the lymphatic glands several ounces of fluid, with a large amount of necrotic material resembling broken-down sarcoma. Although the material was too badly degenerated to make satisfactory section, Dr. Ewing's report states: "The sections show a process which is either very closely related to, or identical with, sarcoma. It is made up chiefly of granulation tissue, spindle cells and giant cells. Much of it is necrotic. The process shows no signs of tubercle." Although not entirely positive. Dr. Ewing's report, together with the chnical history, leaves little doubt, I think, as to the dia,gnosis. November i, 191 5. The patient is still in good health, but a small sinus persists.^ Case XXXII. — Sarcoma of the mesentery. Mrs. M., always in good health up to the beginning of Jan- uary, 1914, when she noticed a lump in the abdominal cavity. This continued to increase rapidly in size and was operated upon in April a mass the size of a child's head was removed. Microscopic examination showed it to be a spindle-celled sar- coma. This diagnosis was confirmed by Dr. S. T. Graves, of Chicago. The tumor promptly recurred, and in August, 1914, a similar growth of nearly the same size was removed. The tumor was found to be attached to the mesentery and the operation was re- garded as an incomplete one. The patient was referred to me for the toxin treatment and admitted to the General Memorial Hos- pital on September 15, 1914. The toxins were given chiefly in the buttocks, the initial dose being 0.5 minim; this was gradually carried up to 7 minims, which latter produced a temperature of 104.5°. During her stay in the hospital she received two :r-ray treatments, one on September 18, another on October 8. She left the hospital on October 12, and after that received three treatments a week at my office for two months, in doses not suffi- 1 The sinus was curetted by his family physician Nov. 16, 1915, and the tissue submitted to a pathologist who made the diagnosis of "Mild form of tuberculosis, based on guinea-pig inoculation." I do not regard this as any evidence that the original trouble was tuberculous. The clinical and microscopic evidence was strongly against it. coley: neoplasms of the lymphatic glands 6 1 cient to caused any marked reaction. No evidence of recurrence developed and the patient returned to her home in the Wesi, where she had the treatment continued by her local physician until August 15, 1915. Her general health has remained good and at the present time there is no evidence of a recurrence. The treatment has been discontinued. With reference to the histological classification of the tumor in this case, Dr. Graves stated: "Several of our best pathologists examined the specimens and confirmed my diagnosis of sarcoma, but we all agreed upon the point that from microscopic findings alone, without consideration of the clinical history and gross findings at opera- tions, there would be doubt as to whether the tumor was a fibroma of a malignant type." Dr. Wilham H. Welch's report on the case, made December 17, 1914, reads as follows: "The microscopic sections show a new growth composed of fibrillated connective tissue, fairly rich in cells and containing a good supply of bloodvessels. The cells appear mostly as fusiform and branching iibroblasts. The basement substance is for the most part rather delicately fibrillated even in places rather mucoid in character, but in some areas it is more coarsely fibrous. It appears to grow some time in a definite relation to the bloodvessels, but this is not everywhere noticeable. The cells are in good number, but hardly so abundant as to warrant the diagnosis of sarcoma, although the distinction is often a matter of individual opinion. There are no glandular elements in the section on lymphatic tissue, so that the origin of the tumor cannot be determined, other than that from connective tissue. Diagnosis: fibroma." Dr. James Ewing reported : "The tumor is a rather cellular myxomatous fibroma. Struct- ure suggests it to be of neural origin. Probably possesses only a local malignancy." 62 coley: neoplasms of the lymphatic glands VII. — SARCOMA OF MEDIASTINAL GLANDS Case XXXIII. — Sarcoma of the mediastinal glands. Clinical and x-ray diagnosis. G. B., male, aged fifty- three years, referred to me by Dr. G. R. Butler, of Brooklyn, on November 25, 1908, for what was believed to be a malignant tumor of the mediastinum. There was no family or personal history of tuberculosis; no history of syphilis. He had first noticed huskiness of voice fifteen months before, which gradually increased; some dyspnea, which slowly became more pronounced. Physical examination on November 25, 1908, showed dulness over the whole mediastinum; the abdomen was distended, some ascitic fluid being present. No swelling of feet and hands. General condition good; no loss of weight. Just above the clavicle and attached to the sterno- clavicular portion of the sternomastoid muscle there was a small, hard gland. No enlargement of thyroid. A careful :r-ray examination made by Dr. Charles Eastmond, of Brooklyn, on September 29, 1908, showed a large tumor occupying the mediastinal region. The patient was immediately put upon the mixed toxins which were given under my direction. A second ;r-ray examination made December 31, 1908, showed some diminution in the size of the tumor. The toxins were continued for one and a half years with occasional intervals of rest. X-ray examinations made from time to time showed a slow, but continued diminution in the size of the tumor with decrease in density,. Examination of the patient made March 13, 191 1, two and a half years afterward, showed his general condition perfectly normal; the hoarseness had remained about the same; the dulness had markedly decreased. X-ray examination showed a decrease in size and density of the tumor. When I last examined the patient, in the latter part of October, 1914, he was in good health, more than six years after the treat- ment was begun. coley: neoplasms of the lymphatic glands 63 The next group of cases illustrates the difficulties in render- ing a definite histological diagnosis in neoplasms of the lymphatic glands: Borderline Cases with Clinical Diagnosis of Hodgkin's Disease, Microscopic Diagnosis of Sarcoma, or Vice Versa Case XXXIV. — Small round-celled sarcoma of neck; clinically Hodgkin's disease. L. B. J., male, aged thirty-one years, clergyman, came under my care on June 22, 1908. Three years before he had noticed a lump in the neck on a Thursday, for which he consulted a physician on Friday, and by Saturday it had increased so much that he was unable to get on his collar. On the following Monday, February 7, 1905, or four days after he first noticed the swelling he consulted Dr. Tinker, of Ithaca, who did a complete block dissection a few days later, after which the patient remained free from trouble until November, 1907, when there was a local recurrence for which a secondary operation was done by Dr. Tinker. The patient's general health and strength became deteriorated and other glands appeared in the neck, axillae, and groins. In March, 1908, a third operation was done, fol- lowed immediately by daily x-rsLy treatment for ten weeks. Microscopic examination by Dr. Nicholson, of the Clifton Springs Sanatorium, showed the disease small round-celled sar- coma. On June 22, 1908, the patient was referred to me by Dr. Tinker. Physical examination at this time showed the patient markedly emaciated (his weight had fallen from one hundred and sixty pounds to one hundred and forty- three and a half pounds). There were very extensive scars in both sides of the neck and the supracla'vicular region. There were two to three small nodules the size of a pea in the cervical region, but no local recurrence; no glands in the axillae; slightly enlarged glands in the groin; spleen not enlarged, but liver markedly so; no ascites. Pulse, 140; temperature, normal. The glandular 64 coley: neoplasms of the lymphatic glands tumors had evidently been very markedly diminished by the previous x-ray treatment. The patient's general condition was so bad that it was not thought wise to give him the toxins. The disease progressed rapidly and he died on September i, 1908. The tumor in this case, while clinically Hodgkin's disease, was pronounced, microscopically, small round-celled sarcoma. Case XXXV. — Lymphosarcoma on neck, or Hodgkin's disease. E. J., son of the preceding case, aged seven and a half years. Personal history: Rather sickly since birth; had measles in Feb- ruary, 191 1, shortly after which enlarged glands were noticed in both sides of the neck; two months later similar enlargements ap- peared in both axillary and inguinal regions. One of the tumors was excised by Dr. Coultas, of Chatham, N. J., and pronounced sarcoma by the pathological department of the College of Phy- sicians and Surgeons. Upon my advice the patient was put upon the mixed toxin treatment which was carried out two or three times a week by Dr. Coultas, steady subsidence of the tumors following. At the end of three months an interval of rest was allowed, whereupon the glands began to enlarge again. The treatment was resumed and pushed to the point of producing rather severe reactions; the tumors soon began to decrease in size again and finally disappeared entirely. Physical examina- tion by me on June 10, 191 2, nearly one year after the beginning of the treatment, showed the patient in good physical condition ; no enlargement of glands was noticeable on inspection, but palpation showed in the right cervical region 5 very small nodules, beginning just above the clavicle behind the sterno- mastoid muscle, ranging in size from a buckshot to a pea. A similar condition was found on the left side, although the glands were smaller in size. Just behind the ear, over the mastoid, was a larger gland, about the size of a bean, not adherent to bone or skin. No glands could be felt in axillae or groins and there was no enlargement of spleen or liver. The patient remained in good health until the end of March 1914, when the glandular tumors seemed to be increasing in size and he was admitted to coley: neoplasms of the lymphatic glands 65 my service at the Hospital for Ruptured and Crippled. He was again put upon the mixed toxin treatment, receiving thirty- six injections in all between April i and July 18. One of the small glands was removed and examined by Dr. James Ewing, who found no evidence of malignancy. The pathological^ report at the Hospital for Ruptured and Crippled stated epithelio- sarcoma. Under the toxins the various glandular tumors again subsided, and the patient was discharged on July 18, 1914. In view of his very much hj^ertrophied tonsils, it was thought possible that the tonsils were the source of infection, and I referred him to the Manhattan Ear and Eye Hospital, where his tonsils were removed by Dr. Monroe. A very careful bacteriological and microscopic study was made by both Dr. Ewing at the Cornell Laboratory, and at the laboratory of the Manhattan Eye and Ear Hospital, and no diphtheroid bacilli were found, nor any evidence of malignancy. The boy was examined by Dr. William L. Culbert on July i, 191 5, and found in good health, four years after the treatment was begun now December 5, 1915. Here, again, we have a case of typical Hodgkin's disease, clinically, which was pronounced sarcoma on microscopic examination. Case XXXVI. — Lymphosarcoma of Neck, or Hodgkin's disease. Miss S. K., aged fifty-five years, was referred to me in Decem- ber, 1913, by Dr. Arpad G. Gerster, with the following history: A tumor was removed from the right side of her neck at Gouver- neur Hospital nine years before. In March, 1913, a second opera- tion was performed by Dr. Erdman for a local recurrence; the tumor removed weighed three-fourths pound, and was pronounced lymphosarcoma by the pathological department of Bellevue Hos- pital. The. tumor again recurred in the fall of 1913, and the patient was then referred to me by Dr. Gerster as an inoperable case. Physical examination at this time (December, 19 13) showed several tumors occupying the right cervical region between the mastoid and clavicle, varying in size from a hickory nut to a hen's egg. The tumors were smooth in outline, freely 66 coley: neoplasms of the lymphatic glands movable, more or less discrete; skin not adherent; consistence only moderately firm; no glands in either axilla or groin. No enlargement of spleen or liver. The patient was put upon the mixed toxins of erysipelas and Bacillus prodigiosus. She proved very susceptible, the highest dose given being 5 minims. After fifteen treatments, the tumors had diminished markedly in size and became more freely movable, so that I believed it wise Fig. 30. — Case XXXVI. Lymphosarcoma; one laboratory. Hodgkin's disease. (Ewing.) to attempt their removal by operation. This was done by my associate, Dr. William A. Downes, on January 15, 1914. Dr. Swing's report on the specimen, dated January 15, 1914, read: ''Typical Hodgkin's disease; granuloma; giant cells; hyaline and fibrin areas." The disease recurred shortly after the operation and grew more rapidly than before. She was then put upon a^-ray treat- ment, under which there was marked diminution in the size of coley: neoplasms of the lymphatic glands 67 the tumor which, however, proved temporary only. Her later history we have been unable to trace. Case XXXVII. — Lymphosarcoma of the neck, clinical diagnosis; microscopic examination; round-celled sarcoma, one report; atypical Hodgkin's disease, another. J. J. D., male, referred to me by Dr. William H. Bishop, on November 6, 1913, with a history of having had cirrhosis of Fig. 31. — Case XXXVII. One pathologist pronounced specimen round- celled sarcoma; another reported atypical Hodgkin-'s disease. liver five years ago accompanied by a severe attack of jaundice. Sixteen months ago he first noticed a small lump in the left cervical region just anterior to the sternomastoid muscle; no pain nor tenderness. The tumor slowly increased in size until October, 191 2, when he was operated upon by Dr. Bishop; no microscopic examination of the specimen was made at that time. In May, 19 13, there was a rapidly growing recurrent growth with involvement of the supraclavicular glands. A 68 coley: neoplasms of the lymphatic glands second extensive operation was performed by Dr. Bishop at the end of September, 1913. Two weeks later a recurrence was notice in the upper part of the scar, which grew rapidly in size in spite of x-ray treatment. On November 6, 1913, the patient was referred to me by Dr. Bishop for the toxin treatment. He had then just recov- ered from a recent attack of jaundice. The report of the micro- scopic examination made by Dr. Louis Heitzmann, of the tumor removed at the second operation, read: "Hypertrophy with lymphadenoma, changing into myxolymphosarcoma; small and large round cells." The toxins were given four to five times a week, and at first there was slight diminution in the size of the tumor; later, however, the treatment apparently had little effect. On Jan- uary 7, 1 9 14, a third and very radical operation was performed by Dr. Bishop (assisted by me) consisting in a complete block dissection of the cervical glands from mastoid to sternum. The largest mass was situated near the upper cervical region, just under the sternomastoid muscle and continued through another group of infiltrated glands which extended forward involving the submaxillary glands. The whole sternomastoid muscle was removed and all of the external fascia including about four inches of the internal jugular vein. The wound was fulgurated for eight minutes with the Keating-Hart apparatus. The toxins were resumed at the end of one week. The specimen removed at this operation was examined by Dr. James Ewing, who pronounced the disease (atypical) Hodgkin's disease. One month later in spite of continued toxin treatment, there was evidence of a local recurrence, forming more of an infiltration of the whole neck, than a distinct localized tumor. On April 20 there was a well-marked recurrence in the supra- clavicular and mid-cervical regions. A gland the size of a hazel- nut was palpable in the anterior cervical region, two inches above the clavicle on the right side and another mass on the left side. He was then given a trial with the mixed toxins of the Staphylococcus aureus and Bacillus prodigiosus under which coley: neoplasms of the lymphatic glands 69 treatment he showed some improvement at first. I then gave him the vaccine of the diphtheroid bacillus removed from another case of mine. There was steady decrease in the size of the tumors, and rehef from pain which had already become constant and rather severe; his weight also began to increase. The improvement was only temporary, however, and on May 9 it was thought best to discontinue the treatment. He "died suddenly, as a result of a cerebral hemorrhage, on June 8, 1914. Tne clinical features of the disease were characteristic of sarcoma rather than Hodgkin's. Case XXXVIII. — Lymphosarcoma of tonsil and neck with metastases in the abdomen (resembling a typical Hodgkins or leukemia) . J. Z., male, aged twenty-nine years. In the fall of 1913, during an attack of tonsillitis he noticed a swelling on the right side of the neck accompanied by some pain. The swelling subsided and returned three times. He entered the New York Hospital early in April, 19 14, and Dr. Eugene Pool removed one of the glands of the neck for microscopic examination. The patho- logical diagnosis made by Dr. Elser read: "probably lympho- sarcoma." The patient had lost about twenty pounds in weight. On April 30, Dr. Pool referred him to me for the toxin treatment. Physical examination at this time showed the whole right supraclavicular and cervical region occupied by a tumor about the size of two fists, extending nearly to the chin in front and the vertebral line behind; the skin was normal in appearance and the tumor smooth in outline; axillary and inguinal glands were enlarged. The left side was occupied by a similar mass which, however, was not so extensive as on the right side. A large tumor was found in the right tonsil. This was probably the primary growth, while the tumors of the neck were secondary. He was admitted to the General Memorial Hospital; weight on entrance was one hundred and twenty-eight pounds. Blood examinations showed on March 10, 1914: White-blood cells, 4800; polynuclears, 42 per cent.; mononuclears, 56 per cent.; eosinophiles, 2 per cent. 70 coley: neoplasms of the lymphatic glands April 29, 1 9 14: White-blood cells, 2000; hemoglobin, 50 per cent. May 24, 1914: White-blood cells, 4000; hemoglobin, 64 per cent.; polynuclears, 25 per cent.; mononuclears, 75 per cent. The patient was treated with the killed cultures of the Staphyl- ococcus aureus, of which he received nine doses, starting with I minim and carried up to 15 minims, which produced a tem- perature of 99° to 102.° This, however, had practically no effect upon the progress of the disease, and a few doses of the mixed toxins of erysipelas and Bacillus prodigiosus were given but were not carried up to the point of producing a moderate reaction. The patient's general condition failed so rapidly that no further treatment was tried. He continued to lose in flesh and strength, and died on June 18, 1914, about fifty days after he had entered the hospital, or eight months after the beginning of the disGiase. On May 21 a small gland was removed and examined by Dr. Ewing, who reported: "Lymph nodes. Various nodes show mild overgrowth of lymphocytes, resembling Hodgkin's but without giant cells. The proliferation is less active than in leukemia but much less active than in lymphosarcoma. In some nodes the vessels are very abundant. In others there is beginning fibrosis. "Spleen: Atrophy of lymphoid cells; much fibrosis. " Epicritical : This case unites some of the features of Hodg- kin's, pseudoleukemia, and leukemia. The lymph nodes are most like atypical Hodgkin's. The liver lesions are indistinguish- able from those of pseudoleukemia, and the excess of leukocytes in the vessels suggests that there was a terminal leukemia." This is one of the few cases in which it was possible to get a full autopsy, which was made by Dr. Ewing, whose report I believe will be of interest: Autopsy Report (June 19, 19 14). Body: Much emaciated, slightly jaundiced. Heart: There are three subpericardial fiat tumors along the anterior coronary artery. Heart otherwise normal. coley: neoplasms of the lymphatic glands 71 Lungs: Show intense congestion and edema of left lung. Fresh pleurisy over right lung. Bronchial lymph nodes rauch enlarged. Acute lobar pneumonia upper lobe, one metastatic nodule in central part. One supernumerary spleen. Spleen: Much enlarged 20 cm. by 10 cm. by 5 cm. Uniformly pale, congested, cellular. Liver: Moderately enlarged, slightly nutmeg on section. Lobules seem oversized. Kidneys: Left kidney much enlarged. Cortex thick, pale, markings indistinct. Right kidney missing and right ureter missing. Inguinal, lumbar, mesenteric, thoracic lymph nodes moderately enlarged. Stomach: Pale but normal. Bladder and Prostate: Normal. Rectum: Normal. Lower Peyer's patches normal. Region of mediastinum is seat of large firm tumor mass, continues with cervical tumors. Follicles at base of tongue slightly enlarged. Tumors of neck considerably compress trachea and bronchi. There is a recent x-ray burn and scar 6 cm. long above the clavicle, beneath which there is diffuse purulent inflammation of subcutaneous tissues. One cervical node shows diffuse casea- tion. The oldest most altered nodes appear in the right mid- cervical region close to the pharynx. Anatomical Diagnosis: Chronic caseous cervical lymph- adenitis. Lymphomata of thoracic and abdominal lymph node, axillary and inguinal nodes. Hyperplasia of spleen. Acute pneumonia. Liver: Portal canals are the seat of miliary and diffuse lymphomatoses. The capillaries contain many lymphocytes as in leukemia. Extensive pigmentation. Larynx : At the base of the laryngeal sinus is a deep necrotic ulcer of rather old standing, measuring 1.5 cm. Mediastinal tumor is composed of diffuse lymphomatosis with much fibrous tissue. Kidney is seat of miliary lymphomatosis. The bloodvessels are packed with lymphocytes; acute degeneration. 72 coley: neoplasms of the lymphatic glands Lungs: Necrotic bronchopneumonia. The clinical history of this case together with the autopsy findings illustrates how difficult it is to distinguish between lymphosarcoma and the conditions designated as pseudoleukemia and leukemia. Here I beheve we had to deal with a primary lymphosarcoma of the tonsil which later gave rise to secondary glandular metastases, resembling the lesions found in leukemia and pseudoleukemia. Case XXXIX. — Lymphosarcoma of the neck. J. J., female, aged twenty-five years. In November, 191 2, she first noticed slight disability of right hand; treated at Van- derbilt Clinic for four months. On February 17, 1913, she noticed a small nodule on the right side of the neck below the inferior maxilla. This grew very rapidly, and was excised at Roosevelt Hospital on April 19, 1913. The specimen was examined by the pathological department of the hospital, whose report dated April 8, 1913, reads as follows: "Simple lymphoma; further sections show numerous large epitheloid cells, some of which are multinucleated, also more eosinophiles ; the struma is not markedly increased, but is definite. This tumor has many of the characteristics of an infec- tious granuloma and is probably due to the early changes of Hodgkin's disease. Chronic lymphadenitis." The disease recurred in June, 19 13, and was accompanied by much pain. A second operation was performed at St. Luke's Hospital. The report of the microscopic examination made at this time (November 12, 1913) reads as follows: "Diagnosis: sarcoma of neck. The tumor tissue proper is formed by small round cells of lymphoid type, arranged loosely, which stain deeply. There is a delicate fibrous reticulum in which there are many thin-walled bloodvessels and numerous areas of adipose tissue. No giant or multinuclear cells are found. Where the cells invade the surrounding muscle, they lose their alveolar arrangement and lie scattered individually in the connective tissue." Again a recurrence took place and on September 23, 191 3, the coley: neoplasms of the lymphatic glands 73 patient was admitted to the General Memorial Hospital. Physi- cal examination at this time showed several large tumor masses occupying the whole right cervical region, some made up of more or less discrete glandular tumors, others apparently formed by fusing together of a number of smaller nodules. A mass was also felt in the abdomen, probably a retroperitoneal gland. Axillary and inguinal glands were slightly involved; no enlarge- ment of spleen or liver. Wassermann negative. Blood exami- nation showed the following: Leukocytes, 14,500; poly- nuclears, 88 per cent.; mononuclears, 10 per cent.; eosinophiles, 2 per cent. There were several pigmented areas and warts over the chest wall. The patient was put upon radium treatment and received seven applications between October 11 and November 20, varying in duration from sixteen to twenty hours. In spite of some local improvement, her general condition gradually became worse, later associated with nausea and vomiting; death oc- curred on December 14, 1913. This case is interesting from the different pathological report at different stages of the disease, as also from the comparatively short duration of life. Case XL. — Lymphosarcoma of the tonsil with metastasis in the neck; generalization of disease; diphtheroid bacillus found in glands. J. McA., male, aged twenty-six years. Family history: no tuberculosis, syphilis, or cancer. Personal history: Always in good health until July, 1913, when he noticed some difficulty in swallowing, and found that the right tonsil had become en- larged. A small lump appeared also at the angle of the jaw, right side, about the same time. Under local treatment, the patient believed that the swelling of the tonsil completely disappeared. Early in September, 1913, it again became en- larged and grew rather rapidly in size; the gland in the neck also increased in size. Tumor of the tonsil was removed in September, and the following month a local recurrence took place. In the beginning of October, 1913, a small gland appeared 74 coley: neoplasms of the lymphatic glands on the left side of the neck. On October 21, 1913, a specimen was removed from the tonsil and examined by the pathologist at Bellevue Hospital; who pronounced it lymphosarcoma. The patient was admitted to my service, at the General Mem- orial Hospital, on November 7, 19 13. Physical examination at that time showed a large tumor. of the right tonsil pushing the uvula to the left, and extending up behind the soft palate, The tumor was of rather firm consistence. On the right side of Fig. 32. — Case XL. Lymphosarcoma of tonsil and neck (Dr. Ewing and also Bellevue Hospital Laboratory). Pure culture of diphtheroid bacillus obtained from gland in neck. the neck was a large tumor, measuring six and a quarter inches by four inches in diameter, apparently made up of several large glands more or less closely fused together. Tumor markedly firm in consistence, skin normal in appearance. On the left side was a gland about the size of an English walnut, freely movable beneath the angle of the jaw. Axillary glands palpable; inguinal glands enlarged; no enlargement of spleen or liver. coley: neoplasms of the lymphatic glands 75 The patient was put upon the mixed toxins of erysipelas and Bacillus prodigiosus on November 8,1913, and from that time on until January 24, he received thirty-seven doses, the highest being 20 minims. Soon after the treatment was begun, there was marked decrease in size of both the tonsillar tumors and the tumors in the neck. The improvement was only temporary, however, and later on the tonsillar and neck tumors began to increase in size. On January 15, 1914, under ether anesthesia a large tumor of the right side was removed as completely as possible. The external carotid was tied and very extensive dissection of the neck was made by my associate, Dr. Downes. From the tumors removed, autogenous vaccine was made by Dr. Weil, and from February 10 to February 30, eight doses of vaccines were given. On February 7, three weeks after the operation, both sides of the neck were almost normal in appear- ance. There was still a large mass in the region of the right tonsil. February 23, the tonsillar tumor was much smaller, and the tumor of the neck showed considerable decrease in size, Soon after, however, the tumors again began to grow rapidly, and some killed cultures of the diphtheroid bacillus, which were found when the tumors were removed at the time of operation in January, were prepared by Dr. Torrey, of the Cornell Labora- tory, and treatment was started. The diphtheroid bacillus cultures were given on March 4, 13, 16, 20, during which period there was considerable diminution in the size of the tumors. This improvement also proved only temporary, and in the latter part of March, the tumors again began to increase rapidly in size. X-rays were then given for a number of weeks, by Dr. Holding, with marked temporary improvement. About four weeks later the disease started to progress more rapidly than ever before; evidence of metastasis developed, and the patient became much weaker. He died of exhaustion on June 14, 19 14 Autopsy Report (June 15, 19 14). Body: Very much emaciated. Large subcutaneous mass in left side of neck, also a large mass in region of right ear. Edema of legs especially left. Recent adhesion of right pleura. Large 76 coley: neoplasms oe the lymphatic glands tumor attached to right side of spinal column in pleural cavity, eroding bone. Glandular enlargement in upper dorsal region in front of spinal column. Large mass present in lumbar region in front of spinal column. Liver: Enlarged, normal appearance, no metastases. Heart: Pericardium normal. Size of heart normal. Valves normal. Multiple subpericardial flat metastases. Lungs: Uniformly congested. No metastases. One small bronchia] node invaded. Spleen: Moderately enlarged, deep red. One small pea-sized metp^stasis. Kidneys: Both kidneys extensively invaded by bulky, diffuse, circumscribed tumor mass. In one the main tumor mass is extrarenal and extracapcular. Invasion is from lower poles of kidney. Renal cortex thick, markings indistinct. Adrenals: Negative. Pancreas: Normal. Stomach: Shows twelve extensive, fiat, ulcerating, submucous infiltrations. Ileum shows many numerous fiat infiltrations, involving chiefly tips of valvulae. Mesenteric nodes all mod- erately enlarged. Bladder: Normal. Prostate: Normal. Mouth: Left side of base of tongue, tonsil, epiglottis, and pharynx is seat of old partly cicatrized ulcer, which connects with several large cervical lymph nodes. Testes : Palpate normally. Microscopic: Ulcer of pharynx, tongue, and epiglottis is backed by a large-celled lymphosarcoma, but the ulcer extends far beyond the limits of sarcoma, and may stand as a probable portal of entry of an infection. Kidney: Diffuse large-celled lymphosarcoma with extensive degeneration of tubule cells. Liver: Shows miliary abscesses about the central or hepatic veins. The intestinal lesions show lymphosarcoma in mucous and submucous coats. coley: neoplasms of the lymphatic glands 77 Spleen: Shows slight hypertrophy of Malpighian bodies with beginning lymphosarcoma. Stomach: Diffuse lymphomatosis of the mucosa and sub- mucosa lymph nodes. Thoracic lymph nodes show diffuse lymphosarcomatosis with fecaj necrosis. Lymph Nodes: Structure varies. Original tumor from neck showed large clear cells of endothelial type. Second neck tumor excised after toxins and ic-ray showed much necrosis and foci of large, round, atypical cells as in lymphosarcoma. Internal nodes at autopsy and metastases all show typical large or medium- cell lymphosarcoma. As the process became more active, the type of cell appears to have changed. Case XLI. — Lymphosarcoma of cervical glands resembling Hodgkin^s Disease. G. A. L., male, aged thirty-one years. Family history nega- tive! Father died of arteriosclerosis and interstitial nephritis; mother and five brothers alive and well; no history of any malignant growth on either side of the family. From 1903 to 1908, the patient has been somewhat subject to tonsillitis; he noticed that the submaxillary and cervical glands had a ten- dency to become swollen and painful at the times of these attacks but the swelling always subsided afterward. In 1906 a scantling fell from a distince of six to eight feet, one end striking him upon the neck. He always claimed that this particular spot became a hard and painful lump at the times of the tonsillar infections and subsided with the sore throat. In October, 1908, following an attack of tonsillitis, the usual disappearance on recovery did not take place. The lump continued to grow and was removed by his brother. Dr. G. E. Leavitt, of Yerington, Nevada. At this operation several small glands, in addition to the larger tumor, which was about the size of an English walnut, were rernoved. Two glands were examined by Dr. William Ophiils, of San Francisco, who reported: "Sections of both glands show a filling of lymph spaces with very large polygonal cells with large vesicular nuclei without intercellular substance. The dividing line between these cells 78 coley: neoplasms of the lymphatic glands and the adjoining tissue is quite sharp in many places, in other parts layers of epithelial cells are interposed between the large cells and the lymph adenoid tissue. There are also nodules and irregular areas of epithelioid cells. Some of these areas show central caseation. The centre of some of the nodules is formed by partly necrotic tumor tissue. Diagnosis: Lymphosarcoma of the cervical glands complicated with tuberculosis." Dr. James Ewing, of Cornell University Pathological Depart- ment, disagreed with the diagnosis of tuberculosis and reported endotheliomata. Early in November, 1908, when the patient came under my care, there were several recurrent enlarged glands in the right cervical region. He was immediately put upon the mixed toxins. At the end of six weeks the tumors had entirely dis- appeared and the patient returned home, where the treatment was continued with occasional intervals of rest. Following his return from New York to June i, 1909, his health was good and his weight remained stationary. Soon after the evidence of a recurrence became apparent. On January 20, 1910, the glands in the right inguinal and right cervical region were excised by Dr. Pickard, of Reno, Nevada. At this time pressure symptoms in the right leg had developed and irregular masses appeared above Poupart's ligament on both sides. Dr. Ophiils's report on the glands removed on January 20, 1910, read: "Section shows the same structure as found in specimen of October, 1908. Much new-formed dense fibrous tissue is encap- sulated in the lymph adenoid tissue. Largely in the region of the lymph spaces the rather badly defined masses of very large irregular cells with vrey large vesicular nuclei without inter- cellular substance. There are large necrotic areas in the centre of some groups of cells. In other places there are areas sur- rounded by epithelioid cells. Diagnosis: malignant lymphoma of cervical and inguinal lymph glands." The toxins were again tried with little or 110 effect; he con- tinued to lose weight rapidly. Later vaccines of various kinds were tried without avail. His abdomen gradually became coley: neoplasms of the lymphatic glands 79 filled with tumors which extended upward from Poupart's liga- ment on both sides. There were no signs of mediastinal involve- ment. Death occurred on November 5, 1910, just two years from the time I first saw the patient. Case XLII. — Sarcoma of the neck. Microscopic examination. Clinical diagnosis: Hodgkin^s disease. R. P., male, aged twelve years, was admitted to the General Memorial Hospital on June 11, 191 5 (referred to me by Dr. Howard Lilienthal) . The patient's father died at the age of thirty- nine years of pleurisy and consumption. No history of cancer in family. The patient had measles at the age of six years; other- wise nothing important in the personal history until nine weeks ago, when he noticed a small, movable, painless lump in the left axilla; since then has had occasional attacks of pain. Very soon after the lump was discovered, he began to have irregular fever which has continued up to the time of admission. He also had a slight cough. Operation four weeks ago at the Jewish Hospital in Brooklyn. Microscopic examination of the specimen removed showed the disease to be spindle- and round-celled sarcoma. Almost immediately after the operation similar glan- dular tumors were noticed on the left side of the neck and a few days later also on the right side. These increased in size rapidly and the patient's general health deteriorated. Physical examination at the time of admission to the General Memorial Hospital showed two large, nodular tumors on each side of the neck, extending from the mastoid above down to the middle of the sternomastoid muscle; tumor fairly mov- able; moderately firm in consistence; skin not adherent. The right submaxillary and submental glands are involved. There is no enlargement of spleen or liver; inguinal glands not en- larged. June 30: The patient has had irregular temperature since he entered the hospital, ranging between 101° to 104° during the first two weeks; he was then put upon x-ray treat- ment and the temperature has now returned to normal; the tumors of the neck have almost entirely disappeared and his general condition seems improved. 8o coley: neoplasms of the lymphatic glands Subsequent History: Almost immediately after the disap- pearance of the tumors in the neck the patient showed evidence of a tumor mass in the epigastric region, which increased rapidly in size. This at first yielded to the :r-ray treatment, but later the rays had Httle effect. At the end of two weeks the glands in the neck which had disappeared under :r-ray recurred and grew rapidly, and the patient's general condition grew steadily worse. He has been confined to his bed since July i. Blood examination made June i6 shows: White-blood cells 8500; hemoglobin, 88 per cent.; polynuclears, 46 per cent.; large mononuclears, 27 per cent.; transitional s, 7 per cent.; lymphocytes, 20 per cent. The high temperature which was present at the time of the patient's admission to the hospital rapidly subsided and became normal after the tumors of the neck had disappeared under the x-ray treatment. However, upon the reappearance of the glands in the abdomen the patient again showed an irregular tempera- ture. He became rapidly worse and died on August 15, 191 5, four months after he first noticed the enlarged gland in the axilla. Case XLIII. — Recurrent round-celled sarcoma of the cervical glands (injective granuloma). C. S. H., male, aged thirty-five years, was referred to me by Dr. H. L. Smith, of Nashua, Me., in October, 1912, with the following history: He first noticed a nodule in the neck on the left side eight years ago. This grew very slowly for six years, but more rapidly thereafter. The first operation, which was a extensive one, was done in July, 1910, by Dr. Smith and con- sisted in ligation of the common carotid and dissection deeply into and behind the pharynx up to the base of the skull. A portion of the parotid gland was removed, also a portion of the auricle. The operation was believed to be incomplete and recurrence was regarded as certain. Dr. Kingsford, pathol- ogist of the Dartmouth Medical School, made the following report : coley: neoplasms of the lymphatic glands 8 1 "Sections show a very marked infiltration of all the tissues with round cells. The remains of the parotid gland can still be made out, but the function of the gland must have been de- stroyed. The round cells have also invaded the connective tissue and muscle, and in many places the round cells are col- lected into clusters resembling lymph nodes. Diagnosis: round- celled sarcoma of very slow growth." The growth recurred promptly and continued to increase in size. When the patient was referred to me in November, 191 2, there was a large mass on the side of the face. The ear was forced outward by the growth, which was mainly above and in front of it. On the inside of the cheek, opposite the superior molars, there was a considerable outcropping of what was presumably the disease, although it might have been of inflammatory character resulting from the interference with the salivary duct. It has been very painful and an infected area appeared at the most prominent part of the growth, which broke down and discharged a moderate amount of grayish, sloughing material. The patient entered the General Memorial Hospital on Novem- ber 30, 1912, and left on January 27, 1913, during which time he received fifteen injections of the mixed toxins, the highest dose being 7.5 minims, which caused a very severe reaction. The tumor showed steady diminution in size under the treatment, which was continued by his family physician after his return home. The improvement continued for some time; then no further decrease was noticeable, and on November 18, 1913, the patient returned to the General Memorial Hospital. The toxins were given in larger doses and x-rsij treatment was added. This was followed by rapid improvement, and when the patient left the hospital, January 27, 19 14, there was no appar- ent evidence of the disease remaining. The toxins were con- tinued by the family physician, but in March the patient devel- oped acute nephritis, to which he succumbed on April 2, 1914. Dr. Smith stated that there was no sign of a recurrence at the time of his death. 82 coley: neoplasms of the lymphatic glands Dr. Swing's report on a section of the original tumor reads as follows: April 2, 19 13. "The section received of a recurrent tumor of the parotid, shows a lymphoid infiltration of the salivary glands. It falls in that group which I term Mikulicz's disease. "The process began as an infectious granuloma and may run into lymphosarcoma. In this case it is difficult to say whether the infectious or neoplastic elements are the more prominent. "There are some features of lymphosarcoma, but they are not prominent; yet, I think the course might closely resemble a malignant tumor. "There is some hypertrophy of epithelial alveoli which I do not regard as important." RARE TYPES OF MALIGNANT DISEASE OF THE LYMPHATIC GLANDS Case XLIV. — Primary neoplasm of the lymphatic glands of the axilla. Histological diagnosis: perivascular hemangioma by one pathologist; mixed-celled sarcoma by another: melanoma by a third. M. E., female, aged thirty-six years, was referred to me by Dr. A. E. Jaffin, Jersey City, on January 27, 1914, with the following history: January 19, 19 13, she first noticed a peculiar sensation in the right axilla; no tumor until two months later, when a small lump appeared in the axilla. This grew rapidly and was removed in April, 1913, one month after it was first noticed by Dr. Jaffin, who states that the tumor was the size of a small hen's egg, soft and glandular in appearance, very juicy, with quite a large area of central necrosis, otherwise appar- ently well encapsulated. The report of the microscopic exami- nation made by Dr. George E. McLaughlin, of Jersey City, under date of April 16, 19 13, reads: "The tissue received on April 11, 1913, which consisted of a large lymphatic gland the size of an egg and a small lymphatic gland, have been sectioned, stained, and examined microscopic- ally, and I would report as follows: coley: neoplasms of the lymphatic glands 83 "The smaller gland showed a lymphadenitis, while the large gland was made up of a fibrous tissue stroma with here and there some coagulation necrosis and large numbers of dilated blood- vessels. Surrounding these bloodvessels were cylindrical bands of endothelioid-like cells which seemingly had their origin in the adventitia of the vessels. The nuclei of these cells took the stain well and were large and somewhat oval. Diagnosis: ,,,^mm'm^^ ' »■■ 'i r-' ''^^^^&1i-. . - ■ f^ ■^^ ,.. j_ ,^ , : .:siS^%.. ^ '-1I I- ""•'" i ■ ^^Sf^SI''':' —-^'./j^V. ■-, :^'>( :X|J|^^.^-^pgv../ ^ - ^^^sn^^^^^^^^H -WKKfSS^ l^^^^^gl^l Fig. 33. — Case XLIV. Axillary glands; rapid progress. One pathologist reported sarcoma; another melanoma. perivascular hemangiosarcoma. This growth is malignant and capable of causing metastasis." On May 17, 1913, one month later, the mixed toxins were begun and given daily or every other day for two months, in doses up to 4 minims. In July a local recurrence was noticed and on July 25 a thorough dissection of the entire axilla was done. The specimen was submitted to Dr. Mandlebaum, of the Mt. 84 coley: neoplasms or the lymphatic glands Sinai Hospital, who pronounced the disease mixed-celled sar- coma. His full report, dated July 30, 1913, reads as follows: "The axillary tumor in the case of M. E. shows mostly large round cells of a sarcomatous type and having very large nuclei. In a few situations spindle cells are also seen. Some delicate connective-tissue fibers are found between the cells in places. Here and there are small capillaries which seem to bear some relation to the tumor growth, though this is hardly sufficient to warrant the diagnosis of a hemangiosarcoma. In my opinion the tumor is a mixed-celled sarcoma, with a predominence of large round cells, and is very likely primary in the lymph nodes of the axilla, even though no lymphoid tissue is to be found in the sections. "The dark areas in the specimen represent localized areas of necrosis." On August 8, 1 9 13, the toxins were resumed and the dose increased to 5 minims. November 29, a small recurrent nodule was found overlying the axillary vein. January 5, 19 14, third operation. The portion of the axillary vein involved by the tumor was resected. Physical examination, January 27, 1914, showed apparently no recurrence. Massive a;-ray treatment advised in conjunction with the mixed toxins. The tumor, however, soon recurred and on February 19, 1914, a fourth operation was performed, which was an incomplete one owing to the extent of the disease. The toxins and x-rays were resumed with little effect in checking the rapid progress of the disease. Examination of the tumor removed at the third operation was made by Dr. James Ewing, who pronounced it a melanoma. Bearing on the possibility of the tumor having been secondary to a primary melanoma elsewhere, it may be mentioned that the patient stated that a year ago, she noticed a small spot three inches above the wrist on the inner surface of the right forearm; this was reddish in color but later became dark. It never ulcerated and never showed any elevation of surface, nor coley: neoplasms of the lymphatic glands 85 did it seem to have the appearance of a melanoma. I excised it and microscopic examination showed no evidence of melanoma. The patient died in August, 1914, at which time the growth had reached the size of a child's head and began to break down. There was enormous edema of the arm and forearm. Case XLV. — Melanotic sarcoma of submaxillary and cervical glands. Fig. 34. — Case XLV. Melanoma; sarcoma of cervical glands; regarded as tuberculosis at first; two operations. Pathological report melanoma. No primary pigments. J. M. M., female, aged forty-three years. One sister died of carcinoma of the breast in July, 191 1, after having undergone two operations. Mrs. M. took care of her the entire time. Shortly after her death she noticed an enlargement of the sub- maxillary lymph gland. This was never very painful nor did it ever show evidence of inflammation of the skin; there is no history of a wart or pigmented mole having been noticed in the vicinity of the tumor. The patient was examined by Dr. Irvin 86 coley: neoplasms of the lymphatic glands Abell, of Louisville, Ky., in October, 191 1, who found a smooth, movable tumor, the size of a guinea-hen's egg in the submaxil- lary region; no evidence of inflammation. The swelling de- creased somewhat under local applications and then remained stationary. Clinical diagnosis: Enlarged lymph gland of sub- maxillary group. In January, 191 2, under local anesthesia, the enlarged gland was dissected out and examined by Dr. E. S. Allen, who pronounced the trouble chronic adenitis, non-tuber- culous. The disease recurred a few months later and a second operation was performed on October i, 191 2, under general anesthesia; a gland the size of an acorn was removed; it was deeply situated and rested right over the left internal jugular vein. A second recurrence followed not long afterward and a third operation was done on April i, 1913. A mass supposed to be an enlarged cervical gland was removed which, on explor- ation proved to be a blood clot, which diagnosis was confirmed by Dr. Allen. The disease recurred locally, and a fourth opera- tion was performed on September 30, 19 14, an incision being made through the former one on the left side of the neck and through the sternomastoid muscle. The tumor involved the internal jugular vein, so that a small portion of the latter was dissected in taking out the mass. The surrounding structures were indurated and clinically, the disease had the appearance of sarcoma. Microscopic examination of the gland made by Dr. Graves, of the University of Louisville, showed it to be melanotic sarcoma. The disease promptly recurred and on December 30, 19 14, the patient was referred to me by Dr. Abell, for the toxin treatment. Physical examination at this time showed the patient in fairly good health. The left cervical region showed several scars. In the upper portion of the neck, anterior to the sternomastoid muscle or partly involving it, is a tumor the size of a hickory nut, movable upon the deep structures, firm in consistence; skin slightly adherent. Just above the clavicle are some in- durated areas. No evidence of tumors elsewhere. The patient was put upon the mixed toxins of erysipelas and Bacillus pro- coley: neoplasms of the lymphatic glands 87 digiosus with the result that at the end of two weeks there was considerable decrease in size and marked increase in mobility. Under ether anesthesia I removed the masses as thoroughly as possible, although the operation was by no means complete. The wound healed by primary union and the toxins were im- mediately resumed and have been kept up two to three times a week ever since by her husband who is a physician in Louisville. Microscopic examination made by Dr. James Ewing, whose report, dated December 29, 1914, showed the disease "mela- noma, malignant." The patient remains free from recurrence at the present time, August 15, 191 5, which is a much longer period than she had been free from recurrence before. Of course, it is too early to speak of a definite result. This case together with the case just reported suggest that melanotic sarcomas or melanomas may originate in the lymphatic glands, contrary to the opinion generally held. Contrary to accepted views, the two following cases of car- cinoma apparently originated in the axillary glands. Case XLVL — Primary carcinoma of the axillary glands. Mrs. L., aged thirty-eight years; married; was formerly a nurse at the Hospital for Ruptured and Crippled. The patient was first seen by me, in consultation with Dr. E. L. Barnett, in October, 1913. Family history negative. Personal history: About nine months previously the patient first noticed a small movable lump in the outer aspect of the right axilla, about the size of a marble. This slowly increased in size, but there was no pain at any time. No lump could be noticed on the breast nor could any tumor, or change in consistence, be made out upon careful examination of the breast. On October 10, 1913, under ether anesthesia, I operated upon her, at the Hospital for Rup- tured and Crippled, and found a freely movable tumor the size of a English walnut in the right axilla. No other glands could be felt higher up, nor could any tumor or induration of any sort be detected in the breast, under anesthesia. A clinical diagnosis of malignancy was made, but in view of the fact that no tumor 88 coley: neoplasms or the lymphatic glands could be felt in the breast, and the disease was apparently pri- mary in the axillary glands, it was thought to be either a sarcoma or Hodgkin's disease. A specimen was sent to Dr. Ewing for examination, whose report, dated October i8, 1913, reads: "Malighajit adenocar- cinoma of lymph node." Dr. Ewing believed it to be secondary to some primary tumor elsewhere, probably in the breast. The patient absolutely refused to undergo a further operation. She was pregnant at the time of the first operation, and a few months thereafter gave birth to a healthy child. Since that time she has been kept under careful observation by Dr. Barnett, who states that at the time of his last examination, a few months ago, there could be found no evidence of any return of the growth, nor has any signs of a tumor in the breast developed. In connection with the preceding case I would like to add the following : Case XL VII. — Carcinoma of the axillary glands, apparently primary. Mrs. C. C. W., was referred to me by Dr. R. R. Sinclair, of Westfield, N. J., on September 11, 1912. Family history good. Persona] history: First noticed a small, hard, gland in the right axilla one year prior to my first observation. This gland slowly increased in size, and later became attached to the skin. No history of malignant tumor in any other part of the body. Physical examination showed a small gland, the size of a hazel-nut in the right axilla, freely movable, hard in consistence, clinically a typical carcinoma. The skin was not adherent. No other glands could be felt in the axilla, or above or below the clavicle. Careful observation failed to reveal any tumor in the breast or any change in its consistence. Under ether anesthesia I removed the tumor, which was examined by Dr. Ewing, and pronounced a typical carcinoma. The patient was then put upon the mixed toxins of erysipelas and Bacillus prodigiosus in the hope of retarding or preventing a recurrence. She remained well for one year, when a small coley: neoplasms of the lymphatic glands 89 local recurrence in the axilla developed, which was again re- moved by operation, and the toxins continued by the family physician. She remained well for almost another year before a second local recurrence developed, which was again removed, and the toxins resumed in small doses. Examination, December 22, 1914, showed that her general health had remained normal. Shortly after this she developed a small swelling above the right clavicle, which has slowly increased in size ever since. During the last six months she has had some swelling of the arm, and there is evidence of a recurrence in the axilla. Up to the present time there has never been any tumor whatever in the breast itself. Her con- dition is gradually getting worse, and the diseases, which has been kept in fairly good control with the toxins during the last three years, is steadily progressing. (Patient died January, 19 16.) Case XL VIII. — Lymphosarcoma of neck, clinical diagnosis "probably endothelioma'' microscopical. G. J. C, male, aged forty-four years; referred to my service at the General Memorial Hospital by Dr. Spencer, of Brooklyn, on November 30, 191 2. Wassermann was negative. In June, 191 2, he first noticed a lump behind the sternomastoid muscle on the right side of the neck. He gave a history of having had severe stiffness on the right side of the neck, one year before, accompanied by some swelling which lasted six weeks, during which time he could neither eat nor sleep and lost twenty-five pounds in weight. The swelling entirely disappeared under local treatment and he became as well as ever. In June, 191 2, the swelling came back apparently at the same place, but more circumscribed, without any stiffness or pain, and without loss of weight. When I first saw the patient, in November, 191 2, physical examination showed a tumor the size of a closed fist, occupying the entire region of the right side of the neck, from the mastoid to the clavicle and from the vertebral line behind to the angle of the jaw in front, firmly fixed, skin not adherent. There were no enlarged glands on either side of the neck; no axillary or inguinal glands; no enlargement of spleen or 90 coley: neoplasms or the lymphatic glands liver. The patient had had ii;-ray and iodide of potassium treat- ment without improvement before going to the Hospital. I made the clinical diagnosis of sarcoma. The mixed toxins were given first systemically, later locally into the tumor. At first there was some diminution in the size of the growth and in- creased mobility. A portion was removed for microscopic exam- ination and submitted to Dr. James Ewing, who reported: "The tissue is composed of diffuse cohesive masses of large polygonal, round, and fusiform cells with hyperchromatic nuclei; many mytoses, one hydropic cell between. There are no definite epithelial characters. There is little connective- tissue ; the cells are often arranged about frozen bloodvessels. There are polynuclear giant cells. Diagnosis: primary tumor of lymph nodes, probably endothelioma." The tumor finally began to increase in size rapidly and the toxin treatment was abandoned after about two months, when the patient returned to his home. Later history unknown. Case XLIX. — Hodgkin^s disease or carcinoma of cervical glands. H. Y. C, male, Chinese, aged twenty-four years; two sisters suffering from gland trouble; both living. The patient first noticed slight pain in the neck in the latter part of the summer of 1910. Soon after a swelhng of the neck was seen to appear almost simultaneously on both sides; this gradually increased in size; in March, 191 1, he noticed that the tonsils were much hyper- trophied; they were promptly removed at the University of Michigan Hospital. Microscopic examination showed no ^ign of mahgnancy. A month later a portion of the tumpr on the left side of the neck was removed and pronounced Hodgkin's disease by Dr. C. B. Nancrede. In the early part of June, 191 1, another portion of the neck tumor was removed at the Massa- chusetts General Holpital, and pronounced small-celled, lymph- adenoma of Hodgkin's type, by Dr. H. F. Hartwell, of Boston. Physical examination at the time the patient was first seen by me, July 7, 191 1, showed the left side of the neck occupied by a tumor extending from the mastoid process to two inches above the clavicle and from the angle of the jaw backward coley: neoplasms of the lymphatic glands 91 nearly to the vertebral line; there is a recent curved cicatrix four inches long, over the upper part of the tumor. The skin is markedly reddened and somewhat adherent to the tumor which is extremely hard in consistence and firmly fixed to the deep structures; apparently all the tissues are infiltrated from the skin to the spinal column. A similar tumor occupies the right side, but the same is not quite as large and the skin is less red- dened. There are no enlarged glands in axillae or groins; no enlargement of spleen or liver. Patient has lost very little in weight. I made the clinical diagnosis of lymphosarcoma. The toxins were tried for two or three weeks without effect. He grew worse rapidly and died a few months later. The clinical features in this case were entirely different from those usually found in Hodgkin's disease, and the microscopic examination of the recurrent tumor made at the University of Michigan laboratory pointed strongly to a true neoplasm, probably of the carcinomatous type. The following case is of interest from the fact that the micro- scopic examination by one pathologist was sarcoma, by another, tuberculosis. The subsequent history proved the disease to be malignant. Case L. — Lymphosarcoma of the inguinal glands. W. C. D., male, aged twenty-four years. Family history: No specific or tuberculous disease; Wassermann negative. The patient was referred to me by Dr. Vail, of Belleville, N. J., on October 16, 191 2, with the following history: Always in good general health until three years before, when he first noticed a small, movable gland, about the size of a hazel-nut in the right groin. This increased so slowly in size, that he did not call a doctor's attention to it until the beginning of October, 191 1, just previous to which time it has begun to grow more rapidly. Physical examination on October 16, 191 2, showed the right inguinal and iliac regions occupied by a tumor the size of two fists, apparently made up by a large number of enlarged glands, more or less fused together, with semifiuctuation in the most 92 coley: neoplasms of the lymphatic glands protuberant portion. The skin is slightly reddened and adherent in places. The tumor was fairly movable below but firmly fixed in the upper part; there was very slight enlargement of the glands on the side, none in the axilla or neck; no enlargement of spleen or liver. A portion of the tumor the size of a goose egg was removed under ether and microscopic examination was made by Dr. Ewing, who pronounced lymphosarcoma. Dr. W. C. Clark, who examined another specimen, pronounced it tuberculosis. The patient was immediately put upon the mixed toxins and at the end of six weeks the tumor had diminished to less than one-third its original size. In spite of continued treatment little further improvement was noticed and soon the tumor began to increase rapidly in size. The patient was then given injections of colloid of copper solution in large doses, for a number of weeks without any appreciable effect. He lost strength and weight more rapidly than before and died on January 13, 1913. The tumor proved to be lymphosarcona. Case LI. — Tumor of carotid gland; microscopic diagnosis; sarcoma of glands of neck, left tonsil the clinical diagnosis. E. E., aged forty-five years; mother died of cancer of brain. Previous history negative. First noticed a swelling beneath the left sternomastoid muscle near its upper attachment in the fallof 1903; it caused no pain, but some difficulty in breathing. The patient was admitted to the General Memorial Hospital on January 21, 1904. Physical examination at this time showed a mass in the left side of the neck, just beneath the sternomastoid muscle, the size of an egg, firm, but not tender. Examination of the throat showed a swelling on the left side of the pharynx involving the tonsil and extending nearly to the right pharyngeal wall. The tumor was firm in consistence but not at all tender. Operation, assisted by Dr. Downes, was performed on January 25, 1904, and consisted in tracheotomy, ligature of the left external carotid, removal of the left submaxillary gland. Al- though the lower jaw was sawed through with a Gigli wire saw, it was found impossible to remove the entire tumor. Micro- scopic examination made by Dr. George Biggs, showed the coley: neoplasms of the lymphatic glands 93 specimen to be a "tumor of the carotid gland." Later history unknown. Fig. 35. — Case LI. Tumor of carotid body (tonsilinvolved). The following case shows the probable influence of trauma as a causative factor in the development of a neoplasm of the lymphatic glands: Case LII. — Sarcoma of inguinal glands. G. S., aged five and one-half years. Always well until May, 1899, when he fell, injuring his right groin. A few days later a soft and rapidly growing tumor developed at the site of the in- jury. Its rapid development and semifluctuating character led Dr. William T. Bull to believe it was an abscess. Incision showed only blood and -a very vascular tumor. Microscopic examination proved it to be a small round-celled sarcoma. The iliac glands became quickly involved. The mixed toxins were tried for one month and while at first the tumor became much more movable and perceptibly smaller, after two or three weeks it began to 94 coley: neoplasms of the lymphatic glands increase in size again and its growth could no longer be con- trolled. The patient died in September, 1899, four months from the time of the injury. Case LIII. — Lymphosarcoma of the tonsil with secondary involvement of neck. Mr. S., aged fifty-five years. Wife died of carcinoma of breast in November, 1908. In the early part of November, 1909, while traveling, he first noticed trouble in his throat. He con- sulted Dr. Landsman, of New York, who found what seemed to be a severe tonsillitis or quinsy and treated him accordingly. His temperature ranged from 102° to 103°. Inasmuch as after a week's treatment his temper ture remained high and his general condition unimproved, he consulted Dr. Clarence C. Rice, of New York, who suspected malignant trouble, and: I was called in consultation. Physical examination on November 26, 1909, showed the patient rather thin, with sallow complexion and a temperature of 102° to 103°, pulse 120. Examination of the throat showed the left tonsil markedly swollen, being of the size of a small hen's egg, ulcerated in the centre over an area of three-quarters of an inch in diameter. The tonsil was covered with a foul, grayish exudate in the central portion. The right tonsil was also somewhat enlarged, but not ulcerated. I made the clinical diagnosis of malignant tumor of the left tonsil, whether sarcoma or carcinoma I was unable to say, its general appearance and consistence was more that of carcinoma, but its size and rapid growth were in favor of the diagnosis of sar- coma. The left cervical glands had become markedly swollen, from the mastoid to the clavicle, some of the tumors being the size of an English walnut. • The glands on the right side of the neck are also swollen, especially in the upper portion. The tonsillar tumor was removed and the specimen submitted to Dr. James Ewing, professor of pathology at Cornell Uni- versity, who stated that the tonsil was undoubtedly malignant but whether it was carcinoma or sarcoma, he could not be sure. He desired another specimen , and, on November 29, under cocaine anesthesia, I removed a small gland from the left cervical coley: neoplasms of the lymphatic glands 95 region, just above the angle of the jaw, about the size of a hazel nut; it was soft in consistence and typically malignant in appearance. Dr. Swing's report on the tumor was as follows: "The lymph nodes contain lymphosarcoma. The structure indicates a high degree of malignancy." After a more careful examination of the specimen. Dr. Ewing stated that he was in doubt whether it was lymphosarcoma or Hodgkin's disease. The tumors of both tonsils continued to increase rapidly in size until they nearly met, making swallowing extremely difiticult. The ulcerated area in the left tonsil spread and soon the right tonsil also began to ulcerate. Apparently the right side had become infected from the other side by con- tiguity. On December 2, six days after my first observation, and three weeks from the first signs of the trouble, his temperature still ranged between 102° to 103°. His local and general con- dition rapidly became worse. At this time (December 2) he received the first injection of the mixed toxins in the pectoral region, one-fourth minim being given. This was followed by a severe chill, rigor and a temperature of 105°. His general condition was so bad that it was thought unwise to continue the treatment and he died on December 5, the entire duration of life from the time of the first symptom to death in this case was three weeks and two days. Case LIV. — Lymphatic leukemia. N. B., male, aged sixty-five years, was admitted to my service at the General Memorial Hospital on June 2, 19 13. Family history good. Personal history: In November, 191 2, he cut his finger; the wound did not heal well and what he called a "dry sore" remained for a number of weeks. This was followed two months later by an eruption upon hands and face and neck. Ten weeks ago he first noticed fairly good-sized lumps on both sides of the neck which came on very suddenly and grew rapidly; he lost fourteen pounds in weight. The eruption is still present over face and body. 96 coley: neoplasms of the lymphatic glands Physical examination on admission showed large masses on both sides of the neck, freely movable, more or less discrete, clinically typically characteristic of Hodgkin's disease; spleen markedly enlarged, liver only slightly. Blood examination June 2, showed white blood cells 200,000. The patient was treated with the ic-ray and later also with vac- cine by Dr. Weil. There was marked decrease in the number of white cells. June 22: White blood cells, 91,600; hemoglobin, 81 per cent. June 25: White blood cells, 70,000; hemoglobin, 69 per cent. July 15: White blood cells, 112,000. There was very marked diminution in the size of the glands under the treatment. General condition remained about the same. Later history not known. Case LV. — Case of pseudoleukemia later changing into leukemia. Mrs. E., aged forty-nine years, married, referred to me by Dr. E. M. Foote, was admitted to the General Memorial Hsopi- tal on March 2, 1915. Family history good. Personal history: Ten years ago, amputation of breast for carcinoma; no recur- rence; glycosuria for a number of years; disappeared recently. Four years ago first noticed a swelling in the submaxillary glands on the left side. A little later appearance of similar glands on the other side of the neck, shortly followed by enlargement of the axillary glands; later the inguinal glands also became involved. The patient was treated at various hospitals and a number of glands were removed at different times for diagnostic purposes. The family physician stated that ic-ray and benzol treatment had been tried, without apparent effect, and that in May, 19 14, her blood count showed 38,000 white cells and 90 per cent, of lymphocytes. She was referred to me by Dr. Foote as a case of Hodgkin's disease. Physical examination at the time of her admission to the General Memorial Hospital showed enormously enlarged glands in both cervical and axillary regions; moderately enlarged inguinal glands; spleen and liver not palpable; some resistance in the region of the abdomen, pointing to an involvement of the mesenteric glands, but on account of her stoutness, these could coley: neoplasms of the lymphatic glands 97 not be clearly made out. Blood examination (March 3, 191 5) showed : White cells, 164,000; hemoglobin 68 per cent.; polynuclears, 7 per cent.; eosinophiles, i per cent.; large mononuclears, 9 per cent.; lymphocytes, 83 per cent. The patient was put upon ic-ray treatment. Two days after the first application the blood count was as follows: White cells, 107,000; lymphocytes, 95 per cent.; large mono- nuclears, 2 per cent.; polynuclears, 3 per cent. Many degenerated white blood cells. Red cells normal. On March 16, after four x-ray treatments, the blood examina- tion showed: White cells, 80,000; red cells, 3,916,000; hemoglobin, 60 per cent.; lymphocytes, 86.6 per cent.; large mononuclears, 10.7 per cent.; pol3mLUclears, 2.7 per cent. The patient was discharged from the hospital on March 23, 1915. The last blood count, March 20, showed white cells 87,000. She received six x-ray treatments during her stay at the hospital and has continued to receive treatment in the out-patient department since. Examination at the present time, August 21, shows a marked decrease in the size of all glandular tumors, but her general condition is rapidly deteriorating, as shown by loss of weight and strength. Case LVI. — Lymphosarcoma or melanoma, apparently primary in the axillary glands. R. B. W., aged twenty-four years, male; graduate of medicine; had been in good health until the last of November, 1914, when he had an attack of influenza; a week later he notice enlargement in the right axillary glands; two days thereafter a small swelling appeared in the posterior cervical region over the lower cervical vertebra at the base of the neck; all tumors increased rapidly in size. He entered the Toronto General Hospital on December 2, 1914, at which time his temperature was 100°. The first two weeks it ranged between 96.5 to 99°, most of the time slightly below subnormal. Blood examina- tion showed: Whites, 8000; reds, 6,400,000; hemoglobin, 85 per 98 coley: neoplasms of the lymphatic glands cent.; differential examination showed nothing abnormal; Was- sermann negative. The patient had a great deal of pain from the beginning, which increased with the progress of the disease; the pain was neuralgic in character and chiefly confined to the chest and right leg. He lost rapidly in weight and strength and on January 9, 191 5, when the patient's father consulted me as to the advisability of trying the toxins, or a little over five Fig. 36. — Case LVI. Round-celled sarcoma; one diagnosis. Melanoma sarcoma. Apparently primary in lymphatic glands of axilla; death in three months. (Ewing.) weeks from the beginning of the disease, he had lost eighteen pounds in weight. He died January 10. The accompanying charts show the origin and distribution of the glandular enlarge- ment. The pathological report of the Toronto General Hospital read "round-celled sarcoma." Some of the slides were sent to me and I had them examined by Dr. James Ewing, of Cornell Medical School laboratory, whose report, dated April 21, 191 5, is as follows: coley: neoplasms of the lymphatic glands 99 "The materia] received consists of stained sections of tumor tissue. The tissue is composed of compact masses of large polyhedral cells arranged in ill-defmed groups separated by a little stroma. The cells are poorly fixed and very hydropic, so that the outlines are not always clear. The nuclei are large vesicular and hyperchromatic with prominent nuclei; miototic figures are very numerous. In many cells there is an abundance of yellow pigment granules and some cells are completely filled Fig. 37. — Case LVI. Small round- celled sarcoma of axillary glands, with very rapid generalization. Fig. 38. — Case LVI. Small round- celled sarcoma of axillary glands, with very rapid generalization. Death in three months. with pigment; some of the stroma cells also contain pigment. Diagnosis: melanoma. It is difficult to believe this a case of ordinary melanotic sarcoma or melanoma, inasmuch as it apparently started in the lymphatic gland. Careful search failed to reveal any primary focus like a pigmented mole in any part of the body. The ex- tremely rapid course of the disease is also a feature which I have never observed in any case of melanotic tumor. I have just made a study of 80 cases of melanotic sarcoma personally loo coley: neoplasms of the lymphatic glands observed, and neither among these cases nor in the literature have I found anything corresponding to such a clinical course. Case LVII.^ — Primary sarcoma of the cervical glands or tumor of thymus gland closely resembling an acute infectious disease M. C, female, aged nineteen years, entered St. Luke's Hospital on August 7, 1 9 14, in the service of Dr. W. A. Downs, on account of a glandular swelling, 3x2 inches in size, situated in the left cervical region; there was no redness; no fluctuation; very slight tenderness. Two decayed molar teeth with abscesses at the roots, were found in the left lower jaw. These were ex- tracted on August 14, and by September 9 the mass of glands had become considerably reduced in size. September 30 the reduction was much less marked, but the swelling was smaller than at time of entrance. October 7, measurement of neck 13 inches, October 19, 13I inches, October 23, glands were noticed for the first time on the right side of the neck. December 30, the left side of the neck was normal; on the right side the glands were enlarged and had the appearance of cellulitis. January 4, some of the molar teeth on the rip^ht side were ex- tracted and the glands incised. She was discharged on January 6: She was readmitted to St. Luke's Hospital on January 13. On January 11 there were first noticed glands in the right axilla. The tissue removed from the inflamed mass in the neck proved on microscopic examination to be a "neoplasm of the round- celled variety; exact type undecided; either sarcoma or car- cinoma; many mitotic figures." January 21, 1915, the patient was transferred to the General Memorial Hospital. The tumor rapidly increased in size, extending in all directions, upward, involving the face, causing extensive edema of the lids of the left eye and the ear; downward, to the right portion of the thorax and laterally into both axillae. The skin was purple in color and ulcerated over the most prominent part of the tumor. The patient ran a temperature ranging between 100° and 102. °5 from the day she entered the hospital. She grew worse very 1 Dr. Downs has kindly given me permission to publish this case as the patient was on his service in the General Memorial Hospital. coley: neoplasms of the lymphatic glands ioi rapidly and finally dyspnea developed, causing death on Feb- ruary 9. Autopsy report, made by Dr. Ewing, showed the tumor to involve the region of the thymus gland and generally the whole region of the thyroid, larynx and pharynx up to, if not into, the base of the skull, with continuous extension into both axillae involving the lymphatic glands and encroaching upon the inter- costal muscles. On section one found medium-sized round and polyhedral and cylindrical cells lying in stroma, chiefly made up of capillaries, covered by large epithelioid cells containing many lipoid globules; many cells resemble plasma cells, others had large, dense nuclei, polymorphism of cells is the most prominent feature; no giant cells; the large groups of cells are surrounded by dense fibrous strands tending to become hyaline. Dr. Ewing's final opinion was a primary malignant tumor of the thymus gland. He will report the case in fuller detail. The whole picture of the disease, closely resembles an acute infection, starting in the cervical glands and yet it was undoubt- edly a malignant tumor. The following cases are of special interest and are reported here more fully than is possible in the tables: Case LVIII. — Sarcoma of the neck and mediastinum. Very rapid growth, causing death in Jour months. G. W., male, aged nineteen years; student; always in good health until November 15, 19 13, when he had a sudden severe pain in both shoulders; later this became less severe and inter- mittent. December 19, 19 13, he noticed a short, dry cough, which gradually grew worse. Shortly after this he first noticed enlarged glands on both sides of the neck, just beneath the angle of the jaw. These gradually increased in size, and in addition the whole neck became symmetrically enlarged, making it necessary for the patient to wear a No. 18 collar — his normal size was No. 15. The entire increase had taken place within a month's time. Marked dyspnea developed, accompanied by rapid heart action. The patient was admitted to my service I02 coley: neoplasms of the lymphatic glands at the General Memorial Hospital on June 20, 1914. Physical examination at this time showed a very marked symmetrical enlargement of the whole neck and face, apparently due to ob- struction of the superior vena cava, dilatation of the superior bloodvessels and some cyanosis. Several enlarged glands, some as large as a hen's egg, could be felt on either side of the neck, deeply placed, moderately firm in consistence, fairly movable non-infiltrating. Measurement of the neck at the base (collar Une) on January 23 was seventeen and three-fourth inches; over the thyroid, sixteen and three-fourth inches. The patient was very weak and unable to walk; marked dyspnea making it necessary for him to sleep sitting propped up in bed. Blood examination showed: Hemoglobin, 85 per cent.; white blood cells, 6500; polynuclears, 73 per cent.; mononuclears, 23 per cent.; basophiles, 4 per cent. X-ray examination showed a tumor occupying the superior mediastinum, continuous with the heart shadow and extending to the root of the neck. The patient was immediately put upon small doses of the toxins; he proved very susceptible, i to ^ gr. causing a reaction. Improvement was noticed almost immediately, as shown by diminution in the pulse-rate, lessening of the dyspnea, marked decrease in the size of the neck, improvement in the cough. January 26 the measure- ments of the neck had gone down one and one-half inches. On January 29, one week after admission to the hospital, measure- ment of the neck at the base was fifteen and three-fourth inches, over the thyroid fifteen inches, being a decrease of over two inches within a week. The patient was given a:-ray treatments in addition to the toxins; his general condition was markedly improved, he was able to go about and take walks out of doors. At the end of two weeks' improvement the condition gradually became worse again, in spite of continued treatment with the toxins and a;-rays. He left the hospital on February 18, 1914, having rapidly grown worse daily, and died about two weeks later. Case LIX. — Lymphosarcoma of neck; clinical diagnosis remark- ably rapid development. coley: neoplasms of the lymphatic glands 103 Mrs. H. P., aged sixty-eight years; always in good health up to July I, 1 9 13, except that she had a small epithelioma removed from the inner canthus of the eye five years before he present disease. Early in July she had a severe attack of la grippe, with a temperature of 102° to 103°, accompanied by cervical enlargement on both sides, sore throat and general symptoms of la grippe. She had three similar attacks during the month of July; each time the glands became rapidly and mark- edly swollen with complete subsidence after the attack was over. On one occasion the doctor was summoned hurriedly by the patient's brother who stated that the gland were twice the size of a hen's egg. Five hours later, when the doctor saw the patient the glands had become reduced to the size of a hickory nut. A little later the glands of the left side again became swollen, but, instead of subsiding as -hitherto, they gradually increased in size. In October the increase became very rapid and was ac- companied by infiltration of the surrounding tissues. The axillary glands soon became involved, more markedly on the. left side, also the inguinal glands. No enlargement of spleen or liver. The patient failed rapidly in general condition and by the middle of December, 1913, was confined to the bed. She was then seen by Dr. J. Erdman, who made the diagnosis of lymphosarcoma. No specimen was removed. I saw the patient in consultation on December 29, 1913. Physical examination at this time showed the patient propped up in hedi unable to lie down; her general condition was ex- tremely bad; pulse rapid and weak; she was unable to open her mouth more than a half-inch. Examination showed the whole left side of the neck, from the clavicle to the mastoid, and the anterior portion of the jaw nearly to the vertebral line, occupied by a diffuse tumor, apparently involving all the cervical and suproclavicular glands with infiltration of the surrounding tissues, including the parotid and enormous dilatation of the superficial veins; paralysis of the muscles of the left face and mouth. About a week ago she had had an attack of almost complete coma; pulse 130. Since this time she has been more or less I04 coley: neoplasms of the lymphatic glands wandering mentally, with occasional recurrence of slow respiration and rapid pulse. No treatment advised. Prognosis: only a few weeks of life. She died shortly afterward. Case LX. — Lymphosarcoma of neck — marked inhibitory action both under the toxin — and later x-ray treatment, which proved only temporary {however). Unusual generalization of the disease. Miss M. L. A., aged forty years; first noticed a tumor above the clavicle in the spring of 1898; this was removed. Shortly after this a recurrence took place in the right cervical region which grew very rapidly, soon involving the axillary glands on the same side. In July, 1900, the axillary tumor was removed by Dr. C. B. Nancrede, of Ann Arbor. The tumor in the cervical region showed such extensive involvement of the deeper structures that it was considered entirely inoperable. Microscopic examination was made by Dr. King of the Dartmouth Medical School, who pronounqed it small round-celled sarcoma. The patient was referred to my by Dr. Nancrede in October, 1900. Physical examination at this time showed a large tumor in the right cervical region, extending from the clavicle to the mastoid process of the temporal bone. There were some enlarged nodules below the clavicle and several small tumors in the region of the cicatrix in the axilla. The toxins were begun on October i and continued, with occasional intervals of rest, for six months. There was a decided decrease in the size of the tumors and increase in their mobility for three months, when the improvement ceased. At the end of six months the tumors began to increase in size and grow more rapidly. In February, 1902, the :r-ray treatment was begun, and at the end of three weeks remarkable improve- ment had occurred. The tumor mass in the neck had decreased to half its former size, and by July i there remained only a small nodule the size of an almond in the sternomastoid muscle. This was removed for microscopic examination. The patient regained her normal weight. In September, 1902, she returned with a local recurrence in the parotid region. Both groins were filled with multiple tumors varying in size from a pigeon's to a coley: neoplasms of the lymphatic glands 105 hen's egg. In addition there was an intra-abdominal tumor the size of a cocoanut, apparently originating in the glands. The x-rsiy treatment was resumed and again the tumors disappeared in the parotid and groin and the abdominal tumor decreased in size. The improvement, however, was only temporary and in the summer of 1903 the old tumors began to increase again in size and many new ones developed in all parts of the body intra-abdominally and subcutaneously, causing death in Jan- uary, 1904. Case LXI. — Small round-celled sarcoma of neck. Held under control for ten years by five operations. Finally disappeared under x-ray; recurred causing death in two years. G. F. H., male, aged seventy years; was referred to me by Dr. Wm. T. Bull, in May, 1901, with the following history: About ten years before he first noticed a lump in the left side of the neck. One year later the tumor was removed by Dr. Bull and microscopic examination proved it to be a small round- celled sarcoma. The patient had four subsequent operations within the following seven years, one tumor was removed from the right side of the neck, the others recurred locally in the region of the original cicatrix on the left side. When first seen by me on May 13, 1901, physical examina- tion showed a tumor the size of an orange occupying the left mastoid region, very vascular and semifluctuating, another glandular tumor behind the jaw on the right side, also a growth the size of a small orange in the right femoral region, and a hard, freely movable glandular tumor in the right axilla, the size of an egg. The patient was treated with the mixed toxins and received thirteen injections between May 13 and June 5, the highest temperature obtained being 102°. On June 5 I tried the externa] carotid artery on the left side. The patient then left the hospital for a short rest and returned on July 16 for another course of toxin treatment, which lasted eleven days. At first slight improvement followed the injections, but later they seemed to have little or no influence upon the disease. I regarded the case as hopeless. On December 22, 1901, the patient placed io6 coley: neoplasms of the lymphatic glands himself under the care of Dr. E. R. Fiske, of Brooklyn, who treated him with the a:-rays. A static machine was used and ten-minute daily exposures were given for the first two weeks then fifteen minutes for the next two weeks and twenty minute- exposures for the fifth and sixth week. The treatment was followed by very rapid improvement in all the tumors. A letter from Dr. Fiske, January 23, 1903,- a little over a year later states that "the patient has been under constant observation and there has been no recurrence. The numerous glandular tumors in the axillae and groins have been treated successively and have yielded to the ic-ray, some slowly, some very promptly. I see him twice a month and he is in fine health." The patient died on September 23, 1903, less than two years after the x-ray treatment was begun. In a leHer from Dr. E. F. Sickenberger it is stated that the patient died under symptoms of cerebral thrombosis. Whether this was the result of the dis- ease or not, can never be determined, as no autopsy was made. The pathological report of the New York Hospital, February 21, 1892, reads as follows: "The specimen is an oval tumor 7 x 4.5 inches, no capsule; on the surface the voluntary muscle fibers are seen invaded by the tumor tissue. Line of incision has gone through the tumor tissue at several points. Microscopically, the tumor is a typical round-celled sarcoma with small amount of fibrous tissue struma, apparently derived from tissues in which the growth originated. " Examination October 24, 1893: "The specimen is a tumor the size of a hen's egg from the left side of the neck, freely movable. Microscopic examination shows this growth to be simple adenitis." The following case is of extreme interest on account of the long duration of the disease and great size of the tumor: Case LXII. — Lympho-adenomaojneck twenty-one years' duration. O. G., male, aged fifty-six years, occupation, engraver; nation- ality, Belgian. Twenty-one years ago he first noticed a swelling on the right side of the neck, apparently originating in the glands. This was soon followed by a similar swelling on the COLEY: NEOPLASMS OF THE LYMPHATIC GLANDS 107 left side of the neck. Six years later the mass on the right side was removed, but recurred soon afterward. Ten years ago he was subjected to a course of x-ray treatment, without any Fig. 39. — Case LXII. Benign tumor of the lymphatic glands of twenty-one years' duration. (Hodgkin's disease; one diagnosis.) Fig. 40. — Case LXII (neck case). Lympho-adenoma, twenty-one years' dura- . tion. (Ewing.) Hodgkin's disease? (Another diagnosis). io8 coley: neoplasms op the lymphatic glands improvement. Five months ago he was admitted to Roosevelt Hospital, where some glands were excised from the left axilla and a vaccine made of the material. Two injections were given without any improvement. Physical examination at the* time of the patient's admission to the General Memorial Hospital on June 14, 191 5, shows a large mass on the left side of the neck, firm in consistence, adherent to the deeper structures, not tender. The mass occupies the whole of the left side of the neck and extends below the clavicle. There is a similar mass, though smaller, on the right side of the neck and another one above the scapula. Circum- ference of neck thirty-one inches, on a level of chin twenty-three inches. Axillary glands palpable on both sides. The lungs present masses of various sizes, which are also shown in the x-ray skiagram. Liver and spleen are enlarged; abdominal cavity contains some fluid. Lower extremities are edematous. Pathological report at Roosevelt Hospital: granuloma of axillary l5rmph gland (probably Hodgkin's disease). Dr. Ewing's diagnosis: lympho-adenoma. Case LXIII. — Unusual type of neoplasm of the neck. {Pos- sibly similar to preceding case). M. W. B., female, aged twenty years. Family history negative; no trauma; was referred to me on June 6, 19 10, by Dr. J. L. Davison, of Toronto, Canada, with the following history: About a year before, patient first noticed a hard, firmly-fixed, lump in the middle of the left cervical region, posterior to the sternomastoid muscle. Very little change in size was noticed until February, 19 10, when it began to increase rapidly. X-ray treatmejnt was started at this time and continued three times a week for about four months, during which period the tumor diminished three-quarters of an inch in circumference. Physical examination, June 6, 1910, showed the whole left cervical region occupied by a markedly protuberant tumor, infiltrating the deep structures and extending from the mastoid to the clavicle; skin normal and not attached. The tumor was very hard in consistence and firmly fixed. Under ether coley: neoplasms of the lymphatic glands 109 anesthesia I made an exploratory incision and removed a portion of the growth cutting at least one-half of an inch into it. The specimen was examined by Dr. Ewing, who stated that he could find no evidence of malignant disease. The patient remained under my care for two months (June and July, 19 10) during which time she received the toxins regularly three or four times a week, and the doses were pushed to the point of producing fairly good reactions. While the tumor did not increase any' in size, there was no marked decrease. The toxins were continued by the family physician, with oc- casional intervals of rest, but with little effect upon the tumor. X-ray and radium were further tried but also without effect. In the summer of 191 2, the patient again came under my care, at which time she was still in good general condition. The tumor, which was still firmly fixed and very hard in consistence, had increased to two or three times its original size. The toxins were again administered for a number of weeks with practically no effect upon the growth. Since that time she remained about the same for a year, and then, without treatment and from no apparent cause, the tumor began to slowly diminish in size and her condition to improve. At present. May, 19 15, her physician writes that she is very well and the tumor is not more than one-half the size it was two years ago. In this case it would seem fairly certain that the malignancy of the tumor had been modified by the treatment. She had toxins, :r-rays and radium during a period of about four years. Case LXIV. — Small round-celled sarcoma of the submaxillary region {carcinoma of the breast in the same individual). Mrs. M., aged fifty- three years. Family history, negative; was operated upon by Dr. E. G. Tuttle, of New York, in 1894, for a typical carcinoma of the breast; diagnosis confirmed by microscopic examination. She remained well until the fall of 1895, when an enlargement of the left submaxillary gland was noticed. This continued to increase very rapidly in size until January, 1896, when it had reached about three inches in diameter, no coley: neoplasms of the lymphatic glands was fairly well fixed to the jaw, and considered inoperable. The patient was referred to me by the family physician, Dr. R. Oliver Phillips of Yonkers, N. Y., in January, 1896. I believed the tumor to be inoperable, and advised the use of the mixed toxins of erysipelas and Bacillus prodigiosus, which were started at once. After one month's treatment the tumor had become very much smaller and movable, and the mass had decreased to one-third its original size. Fig. 41. — Case XXV (tonsil table). Lymphosarcoma of neck and tonsil. Examination of specimen from tonsil called carcinoma. Section is from gland ofjneck. Under ether anesthesia on March 14, 1896, I removed by operation two globular masses, one three-quarters of an inch, the other, one inch in diameter, from the left submaxillary region; both were entirely encapsulated and on section showed, macro- scopically, the typical characteristics of sarcoma. Microscopic examination, however, by Drs. E. K. Dunham and B. H. Buxton (pathologists of the N. Y. Cancer Hospital) failed to show COLEY: neoplasms of the lymphatic glands III any evidence of malignancy, and a diagnosis of "glandular hyperplasia" was made. At this time there was no evidence of any recurrence at the site of the previous operation for car- cinoma of the breast, done two years before. However, in June, 1896, three months later, a well-marked local and axillary recurrence took place at the site of the former breast operation. The disease progressed rapidly and in July, 1896, I removed Fig. 42. — Lymphosarcoma of supraclavicular and retroperitoneal glands; very rapid progress. Patient died in three months. Primary in retroperi- toneal probably. the entire diseased area, together with both pectoral muscles. The patient made a prompt recovery. Microscopic examination of this tumor showed it to be a typical scirrhous carcinoma. A few weeks later a recurrence took place at the site of my operation in the submaxillary region. The tumor grew with great rapidity and was no longer controlled by the toxins. In September, 1896, I performed another operation removing an encapsulated tumor, the size of a small egg, which presented 112 coley: neoplasms of the lymphatic glands exactly the same characteristics as the first. In view of the macroscopic appearance and the prompt recurrence, I felt certain that the tumors in this region were malignant (not hyper- plasia), and asked for a very careful report. The specimens were again examined by Drs. Dunham and Buxton, but a large number of sections were made before any evidence of sarcoma was discovered. Finally, areas were found that showed typical round-celled sarcoma. One month later a second recurrence took place. The tumor grew with great rapidity involving and infiltrating the tissue on both sides of the neck. The patient died of exhaustion on March i8, 1897, five months later. A very slight skin recurrence in the region of the breast tumor was observed before death. This case is interesting from the fact that, in the first place, it is one of the rare cases of sarcoma associated with carcinoma in the same individual, and, in the second place, it emphasizes the fact that in certain cases strong clinical evidence in favor of malignancy, should outweigh negative microscopic evidence against malignancy. Reports of a few of the more interesting cases of sarcoma of the lymphatic glands successfully treated by other men, are included. Case I. — Spindle-celled sarcoma of neck just above the clavicle, recurrent in thoracic wall, incomplete operation followed by toxin treatment. Entire disappearance, patient well for eight years, when she died of an acute pulmonary condition. {Case of Dr. Joseph Grindon, St. Louis, Mo.) Mrs. B., aged fifty years, mother of a large family, consulted Dr. Grindon in April, 1897, for a firm, rounded, painless mass, about 2 cm. in diameter, immediately above the left clavicle and just behind the sternomastoid insertion. It had been noticed only a few days. There was no history or evidence of lues or tuberculosis. A diagnosis of malignancy was made and the case referred to Dr. P. Y. Tupper for operation. He agreed in the diagnosis and operated two days later. On dissecting down, the growth was found to extend into the thorax behind the first coley: neoplasms of the lymphatic glands 113 and second ribs and possibly much deeper, so that complete extirpation, if at all possible, would have necessitated disarticula- tion of the clavicle and ligation of the subclavian vessels. As much of the mass as could be reached without disturbing the clavicle was excised and the wound closed. The growth was submitted to Dr. Kodis pathologist to the medical department of Washington Universtiy, who pronounced it a spindle-celled sarcoma. The incision promptly healed, but a few days later the skin thinned and assumed a bluish look and in a few more days broke down. The mass rapidly regained its former size soon exceeded it and continued to increase in size. The patient began to lose flesh. She became anemic and so weak that she no longer could leave per bed. A supply of Dr. Coley's mixed toxins was obtained from the Loomis Laboratory, and an injection given in the back every third day, beginning with one-half minim and working up to eight minims. She received in all fifty-eight injections between the middle of April and the middle of October. Local and general reactions were severe almost from the first, consisting of a wide zone of erysipelas-like inflammation, spreading from the site of injection, with constitutional disturbances coming on after about two hours, conisting of chill, followed by fever, vomiting, headache and, on one or two occasions, mild delirium. In spite of all this she soon began to gain in weight, strength and general appearance. Meanwhile the growth rapidly sub- sided and finally disappeared. By September the patient was apparently completely well. She received no other treatment than the toxins. In February, 1898, several growths appeared on the right thoracic wall, just below the axilla. Four injections of the mixed toxins were given in February and two in March, without visible effect. In April the case was referred for operation to Dr. V. P. Blair (Dr. Tupper being away). Several masses from 2 to 3 cm. in diameter were removed and submitted to Dr. Carl Fish for microscopic examination. His report was spindle- celled sarcoma. Twenty-two injections in gradually increasing 114 coley: neoplasms of the lymphatic glands doses were given during May, June, and July. The wound healed and the patient remained free from recurrence. She died eight years later of an acute pulmonary condition. Case II. — Small round-celled sarcoma of the glands oj the groin. (Case of Dr. Alfred Jacoby, of New Orleans, La.) W. S., male, aged fifty-eight years; family history good. No history of injury, except a strain in the region of the groin, in March, 191 2. Six days later he noticed a slight swelling of the glands n the left inguinal region. This increased steadily in size more, rapidly during the last four weeks, and on April 25, 191 2, or six weeks after the strain, he entered the Charity Hospital in New Orleans, where Dr. F. W. Parham performed an operation, which, in his opinion, was incomplete. The flap sloughed and a large granulating surface was left. The toxins were begun and carried out under my direction by Dr. A. Jacoby, of New Orleans, on May 21, 1912, the initial dose being 0.5 minim, which was increased daily up to a point of getting a good reaction. The wound healed rapidly under the injections and the patient was entirely well July 13, 1912, although the injections were continued until July 30. The patient was in good health when last seen by Dr. Jacoby, in June, 1915. The pathological diagnosis in this case was small round-celled sarcoma. Case III. — Recurrent small round-celled sarcoma of neck; mixed toxins used after second operation; patient well eight years. (Case of Dr. J. H. Glass, of Utica, N. Y.) M. S., male, aged nineteen years. In the spring of 1905, the patient first noticed a small swelling in the submental region which remained about the same in size until the spring of 1906, when it began to increase rapidly. The first operation was done on February 28, 1906, by Dr. D. M. Marshall, of Toledo, O. A tumor about two inches in diameter was removed from the median line between symphysis and hyoid bone. No micro- scopic examination was made. Within a week after the opera- tion, a recurrence took place, which increased rapidly in size. On March 13, 1906, the patient entered the Faxton Hospital of Utica, service of Dr. J. H. Glass, who stated that he found coley: neoplasms of the lymphatic glands 115 the tumor to extend along both sides of the inferior maxilla, involving the lymph glands. The recurrent tumor together with both sublingual glands was removed. The report of the micro- scopic examination made by Dr. Wm. Smith Nelson stated that the picture was a perfect one of small round-celled sarcoma. The mixed toxins of erysipelas and Bacillus prodigiosus were started almost immediately after the operation in the hope of preventing a recurrence. A letter from Dr. Glass, dated February 11, 1914, stated: "The patient is alive and in good health at present, eight years after the treatment." Case IV. — Lymphosarcoma of neck. The following case was treated by Dr. George P. Miiller, of Philadelphia, and partially reported in the Transactions of the Philadelphia Surgical Society meeting, November 10, 1909, Annals of Surgery, February, 1910. The patient, male, aged twenty-eight years, was admitted to Dr. Frazier's ward in the University Hospital and operated upon by Dr. Miiller for a large lymphosarcoma of the neck. This was dissected out as carefully as possible, but within a month a local recurrence took place along the trapezius, which was also removed. The patient was immediately put upon the mixed toxins and remained well for four years, as per Dr. Miiller's letter of April 21, 191 1. One month thereafter a recurrence was noticed, the patient lost thirty pounds in weight and his general health deteriorated very rapidly. In spite of the resumption of the toxin treatment he died within a year after the onset of the recurrence. Case V. — Mixed-celled sarcoma of neck. A. G. W., male, treated under my direction by Dr. O. S. C. Davies, of Augusta, Me. The patient had first noticed an enlargement just back of the angle of the jaw in July, 1900. On February 21, 1901, the growth which had attained the size of a small hen's egg, was removed as thoroughly as possible by Dr. Davies and examined by Prof. F. N. Whittier, of Bowdoin College, who pronounced it sarcoma. He stated, "The cells seem to be a mixture of large, small and spindle." On April ii6 coley: neoplasms of the lymphatic glands 30, 1901, two months after the operation, the tumor, having returned, was half as large as it was at the time of operation and involved the anterior border of the sternocleidomastoid muscle and the deeper structures. On this date Dr. Davies consulted me about the case, and I advised a trial with the mixed toxins, which were begun at once and continued three times a week until May 25. The treatment was then discontinued for a month, resumed and continued until August 14, at which time the tumor had entirely disappeared. I received a number of communications from Dr. Davies re- garding the later history of the case. One letter, dated December 6, 1905, states, "The patient is still in good health." The patient died in November, 191 2, eleven years after the disappearance of the tumor, of what was supposed to have been pulmonary tuberculosis. The remaining cases successfully treated by other surgeons will be found in tabular form at end of paper. The following tables cover 168 cases of primary neoplasms of the lymphatic glands, including Hodgkin's disease personally observed within the last twenty-four years: With regard to locality, the cases are distributed as follows: 77 cases of sarcoma of the neck. » 25 cases of sarcoma of the tonsil and neck. 10 cases of sarcoma of the retroperitoneal and mesenteric glands. 17 cases of sarcoma of the inguinal glands. 18 neoplasms of the axillary glands (16 sarcomas 2 car- cinomas,) . 21 cases of Hodgkin's disease. I case of sarcoma of the mediastinal glands. As regards the relative frequency of lymphosarcoma in the sexes, my tables show a great preponderance of males over females throughout the entire series, except in the mesenteric gland cases, in which the proportion is equal, e. g.: Retroperitoneal and mesenteric glands, 10 cases (5 males and 5 females). coley: neoplasms of the lymphatic glands 117 Axillary glands, 18 cases (10 males and 8 females). Inguinal glands, 17 cases (12 males and 5 females). Neck, 77 cases (54 males and 23 females). Hodgkin's disease, 21 cases (16 males and 5 females). Tonsil and neck, 24 cases (20 males and 4 females). The duration of life in the fatal cases, so far as definite data are available, may be of some interest: 2 died within ten days. 12 died within a few weeks. 20 died within less than six months. 13 died within six months to one year. II died within one to two years. 5 died over two years after the onset of the disease. A summary of the cases personally observed shows that 26 of the patients have been successfully treated — that is, the tumors (inoperable) entirely disappeared — with the mixed toxins of erysipelas and Bacillus prodigiosus, and have remained well from one to twenty-two years. Nineteen patients remained, well from three to twenty-two years. Of 77 cases of sarcoma of neck, 8 have remained well from two to fourteen years. I round-celled sarcoma of neck, well two years. I sarcoma of neck, well two years. I adenocarcinoma of neck, well three years and then re- curred. I round-celled sarcoma of neck, well four years (the primary tumor was called sarcoma). I round-celled sarcoma of neck, well six years. I round-celled sarcoma of neck, well six and one-half years. I small round-celled sarcoma of neck, well thirteen years. I round-celled sarcoma of neck, well fourteen years. Of 24 cases of sarcoma of tonsil and neck, five have remained well from one and one-half to nine and one-half years. ii8 coley: neoplasms of the lymphatic glands I round-celled sarcoma, well one and one-half years. I round-celled sarcoma, well four and one-half years. I round-celled sarcoma, well six years. I spindle-celled sarcoma, well eight years. I round-celled sarcoma, well nine and one-half years. Of lo cases of sarcoma of the mesenteric and retroperitoneal glands, 4 have remained well from one to twelve years. I round-celled sarcoma, well one year. I round-celled sarcoma, well two years. I spindle-celled sarcoma, well two years. I spindle-celled sarcoma, well twelve years. Of 17 cases of sarcoma of inguinal glands, 3 have remained well from four to seven years. I sarcoma, well four and a half years. I sarcoma, well four years. I small round-celled sarcoma, well seven years. Of 18 cases of neoplasm primary in the axillary glands, 4 have remained well from three to nine years. I round-celled sarcoma, well three years. I round-celled sarcoma, well four years. I lymphosarcoma, well four years. I l3niiphosarcoma, well nine years. I case of sarcoma of mediastinal glands has remained well six years. Of 21 cases of Hodgkin's disease i remained well for seven months after complete disappearance of the disease under five weeks' toxin treatment. The patient refused further treatment and died of a recurrence one year later. In the list of cases of other men, (treated under my direction) one Hodgkin's case recovered and remains well at present, seven years later. coley: neoplasms of the lymphatic glands 119 recurrence after apparent cure with the mixed TOXINS In a certain number of cases in which the tumor or tumors had entirely disappeared under the toxin treatment and the patients were apparently cured, the disease recurred at varying intervals from six monhts to six years. A study of these cases may be of some interest: In one case, after a very large and rapidly growing primary neoplasm of the lymphatic glands had apparently entirely disappeared, the disease returned and progressed rapidly when the dose of the toxins was diminished, but began to decrease again and finally disappear under larger doses of the toxins. The patient is now well two years and a half. In another case, a round-celled sarcoma of the tonsil with extensive metastases in the neck, the tumors entirely disappeared under six months' treatment with the mixed toxins; one and one-half years later a recurrence took place in the glands of the neck, which proved fatal within six months. In a third case, a round-celled sarcoma of the tonsil and glands of the neck, the tumors having almost entirely disappeared under five weeks' toxin treatment, began to increase in size again when the dose was reduced. Under increased doses the tumors completely disappeared. Six months later a recurrence took place which proved fatal within a year. In another case still, a round-celled sarcoma of tonsil with extensive metastases in the neck, the disease entirely disap- peared under eight weeks' toxin treatment. The patient remained well for six years, when a recurrence or a new tumor developed in the opposite tonsil; this tumor recurred very quickly after two operations and caused death within four months. In one case, an intra-abdominal sarcoma primary in the mesenteric glands and small intestine, the disease entirely dis- appeared under four months' toxin treatment, then recurred one and one-half years later and proved fatal within six months. I20 coley: neoplasms of the lymphatic glands In one case, an alveolar sarcoma, primary in the glands of the neck, the disease almost completely disappeared under four months' toxin treatment; the patient remained well for three years, when a recurrence took place; incomplete removal followed by the toxins and :r-rays; patient well at present, six months later. In this case the tumor was pronounced adeno- carcinoma by Dr. Ewing.^ Small round-celled sarcoma of the inguinal glands; complete disappearance under the toxins; recurrence, which again yielded to the toxins ; the patient is well at present, seven years later. In a recent case of recurrent inoperable sarcoma of the tonsil and neck, the tumors decreased to one-fourth their original size under six weeks' toxin treatment. Then the improvement ceased and the remaining tumor was removed by operation followed by toxin treatment which was kept up for about two months. The patient then left for a two weeks' vacation. Examination upon his return showed a recurrent tumor one inch in diameter at the site of the incision. He was again put upon the toxins and while the disease was apparently held in check, there was no noticeable decrease in the size of the tumor. Under the combined toxin and radium treatment which has been con- tinued up to the present time, the tumor rapidly decreased in size and there is now scarcely more than an indurated edge at the site of the tumor. September 21, 1915: Local recurrence with cervical and mediastinal metastasis have developed and general condition is rapidly growing worse in spite of continued toxin, x-ray and radium treatment. For later notes see Case No. XVIII. In connection with these recurrences, a brief reference to my first case treated with the living cultures of streptococcus of erysipelas in 1891, may be of interest: Inoperable spindle-celled sarcoma of the tonsil with extensive metastases on the neck; both primary and secondary tumors almost completely dis- appeared following an attack of erysipelas produced by inocula- tion in October, 1891. The patient remained well for eight ' December i, 19 15 there is now evidience of mediastinal involvement. COLEY: neoplasms of the lymphatic glands 121 years and then had a local recurrence which proved fatal within a year. The most important lesson to be learned from a study of these recurrent cases I believe is that in many cases the treatment was not kept up sufficiently long. I am convinced that it is better to continue the treatment longer than may be absolutely necessary in a certain number of cases, rather than run the risk of a recurrence by too short a course of treatment in certain other cases. In cases in which the toxins fail to control the disease I believe it advisable to use x-rays or radium or both in conjunction with the toxins. A summary of the cases, 36 in number successfully treated with the mixed toxins by other men, shows the following: 6 cases of sarcoma of the mesentery. 6 cases of sarcoma of the retroperitoneal glands. 17 cases of sarcoma of the neck. 3 cases of sarcoma of the tonsil and neck. 2 cases of sarcoma of the inguinal glands. I case of Hodgkin's disease (well seven years). I case of multiple sarcoma. Of these, 30 remained well from one to seventeen years. 7 remained well from twelve to seventeen years. 21 remained well from three to seventeen years. II remained well from five to seventeen years. Most of these cases appear in tabulated form in my paper read before the third International Conference of Cancer Research, Brussels, August i to 5, 1913. 122 coley: neoplasms oe the lymphatic glands Sj5 it^S only died 904; tas- Became rapidly worse; Nov., 1914, operation; curetting; died Dec, 1914 (ex- tension into me- diastinum and probably lungs). ect; life, mp- ths. ft "o 0) ft Pi •a j_. o 'a; ^ oi >> Complete pearance pr es en years. o >. a o a! Improvem temporal January, multiple tasis. Later, no duration from firs toms, S Pi S S i (u n to ;-6 S2 -oBJ S5 S g ,^ S S 6 is o M.^ oj bflS Mfi 0.5 N E ft-iS't^ S g u •ftgg O C S d S^ Si in'^' a? o ft>>g.2 3„ ca „.2 ;-o e- fl5 t! o aSa O ft c '-i^ d -; c! fe o a ^ ftO. •2 " o So « asj o hi ■-I'd. a ft ^ a.^ ° rjj o g ><; w oj CU "tiJ ^ •-'~^ ih.Sj; „ oS c ?^ 5> S 0-3.2 1; c u M c^ ca 00 rt M d r ts o o " 53 C ™ O ft o 1-, C ■* ■-3 ° is 0)^ OS ^.^^ ^ w „* Q-d 1-, vh ra w o C •-« o i-.'d ^ 8" o a as M gags :3.^ M P ^ S-dl :2-S°c5 ftS " ot^ >,g-^°a saSSs > CO CO O M o cS o a cs 3 B jr„p o *4J rt a; a>fi 4J o O ■S a . - S" " .W^ c— o-d aa oQp^ a°'S O M P^ ■d o boa 13 -^ ii31 03 ■^I'S a a •= s &^° CO CO J^& -•a.2. - oi C S 5 fe u So c -d rt.2 R O 4J d « •^.5 coley: neoplasms of the lymphatic glands 123 , P I, OJ ►< — '•-^ — •- Si? -2 w 5 " i- ft lu „ '"_ lu I 5 ^ S ^.S'S.'S g >.•- s g ■^ -so ni'dJH M 2 ft <" ?5 Eft^S 3 rt P u Q^ ;S2 « C iH D •*^ « h c &tJ a rt "^ a^ u J 1^ ol o V •„- u g c S o m'k .2 g g SfS ft..W g OV 2 cs 0\ cs ^ TJ .-3 C t-. o t-* a; o) tH K-,ft M fto.'^ t! 1-. °i^'cd -"ft- : D. &-S-?l« S^cli'S 1 oJ c-^ S.2 -o^ :"2^s - ; - (D a! ..-a >.^-^ So I d o goo. 5 ft^- :2°ot: O (U c o E t, M .. lEsr cs d o '*-. - M+j >• d C •- S 4).i; d^ o ft M ■— 1 « " o c >*-■ .-^ - « ts «> a o I- •- K DO -^ >> =1 ;« ■" -c r ft — 01 > ^ |a-a.s?-^E-sl ^ di- .2 "^ E 121 ftOi' I- KS -do K s "O C3--^ poo E p< s ^E C ft 3E o >> cQ ft oJ E o« offi ES *4-|' *" 3-2 -d 0! SE _" ;„-'d o C g " O w E^ E-g 4J O 3 o ■000 G.H E ° -S 3 in^-d — ' ft 2-^ <" , t»+3 o . 0! (U N >. •- "n Pi r. tn " O 73 O S .agog Q 2 Zi" ^ ^ w m " tB _ > C'- ° _S 2 "^^ t, D d g . « "^ Ut3 o c "i^ a« ^i ya w 3 a .b-^ « rt H 4S « - o a ■t^ a^^ c tS X o o f5— 1:; Cxi .2 a-- ^ S.2 c la X C (U o o ° h wJ3 o ^Ef'a ■^ a (u o lu o p. oj d t3 13 '^ O ""•^ Cm •— a^S^ S. Sjc-d a o .. P S (U ts d 0.5 CM ^— ^ hn H S « >g;oc-yC .0 *^ o 5-? .2 J3 3 c S^ M H c g « i?^ 3.2 c-2 i2 =>- 3 3 fe fe (x! [JH C ^a - C.2 C8 o o Si o ^^ c.2 o o g '- "0 cS eg 3 o — •a a1 e-o ta ft 3E o >>^ >. J3C ga- a; 8cJ2* a ^ ES^'S.saig t5-SSS>>Ji2 ftO a a ■d tij-j2 ■"So U S M "t^ ^ c as.2 II §§ 2 2 CO b S s s s § S b lU bo ,^ N ^ 00 00 < T 1^ N re •a CO s § coley: neoplasms of the lymphatic glands 125 Q ^ > a! M o o c 6SS o c o o rt 01 Q P V > o.HIts 0_rt C 2-a g SB g S 2 c CO > c ti rs T) r^fn s (U en 3 N . < t- i-Sg •a >, d cj c; " <" ^ !n n « ,-; nj 2 o l- ajj^ o 5 D 3 c!i Ji'^i! ,„ " 3 E 9, >- n t:^-2 fto o O 3 -•- O o C-- .!rl ^ 4) „, O 0) V ?. 0-« u C o u tMc w^ 3 C o o -■a C ""t-I o - o t "^ !- ^ " 2 Sj ..c o o a O 10 ■g -|j o> o _- .t^ w E aj " " «^ ■;^2 4) " -^ .. O W-- ^ d -"-S gT3 oJ a! 4> r J-- O u OJ t-. '^ 2 ^ S - ° t; 2 °Q c <= 2 3 fe^ -a g.o S OJ o.inxi o E 0] S r « ""„-«?; < C f! X, H CO .tjQ^i o E o 2 «i f^o 2-^ °>" "^-^ <^ .-a < '5, "" 0>« r^„ O g E°-:2'3"£''^ «• .. I- CO '^ c " Jj •ioKo03»J3l-.go N in ■^ ■^ N ^ *^ '^ " TT 126 coley: neoplasms oe the lymphatic glands I CO < o M o 2 o S C8 E is as >< -d c 2 0\ Oi (U u^ -T ^ o oJ .^ +j 05 .t^ c "5 C8 0) It! & ft a J= la q3 -^ ^ -g c ■j; xt tl m c '& P^ "a o cs a; tH t^ p XI 0! ■d "d 4) •d a ■d 0) Q (5 5 5 S 0) tec > ?! i-l 3 i (U 0) 1 is" 03 03 .+-» a a o; I-. fe 4J ca +j .2 4J +9 >, a 03 '3'5 " p. ni > tH 0) a " o a! 05 ^ o> c p.- u a 3 V OS ft-d 3 C iti 0^ Oi u ft a a (U > aiJ p:; Oj Si.-S 0. « ft OS W J =-( H C-i *^ o o 3 DO 3 O o ^ 4-* > o ■z, P.O •o-d TO cj u 53 >> aa M 3 Oj "3 > 03 oi ft c >1 1-1 ■d 0) a (U a 4J -d ft oi u u a a a a ft ticyiH c; 4J OS a a Is oj ^- « s ft? <" c3 Sol V o o 1-. CD p. O -d G peration, 906; toxins st operation, 901 ; curettin ned gland; C V 3 Cfe 00 0\ M 00" V a a oi (U ft >>oi V S ftte (U r'o ft ii> & i3 (u 01 a •7; ft "ca a >< -•^H o M o o '"' .Ji! "-^ a +^ C! w 1— > 4J > G MM w ca d M lU 4.3 fe (i< E J fH ~T TJ t^ 03 , "O (S cs ta >> OJ ca 03 ca ."3 SS H a 0) a a a d a m,$^ 3 o 'flj a nl 03 s ^ ^ 0! oi 4J a XI} -d 03 a oi MS .2 8 h'-O XJ oi > "d a Q Xi oi a a °l ,—1 QJ ft ft 5 ft a .£P K — 1 S ft fa u a >> E oi X Oi a "ca 1 03 CJ43 a >> M J ►J m J ij o i 77 44 ' ■u i7 ~ , +j , .. . *^5 o a 3 X3'-* d 03 ■d i5 ll M.S 01.3 T3 >.* 3.^ S d o o £1 ^1 §1 ft ft . W tn H H m ^ m TT oT i~N dxi a O u Oi 4J X! 4J X2 '+3 O •S c o a e a B ft a >> 4J a a a' a -4.3 aa a a-;3 S ^ s S£:d !>.tM w 1 a .a a a t- vO w n H 10 N •d ca-« c C.Q a 0) 3>2 o 2 u a Si CO li 03 >> ■z >. ^+-> cS ^ A .i4 .^4 .i. rv u. 00 Man a o « <1 r! to o ° l- fe (U w.S « ni 5! k!i 'S il J^ i-,_p3.t.„Oni (X, o . o ^; MP. ^B P.S. O o o K ., -'E'S c23ci>o H 0/ J: M ^ > feS ° m ^.2' fe cq 1^> ta 3 • o^ _fe S § o •d s s s fe (L, § Ph Ol M VO 10 00 -a- vO > a v 73 (U ft c CU o. «3 >■ !S 15 CS CJ ca a) ft ca ft ti a 4^ Pi O 5 p IS •d D Q CU in u _aj 3 >. (U C o g •d (U W CJ c ca 3 1—1 ca aj r (u-d o-d (u u O B -i |.| ;? 3 J T ft ao o a _g 3^ g mi '3''3 (u o o > g . ca t-i < o c 3 o a 0) -n CC moo" C o n 2 O " «j S g o •d cS ^ 3 O C C3J a o 0) o P.C O OJ O 3 0\ o O. 3 "3 0) ■d "^ 0) . ca u -)-> c ^- M CU M .S ^ ^-d a 0) o MS o «oo" i •d n CU +j ■d > o g o -" ca t^ ca ca 6 c t; ti o I- bo h'~ R ° ^ tH ^ ft o 1 u 0) 0) 3 u it 1- c J) nj P.1-. 0\ O "" O ctJ '^ P. II -)0 ,g W3 - CJ c 5> .2 ^ ;c (U o w ftoo 1-. 2 i la ft ca Lh ca ta 1- o a o bo M g o M cl o o o 00 o "ft a o Q • - . lU o Kp3^S:2g o o o O o ^E s S ""^*^'^"^"^'"' ."tS •a ■d 'd ■d 'CJ Li ca -d ■d •d 'm'S. 0} _i) _2 (U 0) 'oj (U (U CJ .^2 o CJ o CJ o CJ o ■d ■d •d ■d tJ 'D CO •d ^ P.| c ci a c a> C a c ■d a 3 3 3 X 3 o 3 c o o O O S O (J O "ft Pi Oi p; Pi P! Pi CO |l CIS CU a C3 ca ca ca ca B s B a a a a a cS — o o o o o o o o •^ o o o o o CJ Q u t-l tH u bi u. a ca tS C« cS ca ca ca m m m m w w m m (U T3 -* c d o . "3 ^ Jd ^ .^ CJ /4 o o OJ a> (U u v ►J Z 2 2 2 2 2 2 z (U ,n OO C<1 M o 00 t~ Q o o o o o o a o Oi c> 0\ o. a <^ •^ M ^ *^ " [X, s s fe s s S S bo r^ o r^ t-i C3\ 00 00 rO > 00 <3v pi o coley: neoplasms of the lymphatic glands 129 Q ^ O H Q Q Q « Si S ?, ; !s *.I3^ i (jj-o w, W (U & lU (U ti « •■ ^ 3 aa^> 6 S3 O " « K fi c - rt " g-t n! (u 3 (U ™ 5 '■^ O Q.^ 5 „, ca o iu_ o o Odd i2o>.i XI 'H ci « c o /-? £ 6 ^3S°§-ag- - i- o o rt S " ■^ *^ C o o V '^ ^"-^ C 2 - IU.2 o '"^^ g'nj P.C8' a N e'e-J -2 S-: I o c S 3 3 c — OS 3 0) >. H iH ci >. Ph J3 («' u > « r n rt F td * 3 Mm CUtD HH H OT g-TS o a .2 C.23 ni 13 n r/i iH oi hTl'S ; ^ Pi 3^e g2' O Illllill fc- 0. 3 ov — be o ^ S fe S ro CO 0\ I30 coley: neoplasms of the lymphatic glands p4 .S .a la ° t- "5 1/^ ca K^ a M 'o c o d > o '0 « s s o 3 i ca t-i fee 03 00 M ca •d a 2a .o it emporary i m - provement, later no effect. Death the fol- IH ca (U >, M a ^ £ •sa-SQ isSS ^MJ3 O O w Q s H CO Q H ID p.^'o.S si's g "3 a (u s ca g e 0) ro SI:; ca .w sg O 0) (u'lH (D 3 ~Z^ o c* c o ^ +^ > _a Sj -tJ t. ca ca a^S-gs-n o I-, +-> o +j ca ft ft ca a > o u ft .a o a c .. o ■D M cd '^ tH o .a cue 11 3 CO ^1 3 ft„ S ca H m rt w ft. -^^ "« ftS a i3 « a 3 ca.S ca ^--^- ca S S-d S a &2 3 £ H Q w f^ Ph •z p^ (i! T3 o i tH 2S« (U-M ID U>^ ca H ca > .a .11 &g is M •^.i^^ £.r> ca o s Is O C o 0! c\ a o o • if D a o +J a _o *+j ca (H ft ca a tH SS-t; .£ Mw!Xi ft ca ti o xi a ■S-sa tH ca n g O-u ft o ^ >■ a a 3 O °i "ca-d a-u -3 O rt S g c« a ta a ca a ca a ca ca a tS'^S o o ca o o o 5" u la !3 ta !a ^ w w CO CO H CO t^ a ^ O c «jxi -M o ^ ^ C/5 tc ^ "^ 3 Q a a o a O a u ca (U ca >. o ca a o a Men VO n CS cs ^ 00 +5 1-. fli o o >> Anteced trauma infecti -^:t5..2.2 ' o 4-a o ^O oa z CO 'z o o a -^ a So 2 A! 2 2 o 4) •z. 2^ mo c^ to" ^"S'So CO 1 1 l« m >i " •go cT-* a o t, 0\ n o. 1 Q 1 Ov §? Ov 2i^ . 3 0> 1— i" caoo doo ' CO ^ pL. Ch s s S fe § (U d O „ o vO ro •;(• <: < ^O n t^ lO ■^ - 1 ( s I 2 n 2 1—1 ^ K O s % _ N « "* lO vO t^ 00 1 t~ t^ c^ t- t~ coley: neoplasms of the lymphatic glands 131 o w Q o o o o < 3t3 m (U i^:s s i=! o fl " « s^ rt : n! ^ 3 — C OJ u 0) u tj •^3 O 01 CC C >i > i- Tl 2; >. '. O (y *^ O tH l_ (U ^ O t- 28 "U, rt > y P.& O o ^ k^ u -tJ u o cs S 3 rt c S 5 'S Si'^ 0! "^ 3 .12 M M u 1) <-3 H ^ -S - a P. X ■-.s «■ '^ ,0 DO H O H 1 n! •d a C o 3 " o ^ g J) tg B a O.tJ O" 3 >.i! OiS OiR S o o 13 n! o G ^ O r 1 Pi SEE tz! m m CIS t3 H OT , . . ^\ , (1) y trt P. S 3 a ^ C 0^ 0. CD 0} (U 3 60 >< 01 u t: J .-^ «- M o 2; t5 s o ti o o- J, g o ° o o ^ z •z. C 1) o c >;o Ci v C H : '^^ O (3 CI O) C ID O C O c trt o t^ o -^ o C cu C o 10 < w 4) a rt 2; ^ en s s fe fe s s fo Q a 132 coley: neoplasms op the lymphatic glands very r h; de al meta 8 mo begin atment o oj ater growt gener ses, :rom of tre O a " B 1^ i- UdCOi-iS!"2itS 'OS fe ti •d t3 P o 5* S2 w ^ Vi ^ *-> ''5 S 2 £ « d « „h t^ 5 p Q c8 o ^ A § i >> J'c-S'SSge">>'S 13.5 " t!w-i-,(ua)p,tl iH 3 ^.a fto'o o ii B' ft a! s L5e™S.' bag"'' 2=c-S"S •^ (U •- ft"? *-" o ""^ 3 c Ov . a ft c N ? ta o o ^ ,„ .2 i-TS „ ."d O H o ^ ■2 a oa),„S-MSoo gftfi>aj "*■>•= t B'f< "Sna b „ 3 O OM g M o c o-s ■d d u^ «H 3 o ■d " (U 1- ni m m o u'd ■d ca 3 S ^"^ hJ Pi 5 ft o O Pi (U Pi cj o o III CO D Sg.2 d'=' 2 o jj-g : is ^ lU eti Si <- O J) c 6g.2 > •••''' m .ft^S^ V ^ ^ >- it (U "S o OJ & te I- ft goa ^«.2 o c o cS.S • - o O O M O •3 ts-"^ Ch 0) o a a i N vO ro 10 C ■gg-.s ofl res ela . th ack J3 lation cultu s i p onths 2 ;^ "^ c 'S rt 0.5.21^ 3 ^ B Oi? p. D s Q 60 u > >, g.s. rO 0) u 00 o-^ ~ ^ o\ o 3 ■ -S " C O 0! t- - o "■ n Ma fi b ^v o "! -r. o " S'2 i '4'o^ •!; c u =« o S "iT.a O -JjJ U M -^ S.3 5 tH -u o o M ""^vSni— 0>C " K « J^ J5 S <" t. o i;t P» P * oocii-^"^ C-^-rt >= C C > o-^-i3 0*5 g C C oiS Pec « ^§5 2 g s«n ^^ gn 3 g-2 S g g § 8.2^5- g- ■ S >. 1-, M) 0) i- ^'iJ*^ < c c rt M H " J^ ?. H« lU 3 . M ■rt g P t/i J^TS C P,t:! 3 P >. 61 1-1 o hJ -d p a 3 P< g 2S 8 S ° •d 5^ V V ti O' Ui (U oJ 5 OJ ^ p CTJ 6 S R S 2ii PiS 60 P c P c C 0) P c s s ^ fe s S ^ fe ■»J 3 Oi 00 a Ov vp Ifl < •* T " " rO r^ 134 coley: neoplasms of the lymphatic glands o-S^ M U g , a; Oi s s ,_ lu c 0. «i Xs *-' *j J= f' efl d) g M s -a c a 4J 5 ^0 a ojt— , ft 5.9 .— -JO C c >> u 3 OJ •SB se 3 -3 cS ■315 °J <" be ^z P"° Eo (u P^ ^ q""' fe ^'~' ^S a 1 tH ecu si 1 tS 8fe c X OJ ^ 5 OS tC CU ^ 41 ftu h a d J ■" ft 41 4) . > 41 si ag 3 ft 4) 'Sis '+2 ? ™ ma;'-' 4-> d ?, ft 0) 1 o-d eft d§aa SftSac? CU >-< 4) E- e! Pi w z Pi; - CM v^' ri tS ^ 1) ;-< '" i 1° ii ^2i|J a aSS 5 1^ d OJ ft dg^ "-B •-ift M (U 2 j: M *= d Is d i->ft „^-tJ .0 d „ d c d 3 "^i ^ " . „ 4) "d (U r; d d gs .^^"^-t; cS-§?3a|H +j ^ u d d fe ° „ c - V a +J w ^ 3 n! J^ « C t-i d c C3 >— 1 C < ft ^ts ti "S ii-S fe b OJ d ° " s ^ c s H "^E " ■a ■a , .-3 tS a ■3 Si -^a a osis, opic CTj •0 x) ■d -d C 41^ C3 "3 .— I- ^ a! a v-a TS cS »d > J3 d a a & 4) 00 00 H "" [X, ro c fc 03 j21 a d d cS B <-• 1" 3^ XI (0 •-S-S 3 > ^ •z ^ z z Z ■d >, c c3 "tS a^ _rt C3 s _cs cS cS Oi • M OJ ►< fi j< « X X X X K < •< <: < M Ov 0\ 0\ Ov Oi Ol 0\ w H M M "•^ M S S fo S § Ph Ph fc 4) <13 w ■ Oi t-- t- fO w ro N w ■* •* V fe m &^ c i p^ ^ Oh' 6 M N fO t 5 -0 00 coley: neoplasms of the lymphatic glands 13s (U ^ -' C O O O ^ w a; •j2 c! t, a & S 01 ":«- g « a ►< M o P o > •d .2ja ti S 01 "d c ■- y S >< ■s S 3 o tso o O w n O lU .;:i o o " S " M -" lU ■^ . u n! iH . .. . c3 W. '" N dJ > ^-< >.2 Ji . ojJS.j'd-j^ W(£--SO ;; o '^ C »> n " fc°S«,2^t5 O c ?, o o o'r " I H W.iS M ft+J g O "d S w iu_ o o o aa.s-si w o o g , ^E.So.l "^^gs-ao-d u9. o^ fe I j^ P o ^ o- .4J — • (U rt > " t^t S-2rt< tWd '^ 'D "I^'t^ r 33^o3rae.Sg->;'o2gS I—,!—, (u+joi— >On!°Xl-i-'>'3'3 p nl S rt 0^ J3 s I3 >. " « rt 0> -4-> M &3> l-iH w (U en § Ph p!H u •* 00 < « ro Q < O < I— I H w < I— I Q W t: t: 1 > C S n'. ,rt— " ■« C t, Cj Sh .3 c3 V "! K (Li. j lU >,>, h ^^ cs ftC 2 ta t^ C "ie 52 2 nant , clin- a n d diag- J^S.SxS <5 oi (U >. :yr " 1 ^ ttf to 4=1 fc_,*^ M ^"00 0, Z" S ro 10 p: COLEY: NEOPLASMS OF THE LYMPHATIC GLANDS 137 13 c 3 Si. 2 oS & & i) »□ ca ,/, ca V d ^ ca w "ca 4, W M.W o\ ^ "o-d .'dm M d :0 ^•o-S ^ x;^„ ca ns „J3 ca ■d c ■" « S "3 a... g 00x1 c T3 -a c "• E J3 ■«d E -I: at itl u ca ^1 ii 1) •d 3 ca -M ~ E 'd^-i *H c oT '^ " i-" 3-fci w « c III goo" .2 iJ a> ft d t! .■" n Mq O.i: •- bfl --o _'-' ;: d "UQ ^ „ ji^'d'd'SS"' E - c S— 'i^oMpfthcaj^o .d d 2>„o> d " cn'i^ 0" d >- .2 ~ lilli -dS.o-caB •- .. ;n 3 ^ tl ca-o S £Pa 2 3 t^ fe h Bo ta M ft a£d X 60 te £ fe M ■d ca ."ts c E uj CJ ■a •a •G 3 T3 T) '~i a _aj _aj _« CU ^ ca C . C^ ^ Pi W Pi Pi J Crt e " ca ta ca ca ca ca ca Ul'c B H B E a a E CTJ-"' . 5 " u V-( u u iH u ca cB ca ca ca ca ca M OT m m OT w M & ^ "^'S - -ca^« c v£ ?^ ft OJ St? 1 J? C aJ Jf > 3 ca +-> >. 60 c C3 »-. 3 Q -■p C S > ca 2 >> ." ^a Pa c >> tH 60 l-> ♦J eg ca , CM H O) H « •- JH4J ^2 -S d 4J L^ c c OJ £3 ca ° "! c«-B^ca ca ta t- S 2; g t, « . ca ca ca ca ca ca rt .■s .s-s .s-s .S-d .S-d •S-d .S-d •S-S ■3 3 s 3 c 60 iS 60 J5 60^ i_5 C bo C 60 c so c so U 60 d 00 d t>o hH '-' l-H l-H hH '-' i—t (U t ■* >0 Ov Oi 00 ■o la P Ov C3v Ov M !» Oi CTi 00 Ov 00 o\ ^ ^ M . tH ■^ " *^ (X, % S S S 2 ft. 1) 00 ^ :<^ re a r^ <' M -0 1/5 I/- vO ro "^ ca w "Z. D^ W J w aq d hJ f, ^ -c 1~ 138 coley: neoplasms of the lymphatic glands 6^ c.S, ai °5 O C M ■a ti 60 0) w -i in o - '^ j:j p. I-, -M Q y d) 3 o ca o SPh-- 1—1 (-1 3^3 01 (U 'a S Z. "> a u (U "O E CO « jj o'S rt !n K ci< o e V- S ^ S P. >J S c« OJ o J^.3 O D P. ■- 2 a! g c4 '"O S c S ft ?^E 5^ y ><■ m ft! g'o'g lU (U > ftN O C o «S.2 ij t- ca C8 t^ M a g >,§ S 2 « t 2 C>3 O C 03 CD ■_2<3 CD ojQ ft Ooo-g ^ 4) O CD tS! CD O; •s ^_& ° V f, a >^ ! -^ S C! il"" /-; t; cS Moo r cJ^ S- pCnUpniH.S'Ocu^ • r: Gi ^ co tL'^ Jr" ' CD ^■-■B ft tH OJ (•( ^. -I^Op'DCCJKg-IJ .g M C3\ 5 t»w-;:0 cfto "d cS c fi a o o oi _ Tl E ID O ^ *-• O --T in bo"^ W C d N -^ -M u> S^ > ego u-- >. o cs ° ° c-o '^■2 E ^ X E O t! o-^ d o E »; o-r; Eg H ■* -d cs-« <" P o d M 3 p! '3 5 d w d oo '=•§ d M .S-d 6fli2 C bo d sc 0) s ^ c c o ^ fi< w" m «■ o M CM c^ •* to QC ^ w M t-l w ••< coley: neoplasms of the lymphatic glands 139 -o'fe.S '(5 .SS K a O £3 O (U O I- S 3 cU O 0\ > 3 > •" E o — I > > ■3.62 HOC 5 c ft.2 > a >, > K S xplo m turn the mix W W w W ".§ . E >< S o S oft 1) o >>> a X O tl M 140 coley: neoplasms of the lymphatic glands C PS Well Aug. I, 1915, more than i year. Well Nov., 191S. 3 years later. Sinus curetted Nov. IS. 191S. Diagnosis of tu- berculosis in mild form, made on basis of inocu- lation of guinea- pig with pus. Result, immediate 0^0■^^t3ooJ&mOJDw (U oi c i " i ^-"^ « a ai«3 a ° IH " 01 " ^i: M oi 1 « (U fe S bo < 2 CO < Q 3 c c o rt**^ o ■-v ja o > o Ov O O 3 " " C ^ . •i O.'ra'O-S g O « C ft So) s o c! d 5J 5 i> O o a>.5 ■^S'3.e3 3g| CcSOftt.'MbC Eg -a o ft> as 4) ft c " ni CI (UOO >'a 2 " O 4) *j 1 • 1 •- • - "O boo 3 M Q 3 S =* icture lof H auto Ewi 1 H ■SKfe.2?2 QOJ .. cU lood typic kin's Dr. typic kin's land typic km's guin ecu nega W CQ W ffi ta 3 4) S ^E oi >-'d CtS " Co"*" 4>.^ bfl.r^ bOm c3 bflfl i_,.««4-(— . M-- — .jj bo o « no b « oi tn 3JH il M o> moo OsO\ s s s fe ■* M 0\ J? coley: neoplasms of the lymphatic glands 141 6p O (U s? 32s X « s w H H ■ ^ J ^ ■d ts cs ■u >- .S.ya _ g (3 >, w ^ M nj -^ C o.ci a £S^ JM KclS 'P'^B c ^m^ W g.ffi o <^ :gs 6 S^E ^S"S H2 1^1 O •:3 §.S".2,,o> •2j5 S2 ° >.'-^ o o §s S'C, 0<5>5 M 0) o G .2 ^ =0 ftSrt (5 >, a ft 33 _, S 1-1 g G o H ^ 2 Ph 3 o « o *-• ^^ ^ Q ^^ wn----^ (u •S o 5 ts r^ •2 a ij y ca t3 (u o a g u o *->.2 ^ ft ftoi S «B8So^^ 3SS^.2tS2M O o m -UHM +J^' Pi; ft-O ft'O o .2 d§ tS in 13 2 u: cxi.S O M (0 tiB u_ U 'U'O N««-< fttS M !S^''i to " "' ^0,, a»-^ ijt S ■^-Q ^ aJ do >' Ji-S tiSr. R^i^ E-i "s:^ 2 2; rt hr^^ oi « ;;| ^ M^ p.„ ac c„._. M mu3 oi bo •^-.SS 2 2 O ^ *-> ft > o r::.S o 53 0) ft- X 2 « > m^^ etf GO . U3 d o> s S . S S Ph S S f^ S l-l « CO ^ « 10 Pi ai 142 coley: neoplasms of the lymphatic glands O M o J « -J^ g rt I- ^ ^ P Q - S Mig ^^ o^ C . o « g g jj-a p wrs.s . ; S i-|""-2 H-" P-g M aJ 0! uQ O- O.' - 2 ° c > 2^ N O 3 C 'W 3 U J3 O - Ml-.' 5^ hfi ^ ta £ p. t-, ^J 03 I m +j .5 c Co S 2 o P< •-■ ; c; >H (jj ts m m 53 1^ ><-^Q nJ rt o C o $i (U o o o a. 2 w" ". iH o j; ol) jj o PI c OJ o-^ M tj 5 oi a « M rt a 3 bii a a 3 ■d 0! 3 (In I j_, o .g'"^sao-3 •d .grt„ 3S -.2 3« a -ogS-Sesaa-d^ W -1 ffi X Si o a.-s lals 3 0'S2 0) -u •d tfl'^ "J 3.'3 " 5 M ■2d3 ■S 3 CD nger 4 hs pre 11 s 1 y d die eal wel .a^,n «30§-=! 3 a > ^ 3 fa a^'d:5 3 3 3.^ rt.-, M b :3 ■^ ci.o\ 01 (^ 3 o» % Ph % S S fa s S ,^ . |2 ctt u ""Q M JH s " «-S i2 c „- fo e i2 .S n! .a b ol.JJ-j w.«i CJJ rt >, a! Ck Oh (Ih CL, 1-. - d JtiJ C'J J= -^^-e-r ci <3 . ft< tJ fi ■ti fi fi 01 S-fi a ^ ^ ft ■u fc « "S ^SE-d&JHfc^ft O S o e ca-ci O +^ > S h "3 § ^ S"^ fi Is X in CO (U 0) (3 t- ■ c c ? ^^B$'i "^ > .5 o C a G JH.^ CO oJ C t3 - ta _ n! 2 C -tj ft c8 I- -M 7 C • ^H G ^ C J=ij3 3 00 C >-lO '- ■Pi a 144 coley: neoplasms oe the lymphatic glands i=l c« 4-=" M OJ Ii CL W !2 '^ ca p. sa' 13 t-. — . ni I Letter from Dr. 1 Tritch, Jan. 29, j ipi-l, states "pa- 1 tient is in good health without a c 3 than i>i years." Patient in good health, Sept. 1, 191S, 7 years later. Entire disappear- ance of tumor; doses again cut down; recur- rence; toxins showed less and less effect; rapid growth; death, Feb. 7, 1912; complete au- topsy, no metas- tases. ^i ft 0) o i CO Z m 0\ ■a ■a as ■3 c-s.a a C oj "ca c « s iH a ^ ois 2— 5 . ft 5*^ ° J= m -H „ 0.) s « ID .c 0) 13 '".S-S u 3 j5 cS ra _ oi ctJ ■.-< flj • ir: • — ca ■3 .is a ca ca.2 d «J - ft ca cu S C S .^ ?! w a'-P a >. Ong ^g g ca a X ft'd.Sis.a.^'a a ^ cai; w mJ^ ca_ai c H w W w <; "5 <" s* o>, .c! oH CIS ^ ,^ ^ H fr^ H u o a o 5 o a I'sl S c! c!i ftS"-5 XI 5 6 ca" ' >, ca i ftgO 0) a; 1I) aTli ^!> S"^ 3 (J ca ca j ° ft 1 ° a; 3 ID 1^: — . CD tH.S ,Ji ~. a ca;^.2 g i;-j: Pj3 asaspow^ C ft o (u ft (u Sy= M ssa ii t- *-• *^ ca«=l ft C ftC S 3 0.2 ^ ft in ca K o-st;o 3 ft k 2: m w J m M if - TU ClTd ^ Ss§ CJ OJ p M-4 1 ft pi ca ■mM .ti rt "S ;„-'2 c >> ^ _" (UJ3 .2| •d p ca "3) 1 +^ c so."' "ta "ca S-^S' u. ■piss a a •3 ^ .as a*' Mr;: ■" ■d K !i o S O uM ca 13 c ca !! ^ o ro ii -s ■E o o a s •Q S ■ftOi Ov DC (3\ 5 Ov (U o> H <" " 1—1" (X, H 05 +j ii &i "3 o "ca a 1 ° i o u V S c *1 = lU ft - U) - 1 1^ a o 0) D a ■> Q ft - C f~j« a •S 0.2 ^.s-a -H y d - "1 Cl3 ca _ S§.2 1-0 ■>-> Oi n! 1 1^ ■o 1) OJ. Of or •g§c)^a .^s-a 1-. w ca ~o >;.a s s OS." ^ 4) .ca^l^ p Q Q T ^ i: IS Q p d ^ « re 'l 10 t~ ^, " M H M " M >H coley: neoplasms of the lymphatic glands 145 *j tH a 01) rt E C c ta X ii nl (rt - A! b tt a n! [S ^ Qj a> S2 c ago ftS 3 ao- .- o,3°•- :"' o -- 'i' c "■ E P dTi; =? W o o-a o-r >- p-TJ^^s «i o! ft .. 5*0-1 v- "" ta §.2" tS" g c a5 gz3 0.3 « o>,s.2 <"^ 5 0! i-i oj3 hH ;3xi I 3 O o °'2 >^^^ m"" c ^ o 5i,g^.S^ ftii 2a& .0. 4) 0) «J CftcJ o. 4) ^ C o "^ " ■»i ,ntS--^ 110 ft O X Oi ca (5 o o o " ft-- C S -t^ . iH L" o c o >.o S-po J3 i» .- ca ._ c ^ ft b 5,^ >< 0) X o.t! ca iuj3 E c o M >^ss-si|t§| 0).^ S 4) . ^ l-.TD-'-' N mX3 >'^ MH o'S o-^ 8 e « 3 o 0) . .0"?^ SoiJoita E"t«Sfe^6'2 8 d J2 iSi iH £^ 6£i ftH > c S o t^" «.y ..s 'o ft S S u h 1-. Q ii'e E ta •d a tai— 1 •- c X o oE X o og-fi > (3 la >• ca E a —T >> ■ij • • - C & m c?as o 0+^ ^•;:3 ^2 "3 o^ Qw . ca S c3.2 o cjrt .- ) o Xi .•ft 5. 2 2 ""3'ft^ < - ,-T3 M ftZ 2 R ca 0-3 z " 3;gffi-S<2 ca c SE a fe o& . ca W.2 >. a a SE^8 Q Ete O ft c 3 •■■5:S ft 4) 2 o ca -ti .. "■^T^EOL. P O 146 coley; neoplasms oe the lymphatic glands >> 9 cS a> a! ij (U (U M -"i :S ?; B a c o'5 c >, a, M M . tC CU ,£?»; p:^ eei oil ft" ft.s\r a +3 4i P P c apera- tomy; X i n s ncom- t re- oxins ■ - ^° a .2 1- -2 a! I- " in - S lU t3^ C »o Xplora tion, mixe 4 mon perati plete; curre s- a o w (-I'd ft C3 o a 3 a (3 OvTf OHM a o ft^O-^-g „ • Sea E;'ij'=< s a" a --o a; "^ C-O -t^iJt-lTS.-f-l M "H cji-a o ^ O 6 ai 'a § a § 'a § a § S g « X _ X « s a o ft o o g.2 g.2 a.2. coP-coP-doft! 0"°opOopO( -■« 3 a 0.2 ;=:^ o o M 4J n!--; CD o O oJ ■sa «P •d a! =< o O O r-l (U CSS as ■O cci 3 o o o (H >-' >. « >> "bi ■" oi c3 cS ft a! C C CD CU "d ci Cli ft ft T3 3:=; •d 1-1 c c cfl 1-. CD £i c C3 "(5 ,_- ^- K ^ ^ ^ s ^ 11 s ^ 3 bo ^ a t. 2; S; ^ H ^ ei H S; 2: (U t^ lO c^ t^ fO CN 10 "c8 Oi Oi H c» ^ ^ " M " " Ht ^ 3 o> a 00 10 00 Oi <1 -d H ■d 10 ■* " S S ^ -■- % fe S s fe la c "ii ■ 'S > XI cS Oi C CD J 5 a p^2 . Ml-, cS CD p-.a p^f, o r^ 00 Oc j_, (M C3 Tf 10 "^ '"* N •^ ts m c^ m f^ M ro COLUMBIA UNIVERSITY LIBRARIES This book is due on the date indicated below, or at the expiration of a definite period after the date of borrowing, as provided by the rules of the Library orb^ speciakarrange- ment with the Librarian in charge. '^ ^ — ^ DATE BORROWED DATE DUE DATE BORROWED DATE DUE m\!( 2 r f ^""^^r ,. nr^T 5 IS 'i !!? - '" ^<^^ JUL 1419 19 i ^.f (v. hm^ ^^* 1 .^: - -• -^ai«*; ' '"nm: 'r ttii I9g0< m - S .iiir tC'^;;' ':'■■'■■ C28(iI4i)m100 RC6H-6 Coley Primary neoplasms or A m Wi K