UNDIFFERENTIATED ROUND-CELL SARCOMA OF THE ILIUM (EWING TUMOR) CONTAINING HEMOPOIETIC ELEMENTS N. W. ROOME, M.D., AND P. A. DELANEY, Pu.D., M.D. (Prom the Departments of Surgerg and Pathology of the Universily oJ Chicago) The undifferentiated round-cell sarcomata of bone grouped together by Ewing (I) in 1922 as "diffuse endothelioma" are con- sidered an oncological entity by most authors. Considerable doubt exists, however, as to the origin of the Ewing sarcoma. Ewing and his supporters believe that it is derived from an endothelial cell of the bone marrow, possibly the perivascular lymphatic endothe- lium, and now apply the name "endothelial myeloma'' with that significance. Kolodny (2), Oberling (3), and others think that these tumors may arise from the reticulum cells or the reticulo- endothelium. Certain facts suggest a relation to the myelomata: multiple tumors frequently appear early in the disease, there is usually regression under radiotherapy, and the structure may "verge on myelomau( Ewing, I). Connor (4) and Kolodny (2) mention that in a small percentage of cases some myeloid and plasma cells are to be found in the tumor tissue, though neither author describes the method of identification of these cells, nor their relation to the neoplastic cells. In the case to be reported, there was a large primary tumor of the ilium, with skeletal metastases almost completely replacing the bone marrow, and little visceral involvement. These are unusual features for a Ewing sarcoma, but other evidence leads to that diagnosis. Upon the application of special staining methods, there was found scattered among the tumor cells an admixture of differentiated cells, apparently members of the hemopoietic series; and a proportion of the "undifferentiated" tumor cells seemed to resemble the myeloid stem-cell, the hemocytoblast. The possible significance of these findings will be discussed later in this paper. CASE REPORT R. C., a white male, aged nineteen years, entered the University of Chicago Clinics Aug. 9, 1928, complaining of (1) pain in the lower ex- tremities, especially the left, (2) a swelling in the region of the left ilium, 1 This work was done under a grant from the Douglas Smith Foundation for Medical Research. 386 UNDIFFERENTIATED ROUND CELL SARCOMA 387 (3) loss of vision in the right eye, and (4) gradual loss of weight and strength. Two years before admission he began to have transient sharp pains in the left hip region and down the back and outer side of the left leg, which were worse at night and gradually increased in severity. For the past ten months he had had a dull ache in his back, and fleeting pains in the right leg, back, shoulders, and face. Four months before admission he had suddenly lost most of the vision in the right eye, following a severe headache; and a little later he had developed a partial anesthesia of the right side of the face, which slowly disappeared. During the past six months he had gradually become pale, and had lost weight and strength. Tonsillectomy was done six months before admission because of x-ray findings of some disease of the left ilium. Three months before admission a mass was first palpated in that region; two exploratory operations were performed, leading to the diagnosis of osteomyelitis, though the wounds healed per primam, and no relief was obtained. The left leg had been weak for several months, and because of pain and general weakness the pat,ient had been confined to bed since the operations. Physical examination on admission disclosed a pale, weak, emaciated young man, suffering considerable pain. The right eye protruded slightly, and was nearly blind; the left eye showed a contraction of the visual field. The left pupil was the larger; both pupils reacted to light. There was a marked primary optic atrophy of the right eye; the other cranial nerves were objectively normal. No nodules were palpable on the skull, and the cervical lymph nodes were not enlarged. The lung areas were normal, as was the heart except for a soft, non-transmitted, systolic murmur at the apex. The abdomen was normal, except for a fulness of the left lower quadrant, where there was a firm, non-tender mass about the left ilium, filling out the iliac fossa, and laterally resulting in a moderate swelling of the gluteal region. On rectal examination the lower portion of this mass was palpable, filling out the left side of the pelvis; the prostate and seminal vesicles were normal. There were healed scars of operative incisions along the crest of the ilium, and just above the inguinal ligament. The left inguinal lymph nodes were moderately enlarged, firm, and slightly tender; nowhere else in the body were en- larged nodes detected. The muscles of the left leg were paretic, and mo- tion of the hip joint was painful and limited, but there was no sensory disturbance. Palpation of the entire skeleton revealed no other enlarge- ments nor areas of tenderness. The reflexes were normal except for a diminution of the left abdominal and left cremasteric responses. The white blood count was 19,000; the red blood count was 3,000,000, and the hemoglobin 60 per cent (Tallquist). The urine was repeatedly normal; no Bence-Jones protein was discovered. Blood Wassermann and Kahn tests were negative. Roentgenograms disclosed an increased thickness and density of the greater part of the left ilium and adjacent parts of the ischium and pubis. There was evidence of new bone formation on both surfaces of the ilium, appearing laminated on the outer surface, and more irregular 388 N. W. ROOME AND P. A. DELANEY and fuzzy on the inner surface (Fig. 1). No other lesions could be found at the first x-ray examination of the remainder of the pelvis, lumbar spine and sacrum, both femurs, chest, and skull. A tentative diagnosis of Ewing tumor of the ilium, with metastases in the region of the optic chiasm, was made. A series of 31 injections of Coley's toxin was given from Aug. 13 to Oct. 20, 1928, in doses increasing from 0.01 C.C.to 1.2 c.c., with febrile reactions after each, of 103" to 104.4' F. X-ray therapy was begun Aug. 30, 1928, a total of 600 Roentgen units being given, half anteriorly and half posteriorly, centered on the left ilium; a shorter course was also given over the right and left temporal regions, centered on the optic chiasm. Following this therapy the patient felt better. He had less pain and more function in the legs, and the mass in the pelvis decreased slightly in size. The x-ray findings remained almost unchanged. The eyes gradually UNDIFFERENTIATED ROUND CELL SARCOMA 389 became more prominent, and in October the patient complained of numb- ness of the left buccal mucous membrane. On Nov. 4, 1928, an oval tumor about 1.5 X 2.0 cm. was discovered on the right clavicle approximately 3 cm. from its sternal end; a roentgeno- gram showed at the corresponding point evidence of slight periosteal new bone formation with irregular reduction of the bone density beneath. A biopsy was done and a soft grayish tumor was found, which had eroded the bone and projected beyond its surface. Microscopic examination showed it to be made up of masses of closely packed round cells, with oval vesicular nuclei containing scattered finely granular chromatin, and non-staining cytoplasm; there were occasional mitotic figures (Fig. 2). The diagnosis of undifferentiated round-cell sarcoma (Ewing tumor) was thus confirmed. FIG. 2. TISSUEOBTAINED BY BIOPSYOF THE RIGHTCLAVICLE, NOV. 1928. X 835 X-ray studies in November and December showed small scattered areas of reduced density in cortex and medulla of both humeri, femora, tibiae and fibulae, and some periosteal new bone formation in the upper thirds of the humeri; there were no changes in the bones of the forearm and hand. There was irregular reduction of density of the sacrum and right and left pubic and ischial bones. The appearance of the left ilium was little altered. The humeri, right clavicle, and right pelvis were given short courses of x-ray therapy. The red blood count, Nov. 7, was 2,800,000. After December the condition became progressively worse; t,he mass in the pelvis enlarged and there were at times increasingly severe pains throughout the body. In January 1929 the patient suffered minor accidental burns of the abdomen, chest, and hands, which healed slowly. A differential white blood count on Jan. 25 showed 74 per cent polymor- phonuclear leukocytes, 3 per cent large lymphocytes, and 23 per cent small lymphocytes; no abnormal cells were described in the smears. 390 N. W. ROOME AND P. A. DELANEY Edema of the feet and ankles appeared in February and progressed to an extreme degree on the left side; in March the abdomen became distended, and free fluid and rhles were found in the chest. In April decline was even more rapid; on April 9 the white blood count was 8,600, the red blood count 1,260,000, and the hemoglobin 30 per cent. Palpable metastatic nodules appeared on the skull. The patient became incontinent and comatose, and died April 22, 1929. Throughout the illness the mouth temperature had fluctuated irregularly between 98" and 101" F. Necropsy Findings: Necropsy was done about two hol~rsafter death, by Dr. H. G. Wells. The body was extremely emaciated; there was little subcutaneous or omental fat. The mucous membranes, skin, muscles, and viscera were very pale; the skeletal muscles were atrophic. There was moderate edema of the lower extremities. A small amount of clear watery fluid was found in the abdominal cavity and there were a few fibrinous adhesions.