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THE AMERICAN TOURNAL OF CANCER d A Continuation of The Journal of Cancer Research THE THYMOMA AND THYMIC HYPERPLASIA IN MYASTHENIA GRAVIS WITH OBSERVATIONS ON THE GENERAL PATHOLOGY' E. H. NORRIS, M.D (From the DcpnrtmPnt oj Pathology, Unizlersity of Minnerota) Since the comprehensive study by Bell in 1917 no systematic treatise on the thymic tumors of myasthenia gravis has appeared. It might be expected that the past twenty years would have added the records of many more cases to the literature and have extended our knowledge of the pathological anatomy of myasthenia gravis and the associated thymic tumors. On the contrary but few cases with autopsy findings have been reported and our conceptions con- cerning the morbid anatomy of this disease are much the same as they were in 1917. In the period from 1901, the year in which Weigert published the record of the first case of myasthenia gravis with an associated thymus tumor, to 1917, Bell found published reports of 56 autopsied cases of this disease. He wrote: '' The thymus was described as enlarged in seventeen of these cases; and in ten others it contained a tumor. Therefore some form of thymic involvement seems to occur in nearly half the cases of myasthenia gravis." Since 1917 the records of 6 more autopsies have been published and 5 of these showed thymic lesions. Of the 4 cases to be reported here, 2 had thymic lesions which were recognized. I am of the opinion that pathologic changes may be found in the thymus in cases of myasthenia gravis in direct ratio to the care with which they are sought. Thus, prior to 1901, when Weigert first called attention to the association, the presence of changes in the thymus had been completely overlooked. In 1912 Starr reviewed 250 cases of myasthenia gravis, including cases reported prior to 1901 in which the thymus was probably not carefully investigated. His figures showed thymus involvement in only 28 per cent of the cases, while Bell's analysis of 56 autopsies between 1901 and 1917 yielded an incidence of thymic involvement in 50 per cent. W'ith the addition of our 4 cases and the 6 reported elsewhere since Read before the American Association for C;tnccr Research, Boston, Mass, April 8, 1936. For discussion scc pa~e557. 42 1 42 2 E. €1. NORRIS TanLI< I : Reported Lesions of the Thymus in Myaslheizia Gravis * I’n t ien t (‘,lbC No. Eulargetl Age or Per- Tumor sistent _. 1 1901 I.,iquer <ind I2eigerl 30 5 x5x3 Clll. 2 1001 Il‘eigert - A tumor 3 1901 I3urr and MxCaithj 21 7rilargetl 4 1902 Hod1nioser 18 ’nlarged 5 1902 Link 43 1 CI11. long 6 1904 flun, I3lunieraiitl Streeter 3 2 5 x5x5 Clll. 7 1905 Burr 30 22 gn1. 8 100.5 Huzzard 40 ).5 gni. 9 1905 Nuziard 40 59.4 gm. I0 1905 I3uzzard 28 i1 gm. It I905 Dupri. antl I’<ignie/ 32 3 gm.; persistent 12 1007 Steiiiert Hltlerl\ Persistent 13 1908 Mqer 47 Enlarged 14 1908 Hooth 11 11x5.5x1 cni. 15 1908 Marinesco 3 1 Persistent 16 1908 Mandlehnuni antl (‘eller 52 5x3.5X2 em.; 20 gin. 17 1908 12 iener 67 A tumor 18 I 908 Meggen tlor ler 41 A tumor 19 1909 Boudon 17 36 gm. 20 191 1 Moorhead 25 Persistent 21 1911 Slrnes 21 31.4X7.6 ciii 22 191 1 Oppenheini 40 A t iinior 2 3 1912 Klose 23 A tumor 24 1913 Schuniacher ,~ritl l<oth 19 to gm. 25 1914 (’laude, (;i.rq antl I’or‘ik 51 A tumor 16 1915 llart -. 5 x4x4 cn1. 27 1915 Hart 30 Persistent 28 1017 Hell 58 6X3.6X3.5 ciii.; 60 gni. 20 1921 Uouttier and Ikrirand Mid. age Persist eiit 30 1923 MelLi 48 7.5 x5.5 x2.5 clll. 3 1 1929 Alter antl Osnato 31 9X7X6 cui. 3 2 1934 Breni and Lbechsler 27 4x2,s cui. 3 3 1934 Hrem and \Vechsler 54 9x3 Clll. 3 4 1036 Norris 3 7 10X4X4 cni.; 57 gni. 35 1936 Norris 3 3 5.8X4.8X1.2 cni.; 16.6 gin. * In ii .‘rianer bv, I3utt the ureseuce of a thvmoriia two out of seven autopsied cases is men- t ioned. IIoRever, none of these seven cases is given individual consideration and they cannot, for tIi,il rensori, be inclutletl in this t.ible. 1917 the incidence of thymic lesions remains at 50 per cent. This figure probably expresses the frequency of grossly recognizable lesions of the thymus. It seems quite possible, however, that thymic lesions which have produced little or no macroscopic alteration of the suprapericardial tissue may have been overlooked in some of the reported cases. In the first place, as will be pointed out later on, the thymic lesion may not be recognizable without a microscopic examination. In the second place the thymic region in the post-adolescent ages is frequently passed over in the routine necropsy with the most cursory inspection. These facts have doubtless combined to lower the figure which expresses the frequency of reported lesions of the thymus. THYMOMA AND THYMIC HYPERPLASIA 42 3 The reported autopsy cases of myasthenia gravis in which thymic lesions have been found are listed in Table I, in chronological order. The first 27 cases comprise the 17 which were tabulated by Bell and the group of 10 thymic neoplasms which were analytically studied by the same investigator in 1917. These are followed by the 6 cases recorded since 1917, and finally the author’s two cases are appended. It will be convenient first to summarize the cases which the literature already records. (1) BELL, 1917: 2 The patient was a male, fifty-eight years old, with a typical clinical picture of myasthenia gravis and a retrosternal, encapsulated, nodular tumor which meas- ured 6 X 3.5 X 3.6 cm. and weighed 60 gm. The cut surface of the tumor showed soft gray tissue. “ The tumor tissue consists of cells with large vesicular and abundant light-staining cytoplasm, fused together to form a syncytium. Throughout the syncytium are numerous spnces of variable shape and size, containing small lymphocytes. In some areas the lymphoid cells predominate, in other areas the epithelial cells. , The cells with large clear nuclei are thymic epithelial cells. No corpuscles of Hassall are to be seen.” (2) BOIJTTIERAKD BERTRAND,1921: The patient was a middle-aged woman with typical myasthenia. The thymic region showed the presence of small grayish red masses, and these on section proved to be thymic tissue. Lymphoid cells, Hassall’s corpuscles and reticulum cells are described. The fact that thymic tissue was present in sufficient amount to be recognized grossly is enough to classify this as a case of so called persistent thymus. (3) MELLA, 1923: A colored male, forty-eight years old, had typical myasthenic symptoms for nine months. In the thymus a discrete mass measuring 7.5 X 5.5 X 2.5 cm. was found. The structure of this thymic mass is described as made up of closely packed lymphocytes with a few Hassall’s corpuscles and with no signs of degeneration or inflam- mation. (4‘) ALTERAND OSNATO,1929: The patient was a woman thirty-one years old. A large thymic tumor measuring 9 X 7 X 6 cm. was present. This tumor had no regular structural arrangement. It was made up of lymphocytes and epithelial cells, and the presence of young capillaries, eosinophiles and polymorphonuclear leukocytes was noted. Degenerative changes, such as hemorrhage, fibrosis, and calcification, are described. In addition to the mediastinal mass a sepnrate cervical nodule was found which had a calcified capsule. The central soft part of this nodule, however, showed the same structure as did the mass in the thymic region. (5) BREMASD W’ECHSLER,1931: A woman of twenty-seven years had typical myasthenia for three and one-half months. ‘‘ In the anterior mediastinum was a mass, appar- ently composed of two structures, extending down the anterior surface of the pericardium. The upper half had the appearance of a hyperplastic thymus gland, except that it was somewhat firmer than normal; the lower half, rising from the inferior pole of the gland, was a firm, oval, encapsulated nodular mass, measuring approximately 5 cm. in its longest and 2.5 cm. in its shortest diameter. On section, it was grayish white and trabecular and contained several areas of calcification. “Sections through the upper portion of the mediastirial mass showed it to be the thymus gland. The lower circumscribed mass had the typical structure of a thymoma. Sections from different portions of the tumor showed a somewhat varied picture. For the most part, it was composed of large, anastomotic sheets of polyhedral cells, separated by small amounts of vascular fibrous tissue. These cells had large vesicular nuclei and definite nucleoli. The cytoplasm was acidophilic and granular, and the cell outlines were indistinct. Some of the cells had a flattened appearance. Small round cells were scanty and were situated mainly about the blood vessels. In other areas, large amounts of dense fibrous stroma divided the tumor cells into irregular islands, and round cells were more conspicuous. In still other areas, the structure approached that of the thymus gland, round cells pre- dominating over the thin cords of polyhedral cells. The latter lay adjacent to the ca$- laries. R/litoscs were infrequent. No plasma cells, eosinophils or Hassall’s corpuscles were seen.” ”For analysis of CBSCS prior to 1917, see Bell: J. Nerv. & Ment. Dis. 45: 130, 1917.

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