MALIGNANT TUMORS OF THE THYMUS GLAND EDWARD H. CROSBY, M.D.' (Prom the Department of Path~logyoj Albany Medical College and the Pathological Lab- oratorg oj Albany Hospital, Albany, N. Y.) Malignant tumors of the thymus are of interest not only on account of their infrequency but also because of the controversy regarding the histogenesis of the gland. Thymic tumors, which are distinguishable at post-mortem examination from tumors of the mediastinal lymph nodes or of the lung, usually surround and compress the trachea, bronchi, pericardium, and great vessels. By compression, and less often by invasion of the vessels and pas- sages, they cause death by asphyxia and venous obstruction, which may develop gradually or very suddenly. The points indicating the thymic origin of mediastinal sar- comata are summed up by Jones (1) as follows: 1. The situation of a large, slightly lobulated tumor at the site of the thymus. 2. The extension of this tumor downward behind the sternum without infiltration of the bone. 3. The involvement of the pericartlium and of the pleura by direct lymphatic extension. 4. The resemblance to thymic tissue on histological exnmin a t'ion. In connection with the last point some authors insist that all the histological elements of the thymus be found in some form, but a resemblance of the chief cell type to the thymic lymphocyte and the presence of Hassall's corpuscles in some parts of the tumor at least would seem adequate. Ewing (2) gives a classification of thymic tumors which has been widely quoted. His main groups are as follows: 1. 1,ymphosarcoma or thymoma, composed of a diffuse growth of round, polyhedral, and giant cells. 2. Carcinoma arising in the reticulum cells. 3. Spindle-cell sarcorria or myxosarcoma, very rare and somewhat ques- tionably attributed t,o the stroma. The third and first groups are still under dispute because of the This study was made while the author ~2x8Eugene Littauer Research Fellow in Pathology in Albany Medical College. 461 462 EDWARD H. CROSBY questionable mesoblastic origin of the small round cell of the thy- mus. This point will be discussed later. Harris (3) in 1892, An~brosirii(4) in 1894, and later Jories (I), Janeway (5),and others discussed the clinical symptoms of thymic tumors. The first symptonl is usually cough or hoarseness without expectoration or hemoptysis. This leads to the subjective symp- tom of suffocation without physical signs in the chest or visible cause of obstruction in the upper passages. Puffiness about the eyelids and fullness about the neck, toget,her with :L pecu1i:tr pink disco1or:ttion of the eyelids, :ls described hy ('rnver ((i),may 1)e ~)rescntearly in thc course of the disease. Engorgement of the veins of the neck, cyanosis, edema of the face and upper extrcniities, :t feeling of oppression in the chest, palpitj:ttion, and pain beneitth the sternum, which is constrictive and well localized, soon follow and rapidly become more marked. Alteration of the voice, head- ache, dysphagia, and gradually increztsing emaciation :Ire associated with the appearance of a tumor growth in the axilla or in the ccrvi- c:tl region. As the disease progresses, dyspnett becomes extrcrnc, inequality of the pulse is noticeable, hydrothorax develops, ancl the heart becomes displaced. The most common con~plications of thymic tumors are pleurisy with effusion, pericjtrditis with effusion, obliteration of the vessels in the neck, arid obstruction of the esoph- agus and trachea. ,J:~neway(5) has urged the import:tnce of early diagnosis :tnd familiarity with the clinical course of these tu~nors,for in :L lnrgc number of cascs rt~diumor x-ray therapy offers relief, even if not a prospect of cure. However, the result of tre:tt,ment depends not only upon the early diagnosis and institutio~lof trentinerlt but also upon the histogenesis of the tumor. Roentgen examination is of the utmost diagnostic importance. The location and the appearance of the shadow :ire characteristic. The shadow is immediately above the pericardium :tnd higher th:tn the usual location of enlarged peribronchial lymph glands. A circular, sharply defined, flattened, non-pu1s:~tingmass in the anterior wall of the thorax, in the absence of other evidence to the contrary, justifies a tentative diagnosis of thy mom:^. Pool (7) in 1925, Dwyer (8) in 1927, and Doub (9) in 1930 reported cases in which a diagnosis of probable thymoma was made by x-ray. The tumor w:~ssubjected to deep x-ray therapy and some of the patients showed great irnprovemerit in their symptoms. In 1925 Grover, Christie, Merritt, and Coe (10) reported two similar cases. Both MALIGNANT TUMORS OF THYMUS GLAND 463 patients were treated with deep x-ray therapy, and the authors state that the results were very encouraging. The term " thymoma" was first introduced by Grandhomme (11) in 1900. At that time it was applied to all malignant tumors arising in the thymus gland. Brown (12), in discussing the term, states that it should be used only to indicate primary carcinoma, which he considers the only real thymic tumor. Crotti (13), how- ever, believes that this term has the advantage of being accurate whether the cells are derived from endoderm or mesoderm, and that it also clearly associates the tumor with its place of origin. Bell (14), in describing tumors of the thymus associated with myasthenia gravis, uses the term "thymoma" to include non- malignant tumors, and Margolis (15) apparently agrees with Bell. Strauss (16) believes that those growths of the thymus composed of small round cells like those of the cortex should be called thy- moma, those characterized by a rich connective-tissue stroma and showing the presence of spindle cells be called sarcoma, and those growths derived from epithelial cells of Hassall's corpuscles be diagnosed carcinoma. Evert (17) uses the term sarcomatous thymoma because these tumors do not resemble true lymphosar- coma morphologically, and because he regards the term as equally applicable whether the parenchyma is of epithelial or of lymphoid origin. The consensus is that the term "thymoma" should be used to designate any malignant tumor primary in the thymus. To understand the nature of the neoplastic diseases of the thy- mus, it is necessary to review briefly the embryology and the histology of the thymus gland. It is generally believed that the thymus originates from the endodermal epithelium of the third branchial clefts as a paired organ. At about the second month of prenatal life (Hammar, 18), the thymus, which up to this time has been an endodermal organ, begins to be infiltrated with lympho- cytes. These cells migrate into, proliferate among, and separate the epithelial cells of the thymus (Maximow, 19). Danchakoff (20) showed that the thymus cell is a true small lymphocyte and that it may differentiate into granular lymphatic cells or into plasma cells. This differentiation was brought about by treating animals with x-ray. Although most authors agree with this dual interpretation (Badertscher, 21; Danchakoff, 20; Hammar, 18; Brannan, 22; Schaffer, 23; Crotti, 13; Stengel and Fox, 24; Voges, 25), other observers believe that the endodermal cells (endodermal thymic reticulum) differentiate to form the so-called thymic cells. 464 EDWARD H. CROSBY They are of the monist school, which is headed by Ewing (2)) Stohr (26)) and Prenant (27). In 1910 Pappenheimer (28) was also of the monist school, but his views as set forth in his later work have changed so that he may now be termed a dualist. Bell (14) has described transition forms between the reticulum cells and the thymic cells. The origin of the thymic cell is thus still a matter in dispute and, until this dispute is settled, definite classification of thymic tumors is impossible. Schaffer (23) describes the epithelial portions of the thymus gland as follows: "Within the medulla, but never in the cortex, are found peculiar concentrically laminated bodies called the concen- tric corpuscles of Hassall. These are nests of flattened epitheli~tl cells arranged concentrically around one or more central cells, these last having often undergone a degenerative process. Some- times the corpuscles are compound, two or three being grouped together and similarly enclosed by flattened cells." By trans- planting the thymus of young guinea-pigs, Jordan and Horsley (29), quoting the work of Jaff6 and Plavska to support their theories, showed that the concentric corpuscles of Hassall could not be interpreted as remnants of endodermal ducts, as had pre- viously been supposed. Regenerating transplants are said to form new corpuscles by a process of hypertrophy and aggregation of reticulum cells. This agrees with the earlier claims of Hammnr (18). Jordan and Horsley (29) believe that the concentric cor- puscles arise chiefly from hypertrophied endothelial cells of precapillary arterioles and the immediately investing reticulum cells. If Hassall's corpuscles actually represent in part remnants of atrophic capillaries and precapillaries, then similar structures should appear in other lymphoid organs. Structures resembling Hassall's corpuscles were found by Jordan and Horsley in atrophic subcutaneous lymph nodes of the rabbit. It is now generally ac- cepted that Hassall's corpuscles are endodermal in origin. D. B., a young Italian laborer, twenty-two years of age, single, one year in this country, was perfectly well until Aug. 15, 1923, when a mild cough developed, which increased in severity and was associated with discomfort in the upper median portion of the chest. On Oct. 1, 1923, he was unable to go to work because of the severity of the coughing spells, pain in the chest, dyspnea, and cyanosis, associated with distention of the This case has been briefly reported by Hosoi and Stewart in their article on "Dif- ferential Diagnoeis of Mediastinal Tumors," Arch.