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The Differential Diagnosis of Primary Neoplasms of the Mediastinum

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The Differential Diagnosis of Primary Neoplasms of the Mediastinum THE DIFFERENTIAL DIAGNOSIS OF PRIMARY NEOPLASMS OF THE MEDIASTINUM CUSHMAN D. HAAGENSEN, M.D. (From the Memorial Hospital, New York) INTRODUCTION That there are still opportunities for adding to the knowledge of the natural history of disease by correlation of pathologic and clinical findings was the theme of a recent address by Harvey Cushing. He appealed for a more active interest in morbid anatomy on the part of surgeons. There is perhaps no more suitable field for this type of research than primary neoplasms of the mediastinum. The differential diagnosis of the various pathologic types of these tumors is of crucial importance because a few types can be cured by surgical removal, some can be tempo­ rarily controlled by radiation, and others are amenable to no form of therapy. Since biopsy from the mediastinum is so grave a procedure that it must be avoided if possible, the differential diagnosis of the pathologic type of tumor and the form of treatment to be employed must often be attempted on the basis of the history, clinical findings, roentgen study, and the reaction of the tumor to a test dose of radiation. The rarity of tumors of the mediastinum has hindered the acquisition of knowledge concerning them. There are, for in­ stance, only about two hundred cases of primary malignant tumor of this region on record. An exhaustive review of these case reports would be of little value from the point of view of differential diagnosis, however, because most of them do not include the necessary data. Many are detailed presentations of the pathologic findings with few or no clinical data. Others, and here the radiologists (Dwyer, De Witt, and Christie, for example) are most often guilty, are premature reports of the reaction of mediastinal tumors to radiation, containing no information as to the pathologic nature of the tumor and the end-result of the treatment. The knowledge concerning the differential diagnosis of medi­ astinal tumors will be materially advanced only when case reports of these tumors are presented which contain a careful history, 72~ 724 CUSHMAN D. HAAGENSEN detailed clinical findings, roentgenographic studies, information as to the reaction of the tumor to an accurately measured test dose of radiation, the end-result of treatment, and, most important of all, pathologic study, if not by autopsy, at least by biopsy. It is the purpose of this discussion to present reports of a series of nine neoplasms of the mediastinum from the Memorial Hospital 1 embodying this information, and to discuss the differential diag­ nosis of the various types of tumor. CLASSIFICATION Pathologic classification, so necessary to the knowledge of tumors, has been particularly difficult for mediastinal neoplasms The benign neoplasms fall readily into an orthodox classification, but the malignant group has called forth a complicated and confused terminology. Some pathologists have been content to make no attempt at classification and have included all malignant tumors under the ambiguous term "thymoma." Since these tumors include very different types, however, it would seem that the term "thymoma" might well be dropped. The types which have been included under this name may at least be classified on a purely morphologic basis as lymphosarcoma, Hodgkin's disease, carcinoma, etc. Histogenetic classification has been possible for only a few of these types of mediastinal tumors. In the first place, it has not always been possible to determine whether the tumor originated in mediastinal lymph nodes or in the thymus. Since lymphosarcoma and Hodgkin's disease in other regions of the body arise in lymph nodes, it may be maintained that such is often the case in the mediastinum. A thymic origin has frequently been inferred from the location of the tumor and from its gross morphology. On the basis of microscopic study a thymic origin has been most easily demonstrated for an extremely rare type of carcinoma in which the epithelial cells tend to be arranged in concentric whorls resembling Hassall's corpuscles. The histogenetic classification of thymic tumors has been hindered by the fact that the embryogenesis of the different types of thymic cells is still being debated (see Maximow, Schmincke, and Ewing (a) for summaries of the question). The simplest possible classification in keeping with these principles would be as follows: 1 Most of these cases were treated on the service of Dr. Lloyd F. Craver, to whose courtesy the writer is indebted. PRIMARY NEOPLASMS OF THE MEDIASTINUM 725 Primary Neoplasms of the Mediastinum A. MALIGNANT 1. Lymphosarcoma (a) Small round-cell lymphosarcoma (malignant lympho­ cytoma) (b) Large round-cell lymphosarcoma (reticulum-celllympho- sarcoma) 2. Hodgkin's disease 3. Leukemic lymphoma 4. Leukosarcomatosis 5. Thymic carcinoma B. BENIGN (following Heuer (a)) 1. Dermoids 2. Other cysts, including echinococcus cysts and ciliated epithelial cysts 3. Ganglionic neuromas and neurofibromas 4. Benign connective-tissue tumors including fibroleiomyomas, fibromas, chondromas, and lipomas Examples of most of these different types are included in this series of cases from the Memorial Hospital. In conjunction with the description of these cases a brief review of each type of tumor would seem desirable. In these reviews only those case reports will be referred to which, because of completeness of pathologic description, enable satisfactory morphologic classification of the tumor reported. LYMPHOSARCOMA A. Small Round-cell Lymphosarcoma (Malignant Lymphocytoma) Small round-cell lymphosarcoma (malignant lymphocytoma) of the mediastinum appears to be exceedingly rare. To judge from the few available reports, it usually occurs in children, occupies the thymic region, and metasttt~l~eS·,~Tid~h··:. :::Reu3:ult, Cathala, and Plichet reported a eaze 0£.~hi.s t.Yr>e. The. tumor.was. made up of small round cells ftild.showec··::1o Hassall's (~o!ptis~lf:·s. On the basis of its situation rather than from it~ histology they ascribed to it a thymic origin. Gerlach described t1i~:ca~ of a child in whom a large encapsulated tumor was found in the position of the thymus. Its greater portion showed the structure of small round-cell lymphosarcoma, but in one portion of the periphery thymic tissue, including Hassall's corpuscles, was found. Lamarque and Bert reported a case of lymphocytoma in which the pathologic diagnosis was made from a biopsy of a tumor over the sternum which was 68 726 CUSHMAN D. HAAGENSEN continuous with a large mediastinal tumor. The growth was highly radiosensitive. CASE 1: G. H., an Italian boy of fourteen, came to the Memorial Hospital May 5, 1923. Two weeks earlier he had first noticed swelling of the base of the neck on each side. He had become tired and weak. One week previously he had first noticed shortness of breath. He began to cough and to raise greenish yellow sputum. His throat felt sore. He was very dyspneic and orthopneic. At the base of the neck, on each side, were masses of elastic, discrete, movable nodes. There was dullness over the whole right chest anteriorly and over the lower two­ thirds of the right chest posteriorly, with flatness at each base. The area of mediastinal dullness was increased to the left. The breath sounds were absent at the bases, while over the upper portion of the right chest they were bronchial in type. The blood count showed hemoglobin, 70; red blood cells, 5,000,000; white blood cells, 19,400; polymorphonuclears, 83; small lymphocytes, 15; eosinophiles, 2. The urine was negative. A roentgenogram taken May 8,1923 (Fig. 1), showed the right pleural cavity below the level of the fifth rib posteriorly to be obscured by fluid. There was also a slight amount of fluid at the left base. The cardiac shadow was deviated to the left. To the right of the mediastinal border a dimly outlined shadow of a tumor process projecting into the right thorax was seen. On the left there was a rounded shadow projecting beyond the outline of the heart. Its edge was smooth and clear cut. It extended from the level of the 3rd down to the 7th rib posteriorly, capping the cardiac shadow. A diagnosis of neoplasm of the mediastinum being made, treatment was instituted with the radium emanation pack, as follows: MiIIi- Dis- :\Ii 1Ii- nate Time Area Filter tance Region Treated curie curies hours --- [>-6--23 1,591.5 3 br.48 min. 70 sq. em. 2 mm. br ..... 6cm. Right chest, upper anterior 6000 ,';-12-23 2357.3 3 hr. 22 min. 70 sq. em. 2 mm. br..... 6cm. Right chest. upper anterior 80lJlJ [.-20-23 943 2 hr. 6 min. 70 sq. em. 2 mm, br..... 3cm. Left supraclavicular 2000 5-21-23 943 2 hr. 6min. 70 sq. em. 2 mm. br..... 3 em. Right supraclavicular 2000 5-26--23 2309 3hr.20min. 70 sq. em. 2 mm. br..... 6cm. Right chest, upper anterior 80lJlJ ~--""""""~~-' On May 8, 1923. 5::t.O:a.ll of hlo1)d.;t.iti.ged fluid was aspirated from the right chest. No tumor cells-were f~u!l.djn:it-.: "~~nng the following ten days large amoucts of biQo_u.-tjnge~:H.rt11_d_~(~_,,~£tharawn from the right chest on six occasions. The _dy~p!1.~~ slowly improved and the sputum diminished. The cervical u.od~i t'~gr~~se~ to one half of their former size. Ten days later (MhY' ir 1923),' after two radium emanation pack treatments had been given and shortly after thoracentesis had been done, further roentgenograms (Fig. 2) showed the fluid in the right pleural cavity to be much less than in the previous films. Some fluid still re­ mained at the left base. The cardiac shadow had reassumed a normal position. The mediastinal shadow, which could now be well visualized, was seen to be markedly widened to the right.
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