Document BvX1b0bYMVv6K65b2K3gkx9k4

FILE NAME: Oil Industry and American Petroleum Institute (API) DATE: 1956 Nov DOC#: API114 DOCUMENT DESCRIPTION: Journal Article - Malignant Mesothelioma of the Pleura Malignant Mesothelioma of the Pleura H. B. EISENSTADT, M.D., F.C.C.P. Port Arthur, Texas ' Primary mesothelioma of the pleura is a controversial entity referring to a growth originating from the msothlium, the cell layer covering the inner surface of the pleural, pericardial and peritoneal cavities which are derived from the celomic space of the embryo. Willis1 denies their exist J ence entirely and considers isolated masses of the pleura as metastatic de posits of some distant asymptomatic primary focus. Anderson- believes that in most instances neoplastic involvement of the pleura originates from a bronchial cancer, but he admits that in a small number of cases no intra pulmonary growth can be detected with a most meticulous examination. Ackerman and del Regato3 are convinced that primary pleural mesothelio ma exists but consider it a rare disorder. It may be benign appearing as a fibrous mass or malignant showing alveolar, follicular or papillary pat terns. Even the latter types have a tendency to remain localized and to expand by invasion of the neighboring structures rather than by distant mtastass. However, mtastass do occasionally occur into almost any part of the body. Undoubtedly, benign primary tumors of the pleura have been repeatedly recognized ;**therefore, the controversy between the vari ous pathologists must refer to the malignant types which are difficult to classify on account of the great variability of their microscopic appear / ance.4*12 These may be localized tumors varying from coin lesions13 to huge masses occupying one hemithorax, or they may appear as diffuse thickening of the pleura with or without effusion. Their consistency varies from soft to hard, from brittle to elastic; their color has been described as white, grey, yellow, orange, red, or bluish. Their microscopic picture may resemble carcinoma, endothelioma, epithelioma, sarcoma, fibroma, fibromyoma and giant cell tumor. Stout and Murray10 believe to have solved the puzzle of the variable appearance of these tumors by demonstrating in tissue cultures that meso thelioma cells can develop into solid, tubular, or glandular structures of epithelial character as well as into mesenchymal tissues with fibroblasts, col lagen, and reticulum fibers. Sometimes one form of growth predominates but more often there is a mixture present causing a great variability of dif ferent sections of the same tumor. Other authorities,- however, are of the opinion that bronchogenic cancers may reveal all the pathological features described as characteristic of mesothelioma. This confused status / of the pathology of pleural tumor masses makes their clinical evaluation difficult and is apparently responsible for the scarcity and brevity of re ports describing their symptomatology during lifetime which is in contrast to the extensive literature discussing their autopsy appearance. Never theless, the practicing physician will have to face from time to time the problem of dealing with such isolated pleural growth deserving the Reprinted from "D iseases of the C hest/' Vol. XXX. No. 5, November. 1056 Ut* name of malignant mesothelioma. Considering the great variability of the pathologiml picture me Khould expect a multitude of clinical manifestations, laboratory and x-ray findings: It has been stated that some benign types of pleural mesothelioma are asymptomatic and only accidentally discovered during an x-ray investiga tion. If symptomatic, these tumors arc usually responsible for various types of discomfort in the chest and epigastrium among which the typical pleurisy pain aggravated by coughing, sneezing and deep breathing is quite uncommon. Various respiratory disturbances may occur such a3 dyspnea, cough, hemoptysis and mucoid, purulent or blood-streaked spu tum ; digestive discomfort may be present in the form of anorexia, nausea, vomiting, belching and epigastric fullness; general malaise may be notice able with fever, chills, anemia and weight loss. Clubbing of fingers and osteoarthropathy have also been reported.1-* u In the malignant cases in vasion of the diaphragm, the chest wall, the pericardium and the peri toneum is responsible for additional symptomatology. Clinical and roent genological findings are either those of single or multiple solid tumors or of pleural effusions with various types of exudates that are resistant to a conservative treatment. In contrast to those features considered to be characteristic of mesothe lioma, the presented case shows quite a few different findings worth re porting. The diagnostic difficulties of this disease are clearly demon- J strated by the fact that it escaped recognition over a period of several r * It, & i r i n ' a. i-,: i i i i - # -a.' *V r >#*>/jsfv r k ./-- FIGURE 1 FIGURE 2 Figurt i ; Chest film of August 1952, showed pneumothorax and small fluid level. Left hemidiaphragm was slightly elevated (sea position of "mngenblsse") nnd was Im movable.--Figurt t : Chost film of August 19, 1954: destruction of lower ribs with soft Usaue mass adjacent to them. (21 V-k-ttJ I4> V; .u vW --i-^4 Vi j i tS: >i :*?***: " years in spite of the most thorough investigations including exploratory lnpnrotomy and thoracotomy. The patient was seen by n number of phy sicians including specialists of almost any field of medicine: Co Rtport: A 67 year old male refinery foreman was treated on May 5, 1950, for acute posterior coronary artery occlusion with myocardial infarction. Marital and family history were non-contributory. In 1918 he had suffered from a severe attack of influenzal pneumonia. For about 20 years he hail lai n s u ffe rin g from spells of indigestion with "gas pain" In the left upper abdomen and mucus in the stool. fig u re 3: Section of first biopsy: alveolar pattern invading dense fibrous tissue. Dr. Vernie A. Stembrldge (X 48 magnification).--figure 4: Section of second biopsy: medullary pattern. Dr. Vernie A. Stembridge (X 110 magnification). (3) ; -V V ';* < * S ' . - u V . V r V * "* These attacks of bowel dysfunction were frequently ossocintcd with urticaria and attributed to an irritaldo bowel syndrome associated with fond allergy. The heart attack proved to be severe and was followed by a prolonged period of disability with persistent hypotension and marked Q and T wuve changes in the electrocardiogram. There remained a stubborn discomfort from the left lower chest as well as the left , epigastrium. It was difficult to deride if this was an nftermnth of the occlusion or a n v exaggeration of the previously encountered loft flexure syndrome. The pntlent himself attributed it mostly to the intake of incompatible food as well os to Ins constipation and gas formation. In the following years thorough clinical studies were repeated several times but no additional pathology could be elicited. In April 11152, howcvcr.'tho discomfort from the left side of the trunk had become so severe that he consulted three large medical centers in succession. Here, he under went thorough examinations, but only the previous diagnoses of old myocardial in farction of the diaphragmatic surface, functional howel disturbance, food allergy and anxiety neurosis could be confirmed. Nevertheless, Hie treatment suggested on the basis of these investigations failed to bring him relief. Shortly after returning from these clinics to his home city, a routine fluorosrnpie checkup revealed unexpectedly a left spontaneous pneumothorax with small fluid level and slightly deformed, elevated and immovable diaphragm. However, neither the collnpsed lung nor the visible part of the pleura showed any abnormality (Figure 1). The air was aspirated together with the fluid; the. latter contained five grams of protein per ino cc. and quite a few cells, 0 per cent of which were lymphocytes and 20 per cent eosinophils. Smears, culture, guinea pig inoculation and special studies for tumor celts were unrevealing. The origin of the pneumothorax as well as the exact time of its onset could never be clearly elucidated. An x-ray film tnken about four weeks prior to the accidental discovery of this disorder showed a completely normal chest. The patient himself lattributed it to an accident which he had sustained in February 1952. when he slipped from a scaffold and tried to grab a brace to hold himself. At this time he felt a sudden severe pain in the left side. However, an x-ray film taken immediately fol lowing this fall had been entirely negative. The pneumothorax disappeared after several aspirations but the drawing and pulling palm persisted. It was worse In the evening after moving about all day and was temporarily relieved by bed rest as well as by intercostal nerve blocks. In the following weeks a progressive deformity of the left hemithorax was noticed appnrentjy caused by pleural contraction. It was so severe that he walked with his trunk bent over to the left and that he developed murked scoliosis with the convexity to the right. As this finding seemed to be aq unusual sequela of a simple pneumothorax, an exploratory thoracotomy was advised in July 1953. This operation was preceded by bronchography and bronchoscopy which, however, yielded no additional information. The only finding at the time of the surgical exploration appeared to he an extreme fibrothorax which was treated with decortication. The pathologist noticed severe fibrous thickening of the pleura (Figure 3). The pericardium, the left lung and the sub phrenic space were carefully pnlputed during the operation hut no abnormality could be demonstrated. Unfortunately, these surgical efforts brought no relief and he then started to consult various chiropractors and cultiats. but was unable to get help; neither did psychiatric consultation and shock treatment change his symptomatology. Contrary to expectations, the fibrothorax recurred and the scoliosis ns well as the slirinking of the left hemithorax were soon worse than ever before. Physiotherapy and various muscular exercises did not improve the misery; neither did x-ray therapy of the bones and a brace prescribed by an orthopedic surgeon. In the meantime -a considerable loss of weight and strength was apparent approaching the state of cachexia. This was to a large extent caused by the patient's attempt to rclirve his "gas pains" by restriction of food as well as by excessive purging. After a neuro surgical consultation had yieidrd no new clues to his trouble, he underwent an ex ploratory laparotomy July 7, 1954, which revealed no pathology except masses of ad hesions extending from the lower surface of the diaphragm to the spleen and the left flexure of the colon. These were severed but the course of the disease was not changed. The origin of his suffering remained obscure until August 19. 1954, when x-ray films revealed some osteolytic lesions as well as pathological fractures of the left lowcr ribs (Figure 2). Therefore, on September 14, 1954, another operation was performed (Ur. I,. K. Lancaster) to obtain specimens of these destroyed hones. The microscopic examination showed "mesothelioma of the pleura" attached to the destroyed ribs (Hr. Kllen Furey, Pathologist, Hotel Ulcu, Beaumont, Texas; Dr. Yerntc A. Stembridge, University of Texas Medical School, Galveston, Texas) (Figures 4 r.nd 5.) On No vember 26, 1954, he passed away in a state of extreme cachexia. Permission for an autopsy was not obtained. Comment: It must be admitted that the presented case does not fulfill all the requirements of the diagnosis of primary mesothelioma of the pleura t because no autopsy was available excluding any other primary malignancy. Nevertheless, the latter disorder is unlikely on account, of the surgical ex plorations, the pathological findings and the most complete clinicnl inves tigations. It may be argued that this tumor did not originate from the mesothclium itself but from the peripheral pulmonary tissues This pos sibility would be of much more concern to the pathologist than to the cli nician. The latter is mainly interested in the fact that apart from the ab sence of respiratory symptoms no intrapulmonary tumor could be found on x-ray films before, during and after pneumothorax and with bronchos copy, and palpation of the lung during exploration. Thorncotomy showed only an extensive pleural thickening with adhesions. This growth and similar ones described in the literature should at least deserve special recognition ns a clinical entity in order to facilitate the diagnosis even if their origin is uncertain. Any persistent, or recurrent pain and discomfort from one side of the trunk not explainable by abnor mal findings of the thoracic cage, the intrathorncic and intraabdominal l organs, the spine, or the central and peripheral nervous system should alert the investigator to the possibility of pleural mesothelioma. If the x-ray film of the chest is entirely negative one has to realize that the initial lesion may be in the hidden diaphragmatic or mediastinal section of the pleura. In addition, Rabin14 has emphasized that the majority of pleural x-ray shadows are caused by effusions or by inflammatory granulation ( :: ; tissue, and that even an extremely thickened and indurated pleura may | `" fail to be visible on the x-ray film. Therefore, it seems plausible that in i \ the initial stage a diffusely growing pleural tumor without efTusion may j not possess enough opacity to be recognized roentgenoiogically. . i FIGURE 6: Section of second biopsy: alveolar pattern removed from skeletal muscle tissue. (X 473 magnification). . One could speculate about the connection between an infarction of the diaphragmatic surface of the heart and a tumor manifesting itself initially in the phrenicocardiac region. However, the heaa-t attack had all the features of a classical coronary occlusion, and there was never any peri cardial involvement in spite of repeated clinical, cardiographic and roent genologic investigations. Therefore, one must assume that this association is fortuitous. Unfortunately, there was no delim it clinical evidence of the beginning of the pleural tumor, because the various diseases leading to pain and discomfort in the left hcmithorax and upper abdomen over lapped each other. Initially, the patient was suffering from gastroin testinal spasms, left flexure syndrome, food allergy and mucous colitis for several decades. Later, after the sudden coronary occlusion he seemed to have an anginal type of distress which could lie easily' correlated with the persistence of the electrocardiographic abnormalities. In the final stage all these disorders caused symptoms concomitantly with those orig inating from the tumor predominating. * Of considerable interest was* the spontaneous pneumothorax ns the initially presenting sign of the tumor. Such occurrence has apparently not been described in the literature. It is well known that spontaneous pneumothorax can occasionally appear in the iieginning as well as during the course of a brc-.hogenic cancer, and that it is more frequently ob served in metastatic pulmonary sarcomas.15 It is supposedly due to the infiltration of the lung bordering the pleura by malignancy followed by tissue destruction leading to bronchopleural fistula. A similar mechanism could be operating in mesothelioma which Invades the parenchyma from the periphery. In addition to the spontaneous rupture of the lung our case was dis tinguished from the majority of the mesotheliomas reported in the litera ture by the formation of a progressing constrictive pleurisy leading to a severe deformity of the chest as well as the whole body. Such a finding depends obviously on the character of the tumor: a solid growth of tubu lar and glandular elements will either appear as an expanding mass or as an intractable pleural effusion while the formation of mesenchymal tissue with innumerable fibrous layers will lead to chronic fibrothorax. The latter form of growth was present in our patient with such a marked degree of fiber production that at first the diagnosis of benign constrictive pleurisy and later of massive peritoneal adhesions was entertained and that the true character of the disease was not recognized until Ixmo de struction occurred. .SUMMARY . A case of a malignant mesothelioma is described starting in the dia phragmatic portion of the pleura and invading the left hemidiaphragm and the peritoneal cavity. Malignant pleural tumor is a definite clinical entity even if its pathological classification remains a matter of speculation. Persistent or recurrent discomfort from one hemithorax or one side of the epigastrium may be the initial symptom of such a growth in the ab sence of positive roentgenological findings. ( 6) L i U . ; j r ! ; ;.-: ;-::--:1;= f ....... i*;?H * I ! *'-:*:r -`:r - * Spontaneous pneumothorax may occur at any time during the course of this disense or may be the initial feature. Mesothelioma must be included in the differential diagnosis of solid intrathoracic masses, persistent pleurisy with effusion, and progressive fihrolhorax. RESUMES- Se describe un caso de mesotelionia cjue empez en la parte diafragmtica de la pleura e invadi el hcmidinfragnia izquierdo asi como la cavidad peritoneal. El tumor maligno de la pleura es una entidad clnica definida aunque su clasificacin patolgica siga siendo motivo de especulacin. Las molestias persistentes o recurrentes en un hemitrax o en un lado del epigastrio, pueden ser el sntoma inicial de tal neo formacin en ausencia de hallazgos positicos a los rayos X. El neumotorax espontneo puede ocurrir en cualquier tiempo en el curso de esta enfermedad o puede ser el accidente inicial. slEidlams eisnottrealtioormcaicdaesbeoincculaunirdsoe henayeipdleiaugrenssaticpoerdsiifseterennteciaclondedlearsrammaesays > fibrotrax progresivo. RESUME L'auteur dcrit un cas de msothliome malin qui, son point de dpart tant localis la portion diaphragmatique de la plvre, a fini par envahir l'hmi-diaphragme gauche et la cavit pritonale. La tumeur pleurale maligne est une entit clinique bien certaine mme si la classification pathologique reste matire discussion. La gne continue ou intermittente d'un hmithornx ou d'un ct de l'pigastre peut tre la manifestation initiale en l'absence de constatations radiologiques positives. Un pneumothorax spontan peut survenir tout moment de l'volution et peut raliser le symptme initial de l'affection. Le msothliome peut tre compris dans le diagnostic diffrentiel des masses intrathoraciques, des panchements pleuraux chroniques, et du fibro-thorax progressif. ZUSAMMEN FASS UNG Beschreibung eines Falles eines malignen Mesothelioms, ausgehend von^ ^ Zwerchfeilteil der Pleura mit Durchsetzung der linken Zwerchfelihiilfte " und der Bauchhhle. Der bsartige pleurale Tumor ist eine wohl abge grenzte klinische Einheit, auch wenn seine pathologische Einordung. eine Sache der Vermutung bleibt. Anhaltende oder wiederkehrende Beschwerden auf einer Brustkorbhiilfte oder einer Seite des Epignatriums knnen das Initial-Symptom eines solchen Wachstums sein bei Fehlen positiver rntgenologischer Befunde. Ein Spontan-Pneumothornx kann zu jeder Zeit im Verlauf dieser Krank heit auftreten oder kann auch das initiale Merkmal sein. Ein Mesotheliom muss in die Differential-Diagnose einbezogen werden bei soliden intrathorakelen Massen, anhaltender Pleuritis mit Erguss und fortschreitendem Fibrothorax. (7) tr*. **** JfSMJ.-: *;:*.`*:.. :-;** .''*V ;: . > . ; ;1*X..S*.',I, .** i* * . ' '! * i . ' -. ' T.-"...!* V!:?- -.-X : : i t : s^ i j L iii; m i. : -0. V . O ;..- ;-,--.: ; !> l ' ik i-'; ; ,,fJ .V ! ..V '-.Ui r* >***V rtiS:-: ,,: ' SK '.S...X.... O ; ; ; - : : ; : : kx-xpj xH:!1 x-fX': f I i! 's >,_ d'N-iih REFERENCES 1 Will, R. A.; Pathology of Tumors, C. V. Mosby Company, St. Louis, Mo., 1948. 2 Anderson, W. A. D.: Pathology, 2nd edition, St. Louis, Mo., 1354. 3 Ackerman. L. V. and Regato, J. A. del: Cancer, Diagnosis, Treatment aid Progno sis, C. V. Mosby Company, St. Louis, Mo., 1954. 4 Stout, A. P. and Himadi, G. M.: "Solitary (Localized) Mesothelioma of the Pleura," Ann. Surgery, 133:50, 1951. 5 Stout, A. P.: "Mesotheliomas of the Pleura and Peritoneum," J. Tenn. Med. Assoc., 44:409, 1951. 6 Stout, A. 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