Document 3NX7gxj0g6JQ3E4q2XV2LmORy

FILE NAME: Oil Industry and American Petroleum Institute (API) DATE: 1960 Nov DOC#: API166 DOCUMENT DESCRIPTION: Journal Article - Primary Malignant Mesothelioma of the Pleura Primary Malignant Mesothelioma of the Pleura H. B. EISENSTADT, M.D., and F. W. WILSON, M.D. Port Arthur, Texas rHE d ia g n o sis o f primary malignancy of the sible for chest pain and discomfort before being pleura continues to be quite a difficult prob- visible on roentgenograms. Later, they make ;m in spite of all modern clinical skills andthemselves known by pleural effusions, idio dvanced laboratory and x-ray facilities. Un-pathic pneumothorax, or dense massive shadows rrtunately, this disease is quite uncommon, and covering a large portion of the heinithorax. ew investigators have been able to accumulate Microscopically, the benign mesotheliomas broad knowledge of its characteristic features. form fibrous masses, while those that are malig Nevertheless, mesothelioma is perhaps not as nant consist either of solid conglomerations or re as the literature reports and probably may glandular and follicular arrangements of epi e seen but not recognized properly. thelial cells or, more rarely, of fibrosarcomatous This tumor is most frequently confused with tissue. The localized tumors can be eradicated enign lesions of the pleura or the mediastinum, surgically; the diffuse types, however, have been ith primary malignancy of the underlying lung considered inoperable until recently when Harris ssue as well as of the enclosing rib cage, and, and associates4 reported a cure, or at least a nally, with metastatic disease from a distant long-term survival, after radical pleuropneumo- imor. Many diagnostic difficulties are created nectoiny during the early stage of the develop v the great variety of clinical, roentgenologic ment. In addition, Richert and Sherman"' report id pathologic manifestations of this tumor that ed a long-term arrest after early administration ay puzzle clinicians, chest surgeons, roentgen- of radioactive gold. ogists, and pathologists. This peculiar behavior If the experience of these investigators can be as explained at first by Maximow' and later by confirmed by others, it seems mandatory for all :out and Murray- with the aid of cell culture physicians who may encounter mesotheliomas ethods. in their practice to acquaint themselves with The growth originates from inesothelial (ce- the symptomatology and natural history of this mic) cells that are multipotential and can form growth. It is obvious that a tumor of such great great variety of inesothelial as well as mesen- variability will produce a different picture in iymal tissues in manifold combinations/' Thus, each individual case. However, the experience esotheliomas not only differ from each other gained from the observation of 2 patients with it also may show amazing differences in mi- malignant mesothelioma showed a characteris oscopic sections of the same growth/' tic similarity that makes it worthwhile to review Clinically, 2 types can be distinguished: a them. The first ease was previously reported in calized and a diffuse mesothelioma. The loeal- detail," while the second is a new case. -d form is usually benign, fibrous, and asympmatic until late and is often discovered during atine chest x-ray examinations. It forms a 'bular density attached to the chest wall or CASE REPORTS Case 1. A 57-year-old oil refinery foreman noticed a diffuse pain in his left upper chest and upper abdomen, which gradually increased in intensity. The onset was e diaphragm. There are all kinds of transitions tween this tumor and the malignant types aich grow diffusely, invade rapidly, and show r,y symptomatology. The latter may be respon- very insidious, and his initial discomfort was at first not clearly separated from a previously present angina pec toris, in spite of the fact that the chest pain had changed in character and persistence and no longer responded to vasodilating remedies. Initially, an x-ray film of the chest was normal, but B- e is e n s t a d t and f . w . Wilso n are with the St. ,,r!I s Hospital and Park Place Hospital, Port Arlr> Texas. soon this patient experienced a "spontaneous" pneumo thorax without a history of trauma or physical exertion. A roentgenogram taken at this time showed a partly col lapsed lung without abnormal shadows in this organ, in NOVEMBER 1960 511 the pleural space, or in the bony rib cage. A small amount of serous fluid was aspirated but not examined for tumor cells. The chest pain persisted after the air had been absorbed, and a dense fibrothorax gradually developed with shrinking of the entire hemithorax and inward retraction of the lateral chest wall. Thoracic exploration was performed because of un bearable pain, but this revealed only a dense fibrothorax with massive adhesions. Decortication gave no relief. Anorexia and weight loss beeame marked and led to severe cachexia. Neither large doses of narcotics nor neurosurgical procedures reduced the pain. An explora tory laparotomy followed, but only similar adhesions were encountered. No diagnosis was made until a routine stomach x-ray film unexpectedly revealed that several ribs were destroyed. Biopsy of this region revealed pleu ral mesothelioma. Fig. 1. Large mesothelml cells noted in tile bloody pleu ral effusion. Fig. 2. Upper scalloped border of the plenral walls. Cane 2. A 58-year-old oil refinery foreman who had worked with asbestos insulating material for quite a while noticed soreness and a rattling noise in the left hemithorax. Chest examination in January 1959 revealed a bloody pleural effusion. This fluid was bacteriologieally negative but contained large mesotheiial cells, which our pathologist suspected were malignant (figure 1). How ever, his suspicion was not shared by a number of other pathologists who were consulted. The patient's pain con tinued to increase and radiated over the whole left hemi- thorax. The pleural fluid reaeeumulated in spite of re peated thorough paracenteses. Some dyspnea but little cough was noted. Exploratory thoracotomy in a large medical center re vealed multiple hard plaques covering the entire pleural space and extensive pleural adhesions. A portion of the pleura was removed for microscopic studies. The pathol ogist reported "granulomata of unknown origin." A lung biopsy performed at the same time revealed asbestos bodies in the bronchioles. In spite of negative skin and baeteriologie tests, the patient was placed on an anti tuberculous regime after the operation. The fluid did not return, but a dense fibrothorax developed with shrinking of the entire hemithorax. The pleural density increased on successive x-ray films and finally revealed an upper scalloped border (figure 2). The pain was constant day and night and did not respond to large doses of nar cotics. In November 1959, intercostal blocks were performed followed by nerve sections. These procedures were with out benefit, and, in December 1959, a cliordotomy was also done. Shortly after this operation, x-ray examination revealed that several ribs were destroyed. Similar roent genograms had been previously made almost at monthh intervals, but no bony defect had ever been noted. Ex- cisional biopsy of these bones revealed a malign*'11 growth interpreted as "fibrous sarcoma" by the patholo gist (figures 3 and 4). In the following weeks, various other parts of the bom thoracic cage were destroyed, particularly the lower or^ sal vertebrae and the upper sternum. This led to cor^ compression and transection as well as to obstruction < the trachea and esophagus. The patient suffered inixa able pain until bis demise in May 1960. ^ ( The essential findings at autopsy were Mesothe iom of the left pleura invading mediastinum, ribs, verte m liver, spleen, and lungs. H y p o s ta tic p n e u m o n itis , 3So - tosis of the lungs. The primary tumor and the me ^ tases consisted of irregular bundles of spindle ee atypical character with hyperchromatic bizarre nu (figures 3 and 4). 512 THE JOURNAL-LANCET The similarity of th nant mesothelioma reported in the litt y the lack of familiar plain why both of for these patients fa nosis, in spite of the sician alerted them growth. These patiei by various speefah's y this entity until In nted on roentgenog :: confirmed the c-orrei y Any attempt to gif radical surgery or Would require a thon symptomatology of nlust be alerted to a y f recent origin ora s,ty m a middle-ag Physical examinatioi .! may be an une.xpla ^casionally, a spoilt acteriojogjc e.vamii w*ll be negative. It e cells present in t < aSTMal'gnant by the :i; ibe pain is'not i, Fig. 3 (left) and Fig. 4 (right). Fibrosarcoma composed of irregu lar bundles of spindle cells with hyperehromatic bizarre nuclei. DISCUSSION The similarity of these 2 eases of diffuse malig nant mesothelioma and of some of the others reported in the literature,7' 10 is striking. Only the lack of familiarity with this entity can ex plain why both of the medical centers caring for these patients failed to make an early diag nosis, in spite of the fact that the referring phy sician alerted them to the possibility of such a growth. These patients were observed for months by various specialists who failed to recognize this entity until bone destruction, which was noted on roentgenograms, and exeisional biopsy confirmed the correct diagnosis. . Any attempt to give these patients the benefit of radical surgery or successful radiation therapy would require a thorough knowledge of the early symptomatology of this tumor. The clinician must be alerted to a diffuse unilateral chest pain f recent origin gradually increasing in intenSlty in a middle-aged or elderly person. His physical examination may be negative, or there may be an unexplained pleural effusion and, Occasionally, a spontaneous pneumothorax. The hacteriologie examination of the pleural fluid ; will be negative. It remains to be seen whether ' me cells present in this fluid can be recognized : ^ malignant by the pathologists ( figure 1). The pain is not markedly relieved by para centesis or aspiration of the pneumothorax. Ano rexia, weight loss, and cachexia gradually de velop. Administration of narcotics and neuro surgical procedures are without benefit or only slightly useful to the patient. Percussion density and shrinking of the hemithorax, with or with out scoliosis, may be observed. Clubbing of fin gers, articular rheumatism, and osteoarthropa thy have been reported in some cases but have not been observed in our patients. They are ap parently more often seen with the localized be nign mesotheliomas. Chills, fever, cough, dysp nea, and cyanosis are usually mild or absent. The roentgenologist should be aware of the fact that the chest x-ray may be entirely negative for some time. Pleural effusion, fibrothorax or pneumothorax are nonspecific. However, the in creasing density of the fibrothorax, particularly after surgical exploration and the shrinking and narrowing of the entire hemithorax may be sig nificant. Either the mediastinum is pulled toward the lateral chest wall or vice versa. Scalloped margins of the pleural walls or of the fibro thorax (figure 2) are late manifestations. Bone destruction should be constantly looked for with repeated Bucky exposures. If present, this an nounces the final, probably incurable stage. Thoracic exploration is always necessary to confirm the diagnosis. Therefore, the chest sur- NOVEMBER 1960 513 considered it "very unlikely that the patlio--^ sis of the tumor could be related to the asbest*" fibers since they were located in the bronchiolS!'. and not in the pleura." However, asbestos rjtt! ` terial could have reached the pleural tissu** without being demonstrable microscopically^! In addition, along the diaphragmatic surface of the pleural space there was a "thick grey whieh was partially calcified" at autopsy. TfiJi: calcium deposit could be demonstrated on the initial x-ray pictures (figure 5, double arrow*) indicating some pleural scarring prior to the d<y velopment of the malignant growth. Fig. .5. Calcium deposit along the diaphragmatic sur face of the pleural space. geon must be familiar with the various maeroscopie features of the growth whieh forms fine nodules, large plaques, massive adhesions, and a dense fibrothorax. Of utmost importanee is, of eourse, the eorrect pathologic interpretation of the pleural bi opsy on which the decision for radical treatment depends. In the majority of eases, the speci mens have been misinterpreted as fibrous pleural thickening, pleural adhesions, granulomatous tis sues, or metastatic malignancy. The careful pa thologist can only state that the lesions are com patible with malignant mesothelioma, because this diagnosis actually requires a complete au topsy excluding any other primary neoplasm. However, in practice, one should proceed with surgical therapy if a thorough clinical investi gation has eliminated any distant malignancy. Our second case is particularly interesting because of the history of long-time exposure to asbestos and the discovery of asbestos bodies in the lung biopsy specimen. The etiologie associa tion of asbestos and malignant mesothelioma has been repeatedly discussed in the literature.u_ir' Not all investigators agree that exposure to as bestos predisposes to malignancy of the pleu ra.15 However, such history alerted the suspi cion of the authors in the second ease. On the basis of his autopsy, our pathologist SUMMARY The symptomatology and natural course of prf. mary malignant mesothelioma has been illuj. trated by 2 ease reports. In spite of early din* ieal suspicion, early thoracic exploration, ami continuous care by various specialists, these pa. tients progressed to an advanced hopeless stage with destruction of the bony thorax before the correct diagnosis was established. The early clin* ieal, roentgenologic, and pathologic character* ties of this neoplasm must be kept in mind in : order to bring these patients in time to radical surgical procedures or effective irradiation them.; pv that may be curative or at least prolong life.:: The authors wish to express their appreciation to D. John II. Childers, Department of Pathology, Mcdictl Branch, University of Texas, Galveston; and Dr. Stanby Crawford, Department of Surgery, Baylor Medical School. Houston, for their help in the preparation of this paper. ,. REFERENCES ` 1. M a x im o w , A. A .: ber das M esothel ( Deckzellen drf tO r sen H u te ) u n d d ie Z ellen d e r sersen Exsudate. Arch. f. exper. Zellforsch. 4 :1 , 1927. 2. St o u t , A. l, a n d M uiih ay, M . R .: L ocalized pleural nwR*. tlieliom a, investigation of its characteristics and histugnww bv m ethod of tissue cu ltu re. A rch. P ath. 3 4 :951. 1942. 3. 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