Document yreM118dpnkBDz5pJzz5pX0jD

04/14/1998 12:28 *7 00000000000 PAGE 02 Primary Malignant Mesothelioma of the Pleura H. B. EISENSTADT, M.D.. and F. W, WILSON. M.D. Pojt Arthur, Texas he diagnosis of primary malignancy of the sible for chest pain and discomfort before being Tpleura continues to be quite a difficult prob visible on roentgenograms. Later, they make lem in spite of all modern clinical skills andthemselves known by pleural effusions, idio advanced laboratory and x-ray facilities. Unpathic pneumothorax, or dense massive shadows 4 t fortunately, this disease is quite uncommon, and covering a large portion of the hemithorax. J few investigators have been able to accumulate Microscopically, the benign mesotheliomas a broad knowledge of its characteristic features. form fibrous masses, while those that are malig Nevertheless, mesothelioma is perhaps not os nant consist either of solid conglomerations or rare as the literature reports ana probably may glandular and follicular arrangements of epi be seen but not recognized properly. thelial cells or, more rarely, of fibresarcomatous This tumor is most frequently confused with tissue. The localized tumors can be eradicated benign lesions of the pleura or the mediastinum, surgically; the diffuse types, however, have been with primary malignancy of the underlying lung considered inoperable until recently when Harris tissue as well as of the enclosing rib cage, and and associates4 reported a cure, or at least a finally, with metastatic disease from a distant long-term survival, after radical pleuropneumo- tumor. Many diagnostic difficulties are created nectomy during the early stage of the develop by the great variety of clinical, roentgenologic ment. In addition, Richert and Sherman*1 report and pathologic manifestations of this tumor that ed a long-term arrest after early administration may puzzle clinicians, chest surgeons, roentgen of radioactive gold. ologists, and pathologists. This peculiar behavior If the experience of these investigators can be was explained at first-by Maximow1 and loter by confirmed by others, it seems mandatory for all Stout and Murray5 with the aid of cell culture physicians who may encounter mesotheliomas methods. in their practice to acquaint themselves with The growth originates from mesothelial (ce the symptomatology ana natural history of this lomic ) cells that are multipotential and can form growth. It is obvious that a tumor of such great J a great variety of mesothelial as well as mesen variability will produce a different picture in chymal tissues in manifold combinations/1 Thus, each individual case. However, the experience mesotheliomas not only differ from each other gained from the observation of 2 patients with but also may show amazing differences in mi malignant mesothelioma showed a characteris croscopic sections of the same growth/1 tic similarity that makes it worthwhile to review Clinically, 2 types can be distinguished: a them. The first case was. previously reported in localized and a diffuse mesothelioma. The local detail,11 while the second is a new case. I ized form is usually benign, fibrous, and asvmptomatic until late and is often discovered during CASE REPORTS routine chest x-ray examinations. It forms a Case i. A 57-yeJr-o)d oil refinerv foreman noticed a diffuse pain in nix left upper chest and upper abdomen, globular density attached to the chest wall or which gradually increased in intensity. The unset was the diaphragm. There are all kinds of transitions very insidious, and his initial discomfort was at first nor I between this tumor and the malignant types dearly separated from a previously present angina pec-, which grow diffusely, invade rapidly, and show tons, in spite of the fact that the cnest pain haa changed in character and persistence and no longer responded to early symptomatology. The latter may be respon- vasodilating remedies. h. . EisEXCTAirr and r. w. wilson are tcith the St. Mary's Hospital and Park Place Hospital, Port Ar thur, Texas. Initially, ao x-ray film of the chest was normal, but 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 1998 12:28 00000000000 PAGE 03 Ike pleural space, or in the bony rib cage. A smxfl amount of serous fluid w&t aspirated but not examined iOL for tumor cells. The cliest pain persisted after the air laid Im'cu absorbed, and dense fibroehorax gradually developed with shrinking of the entire hemtthorax and iwnru retraction of tkt' lateral chest wall. Thoracic exploration wtu performed because of un bearable pain, but this revealed only a dense fibrothorax with massive adhesions. Decortication gave no relief. Anorexia and weight Joss became marked and led to severe cachcxiu. 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 routine stomach x-ray flint unexpectedly revealed that several ribs were destxovcd. Biopsy of this tegwn revealed pleu ral mesothelioma. ," Cone 2. A Afl-ycar-old oil refinery foreman who had worked with aslicstos insulating materia) for unit* a `'''i1?/v'-^V [*'. *.j while noticed soreness and a rattling noise in the Hi bvmithorux. Chest examination in Jamurv 1939 trvcxkd n bloody pleural effusion. This fluid was Vwctrrwjlogicalh- ncjjutivc hot contained force mesotbeltjd cells, which ooV putlwfogrrt suspected wero malignant (figure 1). How ever. his suspicion wax not shared by a number of other pathologist* wlw> were consulted. Tlie patient's pain continned to increase and radiated over the whole left Hemi- thorns. Tito pleural fluid reaccmnufoted in spite of re* pcatctl tltorough paracenteses. Some dyspnea httt little Fig, I. Liuge mrsothcltnl cells noted ui the blcxxiy pleu ral effusion. S-.^WiW! &MI cough was noted- Exploratory thoracotomy in a forge medical center re. voided multiple hard plaques covering the entire pleural space and extensive pleural adhesion*. A portion of the pleura was removed tor microscopic studies. The pathbU ................. "--`--1---** " " A king asbestos OUUIO ... ..in HIV IHWMMI....V.. -J. ,, . skin and hacteriologlc tests, the patient was placed on an anti, tuberculous regime after tle operation. The fluid did not return, hut 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 dav and night and did not respond to forge doses of n,,i- colics. In November 1950. intercostal blocks were perform'd followed hv nerve sections. These procedures were with, out Ix-nefit. and. in December 1939. a chordotomy w. c - : J* also done. Shortly after this operation, x-ray examination revealed that several ribs were destroyed. Similar menu cenograms had been previously made almost at monihlv mtervalx. but no bony defect had ever been noted Ex. visional biopsy of these hones revealed a malignant growth interpreted ax "fibrous sarcoma" by the pattol*. gist (figures 3 and 4). In (lie following weeks, various other parts of th- hnnv thoracic cage were destroyed, particularly the lower d-w. sal vertebrae and the upper sternum. Tins led to i-otd a compression and transection as well as to obstruction uf the trachea and esophagus. The patient stiffen'd unbrat- able pain until his demise in May I960. The essential findings at autopsy were "Mesothelioma of the left pleura invading mediastinum, ribs, vertebrae, liver, spleen, and lungs. Hypostatic pneumonitis, aibev tosis or the lungs. The primary tumor and the mestxju tUaIsKe9s choVnIs|is\tCeVd oV*f i.r..r..e...g..u...l.a...r....b...u...n. .dle-s of s%pindle cells { atypical character with hyperchromatic bizarre nuclei* Fig. 2. Upper sealioped border of the pleural walls. (figures 3 and -I). m i 512 THE JOURNAL-LANCET ;E!ved timeap: 34 A? IPPINT TIMEADD 1998 12:28 00000000880 PAGE 04 Fig, 3 (left) rtnd Fig. 4 (right). FilinwaKoma composed of irrvgitlur bundles of spindle tells with liypereliromatic bixartv nuclei. DISCUSSION The similarity of these 2 eases of diffuse malig nant mesothelioma and of some of the otliers reported in the literature,7-"* is striking. Only the lack of familiarity with this entity cun ex plain why both of the medical centers caring tor 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 excisional 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 of recent origin gradually increasing in inten sity 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 bacteviologic examination of the pleural fluid will be negative. It remains to be seen whether the cells present in this fluid can be recognized as malignant by the pathologists (figure 1). The pain is not markedly relieved by para centesis or aspiration ofthe 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 heinithonix, with or with out scoliosis, may i>e 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. Jf present, this an nounces the final, probably incurable stage. Thoracic exploration is always necessary to confirm the diagnosis. Therefore, the chest sur- NOVEMBER I960 513 12:28 00080000000 PAGE. 05 considered it "very unlikely that the pathogene sis of the turner could be reluted to the asbestos fibers since they were located in the bronchiole ami not in the pleura.** However, asbestos ma terial could have reached the pleural tissues without being demonstrable microscopically.1* In addition, along the diaphragmatic surface of the pleural space there was a "thick grey rind which was partially calcified** at autopsy. This calcium deposit could be demonstrated on the initial x-ray pictures (figure 5. double arrows), indicating seine pleural scarring prior to the de 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 macro* scopic features of the growth which forms fine nodules, large plaques, massive adhesions, and a dense fibrothorax. Of utmost importance is. of course, the cor rect pathologic interpretation of the pleural bi opsy on which the decision for radical treatment depends. In the majority of cases, 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 arc 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 cose is particularly interesting because of the history of long-time exposure to asbestos and the discovery of asbestos ImkUcs in the lung biopsy specimen. The etiologic associa tion of asbestos and malignant mesothelioma has been repeatedly discussed in the literattuc.11'1" 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 case. On the basis of his autopsy, our pathologist summary .. The symptomatology and natural course of pri mary* malignant mesothelioma has been illus trated bv 2 case reports. In spite of early clin ical suspicion, early thoracic exploration, and continuous can* by various specialists, these pa. tients progressed to an advanced hopeless stage with destruction of the bonv thorax before the correct diagnosis wax established* The earlv clinteal, roentgenologic, anti pathologic characteris tics of this neoplasm must be kept in mind in order to bring these patients in time to radical surgical procedures or effective irradiation thera py that may he curative or at least prolong life. Tlw authors wish to express their appreciation to Dr. John H. Chillier*, 'Department of Pathology, Medical Branch. University of Texas, Galveston; and )r. Stcnlev Crawford, Department of Surgery. Baylor Medical School. Itmiston. for their help in the preparation of this paper. MirXBENCES 1. A. A.; t)it ilai Mmtkrl fDrchfllvn <)*t ,r rfeen HiiiiUO uml il(r Z*`Urf\ dvr Mi(Am Emmlatf, Arch. < *|Kf. Zt'll/nru-h. 4:1. 1927. * 2. SlflVT. A. P.. Krai M. 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