Document bYO77zQMMQa4Y5eKyoJYKOnO

'n,i ,p.. inf f -rfT ly u r . v y 04/14/1998 12:28 v* I # T * . 00000000000 PAGE 02 Primary Malignant Mesothelioma of the Pleura H. B. E1SENSTADT, M.D., and F. \V, WILSON. M.D. Pqjj 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. Un pathic pneumothorax, or dense massive shadows fortunately, this disease is quite uncommon, and covering a large portion of the hemithorax. 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 as nant consist either of solid conglomerations or rare as the literature reports and probably may glandular and follicular arrangements of epi be seen but not recognized properly. ' thelial cells or, more rarely, of nbrosarcomafous 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, ana, 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 anu Sherman* 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 Maximow* and later by confirmed by others, it seems mandatory for all Stout and Murray* 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 1 cells that are multipotential and can form growth. It is obvious that a tumor of such great 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.* 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* while the second is a new case. ized form is usually benign, fibrous, and asymp tomatic until late and is often discovered during routine chest x-ray examinations. It forms a globular density attached to the chest wall or the diaphragm. There are all kinds of transitions CASE REPORTS Case 1. A 57-year-old oil refinery foreman noticed a diffuse pain in nis left upper chest'and upper abdomen, which gradually increased In intensity. The onset was very insidiout, and his initial discomfort was at first not between this tumor and the malignant types which grow diffusely, invade rapidly, and show early symptomatology. The latter may be respon- clearly separated from a previously present angina pec-, tons, in spite of the fact that the chest pain had changed in character and persistence and no longer responded to vasodilating remedies. H. . EUEXSTAirr and r. w. misos are icith the St. Hary'e Hotpltal and Park Place Hospital, Port Ar thur, Texas. Initially, an 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 1900 511 1 1 - *51 aty jrj J) ? \tfry m 1998 12:28 80000808808 PAGE 83 the pleural space, or in the bony itih cage. A small miNMint nf fluid wli* aspirated but rot examined for tumor ceils. The tlittt pain persisted after the air had been absorbed, ami a dense fibrnthotax gradually developed with shrinking of the entire heroithbrax and inward retraction of tin' lateral chest wall. Thoracic exploration was performed because of un bearable pain, but this revealed only a dense fibrothonx - with massive adhesions. Decortication gave no (y. Anorexia and weight loss became marked and led to severe cachexia. Neither large doses of narcotic* nor neurosurgical procedures reduced the pain. An explora tory laparotomy followed, but only sintifar adhesions wot encountered. No diagnosis was' made until a routine stomach x-rwy film iincxpcctedhr revealed that several ribs were destroyed. Biopsy of tills region revealed pint, ml mesothelioma. .~ Oiw . A M-ycar-ohl oil refinery foreman who had worked with asbestos insulating material for unite a while noticed soreness and a rattling noise in the left hvtmthorax. Chest examination in January 1959 revealed n hbxxiy pleural effusion. Tills fluid was httctrrinlogicallv negative hot rontained !rgc msiKXhcIful ceils, which our putisotoRist suspected were malignant (figure 1). flow, ever. bis suspicion was not shared bv a number of other pathologists who were consulted. The patient t pain eontinned to increase ami radiated over the whole left hemi. thorax. Tlie pleural fluid reaccnmulated in spite of re peated tlwrough paracenteses. Some dyspnea Jag iinle Fig. I. Large roosothcliul I'd!* rxrtcd in the hlandy pint* ral effusion. 8T cough was noted. Exploratory thoracotomy in n large medical center re. veiled multiple hard plaques covering the entire pietml space nod extensive pleural adhesions. A portion of the pleura was removed tor microscopic studies. The pathpL ofiist reported "grannloniata of unknown origin.'' A king biopsy performed at the same time revealed asbestos boies in the bronchiole*. In tpite of negative skin and hacteriotogk* texts, the patient was placed on an oti. tuberculous regime after tlie operation. The fluid did nm return, hut a dense fibrothornx developed with shrinking of the entire hemitborax. The pleural denritv increased on successive x-ray films and finally revealed an upper scalloped border < figure 2). Tha pain was constant dav and night and did not respond to large doses nf n,,i. r colics. In November 1950. intercostal blocks were performed followed by nerve sections. These procedure* were with, out tx-nrfit. and. in December 1959. a cltordotomy v* mAid also done. Shortly after this operation. x-ray examination revealed that several ribs were destroyed. Similar nwtu. genogrami had been previously made almost at mmtthtv intervals, hut no bony defect had ever been noted - cilionat biopsy of these hones revealed a malignant growth interpreted as "fibrous sarcoma* hv the pathot*. gist /figures 3 and 4). fn Use following weeks, various other parts of th>- fam- thoracic cage were destroyed, particularly the lower dor. sal vertebrae and tlie tipper stcmitui. This led to void compression and transection as well os to obstruction uf tht* trachea and esophagus. Tln> patient suffered ujvhtar. able pain until his demise in May I960. The essential findings at autopsy were "Mc*othf);Uma of the left pleura invnding mediastinum, ribs, vertebrae, liver, spleen, and lungs. Hypostatic pneumonitis, asbn. tosis of the lungs. The primary tumor and the mestas. tiues consisted of ireewuar hundles of spindle ceJU u{ atypical character with hyperchromatic hirsute nuclei* Fig. 2. Upper scalloped border of (he plcttral walls. (figures T and 41. 512 THE JOURNAL-LANCET IRECE! VED TIMEAPE. !4.B!!:34Afc T!1g5EA?c 1998 12:28 60000060080 > PAGE 04 Fig. 3 (fcft) and Fig- 4 (right). FdiniMKlWM nnitpnxrd of irregu lar bundles of spirnlk crib wiih livpewlirnmutic l>l*arv nuclei. i ( DISCUSSION centesis or aspimtiou oFthe pneumothorax. Ano The similarity of these 2 cases of diffuse malig rexia, weight loss, and cacliexiu gradually de nant mesothelioma and of some of the others velop. Administration of narcotics and neuro reported in the literature,T-,*` is striking. Only surgical procedures are without benefit or only the lack of familiarity with this entity am ex slightly useful to the patient. Percussion density plain why both of the medical centers caring and shrinking of the hemithonix, with or with tor these patients failed to make an early diag out scoliosis, may be observed. Clubbing of fin nosis. in spite of the fact that the referring phy gers, articular rheumatism, and osteoarthropa sician alerted them to the possibility of such a thy have been reported in some cases but have growth. These patients were observed for months not been observed in our patients. They are ap by various specialists who failed to recognize parently more often seen with the localized be this entity until bone destruction, which was nign mesotheliomas. Chills, fever, cough, dysp noted on roentgenograms, and excisional biopsy nea. and cyanosis are usually mild or absent. confirmed the correct diagnosis. ' The roentgenologist should be aware of the Any attempt to give these patients the benefit fact that the chest x-ray may be entirely negative of radical surgery or successful radiation therapy for some time. Pleural effusion, Sbrothorax or would require a thorough knowledge of the early pneumothorax are nonspecific. However, the in symptomatology of this tumor. The clinician creasing density of the Sbrothorax, particularly most be alerted to a diffuse unilateral chest pain after surgical exploration and the shrinking and of recent origin gradually increasing in inten narrowing of the entire hemithonix may be sig sity in a middle-aged or elderly person. His nificant. Either the mediastinum is pulled toward physical examination may be negative, or there the lateral chest wall or vice versa. Scalloped may he an unexplained pleural effusion and. margins of the pleural walls or of the fibro- occasionally, a spontaneous pneumothorax. The thorax (figure 2) are late manifestations. Bone bacteriologic examination of the pleural fluid destruction should be constantly looked for with will be negative. It remains to be seen whether repeated Bucky exposures. If present, this an J the cells present in this fluid can be recognized nounces the final, probably incurable stage. 4% as malignant by the pathologists (figure!). Thoracic exploration is always necessary to The pain is not markedly relieved by para confirm the diagnosis. Therefore, die chest' sur- ^4/14/1998 12:28 00000880888 PAGE 05 r,^V considered it "very unlikely that the pathogene sis of the turner could be related to the asbestos fibers since they were located in the bronchioles ami not in tbe* 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 die. initial x-ray pictures (figure 5. double arrows), indicating seme pleural scarring prior to the de velopment of the malignant growth. Cft * f 1- 'I. summary .. The symptomatology and natural course of pri mary malignant mesothelioma has been illus trated by 2 case reports. In spite of early clin ical suspicion, early thoracic exploration, and continuous care by various specialists, these pa tients progressed to an advanced hopeless stage with destruction of the bony thorax before the correct diagnosis w;c established. The early din. Fi^c. 5. Calcium deposit dong the diaphragmatic Mir. face of the pleural apace. icnl. roentgenologic, ami pathologic charaetcristics of this neoplasm must be kept in mind in order to bring these patients in time to radical surgical procedures or effective irradiation them.- geon must be familiar with the various mstcro* scopic features of the growth which forms fine nodules, large phiques, massive adhesions, and a dense fibrothorax. Of utmost importance is. of course, the cor py that may be curative or at least prolong life. The authors wish to express their appreciation to Dr. John M. Childers, 'Department of Pathology, Medial Brandi, University of Texas, Galveston; and Dr. Stnnlev Crawford, Department of Surgery. Baylor Medical School. Houston, for their help in the preparation of this papn! rect pathologic interpretation of the pleural bi REFERENCES opsy on which the decision for radical treatment I, Maumow. A. A.: Cl*x <ta Mcvnthvl , DvckavtWi, dvr u- depends. In the majority of cases, the speci mens have been misinterpreted as fibrous pleural rixypn HSiilr) mat dtv 2,'llrn dvr rvn Eaandalv. Atd,. I ,.|rv, ZrttfnneS. 4:1. 1927. ` J. Sxnvr. A. f.. i St. R-; Ucdimt plvnrat thickening, pleural adhesions, granulomatous tis sues, or metastatic malignancy. The careful pa thvJiffm*. fmvxMgatiim nf to chAMrtvriMM and hbtnv>rv. tijr Mrthwl ,>l Imw culniy. Arch. Path. 34:951, 19421 3. Cw neon) of lh>* Miurtmrtr Cmvral ftmpilal. No. 43t0] thologist can only state that the lesions arc com patible with malignant mesothelioma, because NV* EnRlamt J, Mvt.360,491. J959. * 4. ItaftMO. M. 5.. HtMaX, SI. M.. and Xt'in, D. ft.: A ir. pcexatilv form of muUijiW mnolWiOra. Do. CKol this diagnosis actually requires a complete au 1950. . Richaat. X. and ` C. D.. Jo.: Prolnncvd laninl topsy excluding any other primary neoplasm. However, in practice, one should proceed with in (tittwic plvumi mvaothvlinma tnratvd with At'"*. Conor? u. 799, 1939. ' . Eircxoraot. H. B,i Malfeniuit mnntbrlioma nl thv iL,, surgical therapy if a thorough clinical investi gation hats eliminated any distant malignancy. Oh. Cbrtl 30:549. 4936. '' 7. WoiCorr. M. 'V. Swo, IV. A., H. E.,and Fiw 4tv. E. D.:MoolWhnat of thvplvnjra. DO. CMl 1. Our second case is particularly interesting tin. 1939. ' H. Crrtwv. J. TV. MnthrKo of lh>- plow*, Am. J. XI. because of the history of long-time exposure to asbestos and the discovery of asbestos Wlies in 225:630, I9S4. 9. SmuK. M. A., irad Have. IV. .1,: Diffuir malignant mr-.. (hvtionu, 14 thv (ilvura, Am. Kw. Tubvtc. 79:2(55. 1454. the lung biopsy specimen. The etiologic associu- f 10. XtlLLcM. K. D.. OutiKiurer. M. B.. and hexserr. XV. Mammary oniwiM.1 Inlinmrd after 25 yean hv primary a.. tion of asbestos and malignant mesothelioma has lijmint plvtiral mentbdwflt. Arch. Sur- 76:16(1. 1935. been repeatedly discussed in the literatuK*."*'' j tt. Vax au Scitnor. H. C. M.< Aln-tn*H vn flvo*sre-,ltvn. ,W<irrl. Ii|,lchr. grnvt'ik. 102:1(23. 1939. . Not all investigators agree that exposure to as 12. Fvakcja. A., and MoxaUca. C.: Ailmlai v carcinoma fy*. mnnnrr. Miot*rva iwrd. (T; 196. 1936. bestos predisposes to malignancy of the pleu- 13. HtJvn. C. W., and Rrisnvtis, tt.: Aabratme hvi ra.,s However, such history alerted the suspi cion of the authors in the second case. ` Xrztl. IVaehr. 14,361. 1959. 14. Smith. K. W.: 1`utmoMty di-hlHly In atbwtu* workvn. Aid, tnduai. Health 125196. 1953. On the basis of his autopsy, our pathologist 15. PeKncnoaAM, E. P.: The PiwomwMmJmii Problem. $p,m.. Kviri. III.! Charlv* C Thomai. 1939- 314 THE JOURNAL-LANCET DECEIVED T1MEAPH. 14 : ?4AN lW'T ''Hit