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Voi. :6j No. 14 CASE RECORDS OF TUE MASSACHUSETTS CENERAL HOSPITAL. 7 c27 747 801910 CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL Weekly GInicopuhological Exercises rovxoes 8y ueiiAao e. casot Bt-vjAiiuc C*S7UHAN, M.Dn Editor Betty U. Kusce, Assistant Editor GISE 62-1963 Pilesextattox or Case A fifty-wx-ycar-oid plumber was admitted to the hospital because oi pain in the chest. The patient had been in good health until twentyone months previously, when he began- to experience right-sided chest pain. Six months later he was told (hat an x-ray dim of the chat'was abnormal. Twelve ntenths before admission he entered another hos pital because of persistent chat pain accompanied by dyspnea and a cough productive of white spu tum. There had been no chills, (ever, weight las or fatigue. A tuberculin skin test (second-strength PPD) was reported as strongly positive, but studia of the sputum and gastric washings for tuberculosis were negative. X-ray films of the chest demonstrated a pleural density on the right side, which was thought to represent partially organized hydrothorax; branchoscopic and bronchographic studia were negative. Right-sided exploratory* thoracotomy was performed, with decortication of the pieura; the pathological di agnosis was "dense fibrodc picurids." He was dis charged home on isontarid, ICO mg. three times daily. Nine months after discharge the patient re-entered the same hospital because ot continuing chat pain, which had cot been improved by nerve block per formed in a surgeon's office. An x-ray film of the chat revealed thickening of tiie apical pieura on the left side and a linear density overiying the diaphragm adjacent to the left cardiac border; on the right side a. dense, homogeneous shadow compressed the lung downward and medially and extended from the apex to the level of die second rib; another density extended from the third costal interspace to the dia phragm. The fourth, fifth and sixth intercostal nerves were divided la an attempt to relieve tiie pain, and histologic examination of a specimen of the pleura re vealed "chronic inflammation and fibrosis.'* Shortly after discharge his wife observed that the patient's pupils were unequal in size. The chat pain was not relieved Ijy the o()cration, and lie was referred to a psychiatrist for further evaluation and treatment. Two weeks before admission he entered a mental hos pital for management of depression. Anisoenria was observed on admission. An x-ray film of the chest showed a decrease in volume of the right hentithorax, with partial collapse of the right lung, pleural effu sion, shift of (.lie mediastinum to the right and an extensive density in the right-middic-iung fluid.. Transfer to this hospital was arranged. Bilateral nerve deafness had been present for sev enteen years. The patient had worked as a piumiscr for forty years, having spent about iiaif of that period installing insulation on hoilen and pipes. He had sinoked I 'A packages of cigaretta daily for many years. Five years previously x-ray films were inter preted as showing a peptic ulcer. There had been a loss of 30 pounds in weight during the three months before entry. Physical examination disclosed a picasant man who did not appear depressed. A right-sided Hor ner syndrome and drooping of the right shoulder, were observed. Dullness and diminisiicd breath sounds were heard over the lower third of the right lung; the heart was normal, and there were no mur murs. The liver edge was felt 2 fingerbrcadilts below* the right caul margin. Tie temperature was 98.6?., the pulse 113. and the respirations 22. Tic blood pressure was 120 sys tolic. 70 diastolic The urine was normal excqsc for a rare red cell and I or 2 white ceils per high-power field in the sediment. Tic hematocrit was 38 per cent, and the white-<vli count was 11,330. The tasting glucose was 100 nig,, the urea nitrogen 13 mg., the calcium 9.0 mg., the phosphorus 3.0 mg., the bilirubin 0-5 mg., and the protein 6.8 gm. (the albumin 4.4 gm., Fir.t.'nr I. Peutreanltrinr FXm d ikt C'-.rtt Tairn <* Admtuwn, Shi>u/tnf an tCjitnttre PUnr.il i\'Sc::an on ih< ilifht Si~* JA4 a ScatUrt4 ?uimoncry Irtriiimuon. 9' C.Y- - Z o o o - 2 748 T!t NEW ENGLAND JOURNAL OF MF.DtCtNS Oeu 3, 1963 TTGTto8 .md the globulin 2.4 gnu) per 100 ml. The scrum glutamic oxalacrtic transaminase (SCOT) 'v:u 1+ units, and 'the alkaline phosphatase was 3.4 Ilodansky units. Culture of the sputum yielded a mod erate growth of pneumococci. X-ray Sims of tiic chest (Fig. 1) disclosed irregular thickening of the pleura on the right side, with elevation of the right hemidiaphragm and a slight shift of the mediastinum and heart to the right; a lesser degree of picural thickening was visible on the left side. X-ray films of the bones (Fig. 2) revealed destruction of die fourth through the sevendi ribs on the right side; the. dorsal spine was not well seen, but the lumonr spine, pelvis and skull were normal. Fluoroscopic study of Use chest showed infiltrations within the parenchyma of the right lung (Fig. 3), with miid com pensatory emphysema of the left lung; the left ventri cle was slightly enlarged; the left hemidiaphragin moved normally with respiration, but die right hciniaiaplirngm was obscured by a large quantity of fluid and picural thickening extending to die apex of the lung. An electrocardiogram was within nnrmal lim its. Tubcrcuiin (intermediate-strength PPD), histopiasmin, biastomvein and cocddioidin skin tests were negative. Ventilatory studies, which were un satisfactory because of severe pain, revealed a onesecond vital capacity of 1.50 liters, a total vital capacity of 1.62 liters (43 per cent of predicted nor- FlCuiir. 3. One'penetrated Film ol the Right ffemtthorax. Defining the Extent of the P'-ettrat Thttitening. There it tot tieol dettraeiian of portiant of the right fattrth and fifth nht (arreuttj. F:Cfe 3. Fluomteapie Spot Film of the Right Lung. Showmg a'lletitnUx Pattern of Fiaretu and a Sadtutt In* filtration. mai value) and an estimated maximum breadline capacity of 60 liters per minute. P.rcnr.r.oscopic examination and cytologic studies of brondilal wash ings and sputum were negative. Eiopsy of die. right scaiene fat pad revealed r.o evidence of tumor. An operauon was performed on die ninth hospital day. Dtrrrax.vrt.vL Diagnosis Dr. Jottx H. Knowles*: This lifty-tix-ycar-old plumber of forty yean' standing was a heavy smoker and. even more importanuy, had spent a great deal of time installing insulating material on pipes and boilers. It is probable, therefore, that he was heavily and chronically exposed to die inhalation of asbestos fibers, since asbestos is by far die most common ma terial used for insulating purposes. The history of his illness spanned a year and three quarters and began with chest pain, which apparently pcrsisict; throuchoui die course. Symptoms and signs of an infectious process were eidreiy iacking. Tiic diesi pain, which is not fully described, was unrelieved by divisinn of the fourth, nfdi and sixth incercostn: nerves. When I read that he underwent psychiatric care, the thought transiently entered my mind that this man had enough disease and chronic pain u result in an exogenous depression. Tiic second thougiit that occurred to me is tiiat the use of isoni..- rid occasionally is associated with mental irritauiiit' and even the production of psychosis. However, ! doubt very mudi that tnii cptsooc in terms of the patient's basic disease. Dr. Dreyfuss. may we review the x-ray Suns now- Dn. Jack !v. Drcytvss: Tac Sims taken on adtni. 'fVnfral im MjysarhtwrcM !l" ^tui; irciurff aw iwtMm*, Miuca* Voi.' 2C9 iVo. H CASE AEC0R05 OF THE MASSACHUSETTS CE.VERAL HOSPITAL 749 jion provide .wend interesting findings. First of all, we see a fairly extensive reaction along the. periphery of the right lung (Fig. I). Its outline is irregular, and it seems to be a soft-tissue reaction extending around the entire lung. This change means a de cease in volume of the lung, which is further indi cated by elevation of the right leaf of the diaphragm and by retraction of the heart and mediastinum to ward die right side. Within the lung field there is a ;saltern of fine fibrosis and perhaps a nodular inni trate. I am less certain about the findings on the left side, but there appears to be pleural chickening along the left lateral chest trail, as well as a similar but much less marked pattern of librosis and nodular infiltrate. The abnormality is confined almost en tirely to the perihiiar and basal regions of the lungs. The lateral film of the chest taken at die same time .cain demonstrates the elevation of the diaphragm tr.d the extensive alteration that is apparently a Seurat reaction. A fluoroscopic spot Him (Fig. 3) 'aken shortly thereafter reveals a fine, linear, reticular pattern that is probably indicative of fibrosis, and nixed in with that change or superimposed upon it .-.-c see a pattern composed of very small nodules, *hich hi ':ne areas, particularly in the lower zones, coalesc. - -> conglomerate shadows. Finally, a high;.eaesra- - ' .rn (Fig. 2*, which was. taken primarily a show : rtent of the apparent pieurai reaction, aba den: .rates very nicely that in at least two -fas, the right fourth and the right fifth, the an terior parr of the cortex is missing. This picture is certainly consistent with erosion or destruction, and . '.ere is probably also slight erosion of the sixth and -cveath ribs. Da. Kxowus: The films demonstrate that this man had bilateral pleural involvement, but pre:->minant!y of die right side Furthermore, he had bilateral parenchymal changes that were largely con fined to the lower lobes. He also had erosive dbsoluI-on of at least two ribs on the right side I'd like to sk a few questions pertaining to the radiologic .'oidics because the crux of the problem, as I see it, s whether the patient had either bronchogenic carcaotna or a pleural mesothelioma as a complication -.f what I believe was diffuse pulmonary asbestosis. 'ts Dreytuss, will you tell me about the' character i tile oWflfly in view of the fact that there might %ave been metastatic malignant disease in the con' Iguous lymph nodes, w hich would distort it? ' Dr. Darrruss: Tiie outline of tlie carinn is slurp, .-<i that fact is against signif.cant subcarinai ade: y.a thy. Dr. K.vosvuzs; Secondly, w-ould you say that the ieural fibrosis on the right side definitely extends -to titc mediastinal structures and even into the r erode inlet on that side? Da- Dbeytuss: The change tlut appears to be - -aural fibrosis or thickening definitely, and probably k^-aincantlv. extends along the medial surface of the Plsg, and it is particularly striking at the base of the right lung along the cardiac and mediastinal border. Da. .%.vmvi.ss: Do you set* any evidence of a Pancoast tumor, or so-caiied superior-sulcus tumor, in vading the soft tissues of the right thoracic inlet and thereby giv'nc rise to the Homer syndrome? Dr. Drrvfvss : Of course, a soft-tissue lesion above the apex of the lung always raises die suspicion of a superior-sulcus tumor, but I interpret the altera tion in tisis ease as a continuous process actually encasing the iung. Another due that I should like to see before tnakinc a diagnosis of a Pancoast tu mor is evidence of erosion or destruction of the first, second or third rib. which is not indicated on these films.. Dr. Kxowtxs: Can you state fairly dcfinitdy tlut 'fluid was absent and that die major portion of the diangc was due to fibrotie disease? Or. Dartvruss: I am quite certain of the absence of a significant amount of fluid. The left leaf of the diaphragm is very sharp, and the usuai tapered sign of fluid extending up the posterior gutter is lacking on the right side. Dr. K.vosvua: One other point is chat even though the right hrmidiapiiragm was elevated the liver extended 2 fingerbreadths bdow the right costal margin. So I assume that there was significant hepatomegaly. Dr. Dtorvrvss: It is certainly suggested. Dr. Kxmvucs: As I sec it, the argument in this case rests on four key* findings: the disease was bilat eral and isodi pleural and parmdiymal; the pauent had persistent rhest pain',- erosive dissolution of the ribs had occurrrd: and a right-sided Homer syn drome had developed. The last three features sug gest a malignant process and remove the disease from the simple class of just a fibrotie reaction to asbestosis. 'Hie only conclusion that I ran reach is that he had chronic pulmonary asbestos!*, and that a complication of some type iiad developed. At this (>oinc perhaps a brief historical review of asbestosis is in order.' Asbestos is a Creek word meaning unquenchable or unconsutnable in the sense of being indestructible. In 430 11. C. the Ro mans discovered tlut clothing made of this flexible liber facilitated die collection of the ashes after cre mation. Its contemporary use is as insulating ma terial for pipes, linings lor chemical containers and brakes on automobiles, insulating slabs and shingles, firefighter suits, dteater curtains and undcrcoating for ships and automobiles.* Two years sgo_pjiimonary aslcsiols was reported in Massachusetts in a man whose occupation included snraving undercoating on cars*: tiu- --atc--.ni i-ti uir; ........ y-iir oasc wtti~ahpnt if. ,-u-r cent aiystr*. true puimon.t.-.- asbestos is. Asbestos is the name given to a series ot minerals composed of certain fibrous silicates, magnesium and iron. It is mined as crushed rock and is then carded, woven and spun or ground and mixed with cement or plastics. Cana- ^ trtds 750 THE NEW ENGLAND JOURNAL OK MEDICINE Ocu 3, 1561 da, Italy and South Africa produce most of tin* mincraJ. The dust given mT during the maivtfaciuir or even during the installation of insulating material a usually around 5 to 10 millimicrons in diameter and may he as long as 50 millimicrons. The longer fibers seem to oe the most disease provoking. Ac cording to the current view tltc disease is produced purely by mechanical irritation by the inhaled fi bers, although chemical irritation is considered an important factor by some authorities. Tltc asbestos body if found either under the skin or actually in the pulmonary parmchytna and. consists of a central asbestos fiber surrounded by a protein sheath heavily laden with iron salt. In addition, there may he true granulomatous inflammation around the asbestos bodies. The disease is most heavily confined to the lower lobes of the limp and may give rise to both extensive pleural fibrosis and nodular interstitial parenchymal fibrosis. The first case of asbestosis was described as recently as 1907,1 even though the material luu been used for centuries. The disease may develop anywhere from ten months to as long as twenty yean after ex posure. The moil common symptoms are dyspnea, and a dry cough, although the disease may remain asymptomatic and be recognized incidentally on a routine radiologic examination of the chest. The x-ray films show a variety of findings. Tlicrc may be striking pleural fibrosis, with or without calcifica tion, or a difTuse interstitial fibrosis or a fine nodular fibrosis with a ground-glass appearance may pre dominate. The lower lobes are most heavily involved. Pleuropericardial adhesions giving a very shaggy appearance to the left heart border on the x-ray films sometimes serve as a clue to the diagnosis. In a case that was reported from England4 post-mortem pictures of the lungs dramadeal!/ illustrated the tremendous pleural fibrosis that sometimes occurs as a manifestation of asbestosis, with heavy involvement of die lower lobes and the fissures, in addition to the characterisnc interstitial pulmonary fibrosis with a fine, reticular, mottled appearance. Asbestosis may be associated in more than a for tuitous fashion with a pleural mesothelioma. Inves tigators in South Africa1 found 33 eases of mesotheli oma over a period of four years - among the people who worked or lived in the Cape asbestos-mining .fields. Asbestos fibers adjacent to the developing mesothelioma were demonstrated in only 3 of them, however. Regardless of whether or not the pleural mesothelioma is causally related to asbestosis, we muse consider whether die nonspecific pleural fibrosis of asbestosis existed in this patient or whether the pleural disease was a true pleural mcsoihciienta. The two pleural biopsies leave us with oniy a sii:n chance that a mesothelioma was. missed, although the neoplastic ceils may be so sparse and die uurosis so predominant in these turnon that even two negative biopsies do not rule out the diagnosis. The clinical counc is compatible with this type of tumor, as is the associated asbestosis. Mesotheliomas are capable of invading the chest wail, the mrdiastinun and even the diaphragm and on rare occasion extra throuch tltc diaphragm into the liver. Perhaps the eroded ribs, die Homer syndrome and the hepato megaly in this ease indicate invasion of ail three of tlirsn areas by jurit a tumor. There seems to be general agreement at the pres ent time diat bronchogenic carcinoma is associated with asbestosis. The evidence is inferential but per suasive. The incidence of bronchogenic carcinoma in cases of asbestosis is 13.1) per cent.*-' and tlicrc is a much higher incidence in the female aulicted with asbestosis than in the female population at large. Tltc cancer is almost invariably found in the lower lobes, where the concentration of asbestos - fibers is greatest, in contrast to the predilection of broncho genic carcinoma for the upper lobes of the lung ir. die general population. In 1953 Issclbachcr and Hi* associates.' in studying* this association in a case from this hospital, observed coexistent squamous metaplasia in the affected air tubes and speculated lluu the chronic mechanical irritation by the asbestos fibers produces the cancer. The average period of continuous exposure to asbestos fibers before the de velopment of tha cancer is between sixteen anc eighteen years. In this case I suspect that a pleural mesothelioma or, less likely, a bronchogenic carcinoma, was super imposed on chronic pulmonary asbestosis, as judged by the persistent chest pain, die erosive dissolution of die anterior ribs and the development of die Homer syndrome. These three findings take the pleural disease out of die rcaiui of the simple pleural fibres!* of asbestosis. Can the chest pain be characterise further? ' Was it so-called post-thoraentoray chest pain engrafted on die initial chest pain, or did it start- and finish in the area corresponding to the destroyed ribs? Da. Earlz W. Wiuttxa: It was my impression from talking with the patient that he initially ex perienced a sensation of tightness in the chest, r.ot .*. real pain, and then superimposed on this discomfort he did have post-dioracototny pain. The chorae;.* surgeon who saw him apparendy thought so. tor,, because he performed an intercostal neurectomy. Dr. Knowlu: Did the pain ever correspond the area of the eroded ribs? Dr. Wttxtxs: By the time that we saw him it did Dr. fctowxu: Was there any pain w'natsoew: in the inner arm, the shoulder or the upper porrio: of the thorax? D*. Wtucsss: No. Dr. Ksowus: That information is helpful in . negative way. I'd also like to ask if clubbing w.v present. C.ubbing can accompany asbestosis. and . is particularly common with picurai mesothelioma occurring in over naif the eases. Dr. BeNjAitt.s G^aTixatAX: There was no eta. bing. Da. Knowlxs: Was die sputum examined for a.-bestos fibers? VV^ :S3 Nu. K CASE HECOKOS OF THE MASSACHUSETTS CENERAL HOSPITAL 731 Da. Ca3TTjoia.\': The sputum was examined for both uuiior cells and asbestos fibers, and neither were found. Dr. Kxowuu: My argument is becoming less tenable by die moment. Were die so-called asbestos' corns observed on physical examination? These are small, nodular fibrous areas ilia:. may develop on the Itands, antis and legs of people'who work with asbestos fibers. Dr. Castijuiak: None were found. Dr. K.vowus: I should like to say a word about die patlioiogic physiology of this disease, although it requires extraordinary courage to stick with my original premise after ail these questions have been answered in die negative. Pulmonary ashestosis is commonly associated with die alveoiar-capillaty-block syndrome.* The full-blown syndrome is characterised by reduction in lung volume, unobstructed air flow, increased respiratory ram and ordinarily cyanosis on exercise, but with a normal carbon dioxide level or even mud respiratory alkalosis since there is no obstruction to die diffusion of carbon dioxide. What else should be considered in the differential diagnosis? Tuberculosis and fungous disease such as actinomycosis are |possibilities, since both cause pleu ral fibrosis and biiatcral chronic disease, but there vas no-evidence of chronic infection in this patient. Fungous disease, with die exception of actinomy cosis, does not erode ribs but causes a periosteal proliferative reaction. So I can dismiss those two diagnoses. The presence of the Homer syndrome bothered :nc considerably, but there is no question that a ncoaIastic mesothelioma, by invading the lower cervical ganglions and sympathetic fibers or the upper thorac ic fibers, could be responsible for this eondidon. The fact that it was noticed soon after the operation made me worry about metastatic disease or ever, a iittie infarct in the medulla, but with no other associated neurologic findings of the so-called lateral medullary or Wallenberg syndrome one has to place the cause of the Homer syndrome peripheral to the spinal cord and to the medulla. A superiorsulcus tumor with invasion of the sympathetic stel late ganglion or compression of die stellate ganglion by a ecrrical rib, pcriiaps due to manipulation dur ing' the opemtion, seems unlikely on both clinical and radiologic grounds. A final |ioint u> lie explained is the elevated alkaline phosishatasc level. It is pos sible tliat the high value rejected rr.ctastascs to. the oonc or the liver from a bronchogenic carcinoma. Vat I interpret the elevation of the right leaf of the diaphragm as a sign of significant hepatic enlarge ment and choose to say that a pleural mesothelioma invaded the diaphragm and also the iiver. My conclusion is drat this man sutTcred from pul monary asbestosis, with diffuse parenchymal intcrrotiat and nodular fibrosis as weil as extensive pleural kfibresis. Tn addition, I believe that he had a pleural "mesothelioma rather than a bronchogenic carcinoma rucked away in the right lower lobe. I base that choice on the negative evidence -- that is, the nega tive broncliosconic study, the nonspecific radiologic findings witii no suggestion of a localized mass and (he negative sputum examinations. I think that the operation was another right-dried thoracotomy, with, I hope, pleural ana pulmonary biopsies, and per haps even biopsy of a diseased rib. I doubt whether curative surgery could he done. Dr. Lahak Soumat: Why do you chink the pa tient lost so much weight? Dr. Knowles: I attribute the weight loss to the debilitating effects of dtronic pain and ultimate in vasion of litc iiver, either by metastatic disease or by direct extension. Loss of appetite may be tite key symptom of hepatic involvement. Dr. Kenneth T. Biro: DitTusc lung disease, whctlicr or not of occupational origin, may result in weight loss. This cfTcct is probably a manifestation of persistent hypoxia. For example, the presenting complaint of die patient with pulmonary emphysema is often progressive weight,loss. It is important to note that the crystalline form and size of inhaled particles ntay determine the re sponse of use host in pulmonary disease associated with occupational exposure. Crocidoiite, one of the several varieties of asbestos fibers, may give rise not only to parenchymal and pteutal disease but also to peritoneal manifestations.* Chrysotiie. 3MgO 2S10- * 2K-0. is cite main asbestos of commercial use. Da. Castlzman: Dr. Isseibacher, do >-ou have a comment? Dr. Kurt J. DseuucttrJt: As Dr. Knowia men tioned, in 1933 we became interested in a possible relation between aslscstosis and the developMer.i of bronchogenic carcinoma. It seemed important to document such a relation, if it existed, because of the magnitude of the asbestos industry in this coun try. We were impressed by the preponderance of in volvement of the lower lung when the carcinoma occurred in association with asbestosis. Another fac tor pointing toward an association of die two en tities was die high incidence of bronchogenic carci noma -- namciy. 13.8 per cent. A third feature, which Dr. Knowles has emphasized in diis case, was die bilateral nature of the disease. In view of the occupational history in the present ease, I find Dr. Knowles's diagnosis most attractive. Conical. Diagnoses ? .Asbestosis. . ? Carcinoma of lung. Dr. John H. Knowles's Diagnoses Pulmonary ashestosis. Pleural mesothelioma, with invasion of medias tinum, chat wail, right hemiciiapliragm and liver. Pathological Discussion _ Dr. Castlsman: Dr. Monaco. will you tell us wnat vou found at die first ooeracion? VTGT08 i. i: t TGT08 rsz TTIE NEW ENGLAND JOURNAL Of MEDICINE Oc*. 3, 1303 Ok. Axtsioxy ?. Monaco: Tr.e operation per formed it this hospital wu, as Dr. Knowles has tore- told, an open biopsy of the pleura and lung. The parietal pleura was markedly thickened, in some areas to a thickness of 2 os 3 cm. It was markedly fibrotic. but also sodular and in some portions stony hard, and a generous- biopsy of a stony-hard area was taken. The underlying lung sras also fibrotic and nodular, and we made a wedge excision of a nodular area. It was our impression at the time that the lung changes were most consistent with some type of granulomatous disease of the lung, and that the pleural elianges were most consistent with either severe chronic pieuritis or metastatic involvement of the pleura. Da. GASTtaatAN: Examination of the biopsy speci men rescaled very cense pieuritis. There were masses of collagen with a few scattered lymphocytes, which are characteristic of the dense, fibrous, chronic plcuri- ds that one comtnoniy finds in patients with asbes- tosis (rig. 4). In fact, when the pathologist sees this type of pieuritis he should look very carefully for asbestos bodies. We searched for evidence of a . mesothelioma, but in most of the fields found only a pleural reaction with normal mesomelia! cells, as is seen with any chronic pieuritis. The mesotheiiai cells were small and perfectly normal and certainly did not suggest a mesothelioma. Knowing that as* bestas bodies are often covered with iron and appear brown or very dark in the section, we hunted for' pigmented areas and in one field were rewarded by finding long, corrugated, brown structures that did prove to be asbestos bodies (Tig. 5). Ac the time of this operation, therefore, we were able to make a diagnosis of severe, chronic pieuritis, undoubtedly as sociated with ashestests. No tumor cells were seen. Dr. Wilkins, will you teQ us the follow-up ? Dsu WtutiNs: After discharge the patient was followed at first in the clinic He did not do well. The pain was not relieved, and the dyspnea became store marked. He began to complain of abdominal pain and distention, and at one time intestinal oo- siruciicn seemed to be developing. When he re turned to the hospital three weeks after the operation we rapidly determined that he did not have intes tinal obstruction. It was bard to escape the clinical impression that this man had a malignant process, as Dr. Knowles has implied. The only other avenue that we could pursue to establish that diagnosis was study directed toward the liver. By means of a peri toneoscope we surveyed the surface of the liver, Ficvui 5. Small Crjup o{ Aiietui Ctdiet. fXrtO) A'ou iAt retain nonmeoflanie meitineli.il eelU so'o.t. which was studded with little white nodules that looked like metastatic tumor, and we were actually able to do a needle-aspiration biopsy of these nodules least, was removed from the abdomen. Microscopicalexamination of tills nodule resvaied, in addition to lire previously observed collagen. large epithelial- through the peritoneoscope In addition, the perito neal surface ot the enure upjacr portion of the ab domen was covered with what appeared to be carci likc ceils, which were much larger titan those seer, on the pleura, and or. the basis of this biopsy wc could say definitely tlu: this was a malignant lesion. noma, and we took a direct biopsy of a nodule in Wc were not certain whether it was a mesothelioma due region. or carcinoma, but because of the dense collagen wc Da. CAsrta.MA.N: I assume. Dr. Knowles, that you leaned a little toward a mesothelioma, which can be are reassured now that you know that a noduic, at predominantly fibrous. CT .. VoL Jii" Si.'14 CASS RfiCOROS OF THE- MASSACHUScTTS GENERAL. lJOSFlTAL 733 "Hie patient died trr. {Lays after this operation. ' ,\t autopsy tiic entire right side of die chest was ohH-tcratcd by dense fibrous tissue dial in many places *.r.s odiously neoplastic In the region of the right :-,wcr lobe the picura had a thickness of as. much as i cm. As Dr; Knowles surmised, the picurai tumor .ad extended through. the diaphragm and overlay 'he surface of die liver (Fig. o). However, the paren chyma of die liver was snared except for a few small metastatic nodules. The neoplastic tissue extended>to Use lower lobe of the right lung, producing die serrated or cobblestone margin, as it projected from die pleura into die lung, tiiat is characteristic of tiic mesothelioma. Tiic left lung was also involved by this dense pleural tumor, and dscrc were a few small r.ietastadc nodules within its parenchyma. Tiie tremendous inns? of the mesothelioma in* -olved the entire mediastinum, and compression of .he subciavian veins on the right side accounted :>r .'O Homer syndrome Tiic tumor extended downv; involve the pericardium as wcil, and there were `wo small nodules on the epicardium. From die nlcura it attended into the ribs, as was seen on die .ray films, and two of the ribs were completely -'estroyed. The vertebras were also involved, no: by -dree: extension but by actual metastasis. As I men' oned, the huge tumor extended down from the chest and overlay die right lobe of die liver, and when it as peeled oiT nodules were seen on the surface of with mesothelioma implants, which were present throughout die abdomen, especially in die region of die right low er rmadrnnt over the cccutn, the ascend ing roifiu and the. terminal ilctinu Microscopical examination of one of the mviastascs within the left lung (rig. 7) revealed mesodiclial ceils with a tremendous fibrous-tissue counterpart, which is l iiamrtcrisiic of the inesodtciioista, as I indicated (Fig. 8). In fact, an occasional tncsodicii. ouia is almost entirely fibrous, and at dines it is very difficult for die- padiologist to ciifTcrentiatc it from merely dense collagen or a fibrosarcoma. We know from experimental evidence diat die mesothelioma cell, when grown on tissue cuiturc, may produce col lagen, and that is.wiiat it was doing in diis metas tasis. On the other hand, other mesouicliomas are predominantly mndc up of large mcsodielial cells. 9T6T08 t. Ftausc 7. ifclittalie tfadnU in Ike Left Lung. (XIS) it':.(Sexit li. Sagtlttit Haeliun through lite l.uiett Lai/* nj the flight Loti.r, Diaphragm and Lie**. It* mesathaiiema tneirriea ihr lung (adage) and aeeeliti :ht sntgtior iurjtut at '.he ihtr (btiota). ,Va(< ike pieueal noduiet mending into tag ittng petcr.ehpma. V'lOTWK tt i'rfpfKutrcnct <jf Kfbi TUju4 SUrtwm:. (X '20) / I 801917 75+ tiie new enceand joCsn'ae of medicine Oct. 3, 1063 sometimes in. an acinar or papillary arrangement, la fact, many of the cases in which a tumor has been described u a complication of asbestosis and called an adenocarcinoma of the iung probably be long in tiic category of rr.esothciiomas ratlicr than adenocarcinomas. In this metastasis we were able to lad. a very nice asbestos body among the mesotiicilai tumor ceils (rig. 9). Fwi*x 9. Athtstot Itody tritkin a Fihrotu Area of the .1ftso~ tktlioma (:ho C'.uoSjuiptd tfarUan:al Sirueturt im lha Lotr- tt Third at too Photograph). (XSCO) Just a few months ago we saw another case of mesothelioma. That patient had not been exposed to asbestos, but the case brought out a number of interesting paints about this type of tumor. The pleura was very dense, as la the case under discussion today, and the tumor had similarly extended down through the diaphragm to the abdominal cavity, where loops of snail bowel were intcrauhcrent be cause of the resultant peritoneal thickening, w'uich was composed of malignant mesothelioma ceils. There has been some discussion regarding whether a. mesothelioma of the peritoneum can occur without involvement of the pleura in cases of asbestosis. In' all the eases that I have seers the tumor lias extended down from the pleura, as it had in the ease discussed by Dr. Knowles. I might point out that mesothelioma ceils secrete hyaluronic acid, whereas carcinoma cells do not. Thus, if one has fresh tissue one can stain it metachromatidily with toluidlnc blue, and if the hy aluronic acid in the ceils is digested by spermatic hyaluror.id.uc it indicates tltat the ceil is mesomelia! ratiicr than epithelial. Dr. Knowics, do you want to comment further? Da. Kxowusa: I'm a little distressed that on two pleural samples we sail couldn't hit somethin? that told us that this patient's lesion was a mesothelioma, although I realise ;ha: there may he a relative pau city of ceils, with fibrous disease predominating. The other important point is tltat a mesothelioma ran indeed metastaaize, as lias been emphasized by the studies in South Africa. Regarding your point about adenocarcinoma, in view of the squamous meta plasia that is associated with chronic irritation by these fibers I would expect to see squamous-cell car cinoma more often than adenocarcinoma. Is. that not true? Du. CaaTutatAX: In about half the reported cases the tumor has been squamous-cell carcinoma, and I agree (hat it is what one would expect. If we be lieve that the asbestos body is an irritant, it is logical to assume that it stimulates squamous metaplasia in the bronchial or the bronchioLar epithelium, which then nay progress to carcinoma, but in the ease that Dr. Isscibachcr and his associates reported, for exam ple, although there was squamous metaplasia the carcinoma was an adenocarcinoma. Perhaps the le sion was a mesothelioma! Da. Paul. S. Russell: Dr. Castlcman, I know that the degree of invssivcncss of these tumors varies considerably, and that they somedmes remain confined to die pleural space for a remarkably long time, whereas I've encountered some that invaded into die chest wall and even into die abdomen, as in the case that you referred to. But I have never seen a mesothelioma with involvement of the bone. Is that a common occurrence in your experience? Da. CASTLeatax: In the eases in which the meso thelioma does metastasize bone involvement is not infrequent. Da. Soutter: Isn't there a benign type of meso thelioma also? Da. Castlemax: There is a lesion that is charac terized by proliferation of benign mesothcliai ceils. Tills may occur with any chronic infection; tor ex ample, tuberculosis can stimulate the mesothcliai ceils sumdendy to provoke an appearance that is almost neoplastic. It prohably is not a true tumor, but there are eases of so-cailcb benign mesothelioma. Anatomical Dcacxoses Pulmonary asbestosis. Pleural mesothelioma, bilateral, with extension into lung, mediastinum, perieerdium, ribs, diaphragm and user ssid vsiik metastascs to lungs, liver and vertebras. Refeksices U 0. Tt* <*! Qftvfiiik+m. S*co*4 1044 r?- liifie. Crown. i'.UT. J. Urnoc". II. G-. Jtwl SUvItfT, If. l v*Krr ro.uw^j In umtimmoImI# wiik'muuiig, Snr /. Aro. ZlJi.7,Vi4l. 3. Mufiw, M. (a Atilun fltrtfimsm .it ('/mmitttt .* Mia l.of tmJmftrtm Oiirttn. C*-w4tm: Hu .\U|niT i Suiitncry Cifsoe. \y>7. \\L V>3, j*. U. Co. j. :J7. 4. v yrt*. If. A/. /. Zi.'-at. 10*1. 3. W^iirr. J. C. Girevs, G A., ud NLt/ciumi. i*. I5n?ua* iiUnirat mImrMtn/.rlilt*iM**att,.urAn//. eniHi+oati in .N'orih \Veu#f w?i 9. Twritihuapiin, mMir.v, cimarcrssuHnMnum4<i*nf,unAt.f, h. rPvt'muMit^akaiafT ivmimit:ami attCAdn rarruHima m <9<iac't. .Irth. 13)1, 7. faMnisaenn*. K, l . if.. an iL~*u*. It. I*. ^UKAiiei<ir. nrciMWtti; fftwri *n awirnmcu ra+4 *mj rr*ow m' avasiaiM# itirfAiwrr. Am. /. IJ;7?I**^C. *5*3. 3 *4Mf. K. A., Ami hns*o:T, 1. J- rui.nonarr fiwfian in 4snt)*q *4 luu^i Ti-rra iT<wo<a. Am% /. A/r* t