Document darrZe9kw9950v3MeVr9d3ope

if . . .<m 4/. * THE AMERICAN JOURNAL ' OF PATHOLOGY rf. Official Publication of The American Associate n of Pathologists and Bacteriologists BOARD OF EDITORS CARL V. WELLER, Eorro-u-CniTJ MALCOLM H. SOULE, Assiitamt Eorroi J. HAROLD AUSTIN - TRACY B. MALLORY PAUL R. CANNON SHIELDS WARREN HOWARD T. KARSNER HARRY M. ZIMMERMAN VOLUME XXII i (January, March, and May) 1946 ANN ARBOR MICHIGAN U. S. A. V \ V-- PLAINTIFF'S EXHIBIT Cfl < I COEXISTENT PULMONARY ASBESTGS1S ANT> SARCOIOOSI Joint H. Skjwlkk, M.D., nd Ruhhit J. Firrr 'sum, M.D. ... (Prom '.kt Percy ShULls Laboratory t of Di.niuim IfospHol, Ci*o!n*all f^Okh) i Pulmonary a Jiestosia, regarded as a "rntj rn disease" by Gloyne and Alerew: tli, iv. is first descriltcd by Murray * iu 1900. Although Fahr * described a case in 1914, interest in this disease w;i3 not re awakened until the case of Cooke and McDonald was described in 1927.* Since that time, there have appeared in the available irterain.e reports upon approximately 150 necropsies on cases of pulmonary asbesiosis.*'12 The paucity of proved cases, in cfltnparison'wUh those of silicosis, is not due wholly to failure to report such cases, for In large necropsy series asbestoris is apparently of infrequent occur rence.*"13 Further, despite the widespread u^age of asbestos prod ucts, there are comparatively few people engaged in the asbestos industry. As of O' lor, 1944, only 19,700 people were employed in this industry in lii- United States.14 Much has been written about the clinical, roentgenologic, and biopslc aspects of sarcoidosis. However, because of the infrequency joid relatively benign character of this di'ease there are only isolated detailed necropsy reports. From the available literature there have been found only 53 reports of necropsies on cases of sarcoidosis.1* Jl Most of these were summarized by Pinner.1* These two diseases present many clinical and roentgenographic similarities, and, also, their more frequent fatal complications ate alike: pulmonary tuberculosis and cardiopulmonary insti/iicicncy. Bronchogenic carcinoma, a frequent complication of pulmonaiy asbestosis, has not, however, been described as associated with sar* coidosis. Likewise, there has not been a previous description of asbestosis with coexistent sarcoidosis. It is the purpose of this report to present the findings in such, a unique cose, the only example oi either pulmonary asbestosis or sarcoidosis in a scries of 1873 necrop sies done at this hospital. Revirt of Case The patient tva.i a white male, 41 years of a. Si.bsia.ucnt to hemorrhoidectomy in December, 1943, he had noiucd that slight activity produced shortness of breath. He did not experience nocturnal dyspnea and he .vas able to lie fiat in b*'d without respiratory difficulty. Thera was r.o history of cmirfh, hemop'jjis, or catJLac embarrassment. Notwiths; 'aiding a I'o-al appetite and (lie absence of gastric Received for | iilhealiun, May 9. t;,j I -\ 'tilt-. Irp_; In t nr lac 11.-, iriricn' .( r.( I 'n.liunll. i'ie, laii.iv >1 Medicine. t'nlviiai* 1 4* s>TP|'ims, there wax a weight Injs of aa pounds fr^Hreccmber, 1943, t t.irch, 19 ti. if which time he presented himself for medicaTcare. The patieot had worked in an asbestos plant for 25 years, the last iu years having been in a supervisory position. During this entire time he had worked in nnc ilrpirtnu-nt in which asbestor. pipe was made. There was a slight but appreciable dust hazard associated with the sawing and splitting of the dried asbestos pipe, despite precautionary exhaust v ntilation. The total time the pati.-ul hnl spent upon this final operation of saw ng was unknown; nor was it learned whether he had Itcen negligent in using the ; rovided respirators. To the company's knowledge, this was their first case of asbest isix. !'!>'ical examination reveale tbe following findings: Temperature, 37* C.; rrspir nion, 12 per minute; ai erial blood pressure, 105/70 mm. Hg; height,, tyo 1 mi ; weight, 67 kg. The hest was of increased anteroposterior diameter. Rr*pir >tnry excursions were eqiv but decreased. Tbe percussion note was resonant and .M'.cultation revealed fine r: es over the bases of the lungs, posteriorly. There wet.- f.. evidences of cardiac enl: gement, irregularity, or decompensation. Cyanosis and 1 In! l-ing of the fingers were ihsent. Tbe liver was barely palpable. i'-, -t mi the roentgenogram of the chest (Fig. t) was as follows: "The bony ft.M........rk is normal, 'lhc t#a lea is-in the midline. The hilum shadows are tin -h i 'inly enlarged, bilaterally. One small calcified area is present in each hilum. Tli- t-- are numerous small nodular densities scattered throughout both lung fields, e.i't '!!>- throughout the lower lobes. There is some confluence of these densities in t ! li ft lower lobe. Emphysema is present." I ruiinatinn of the blood 'lowed erythrocytes, 5.5 million; leukocytes, 6.6 tho....... I; 73 per cent neutrocyt.'c; xi per cent lymphocytes; 5 per cent monocytes; 1 j.'-r , mt eosinophils; srdinn- nation rate, j6 mm. No abnormality was found in 1! nine. The vital cap.nfW, 1:00 cc., was $1 per cent of normal. Tuberculin ic,i, not done. 1 - iMt nt was seen at reguhr intervals and his only complaint was increasingly '<'' "rertional dysnnea. A n ,'rdgcnogram of the chest 4 months after the initial chc"-* Mm revealed no new findings. Although the patient greatly limited his activities, dyspnea became progr.-ssively more severe so that eventually, even at' bed r> st, there was extreme air h: nger. At no time were there evidences of cardiac failitr. He died approximately 1 months after the onset of symptoms, apparently from respiratory failure. A utopsy Findings Tim ni'cropsy was performed 5 hours after death. Superficially, there was considerable decrease in the subcutaneous tissues and the hr ' -imsculature. There was no clubbing of the nailbeds or dependent cdiu'.t. The mediastinum was in the midli/te. Each lung completely filled 'ts homithorax and extended far into the anterior mediastinal spate. The diunes of the diaphragm, anteriorly, were at the level of the fourth interspace and fif h rib, right and left respectively. The lungs were encased n markedly thickened, tough, yellowish white, generally fused pleura . The interlobar fissures were obliterated by r.r.ily broken adhesions. Lobalion was normal. Hemorrhagic fi brinous material, present o* cr the posterolateral aspect of the left lower lobe, loosely bound th< thickened parietal pleura to the lung in tlii <i'.i. The .frontal sex tbe left lung (Fig. 3) revealed coarse, lacy, . tannlsh brown, i pitant tissue throughout both lobes. Innu merable slightly >i- I, grayish green, irregular, firm nodules, r to a mm. in diameter, were present throughout the lung. Thin, radiating, fibrous bands surrounded and connected these nodules. Also, slightly thickened plefiral septa extended into the lurtg substance for variable depths. In the lung tissue about the bronchi of the second and third interspaces these nodules were somewhat confluent and & similar change was noted in the subpleural tissues for a depth of 3 to 5 mm. (generally, these nodules, present in moderate numbers, were sepa rated by wide'zones of . dry emphysematous lung tissue studded'by numerous minute, grayish tubercles.' Dissection of the bronchi of the -'lower lobe disclosed that they were moderately dflated, cylindrically and saccularly, and lined by glistening white mucosa. In thl right' lung the same changes were observed as were present throughout the left. However, the grayish green, irregular nodules tended to be more numerous, larger, and more confluent. This was particularly true of the anterior portions of the lower and middle lobes. Also, the nodules were connected by thicker grayish black and graybh white interlacing bands of fibrous tissue. Extending deeply into the lung substance, thickened pleural septa communicated with the fibrous tissue in and about tbe clusters of tubercles. Except for more pronounced dilatation and thinning of the mucosa, the bronchi of the right lung were similar to those of the left. The tracheobronchial lymph nodes were moderately enlarged and * on section consisted of dense, rubbery, antbracotic centers and thin rims of yellowish white tissue. Calcification was not grossly de monstrable. The embalmed heart weighed 280 gm. and had the following measurements: tricuspid valve, 120 mm.; pulmonary valve, 80 mm.; mitral valve, 85 mm.; aortic valve,.65 mm.; right.ventricle wall, 3 to 8 mm.; left ventricle wall, 15 mm. The greatest transverse cardiac diameter was 13.5 cm. (The estimated normal heart weight on the basis of body length is 317 gm., plus or minus 401") The trlcus- pid/aortic valve and pulmonic/aortic valve ratios were 1.84 and t.23, respectively. (These normally should be 1.68 and 1.03, respectively.**) : The right ventricle was dilated and its columnae carnea'e and papillary muscles were more prominent than usual. No mural thrombi were demonstrable and the valvular endocardium was normal. The enlarged spleen was of normal configuration and measured 18 |v <) by t\ tin. It \vn covered by tt 'month cajvmle ;mil tbe '-picnic substance was firm and pe -pliah. red wilh^fcjmal markings. No tubercles were seen. The li' tt" measured 22 w^i6 byio cm. The remaining organs showed pru ive hyperemia and moderate generalized arteriosclerosis. > Afici 1SCOf>ic Findings Thr oughout the lung (he : was a conspicuous linear, i tpihcing, l>eril>i 'ncliial and sep* '' pul aonafy fibrosis (Fig. 2). This w.o> particul -t? 1 v prominent in the jbpleural tissues. The intervening lung tissue was moderately cmpl ysematous. Innumerable tubercles were prtvnt in the linear and per bronchial fibrotic areas and were present to a l<"cser extent in the wais of the respiratory bronchioles and the adj.u i nt alveolar walls. Gererally, these tubercles were of two type?: sarcniiUl and foreign body granulomas. The former predominated by approximately ten to one. T ibercles of these types were intimately as sociate and, in addition, rn.rny intermediate types were presented. The sarcoidal tul>crcles (Fig. 4) were free of caseation, contained no demonstrable organisms and were, for the most part, in the same stage of development; hov ever, a minimal number presented some peripheral fibrosis and the e was an occasional, coarse, collagenous hall. Generally, the tubercles were sharply demarcated, surrounded by delicate reticulum, and did not present peripheral rims of lympho cytes. They consisteff^of peripherally arranged epithelioid cells sur rounding central, loosely arranged epithelioid and monocytic cells. Giant cells were, for the most part, centrally located and often com prised over half of the hulk of the nodule. The giant cells appeared to be of two types: I.anghans* cells and foreign body giant cells, with the farmer predominating. In many of the Langhnns' cells there were numerous small vacuoles, each containing a pink, round body. Other I.anrlians' cells contained arge, clear vacuoles; and, rarely, in those <11!:; containing one large vacuole there waa present an "asteroid" 1'cviv, an intensely eosinof uilic stellate mass, 15 to 20 (t in diameter (Fig. 5)- i More frequently, the anghans' cells contained round, oval, or sm:.;cstivcly budding, intr cytoplasmic Bodies of Schaumann,' 25 to 50 a in diameter. Rarely, hese bodies appeared to lie outside of giant cHF, and some enclosed j egular yellowish material (Figs. 6 and 7). Tlmse bodies stained bh * with hematoxylin and in ferrocyanide Preparations were strong j positive for iron. Dr. Leroy U. Gardner,14 r w!v> also studied this case, stated that these bodies stained "red with and fudisin of van Gieson-Weigert instead of black like elastic tissue" * SthjwruiDn, J. On the nature oI eertaJn peculiar eorpusrlci present In tissue v-l I t iu| lmi;i jiiiilii'n.ith'lt .Ifid Wi'il, 1041. and that "von^fesa's calcium stain is negative." Re-study of ap propriately stal^W sections revealed, as pointed out by Gardner, that the Schaumann bodies did stain red; however, a moderate number also contained calcium in variable degrees, as demonstrated by von Kossa's stain. An occasional giant cell contained one or more clefts suggestive of cfiolestcrol crystals. More frequently, however, doubly refractile, irregular spicules, plaques, and conchni lnl masses were observed in giant cells. These doubly refractile masses were often.about, or In, the Schaumann bodies, particularly the smaller and partially calcified forms. ' The foreign body tubercles were indefinitely demarcated and con sisted of rather closely packed, indefinitely arranged, large monocytes, and one or more foreign body giant cells. These tubercles, for the most part, were within the dense zones of fibrosis. Some, however, were present in alveoli and respiratory bronchioles. Golden yellow discoid, verruciform, and incompletely segmented asbestos bodies, many of which were in giant cells, were observed in and about the nodules (Fig. S). Asbestos bodies, singly or in clusters and in mod erate numbers, were present also in the dense fibrotic areas (Fig. 9) and occasionally within alveoli (Fig. 10). Rare, laminated, calcified masses, enclosing apparent asbestos bodies (Fig. 11) and other bodies which appeared to be of the Schaumann variety, were present in the linear fibrotic bands. Asbestos bodies were also encountersd in about the sarcoidal tubercles and in the associated sarcoidal .,uut < t of both varieties, but more frequently in those of foreign body type. Iron preparations clearly demonstrated the bizarre forms of the'as- bestos bodies. In many areas it was difficult to distinguish between the two types of lesions. This was particularly true throughout the stibplcurnl re gion where both the lesions and asbestos bodies were more numerous, clustered, and embedded in a dcn-:e matrix of collagen, masses of coarse elastic fibers, and fine reticulum. The larger bronchi were remarkable only for slight chronic imlara- mation. The bronchioles and respiratory bronchioles, embedded in dense collagen and surrounded by tubercles, were moderately dilated and presented conspicuous focal squamous mc'aplasia and modi , ate' chronic submucosal inflammation. In the subpleural regions where the asbestotic fibrosis and the granulomatous reaction were most in tense, the bronchioles were irregularly dilated and lined by alternating strips of tall columnar and squamous epithelium. Only a lew bron chioles contained ucutrncytic exudate. Flu* respiratory bronchioles were eoivlr'i I ,:ir,,;n! I y . iimny contained asbestr i bodies 'and; the associated granulomatous reaction. Within the per bronchial fibrou^Bsue there was a moderate amount of hemosiderin lforariy dispose granules, and fine lipoid droplets. The 'W'1" j"dt onary arteries and arterioles presented slight inj'mal thickening, aiul.i rose in the subpleural /one were surrounded l.'v rhick collars of elastic fibers* The intervening alveol were moderately dilated, the 1 .ipi'i.tries were cm.ecsted, and there waj a slight increase in collagen in the alveolar v.-ads bordering the fibre j. masses. Focally, clusters of alveoli con tained lipoid-laden macroohages. "Heart lesion cefls" were infrequent. Sections of the pleura revealed dense,laminated, and oval fenestrated bundles of collagen. Focally, there were Indefinitely demarcated nodules which consisted of circularly disposed lamellae of collagen. Suiv-rficially, the pleura presented slight fibroblastic activity and an of casional perivascular accumulation of lymphocytes and monocytes, some of the lat'.cr occasi mally containing hemosiderin. No asbestos bodies were observed. Tl e pleura over the left lower lobe, in addition, bore organizing fibrinous exudate on its visceral aspect. Sections of the tracheol ronchial lymph nodes presented a repetitious pattern of sarcoidal tuber-dea with almost complete replacement of the lymphoid tissue. Th^gughout the nodes there were minimal diffuse fibrosis and several nodular masses of coarse collagen. The tubercles, were similar to those in the lung as to structure and stage of develop ment'. Inclusions of Schaumann were not observed and only a rare "asteroid1' was present, /jbestos bodies,were not identified. A mod erate number of hemosiderin-containing macrophages were present in th^ remaining lymphoid tissue. Similar sarcoidal tubercles were present to a slight degree in the rplfi-n and liver, and to a lesser extent in the kidneys, diaphragmatic muscle, and the right and lift ventricular myocardium. These sarcoidal tubercles, however, were iot as compactly arranged as those in the lung and tracheobronchial lymph nodes, and were surrounded by and permeated by lymphocyte; "Asteroid bodies" and Schaumann bodies n i're not present in the pant cells of these tubercles. No asbestos bfdi-s were found. Thost La the right ventricular myocardium were awiated with considerat e fibrosis. The results of chemical and spectrographic analysis of lung tissue, jwrformed under the direr tion of Dr. Leroy U. Gardner,** are pre sented in Table I. The final diagnoses weri: Moderate pulmonary asbestosis; exten sive sarcoidosis of pulmo-ury and tracheobronchial lymph nodes; milked chronic piilnme.uv emphysema; slight srlerodi <>i the .-nvdl 4yy ^ arteries arterioles in the lungs; marked nodular obliterative pleural d^^is; local organizing fibrinous pleuritis; minimal sar coidosis of the heart, liver, spleen, and kidneys';- right ventricular cardiac dilatation and relative right ventricular hypertrophy; acute passive hyperemia of the viscera; slight cirrhosis of the liver; slight generalized arteriosclerosis; minimal focal chronic adrenal ids and nephritis; chronic posterior urethritlk aud interstitial prostatitis. Tabu* I Chemical and SptctrofrapUe Analysis of Aik (Dry Tiuvi, Approximately r{_t% of Xtolrt Tiuuo, Aik, of Dry Tiinto.) A* aside* (escept Cl) A* Cfcatmcal analysis Cu, Ag, n*i Pb, Bi. C.H Mo 1 SiO, Fe.O, AI.O, UeO ZnO MnO CaO MjO IUO SrO TiO, v,o, CnO( NiO. CoO n.,6 KiU P.O, Cl C0| Tout Per uri <O.IJ >.76 , B.oj 0.37 None found 0.39. 0*03 4 3.9* I.l8 None found None found None found None found 0.07 <o.oj 5-44 44-40 18.41 46I Present 88.81 Chtmksl lulyik Sjw*tr<cr*i'hie luatyen Per tni Athttfry n+ti f Na K 4 3*5-7 Sr None found IU None found c j.r At o.a Mg P 0-7 80 SI Fc *3 sa Mn 0.03 Tl ' None found Cu Ag Sn Cr 0.05 a Be None found ph Zn o-3 M Pt Cl 4- 7S too -I s 80 50 7J 60 iOO 75 ,J '5 J5 3 3 3 r 0 35 5 to 3 0 Discussion Clinically, in view of the significant history of exposure to asbestos, the possibility of sarcoidosis was never entertained. In retrospect, the rapidly progressive, disabling dyspnea, unaccompanied by evi-* dences of enlargement of the right heart or cardiac failure, should have aroused suspicion that there was a concomitant pulmonary lesion. Asbestosis alone is not usually accompanied by such profound, rapidly developing, respiratory embarrassment. In this case, however, there were no collateral clinical evidences of sarcoidosis. It would seem that a clinical diagnosis oi coexistent asbestosis and sarcoidosis would l><jn.-lim'd onlv 1>V bmp-A' of .1 lvm; It nm*- <. >>, ............ 500 SICAVIJ'U AND Kllll.UlJOii' . i f i . strate sarcoid le?i ns and the dil^ery of asbestos fibers in the sputum, with a hi lory of adequate exposure to asbestos fibers and romtgenographic ( 'idonces of diffuse pulmonary, fibrosis. Asbestosis of the degree obs rved, alone should not have caused death, and sarcoidosis has gen rally been regarded as a benign process. Reisner,1* however, on the b: sis of his observations on cases oi pulmonary sar coidosis, stated "t! it one is not justified in assuming too confident an attitude regarding the ultimate outcome." This statement is particu larly true when, as in this case, sarcoidosis complicates pre-existing pulmonary disease. ' Pathologically, there were exidcnces of right heart strain in that there was marked iilatation of the right heart, evidenced by increased tricuspid and pulr onic/aortic valve ratios and slight passive hyperemia of the viscera. The total heart weight, however, on the basis of body length,-* was norn al. As determined by the ratio of the left and right ventricular weight;, it has been shown that there may be considerable relative right ventricular hypertrophy without an increase in the total heart weight. However, relative right ventricular cardiac hypertrophy in Higgins' series s was not usually accompanied by evidences of right ventricular failure. In view of the significant dilatation of the right side of the hMrt and the slight sclerosis of the pulmonary arterioles, there was, in all probability, some degree of pulmonary hypertension in this case. However,7 in | the absence of an increase in total hea.rt weight and in the absence of evidences of chronic passive hyperemia of the viscera the'e was probably no, or insignificant, exaggeration of air hunger due tc heart failure. It has been sug gested that dyspnea in the pneumoconioses is due to capillary and arterial blockage by the fibrotic process. This, in all probability, is tr; e to a variable degree in those persons with severe fibrosis of the conglomerate type with attendant extreme chronic emphysema. Th . hypothesis, however, does not explain the severe dyspnea that is s en in occasional cases of diffuse miliary studding of the framework * f the lung by silicotic, tuberculous, sarcoidal, or neoplastic tuberc es. It may be that the mechanism of dyspnea in such instances is due to irritation of the vagus nerve endings with reflex stimulation of the respiratory center (Hering-Rrcuer reflex). In view of the equivocal evidences of hypertrophy of the right heart in this case, mechanical obstruction to the blood flow would not appear to he the responsible factor but, more likely, because of the diffuse active inflammatory process throughout the lungs, the Hering-Brcuer iHlcx w;i; rx:i"|'iT:it!,il. Pre amiably, there was cillirr a severe re- spir alkalosis or acidosis. Tissue changes suggestive of alkafosi^ such as calcification of the renal tubules, were not found. Microscopically, there was. some difficulty in differentiating the two types of tubercles since there were many sarcoidal tubercles which contained asbestos fibers, and tubercles of indeterminate type, not containing fibers or inclusion bodies, were sometimes seen. It was difficult to determine how much of the fibrosis was due to asbestosis. Morphologically, since the majority, by far, of the sarcoidal tubercles were without evidences of fibrosis and apparently of the same age, it is suggested that this process was engrafted upoq, an established as bestosis. Further, on the basis of Gardner and Cumming"'experi mental studies on asbestosis; the marked peribronchiolar fibrosis with sequestrated asbestos bodies, the marked pleural fibrosis and pleural septal fibrosis, and the metaplasia of the bronchiolar epithelium In dicate that the asbestosis was well established and over 700 to 800 days old. Dr. Leroy U. Gardner, who kindly examined the material, stated: ;<In comparison with our other material the pigmented foci in your case seem to show more fibrosis and less localized emphysema. Histologically, this can probably be explained by the presence of sarcoid nodules within the asbestotic zones of reaction. I would infer that in your case the two conditions developed more or less simul taneously, but that probably the asbestosis was present to some d> pTi*-* before the sarcoid appeared. This opinion is bn: il up e rence of asbestos fibers and other iron-containing pail: ' j 11 1 tie interior of the tubercle-like nodules and in some cases within the giant cells themselves. The number of asbestos bodies is smaller than seen in many cases." Inclusions of the Schaumann variety, found only in the lung, oc curred in 4 per cent of the( giant cells. Some of these enclosed golden- yellow, irregular bodies suggesting asbestos bodies, but similar to or ganic material previously described within such bodies. Yet there were definite asbestos bodies enclosed by similar dark blue material. Schaumann inclusions have been described in only 4 per cent of the reported necropsies on sarcoidosis as summarized by Rubin and Pin ner," who did not regard these inclusions ns specific for sarcoidosis. Rich," who was impressed by the frequency of Schaumann inclusions in sarcoidal lesions and by their absence in unequivocal tuberculous lesions, noted that Metchnikoff reported the presence of calcified in clusions in the hyperplastic tuberculous lesions of experimentally in fected Algerian rats. Kraus *" stated that the presence of calcified inclusions was a feature not found in any known granuloma except sarcoidosis. Gai Iner.24 pointed <u^iat, in bis sarcoid material, these bodies, regarded by many to conP of calcium or c.ddfied remnants, of elastica, do i it, by the von Kossa method, contain calcium, but, by the ferrocyai de method, give a strong reaction for iron. Only a __ moderate numhe of the-Schaumann bodies oh'-erved in the present f case were cither wholly or partially calcified, nil gave a strong S >,ji * - *t-* reaction for iron. Studies on sarcoid lesions of lymph nodes and spleen from another erse revealed only a few iron-stalnlng. noncalcified Schaumann bodies. The presence of doubly retractile, nonlipoid sub stance in giant cells and frequently in close relation tn Schaumann bodies has not been emphasized in the literature on sarcoidosis. It* has been noted, however, that colorless and yellowish tinged refrac^ilo material is often enclosed by the.Schaumann body. The fact that. these masses are frequently doubly retractile has not been stressed. ' It has oc .*n suge` ted that these enclosed masses represent disintegrat ing elastica; how ;ver, van Gieson-VVeigert stains do not confirm this suggestion. The crigin of this retractile and doubly retractile material is not known. Ilei lg in and about many of the small, partially calcified bodies, this doubly retractile material appears to be associated with - the development of the Schaumann body. The larger and more densely stained bodic*were not as frequently associated with visible doubly *1 refractile substance. * However, fractured and fragmented, apparently old, Schaumann bodies; as' seen in control sarcoid material from lymph node and spleen, usually contained moderate amounts of doubly re fractile substance. Apparently then, the Schaumann body, which stains . blue with hemator din and red with acid fuchstn, is formed in response ; * to doubly refrac'.ili, nonlipoid substance and initially is impregnated by iron and later, in amounts demonstrable by von Kossa's stain, by . f m calcium. * Wolbach,21 in r< a, Jadassohn, in 1919,18 and Friedman,18 in 1944, have described a ; eculiar intracellular body in cases of sarcoidosis. This body, stellate ia shape, varies in size up to 25 ft, generally lies -|t in an intracytopla; mic giant cell vacuole, and stains intensely with acidophilic stains e: cept the central area which is basophilic. Wolbach described them as 1 ing free in tissue spaces, in endothelial leukocytes, and*in giant cells. Friedman found such bodies in only 6 to 8 per cent of the giant c;lls In bis case. Both investigators attempted to determine the chemical structure of this stellate body by specific stains; however, they were unsuccessful. Both considered the pos sibility of its being an extraneous organism, although questionable. Wolbach regarded it as a nonspecific biochemical alteration of the ry'oplasm. He v.-ns never able to ilmnon or itc trllate l.e.lvs in nihr:' COEXISTENT ASBESTOSIS AND SABCOIDOSIS m^nal and decided that they were not similar to inclusions some times seen in cases of sarcoma. Friedman regarded these bodies as nonspecific but highly characteristic of sarcoid lesions. Friedman pro posed that these bodies be called "asteroids," but perhaps it would be better, eponymically, to call .them Wolbach's asteroids! rhey have been described in 7 cases of sarcoidosis, and never in association with the Schaumann calcified inclusion body. In the present case asteroids were present in approximately 1 per cent of the giant cells in the - lungs and tracheobronchial lymph nodes* Definite transition stages of asteroid formation were suggested by the presence of spicules on the .pink, coccoid, intravacuolar, intracytoplasmic bodies, particulafly\ln those giant cells in which the small vacuoles were clustered and dis integrating. In addition, an occasional Wolbach's asteroid, instead of lying in a large, clear vacuole, was surrounded by agmlnatcd ruptured vacuoles. In view of the presence of similar pink, coccoid, Intra vacuolar bodies, similar asteroids, and the same suggestive stages of asteroid formation in the giant cells of talcum powder granuloma, as observed in one case in thi3 laboratory, these giant cell cytoplasmic changes must be regarded as Wolbach originally suggested, nonspecific * biochemical cytoplasmic alterations^ In addition, such an asteroid is ' depicted in the giant cells of leprous lesions by Mallory " w > them "spiculated" bodies. No transition staged i,ctwecu . . h ,tis asteroids and Schaumann's inclusions were even remotely suggested. The pathogenetic relationships of asbeatosis and sarcoidosis are &- dependent upon the chronologic development of the lesions and the hature of the causative agents. Historically and histologically, in this case, it is most likely that asbestosis preceded the development of sar v. coidosis. The predominant localization of the sarcoidal tubercles with in asbestotic zones of fibrosis with attendant morphologic modification of both lesions, as evidenced by asbestos bodies within sarcoidal tubercles and lesions of indeterminate type, would suggest an analogy to the intimate relationship existent between tuberculosis and the pneumoconioses. It must be remembered, though, that even in un complicated sarcoidosis the lesions occur in the framework'of the lung, and therefore the morphologic relationships of the two may be coincidental. This would be in agreement with those who believe that morphologically sarcoid is not reconcilable with tuberculosis. How ever, to those who regard sarcoidosis as a peculiar form of tuberculosis, this case then would be one of asbestosis with superimposed non- enseating tuberculosis. r.ie uiitlmis Or, l.nm* IV fl.mli *rr wl.* tin\v 1 504 i * ili.WLEM AND RITTr.RIIOFP ^. M ENCES i. Gloyne, S. R., and Merewelher, E. R. A. Asbestos. Occupation and Health Supplcin nt. International Labour Office, Geneva, 2938. (Cited by Sayers, R. R., : id Dreessen, W. C. Asbestosis. Am. J. Pub. Health, 19.29, ag. 205-224 1 2. Murray, A . Citerl by Egbert. (Charing r- t/ Hasp. Go:., 1900. Also: Departmental Committee on Compensation for Industrial Diseases. Minutes ot Evidence, Appendices and Index, 1907. Cd. 3496, p. 127; Report, 1907. Cd. 349;, p. 14.) 3. Fahr, T., and Feigcl. Kristallbildung in dcr Lunge. Deutsche mcii. IVchnschr., . 1914. 4*. *54--1549. (Cited by Eghert.) 4. Cooke, W E. Pulmonary asbestosis. Brit. .If. 19:7, a, 1024-1025 Mc Donald, S. Histology of pulmonary asbestosis. Ibid., 1927, a, 1025-1026. (Cited -iy Egbert.) ,, 5. Egtart, D S. Pulmonary asbestosis. Report of a case with necropsy findings. .Ins. Rt 9. Tuberc., 1935. 3D J5-346. Shull, J, 1. Asbestosis. A roentgcnoloeical review of 71 cases. Radiology, 1936, a 279-292. 7. L.mca, A. J. Asbestosis. J. A. .If. .4., 1936, 106. 568-369. 8. Lynch, K M. Pulmonary asbestosis. IV. The asbestosis body and similar objects n the lung. J.A. .If. .4., 1937. 109, iq74-iq;3. 9. Williams, E. The presence of "curious bodies'' in the lungs of South African goldinir crs. J. rath. & Bad., 1939, 48, 47S"477to. Sutherland, C. L. Tuberculosis in the silica-risk industries. Lancet, 2940, 1, 80-8oo. tr. Ha miessoo, II. A case of pulmonary asbestosis accompanied by pulmonary tuberculosis. Tubercle, 2941, aa, 40-44. 12. Ilomhurgtr, F. The co-incidence of primary carcinoma of the lungs acJ pulmorary asbestosis. Analysis of literature and report of three cases. Am. J. rati ., 1943. 19, 797-807. 23. Auerbach O. The pathology of the pneumoconiosis. Quart. Bull., Sea View Uoip., 193&-37, a. 3-17 14. Monthly Labor Review, U.S. Department of Labor, Bureau of Labor Statistics, 1946, ; a, p. 253, table 2. 15. Pinner, S. Noncaseating tuberculosis. An analysis of the literature. .4m. Rev. : uberc., 2938, 37, 690-728. 16. Ilorlon, (., Lincoln, N. S., and I'inncr, M. Noncaseating tuberculosis. Am. Rev. T there., 1939. 39. 186-203. 27. Rubin, I . IL, and Pinner,' M. Sarcoidosis. One case report and literature review of autopsied raifs. Am. Rev. Tuberc., 1944. 49. 247-269. 28. Reisner, !). Boeck's sarcoid and systemic sarcoidosis (Besnier-Boeck-Scnau- mann disease): study of 35 cases. .4m. Rev. Tuberc., 1944, 49, 289-307; 4J7-4r > 19. Friedm.n , M. Sarcoidosis of the spleen. Report of a case with autopsy and a stud of intracellular "asteroid bodies." Am. J. Path., 1991, 20, 622-635. 20. Krnuj. f. J. Sarcoidosis (Bocck-Besnier-Scbaumann disease) as the cause of a pituitary syndrome. J. Lab. & Clitt. Med., 29;:, 28, 140-246. 22. Wolbaeh. S. B. A new type of cell inclusion, not parasitic, associated with dis;jrr.inated granulomatous ! sions. J. .If. Reuar h, 1911, 24, 243-257. 22. Zeck, P. M. Heart weight. I. The weight of the normal human heart. .-IrcA. Pall:., 1042, 34, 8:o-S )2. M y F. 11. l'.i'lv l..--:. :! T ,:<| 12 W 1! 1 11 :>, 1, hi I V 34. fner, L. U. Personal communication. *5- WgJg`iins, G. K. The effect of pulmonary tuberculosis upon the weight of heart. Am. Rev. Tuberc., 1944, 49, 255-275. 26. Gardner, L. U., and Currantngsf D. E. Studies 00 experimental pneumonokoniosis. VI. Inhalation of asbestos dust: its effect tgion primary tubcrcidous infection. J. Indust. Uyg. Gr Toxicol., 1932, 13, 65-81. *7- Rich, A. R. The Pathogenesis of Tuberculosis. C. C. Thomas, Springfield & Baltimore, 2944, p. 722. , 28. Jadassohn. Zur l'rage der "S.11 des Lupus pernio und des 1 opus miliaris in {Combination mil "Acnitis. Cor.-Bl. /. schweiz. Aerzte, 1919, 49, 455 458. 29. Mallory, F. B. Toe Principles of Pathologic Histology. W. B. Saunders Co., Philadelphia & London, 1928, p. 207. [ Illustrations follow ] Fig. i. Initial roentgenogram of the chest. Fia 3. I'hauimirrograph of Iunn and adherent pleura showing subplcural. septal, peribronchiolar, and marked and locally nodular pleural tibroais. X 4. 1 joft 1 't ! \' J I'LlIt IO| I IC. 3. I'ronlnl M-ilion 01 U11 Inn C.' 1 i i I'UII (0$ I n;. 4. Lung. duming a duster of sarcnitbl UibcriL*. , ttc. I'm. 5. Lung. Tlie giant cel! %%hich nearly nils ilie lielil cotu.iins .in .in iifH'.icyto|>bsmic varuole. X 1090. mill" in t # k jk Plate 106 4 I Fic. 6. Lung. An inclusion oi Schaumann encloses an ov.il yellow hotly. With polarized lis'ht, doubly refradile material surrounds this calcified mass. X 725. Frc. 7. A giflifit cell from the lung with inclusions of Schaumann. X 725. 1 PLCTE 107 l ie. 3. Lime with iulwrcUrs of foreign body type. The central tubercle has an asbestos bod' .11 its periphery. X 160. Fie. 9. I.une shna pr asbestos bodies and clusters of hcmoddcrin-ladcn macro phages within n area of fibrosis. X 7:5. I t St. 'till. I M't t.'i'll lilMl'i ' ii 1.1 V ' t t Fig. i Fig. i I'l Alt IOS I. . An asbc$t..-r *.")> i? shown in ;in alvroluv ^ > ? .ing an ;iu? body encrusted with iron and calcium. X 725. 1 1 i ;n : It.'triln.li <*.. s! c