Document 6wGjEmv8YvpGjZZwQDOdogvjR

FILE NAME: RT Vanderbilt (RTV) DATE: 1955 DOC#: RTV238 DOCUMENT DESCRIPTION: Saranac Studies of NY State Tremolite Talc, Arch. Indust. Health - The Effects of Inhaled Talc-Mining Dust on the Human Lung --- . - a M C ZJk* C ffc U o fJ n liJ e d O Jc-W h n in f 2 .W on the ~2hima.n oC. lu n $ a W. H. SCHEFERS, MJ), Die. end . T. M. DURKAN, M.E, Somme Lake, K Y. Talc belongs in the group of silicates that have been under suspicion for many years as a cause of pneumoconiosis. The literature contains a number of reports of studies which indicate that industrial workers exposed to talc dust sometimes develop changes in the lung, and several investigators have used the term "talcosis" to describe the pulmonary condition produced in those exposed workers. Pure talc, a hydrous magnesium silicate, is a specific mineral, but, as Schulz and Wil liams 1 pointed out, the word "talc" as used in industry usually refers to a product which meets certain physical requirements rather than to a substance of definite chemical com position. In commercial talc, the mineral talc itself may he. only a minor component. Sehul* and Williams found that in '51 samples of commercial talc the amount of the talc com ponent, based on the count of particles smaller than lU/i, never exceeded 52 jb of the sample. Other prominent minerals in their samples were serpentine, dolomite, and tremolite. A review of the data on 35 "talc" samples re ceived at The Saranac Laboratory for routine analysis revealed that the composition varied widely. In 8 of the 35 samples there was no more than a trace of the mineral talc present,, and all the 35 contained a substantial amount of one or more other components, such as tremolite, mica, carbonates, and clay min-' erals. Recorded for publication April 7, 1955. Director (Dr. Schepers) and .Chief Chemist (Mr. Durkin), The Saranac Laboratory. 180 The extent to which the mineral talc is responsible for the changes in the lungs is still in doubt. Certainly the experimental and clinical evidence incriminating pure talc as the principal etiologic agent in so-called talcosis has sp far been much less convincing ' than similar evidence supporting the view s that silicosis is caused by inhaled quartz dust or that asbestosis is provoked by inhaled asbestos fibers. Nor is there complete cer tainty yet concerning the pathognomonic fea tures of the specific talc disease. In spite of these uncertainties, reports on - 21 clinical and roentgenological and 13 autopsy studies exist in the literature, com mencing with the first paper by Thorel * in 1896. Jaques and Benirschke1 have recently reviewed these cases. The main emphasis ap pears to be on a radiological pneumoconiosis, ranging from diffuse bilateral reticulation without predisposition to tuberculosis to con glomerate massive shadows frequently tuber culous in nature. Qinically the disease varies from a benign to a rapidly developing fatal process, with emphasis on cor pulmonale as the cause of death. There may be a prolonged symptom-tree induction period. Tuberculosis, emphysema, and bronchitis vary in their prevalence. Pathologically the condition has been described mainly as a dense type of fibrosis, with peribronchial and perivascular prevalence and sometimes with nodularity. Talc has been demonstrated in the tissues of some cases, and the suggestion has been ad vanced that the talc shows certain erosion changes in the human tissue cot present in the original state. A point which has by no means previously been settled concerns the role of substances inhaled in association with the talc as the cause of the disease proc ess. Speculation has mainly concerned the effect of the quartz, which has frequently' been demonstrable. On the other hand, cases '. 3T I1 SC-RTV-2200 \'U o l . neral talc is the lungs is omental and pure talc as in so-called s convincing g the views quartz dust by inhaled mplete ceromotuc fea- reports on U and 13 lture, com Thorel * in ve recently nphasis apnoconiosis, eticulation sis to conntlj er ase ories ping fatal monale as prolonged xrculosis, in their lition has : type of vascular dularity. issues of bent aderosion esent in has by oncems xiation e procled the luently . cases EFFECTS OF INHALED TALC-MINING DUST ... exist in which neither quartz nor talc have been demonstrable. ' Passing reference should also be made to the extensive literature on the granulomata associated with the surgical use of talc and the fact that talc lesions have been observed not only in the lungs but also in the peri cardium, the epicardium, and the gastric mucosa, besides surgical wounds. I t is evi dent that a great deal may yet be added to the sum total of our current knowledge con cerning this dust disease. W ith this object in mind, observations are presented in this paper on dust surveys conducted by The Saranac Laboratory of certain mines and mills of the talc industry of Northern New York State, together with the chemical find ings and histopathology of eight deceased em ployees from that same industry.* SURVEY OF DUST CONDITION I N CERTAIN M INES AND MILLS OF T H E TREMOLITE TALC INDUSTRY OF NORTHERN N EW YORK The rock mined and milled in the area in Northern New York studied by The Sar anac Laboratory, although sold as talc, is a mixture of talc and tremolite accompanied by a smaller amount of anthophyllite. All three minerals are silicates. The talc usually de velops in thin, flexible, white laminae that are characteristically greasy to the touch, but in some samples from this area it occurs in fine fibers instead of the usual plates. The tremolite and anthophyllite normally occur as coarse crystal grains, but in the area studied These cases are part of a series collected by the late Dr. L. U. Gardner. A manuscript under, preparation by Dr. Gardner had not been com pleted by the time or his death. The present account js an independent study ot the material without reference to this manuscript. and elsewhere those minerals sometimes break up into long narrow fibers and then exhibit the structure and properties of as bestos. It should be pointed out that the term "asbestos" does not refer to one specific mineral but rather to any mineral capable of splitting into long, thin, flexible fibers and resistant to beat and chemical agents. Two distinct types of mineral are used commerci ally as asbestos: the bulk of the product is chrysotile, which is a fibrous variety of the silicate mineral serpentine; the important remainder belongs to the group of silicates known as amphiboles and includes the var-' ieties amosite and crbddolite. Tremolite and anthophyllite are also members of the amphi bole group. Since the experience in South Africa shows that at least one of the asbestiform amphiboles--croddolite--is capable of causing, typical asbestosis, there is reason to suspect that the fibrous amphiboles from the area studied by The Saranac Laboratory also might cause reaction of the asbestosis type. It is likewise possible that any portion of the talc which may be present in fibrous form might have a similar-effect on tissue. Representative samples of the mine product from three mines and of ground talc from two mills in the area were analyzed by chemical, petrographic, and x-ray diffraction techniques. The results appear in Table 1. A t the same time samples of air-borne dust were collected with an electrostatic precipi tator in two of these three mines, near a miner operating a jackhammer drill, and in the working area of both mills. Later preci pitator samples were collected in the third mine also. Analysis revealed that the dis tribution of minerals was somewhat different in the atmospheric samples (Table 2) than T able 1.--Competition of Mint Product and of Milled Talc from Tremolile Talc /tutustry of iXorthem .Xrw York Mine P ro d n et Milled T ele M ineral ' Mine A. Per Cent Mine B. Per Cent Mine C . ' " MiU D. Per Cent Per Ceot m u E. ' Per Cent T e l e - .......... ................................................ T rem o lite-.................................................. A n tP o p b y ilite ........................................... ........... 35 S e rp en tin e .................................................. C e itit* ......................................................... Q u a r ti.............................................. ......... ........... 4 40 50 1 30 3S 55 a 3 7 TO i 3 5 8 . s 4 3 ; l 0 <0-1 3 . 0* MIO D used th e m ine p ro d u c t o t M ines B a n d C, t o d MID v e applied b j Mio C. 181 SCHEPERS AND DURKAN T able 2.-- Composition of Atmospheric D ust Collected w ith Electrostatic Precipitator in Mines and Mills of Tremolite Talc Industry of Northern N ew York Atm ospheric Dost Mineral Q naztz_............................................... " PvrCenc (a) percent > 55 1 1 cn 1ft 7 Mine B. Per Cent ts 15 5 7 0 Mine C. Per Cent 13 40 40 a t OJ Mm d . Per Cent 25 35 13 1 * Mm e . Per Cent U 10 OJ * Tb* t r o samples o f atmospheric dost from Mica A w en collected lo dU fcnat levels o f the a lo e . They were takes several m onth* later rban those from Hines B and C and Mills P and E. in the mine product and in milled talc. This finding is in agreement with previous ob servations * that the composition of air-borne dust may differ considerably from that of the source material from which the dust originated. Even in the same mine there may be substantial difference in the com position of the air-borne dust: one atmos pheric sample collected in Mine A had a quartz content of 7Jo, while for' another sample, taken at about the same time but in a different level, the quartz value was only 2Jo (Table 2). This variability in the quartz content is illustrated again by comparing the analyses of various samples of rock, mineproduct, and air-borne dust taken in Mine A and in Mine B (Table 3). It will be noted that the per cent of quartz in the Mine A samples ranged from 21% to 03 Jo, and in the Mine B samples from 41% to 9%. This matter of quartz content is men tioned in some detail: first, because previous investigators 1 have reported that they found only a negligible amount ot quartz in sam ples of rock and of ground material from this area; second, because it has been dem onstrated (Table 4) that at least some quartz was present in the lungs of one miner and one miller from this local industry who had no other industrial exposure to dust, and, third, because quartz is a known pulmonary pathogen. The quartz may not be uniformly distributed throughout the entire tremolite talc bed, but' the analyses in Table 3 show that it can be present in substantial amount. Owing to erratic distribution, the quartz de posits may be missed by random sampling. I a attempting to take cognizance of the potential pathogenic role . which may be played by the quartz in the talc, sight must not be lost of the fact that the quartz found in the lungs of deceased miners who had also worked in other industries may have been derived from exposures in those industries. CHEMICAL AND PETSOGRAPHIC STUDY OF T H E LUNGS OF EIG HT DECEASED TALC-INDUSTKY EMPLOYEES The series of autopsy specimens studied consisted of the lungs of seven miners and one miller from the tremolite talc industry. All the miners had been engaged in drilling rock for periods ranging from 10 months to 27 years. The mill worker (Case 3) had been employed for six years, bat. as his body had been exhumed for study 18 months after his death, the findings are only of lim- ited value. A portion of the autopsy ma terial was taken for gross specimens and for histologic examination, and the balance was reserved for chemical, petrographic, and x-ray diffraction examination. For the com--- ponent chemical analysis and a iew ot the mineralogical analyses, samples of tissue T able 3----Q uart: Content of Rock, of M ine Product, ond of Atmospheric D nst from Mines A and B Quartz Coo teat 511 A, P rr Cent i l l B, Per Cent Bock e b f p i ............................. ...................................................... OJ 11 11 Mioa p ro d u ct ...................................................................................... . . . . . . . . . . . U ....................41 . . < 2 1 .................................... 20 II A tm ospheric d u i t ..................................................................... 2 7 9 ...... 10 17 9 . . . T a b l e A.-- A nalysis of Lungs of Industrial W o rkers Exposed to D ust in the Trcm oiitc Tale Industry of Northern N ew York A utopsy Cas >'o. 1 3 4 5 Asb, per cent o f dried tissue.................................... .Mineru Mloei Q uartz ................................................................ , Talc ................................................ - .................... Trem otlte ............................................................ ADtbopbyQJta ........................... . ................................ Feldspar .......................................................... XJoerali mineral C Q u a r t s ................................................................. Tale ................................ ..................................... TremoIIU ............................................................. A atbopbyttlte ................ .................................. ......... F e ld s p a r ......... : ......... ........................................ Components Com SiOt ................................... . .................................. F e s O .................................................................. A lsO ..................................................................... P*0* .............................................. CaO .................................................................. 11*0....................... ....................... Se*0 ......................................... .... KsO ................................................................... **% 17.41 11-25 17JO 8JO 12-41 njtltuenta. Per Cent ot Aah 33.1 8-3 03 *5 144 Tr 25 18 10 8 14 18 14 St 12 8 4 4 ................... ....... Tr UCDU, Per Cent ot DriedTissue 54 1.0 0.4 04 14 Tr 2.4 4.4 14 14 Xt 04 24 14 1.7 SSt C* 24 0.7 04 8 .... .................. Tr ;AaftJysU. Per Cent Of Atb 601 40J0 514 300 501 4.4 14 54 114 114 0.4 103 2-1 OI e.T 214 OI 102 84 0.8 44 07 3.4 24 13 154 lit 10* 124 a 34 S3 54 It 44 44 OI 104 02 5 Lett * 1342 .... a... .... .... ----- 900 92 74 03 24 124 24 02 0 d7 3 Rifht Lett % r. r* 047 7.45 449 5.72 8.0 3.2 2.4 5 2 11 4 1m9 3 4 7 Tr .... 04 0 * 0.1 04 04 14 04 0.2 OI O.i 0 * 0.4 Tr .-- .... .... 29.4 334 174 284 144 154 6.1 74 04 64 04 04 204 17* 324 254 34 2 4 3 4 .- 44 04 4.7 74 6.4 84 08 114 94 64 6.4 114 8 4 211-- nos* found. were removed from representative portions of the lungs and mixed. The camples were then dried overnight at 105 C and ashed in a muffle furnace. Most of the mineralgica! determinations were based upon other mixed portions of tissue digested with 30% hydro gen peroxide by the method of Sundius and Bygden* to avoid the alteration in mineral structure sometimes caused by dry ashing. The results of the chemical and mineralogical determinations are shown in Table 4. It should be pointed out that the values given for some oi the minerals are only approxi mate estimates. The quartz content was determined Ijy a special chemical and petro graphic method and is fairly accurate, but the values in the table for talc, tremolite, and anthophyllite may be somewhat above or below the true value. PULMONARY KISTOPATHOLOCY ASSOCIATED W ITH TALC-DUST EXPOSURE Though our series of eight cases appears limited, we were particularly fortunate in having available for study such a diversified range of dust exposures and lung lessons (Table 5). At the one end of our scale we have Case 1, with but 10 months' exposure to talc dust as a miner and 17 rears' general mining. At the other extreme is Case 8, with 27 years' talc mining exposure and 10 years' general mining. The associated exposures included service as miners of zinc, lead, coal, and iron py rites. This helps to elucidate the essential - talc reaction, as the normal result of exposure to dust hazards in mines of the latter types is fairly well understood. Our best fortune, however, for the present purpose is Case 7, a person who had worked 23 years only as a talc miner before dying from an unrelated cause without any inter current superimposed pulmonary disease. This case may therefore serve as a classical example oi a talc miner pneumoconiosis. Case 3 would have been equally valuable, as this worker had been exposed during his six years of employment as a surface crusher man and mill sweeper. Unfortunately, the studies were not made until his body was exhumed 18 months after burial, and so not much detail was preserved. However, it confirms certain essential points. - fundam ental pulm onary talc REACTION The primary reaction present in Case 7 consists oi multiple irregularly shaped foci (1 to 3 mm. in diameter) comprised of vir tually pure fibrocytic proliferation and macro- 183 T a ble 5.-- Industrial Exposures, Causes of Death, and Pulm onary Pathology in Eight Deceased Tremalite Talc-Industry Employees Dost Exposure A-C* ,___ -*- - at So. Tole Other Demth Death 1 Sime Zinc muw C'or pulmonale 10 yr. 10 mo. Unknown 1 yr. Hia Leadmin 38 Corpulmnal* DrflUnt Syr. 4 yr. Iron min lyr. S Surface 48 * Crusher Syr. Sweeper 4 yr. 4 Mine Zincmis* 49 Tuberculosis DrflQot lyr. 14 yr. 1 Mine Coalmica SI Corpulmonala DrfDisr Syr. Ifl yr. Iron mine 6 acw ITyt. 7 Hint Syr. Sin mini 2 rr. Pyrtte* Tuberculosis yr. 37 Nephritiswith catdUc Ulhut 7T. S Hint T STyr. Mtolnr 10 yr. Conrestire cardiac laflura Dom inant Pulmonary Lesions Tale Pneumoconiosis Flhroceumar. wm perivascular rranulomatosls Silicosis Aonneefl ornase, with hyalinlxatlon; isolated nodules Infection XU Massive diffuse Diffuse with focal flhroceular --- necrosis ? Histoplasmosis Diffusedominant* no 1/ cellularperi vascular Basal lobestuber* culosis Massive flbrocellular '"' Multifocal massive flbrocellnlar - Diffuse massive dbrocePuiar Massive confluent and multifocal Confluent nodular andmatsir flbrocellulmr TubrculosPicotic Cbrontebasal tuber culosis with bronchorentespread TUbemUosilteoaia with necrosis TubcrruhftOfeosls with cavitation Perivascular dlscetetoecl Diffuse flbrocellular xn NO Massivemultifocal nh phage accumulation. The cellular deposit tends to be arranged in a stellate manner around medium-sized and smaller blood ves sels (Fig. 1A ). There is fairly abundant visible pigment, which either is found within isolated koniophores or seems to lie in the interstices between the fibrocytes. Some of these particles are brilliantly biretringent and may be present as spicules, some of which measure 0.5/1 by 5/i (Fig. IB ). These characteristic macules are easily dis tinguished from isolated mature silicotic nodules which are also present. Some of the latter possess a halo of cellular elements and are probably composite talc and silicotic lesions (Fig. 4B ). Elongated terminally clubbed bodies, measuring 20p to 50p long and in no obvi ous respect distinguishable from asbestos bodies, are present in fair abundance (Fig. 7 ) -mainly within alveoli, where they tend to occur in clusters held together by konio phores (Fig. 8A ). A moderate number also occur among the fibrocytes, and in these sites where there are fewer dumbbell types, there' are also more instances of degenerative changes. The intra-alveolar "talc bodies" are generally stained intensely by means of 184 Prussian blue, while .those, which lie among the fibrocytes may be losing their iron-con taining sheaths as the Prussian blue reaction is fainter and more widely dispersed. Many of the koniophores in the alveoli show this, blue staining too. The larger-blood vessels trapped within these fod do not show much deviation from the normal. It should be clearly appreriated that the focal lesions appear as isolated macules in section only and really represent cellular sheaths accompanying the blood ves sels for variable distances. The smaller arterioles may show some endarteritis ob literans, and rarely a talc body may be found embedded in the vascular walls. The fibro- cytic infiltrate abuts directly on the vascular adventitia. However, there is no appreciable modification of the -lamina elastica of the blood vessels. Capillary rirculation through the fibrocytic masses is poorly developed. But little collagen is laid down among these fibrocytes. The supporting stroma in stead consists of a delicate web of reticular fibers embraring groups oi fibrocytes rather than subtending individual cells (Fig. 2A ). Elastic tissue is absent from the centers of the cellular areas (Fig. 4A ). an d DVRKAN Fight Deceased -does SB 'Ktioa t BUCSPlUlBOUf BiulM aUb culosis , Cferaalc b < u l l e b o eoiasis w ith b n o ctaialc ip m 4 . Tobocolosllfcmli - vltB ocem t* TobcmilofOIraili t lit csriutloa Sv ^ .' Ira ti.- rhich lie among jtiieir iron-con an blue reaction ispersed. Many toK show this trapped within devia^oji from rfy4. xiated T. isolated rally represent he blood vesThe smaller "larteritis obJay be found ^ The fibro".the vascular 5 appreciable of the ?*on. through developed. 50Wn among *troma in.,of reticular ? 5ytes rather 2A). EFFECTS OF INHALED TALC-MIXINC DUST Fig. 1.--Primary lesion: talc mine dust exposurl only. A . perivascular cellular aggregation. D, cr view, showing massed macrophages a::d fibrccyres and talc- "icttirs. Fig. 2.--Stroma of perivascular deposits of talcosis. A , reticulum supporting the macro phages and fibrocytes in the primary lesion, with talc components only tlow quartz content in lung ash). B, collagen abundantly deposited with fewer cells (high quartz content in lung asm . 185 '. y*r l13 Sa*A V SCHBPERS A.VD DURKAN ^t t s . j , . SSit-- r C L r. ilr ' ;` T* : \ -. Pis'. 3.--Pcri-raKuUr fibrosis in talcosis. 4, abundant fibrocellular reaction around vessel (moderate quartz content in lung ash). B, marked collagen deposition with paravascular nodule (high quartz content in lung ash). Fig. 4.--Parenchymal nodules found in talcotic lung. A , dominantly cellular nodule, with central amorphous change and talc bodies (low quartz content in lung ash). B, hvalinized whorled nodule, with peripheral cellular reaction (high quartz content in lung ash). Tv. M i as M g* tH it w 'Jl 186 EFFECTS OF HALED TALC-.\I1.\ I S C DOST At isolated sites focal necrosis has super vened within the cellular areas. There is no apparent zonulation around these necrotic areas o r any tendency to collagen deposition or caseation. No suggestion of tuberculosis exists, and the cause may be ischemic in view of topographically evident arteriolar occlu sion or luminar narrowing. On the other hand, the histological features are highly suggestive of histoplasmosis. T h e perivascular fibrocytic deposits tend not to invade adjacent alveolar walls in mas sive columns, though large numbers of alveo lar walls are moderately thickened owing to cellular infiltrates, and this change is the more evident at the points of junction of in dividual septa. A t isolated pointa th e alveo lar walls are inclined to be thin, but there is only a slight tendency toward rupturing, a s . alveolar spaces are inclined to be moderately reduced in diameter. The resultant tendency to atrophic emphysema is most distinct toward the lung periphery. ` . . Septal cells are not conspicuously devel oped, and there is no evidence of macrophage or septal cell catarrh into the alveolar spaces. Virtually no excessive collagen is present within these alveolar walls, but a ' delicate reticular skeleton supports its center. Elastic bundles are poorly rep resented and occur in a fragmented fashion among the fibrocytes. Alveolar wall capillaries are occluded along some stretches where fibrocyte deposition is particularly*abundant, but tpore generally the capillary circulation is undisturbed. Columns of cellular reaction accompany the interlobular septa to the pulmonary pe riphery, thus producing a coarsely webbed sectional effect. There is more collagen in these septa than elsewhere (Fig. 1 1 5 ). The pleura shows slight cellular infiltration and mild collagen deposition internally to the lamina elastica. Numerous talc bodies may be found here, and some can be seen to par tially penetrate the elastica. Superficial to the latter, a vascular zone of fibroccllular re action of variable thickness is to be seen. Isolated silicotic nodules occur in this zone. It is covered by msothlium (Fig. 12). Lymphoid tissue is scantily present in the lungs, and the granulomatous reaction ap pears to avoid these foci almost completely, though these granulomata may abut on such lymphoid tissue. The hilar lymph nodes show hardly any hyperplasia and exhibit minimal p igm en tation on ly. N o talc bodies are to be found. However, minute circumscribed sili cotic nodules are present. Many of the bronchioles and sonic of the smaller bronchi are markedly distended and distorted and are the seat of chronic inflam matory change without, however, any ma terial impairment of the epithelium (Fig. 9 5 ) . The latter indeed tends to be hyper trophic, with goblet cells predominating. The bronchial glands are also somewhat hyper plastic A little plasma cell infiltration into . the mucosa is evident, but there is no collagen deposition. The muscularis mucosae does not seem to be hypertrophic because its com ponent columns are so widely separated. However, this is illu sory, and th ere is in reality fairly well-marked muscular hyper- trophy. Sometimes this is focal in distribu tion (Fig. 9 A ). How effectively this muscu lar system may operate is left in some doubt, in view of the patent invasion of the bronchiolar adventitia by fibrocytes at many sites, as the peribronchial veins and arteries are similarly invested by the proliferating reac tion. M O D IF IE S T A L C L E SIO X S ' The basic lesion just described may be recognized throughout this series of cases, though modified by the associated pathologi cal processes induced by other dusts. It is the more remarkable to note that the cellular proliferative phenomenon is present even in Case 1, where the history of talc-dust ex posure is as short as 10 months,, and persists in virtually similar form not- only in Case 7, with a history of 23 years of talc exposure, but also in the instance of Case S, where there was a 27-year talc-exposure history,-- together with 10 yea rs' exposure to dusts encountered in zinc and. lead mining. There may be a greater tendency toward the formation of massive lesions and sub pleural reaction where there is an associated . ' 187 ........... - - ........................................ ....... ......................... --. - 1__________________________________________________ ini r .-? r X -> - if m (Afr: ,^r j *5?Ar^ -*^>5-^V- FK . ' !& j A- Fig. 5.--Parenchymal cellular deposits in talc miners. A , loose cellular vreb, with atrophic alveoli (moderate quarts content in lung ash). B t pigmented iron-staining stellate celiuiar deposit (moderate quartz content in lung ash). - Fig. 6.--Stromal reactions in taleosis. A , pigmented fibrocellular granulation tissue, with atrophic alveoli (moderate quartz content in lung ash). B. dense dittuse fibrosis, with surviving elastic skeleton of occluded blood vessel (high quartz content in lung asii>. . 'T-S 2'nxs3 ......................... 188 ^ <.' C . A . i . v : ; v> < S A ^ *3* : # ' S'-i '/* 1. J.l atropuic 3* r deposit Fig'. 7.--"Talc" bodies in human long tissue. A . slender elongated "taic" bodies embedded in fibrous tissue. B, short dumbbell body partly engulfed by a macrophage and sliounng intense iron staining. - se, with irviving Fig. 8.--Talc bodies in human lung tissue, A. accumulation oi koiiiouhorcs. showing a high degree of iron staining and containing short let:gths of .talc fibers. B, trie body among erytiirocytcs within the Icme:: of a bicod vessel. SCHEPERS AND DURKAN quartz reaction. In Cases 2 and 6, collagen tially, then, there are three cortical zones, formation is restricted to a minimum and viz., a fibrocellular internal component which the su pp orting strom a tends to be o f a r clicu - may be variably pigmented and which may lar nature of variable density. In Cases 1, contain distended bronchioles, an intermedi S, and 8, there is a greater' tendency toward ate exaggerated lamina elastica, and an ex collagen formation. It is to he noted that of ternal highly vascular fibrocellular layer usu these cases Cases 1 and 5 yielded a relatively ally covered by mesothelium (Fig. 12B). high value for quartz in the lung tissue but The parenchymal stroma- is considerably Case 8 showed a very low quartz leveL Bir exaggerated in the presence of a quartz reac fringent quartz particles are a prominent fea tion superimposed on the. talc phenomenon ture of the tissues in Cases 1 and 5 and are (Fig. 5 ). This is largely a periveno'us but poorly demonstrable in other instances. .change, and within these linear columns of The interstitial alveolar wall reaction is fibrosis partially o r wholly occluded blood also more marked in the cases with heavy vessels may be seen, sometimes so effectively quartz-dust exposure, and there is consider incorporated within the scars as to be. be able collagen deposition even with some hya- trayed only by their residual elastic tissue linization in Cases 1, 2, 5, and 8. Indeed,, in skeletons (F ig. 6 ). . .. these cases the alveolar wall involvement is so Vascular damage is indeed very much pronounced a s to oversh ad ow -som ew hat th e m ore in ev id en ce in those cases with the long essentially perivascular distribution of the est history of hard-rock mining or where the underlying talc reaction. ' - highest free-silica content was discovered. The damage sustained by the alveolar walls Two essential processes are present, namely, is further modified by the presence of quartz an endothelial proliferation in the least ves particles which involve marked macrophage sels ending^as endarteritis or endophlebitis and plasma cell infiltration, marked enlarge obliterans and a periarteriolar fibrocvtic pro ment and proliferation of the superficial sep liferation, with fibrotic stricturing or partial tal cells, otten associated with cellular catarrh invasion of the muscular coats (Figs. 2B, into the alveolar spaces, and finally moderate ZB, 10, 11). T his process is present in its to m arked im pairm ent o f tlie capillary circu most exaggerated form in Cases 1 and 6. in lation through these alveolar walls. The latter which multiple periarteriolar granulomata is not, however, a constant phenomenon, and may be found. Such lesions cause marked there may be advanced alveolar wall disease pulmonary ischemia, the more so as the le without appreciable loss of capillaries (e. g.. sions are not limited to the pulmonary circu Case 6). . lation but may also involve the bronchial W hen collagen is present, it fails to be vascular system at numerous points, thus arranged in the form of silicotic nodules in effectively precluding establishment of any all but'rare locations (e. g.. Cases 1 and S). collateral circulation. Incipient fibrous whorls are present also in While the essential reaction to talc ap Cases 2 and 8. Some lie against blood vessels pears to include exaggerated distention of (Fig. Z B ). It seems possible that the abun bronchioles and smaller bronchi, this change, dantly cellular talc reaction is incompatible though present in a variable degree in all w ith the com p lete evolu tion of th e nodular cases of the present series, is not universallv silicotic lesions. .. observed throughout the lungs where reac Subpleural deposits follow the same pat tion to quartz dust is concurrently present. tern, being most marked where exposures to Instead, there is a tendency toward narrow both talc and quartz have been considerable. ing of the bronchial lumen, epithelial desqua The resultant lesion is, however, an .exag-. mation,' mucosal' hypertrophy, sometimes, geration of the primary talc reaction except with papilloma formation, and inflammatory for the greater prominence of the collagen infiltration, with- adventitial fibrosis and where quartz is abundantly present. Essen cicatrization at multiple sites where exposure ISO VD D U R K A N con- zones, npon<_< which nd which may an intennedia, and an exilar layer usuFig. 12B). > considerably a quartz reac: phenomenon a perivenous ir columns of xluded blood so effectively as to be be* elastic tissue very much nth the longor where the discovered, ent. namely, le least vesndophlehitis rocvtic pro5 n rtinl (F.s .. ZR, esent in its 1 and 6, in ranulomata ise marked as the lclary circu- bronchi.il lints, thus nt ot any i talc apention of is change, ee in all liversally ere reac- present. narrowI desqua* metimes nmatory sis and xposure e f f e c t s o f i n h a l e d t a l c -m i x i n g d u s t Fig. 9.--Bronchial damage in talcosis. A . irregular focal proliferation of muscularis mucosae (low quartz content in lung ash). B, submucosal fibrosis, with lymphatic distention but no injury to the epithelium (moderate quartz content in lung ash). Fig. 10.--Vascular damage in talcosis. A , perivascular fibrosis and intimal swelling (high quartz content in lung ash). B, talcotic nodules in the walls of blood vessels (low- quartz content in lung ash). ' 191 SCHEPERS A.VD DURKA.V to quartz dust was adequate. This combina tion of chronic hypertrophic bronchitis, oblit erative bronchiolitis, and the peripheral brondu olectasia superimposed on the fibrocellular changes throughout the lungs may lead, on the one hand, to extensive areas of partial atelectasia o f the relevant lung fields or, on the other, may be associated with the develop ment of multiple epithelium-lined peripheral cysts. The latter are essentially ballooned-out terminal segments of the respiratory passages and may be readily distinguished from em physematous bullae by the presence o f the epithelial lining, the residual basement mem brane, and the irregular presence of support ing muscle fibers. True emphysema is rela tively infrequently seen and, when present, 5, 6. and 7. In Case 2 histoplasmosis is the obvious answer, while in Cases 4, 5, and 6 th e lesio n s arc w o r e suggestive of tubercu losis or tuberculosilicosis. There is some tendency toward inflammatory reaction at the periphery of the lesion s in the latter three cases only. On the other h^nd, the necrosis also involves the stromal elements, favoring histoplasmosis once more. In the majority of other cases, it seems possible that the necrosis may be explicable on an ischemic basis, eitherbecause the cellular hyperplasia had out stripped its vascular supply or because the latter had been cut off through regional vas cular occlusion. However, as all these cases came from the St. Lawrence Valley area at the time of an epidemic in that region, it is consists of the atrophic vesicular variety. . possible that histoplasmosis may be a factor. T he differential involvement of lymphoid The process seen in Cases 4, 5, and 6, if tissue in the reaction to talc dust and to talc tuberculous, has been modified considerably ^ dust combined with quartz dust is clearly by the abundance of fibrous tissue and cells. demonstrated in the present series. Whereas A large thick-walled cavity, without a dis the talc reaction tends sedulously to avoid the lymphoid tissue, the contrary condition pre vails when quartz is abundantly present or where there is an associated tuberculosis. Talc bodies are, however, never seen in the tinctive fibrous capsule or even components, is present in the latter instance. Atypical tubercles are present within this wall at the edge of the broad inflammatory zone. While the temptation exists to interpret this cavity lymph nodes, and the reaction present in most instances is limited to medullary macro ph age infiltration and pigmentation.. Silicotic as tuberculous, it may represent merely a ch ron ic discharging abscess. The lesion is also compatible with a diagnosis oi histoplas or tuberculbsilicotic nodules are present in mosis. Attention may also be drawn to the but a few instances (Cases l and 5). Despite marked peribronchitis and ulcerative bron the fact that multiple nodules and necrotic chitis in the passage draining this cavity. No foci are present in the lung substance, the tubercles were observed here. hilar node involvement is not marked. This Pneumonic areas w ere observed in the state of affairs is the reverse of w hat p revails cases with exposures to both quartz dust and in the presence of exposure to quartz dust talc dust, especially Cases 2 and 4, but not unaccompanied by an exposure to talc dust. where only talc dust was the responsible etio One is consequently inclined to infer that the logical agent. This pneumonic process tends simultaneous presence of talc dust and quartz . to show healing by organization in various dust in the lungs militates against the trans stages of progression, and numerous talc portation of the quartz dust to the hilar nodes. bodies arc th u s trapped. It seems likely that Alternately, though talc bodies are not seen in those present in the formed lesions may have the hilar nodes, their liberal transference is been incorporated in this manner through not yet precluded, and the inhibitory tendency earlier episodes of inflammation.. of the talc on the silicotic reaction, which is . manifest in the lung substance of this series, COMMENT may prevail also in the lymphoid tissue. The chronic or long-term effects of the Necrotic foci were ohserved w ithin the . inhalation of dusts, such as are generated in areas of cellular proliferation in Cases 2, 4, talc industries, are thus demonstrated by this 192 .VD DURKAU :lasn is the ;es 4, ,,, and 6 ive of tubercuPlicre is some ' reaction at the he latter three id, the necrosis rents, favoring the majority of lat the necrosis lie basis, either asia had out- >r because the t regional vas al! these cases /alley area at t region, it is y be a factor. , 5, and 6, if considerably :ue and cells. ithout a dis- ' - components, - e. Atypical : wall at the one Vhile t this cavity it merely a ie lesion is >f histoplaswn to the Hive broncarity. No ed in the 12dust and 4. but not ssibie etioess tends *n various :rous talc Skely that have ; through t ' . i'.r t * the in i b this Fig. 11.--Vascular damage in talcosis. A . progressive loss of venous lumen through pro gressive proliferation ot intima (moderate quartz in lung ash). B, fibroelastic scar in interlobular septum, representing the remains of obliterated blood vessels (moderate quartz in lung ash). series of cases to van- considerably according other industries to which the person may to the extent or nature oi associated dust in have been exposed, either preceding or suc- Fig. 12.--Pleural damage in talcosis. A . diffuse fibrocellular. partly pigmented, and highly vascular reaction (low quartz content of lung ash). B. loose fibrous proliferation external to lamina elastica, with wborled nodule: talc plaque (high tree-silica content oi lung asiil. 193 I SCHEPERS AND DURKAN feeding the period during which talc dust fies appreciably the type of reaction to the 'y a s breathed. quartz dust. Though considerable quantities . The histopathological features enumerated of free silica were, demonstrable in the lung are alm ost entirely explicable in terms Of the tissue (Table 4) in some instances (Cases 1, mineralogical analyses of the lung ash pre 2, 4, 5, and 6 ), there was not in this series a sented in Table 4. clear-cut tendency to nodular silicosis. I t is seen, for instance, that for both of our Tuberculosis or histoplasmosis may have key cases of pure talc pneumoconiosis (Cases been a factor in the pneumoconio'Bc reaction 3 and 7) the quartz content of the lung ash in some of these cases. While doubt persists (2 3 % and 3 2 % ) was about the same as as to the diagnosis of a true infective process, the corresponding value for many normal it does seem certain that if the latter diag-.. persons never exposed industrially to quartz nosis has' to be accepted the presence of the dust. Among this series, the amount of lung talc reaction induced an aberrant type of a<h of Case 7 is particularly low (4.69% of chronic inflammatory process. dried tissue), and so is the total silica con While it has been postulated that the fore tent (17.9% of ash) which includes the silica going observed deviations irom the primary in the silicates present in these tissues. process may all be due to coincidental quartz Q uartz was present in Cases 1, 2 . 4 , 5, exposure to tuberculosis or histoplasmosis o r and 6 in concentrations compatibly ' with to nonspecific pneumonia, reference should nodular silicosis. Indeed, the average] quartz be made to the fact that there is insufficient content of the silicosis cases studied-at The knowledge in the present instances concern Saranac Laboratory is 9.3% of the lung ash. ing the differences in the talc dusts to which Cases 1 and 5, therefore, had unusually large the men were exposed or to the concentra amounts of quartz dust lodged in their lungs. tion and rate at which' the talc dust was de Yet nodular silicosis was conspicuous by its posited in their lungs. The latter factors alone absence in Cases 2, 4, and 6 and only sparsely are known to influence the nature of the sili present in Cases 1 and a. cotic reaction which may follow exposure to Attention is drawn to the demonstrated quartz dust, and the precise composition of presence of talc, tremolite, and anthophyllite the talc may therefore necessarily be a factor in the lung ash of Qasc 7. T h ere is no appar too. In this connection it is interesting to ent correlation in this series between the note that the majority of talc bodies were in length of exposure and the concentration of a range of 20/t to 5Qk, being somewhat longer these minerals in the lung ash. and thinner than the asbestos bodies generally The factor which seems most obviously to found in asbestosis. In rare instances some . be responsible for the modification of the slender fibers, measuring up to 200fi, were essential reaction to talc dust is the abundant also present. T erm inal clubbing was a factor amoimi of.quartz dust coexistent with the talc in all but two cases (Cases 2 and 3 ), and in the pulmonary tissues. Five of the eight occasionally an intermediate bead could be deceased talc employees had been miners also seen. Segmented forms were but rarely seen. of lead, zinc, or pyrites. Attention is drawn In all cases-the mantle of the body showed an to the minor differences in the mineral com intense iron-staining reaction, but degenera ponents of the lung ash. While we do know tion of this coat was demonstrable in m ost that quartz is an active pulm onary pathogen, cases where the talc bodies were present in we do not yet know whether the additional the newly formed fibrocellular tissue. substances demonstrated (e. g., feldspar) are In addition to the talc bodies and the- capable of playing a material role in modi chemicallv demonstrable quartz, there were in fying the response to either the quartz or the most instances pigment granules and birefrin- talc or are themselves pathogenic. gent particles, spicules, and crystals within- It does seem permissible, however, to infer the interstitial tissu es and in the koniophores- that the presence of talc dust in its turn modi trapped within alveoli. The variable abundant: 1 eff e c ts of w h a l e d ta lc -m w w g d u s t presence of such elements at sites of maximal A mineralogical analysis of the lung ash fibroid or cellular reaction may undoubtedly from eigh t deceased talc-industry em ployees bear some relation to the differential patho revealed the presence of appreciable quan logical effects observed in the present series. tities of talc, tremolite, and anthophyllite. The pigmented particles, though present in Quartz was present in significant amounts all cases, were most abundant in Cases 1, 3, only in the cases where the men had been 6, and 8. Brilliantly birefringent particles, on additionally exposed to dust in mining indus the contrary, were conspicuous features tries other than in the talc industry. mainly in Cases 2, 3, 4, and 8, and in this T he histological features suggest that series large numbers of such particles were tremolite may be the main pathogenic agent dispersed among the fibrocytes comprising in provoking the" characteristic " talc" lung th e pu lm on ary lesio n s. T h e se particles w ere lesion. The role of talc and of anthophyllite identified as talc. has not been wholly excluded. The "talc bodies" described may be an indi cation of the main pathogenic agent in the present series of cases o r may be merely inci dental features. W ere the. former to be the case, it would perhaps be advisable to rename them "tremolite bodies." . They were relatively sparsely represented in Cases 1, 6, and 8, and it is interesting to find that in these very three cases the tremo lite content of the lung ash was least They were present in greatest profusion in Cases 3, 4, and 3, and once more the mineralgica! analysis confirms the relatively high inci The presence of quartz modifies materially the nature of the "talc" reaction. The presence of "talc" dust in the lungs modifies both the response'to quartz dust and the course of associated infection. Marked pulmonary vascular damage was present in the cases where the quartz content of the lungs was highest, and this feature is in harmony with the tendency to cardiac deaths. Bronchitis, bronchiolitis obliterans, and bronchiolcctasis arc associated m ajor findings in this series. dence of tremolite in these three cases (T able 4 ). T h e anthophyllitc .values, on the contrary, do not correspond with the histopathological findings. I t may therefore be iairly safely inferred that the "talc" bodies The chemical analyses presented in Table 4 w e r e m a d e b y A . J. R e d ltn , e h e m ic t, S a r a n a c Laboratory. E. S. Larsen. 3d. Ph.D_ oi the U. S. Geological Survey, iormerly petrographer ot The Saranac Laboratory, made the petrographic and X-ray diffraction analyses. are of tremolite origin. In view of the fundamental similarity be tween the talc reaction seen in this series and the- histopathological changes present in asbestosis. one is constrained to speculate whether the tremolite component, being an REFERENCES 1. Schulz. R. Z.. and Williams. C. R .: Comuciciat T alc: Animal and Mineralogical Stuoies. J. Indust. Hyg. & Toxicol. 24:75, 1942. 2. Thorel, C : Die Specksteinlunge. Beitr. path. Anat. 20:85, 1896. asbestitorm mineral, is not after all the main 3. ' Jaques. \V. EL and Benirsehke. K .: Pulmo source of mischief. It remains for animal ex periments to shed some light on this subject. nary Talcosis with Involvement oi the Stomach and the Heart, A. M. A. Arch. Indust. Hyg. S: 451. 1952. SUM M A RY A survey of the talc industry in Northern 4. Hatch, T , and Moke. C. B.: Mineralogical Composition oi Air-Borne Foundry Dust, J. Indust. Hyg. Sc ToxicoL 18:91. 1936. New York State revealed that the talc mined 5. Sitgal. W .; Smith, A. R , and Greenburg, and processed there consists of a mixture oi laic, tremolite, and anthophyllite. Quartz is also present in m oderate am ounts in the dust generated in mining and processing the com mercial talc. . - L .: Dust Hazard in Tremolite Talc Mining, Including Roentgenological Findings in Talc Workers, Am. J. Roentgenol. 49:11, 1943. 6. Sundius, N.,- and Bygden, A .: Isolation of Mineral Dust in Lungs and Sputum. J. Indust. Hyg. St Toxicol. 20:351. 1938.