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FILE NAME: Asbestos in India (IND) DATE: 1976 DOC#: IND005 DOCUMENT DESCRIPTION: Journal Article - Mesothelioma in an Agricultural Community of India: A Clinicopathological Study MESOTMKUnxr \ i.\ i \ | ) i \ MKS | MESOTHELIOMA IN A.N AGRICULTURAL COMMUNITY 01 INDIA: A CLINICOPATHOLOCilCAL STUDY P. B. D a s ,1 A. G. F lutcmi k. ; r- a n d S. G. i D eodhare3 S Departments oj Cardiothoracic Surgery and | Pathology, ipanless Hospital, M iraj Medical I College, Maharashtra, India | f Mesothctioina is an uncommon neoplastic condition. Its association zeith asbcslo- exposure is zvelt established, but it occurs cz'cn in non-industrial ziorkers. and naturallx 1 there must be some other factors in its (etiology than asbestos exposure, hi this report, ' five patients w ith prim ary mesothelioma, all belonging to a rural agricultural community ' zvith no chance o f any asbestos exposure, have been documented. T h ere zeas one f common interesting observation, in that all fizic patients w ere associated zeith suoar-c m e s farm in g or an allied trade. W hether this observation is coincidental or has any (ctiotogicad bearing on m esotheliom a needs fu rth er investigation. Its histopalhotogical features. ! symptomatology, diagnosis, and treatment are discussed, zeith a b rie f rezicze o f the literature j M esothelioma is an uncommon neoplastic condition arising from the pleura and also rarely from other serous membranes. Its incidence has been reported to range between (y02/( and o-2% of all autopsies, with a 2 : 1 male preponderance ("Borrow et alii, 1073). Viler Wagner published an account of the first documented case of primary diflu.se mesothelioma in 1870, only relatively few case reports appeared in the literature' till i960 l Gels et alii. 1 9 7 1) . However, the past 15 years have seen many series published, though none of them could really be called large, except those of Wagner et alii (i9 60). Gels et alii ( 1 9 7 1 ) and Borrow et alii (19 73). Meso thelioma is of special interest because of its known induction hv occupational exposure to asbestos (Grundy and Miller, 1972). Exposure to asbestos as an important causative factor ' Associate Professor and Head of the Department of Cardiothoracic Surgery. s Professor of Surgery and Head of the Depart ment. 8 Professor and Head of the Department of Pathology. Address for all communications and reprints: D r P. B. Das, M.S., I'.R.C.S. ( C ) , etc., cardiac surgeon, Safarjang Hospital, New Delhi, 110016, India. 218 has also been supported l>v the experimental j production of mesothelioma hv Wagner (1962). 1 However, its exact retiologv is still unsettled, j as it is also found in non-industrial workers, t Furthermore, its morphology is still not well understood, and its histopatho]ngic;i1 picture : and biological behaviour have been the sale jects of controversy. There is no satisfactory treatment for malignant mesothelioma. This presentation is based on the experi- ? ence in the management of five cases of meso- j thelioma belonging to the non-industrial rural J communities of India, treated at the Wanless s Hospital. Miraj Medical College. Miraj. s Maharashtra, between January 107 1 and March | 1976. and aims at elucidating its etiology and f pathology and updating its therapy and j prognosis. ( C l in ic a l R ecords j C ase i .-- A 35-year-old agriculturist, engaged in 1 intensive sugar-cane farmin g was hospitalized with principal complaints of chest pain and dyspnoea of four months' duration. On examination his chest was normal in shape and size. There was a dull percussion note in the left lower and middle lung fields, with markedly diminished breath sounds. j Sk iagram s o f the chest revealed a large mass continuous with the cardiac shadow and occupying \ most of the left hemithorax. Thoracocentesis and .. endoscopy were unproductive. A r s r . X .Z . j . Sri',., V<n.. 46 -- Xu. A n . i ' s i . 1076 S-anj Y'm: ! i; oi ! 11 LYTr- l>m ai Uaja-' 0. 4' I Ii'o aiul 0 >in Oi 1 AMIt 1r Ucr\ emit ORDT U'lll .U km.; ill aita ttm! 1'1'TV tko SO,] \r a s i i H sm sm si M ESOTHELIOM A JX INDIA DAS F.T Aid! a homogeneous opacity o f the entire left hemi- t orax with shift o f the mediastinum to the right ( lgure 2 ). The pleural fluid contained no orga- msms or malignant cells. " appearance, with areas of necrosis. The left lung with the main bronchi measured i i cm x 7-5 on x ; cm. ... mall and large greyish-white nodules were present all over its surface. Its cm surface showed H ospih *1 am rsc.- T h e patient underwent left one greyish-white oval growth with central necrosis lt u m 'a n d 't h ' !M' ' C " a f .dtIls0 adhesion between the ( 5s ccmto. *iho`<1,mIc),,lran'od' vu,hl'a,drl awndas nfir,amr,k`ia%nd tghaivcekentheed measuring -'-.3 cm x gem, with several similar areaol -mailer si/e. Another area of the lung showed spic.ad 01 the tumour iron, ;1H -,,rim a to tin Uing^Tldc f d' tlmiol,rs casing the collapsed oft tthhee ,thora" caicS cmavritey 1)arnodnoouvnecrei1thien dthiaephlorawgemr paanrdt depth of the lung along the bronchus. Micro scopically, the sections of the pleural masses showed tumour cells arranged in tubular fashio.. or forma the mediastinum, [he tumour mass extended to the tion Ot papillary processes on the cores of connective m tissue I he tumour cells were cuboidal, columnar ct or polyhedral m shape, and contained hvnerckro- <* mauc nuclei (F igure 3) . Manv acini contained In.nine eosinophilic material. The stroma of the tumour consisted o f abundant acednlar fibrous tissue. He sections Horn the lungs showed metastatic deposits. Ihese deposits were well circumscribed. V F aSC 3 : l,oslero-anterior skiagram of he chest showing complete opacification of the hemithorax and shift of the mediastinum to the right. i w i v Si T T V` ,rosternal H>acc and com- m p ' c m ' l 10 c:udiophremc and costophrenic an.-hs. Suhtoial removal of the pleura! mass (appioximateK 2,500 gm ) was -done to free the up. but the decorticated lung failed to expand. It appeared to be involved bv the tumour, and there was extensive air leak, necessitating left pneu.no- ne< ioniy. Mrs postoperative course was stormy .Subsequently he received a course of . adiotberrmv and chemotherapy (cyclophosphamide) and res'- ponded well. He is still doing well since his sm-gerv ni June 1975. ' M orbid unatom y.- The specimen consisted of big tumour masses, weighing a.soogm. The largest piece measured 12 cm >: 7 cm x 3 ern and was com posed o f several small and large nodules. The cut -nr face showed a greyish white homogeneous 20 S t fV V .. I icrm 3 : Case 3 ; photomicrograph o f section irom the tumour mass showing tubulopapillarv h'die o! mesothelioma (lia-matoxvlin and eosiii. x 350) ; and w m separated from the lung parenchyma by a layer o f lymphocytic tissue. The bronchi were norma . There was no evidence of asbestos bodies or asbestos-like bodies. A diagnosis o f diffuse metastasizing mesothelioma of the pleura (tubulopapillarv type- ) vvas made. A c t. X . / . J . Sntr;., Y ut.. gfi - \ i AirtrsT, 107b i T M .li M ESO TH ELIO M A , x , v j ){ a 1/ospitai coiti'sc_-Af - partly solid and partly m E c ^ 10" * huge mass, continuous with the ,, ' / ) 'C| as lound. It was ot the left side'of the ches" most except m one area when' if ' We,! encapsulated upper lobe of the left W S u f af!!llereilt to the pi the pericardium appeared iT e,ntlr.c left aspect thi' ".ass of whir,, ' VOlved. and incor- acluaUy lodged i,, tilc , c major part was ... ' * 'e ,JAS ET ALU S t ; t h h ' a ' wh0 T l7 !aci,,ff ^mdles and i,, ,<:dl* shelved eo.sinophil!rcyfoDH" e ra -The tun>"r pperdirom atic nuclei. |n PHces tiT " elonSated teration oi mesothelial J f f , L ^ was a Proli- paltern (Ensure 1 ). Areas of rmm a glandular degeneration of stroi,ril * 11, necrosi-s and myxoid 0 f imlnionar,-' s y wi H alS ^ a'vcoli was prese , n0,!r glallt cells ,rVvcal ashestos bodies or - 8 f.ections did not instopatholopical dia-mosis" " rd S` bodlKS- A ; ' " la AnhulojcipilHry V a r i e i y > TM i f ? " *,c.lnCS0- ' 'montai ( 19f3 2 ) . ! "settled, workers, "o t well picture Sul). i'-kictory oxperi1'f n leso c i niral ^A'an less M irai, M March "My and `Py and !aged in !'r:ed with dyspuofj his chest m, a dull 1 die l,,ns 1 sounds C o mas= oerupvinj, ,u'sis and '976 v > rk ;'` V ir iti '< - a m ? engaged bl - rural Jiitahzed with exe rtioin i dvsn { * nm } * " 'as lies- nl 1" " p e r a t u r e of one momM0" ! a 'K cvclli" g rise episode o f lia'inru.lvsis i ' !uTM t.ll,n- 'S 1`e had examination there wm \ h i - I w "-IK !hls heriocl. On "'< r hesi. r i w ,,.. S . :,;1 I , l , i g e <1'C left side Of X ` > apical impulse was palp-th e ^ 7 / thC n'Rht` " " ,,:u,r i ' ! percussion note M ? Aetre was a" ^'mds in the lo u rr ,n r t 'V A 'i'/ma'shed breath Msiafirams o f 7 1C [,, \ eft . s a l of the T ^ i i i % W & * *" nieasurin-j s < ' c m x , ,Vclli'X.,,!" ralion a large tumour. P<'Stenor low(T (>f ' iVf/' 7j 0<X' ul,-vi' the was lound. The parietal ,,1,..,,, 1(-ft .thoracic cavity, " ,a- - "',,VI, was easily f ^ f " lvoI,ved ia ` he -" on. I'liere was .1. 'ol.cst v-.t? -t x t ^a P,c ral dis * V '- . ^ r [lie' n.aii m ^ S mm 8,':,,h f ththoma (haunatoxyli,, a ^ e o U r x I s o 'r * 0' Jobe the tumour wit 1 - ,, 0 m ' COmi,i e extirpation tiltin' left aspect i F TM 1 m" rem, the rme and left upper i l / h T / T 'Uft h l'-nic niithmitty with the tlra, ri,, r T ? , *?cn,ficed m iterative course was ,me\ . J f ,,a" fei,ts P TM anutiiu'd well sinc-er hmiss ssumrpceeriyv m 'JIanJ1uUary ll1e074has Morbid amuomv --The in . tree, greyish sotYtissuc mass' 10 cm v ? ! * " ! o f a a sin. with part of the !u,,o- V 0 m. X 20 CIn .relied to it. 1, ]Kul a varico . '?, du(` Pericardium lii'sliy areas alternating w it h Y Y V r 8'e`Ua/ U7 ' " il1' liatic area.-. It ua< well tK,' and hanno,- ihe'ana where it w a s " l e n ' m " / except in eopiraily i, was composed of 'h ^ / V s ;. X ./ . J. S l iiC. \ TOJ, . Nh ccs-i, 1076 ......... . h M ' i i r " : : " ;,, TiM ,;iM i,n<" ............ . ' " " ` r l"he anij |,a r [ ,,f ti,, , ' < ', with the left It had a varieeated '<fn' ' ,,c,,ra Itachcd cireuiiiscrihed except in one a re a '" m i '' U ^ wel1 turns revealed a t n m , ,, - V JV,lcroscopic sec- vlU with nueha- wl ie , I n T ! ' 0 ^ 'P *P,im lh s>*Ped re arranged in a wd,,r l l ' Cnds- Tlll; cells 7 an mterlaeiny , ,, a,,uer. A r(. w ` S la,nf! in ' >la<'l' s m>*'! c also St-on 't' i r `induiai slructures h.enion liayir areas ,-u I '4r?" s o ! " -"n showed infill ration. Thev were r ' mf,am"'a torv cell sections showed' no e v i l V" il,ni01" - Also, the histological H: nn"sir " T - r aShCStOS !,odi(' - A made. ' " M ol ' '" " S n mesothelioma was ( asi: \ 'ifintiilod to ,, . j farmer was h f. sided chest .{ S y ! ,>r `''ghtcen months. A , ,, ^ a,n,s . " f ^reatlilcssl ''^ .n 'dating hack hreatlilessness had become ,,O le e ! ! A'(l'i1,s,s,on- ' `is 'ad recurrent pleural effusih ,, Y ' - U 'm *C lad also lla`j repeated tlioracnc.mteses \ '| u L l" " C' > ,,ad a," d aho received a course r f r , ,! S(,h',iol,i ineraiiy, apparenflv without anv ' !be: ni!oiis " l" ' r mdicaiioii. O n e x a, L ,, 1 1(-'r,0,0meal or -hiitcd to the ri.d,l T ` " " V " ,C ` 'achea n;a s "- e m a r k M I, .e stric le d muMhe!-?.'0 0 ' ,,) Vi'm e n :-^ -- on ,cft-sid,. o f ' i i a c W 7 S' 0,l-V dl' ,b ahsem tf,;.. . l ueath soumis ' <st dsiaei-ams revealed "i MESOTHELIOMA IX INDIA C a s k 4.-- A 54-year-old sugar-cane farmer was transferred to the cardiothoracic unit for exploratory surgery tor a recurrent and persistent right-sided pleural effusion. His symptoms had commenced diree months previously, when he developed right sided chest pain and breathlessness. H e was treated by his physician with antituberculosis drugs, with out any apparent benefit. On examination, the H-i ii ntorv movements were restricted on (lie rightode, and a dull percussion note with succussion splash was also present. Breath sounds were absent in the right lung field. H e had several thoraco centeses before and after admission. The pleural (tin-ion reappeared rapidly each time. Tile, pleural thud contained no organisms or malignant cells. Skiagram- of the chest revealed a right-sided pleural effusion. Skiagram s taken following thoracoccntesi- showed obliteration of the cardiophrenic angle and thickening of the right cardiac border, and the radiological sign o f scalloping was present in cr the diaphragmatic and mediastinal pleura. D A S F.T Al . i l were y e n over the lung surface and the parietal pleura. A rounded deposit, 3 cm > 2 cm in size, was present on the medial aspect of the right upper lobe near the fissure. One large deposit was found 011 the chest wall, involving the latissimus dorsi muscle at the site of a previous thoracocentesis. Multiple biopsy specimens were obtained from the various sites. H is postoperative course was unremark able. lit lias received a course of radiotherapy and chemotherapy (cyclophosphamide), l i e has remained well since his surgery in August 1075. -r- .#* , A' c -h x -'T .'V - ,1 Zs S . n * v p -c ... " V v> -. a ';* '? / '* t.ir* r y - fiI t s \y O^r- ** .-Hhi* '' i'n,!; ki: 5 : ( ;ist. 5; ; po-tm o-anteriur skiagram oi tilt-, s'best showing; massive pleural effusion 011 the right side. !ui;nu: 4: Case 4; photomicrograph of section i'cc.m the tumour showing fibrous type of iiesolbe!ioma ( lueniatoxylin and cosiu, 350), lusj-ilat to u rsc .--The patient underwent right .tioracotoniy. The pleural cavity contained about 1000 nd of straw-coloured fluid. There was a .I'gai-e and nodular growth of the mediastinal and .li'aphraginatic pleura, the thickness of which varied C`,,m one to two centimetres. .Multiple small deposits Mar Hd analfiir. The biopsy speeimen- were 'j ri-yisl i wh i.K- an<[ soft. _\1 ierosco; icaliy, the .sections ' how i '.! a tumour composed of dense coliagencus liliMM~ enel OMliy S'e\era! elusters of tumour cells ( l-'iguire 41i. In pi:aces, focal collections of chronic inllamniato ry cells: were seen. The findings were similar in till the specimens. The specimen from die chest wall deposit was greyish while and homo geneous. Microscopic sections from the deposit showed thick (ihrotis tissue with skeletal muscle. There were areas of granulation tissue with con gested capillaries and lymphocytic infiltration. There were nianv cystic areas lined by single cell and multiple cell layers, with hvp(achromatic nuclei with pleomoi phism. Their cytoplasm was scanty and eosinophilic. They were mainly present_ in the fibrous tissue, but had invaded the muscle in many places. A histological diagnosis of malignant meso thelioma ffibrous type) was made. tMsi. : . A 30-year-old male, rheniist 111 a sugar taetoi v wa- hospitalized with a cough o f is davs' 07b \rsi- N.Z. I. Scue,. V. -D X \ r c . r s r . 1076 m i -; I'l l 1!M \ and ';:ui a,-=<iy ri'vivfi! spncea rlln-inn i was ' ' K tuJ) soiij kU p , . . . , ,,,mic [ ,, . : l,lr !it- V " ! --.ifiin-m. hut hi:: '-"'I'* < a ng/it-sidcd '"c entire right ' ' l n 01 'iiniinislii-rl i * \ s i-.r u i : f t t t y t n t t e o n t r d ,o ^ 's-ioi.ca ,, A ir E A ,,.,11;;:..."v i " ' n|!'k,t foll owing 1:1. Ah iii! of |,.p ,. . n i `i ` , " SSIOM yielded ''"<! - a ,,: ' ,U` >aec l;,l'l",,g. Tla- ,.1,-aral lb,,',. , k' , !V'l""aM daily or malignant cells 1 ' 1" 1nu'' 110 organisms reduost o u b s 1: ; :; :;; :;: ;' 10 i^ m af m * < t l o p ^ S ,a' v l i , v a r ' h WCi e po,- ^ "a'1 th h Ita ly 'ear r t - n T , firaimlar and eosinophilic with wcr I rt.e .|,d ' m' V , he " r a i o r i t v o f cells -- present S ' , Fibrous t -,L 111 on.ielmsg aieas were also tumour cells h u t i i ^ areas sc!?ara' ed the groups of 'm..or,,luc or ,,`tilted tyjie Iras'm ade 'ma 'h-static deposit i a ti":,, Itant'pitot iron ilf,: S " " " TM : - ' ' ' ft section -- i-eiicnf-'o;;;,,,;!:;;""; ^ ..^ o - H ospital course.... |u v ;(... , mulation <,f nlcur'il ft,,; i i K reaccu cxploratorv thoracotomy T 'C .,ln,'erwent right " a s filled withh TM r'T a -!'C p,e'"'al collapsed and bound dowi lu "f I 1C ,,n? M'l'^ r c d deposits on its surface \ ''' T P ^ '>uour mass was present over lar^e a r e a f o T m ^ tum ,,r and lower parietal nh-m-. i ! , f thc I'ster or H.c diaphraRm and Vl,^ "I ' !'C an le ''ctweeu Innumerable small tumour 11> >'<c!ri,)r cbest wall, of the Visceral and S , ;ll,`" os" s a>< aspects so in the lower portion o i t " ^ 't WCre Scc"' niorc 'he diagnosis o f i n . J J . e In ff 'CSt " ' ' Y W i" ' 6 " aS trea*Pd radiofht rapy ' an^'ttltiphos-' I'lcural n n - s o t b e l i , " ,!U',a ' l:l5,s ! r ">- the nrscrssmv Afesotbi-li,,,,,,, is a hi-noitr, am! its i behaviour n - t ;.. it /' dniplcx tlierapeutic problem. T ile I' r f ' ' 'aS <!,V,f,wl in t" tw o owups. n s. group co ,,s,sts of solitary, 'h e n i " ' I t ' t 'Vl'T h a n ' ^Ticallv resectable and a " nn<! Prtnrnosis. whereas the second S i TM T , T n ffUSe tumours Ot r T 0ca,,-v ;? a P a s s i v e ,,tanner, fitallv ) l" av<;ura,),e Pro?nosis and end p,;,,TM o>*w "' Site of Origin . . r l 'i u s 1' ' 1]rl,,cc>,!t,m " ; : r s ';ilf : : <- ,,f. ris :p lining!] less frequently, from the pmiomeum pencare!,,tnt and other serous membranes. In 1 enes, four patients had pleural mesotheliomas and one had a pericardh meso hehoma. Front our review of 'the Htera- ' !t " l,Id sce|u that there has l.een much A i si. K.Y.. j . Sin;., \ 'oi. 4*0(i V-no0. 3,, A\ ,c.c.rsT, 1076, MKSt 1 i Cfatlus i, and 11a variahil- matn-, prevail;' cept t; endotla Ruber; .helievc hig- to t an o( siittrco. Ral iin nated and it - Or, The largels 7<>1111 -.1, holies ireact it 1 matnrcert run PUllli. i! (Wam Selikui prothu ashc-A, i\V ;ipatioii- ('X|)< I--I the rn -''lipa; patie-r itlcr ( , and th f indie patien Phis ; in the the allied remai proce- dried and < say at the p cess, prod-c, ashes' Acs UI >or. ral he tich e a wnthe kms mps .uity vith cells ace. In i>eri>il V h a 'o<is also of cells also i>tOa of posit i 1)V : ceil The i'ph.ic cells i ni deal tile : its iour ileni. nips. ;ign" and fond ours nner. end and >ngm mate, K'tun, In enral i reliai iteramuch . ir>7fi M E S O T H E L IO M A IX 1X1)1.\ 1 j confusion and controversy regarding the origin i and nature of this lesion. Its histological variability from a sarcomatous to a carcino matous appearance has also contributed to the prevailing confusion. The time-honoured con cept that this tumour originates as an endothelioma lias been discarded. However, Robertson and Willis (1967) did not believe that these tumours existed, and accord f ing to them, they represented mtastass from an occult, unrecognized or latent primary source, possible in the lung. Klemperer and Rabin ( <173 ! b felt that the solitary type* origi nated from the suhpleural connective tissue and iti- diftn-e varit from the pleural surface. Occupational Exposure, uhtwloc/v and Ilistoc/cnesis : The retiologv of mesothelioma remains f largelv unsettled. However, llrown .and Johnson 1105C1 and mane' other worker believed that it resulted from the histological = reaction si-condarv to the irritation and inflaminalorv process in the pleura. 'Phis concept certainly suoports the clinic nl association ot pulmonary ashestosis with mesoihelioma IWagner of alii. 1<)<*>: I'lotinhane, 19* >1 \J Selikoff et alii. 1964), as does the experimental production of mesothelioma by instillation of a.diestos dusts into the pleural cavitv of rats i Wagner. 19621. Hut in none of our five patients was there anv chance of occupational exposure to asbestos, as thex all belonged to die rural contimniiiv. having association with ! sugar-cane tanning and related trades, Four ,,atienis belonged to the non-industrial fann ing community, engaged in sugar-cane fanning mid the making of jaggery fgur) and molasses (indigenous sugar-cane products). The fifth i patient was a chemist in a local sugar facture. [ 'fids observation provides one more possibility I in the unsettled etiology of this lesion. Whether the association of sugar-cane fanning and allied trades has any tinlogical hearing or not remains wide open for speculation. In the process of preparing jaggery and molasses, dried and crushed sugar-cane is used as fuel, ,nd emits irritating fumes, ft is difficult to -iv at this stage if these fumes could irritate the pleura and promote an inflammatory pro cess- However, since mesothelioma 1ms been winced experimentally hy instillation of la"s'1bestos, dust into the pleural pace oi rats Me X / 1. V.M \l [!>"0 i )AS ET AI.I I (Wagner, 11)62) and by the use of diatomaceous earth and polyurethane (Hueper, 1964), it is quite possible that the dust or fumes from the burnt or burning sugar-cane could also produce irritation and an inflammatorv process in the pleura and result in the production of a mesothelioma. This certainly calls for a critical analysis ot all cases reported from the sugar-cane growing areas and neces sitates a lookout for any new case coming from these areas, before one can blame sugar-cane as one of the a-liological factors. Also, some experimental work in laboratory animals may he essential to prove this point. In this regard, we have reviewed seven autopsy cases, five reported hv Aikat et alii ( 1474) and two by Kshirsagar et alii ( 1 9 7 1 1 . and three docu mented cases reported by Reddy (1950), Keddv et alii ( 1974). and Chandurknr et ah: ( IQ/O. and found that all these cases also came fmm the non-industrial rural community. However, it is not clear trom the case histories whether or not anv of these patients was associated with sugar-cane fanning, hut two autopsy cases reported hv Kshirsagar et ahi U971O and the case of C'haudurkar et alii ( 197C) did come from Maharashtra, a belt oi intensive sugar-cane tanning in India. litis observation, along with our finding in five patients intimately associated with sugar-cane fanning or an allied trade, indicates that there must be a factor in the non-industrial rural areas connected wit It fanning responsible for inducing mesothelioma in the same wav as asbestos is. Further investigations are required to prove this point. The histopathological variation of rneso thelioma can be explained ;etiologica11y ot embrvolngicallv. The pleural cavity is lined by somatopleura and splanclmopleura, both o! which develop) from the mesoderm, and there fore both epithelial and endothelial structures could develop either separately or in combina tion (Hrschel and I'aulson. 1964). I tilizing the tissue culture technique of IMaximow, Stout and Murray (19 4 2 1 and Sano et alii (0)50) con firmed the mesothelial origin of these tumours, and Stout and Murray ( 1 9 12) demonstrated the traiixfonnatmn of mesothelial tissues into fibroblasts with the production of collagenous material. Thev also showed that a benign mesothelioma can produce epithelial cells in ii-'Mic culture. Satio t'l alii i o p r 11 demonstrated M E S O T H E L I O M A L\' IN D IA D A S L T Al.lt that the malignant variety of mesothelioma can also produce epithelial cells which ordi narily are not seen in the sections. I ater Manguikian and Prior (11/13) confirmed that the reaction of msothlium to injury could be m the form of cuboidal. columnar and epithelial patterns accompanied by papillary processes. Thus the multipotentialily of the tumour is demonstrated on a cellular basis and is con firmed by its clinical behaviour. It has been seen that many of the benign mesotheliomas appear malignant histologically, while some of the clinically malignant mesotheliomas lune a benign histological appearance (Urschel and Paulson, 1065). Diagnostic Methods Besides a detailed clinical history, physical examination, and routine investigation inclu ding skiagrams of the chest, diagnostic modalities such as thoracocentesis, pleura' biopsy, and ultimately exploratory thoracotomy, are available to establish the final diagnosis Skiagrams of the chest, if pleural effusion i> not present, would reveal the intrathoracic or mediastinal mass if present and would show the radiological sign ,,f scalloping : Ursclwl and I aulson. ipoyi. riioracoccnto''' could he helpful in more than one wav. In addmon D recovering pleural fluid for bacteriological biochemical and, cytological studies, i; clear.' the way tor a better skiagram in which; without Symptomatology it the intrathoracic mass or tire radiological .The classical presenting features of a patient with mesothelioma^ are chest pain, breathless ness and cough, lint patients may also have If. ss frequent complaints such as loss of weight , weakness, fever, abdominal symptoms, chills, sensation of fullness and tightness in the chew' and backache. In the patients described in this report, breathlessness and loss of weight fall five patients) and chest pain (four patients) were the most frequent complaints. However, fever with chills and hemoptysis were present in one patient (Case 2). ' . Physical examination of a patient with diffuse mesothelioma usually reveals signs of pleural _effusion or a large intrathoracic or mediastinal mass. Occasionally, clubbing of the fingers and features of osteoarthropathy mav he present. In this report, three patients had sign ^of scalloping could lie ma-kw] by tie' effusion. Needle biopsy of the pleura is a bed side procedure and. if done properly can provide the diagnosis. The use of a manually operated high speed drill is an improvement over : " ordinary needle biopsy. However, the disadvan tage of needle biopsy is that it provides nnlv a small piece of tissue, which makes the defini tive diagnosis difficult in these histologically variable tumours (Urschel and Paulson, 1065V Dndoscopy has no role in the diagnostic work-up. and lymph node biopsv is usually not called for. Whenever these diagnostic modali ties fail to yield a histological diagnosis, exploratory thoracotomy becomes neces>arv. In I all five patients in this report, exploratory I thoracotomy was done with a view to diagnosis I and possible surgical treatment. massive pleural effusions (Cases 3, 4 and 5). which_ reappeared immediately after thoraco centesis. The pleural fluid was blood-tinged in one patient (Case 5). No evidence of clubbing or pulmonary osteoarthropathy was present in any of our patients. Metastatic nodules were found on the chest wall in Case 4. apparently at the site of one of several thoracocenteses, and on the scalp in Case 5. The metastatic nodule on the chest wall illustrates how this tumour can spread along the track made hv needle puncture. The scalp nodules in Case 5 were metastatic deposits. Distant metastasis in mesothelioma is unusual, as normally it spreads locally and involves the surrounding structures by direct extension (Urschel and Paulson lo 6 5)- ' PaltiotogicaJ Features Tn the cases described in this report, the tumour was of pleural origin in four patients and of pericardial origin in one (Case 1 ) , in whom it gave rise to a lame mediastinal mas.' which encroached into the left hetnithorax and involved the left upper lobe, three patients had recurrent and persistent pleural effusion t (Cases 3, 4 and 5 !. and repeated bacterio s logical and cytological studies were unreward ing in all five. Cross pathological features \arv according to the type of the tumour. The solitary type is often encapsulated, pedunculatc-d. and easily removable, whereas the diffuse or malignant mesothelioma is characterized bv findings ranging from multiple papillary projections on j 224 \ ust. J. S udc,, Voi.. 46 -- Xo. 3, -\ucrwr. tq" m MESt > th w: the et n'nd < pleura pleura, (ippea; of thi dense whitf turni 1 IO lice lolic appeavarie- Uhi- In ( xten also e mar!,., obli!. : augi-, weiv "Il f and dirq,! wiii. Case che-' m ela li malia t i l d i . Ili'!. tubi patiw logii Pl'o-ri bei,.; a type ubi-.,a the w al an simi..! filer, ,i; ci m ; i type a and t i-t i l a ihai d< ,, - %e.'- L MF.SOTHF.LIOMA IX IXDIA the visceral and parietal pleural surfaces to the encasement of the entire lung in a thick rind of tumour tissue involving the visceral pleura with similar findings in the parietal pleura (Urschel and Paulson, 1965). The appearance of the tumour, in general, consists of thickened visceral or parietal pleura with dense fibrous, firm, pink, white or yellowishwhite nodules or plaques. In our Case 1, the tumour originated from the pericardium, grew to become a big mass, and infiltrated the upper lobe of the left lung. It had a variegated appearance. In Case 2, the tumour was also variegated in appearance. Though the lower lobe was stuck to it. it was well circumscribed. In Case 3. the tumour was really diffuse and extensile. It had encased the left lung and also infiltrated it. The parietal pleura was also markedly thickened and nodular and had obliterated the cardiophrnie and eostophrenic angles. In Cases 4 and 5, the gross appearances were more or less the same. The lesion was on the right side in both. There was diffuse and nodular growth over the mediastinal, diaphragmatic and posterior parietal pleura, with multiple small deposits everywhere. In Case 4 there was a metastatic deposit 011 the chest wall, and in Case 5 there were multiple metastatic nodules in the scalp. ' T11 this series, there were four diffuse 1 malignant mesotheliomas and one benign mesoI heliomn. though this was not localized. Histologically, there were two cases of uihulopapillary type (Cases r and 3'). Two patients (Cases 2 and 4) fell into the histo logical category of fibrous mesothelioma. One of these tumours (Case 2 1 was benign. Bmmrphic or mixed histological features were present in Case 5. Thus the cases in this report i belonged 10 the three principal histological tvpes 01 mesothelioma, viz., tuhulopapillarv, fiiirmi' and himorphic (Oels cl alii. 10 7 1). In i the tulmlopapillary variety, there is an attempt 1 at acinar and papillary formation with oecasional duets of epithelium-like cells. The | fibrous mesothelioma consists of spindle cells and collagenous fibres and resembles fibrosar coma. The himorphic variety is really a mixed tvpe and presents a varied mixture of epithelial and fibrous elements. The interesting feature of the biological behaviour of mesothelioma is that its benign histopathological appearance Joes not necessarily mean that the tumour is Acst. NT. T. S urg.. Vol. 46-- Xo. 3, Acgusi, 1976 HAS f t ALII indeed benign, and similarly its malignant picture docs not necessarily correspond with its benign behaviour (Urschel and Paulson, I 96S)Distant metastasis is uncommon in meso thelioma. In our cases, evidence of metastasis, by direct extension or by hacinatogenous spread to remote areas, was found in four patients. In Case 3 the tumour deposits were found in lung tissue, apparently due to direct extension, and in Case 1 the pericardial mesothelioma had invaded the lung by direct extension. The tumour deposit on the chest wall along the needle track of a thoracocentesis, seen in Case 4, is an interesting finding and brings the hazard of the needle puncture of a tumour into sharp focus. The only example of distant metastasis was seen in Case 3. Clagett ct alii (19 5 2 ), Kshirsagar ct alii ( 1 9 7 1 ) , and Reddy el aln ( 1 9 7 3 ! found no evidence of distant metastasis in their cases. Generally, metastasis in a case ot mesothelioma is bv direct extension, but occasional Ivmph node metastasis has been reported in isolated cases, particularly in the till ndopapillary variety ( Whitewell and Raweliffe, 19 7 1). The finding ol metastatic deposits in the scalp in Case 3. who had the himorphic type of malignant mesothelioma, is definitely an unusual finding. In three eases in this report, pulmonary resection became necessary, providing an opportumlv to examine the pulmonary tissue lor evidence of asbestos or asbestos like bodies, and apparently none was found. Urschel and Paulson 1 11)65) also were unable to demon strate asbestos Imres m anv of their cases. !'i t'dtm ai! ami / 'rt><;nosis Treatment of diffuse mesothelioma in general is not -sUislaclmw. but for the localized varietv, surgical excidon i- the preferred therapeutic modalitv. However, the treatment of a case ot malignant mesothelioma is frus trating. There have been no cures. Isolated instances of survival of four to six vears have been reported (f.eRnux. 19112; Urschel and Paulson, 1965; Porter and Cheek, 1968). However, malignant mesotheliomas have been treated by thoraeoloiuv and biopsy, followed by radiotherapy and chemotherapy. Earlier, pleuro-pncuinouectomy was advocated, even if it was subtotal, to accomplish an obliterative reaction and prevent reformation of pleural 22^ m e s o t i i k i .iom \ y i \ im \ Hiii-I I l rsrhel and 1 'aui: mi, 1,4,3), 'Die currcn! trend is to treat these patients with dosed luhe thoracostomy. As an alternative to surgic.d excision, tadiotlierapy and chemollicrnpv I m e been used. Wide variation in results and survival times makes any critical evaluation difficult. .Nevertheless radiotherapy is recom mended when excisinnal surgery is impossible or incomplete i i-eRonx. T062; Porter and Cheek, J<j6S). Urschel and Paulson iioC -) also noted improvement in many of their patients following radiotherapy. T11 this review, the result of surgical extirpation with a good surgical margin has been quite good i i A w o patients (Cases 1 and _m , hut in a third patient (Case 3), in whom even with pieuropneumonectomy the resection of the tumour was incomplete, surgical treatment had to he supplemented with radiotherapy and chemo therapy. hi the remaining two patients the tumour was not resect able 011 exploration. Radiotherapy in conjunction with chemo therapy (cyclophosphamide) proved quite beneficial in Cases 3 and 4. They experienced considerable improvement in lheir general con dition, with relief of pain, and there was reduc tion 111 the size of the mass. Those patients are still doing well, ten and eight months icspectivcly following their diagnosis. TTowr \ t*i, there was no response to radiotherapv and chemotherapy in our Case 5. Actuallv, the patient started going downhill and had already developed distant metnstases. Two patients. Cases 1 and 2, who had satisfactory extirpation of then tumours, arc doing well and have remained asymptomatic 26 and 24 months respectively since their surgery, with no evidence of recurrence or dissemination. , The prognosis in malignant mesothelioma is poor. Most patients die within a year or two fi(mi the time 01 diagnosis. The prognosis is worst in patients with the bimorphic variety of the tumour. The variation in survival lias D A S KT AMI iar ranged in mi [our months to live jean ` Urschel and I'atilson, 1903). i\ 1 :o ki' x , i AlK.yi, Li. tv., R x i j i i a k r i s h x a x , V . V. and M alis. , R- M'074), Indian J. Cancer, 12 1 93, lioHKKow, M.. Co n s ig n , A, I.ivoicxKsy L :w ; ScicM.1,1, X. (1974), Dis. Chest, 64: 641. J-.icowx, \ \ . J, and J o h n s o n , L. C. ( 1 951), .'Ml' Xii/a/., 109: 415. ' ' C-i 1AXLiUK KAR, S. N., K h a x u k k a r , a . L ,, S hivo : -V. V. and K:iii:k, A . V. f 197c t , Indian J. Che: , lh s ,, 17 : 139. t. i.AGKir, O. T., M cDonald, j . 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(1024V, J . Cancer Res., 8: 317. S axo , M. In, W e i s s . E., and G ault, E. S. (1930), J. thorae. Snrg., iq : 783, ' S eliko ff, I. V. C hurg, J . and H ammond, E. C. (1064), /. .h a rr. wed. Ass., 188: 22, S tout, A. P, and M u rray. M. R. (1042), dreh Path 34: EM. U r s c h e l , H . C. and P a u l s o n , D. L . (39 6 ) , Ann. thorae. Snrg. 1 : 559. ' ' W agner, J. 0 . (1962), Nature (Loud.'). 196: 180. W agner, J . (.., S legos, C. A. and M arcttand, P. | (i960), Brit. J. industr. Med., 1 7 : 260. i W il l is , R. A. (1067), " Pathology of Tum ours", 3rd j edition, Biiiterworliis, Washington, f).C : jSo. 1 W h ite w e l l , !'. and R awcl iffe, R, M. f ro 7i) i Thorax. 26: 6. ' f1 TRAUMs nun Tu.\ 1 child i surge m the a y dislocai and u h Some prcvii u Tl, survevi area w skeh-i a ' 2-8 n, 1 1-5 M Tin- of ihiot the assoc mi stain-. either aliniir; moti' or lini radii >k < )\ groW orca i' 1 Pr, Zcalan R. ' Orli' 1 koto- e 226 A u s t . N.Z. J. S lu g,, V ol. 46 -- No. 3, A u g u s t , Am.. I V !