Document gDp1Mk6NpDjprrdyYDRY6pkk9

.ITEtLA........ COPIED BY MCA FOR DISTRIBUTION TO THE VINYL CHLORIDE TECHNICAL/ PANEL, NOVEMBER 11, 1976, MR. MILTON FREIFELD /C^ HEPATIC ANGIOSARCOMA IN A VINYL CHLORIDE WORKER P. M. Smith, M.D., M.R.CP. D. M. J. Wiluams, ALB., B.Ch. AND D. M. D. Evans, Al.D., M.R.C.P., F.R.C Path. Iteprinted from m'M.r.TIN <>P TI1K NKW YOUK ACADKMY OP MKOICIKK S^vfiiul vol, .v,\ net. 4, ]i]. 417* M*2, May 1970 IV/6, !>- ihf \tw Vrk A<;<l(iit)r <if Medictfi* ucc 002776 HEPATIC ANGIOSARCOMA IN A VINYL CHLORIDE WORKER P. M. Smith, M.D., M.R.C.P.; D. M. J. Williams, M.B., B.Ch.; and D. M. D. Evans. M.D., M.R.CP., F.R.G Path. Lkodouffc Hospital B.F. Oicwcslt International United Sully PmartK, Glamortio, Wild Endand ore than 38 cases of angiosarcoma so far have been confirmed M among workers exposed to vinyl chloride monomer gas (VCM) during the manufacture of polyvinyl chloride (PVC). The median in terval from first exposure to diagnosis was 17 years; the average time of exposure was 16 years.1 We are reporring on a patient whose exposure to VCM lasted only 3 '/ years. A 36-ycar-oM white male was admitted to the hospital for treatment of peptic ulcer pain that had recurred intermittently for 15 yean His health otherwise had been good; he did not smoke and he drank very little alcohol. For 3 % years he had worked as a "polycleaner," a cleaner of polymerization vessels in a factory where VCM is processed to PVC. Afrcr this he had worked for three years prior to admission as a store man of raw materials, handling resins only. On examination the patient looked well; the only abnormal physical sign was a liver palpable to 6 cm. Barium meal revealed the presence of ucc 002777 44 8 i*. m. `'Mini and oim.us Fig. 1. Focal severe sinusoidal dilatation on liver biopsy ( X 500) a deformed duodenal cap. At operation a large duodenal ulcer was found, for which a P61ya parrial gastrectomy was performed. The liver 1 appeared cirrhotic, with grossly distended veins forming a collateral circulation in the anterior abdominal wall and the falciform ligament. Tests of liver function gave normal results, but an operative liver biopsy showed noncirrhotic fibrosis; there were several foci of severe dilata tion of the sinusoids (Figure i). Recovery from operation was uneventful. The scrum alkaline phos phatase level rose to 87 I.U./L (normal range: 15 to 40) after six weeks, but all other liver-function tests and the erythrocyte sedimentation rate were normal, apart from a bromsulphalcin retention of 17% (4J min.). Tests for smooth-muscle and mitochondrial antibodies and for Australia antigen were negative. One year after operation rhe patient was working full rime as a dock laborer. There were no abnormal physical signs apart from the enlarged liver. Liver-function tests now showed a further rise in the scrum alka line phosphatase level to 115 I.U./L, with an elevated bilirubin value of 31 /imolc/L (normal range: j to 17). Bull. N.Y. Acid. Med. UCC 002778 HEPATIC ANCIOSAKCOM \ 449 4 m , vn liver rcral nent. opsy llata- ihosecks, rate fin.). ralia Jock rged ilkaalue Med. Fig. 2. Gross appearance of liver at postmortem Four months later he was admitted to the hospital as an emergency patient. He now had dyspnea, ascites, ankle edema, and jaundice. He looked ill and wasted. Liver palms and numerous spider nevi were pres ent. The liver extended io cm. below the costal margin. Diuretics caused an appreciable loss of edema, with great relief of the dyspnea. Results of the liver-function tests were grossly abnormal: serum biliru bin 103 /*mole/L, alkaline phosphatase no l.U./L, serum glutamic oxalacctic transaminase 35 I.U./L, albumin 17 gm. 'L, globulin 40 gm./L. During the next month the bilirubin rose steadily to 390 /uno!e/L. A scan showed the liver to be massive, with numerous areas of decreased uptake. A hepatic arteriogram revealed a widespread pathological cir culation, with multiple areas of tumor blush, suggestive of a highly vas cular multicentric hepatic neoplasm. Tests for o-fctoprotcin and carcinoemhryonic antigen were negative. A barium-swallow test demon strated varices. Dilated veins appeared on the anterior abdominal wall, but at no time was a hepatic bruit heard. Soon afterward the patient lapsed int hepatic coma and died. At necropsy there was edema of both lungs. The right lower lobe Vol, 52. No. 4, May 1976 ucc 002779 Fig. 3. Postmortem hqiuUc tttiugruiii showed patchy collapse and consolidation and evidence of several hem orrhages. The pericardium contained clear yellow fluid but there was no significant ascites. Apart from the old parrial gastrectomy, the ali mentary tract was normal. l'hc fiver weighed 3,140 gm. and was greatly enlarged by a vascu lar tumor which had almost completely replaced normal hepatic tissue (Figure i). Large blood lakes and cavernous vascular spaces were shown well by injection of barium suspension into the hepatic vein after death (Figure 3). Hie spleen was congested and very firm, bur weighed only 100 gm. Microscopy showed replacement of much hepatic parenchyma by hemorrhagic and necrotic tumor tissue. The tumor consisted of vascular channels, varying grcatlv in size and shape, lined hv plump endothelial cells ami also by large multinuclcatc. tumor cells (Figure 4), believed IIITA I ir. angiosarcoma 45 i Fig. 4. Microscopy of turnor (X 500) to be malignant Kupffer cells. In some parts of the tumor these cells were sparse and the dilated sinusoidal structure resembled that seen in ihc biopsy specimen, bur in other parts these giant tumor cells were very numerous. A few had desquamated into the vascular channels and there was evidence of ruinor-ccll embolism in the pulmonary hemorrhages, although no cohesive metastatic tumor tissue was found in the lungs or other organs. Discussion I his patient was remarkable in several respects. The duration of ex posure to VCM of 3 fi years, compared with the mean of 16 years for rhe previously reported 38 cases of angiosarcoma, was unusually short. Only one younger case has been described. The latent period from rhe first exposure to VCM to diagnosis was eight years, whereas for the other reporred cases ibe mean interval was 17 years (range: it to 30 years).1 Wc have no evidence that the exposure to VCM was in any way unusual; in particular, tlu- patient bad nor been a gas "sniffer" and Vol. 5?, No. 1 May 1970 ucc 002781 ) 4J J 1`, M. SMITH AND OIIII l(S liis subsequent periods <4 employment bad consisted of laboring and bandling bananas. He had. however, been a polyclcancr, and 84% of cases of V'CM-treated angiosarcomas so far described have occurred in persons similarly employed.1 2I fc is only the second patit nt with angio sarcoma to be reported in Hritain, lhis patient also was tj111usu.il in thar the liver biopsy performed 1$ months prior ro his death (revealed striking focal dilatation of the sinus oids. This change has been described recently in the early stages of some other angiosarcomas linked to vinyl chloride.* We have pirformed liver biopsies on a number of other VC\I workers with apprcci ible periods of exposure, bur have seen only a noncirrhotic fibrosis11 ana arc unable to confirm that the sinusoidal dilatation can be considered a precursor to. the formation of tumor, k is to be hoped rhat stricter environmental controls will prevent furthjcr angiosarcomas arising Ac novo, bur work ers who have already developed portal hypertension and those who have been exposed to high concentrations of the chemical in the past must be monitored carefully in the future. Summary A man aged 36 years who had been a VGM process worker for only 3 Vi years was unexpectedly found at laparotomy for a ptptic ulcer to have an enlarged liver and porral hypertension. Biopsy showed striking focal dilatation of the sinu^iids. Fifteen months later the patient died of a hepatic angiosarcoma, i Acknowledgment We thank Dr. G. dc B. l lindc for the radiological sri dies and Mr, D. A. Aubrey for referring the patient. RRh'ERK .V C E S 1. J.lmi!, M',: Aii{tiiMtrnmm ! (if (he liver ii> vinyl diloridr/|M*lyvmJd diln* riU* workers. J. (Peruft, Mnl. I9T1 2, 'Hhhii.i.s, I,, 11.v I'lntjtcr,, II., Itcrlf, I*. 0.t KrlikufT, I.t rtiul Kuffc, If.; dii- ride imlitvod liver diuuse. ,V#v J. Metl kt:17*. 1971. Smith, l*. M. aimI Willi-iiiif, D. M. J.: Vinyl dili*ri<|f nmt d /JiyrWuiN *21, 1971 t d Outlet C Mm&mi C., Inc., N.Y.G ucc 002782