Acta Pathol. Jpn. 37(3) : 375-383, 1987

A QUANTITATIVE STUDY ON THE DISTRIBUTION OF ASBESTOS BODIES IN EXTRAPULMONARY ORGANS

Hiroshi KOBAYASHI, Zhang Wei MING, Hisashi WATANABE, and Yoshihisa OHNISHI

Department of Pathology, School of Medicine, Niigatu University, Niigatu

We made a quantitative study of the distribution of asbestos bodies (ABs) in 13 extrapulmonary organs. We selected 26 male subjects and subdivided them into three groups : Group I had loz to less than lo3 ABs per gram of wet tissue in their lungs ; group I1 had 10 to 99 ABs ; and group I11 had no ABs. In group I, one or more ABs were identified in at least 6 (53.8%) of the examined extrapulmonary organs. In group II,23.7% of the examined organs had one or more ABs. In group 111, no ABs were found. These results seem to indicate that with modest exposure in the lung, the other organs are often exposed to asbestos with some degree. Moreover, the number of AB in the esophagus was significantly larger than that in 9 of the other 12 organs in group I. The pancreas and the spleen were also supposed to be more preferential sites of exposure. However, the relationship between exposure and its effects in extrapulmonary organs remains to be elucidated. ACTA PATHOL. JPN. 37 : 375 - 383. 1987.

Introduction

ABs are found with a high rate in the lungs of the general p ~ p u l a t i o n . ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ Therefore, the air pollution of asbestos seems to be quite certain. Moreover, asbestos fibers (AFs) are present in the ~ a t e r , ~ . ~ ~ beverage^,^ and drugs.1° So, the possibility of exposure by way of the alimentary canals are d i sc~ssed .~J~ Several epidemiologic studies indicated the increased risk of gastrointestinal malignancies in high level of e x p o s ~ r e . ~ J ~ . ~ ~ In addition, a few investigators reported an association of extrapul- monary diseases such as rnyel~ma,~ immunoblastic lymphaden~pathy,'~ and autoim- mune diseasesz2 with asbestotic patients. We also previously reported a case of asbestosis with generalized fibrosis and demonstrated the presence of AB and AF in various affected organs.13

A small number of ABs and AFs were found in pleural plaques and the migration of AF through the visceral to the parietal pleura and through the diaphragma to the peritoneum were suggested.26 Some authors discussed a few ABs were occasionally

Accepted for publication June 13, 1986. Mailing address : Hiroshi KOBAYASHI (+;Mia), Department of Pathology, School of Medicine, Niigata University, Asahimachi-dori 1-757, Niigata City 951, JAPAN.

3 76 ASBESTOS BODIES IN EXTRAPULMONARY ORGANS Acta Pathol, Jpn .

present in extrapulmonary organs on tissue ~ections. '~-~' In experimental animals injected AFs were proved to migrate to various organs.11J6 Thus, we have acquired some certain knowledges of the movement of AF to the visceral organs.

However, few informations have been given on the true intestity of burdens in extrapulmonary organs and the exact route of migration. And, the causal relationship between asbestos exposure and the changes of extrapulmonary organs has been poorly established. To our knowledge, only one study demonstrated the semi-quantitative results on asbestos distribution in various organs.' In this paper, we report the quantitative study on asbestos burdens in thirteen extrapulmonary organs of 27 subjects.

Materials and Methods We selected twenty-six male subjects over the age of forty years among the consecutive 656

autopsy cases. We had previously examined AB and AF counts in the lungs of these 656 patients and reported in another paper.'' Twenty six patients were separated into three groups according to the degree of asbestos exposure in the lungs ; the first group had lo2 to less than lo3 ABs per gram of wet lung ; the second had ABs ranging from 10 to 99 ; and the third had no ABs in the lungs. In addition, one case with high level of exposure was available for this study. Only this patient had a past history of handling asbestos, pulmonary asbestosis, and over a thousand of ABs in the lung. This patient was not included in group I. And, since several organs of this patient had been embedded in paraffin, we did not employ this case for statistical analysis.

We took five grams of formalin-fixed wet tissues from 13 organs including the esophagus, stomach, small and large intestines, spleen, pancreas, liver, heart, kidney, urinary bladder, bone marrow, thyroid gland, and adrenal gland. If 5 g of tissue were not available, the tissue used was weighed and the observed number of AB was converted into the number per 5 g of tissue. We employed the KOH digestion method modified by us as described previously.14 Bone marrows were decalcified in trichloroacetate before digestion. ABs were collected on membrane filter with 0.8~ pore size and counted by light microscopy at x 200 magnification. We regarded ferruginous bodies with transpar- ent, colorless core as AB. The subject's age, occupation, and primary disease were obtained by review of the subject's chart.

Results

The ages, occupations, and primary diseases of the subjects are listed in Table 1. Asbestos distribution in groups I and I1 is shown in Tables 2,3, respectively. In group 111, all 13 organs were available for counting of AB, but no ABs were found in any examined organs. In group I, one or more ABs were identified in at least 6 (53.8%) of the organs. Its mean incidence was 66.8%. In group 11, from 0 to 53.8 (mean 23.7) yo of the examined organs had one or more ABs. This result revealed that group I had a higher incidence of AB than group I1 and I11 (P<O.OOOl). And, group I1 had also a higher incidence of AB in organs than group I11 (P < 0.0001).

In group I, a large number of AB was found in the esophagus and comparatively large number of AB was also found in the spleen, pancreas, bone marrow, and thyroid gland. As shown in Table4, the number of AB in the esophagus was significantly larger than that in 9 of the other 12 organs. The spleen and the pancreas also had more ABs than 6 of the other 12 organs (P<0.05). But the difference in the number

37(3) : 1987 H. KOBAYASHI et al. 377

Table 1. Age, Occupation, and Primary Disease of Subjects

Occupation Primary disease Subjects' number Age

1 59 Asbestos spraying Asbestosis, pulmonary ca. 2' 62 Construction worker Pulmonary ca. 3* 71 Steel-mill worker Pulmonary fibrosis and ca. 4' 70 Welder Gastric ca. 5* 64 Factory worker Pulmonary ca. 6* 70 unknown Agranulocytosis 7' 80 unknown Renal ca. and reticulosis 8* 41 Plumber Gastric ca.

9.1 78 unknown Pulmonary thrombosis 10" 66 unknown Hodgkin's disease 111' 69 Steel-mill worker Multiple myeloma 12'. 65 unknown Hepatoma 13** 47 Carpenter Liver cirrhosis 14.. 74 unknown Rectal ca. 15.' 64 Police officer Bronchopneumonia 16" 50 Clerk Hepatoma with cirrhosis 17** 79 unknown Rectal ca. 18" 71 unknown Esophageal ca. 19** 67 unknown Pulmonary ca.

20** * 21*** 22*** 23"' 24*** 25** * 26* * *

27***

70 87 58 70 60 53 61

59

unknown unknown Teacher unknown unknown Clerk Automobile service man

Carpenter

Gastric ca. Colon ca. Pulmonary ca. Peritonitis Liver cirrhosis Pulmonary ca. Hepatoma Colon ca., Ca. of urinary bladder

* : group I, : group 11, **I : group 111, ca. : carcinoma

of AB was not significant in the bone marrow and the thyroid gland. In group 11, the esophagus had the largest number of AB. This number, however, was not statistically significant as compared with that of any other organs.

As shown in Table5, the difference in the number of AB was identified in the esophagus and the small intestine between group I and I1 (P<0.05). Namely, in these two organs the number of AB in group I was larger than in group 11. There was a similar tendency of the difference in the spleen, pancreas, kidney, and thyroid gland, but their differences were not significant. The difference in the incidence of AB between group I and I1 was demonstrated in the esophagus, pancreas, heart, bone

3 78 ASBESTOS BODIES IN EXTRAPULMONARY ORGANS Acta Pathol. Jpn.

Table2. Distribution of

1 3,000 214 1 2 1 2 460 9 1 2 0 3 396 23 1 2 5 4 202 21 1 N.E. 1 5 986 12 4 2 1 6 698 3 2 0 0 7 228 N.E. 2 1 2 a a9o 25 0 0 0

0' 7 6

20 2 3 0 a

Mean 551.4 15.5 1.6 1.2 1.1 6.6 S.D. 288.9 8.0 1.2 0.9 1.6 6.1

100 85.7 66.7 57.1 85.7 Incidence (Yo)

I : digested from paraffin embedded tissue. and that in other organs per 5 gram.

N.E. : not examined. S.D. : The mean number, S.D. and the

Table3. Distribution of

Case

9 10 11 12 13 14 15 16 17

19 ia

52 5a 46 40 52 44 34 66 60 68 26

1 0 2 0 0 6 0 0

38 0 0

0 0 1 0 a 4 0 0 0 1 0

N.E. 1 1 0 0 0

N.E. 0 1 0 0

0 10 1 0 0 3 0 0 0 2 0

2 2 2 0 0 4 2 0 0 0 0

Mean 49.6 4.3 1.3 0.3 1.5 0.9 S.D. 12.6 10.8 2.4 0.5 2.9 1.3

36 Incidence (Yo)

36 33 36 45

N.E. : not examined. S.D. : standwd deviation. The number of AB in the

37(3) : 1987 H. KOBAYASHI et at. 3 79

Asbestos Body in Group I

Urinary Bone Thyroid Adrenal gland gland Pancreas Liver Heart Kidney bladder m&pTow

37 21 38 19 1 0 2 3

0 36 0 0 0 7 1 N.E.

10 11 1 1

N.E. N.E. 5 1

0' 7 9 0 1 2

N.E. 2

0' 0

134 0 1 0

N.E. 0

12 0.7 0.6 1.1 2.8 4 3.5 22.5 13.4 1.4 0.5 1.4 3.6 4.3 3.3 49.8

85.7 28.6 57.1 42.9 66.7 80 83.3 33.3

standard deviation. The number of AB in the lung is per 1 gram of wet tissue incidence are of seven patients in group I.

Asbestos Body in Group 11

Urinary Bone Thyroid Adrenal gland Pancreas Liver Heart Kidney bladder m&pTow gland

1 0 0 0 0 0 N.E. 0 0 0 0 0 1 5 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 8 0 0 0 0 2 0 0 0 0 1 5 2 0 1 0 0 8 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 3 0 0 0 0 0 0 0 0

0.4 0.7 0.7 0.1 0.5 0.6 0.2 0.4 0.6 2.3 2.3 0.3 1.4 1.5 0.6 0.9

27 9 9 9 18 18 10 18

lung is per 1 gram of wet tissue and that in other organs per 5 gram.

Tab

le4.

Th

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me

in N

umbe

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esto

s Bo

dy b

etwee

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o fiferent Organa in

Grou

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row

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and

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test

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-

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.. I.

-

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phag

us

n.t.

Sple

en

-

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* *

. -

-

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-

-

-

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-

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-

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Thy

roid

gl

and

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w

The

sig

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sign

ific

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: P<

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Tab

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Th

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fmn

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Num

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Inci

denc

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Asb

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s Bo

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the Same O

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Gr

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Bon

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Adr

enal

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leen

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Num

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AB

1-

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The

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is tested

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37(3) : 1987 H. KOBAYASHI ct al. 381

marrow, and the thyroid gland. And, i t was also identified in all organs except the kidney and adrenal gland between group I and 111. However, such difference was not shown between each organ of group I1 and 111.

Discussion Our patients in group I did not handle asbestos directly. And the number of AB

in the lungs ranged from 202 to 890 per gram of wet lung tissue. These counts could not be considered large as compared with those of asbestotic patients because primary occupational workers including miners, millers, and persons who handled large amount of raw fiber had usually at least more than lo3 ABs per gram of wet lung t i ~ s u e . ~ Accordingly, these patients may be secondarily exposed to asbestos with modest degree. And our present data showed that at least 6 (53.8%) of the examined organs had one or more ABs in these patients. Therefore, this finding strongly suggests that when people have modest or secondary exposure to asbestos in their lungs, at least one or more ABs are present in many extrapulmonary organs. Unfortunately, only one subject with a high level of exposure was available for this study. But, this patient had comparatively large number of AB in several oragns except the spleen, thyroid gland, and adrenal gland which had been embedded in paraffin. AUERBACH et al. demonstrated that ABs were found in many extrapulmonary organs of the subjects including 19 cases with diagnosis of asbestosis and 18 with pleural plaques.' These findings seem to confirm that if the lung is exposed to asbestos with moderate or high degree, the other organs are often exposed to asbestos with some extent.

In general, the portals of entry of AF are thought to be respiratory tract, alimen- tary tract, skin, uterus, and anus.2 The former two tracts may be most probable. Our data showed that the incidence and the number of AB in extrapulmonary organs usually increased as the pulmonary level of exposure rose. This finding probably suggests that the main portal of entry in our subjects was the respiratory tract. In addition, the patients in group I11 whose number of AB was zero in the lung did not have any ABs in other organs. Thus, in our subjects the exposure through contamina- tion of drinking water, beverages, and drugs may be none or slight if any.

Several routes of transmigration of AF and/or AB to various organs are supposed. Namely, asbestos moves by the route of blood and lymph stream to various sites of the body,11*13*15 by penetration through the visceral pleura to the pleural cavity and through the diaphragma to the abdominal cavity,26 and by the transportion from the respiratory tract on the mucociliary blanket to the buccal cavity.2 The present study showed the existence of AB in extrapulmonary organs. In addition, Table 4 indicated that AB preferentially existed in a few organs as the esophagus, spleen, and pancreas. The reason why AB accumulates in these organs cannot be answered in this paper. However, if asbestos migrates only by the route of blood and lymph stream, such predilection of AB in these organs may not find a plausible explanation. We venture to think that one of the most probable route to the esophagus may be swallowing from the buccal cavity where a certain amount of asbestos in the air must enter and is

382 ASBESTOS BODIES IN EXTRAPULMONARY ORQANS Acta Pathol. Jpn.

transported from the respiratory tract on the mucociliary blanket. AUERBACH et al. also showed a higher incidence and larger mean number of AB in the spleen.' One of explanations for this fact may be that the spleen is a major organ of mononuclear phagocytic system where migrated asbestos may be arrested.

Malignancies of gastrointestinal tracts are reported to increase in asbestotic patients from epidemiological s t ~ d i e s . ~ J ~ J ~ But no study in relation to asbestos burdens in the alimentary canals have been done to date as far as we know. As described above, the esophagus was one of the most preferential site of exposure. In addition, Table 2 showed high incidence of AB in the stomach and Table 3 also indicat- ed a higher incidence of AB in the alimentary canals including the esophagus, stomach, small and large intestines than the other organs. From these results we should not draw too-sweeping conclusions. However, we believed that the study on the relation- shop between asbestos burdens and the diseases would elucidate this problem.

Acknowkdqements : We thank Dr. Kazuo ENDO for his statistical advice (Department of Hygiene and Preventitive Medicine, School of Medicine, Niigata University). We also thank Mr. Tomiyoshi HASECAWA and Mr. Susumu MOMOZAKI for technical assistance and Mrs Michiko TANABE for assis- tance in preparation of this manuscript.

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

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