AppendixTissue Digestion TechniquesVictor L. Roggli

Method A

The digestion procedure used by the authorl is a modification of thesodium hypochlorite digestion technique described by Williams et al.2

The details of the procedure are as follows:

Materials

0.4mm pore-size, 25mm diameter Nuclepore® filtersNuclepore® filtering apparatus, including cylindrical funnel (10cc),

fritted glass filter support, and 250cc side-arm flaskVacuum source, vacuum tubing, trap20cc plastic screw-top scintillation counter glass vialsAliquot mixer for blood tubes (Miles Laboratories)Two-sided sticky tapeScalpel handle, clean scalpel bladesForceps (coarse and fine tip)25mm diameter rubber “O”-rings for filtersPasteur pipettes with rubber bulbsRectangular plastic weighing dishesAnalytical balance

Reagents (all reagents prefiltered through 0.4mm pore size filter)

5.25% sodium hypochlorite solution (commercial bleach)8.0% oxalic acid solutionAbsolute ethanolDeionized waterChloroform (caution: cannot filter through Nuclepore filter, as it will

dissolve the filter!)

Methods

Step 1: Selected specimen (up to approximately 0.3gm) is weighed wetin plastic dish on an analytical balance after gently blottingexcess fluid with a paper towel.

402

Step 2: Tissue is minced into 1 or 2mm cubes within plastic dish usingfresh scalpel blade and coarse-tip forceps.

Step 3: Two Pasteur pipettes full of filtered sodium hypochlorite solution are added to plastic dish, and tissue in hypochloritesolution is carefully transferred into a 20-cc plastic screw-topscintillation counter vial.

Step 4: An additional aliquot of hypochlorite solution from a Pasteurpipette is used to rinse the weighing dish, and this is addedto the vial. Two more aliquots (total of 10cc) of hypochloritesolution are added directly to the vial.

Step 5: The vial is labeled for identification and placed on an aliquotmixer with double-sticky tape (Figure A-1). Digestion pro-ceeds until tissue fragments are no longer visible to the nakedeye (usually 20–25 minutes for a 0.3gm sample; however,more time may be required for severely fibrotic or deparaf-finized specimens).

Step 6: The digested suspension is transferred into the glass cylinderof the assembled filtration apparatus (Figure A-1). It is best toadd no more than approximately 25% of the suspension to thefilter at any one time.

Step 7: As the filtration slows, aliquots of 8.0% oxalic acid, absoluteethanol, and fresh hypochlorite solution may be added to the filter surface with a Pasteur pipette to reduce buildup of any

Appendix: Tissue Digestion Techniques 403

Figure A-1. METHOD A: Technique for extracting mineral fibers and other inorganic particulates fromlung tissue. Tissue is first digested in sodium hypochlorite solution (commercial bleach) and the residuecollected on a Nuclepore® filter. The filter may be mounted for light, scanning electron, or transmissionelectron microscopy. See text for details.

organic residues. An aliquot of deionized water should beadded between additions of oxalic acid, ethanol, or hypochlo-rite solution to prevent crystal deposition on the filter surface.

Step 8: After the final portion of the suspension has passed throughthe filter and a final rinse with oxalic acid, ethanol, andhypochlorite solution has been effected, then a final aliquot ofabsolute ethanol is washed through the filter.

Step 9: The filter is transferred from the filtering apparatus onto thesurface of a glass slide using fine-tip forceps. The peripheryof the filter should be attached to the surface of the slide withsmall, torn portions of white, lightly adhesive tape (to preventfolding and buckling of the filter when chloroform is added).

Step 10: After the filter has completely dried, chloroform is addeddrop-wise to the filter surface with a Pasteur pipette until thefilter is covered and cleared. The tape securing the edges ofthe filter can now be removed with fine-tip forceps before thechloroform dries.

Step 11: After the chloroform dries, a coverslip can be added to theslide in a suitable mounting medium (e.g., Permount), and theslide is now ready for viewing by light microscopy.

Step 9a: If one wishes to examine the filter by scanning electronmicroscopy (SEM) rather than light microscopy, the filter canbe mounted on a 25mm carbon disc with colloidal graphiteand sputter-coated with gold, platinum, or carbon (Figure A-1).3 If the examiner wishes to employ transmission electronmicroscopy, then a small portion of the filter can be cut outand transferred onto a TEM grid and the filter materialremoved by chloroform using the Jaffe wick technique.4,5

Notes Regarding Digestion Procedure

In selecting tissue for digestion, one should avoid areas of tumor, con-gestion, or consolidation as much as possible. These would affect thedenominator in calculations of asbestos fiber or body concentrations,and thus would tend to falsely lower the calculated value. The authorprefers formalin-fixed tissue, although fresh lung tissue works just aswell. An adequate sample is at minimum an open lung biopsy; lobec-tomy, or pneumonectomy. Autopsy tissue is even better. Transbronchialbiopsies are inadequate to give meaningful results.6 For lobectomy orpneumonectomy specimens, the author generally prepares two or threefilters, and for autopsy cases, four filters (one from the upper and lowerlobes of each lung). One filter is typically examined by SEM for asbestosbodies and uncoated fibers; the rest are examined by light microscopyfor asbestos body content.

In some cases, only paraffin-embedded lung tissue is available. Insuch cases, a portion is selected from the block, deparaffinized inxylene, and rehydrated through absolute and 95% ethanol. The usualtimes for deparaffinizing tissue are doubled to maximize paraffinremoval, because residual paraffin clogs the pores of the filter, obscur-ing fibers and bodies. The wet weight is obtained from the specimen

404 V.L. Roggli

in 95% ethanol. A correction factor has to be applied to deparaffinizedspecimens because of lipids removed at the time the tissue was origi-nally processed6 (See below).

There may be some variability in Steps 6 and 7 (filtration) dependingupon the individual sample. Some samples pass readily through thefilter and require little rinsing with oxalic acid, ethanol, or hypochloritesolution to remove residues. Other cases may sharply decrease their rateof filtration and require considerable effort to remove organic residues.Sometimes ethanol most readily restores the filtration rate, while inother cases oxalic acid is more effective. The use of warm water rinseshelps to reduce crystal accumulation on the filter surface. If there is sys-tematic slowing of filtration on multiple samples, this may be due toclogging of the fritted glass filter support. This can be rinsed withacetone or hot double deionized water to remove such residues.

Method B

In some cases, the asbestos body content is too low to obtain an accu-rate estimate from a 0.3 gram sample. If an accurate quantification isdesirable in such cases, then the original method of Smith and Naylor7

employing a larger sample size may be preferable. The details of theprocedure are as follows:

Materials

0.4mm pore-size, 25mm diameter Nuclepore® filtersNuclepore® filtering apparatus, including cylindrical funnel (10cc),

fritted glass filter support, and 250cc side-arm flaskVacuum source, vacuum tubing, and trap300-cc glass jar with lidScalpel handle, clean scalpel bladesForceps (coarse and fine tip)25mm diameter rubber “O” rings for filtersPasteur pipettes with rubber bulbs50cc screw-cap conical centrifuge tubesRectangular plastic weighing dishesAnalytical balanceDesktop centrifuge

Reagents (filtration optional)

5.25% sodium hypochlorite solution (commercial bleach)Chloroform95% ethanol50% ethanol

Methods

Step 1: Selected specimen (approximately 5gm) is weighed wet inplastic dish on an analytical balance after gently blotting excessfluid with a paper towel.

Appendix: Tissue Digestion Techniques 405

Step 2: Tissue is minced into 2- or 3-mm cubes within plastic dishusing fresh scalpel blade and coarse-tip forceps.

Step 3: Tissue is transferred from dish into glass jar with scalpel blade.The dish is rinsed with a 2-cc aliquot (one Pasteur-pipette-full)of sodium hypochlorite solution which is added to the jar.Approximately 250cc of hypochlorite solution are then addedto the jar (approximately 50-cc hypochlorite solution per gramof tissue).

Step 4: The glass jar is allowed to sit for several days to allow timefor the tissue to digest and for the asbestos bodies to settle tothe bottom (Figure A-2).8

Step 5: The supernatant is removed by gentle aspiration using aPasteur pipette attached to the vacuum system, being carefulnot to disturb the sediment at the bottom of the jar.

Step 6: A 20-cc aliquot of chloroform is added to the jar to suspendthe asbestos bodies embedded in the sticky layer on thebottom of the jar. After swirling the chloroform to dissolvethese residues, a 20cc aliquot of 50% ethanol is added to thechloroform suspension. The ethanol chloroform mixture isthen transferred to a 50-cc screw-cap conical centrifuge tube.

Step 7: The centrifuge tube is labeled for identification and placed ina table-top centrifuge. A tube from another sample or a tubefilled with water is used as a counterbalance. The specimen iscentrifuged at 200g for 10 to 15 minutes.

Step 8: The supernatant is removed by gentle aspiration using a Pasteur pipette attached to the vacuum system, being care-ful to remove pigment and lipid residues at the chloroform–ethanol interface and leaving approximately 5cc

406 V.L. Roggli

Figure A-2. METHOD B: Technique for extracting asbestos bodies from lung tissue. Tissue is firstdigested in sodium hypochlorite solution (commercial bleach), followed by a centrifugation step to sep-arate the inorganic particulates from inorganic carbon and undigested lipid residues, the latter remain-ing at the chloroform–ethanol interface. The residue is recovered on a Nuclepore® filter, which maythen be mounted on a glass slide for examination by light microscopy. See text for details. (Reprintedfrom Ref. 8, with permission.)

of chloroform and sediment at the bottom of the tube (chlo-roform is heavier than ethanol and settles to bottom).

Step 9: If the sediment remaining after Step 8 is black, then an addi-tional 20cc aliquot of chloroform and 20cc of 50% ethanol maybe added to the centrifuge tube and Steps 7 and 8 repeated.Otherwise, approximately 15cc of 95% ethanol are added tothe sediment and residual chloroform.

Step 10: The sediment is suspended in the 95% ethanol, using vigor-ous shaking or a vortex mixer, if necessary. This suspension isthen transferred into the glass cylinder of the assembled fil-tration apparatus (Figure A-2), and the sediment collected onthe filter surface.

Step 11: The filter is transferred from the filtering apparatus onto thesurface of a glass slide using fine-tip forceps. The slide is thenprepared for examination by light microscopy as described inSteps 9 to 11 under Method A (see above).

Notes Regarding Digestion Procedures

Tissue selection guidelines are similar to those outlined for Method Aabove. Generally, a lower lobe sample abutting the pleura is used. Thevalues obtained for asbestos bodies per gram of wet lung using MethodB are generally quite comparable to those obtained with Method A. Ina study of 10 cases in which both methods were used to quantify theasbestos body content, the average ratio of the results obtained byMethod B to those obtained by Method A was 1.1 (range, 0.3–3.5).9

Although filters prepared by Method B can also be examined by analytical electron microscopy, the author does not recommend thisbecause there is evidence of a significant uncoated fiber loss at the chlo-roform–ethanol interface during the centrifugation step (unpublishedobservations). Others have also reported fiber losses with each sequen-tial centrifugation step.10

It is important to emphasize the necessity for maintaining scrupu-lously clean glassware. Studies have shown that asbestos bodies andfibers adhere to glassware surfaces and may be removed with diffi-culty.11,12 Such loss of fibers or bodies may give a falsely low count. Ofgreater concern, however, is the contamination of glassware with carry-over of bodies or fibers from a case with a heavy burden to a case withvery low tissue asbestos content.13 A new scalpel blade, centrifuge tube,or glass vial should be used for each case. The cylindrical glass funneland the glass jars are carefully cleaned with warm soapy water and ascrub brush between cases, rinsing with copious amounts of deionizedwater. Cleaning with acetone in an ultrasonicator is recommended aftercases with a particularly heavy asbestos burden.

Filtration of reagents is optional for Method B because asbestosbodies derive only from biological systems and do not contaminatethese reagents. (Uncoated fibers, on the other hand, may contaminatemany different reagents and give falsely elevated fiber counts by electron microscopy. This is especially problematic for small chrysotilefibers, which are ubiquitous. Reagent blanks should be prepared and

Appendix: Tissue Digestion Techniques 407

examined to control for this possibility whenever electron microscopictechniques are employed for asbestos fiber quantification.)

Bronchoalveolar Lavage Fluid

In some circumstances, it may be of interest to analyze the asbestoscontent of bronchoalveolar lavage fluid (BALF). This procedure is typ-ically performed by digesting the BALF pellet in sodium hypochloritesolution and collecting the residue on a Nuclepore® filter. For thispurpose, we typically use a 13mm filter, which further concentrates thespecimen since this filter has only 25% of the area of the 25mm filterused for lung digests. The filter may be mounted on a glass slide forasbestos body quantification by light microscopy or on a carbonplanchet for examination in the scanning electron microscope. Count-ing rules are the same as for lung digest samples (see below). Theresults may be reported per ml of BALF or per million (106) cells.13

Counting Rules and Calculations

The morphologic features of asbestos bodies are described and illus-trated in detail in Chapter 3. Asbestos bodies, which have thin translu-cent cores, are to be distinguished from pseudoasbestos bodies, whichhave broad yellow sheet silicate or black cores. The author enumeratesthe true asbestos bodies and pseudoasbestos (nonasbestos ferruginous)bodies separately. Except in rare cases, true asbestos bodies are morenumerous than pseudoasbestos bodies. Indeed, asbestos bodies areidentified in more than 90% of cases, whereas pseudoasbestos bodiesare observed, in the author’s experience, in approximately 25% ofcases. Identification of asbestos bodies by scanning electron microscopyis dependent upon morphologic features in combination with elemen-tal composition as determined by EDXA, since one cannot appreciatethe additional information regarding the color of the core fiber that isavailable from light microscopic observations.

Fibers are defined as particles with a length to diameter (aspect) ratioof at least 3 : 1 and roughly parallel sides. The author does not countparticles with aspect ratio less than 3 :1 or with sides that are nonpar-allel or excessively irregular. Clumps of fibers are seldom encounteredwith the digestion procedures described above. Both asbestos andnonasbestos fibers are counted together (total uncoated fiber count).Although there is considerable morphologic overlap, most of the fibersthat are 10mm or greater in length with aspect ratio greater than 10 :1are asbestos, whereas nonasbestos mineral fibers tend to be shorterthan 10mm in length and have aspect ratios less than 10 :1. Asbestosfibers are distinguished from nonasbestos mineral fibers on the basisof their morphology and elemental composition as determined byenergy dispersive spectrometry (see Chapter 11). Asbestos fibers mustalso be distinguished from crystals that may form on the filter surface,which often have pointed ends. Such crystals are not included in thetotal fiber count.

408 V.L. Roggli

Quantification of the asbestos body content of a lung tissue samplerequires a determination of the numbers of bodies per unit area of filtersurface. This can usually be accomplished by counting the number ofbodies in a portion of the filter of known area, and multiplying thisvalue by the total effective surface area. The author usually counts thenumber of bodies in two perpendicular strips at a magnification of 400¥(Figures A-1 and A-2). In cases with a low asbestos body burden, theentire filter surface may need to be counted to obtain accurate results.In quantifying the asbestos body and uncoated fiber burdens by scan-ning electron microscopy, the author counts 200 fibers or 100 con-secutive 1000¥ fields, whichever comes first. The latter amounts toapproximately 1% of the surface area of the filter. The total numbers ofbodies or fibers on the filter can then be determined by multiplying thenumber of bodies or fibers per mm2 of surface area by the total effec-tive surface area of the filter. Determination of asbestos body or fiberconcentration can then be accomplished by dividing the numbers perfilter by the amount of wet tissue digested in preparing that particularfilter. For paraffin blocks, the value must be multiplied by 0.7 for theresults to be comparable to wet fixed lung tissue9 (see above). Someinvestigators prefer to report their results in terms of bodies or fibersper gram of dried lung. In this circumstance, a portion of lung adjacentto the one actually digested should be weighed wet and then dried toconstant weight in a 60 to 70°C oven. Then the asbestos body or fiberconcentration per gram of wet lung can be multiplied by the wet-to-dry weight ratio, yielding an asbestos body or fiber concentration pergram of dried lung (see also Chapters 3 and 11).

Sample Calculations

Example 1: Light Microscopy

Sample weight: 0.308gmTotal effective filter area = pr2 = p (10.5mm)2 = 346mm2

Asbestos bodies counted in two perpendicular strips of filter (seeFigures A-1 and A-2) = 423

Area of two perpendicular strips = 2 ¥ 21mm ¥ 0.42mm (empiricallydetermined diameter of one 400¥ field) = 17.6mm2

Asbestos bodies (AB) per mm2 = 24Therefore,

Example 2: Scanning Electron Microscopy

Sample weight = 0.299gmUncoated fibers counted in 100 fields = 35Total area of 100 fields = 2.3714mm2

Effective area of filter = 346mm2 (See above)

AB gm24 mm 346mm

0.308gm27,000 AB gm

2 2

=( )( )

=

Appendix: Tissue Digestion Techniques 409

Fibers/mm2 = 14.76Fibers/filter = (14.76 fibers/mm2) (346mm2) = 5110Fibers/gm = (5110 fibers/filter)/0.299gm = 17,100 fibers/gm

References

1. Roggli VL, Brody AR: Changes in numbers and dimensions of chrysotileasbestos fibers in lungs of rats following short-term exposure. Expl LungRes 7:133–147, 1984.

2. Williams MG, Dodson RF, Corn C, Hurst GA: A procedure for the isolationof amosite asbestos and ferruginous bodies from lung tissue and sputum.J Toxicol Environ Health 10:627–638, 1982.

3. Roggli VL: Scanning electron microscopic analysis of mineral fibers inhuman lungs, Ch. 5 In: Microprobe Analysis in Medicine (Ingram P, ShelburneJD, Roggli VL, eds.), New York: Hemisphere Pub. Corp. 1989, pp. 97–110.

4. Churg, A: Quantitative methods for analysis of disease induced by asbestosand other mineral particles using the transmission electron microscope, Ch. 4 In: Microprobe Analysis in Medicine (Ingram P, Shelburne JD, RoggliVL, eds.), New York: Hemisphere Pub. Corp. 1989, pp. 79–95.

5. Churg A, Sakoda N, Warnock ML: A simple method for preparing fer-ruginous bodies for electron microscopic examination. Am J Clin Pathol68:513–517, 1977.

6. Roggli VL: Preparatory techniques for the quantitative analysis of asbestosin tissues. Proceedings of the 46th Annual Meeting of the ElectronMicroscopy Society of America (Bailey GW, ed.), San Francisco: San Francisco Press, Inc., 1988, pp. 84–85.

7. Smith MJ, Naylor B: A method for extracting ferruginous bodies fromsputum and pulmonary tissues. Am J Clin Pathol 58:250–254, 1972.

8. Roggli VL, Shelburne JD: New concepts in the diagnosis of mineral pneu-moconioses. Sem Respir Med 4:138–148, 1982.

9. Roggli VL, Pratt PC, Brody AR: Asbestos content of lung tissue in asbestosassociated diseases: A study of 110 cases. Br J Ind Med 43:18–28, 1986.

10. Ashcroft T, Heppleston AG: The optical and electron microscopic determi-nation of pulmonary asbestos fibre concentration and its relation to thehuman pathological reaction. J Clin Pathol 26:224–234, 1973.

11. Corn CJ, Williams MG, Jr., Dodson RF: Electron microscopic analysis ofresidual asbestos remaining in preparative vials following bleach digestion.J Electron Microsc Tech 6:1–6, 1987.

12. Gylseth B, Batman RH, Overaae L: Analysis of fibres in human lung tissue.Br J Ind Med 39:191–195, 1982.

13. Roggli VL, Piantadosi CA, Bell DY: Asbestos bodies in bronchoalveolarlavage fluid: A study of 20 asbestos-exposed individuals and comparisonto patients with other chronic interstitial lung disease. Acta Cytolog30:460–467, 1986.

410 V.L. Roggli

as mesothelioma cause, 108, 325physicochemical properties of, 4, 5

Amosite asbestos fibers, with calcium oxalatecrystal coating, 41–43

Amphibole asbestos, 1, 2, 3, 4–5, 5, 7, 8. See alsoActinolite asbestos; Amosite asbestos;Anthophyllite asbestos; Crocidoliteasbestos; Tremolite asbestos

as asbestos body core, 53–54in bronchoalveolar lavage fluid, 247–248as cosmetic talc contaminant, 225crystallographic structure of, 5, 7, 8as lung cancer cause, 198, 199as mesothelioma cause, 108, 325–326

medicolegal aspects of, 396as parietal pleural plaque cause, 178physicochemical properties of, 4–5selected area electron diffraction pattern

from, 315Amphibole asbestos fibers

clearance from respiratory tract, 262, 264deposition in respiratory tract, 260, 261retention time in lung, 262

Angiosarcomaas mesothelioma mimic, 113as primary pleural tumor, 140

Animal models, of asbestos-related diseases.See Experimental models, of asbestos-related diseases

Anthophyllite asbestos, 2, 3, 4as asbestos body core, 53–54in bronchoalveolar lavage fluid, 246–247as cosmetic talc contaminant, 225energy dispersive x-ray spectra from, 314geological features of, 2as parietal pleural plaque cause, 179physicochemical properties of, 5

Index

AActinolite asbestos, 2, 3, 4

geological features of, 2physicochemical properties of, 5

Adenocarcinoma, pulmonary, 201, 203, 204,205, 208

cytopathology of, 235, 236differentiated from mesothelioma, 123, 124,

125, 126, 127, 128, 139, 240in experimental animal models, 279, 281as malignant pleural effusion cause, 238,

240as mesothelioma mimic, 113, 115, 123metastatic

differentiated from epithelialmesothelioma, 139

mucin-producing, 145–146pseudomesotheliomatous, 113

Adenomatosis, pulmonary, 85, 86Adenosquamous lung cancer, 205, 208Air, asbestos content of, 25

measurement of, 26–27threshold limit value (TLV) for, 362

Aluminum silicates, in sputum specimens, 233American Cancer Society, 388American Thoracic Society, asbestosis

diagnostic criteria ofmedicolegal implications of, 363–365, 385,

386radiographic, 76

Amosite asbestos, 2, 3, 4as asbestos body core, 53, 54as asbestosis cause, 73cytotoxicity of, 272energy dispersive x-ray spectra from, 314geological features of, 2as lung cancer cause, 198, 199, 204

411

Antibodies, as mesothelioma diagnosticmarkers, 240, 241

Antigorite, 3AP-1 transcription factor, 277Arachidonic acid metabolites, 275Armstrong Contracting and Supply, 362Asbestos. See also specific types of asbestos

ban on, 18, 19, 28, 370blue. See Crocidolite asbestosbrown. See Amosite asbestoschemical formulas of, 4, 5definition of, 1emission from natural sources, 25exposure to. See Exposure, to asbestosfire-resistant properties of, 1–2, 17–18as fortifying additive, 18mineralogy of, 1–16

crystallographic structure, 5–7geological features, 2–3historical background of, 1–2physicochemical properties, 3–5

removal of, 23–26, 28governmental regulations for, 23, 31

techniques for identification of, 7–15analytical scanning electron microscopy, 9,

13–15infrared spectroscopy, 9, 11magnetic alignment and light scattering, 9,

11phase-contrast microscopy, 7, 9, 10polarizing microscopy with dispersion

staining, 9, 10–11scanning electron microscopy with EDS, 9selected area electron diffraction (SAED),

5, 8, 9, 13transmission electron microscopy, 9, 13–14transmission electron microscopy with

EDS, 6, 9x-ray diffraction, 9, 11–13

worldwide production and consumption of,19, 21

Asbestos airway disease, 93Asbestos bodies, 34–35, 34–55

as asbestosis diagnostic marker, 72, 77, 93,94, 178, 366, 367

in cytologic preparations, 81–83, 242–250in bronchoalveolar lavage fluid, 81–83,

244–248, 251in fine needle aspiration biopsy specimens,

248–250in sputum specimens, 232, 242–244

definition of, 34diameter of, 232electron diffraction pattern from, 315

412 Index

in fibrotic interstitium, 83, 84in foreign-body giant cells, 83formation of, 35–36, 38–40, 325in histologic sections, 46–47, 94historical background of, 34–35length of, 232, 234within lymph nodes, 83occurrence and distribution of, 44–45phagocytosis of, 231, 232quantification of, 45–55, 312

asbestos body count/uncoated fiber countcorrelation, 54, 56

in extrapulmonary tissues, 52–53by fiber type, 53–55in histologic sections, 46–47in lung tissue digests, 41, 47–50in lymph nodes, 50–52

structure and development of, 34, 35–44, 325Asbestos fiber analysis. See Tissue mineral fiber

content analysisAsbestos fibers

clearance from respiratory system, 260–265conversion to asbestos bodies, 35–36, 38–40deposition in respiratory system, 258–260diameter of, relationship with mesothelioma

risk, 283length of

relationship with carcinogenicity, 282–283relationship with cytotoxicity, 272–273relationship with mesothelioma risk, 325,

326–327relationship with pulmonary fibrogenesis,

266–270respirability of, 231, 233sputum content of, 218tissue content analysis of. See Tissue mineral

fiber analysisAsbestos Hazard Emergency Response Act

(AHERA), 25Asbestosis, 71–103

alveolar dust clearance capacity and, 264–265asbestos bodies in, 34–35asbestos lung tissue content analysis in,

317–323, 326, 328aspergillosis associated with, 88, 89, 248,

249clinical features of, 74–75definition of, 71, 72diagnosis of, 76–92

cytologic, 81–83histopathologic, 83–88, 89medicolegal aspects of, 383–386minimal histologic criteria for, 72pathologic, 78–81, 366–368

radiographic, 76–78ultrastructural, 89

differential diagnosis of, 90–92epidemiology of, 72–74first death attributed to, 355first description of, 71grading scheme for, 94–97historical background of, 71–72latency period for, 73–74pathogenesis of, 75–76pleural plaques as risk factor for, 180pneumoconiosis associated with, 90relationship with lung cancer, 75, 194–197,

330, 331–333, 367, 375risk assessment of, 32

Asbestos manufacturing plant workersmesothelioma in, 327pulmonary asbestos content in, 336

Asbestos School Hazards Abatement Act, 31Asbestos Textile Institute, 361Ascites, 238–239, 241Aspergillosis, asbestosis-associated, 88, 89, 248,

249Atelectasis, rounded, 169, 170, 183–186

differentiated from lung cancer, 185–186Auerbach, Oscar, 388Automative workers, mesothelioma in, 327

BBabcock and Wilcox, 378Benign asbestos-related pleural diseases,

169–192diffuse pleural fibrosis, 169, 170, 181–186

clinical implications of, 183pathologic findings in, 181–182radiographic findings in, 181

pulmonary tissue asbestos content in,328–330

Ber-EP4, as mesothelioma diagnostic marker,131, 139, 141, 240

Beryllium, as mesothelioma cause, 111Biopsy

for asbestosis diagnosis, 77, 92fine-needle aspiration, 248–250for mesothelioma diagnosis, 241

Blue asbestos. See Crocidolite asbestos“Blue bodies,” pulmonary, 44, 85, 88Borel, Clarence, 358Borel v. Fibreboard Corporation, 358, 360, 377Brake repair workers, pulmonary asbestos

content in, 336, 339–340Brakes, asbestos-containing, 22, 25Bronchoalveolar lavage fluid, asbestos bodies

in, 81–83, 244–248, 251

Index 413

Brown, Vandiver, 361B72.3, as mesothelioma diagnostic marker,

131–132, 139, 141Building occupants, pulmonary asbestos

content in, 336, 341–342

CCadherins, as mesothelioma diagnostic

markers, 133, 139Calcium oxalate asbestos bodies, 41–43Calcium phosphate asbestos bodies, 43–44Calretinin, as mesothelioma diagnostic marker,

130, 132, 139, 240Carbon fibers, as ferruginous body core, 58Carcinoembryonic antigen (CEA), as

mesothelioma diagnostic marker, 127,128, 130, 131, 139, 141–142, 240

Carcinogenesis, asbestos-related, 217-230. Seealso specific types of cancer

environmental exposure-related, 356–357in experimental animal models

asbestos as promoter vs. initiator in,286–287

asbestos manufacturing companies’ reporton, 361

in vivo inhalation studies, 279–282man-made mineral fiber studies, 287–289mechanisms of, 284–286role of fiber dimensions in, 282–284role of immune function n, 282

retinoids-related inhibition of, 286vitamin C-related inhibition of, 286

Ceramics/glass workers, mesothelioma in, 327Chemical cocarcinogens, as mesothelioma

cause, 111Chemical refinery workers

mesothelioma in, 327pulmonary asbestos content in, 336, 338–339,

339Chemotherapy

for mesothelioma, 152as pulmonary interstitial fibrosis cause, 92

Chest pain, mesothelioma-related, 112Children, mesothelioma in, 111Chrysotile asbestos, 2, 3, 4, 5, 6

annual production of, 231as asbestos body core, 54, 55, 94as asbestosis cause, 73in bronchoalveolar lavage fluid, 20crystallographic structure of, 6, 7cytotoxicity of, 272energy dispersive spectrum from, 20environmental exposure to, 25as gastrointestinal cancer cause, 218, 219

Chrysotile asbestos (cont.)geological features of, 3as lung cancer cause, 198, 199, 204as mesothelioma cause, 108

chrysotile fiber length in, 326–327medicolegal aspects of, 368–369, 396–397

physicochemical properties of, 4as pulmonary fibrosis cause, 269–27

Chrysotile asbestos bodies, quantification of,54, 56

Chrysotile asbestos fibersclearance from respiratory tract, 262, 263, 264deposition in respiratory tract, 259, 260, 261,

263length of, relationship with lung cancer,

282–283pulmonary tissue content analysis of,

367–368retention time in lung, 262

Clean Air Act, 18, 357Clinochrysotile, 5College of American Pathologists

asbestosis diagnostic criteria of, 366, 385asbestosis grading system of, 94, 95

Computed tomography (CT)of asbestosis, 76–78of diffuse pleural fibrosis, 181, 183of mesothelioma, 113, 114, 141of parietal pleural plaques, 173, 174of rounded atelectasis, 183, 185

Construction materials, asbestos-containing, 22,25

Construction workersmesothelioma in, 327pulmonary asbestos content in, 336, 338

Consumer Product Safety Commission, 357Cooke, W.E., 355Cor pulmonale, asbestosis-related, 74Cough, asbestosis-related, 74Crocidolite asbestos, 2, 3, 4

as asbestos body core, 53, 54as asbestosis cause, 73as cancer cause, 286

in experimental animal models, 279gastrointestinal cancer, 219lung cancer, 198

clearance from lung, 289cytotoxicity of, 272energy dispersive x-ray spectra of, 314geological features of, 2as mesothelioma cause, 106, 108, 369

crocidolite fiber length in, 326medicolegal aspects of, 396

physicochemical properties of, 4, 5

414 Index

Crocidolite asbestos fibersclearance from respiratory tract, 262, 263deposition in respiratory tract, 260, 263

Cytokeratinsas lung cancer diagnostic markers, 207as mesothelioma diagnostic markers,

127–128, 129, 130, 139, 140–141as synovial sarcoma diagnostic markers,

140–141Cytopathology, of asbestos-related diseases, 77,

231–255of bronchial epithelial atypia, 233, 234–238exfoliative respiratory, 233, 234–238historical background of, 233of pleural or peritoneal effusions, 238–241techniques for

bronchoalveolar lavage, 244–248, 251fine-needle aspiration biopsy, 248–250sputum analysis, 233, 242–244, 251

DDesmosomes, “giant,” 135–136Diaphragm, as parietal pleural plaque location,

173, 175, 176Diatomaceous earth

as ferruginous body core, 62–63in sputum specimens, 233

Doll, Richard, 388Dyspnea, mesothelioma-related, 112

EEffusion cytology, 238–241Elastic fibers, as ferruginous body core, 64Electron microscopy. See also Scanning electron

microscopy; Transmission electronmicroscopy

analytical, 13–15for mesothelioma diagnosis, 142

Emphysema, asbestosis-relatedpathologic features of, 78, 81, 82radiographic assessment of, 76–77in smokers, 81, 82

Environmental exposure, to asbestos, 25–26. Seealso Occupational exposure, to asbestos

historical background of, 356as mesothelioma cause, 107regulation of, 18

Environmental Protection Agency (EPA), 18, 19,26, 27, 28, 31, 32, 357, 370

Enzymes, hydrolytic, 275Epithelial membrane antigens, as

mesothelioma diagnostic markers, 132,139

Erionite, 31

as ferruginous body core, 64as mesothelioma cause, 109, 283–284as parietal pleural plaque cause, 179

Eskridge, William H., 359Esophageal cancer, asbestos-related, 32, 219,

220–221Experimental models, of asbestos-related

diseases, 256–308carcinogenesis in, 279–291

asbestos as promoter vs. initiator in,286–287, 289–291

in vivo inhalation studies, 279–282man-made mineral fibers studies, 287–289mechanisms of, 284–286role of fiber dimensions in, 282–284, 284role of immune function in, 282Saranac Laboratory report on, 361

deposition and clearance of asbestos fibersin, 257–263

fibrogenesis in, 263–279in vivo inhalation studies, 265–266mechanisms of, 270–279role of fiber dimensions in, 266–270

historical background of, 257Exposure, to asbestos. See also Environmental

exposure, to asbestos; Occupationalexposure, to asbestos

governmental regulation of, 28–31historical background, 356, 357

lack of known safe limit for, 370measurement of, 26–27nonoccupational, 25–26

as mesothelioma cause, 106–107risk assessment of, 31–32

threshold limit value (TLV) for, 362Extrapulmonary tissue, asbestos body

quantification in, 52–53

FFerruginous bodies

as asbestos bodies. See Asbestos bodiesdefinition of, 35nonasbestos, 35, 55–64

carbon fibers, 58diatomaceous earth, 62–63elastic fibers, 63fibrous glass, 58–59, 61, 62in histologic sections, 93manmade mineral fibers, 58–62metal oxides, 58, 60sheet silicates, 55–56, 58silicon carbide ceramic fibers, 35, 63zeolite bodies, 63

Fibreboard (corporation), 357–358, 360, 362

Index 415

Fibrosis, pulmonaryasbestos-related, 74–93diffuse pleural, 169, 170, 181–186

clinical implications of, 183pathologic findings in, 181–182radiographic findings in, 181

historical background of, 355–356interstitial, 76, 78

asbestos fiber content in, 94asbestos-related, 92–93cancer therapy-related, 92in experimental animal models, 265–279fibrous glass-related, 61first description of, 71–72gross morphology of, 78–80, 81histopathologic findings in, 83, 84, 86, 87idiopathic, 386in vivo inhalation studies of, 265–266mechanisms of, 270–279medicolegal aspects of, 386non-asbestos-related, 61, 90, 93role of asbestos fiber dimensions in,

266–270systemic manifestations of, 74–75

peribronchiolar, 85, 93, 178, 366Fine-needle aspiration biopsy, 241, 248–250Folded lung syndrome, 183Food and Drug Administration (FDA), 28

GGastrointestinal cancer, asbestos-related, 32,

217–221Gene expression, asbestos-related alterations in,

276–277Giant cells, foreign-body type, 83, 85Glass, fibrous

as ferruginous body core, 58–59, 61, 62toxicity of, 287, 289

Glutathione, 271Glycoproteins, as mesothelioma diagnostic

markers, 128, 131–132Glycosaminoglycans, in pleural effusions,

125(W.R). Grace company, 378Granulocytes, 277Growth factors, 274, 275, 276

HHBME-1, as mesothelioma diagnostic marker,

133, 240Hemangioendothelioma, epithelioid

as mesothelioma mimic, 113as primary pleural tumor, 140

Hepatitis, alcoholic, 85, 86

HMFG-1, as mesothelioma diagnostic marker,139

Household contacts, 340, 341Household exposures, 340, 341Hueper, Wilhelm, 356–357Hyaluronic acid, as mesothelioma marker, 123,

125, 127, 136

IImmune system, asbestos-related dysfunction

of, 75, 277–278as lung cancer risk factor, 282

Immunohistochemistry, of mesothelioma,127–134, 141–142, 241

Industrial Hygiene Foundation, 361Infants, pulmonary asbestos body content in,

45Inhalation studies

of asbestos-related carcinogenesis, 279–282of asbestos-related interstitial pulmonary

fibrosis, 265–266Insulation materials

asbestos-containing, 22, 31as asbestosis cause, 84as asbestos-related disease cause, 358medicolegal aspects of, 358, 368–369as mesothelioma cause, 106, 368–369

liability litigation related to, 368–369manmade mineral fiber content of, 58

Insulation workersmesothelioma in, 327pulmonary asbestos content in, 335–336

Interleukin-1, 274, 282, 285Interleukin-6, 285International Labor Organization (ILO)

interstitial fibrosis radiographic diagnosticcriteria of, 364

pneumoconiosis radiographic diagnosticcriteria of, 76

JJohns-Manville, 360, 361, 362, 378

KKaolinite core, of sheet silicate ferruginous

bodies, 56Kaolin refractory ceramic fibers, carcinogenicity

of, 284Kidney cancer, asbestos exposure-related, 32

LLarge-cell carcinoma, of the lung, 201, 203,

204–205, 208cytopathology of, 236, 237, 238

416 Index

Large intestine cancer, asbestos-related, 219Larynx cancer, asbestos-related, 32, 221–222Leukemia, asbestos-related, 224–225LeuM1 (CD15), as mesothelioma diagnostic

marker, 131, 139, 141, 240Light microscopy. See also Phase-contrast light

microscopyfor asbestos bodies quantification, 312

Litigation, asbestos exposure-relatedasbestos-related cases

defendants’ perspective on, 383–386, 398plaintiffs’ perspective on, 360–369

bankruptcy protection against, 359–360, 378causation determination in, 360–369, 381–383defendant’s attorney’s perspective on,

377–401development of, 357–360, 377–378doctrine of strict product liability in, 358effect on judiciary, 359jury in, 379–381lung cancer-related cases

defendants’ perspective on, 386–392, 398plaintiffs’ perspective on, 367

medical and scientific witnesses in, 365–369,377, 378–379, 380–383

mesothelioma-related casesdefendants’ perspective on, 392–398plaintiffs’ perspective on, 365, 368–369

national settlement class actions, 359pathologist’s role in, 360–365, 378, 385plaintiff’s attorney’s perspective on, 355–376retrospective exposure analysis (REA) in, 398trial procedure in, 379

Lizardite, 3Lung cancer. See also Adenocarcinoma,

pulmonary; Mesotheliomaasbestos-related, 193–216

adenosquamous, 205, 208among nonsmokers, 198, 205asbestos fiber burden in, 367differential diagnosis of, 208differentiated from rounded atelectasis,

185–186dose-response relationship in, 194–195epidemiology of, 194–199in experimental animal models, 279gross morphology of, 199–201, 202histopathology of, 201, 203–208historical background of, 193–194immune dysfunction in, 282large-cell carcinoma, 201, 203, 204–205,

208, 236, 237, 238as mortality cause, 193, 209pathologist’s role in identification of, 209

pathology of, 199–208pleural plaques as risk factor for, 180pulmonary asbestos fiber content in,

330–333relationship with asbestosis, 75, 194–197,

330, 331–333, 367risk assessment of, 31–32role of fiber type in, 198–199small-cell carcinoma, 201, 203, 204, 208sputum cytology in, 234squamous cell carcinoma, 201, 202,

203–204, 208tissue mineral fiber content analysis in,

330–333small-cell carcinoma, sheet silicate

pseudoasbestos bodies-related, 57smoking-related, 193, 209

in experimental animal models, 286–287synergistic interaction with asbestos

exposure, 73, 74, 194, 197–198, 286–287,365, 370

treatment for, as iatrogenic pulmonarydisease cause, 92

Lung tissue digests, asbestos bodyquantification in, 47–50

Lymph nodesasbestos body quantification in, 50–52mesothelioma metastases to, 123

Lymphoma, asbestos-related, 75, 224–225

MMacrophages

as asbestos-related injury mediator, 273–276,277

phagocytosis byof asbestos bodies, 231, 232of asbestos fibers, 35, 40–41, 262, 273

tumor necrosis factor-a production by,275–276

Magnesium sulfate fibers, carcinogenicity of,284

Magnetic alignment and light scattering, 9, 11Magnetic resonance imaging (MRI)

of mesothelioma, 141of parietal pleural plaques, 173in pleuropneumonectomy patients, 113

Malignant mesothelioma. See MesotheliomaMan-made mineral fibers

as asbestos substitutes, 287–289carcinogenicity of, 284, 287–289as ferruginous body core, 58as pulmonary fibrosis cause, 287–289

Manville Asbestos Disease CompensationFund, 360

Index 417

Manville Trust, 360Medicolegal aspects, of asbestos-related

diseases. See Litigation, asbestos-related

Merchant Marine seamenmesothelioma in, 327pulmonary asbestos content in, 336, 338

Mesothelial proliferations, differentiated frommesothelioma, 137–139, 241

Mesothelioma, asbestos-related, 104–168adenoidcystic, 118adenomatoid, 118amphibole asbestos-related, medicolegal

aspects of, 396asbestos-mesothelial cell interaction in,

285–286, 291biphasic, 116, 144in children, 111chrysotile asbestos-related, 55

chrysotile fiber length in, 326–327diagnosis of, 368–369medicolegal aspects of, 396–397

crocidolite asbestos-related, 369crocidolite fiber length in, 326–327medicolegal aspects of, 396

cytopathology of, 239–239deciduoid, 118definition of, 104desmoplastic, 116, 119, 120, 122diagnosis of, medicolegal aspects of, 368–369,

395–397differential diagnosis of, 136–142differentiated from

adenocarcinoma, 123, 124. 125, 126, 127,128, 139, 240

reactive mesothelial proliferations, 241epithelial, 116, 117, 118

histologic subtypes of, 117, 118hyaluronic acid as marker for, 123, 125immunohistochemical staining of, 128, 129,

130mucin-positive, 125

erionite ferruginous body-related, 64in experimental animal models, 279–281familial aggregations of, 109, 111first description of, 106genetic predisposition toward, 109, 111historical background of, 105–106incidence of, 104

gender differences in, 107in utero development of, 111latent interval in, 107liability litigation related to, 365lymphohistiocytoid, 119, 121

Mesothelioma, asbestos-related (cont.)medicolegal aspects of

defendants’ perspective, 392–398plaintiffs’ perspective, 365, 368–369, 393,

394, 395metastatic, 113, 122–123as mortality cause, 105pathologic features of

gross morphology, 111–115histochemistry, 123–127histopathology, 116–123immunohistochemistry, 127–134, 240ultrastructural features, 134–136

pathophysiology of, 104pericardial, 148–149pericardial and peritoneal effusions

associated with, 239peritoneal, 107, 116, 142–147

asbestos-related, 146–147cystic, 145diagnosis of, 143–144epithelial, 144, 146histology of, 144–146immunohistochemistry of, 141misdiagnosis in women asbestos workers,

225pathophysiology of, 142–143in women, 146, 225

pleomorphic, 118pleural, 111–113, 116

diagnosis of, 395–397immunohistochemistry of, 141–142medicolegal aspects of, 392–398, 395–397pericardial invasion by, 149pleural plaques as risk factor for, 180

prognosis of, 149, 151, 152pulmonary tissue asbestos content in, 108,

323–328retrospective exposure analysis (REA) in,

398risk assessment of, 31–32sarcomatoid, 116, 119, 120, 122, 144

differentiated from other spindle cellcancers, 128, 129

histologic subtypes of, 119, 120, 121,122–123

immunohistochemistry of, 129, 141small-cell, 118staging of, 149, 150, 151treatment for, 149–151tremolite asbestos-related, 326–327of tunica vaginalis testis, 147–148well-differentiated papillary, 117, 118in women, 146, 225, 325, 326

418 Index

Mesotheliuminteraction with asbestos, 285–286normal, 104, 105

Metal oxides, as ferruginous body core, 58, 60Metal workers, mesothelioma in, 327Mica core, of sheet silicate ferruginous bodies,

56Microscopy. See specific types of microscopyMineral fiber analysis. See Tissue mineral fiber

analysisMine Safety and Health Administration, 28Molten metal workers, pulmonary asbestos

content in, 336, 337–338Mucopolysaccharides, as mesothelioma

markers, 123, 124, 125Multiple myeloma, 224Murray, H. Montague, 355

NNational Emissions Standards for Hazardous

Air Pollutants, 31National Institute for Occupational Safety and

Health (NIOSH)asbestosis grading system of, 94, 95permissible asbestos exposure level (PEL)

standards of, 28, 29–30New York Academy of Sciences, 377Nickel, as mesothelioma cause, 111North Carolina Asbestos Abatement Program,

24Nuclear factor-kB, 277

OOccupational exposure, to asbestos, 19–25

in asbestos-containing productsmanufacturing processing, 19, 21

asbestos friction materials-related, 22as asbestosis cause

intensity/duration of exposure in, 72–73synergistic interaction with smoking, 73

in asbestos processing, 19, 21in asbestos removal, 23–25in construction materials, 22health risk associated with, 32historical background of, 17–19, 355–357in insulation material installation, 9, 22medicolegal aspects of, 394, 395as mesothelioma cause, 106–108in shipbuilding, 19, 23

Occupational Safety and Health Act, 357Occupational Safety and Health Administration

(OSHA)asbestos exposure standards of, 231, 357,

383–384

permissible asbestos exposure level (PEL),28, 29–30, 32

statement on asbestos-related diseases, 370Ochsner, Alton, 388Ocular cancer, 226Oil refinery workers

mesothelioma in, 327pulmonary asbestos content in, 336, 338–339

Oncogenes, 285, 287Ophiolites, 2Orthochrysotile, 5Ortiz v. Fibreboard Corporation, 357–358Ossification, dendriform pulmonary, 85, 87Ovarian cancer, 225Owens-Corning, 362, 378

PPancoast tumors, 205, 206Pancreatic cancer, 219, 225Paper mill workers, mesothelioma in, 327Parachrysotile, 5Parenchyma, pulmonary

asbestos body formation in, 35–44asbestos fiber deposition in, 260mesothelioma-related mass in, 112–113

Pathologists, role in asbestos-related diseaselitigation, 360–369, 378, 385

Penile cancer, 226Pericardium, mesothelioma of, 148–149Periodic acid Schiff stain, 123, 124, 125Peritoneal cancer, asbestos-related, 221–222Peritoneal effusions, cytopathology of, 238Peritoneum

mesothelioma of. See Mesothelioma,peritoneal

primary papillary serous tumors of, 146Peto, Julian, 388p53, as mesothelioma marker, 137, 139Phagocytosis, of asbestos fibers, 35, 40–41, 231,

232, 262Pharynx cancer, asbestos-related, 221–222Phase-contrast light microscopy, 7

for tissue mineral fiber burdenquantification, 312–313, 314–315, 316,317, 319

in asbestosis, 317, 319in benign asbestos-related pleural diseases,

329, 330in lung cancer, 331in mesothelioma, 323

Platelet-derived growth factor, 274, 276Platelet-derived growth factor-a, 271, 285Pleura, primary vascular malignancies of,

140

Index 419

Pleural diseases, asbestos-relatedasbestos-related, 364benign, 169–192

asbestos lung tissue content analysis in,328–330

benign asbestos effusions, 169, 186–187diffuse pleural fibrosis, 169, 170, 181–186overlap among, 169, 170parietal pleural plaques, 169, 170–180pathogenesis of, 169–170rounded atelectasis, 169, 170, 183–186

differentiated from asbestosis, 72Pleural effusions

benign, 169, 186–187cytopathology of, 238

malignant, cytopathology of, 238–241mesothelioma-related, 113, 114

glycosaminoglycan content of, 125Pleural plaques

asbestosis-related, 90gross morphology of, 79–81

parietalclinical implications of, 179–180epidemiology of, 178–179historical background of, 170–171laryngeal cancer-associated, 221, 223pathologic findings in, 173–178radiographic features of, 171–173

Pleuritischronic organizing, 137, 138diffuse pleural fibrosis-related, 182

Pleuropneumonectomy, magnetic resonanceimaging prior to, 113

Pneumoconiosisdefinition of, 71radiographic assessment of, 76welders’, relationship with asbestosis, 90

Pneumonectomy, radical extrapleural, 152Pneumonia, cryptogenic organizing, 91–92Pneumonitis, radiation, 92Pneumothorax, therapeutic, as mesothelioma

cause, 111Polarizing microscopy, with dispersion

staining, 9, 10–11Polio vaccine, simian virus 40-contaminated,

110–111Polycyclic aromatic hydrocarbons, 286, 287Power plant workers

mesothelioma in, 327pulmonary asbestos content in, 336, 337

Psammoma bodies, in well-differentiatedpapillary mesothelioma, 118

Pseudoasbestos bodies. See Ferruginous bodies,nonasbestos

RRadiation, ionizing, effect on oncogene

transformation, 287Radiation therapy

for mesothelioma, 151–152as mesothelioma cause, 109–110

Railroad workersmesothelioma in, 327pulmonary asbestos content in, 336, 339

Raybestos-Manhattan, 361, 378Reactive oxygen species, 271–272Rectum cancer, asbestos-related, 219Refractory ceramic fibers, toxicity of, 287, 288,

289Renal cell carcinoma, asbestos-related, 222–

224Respiratory failure, asbestosis-related, 75Respiratory system

asbestos fiber clearance from, 260–265asbestos fiber deposition in, 258–260host defense mechanisms of, 257–258

Retinoids, anticarcinogenic activity of, 286Retrospective exposure analysis (REAs), 398Riebeckite, 3Rural area residents, pulmonary asbestos body

content in, 44–45

SSaranac Laboratory report, on asbestos-related

carcinogenicity, 361Sarcoma

metastatic pleural, 139–140synovial, 140–141

Scanning electron microscopy (SEM)of asbestos body formation, 41with EDS, 9for tissue mineral fiber quantification,

312–313, 316in asbestosis, 318, 319–321in benign asbestos-related pleural disease,

328, 329, 330in lung cancer, 332–333in mesothelioma, 323–324, 325

Scanning optical microscopy, confocal, fortissue mineral fiber quantification,314–315

Scanning transmission electron microscopy(STEM), for tissue mineral fiberquantification, 315

Schools, asbestos exposure in, 25, 26, 27, 31,341, 342

Scleroderma, 75Selected area electron diffraction (SAED), 5, 8,

9, 13

420 Index

for tissue mineral fiber contentquantification, 313–314, 315

Selikoff, Irving J., 18, 377, 388September 11, 2001, 19Serosal membranes

benign tumors of, 104–105mesothelioma of. See Mesothelioma

Serpentine asbestos, 2, 3, 5. See also Chrysotileasbestos

asbestiform, 2, 3crystallographic structure of, 5, 6, 7

Serpentine, nonasbestiform, 3Sheet silicates, as ferruginous body core, 55–56,

58Shipbuilding, asbestos exposure in, 23Shipyard workers

asbestos exposure in, 90as mesothelioma cause, 106, 327, 369

pulmonary asbestos content in, 336–337Silica fibers, as mesothelioma cause, 111Silicon carbide ceramic fibers, as ferruginous

body core, 64Silicosis

differentiated from asbestosis, 90extrapulmonary manifestations of, 75

Silicotic nodules, extrapulmonary, 75Simian virus (SV) 40, as mesothelioma cause,

110–111, 365Simpson, Sumner, 361Small-cell carcinoma, pulmonary, 201, 203, 204,

208cytopathology of, 235–236, 237

Smith, Kenneth, 362Smokers

asbestos exposure inemphysema associated with, 76–77interstitial fibrosis associated with, 90–91

chest x-ray findings in, 76pulmonary asbestos body counts in, 44

Smokingas lung cancer cause, 193, 209

in experimental animal models, 286–287medicolegal aspects of, 388–391synergistic interaction with asbestos

exposure in, 73, 74, 194, 197–198, 199,286–287, 365, 370

negative correlation with mesothelioma, 111medicolegal aspects of, 365

as obstructive lung disease cause, 365synergistic interaction with asbestos

as lung cancer cause, 73, 74, 194, 197–198,199, 286–287, 365, 370

as parietal pleural plaque risk factor, 179Spectroscopy, infrared, 9, 11

Sputum cytology, 233, 242–244, 251Squamous cell carcinoma

cytopathology of, 234–235in experimental animal models, 279laryngeal, 222, 223pulmonary, 201, 202, 203–204, 208

Steel workers, mesothelioma in, 327Stephenson, Ward, 358Stomach cancer, asbestos-related, 219Superior sulcus tumors, 205, 206SV (simian virus) 40, as mesothelioma cause,

110–111, 365

TTalc

amphibole asbestos contamination of, 225anthophyllite asbestos contamination of, 225as parietal pleural plaque cause, 179tremolite asbestos contamination of, 225

Talc core, of sheet silicate ferruginous bodies,56

Talcosis, as pleural plaque cause, 171Talcum powder, asbestos contamination of,

53–54Testis, mesothelioma of, 147–148Thrombomodulin, as mesothelioma diagnostic

marker, 132–133, 139Thyroid transcription factor-1, as mesothelioma

diagnostic marker, 130, 133–134, 139,141–142, 240

Tissue mineral fiber content analysis, 309–354in asbestosis, 317–323in benign asbestos-related pleural diseases,

328–330historical background of, 309–310identification of fiber types in, 342–346

asbestos fibers, 342–344nonasbestos mineral fibers, 344–346

in lung cancer, 330–333medicolegal aspects of, 397in mesothelioma, 323–328methods for, 310–317

digestion technique, 311–312, 402–408fiber identification and quantification,

312–315tissue selection, 310–311

in normal lungs, 333–334in specific occupational/environmental

exposure groups, 334–342asbestos manufacturing plant workers,

336brake repair workers, 339–340building occupants, 341–342construction workers, 334–335, 338

Index 421

families of asbestos workers, 340–341insulators, 335–336molten metal workers, 337–338oil and chemical refinery workers, 338–339power plant workers, 337railroad workers, 339shipyard workers, 336–337steelworkers, 334–335U.S. Navy/Merchant Marine servicemen,

338variability of results in, 315–316

Tomplait, Claude J., 358Toxic Substances Control Act, 357Transcription factors, 276–277Transmission electron microscopy (TEM)

of asbestos-related ultrastructural changes,89

for asbestos measurement, 26with EDS, 6, 9, 13, 14for tissue mineral fiber quantification,

313–314, 315, 316in asbestosis, 317, 319, 320in benign asbestos-related pleural diseases,

328–329, 330in lung cancer, 331in mesothelioma, 324

Tremolite asbestos, 2, 3, 4as asbestos body core, 53–54in bronchoalveolar lavage fluid, 248as cosmetic talc contaminant, 225energy dispersive x-ray spectra of, 314geological features of, 2as mesothelioma cause, 108

tremolite fiber length in, 326physicochemical properties of, 5

Trudeau Foundation, 361Tumor growth factor-a, 271, 276Tumor growth factor-b, 274, 276, 285Tumor necrosis factor, 285Tumor necrosis factor-a, 271, 274, 275–276Tunica vaginalis testis, mesothelioma of,

147–148

UUltrastructural studies, of asbestosis, 89United Kingdom, asbestos exposure level

standards in, 29–30United States-Canadian Mesothelioma Panel,

393United States Gypsum Company, 378United States Navy servicemen

mesothelioma in, 327pulmonary asbestos content in, 336, 338

United States Surgeon General, 388

Urban area residents, pulmonary asbestos bodycontent in, 44–45

VVimentin, as mesothelioma diagnostic marker,

142Vitamin C, anticarcinogenic activity of, 286Vitreous fibers, as ferruginous body core, 58

WWagner, J.C., 377Waste disposal, of asbestos, 25Wisdom, John Minor, 358World Trade Center terrorist attack, as asbestos

exposure source, 19, 20W.R. Grace company, 378

422 Index

XX-ray diffraction, 9, 11–13X-rays, chest

of asbestosis, 73, 76–77, 364of mesothelioma, 114of parietal pleural plaques, 171–173of rounded atelectasis, 184

X-ray screening, for asbestos exposure, 384–385

ZZeolites

as ferruginous body core, 64as mesothelioma cause, 109as parietal pleural plaque cause, 179