Pathology of Asbestosis: An Update of the Diagnostic Criteria Response to a Critique.
Recently a critique of some of the findings and conclusions of the committee was published. (3) We believe that it would be of interest to the readership to understand the reasoning and deliberations involved in our decisions on these issues. A point-by-point response to the critique is therefore provided in the following pages.
2010 ASBESTOSIS GRADING SCHEMA
The critique takes issue with the elimination of bronchiolar wall fibrosis as part of the definition of grade 1 asbestosis. This was a unanimous decision by the committee. Individuals with bronchiolar wall fibrosis alone typically have obstructive findings on pulmonary function test rather than restrictive findings when alveolar septal fibrosis is involved. (4) Indeed, this concept is applicable to other mineral dust-induced lung disease, in which it has been recommended that the term "mineral dust airways disease" be used. (5) Most of the other dusts that produce this type of bronchiolar pathology do not produce diffuse interstitial fibrosis. Hence, this rationale is by no means limited to asbestos-induced fibrosis and suggests that bronchiolar disease and interstitial fibrosis are completely separate processes. Bronchiolar wall fibrosis is commonly observed in non-occupationally exposed individuals (23% of 254 British persons) and relates to multiple factors, including aging and smoking. (6) This should be kept in mind when examining potential cases of asbestosis.
Concern is raised that the inclusion of "No appreciable peribronchiolar fibrosis or fibrosis confined to the bronchiolar walls" as grade 0 asbestosis means that the committee considered these as equivalent. That is certainly not the case; rather, the clear implication is that neither of these should be considered asbestosis. The implication is made that the committee made this decision to affect an individual's ability to seek compensation for an asbestos-related disease. Medical-legal issues were not the focus of the committee, and indeed most of the coauthors of the 2010 document are not involved in medical-legal activities. There is no inherent reason why an individual could not seek compensation for asbestos airways disease.
Issue is also taken with 2 of the figures in the 2010 document (Figures 9, A, and 12). Although there may be some legitimate debate about whether or not alveolar septal wall fibrosis is present in the earliest or mildest cases, there should be no debate, as indicated above, that the presence of alveolar septal wall fibrosis is necessary for a pathologic diagnosis of asbestosis.
Asbestos bodies are the hallmark of asbestos exposure. (7) Because there are numerous causes of interstitial lung disease, asbestos bodies provide the necessary specificity for the pathologic diagnosis of asbestosis. Even though asbestosis tends to be centered on airways, there are other disorders with this pattern. (8) Here, again, asbestos bodies provide the necessary specificity.
The critique takes issue with the number of asbestos bodies required for a pathologic diagnosis of asbestosis, noting that chrysotile does not form asbestos bodies as well as the amphiboles. (3) However, in chrysotile miners and millers with heavy exposures sufficient to cause asbestosis, asbestos bodies are indeed found in histologic sections, (2) and some of these contain chrysotile cores (others contain tremolite, a known contaminant of chrysotile). (9)
The requirement of 2 asbestos bodies per square centimeter did not originate with the 2010 committee, but was in fact proposed by the 1997 Helsinki consensus report and reaffirmed by the 2014 Helsinki meeting. (10,11) The experience of all these groups was that most asbestosis cases had levels well above this number. One of the problems with the original 1982 document is that in cases of interstitial fibrosis, a loophole was provided in which an unlimited number of iron-stained sections could be searched in order to find 2 asbestos bodies and call the case asbestosis. It makes no logical sense to sacrifice specificity with such a loophole at a time when asbestosis is becoming less common. The 2010 document closed this loophole with the requirement of 2 asbestos bodies per square centimeter.
The critique claims that 2 asbestos bodies per square centimeter correspond to 4000 asbestos bodies per gram of wet lung tissue. In fact, they correspond to 800 asbestos bodies per gram of wet lung. (12) The authors of the critique refer to the 20 asbestos bodies per gram as the upper limit of background relied on by Roggli, without noting that this is the same range relied on by one of the authors of the critique in his own textbook. (13) Based on this upper limit of background, one might expect to find a single asbestos body in five 2 X 2 [cm.sup.2] sections of lung parenchyma (as opposed to the 50-100 or more lung sections claimed). The authors of the critique offer anecdotal evidence of cases of asbestosis based on fiber analysis with no asbestos bodies found in histologic sections. (3) However, we have shown mathematically that in cases satisfying the histologic criteria that we have described, there is little or no overlap in the lung tissue fiber burden of bona fide asbestosis cases compared with interstitial lung disease cases not meeting criteria for a diagnosis of asbestosis. (14,15) Thus, it is far more likely that a false-positive diagnosis of asbestosis will be made using the criteria advocated by the authors of the critique than that a false-negative diagnosis will be made using the 2010 criteria. Further, fiber burden analysis (see below) could be applied to the occasional case in which there is a strong suspicion for asbestosis but the asbestos body count is below 2 per square centimeter.
It should be noted that 800 asbestos bodies per gram is 40 times the upper limit of the background range of asbestos body counts. It is the overwhelming medical scientific consensus that there is a threshold for asbestos-induced pulmonary fibrosis. (15-19) Thus, the requirement for 2 asbestos bodies per square centimeter is entirely consistent with a threshold for asbestosis.
The authors of the critique inquire as to whether the 2010 Asbestosis Committee recommends using iron stains in all cases of interstitial fibrosis before one can exclude a diagnosis of asbestosis. The committee made no such recommendation because this decision should be made on a case-by-case basis. Idiopathic pulmonary fibrosis is far more common than asbestosis, and in cases with typical clinical, radiographic, and pathologic findings, it would be a waste of time and resources to perform iron stains. If the patient has pleural plaques radiographically or a compelling exposure history and asbestos bodies are not readily identified on hematoxylin-eosin-stained sections, then the pathologist may choose to perform iron stains to assist in the identification of asbestos bodies. There was no consensus by the committee regarding the routine use of iron stains in diagnosing asbestosis.
The authors of the critique note that there is a significant variation in what one can see using transmission electron microscopy at X15 000 versus scanning electron microscopy at X1000 and seem to be implying that asbestos body counts by light microscopy are more reliable. The variation in numbers of fibers counted between scanning electron microscopy and transmission electron microscopy is irrelevant because any laboratory performing an analysis to determine whether a case falls within its range for asbestosis should be comparing cases performed in its own laboratory with its own methodology, and not relying on numbers from another laboratory. (20) As to the claim of the greater reliability of asbestos body counts by light microscopy, we have shown that the severity of fibrosis in asbestosis correlates best with amphibole fiber counts measured by scanning electron microscopy and not with asbestos body counts determined by light microscopy. (14,15)
The 2010 committee recognized that there may be some patients who are poor asbestos body formers who would not meet the criteria of 2 asbestos bodies per square centimeter and that such cases could still qualify as asbestosis if the lung fiber burden exceeded the 5th percentile for the asbestosis range. Studies have shown that most cases of pulmonary fibrosis with an asbestos exposure history that do not meet the histologic criteria for a diagnosis of asbestosis do not have fiber burdens within the range of asbestosis either. (14,15) Fiber analysis criteria are nonetheless available for possible cases of asbestosis not meeting the 2010 histologic criteria.
ISSUES REGARDING LACK OF NATIONAL INSTITUTE OF OCCUPATIONAL SAFETY AND HEALTH ENDORSEMENT, AND CONFLICTS OF INTEREST
The authors of the critique lament that no comment or endorsement by the National Institute of Occupational Safety and Health (NIOSH) was included in the 2010 College of American Pathologists/PPS criteria. Because some of the authors of the 1982 document were affiliated with NIOSH and NIOSH was included in the title of the document, then it follows that NIOSH might endorse the document. (1) The members of the 2010 committee were chosen from the PPS, and none were affiliated with NIOSH. There is no inherent reason why NIOSH might not endorse the 2010 document if it chooses to do so.
(1.) Craighead JE, Abraham JL, Churg A, et al; for Pneumoconiosis Committee of the College of American Pathologists and the National Institute for Occupational Safety and Health. The pathology of asbestos associated disease of the lungs and pleural cavities: diagnostic criteria and proposed grading schema. Arch Pathol Lab Med. 1982; 106(11):544-596.
(2.) Roggli VL, Gibbs AR, Attanoos R, et al; for Asbestosis Committee of the College of American Pathologists and the Pulmonary Pathology Society. Pathology of asbestosis-an update of the diagnostic criteria. Arch Pathol Lab Med. 2010; 134(3):462-480.
(3.) Hammar SP, Abraham JL. Commentary on pathologic diagnosis of asbestosis and critique of the 2010 Asbestosis Committee of the College of American Pathologists (CAP) and Pulmonary Pathology Society's (PPS) update on the diagnostic criteria for pathologic asbestosis. Am J Ind Med. 2015; 58(10): 1034-1039.
(4.) Churg A, Wright JL, Wiggs B, Pare PD, Lazar N. Small airways disease and mineral dust exposure: prevalence, structure and function. Am Rev Respir Dis. 1985; 131(4):139-143.
(5.) Churg A, Wright JL. Small airways disease and mineral dust exposure. Pathol Annu. 1983; 18(pt 2):233-251.
(6.) Attanoos RL, Gibbs AR, Corrin B. The dilemma of 'asbestosis or lung fibrosis'-a case-referent study of 188 asbestos exposed naval dockyard workers and 175 UK non-exposed 'control' subjects. Lab Invest. 2006; 86(1):302A, 1405.
(7.) Roggli VL. Asbestos bodies and nonasbestos ferruginous bodies. In: Oury TD, Sporn TA, Roggli VL, eds. Pathology of Asbestos-Associated Diseases. 3rd ed. New York, NY: Springer; 2014:25-51.
(8.) Virk RK, Fraire AE. Interstitial lung diseases that are difficult to classify: a review of bronchiolocentric interstitial lung disease. Arch Pathol Lab Med. 2015; 139(8):984-988.
(9.) Holden J, Churg A. Asbestos bodies and the diagnosis of asbestosis in chrysotile workers. Environ Res. 1986; 39(1):232-236.
(10.) Henderson DW, Rantanen J, Barnhart S, et al. Asbestos, asbestosis and cancer: the Helsinki criteria for diagnosis and attribution: a consensus report of an international expert group. Scand J Work Environ Health. 1997; 23(9):311-316.
(11.) Wolff H, Vehmas T, Oksa P, Rantanen J, Vainio H; for Helsinki Criteria Updating Group. Asbestos, asbestosis, and cancer, the Helsinki criteria for diagnosis and attribution 2014: recommendations. Scand J Work Environ Health. 2015; 41(1):5-15.
(12.) Roggli VL, Pratt PC. Numbers of asbestos bodies on iron-stained tissue sections in relation to asbestos body counts in lung tissue digests. Hum Pathol. 1983; 14(4):355-361.
(13.) Hammar SP, Dodson RF. Asbestos. In: Tomashefski JF, Cagle PT, Farver CF, Fraire AE, eds. Nonneoplastic Lung Disease. 3rd ed. New York, NY: Springer; 2008:950-1031. Dail and Hammar's Pulmonary Pathology; vol. 1.
(14.) Schneider F, Sporn TA, Roggli VL. Asbestos fiber content of lungs with diffuse interstitial fibrosis. Arch Pathol Lab Med. 2010; 134(3):457-461.
(15.) Roggli VL, Sharma A. Analysis of tissue mineral fiber content. In: Oury TD, Sporn TA, Roggli VL, eds. Pathology of Asbestos-Associated Diseases. 3rd ed. New York, NY: Springer; 2014:253-292.
(16.) Churg A. Nonneoplastic disease caused by asbestos. In: Churg A, Green FHY, eds. Pathology of Occupational Lung Disease. 2nd ed. Baltimore, MD: Williams & Wilkins; 1998:277-338.
(17.) Browne K. Is asbestos or asbestosis the cause of the increased risk of lung cancer in asbestos workers? Br J Ind Med. 1986; 43(3):145-149.
(18.) Browne K. Asbestos-related disorders. In: Parkes WR, ed. Occupational Lung Disorders. 3rd ed. London, UK: Butterworth-Heinemann Ltd; 1994:411-504.
(19.) Hughes JM, Weill H, Hammad YY. Mortality of workers employed in two asbestos cement manufacturing plants. Br J Ind Med. 1987; 44(3):161-174.
(20.) Gylseth B, Churg A, Davis JMG, et al. Analysis of asbestos fibers and asbestos bodies in tissue samples from human lung: an international interlaboratory trial. Scand J Work Environ Health. 1985; 11(2):107-110.
Victor Roggli, MD; Allen R. Gibbs, MD; Richard Attanoos, MD; Andrew Churg, MD; Helmut Popper, MD; Bryan Corrin, MD; Teri Franks, MD; Francoise Galateau-Salle, MD; Jeff Galvin, MD; Philip Hasleton, MD; Koichi Honma, MD
Accepted for publication December 30, 2015.
From the Department of Pathology, Duke University Medical Center, Durham, North Carolina (Dr Roggli); the Department of Histopathology, Llandough Hospital, Penarth, United Kingdom (Dr Gibbs); the Department of Cellular Pathology, Cardiff and Vale University Health Board, Cardiff, Wales (Dr Attanoos); the Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada (Dr Churg); the Department of Pathology, Medical University Graz, Styria, Austria (Dr Popper); the Imperial College London National Heart and Lung Institute, London, United Kingdom (Dr Corrin); The Joint Pathology Center Pulmonary & Mediastinal Pathology, Silver Spring, Maryland (Dr Franks); the Department of Biopathology, Centre Leon Berard Mesopath, Lyon, France (Dr Galateau-Salle); Department of Radiology and the Division of Pulmonary & Critical Care Medicine, University of Maryland School of Medicine, Baltimore (Dr Galvin); the Department of Pathology, Wythenshawe Hospital Department Manchester, United Kingdom (Dr Hasleton); and Diagnostic Pathology, Kameda General Hospital, Kamogawa, Japan (Dr Honma).
Dr Roggli has consulted with plaintiff and defense attorneys in asbestosis litigation in the United States and abroad. Dr Churg has consulted with plaintiffs and defendants in asbestos litigation. Dr Attanoos provides expert testimony in medical-legal asbestos litigation. The other authors have no relevant financial interest in the products or companies described in this article.
Reprints: Victor Roggli, MD, Department of Pathology, Duke University Medical Center, Green Zone Room @355M, 200 Trent Dr, Durham, NC 27710 (email: firstname.lastname@example.org).