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Published in: BMC Pulmonary Medicine 1/2021

Open Access 01-12-2021 | Idiopathic Pulmonary Fibrosis | Research

Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project

Authors: Robert Camp, Maxwell L. Smith, Brandon T. Larsen, Anja C. Roden, Carol Farver, Andre L. Moreira, Richard Attanoos, Raghavendra Pillappa, Irene Sansano, Alexandre Todorovic Fabro, Robert J. Homer

Published in: BMC Pulmonary Medicine | Issue 1/2021

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Abstract

Background

Current interstitial lung disease (ILD) diagnostic guidelines assess criteria across clinical, radiologic and pathologic domains. Significant interobserver variation in histopathologic evaluation has previously been shown but the specific source of these discrepancies is poorly documented. We sought to document specific areas of difficulty and develop improved criteria that would reduce overall interobserver variation.

Methods

Using an internet-based approach, we reviewed selected images of specific diagnostic features of ILD histopathology and whole slide images of fibrotic ILD. After an initial round of review, we confirmed the presence of interobserver variation among our group. We then developed refined criteria and reviewed a second set of cases.

Results

The initial round reproduced the existing literature on interobserver variation in diagnosis of ILD. Cases which were pre-selected as inconsistent with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) were confirmed as such by multi-observer review. Cases which were thought to be in the spectrum of chronic fibrotic ILD for which UIP/IPF were in the differential showed marked variation in nearly all aspects of ILD evaluation including extent of inflammation and extent and pattern of fibrosis. A proposed set of more explicit criteria had only modest effects on this outcome. While we were only modestly successful in reducing interobserver variation, we did identify specific reasons that current histopathologic criteria of fibrotic ILD are not well defined in practice.

Conclusions

Any additional classification scheme must address interobserver variation in histopathologic diagnosis of fibrotic ILD order to remain clinically relevant. Improvements to tissue-based diagnostics may require substantial resources such as larger datasets or novel technologies to improve reproducibility. Benchmarks should be established for expected outcomes among clinically defined subgroups as a quality metric.
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Literature
1.
go back to reference Larsen BT, Smith ML, Elicker BM, et al. Diagnostic approach to advanced fibrotic interstitial lung disease: bringing together clinical, radiologic, and histologic clues. Arch Pathol Lab Med. 2017;141:901–15.CrossRef Larsen BT, Smith ML, Elicker BM, et al. Diagnostic approach to advanced fibrotic interstitial lung disease: bringing together clinical, radiologic, and histologic clues. Arch Pathol Lab Med. 2017;141:901–15.CrossRef
2.
go back to reference Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. N Engl J Med. 2018;378:1811–23.CrossRef Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. N Engl J Med. 2018;378:1811–23.CrossRef
3.
go back to reference Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–82.CrossRef Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–82.CrossRef
4.
go back to reference King TE, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083–92.CrossRef King TE, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083–92.CrossRef
5.
go back to reference Wells AU, Flaherty KR, Brown KK, et al. Nintedanib in patients with progressive fibrosing interstitial lung diseases—subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Respir Med. 2020;8:453–60.CrossRef Wells AU, Flaherty KR, Brown KK, et al. Nintedanib in patients with progressive fibrosing interstitial lung diseases—subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Respir Med. 2020;8:453–60.CrossRef
6.
go back to reference Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788–824.CrossRef Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788–824.CrossRef
7.
go back to reference Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198:e44–68.CrossRef Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018;198:e44–68.CrossRef
8.
go back to reference Lynch DA, Sverzellati N, Travis WD, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a fleischner society white paper. Lancet Respir Med. 2018;6:138–53.CrossRef Lynch DA, Sverzellati N, Travis WD, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a fleischner society white paper. Lancet Respir Med. 2018;6:138–53.CrossRef
9.
go back to reference Mäkelä K, Hodgson U, Piilonen A, et al. Analysis of the histologic features associated with interobserver variation in idiopathic pulmonary fibrosis. Am J Surg Pathol. 2018;42:672–8.CrossRef Mäkelä K, Hodgson U, Piilonen A, et al. Analysis of the histologic features associated with interobserver variation in idiopathic pulmonary fibrosis. Am J Surg Pathol. 2018;42:672–8.CrossRef
10.
go back to reference Hashisako M, Tanaka T, Terasaki Y, et al. Interobserver agreement of usual interstitial pneumonia diagnosis correlated with patient outcome. Arch Pathol Lab Med. 2016;140:1375–82.CrossRef Hashisako M, Tanaka T, Terasaki Y, et al. Interobserver agreement of usual interstitial pneumonia diagnosis correlated with patient outcome. Arch Pathol Lab Med. 2016;140:1375–82.CrossRef
11.
go back to reference Nicholson AG, Addis BJ, Bharucha H, et al. Inter-observer variation between pathologists in diffuse parenchymal lung disease. Thorax. 2004;59:500–5.CrossRef Nicholson AG, Addis BJ, Bharucha H, et al. Inter-observer variation between pathologists in diffuse parenchymal lung disease. Thorax. 2004;59:500–5.CrossRef
12.
go back to reference Walsh SLF, Wells AU, Desai SR, et al. Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study. Lancet Respir Med. 2016;4:557–65.CrossRef Walsh SLF, Wells AU, Desai SR, et al. Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study. Lancet Respir Med. 2016;4:557–65.CrossRef
13.
go back to reference UIP Consensus Trial. www.virtualslideshare.org/2. Accessd 21 Dec 2020 UIP Consensus Trial. www.virtualslideshare.org/2. Accessd 21 Dec 2020
14.
go back to reference Smith ML, Hariri LP, Mino-Kenudson M et al. Histopathologic assessment of suspected idiopathic pulmonary fibrosis: where we are and where we need to go. Arch Pathol Lab Med. 2020 Smith ML, Hariri LP, Mino-Kenudson M et al. Histopathologic assessment of suspected idiopathic pulmonary fibrosis: where we are and where we need to go. Arch Pathol Lab Med. 2020
15.
go back to reference Andrade J, Schwarz M, Collard HR, et al. The idiopathic pulmonary fibrosis clinical research network (IPFnet): diagnostic and adjudication processes. Chest. 2015;148:1034–42.CrossRef Andrade J, Schwarz M, Collard HR, et al. The idiopathic pulmonary fibrosis clinical research network (IPFnet): diagnostic and adjudication processes. Chest. 2015;148:1034–42.CrossRef
16.
go back to reference Staats P, Kligerman S, Todd N, Tavora F, Xu L, Burke A. A comparative study of honeycombing on high resolution computed tomography with histologic lung remodeling in explants with usual interstitial pneumonia. Pathol Res Pract. 2015;211:55–61.CrossRef Staats P, Kligerman S, Todd N, Tavora F, Xu L, Burke A. A comparative study of honeycombing on high resolution computed tomography with histologic lung remodeling in explants with usual interstitial pneumonia. Pathol Res Pract. 2015;211:55–61.CrossRef
17.
go back to reference Churg A, Bilawich A, Wright JL. Pathology of chronic hypersensitivity pneumonitis what is it? What are the diagnostic criteria? Why do we care. Arch Pathol Lab Med. 2018;142:109–19.CrossRef Churg A, Bilawich A, Wright JL. Pathology of chronic hypersensitivity pneumonitis what is it? What are the diagnostic criteria? Why do we care. Arch Pathol Lab Med. 2018;142:109–19.CrossRef
18.
go back to reference Raghu G, Remy-Jardin M, Ryerson CJ, et al. Diagnosis of hypersensitivity pneumonitis in adults. An official ATS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2020;202:e36–69.CrossRef Raghu G, Remy-Jardin M, Ryerson CJ, et al. Diagnosis of hypersensitivity pneumonitis in adults. An official ATS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2020;202:e36–69.CrossRef
19.
go back to reference Yagihashi K, Huckleberry J, Colby TV, et al. Radiologic–pathologic discordance in biopsy-proven usual interstitial pneumonia. Eur Respir J. 2016;47:1189–97.CrossRef Yagihashi K, Huckleberry J, Colby TV, et al. Radiologic–pathologic discordance in biopsy-proven usual interstitial pneumonia. Eur Respir J. 2016;47:1189–97.CrossRef
20.
go back to reference Crystal RG, Fulmer JD, Roberts WC, Moss ML, Line BR, Reynolds HY. Idiopathic pulmonary fibrosis. Clinical, histologic, radiographic, physiologic, scintigraphic, cytologic, and biochemical aspects. Ann Intern Med. 1976;85:769–88.CrossRef Crystal RG, Fulmer JD, Roberts WC, Moss ML, Line BR, Reynolds HY. Idiopathic pulmonary fibrosis. Clinical, histologic, radiographic, physiologic, scintigraphic, cytologic, and biochemical aspects. Ann Intern Med. 1976;85:769–88.CrossRef
21.
go back to reference Katzenstein AL, Zisman DA, Litzky LA, Nguyen BT, Kotloff RM. Usual interstitial pneumonia: histologic study of biopsy and explant specimens. Am J Surg Pathol. 2002;26:1567–77.CrossRef Katzenstein AL, Zisman DA, Litzky LA, Nguyen BT, Kotloff RM. Usual interstitial pneumonia: histologic study of biopsy and explant specimens. Am J Surg Pathol. 2002;26:1567–77.CrossRef
22.
go back to reference Takemura T, Akashi T, Kamiya H, et al. Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia. Histopathology. 2012;61:1026–35.CrossRef Takemura T, Akashi T, Kamiya H, et al. Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia. Histopathology. 2012;61:1026–35.CrossRef
23.
go back to reference Akashi T, Takemura T, Ando N, et al. Histopathologic analysis of sixteen autopsy cases of chronic hypersensitivity pneumonitis and comparison with idiopathic pulmonary fibrosis/usual interstitial pneumonia. Am J Clin Pathol. 2009;131:405–15.CrossRef Akashi T, Takemura T, Ando N, et al. Histopathologic analysis of sixteen autopsy cases of chronic hypersensitivity pneumonitis and comparison with idiopathic pulmonary fibrosis/usual interstitial pneumonia. Am J Clin Pathol. 2009;131:405–15.CrossRef
24.
go back to reference McDonough JE, Ahangari F, Li Q et al. Transcriptional regulatory model of fibrosis progression in the human lung. JCI Insight. 2019;4:e131597.CrossRef McDonough JE, Ahangari F, Li Q et al. Transcriptional regulatory model of fibrosis progression in the human lung. JCI Insight. 2019;4:e131597.CrossRef
25.
go back to reference Han Q, Luo Q, Xie JX et al. Diagnostic yield and postoperative mortality associated with surgical lung biopsy for evaluation of interstitial lung diseases: a systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2015;149:1394–401.e1.CrossRef Han Q, Luo Q, Xie JX et al. Diagnostic yield and postoperative mortality associated with surgical lung biopsy for evaluation of interstitial lung diseases: a systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2015;149:1394–401.e1.CrossRef
26.
go back to reference Hutchinson JP, Fogarty AW, McKeever TM, Hubbard RB. In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States. 2000 to 2011. Am J Respir Crit Care Med. 2016;193:1161–1167.CrossRef Hutchinson JP, Fogarty AW, McKeever TM, Hubbard RB. In-hospital mortality after surgical lung biopsy for interstitial lung disease in the United States. 2000 to 2011. Am J Respir Crit Care Med. 2016;193:1161–1167.CrossRef
27.
go back to reference Wells AU, Brown KK, Flaherty KR, Kolb M, Thannickal VJ, IPF CWG. What’s in a name? That which we call IPF, by any other name would act the same. Eur Respir J. 2018;51:1800692CrossRef Wells AU, Brown KK, Flaherty KR, Kolb M, Thannickal VJ, IPF CWG. What’s in a name? That which we call IPF, by any other name would act the same. Eur Respir J. 2018;51:1800692CrossRef
28.
go back to reference Marchevsky AM, Walts AE, Lissenberg-Witte BI, Thunnissen E. Pathologists should probably forget about kappa. Percent agreement, diagnostic specificity and related metrics provide more clinically applicable measures of interobserver variability. Ann Diagn Pathol. 2020;47:151561.CrossRef Marchevsky AM, Walts AE, Lissenberg-Witte BI, Thunnissen E. Pathologists should probably forget about kappa. Percent agreement, diagnostic specificity and related metrics provide more clinically applicable measures of interobserver variability. Ann Diagn Pathol. 2020;47:151561.CrossRef
29.
go back to reference van der Wel MJ, Klaver E, Duits LC, et al. Adherence to pre-set benchmark quality criteria to qualify as expert assessor of dysplasia in Barrett’s esophagus biopsies - towards digital review of Barrett’s esophagus. United Eur Gastroenterol J. 2019;7:889–96.CrossRef van der Wel MJ, Klaver E, Duits LC, et al. Adherence to pre-set benchmark quality criteria to qualify as expert assessor of dysplasia in Barrett’s esophagus biopsies - towards digital review of Barrett’s esophagus. United Eur Gastroenterol J. 2019;7:889–96.CrossRef
30.
go back to reference Richeldi L, Scholand MB, Lynch DA et al. Utility of a molecular classifier as a complement to HRCT to identify usual interstitial pneumonia. Am J Respir Crit Care Med. 2020;203:211–20CrossRef Richeldi L, Scholand MB, Lynch DA et al. Utility of a molecular classifier as a complement to HRCT to identify usual interstitial pneumonia. Am J Respir Crit Care Med. 2020;203:211–20CrossRef
Metadata
Title
Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project
Authors
Robert Camp
Maxwell L. Smith
Brandon T. Larsen
Anja C. Roden
Carol Farver
Andre L. Moreira
Richard Attanoos
Raghavendra Pillappa
Irene Sansano
Alexandre Todorovic Fabro
Robert J. Homer
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2021
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-021-01522-6

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