Analysis of the Histologic Features Associated With Interobserver Variation in Idiopathic Pulmonary Fibrosis

The histologic manifestation of idiopathic pulmonary fibrosis (IPF) is usual interstitial pneumonia (UIP), which is a good prognostic determinant of survival compared with other histologic interstitial lung disease patterns. According to the current international guidelines, the histologic features of suspected IPF/UIP are divided into 4 categories: UIP, probable UIP, possible UIP, and not UIP pattern. Four pulmonary pathologists who were blinded to clinicoradiologic information reevaluated 50 surgical lung biopsies (83.3%), 6 lung explant (10.0%), and 4 autopsy samples (6.7%) from the FinnishIPF registry (N=60) using the current diagnostic guidelines. Additional histologic features atypical for UIP were also evaluated and compared with clinicora-diologic information. The interobserver agreement of pathologists was examined by Cohen kappa (κ) coefficient; the survival of the patients was estimated with Kaplan-Meier curves. The histologic reevaluation indicated that 38 of 60 patients (63.3%) had definite UIP. Inflammation was the most common additional histologic finding (15/60, 25.0%). The interobserver agreement on histologic diagnosis ranged from slight (κ=0.044) to substantial (κ=0.779). The interobserver agreement varied extensively with regard to the presence of giant cells. The observed histologic features displayed no association with radiologic patterns or survival. Definite UIP and honeycombing findings in high-resolution computed tomography correlated with poor prognosis. A high level of interobserver variability was observed between pathologists, even in this well-defined cohort of IPF patients, which highlights the importance of multidisciplinary decision making in IPF diagnostics and stresses the need for a reassessment of the histologic criteria. Conflicts of Interest and Source of Funding: K.M. has received grants from the Foundation of the Finnish Anti-Tuberculosis Association, the Research Foundation of the Pulmonary Diseases, the Väinö and Laina Kivi Foundation, the University of Helsinki, and the Biomedicum Helsinki Foundation. U.H. has received congress and meeting travel costs from Boehringer Ingelheim, Chiesi, and Roche, and lecture fees from Boehringer Ingelheim and Roche. E.L.-B. has received grants from the Foundation of the Finnish Anti-Tuberculosis Association, lecture fees from Oy Eli Lilly Finland, Pfizer, and Roche, congress and meeting travel costs from Astra Zeneca, Roche, BMS, and MSD, and advisory board fees from Pfizer and Roche. M.M. has received grants for the FinnishIPF study from Sigrid Jusélius Foundation and the Academy of Finland, Roche, and Boehringer Ingelheim. R.K. has received congress and meeting travel costs from Roche, Boehringer Ingelheim, and Orion, a lecture fee from Roche, an advisory board fee from GSK, and grants for the research group from the Foundation of the Finnish Anti-Tuberculosis Association, the Research Foundation of the Pulmonary Diseases, the Health Care Foundation of North Finland, and state subsidies of the Kuopio and Oulu University Hospitals. For the remaining authors none were declared. Correspondence: Kati Mäkelä, BM, Transplantation Laboratory, Pulmonary Diseases, B410b, Haartman Institute, Haartmaninkatu 3, Helsinki FI-00290, Finland (e-mail: kati.makela@helsinki.fi). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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