Interobserver variation among pathologists and refinement of criteria in distinguishing separate primary tumors from intrapulmonary metastases in lung Journal Article


Authors: Nicholson, A. G.; Torkko, K.; Viola, P.; Duhig, E.; Geisinger, K.; Borczuk, A. C.; Hiroshima, K.; Tsao, M. S.; Warth, A.; Lantuejoul, S.; Russell, P. A.; Thunnissen, E.; Marchevsky, A.; Mino-Kenudson, M.; Beasley, M. B.; Botling, J.; Dacic, S.; Yatabe, Y.; Noguchi, M.; Travis, W. D.; Kerr, K.; Hirsch, F. R.; Chirieac, L. R.; Wistuba, I. I.; Moreira, A.; Chung, J. H.; Chou, T. Y.; Bubendorf, L.; Chen, G.; Pelosi, G.; Poleri, C.; Detterbeck, F. C.; Franklin, W. A.
Article Title: Interobserver variation among pathologists and refinement of criteria in distinguishing separate primary tumors from intrapulmonary metastases in lung
Abstract: Multiple tumor nodules are seen with increasing frequency in clinical practice. On the basis of the 2015 WHO classification of lung tumors, we assessed the reproducibility of the comprehensive histologic assessment to distinguish second primary lung cancers (SPLCs) from intrapulmonary metastases (IPMs), looking for the most distinctive histologic features. An international panel of lung pathologists reviewed a scanned sequential cohort of 126 tumors from 48 patients and recorded an agreed set of histologic features, including tumor typing and predominant pattern of adenocarcinoma, thereby opining whether the case was SPLC, IPM, or a combination thereof. Cohen κ statistics of 0.60 on overall assessment of SPLC or IPM indicated a good agreement. Likewise, there was good agreement (κ score 0.64, p < 0.0001) between WHO histologic pattern in individual cases and SPLC or IPM status, but the proportions diversified for histologic pattern and SPLC or IPM status (McNemar test, p < 0.0001). The strongest associations for distinguishing between SPLC and IPM were observed for nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intraalveolar clusters, and necrosis. Conversely, the associations for lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization, and emperipolesis did not reach significance with tumor extent. Comprehensive histologic assessment is recommended for distinguishing SPLC from IPM with good reproducibility among lung pathologists. In addition to main histologic type and predominant patterns of histologic subtypes, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate strongly correlate with pathologic staging status. © 2017 International Association for the Study of Lung Cancer
Keywords: clinical article; controlled study; human tissue; human cell; histopathology; cancer staging; reproducibility; cell death; observer variation; cohort analysis; lung cancer; pathology; lung metastasis; lung adenocarcinoma; cell size; mitosis rate; second cancer; cancer classification; pathologist; nucleolus; interobserver variation; lymphocytosis; cell nucleus inclusion body; lymph vessel metastasis; multiple tumors; human; priority journal; article
Journal Title: Journal of Thoracic Oncology
Volume: 13
Issue: 2
ISSN: 1556-0864
Publisher: Elsevier Inc.  
Date Published: 2018-02-01
Start Page: 205
End Page: 217
Language: English
DOI: 10.1016/j.jtho.2017.10.019
PROVIDER: scopus
PUBMED: 29127023
PMCID: PMC6276791
DOI/URL:
Notes: Article -- Export Date: 2 April 2018 -- Source: Scopus
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  1. William D Travis
    743 Travis