Reproducibility of histopathological subtypes and invasion in pulmonary adenocarcinoma. An international interobserver study

Erik Thunnissen, Mary Beth Beasley, Alain C. Borczuk, Elisabeth Brambilla, Lucian R. Chirieac, Sanja Dacic, Douglas Flieder, Adi Gazdar, Kim Geisinger, Philip Hasleton, Yuichi Ishikawa, Keith M. Kerr, Sylvie Lantejoul, Yoshiro Matsuno, Yuko Minami, Andre L. Moreira, Noriko Motoi, Andrew G. Nicholson, Masayuki Noguchi, Daisuke NonakaGiuseppe Pelosi, Iver Petersen, Natasha Rekhtman, Victor Roggli, William D. Travis, Ming S. Tsao, Ignacio Wistuba, Haodong Xu, Yasushi Yatabe, Maureen Zakowski, Birgit Witte, Dirk Joop Kuik

Research output: Contribution to journalReview articlepeer-review

206 Scopus citations


Histological subtyping of pulmonary adenocarcinoma has recently been updated based on predominant pattern, but data on reproducibility are required for validation. This study first assesses reproducibility in subtyping adenocarcinomas and then assesses further the distinction between invasive and non-invasive (wholly lepidic) pattern of adenocarcinoma, among an international group of pulmonary pathologists. Two ring studies were performed using a micro-photographic image-based method, evaluating selected images of lung adenocarcinoma histologic patterns. In the first study, 26 pathologists reviewed representative images of typical and difficult histologic patterns. A total number of scores for the typical patterns combined (n94) and the difficult cases (n21) were 2444 and 546, respectively. The mean kappa score (±s.d.) for the five typical patterns combined and for difficult cases were 0.77±0.07 and 0.38±0.14, respectively. Although 70% of the observers identified 12-65% of typical images as single pattern, highest for solid and least for micropapillary, recognizing the predominant pattern was achieved in 92-100%, of the images except for micropapillary pattern (62%). For the second study on invasion, identified as a key problem area from the first study, 28 pathologists submitted and reviewed 64 images representing typical as well as difficult examples. The kappa for typical and difficult cases was 0.55±0.06 and 0.08±0.02, respectively, with consistent subdivision by the same pathologists into invasive and non-invasive categories, due to differing interpretation of terminology defining invasion. In pulmonary adenocarcinomas with classic morphology, which comprise the majority of cases, there is good reproducibility in identifying a predominant pattern and fair reproducibility distinguishing invasive from in-situ (wholly lepidic) patterns. However, more precise definitions and better education on interpretation of existing terminology are required to improve recognition of purely in-situ disease, this being an area of increasing importance.

Original languageEnglish (US)
Pages (from-to)1574-1583
Number of pages10
JournalModern Pathology
Issue number12
StatePublished - Dec 2012


  • adenocarcinoma
  • histopathology
  • invasion
  • lung
  • reproducibility
  • subtyping

ASJC Scopus subject areas

  • General Medicine


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