Reproducibility of histopathological subtypes and invasion in pulmonary adenocarcinoma. An international interobserver study.
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 (n=94) and the difficult cases (n=21) 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.
Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands. e.thunnissen@vumc.nl
Erik
E
Thunnissen
Mary Beth
MB
Beasley
Alain C
AC
Borczuk
Elisabeth
E
Brambilla
Lucian R
LR
Chirieac
Sanja
S
Dacic
Douglas
D
Flieder
Adi
A
Gazdar
Kim
K
Geisinger
Philip
P
Hasleton
Yuichi
Y
Ishikawa
Keith M
KM
Kerr
Sylvie
S
Lantejoul
Yoshiro
Y
Matsuno
Yuko
Y
Minami
Andre L
AL
Moreira
Noriko
N
Motoi
Andrew G
AG
Nicholson
Masayuki
M
Noguchi
Daisuke
D
Nonaka
Giuseppe
G
Pelosi
Iver
I
Petersen
Natasha
N
Rekhtman
Victor
V
Roggli
William D
WD
Travis
Ming S
MS
Tsao
Ignacio
I
Wistuba
Haodong
H
Xu
Yasushi
Y
Yatabe
Maureen
M
Zakowski
Birgit
B
Witte
Dirk Joop
DJ
Kuik
D000230:Adenocarcinoma / Q000145:classification* / Q000473:pathology*; D006801:Humans; D007391:International Cooperation; D008175:Lung Neoplasms / Q000145:classification* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D015588:Observer Variation; D015203:Reproducibility of Results