P3.01-018 Reproducibility in Classification of Small Lung Adenocarcinomas: An International Interobserver Study

The 2015 WHO classification for lung adenocarcinoma (ACA) provides criteria for diagnosis of adenocarcinoma in-situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (INV). Differentiating these entities can be difficult, and as understanding of prognostic significance increases, inconsistent classification is problematic. Sixty cases of lung ACAs (≤2cm) were reviewed by an international panel of 6 lung pathologists. One slide reflecting overall morphology of each case was digitally scanned to an internet browser-based viewer. In round one, the panel independently reviewed each case to assess predominant pattern, invasive component size, and final diagnosis (AIS, MIA or INV). After a consensus conference among participants, a second round of independent review of the cases was performed. Additionally, a discussion on interpretation of elastic stain for evaluation of invasion will precede a third round of review with assessment of a concomitant elastic stain for each case. Statistical analysis was performed for each round. In round one, the overall kappa value for AIS versus MIA and INV was 0.34 (fair agreement), and that for AIS and MIA versus INV was 0.44 (moderate agreement). The raters had 100% agreement on final diagnosis in 10 cases (AIS, n=2; MIA, n=2; INV, n=6). In 28 cases with poor agreement on final diagnosis and invasive measurement, inconsistent measurement of multifocal invasion led to wide variance in 5 cases, and subjectivity in pattern recognition led to variance in 23 cases. Misinterpretation of the WHO criteria for MIA resulted in 18 instances of misclassification across all raters. A case with a predominant mucinous lepidic pattern had a range of diagnoses (AIS, n=1; MIA, n=1; INV, n=4). In round two, the overall kappa value for AIS versus MIA and INV is 0.40 (fair agreement), and that for AIS and MIA versus INV is 0.36 (moderate agreement). The raters had 100% agreement on final diagnosis in 12 cases (AIS, n=3; MIA n=4; INV, n=5). Misinterpretation of the WHO criteria for MIA was seen in 6 instances. The intraobserver kappa coefficient ranged widely from 0.259 to 0.859. Interobserver agreement on diagnosis of small lung ACAs between raters was fair to moderate, with minimal improvement after a consensus conference. Inconsistent measurement of multifocal invasion, subjectivity in pattern recognition, misinterpretation of the WHO criteria, and subjective interpretation of mucinous ACA have contributed to interobserver discordance. A third round of evaluation is currently ongoing to assess for improvement and the utility of elastic stains.