Reproducibility of visual estimation of lung adenocarcinoma subtype proportions

In 2011, a new classification of lung adenocarcinoma was published. Since then there have been multiple studies regarding observer variability in predominant subtype determination, with levels of agreement generally in the weak to moderate range. In the 2011 and subsequent WHO 2015 classification, a recommendation was also made to visually assess and record the percentage of each subtype in 5% increments. The present study was initiated to determine the reproducibility of such gestalt assessments and to compare these data to a formal morphometric assessment. Five experienced pathologists reviewed multiple single images of 25 adenocarcinomas, taken at 2× and 10×, and estimated the percentage of lepidic, acinar, papillary, micropapillary, and solid components in 5% increments. After 2 months all the pathologists again reviewed the same images presented to them in a different order. We found that there was poor reproducibility within observers at 2× power using a 5% evaluation, but that this improved using 10% or 25% cutoffs. Use of 10× magnification allowed weak to moderate reproducibility at 5% increments, and this was again improved using 10% or 25% cutoffs. Correlation with morphometric assessment was poor except for the papillary and micropapillary subtypes. Differences among pathologists were generally low except for the acinar and, to a lesser degree, lepidic subtypes, which showed a wide spread of data. When estimating tumor subtype proportions, use of a 10× objective, and utilization of 10% or preferably 25% cutoffs provides a greater degree of consistency than a 5% cutoff.