197 Pattern recognition in pulmonary AdC; a modified classification A scar could be relevant as a sign of invasive growth and has been described as a potentially unfavourable prognostic feature in the 1980’s by Shimosato et al.276, whereby the composition of the scar itself was also identified as a prognostic criterion. Hyalinized scars in patients with a resected adenocarcinoma of 3 cm or less were associated with more lymph node metastasis or pleural invasion than those without scar or more fibrotic scars. Suzuki et al. found that patients with a central scar of less than 5 mm had a 100% 5-year overall survival rate334. More recently, Bittar et al. showed that adenocarcinoma with a scar was associated with a better prognosis335. Interestingly, their discussion mentions: “From a morphological standpoint, there is no histologic feature that could separate pre-existing subpleural scar/apical cap from scars associated with carcinomas”. This suggest that they observed increased elastin in line with biological collapse and associated good prognosis10. Comparable to Bittar et al335, our study consisted of a cohort without lymph node metastasis and an occasional case with pleural invasion, but their cases also included tumours larger than 3 cm (range 1-5). Also, in our study the majority of scars had a fibroelastic appearance (80%). Similar to Noguchi type B, we found in 5 of the 10 AIS cases a scar-like area10. In H&E staining, fibroelastosis is not always easily recognizable, while in the elastin staining, prominent increase of elastin supports proper interpretation. In those cases, with fibrotic and biologic collapsed scars, most (85.7%) had at least focal areas of invasion. Invasion was observed in all 7 ‘fibrosis only’ cases and a lower fraction in the ‘biological only’ cases (54.5%). In contrast to the studies of Shimosato and Bittar, nor the presence of a scar, neither the composition of it, was correlated with RFS nor OS in our study. This could be explained by the fact that in our study, cases with lymph node metastasis were excluded and the cohorts contained just one case with pleural invasion and contained just tumours of 3 cm or smaller. Recently, Yambayev and colleagues performed a study in the same pulmonary adenocarcinoma domain, searching for a “low malignant potential” subgroup with a better prognosis336. Their proposed criteria for “low malignant potential” adenocarcinoma among non-mucinous adenocarcinoma were a total size of ≤3 cm, exhibiting ≥15% lepidic growth, and lacking non-predominant high-grade patterns (≥10% cribriform, ≥5% micro- papillary, ≥5% solid), >1 mitosis per 2 mm2, angiolymphatic or visceral pleural invasion, spread through air spaces or necrosis336. They followed the managerial process of the current WHO classification19 and did no attempt to distinguish morphological invasion. Interestingly, they accepted high grade patterns, but with low thresholds: “low malignant potential” may have up to 10% cribriform and micropapillary and 5% solid pattern. In comparison with our study this may encompasses cases with tangential cutting of lepidic AIS, which may mimic focal high-grade (solid) patterns and explain the prognostic association in their study. It is likely that cases in our study may represent the same subgroup as in the study of Yambayev and colleagues. For example, in their figure 1D, diagnosed as acinar predominant adenocarcinoma, we would diagnose this as collapsed AIS. 14
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