195 Pattern recognition in pulmonary AdC; a modified classification Therefore, in analysis of follow-up of AIS, the two cohorts were combined. The 5-years RFS of the 10 patients with AIS was 100% as compared to 77% of the 60 patients with invasive adenocarcinoma (p=0.11, Figure 6). The 5-year OS for the patients with AIS was 100% and with invasive adenocarcinoma 74.5% (p=0.072). In one of the reclassified cases, 6 years after the primary resection, there was suspicion of recurrent disease in a mediastinal lymph node (N7). After further analysis, this turned out to be a second primary with a different cytology and immunohistochemistry: large cell neuroendocrine carcinoma. Survival analysis in patients with or without scars revealed no significant differences in RFS and OS. Figure 13. Kaplan-Meier curves of the RFS of the 10 patients with AIS cases compared to the 60 invasive adenocarcinomas (p=0.11). Discussion This study, using a mathematical model and histologic arguments, explained how iatrogenic collapsed pulmonary parenchyma causes wrinkling of the alveolar walls and alteration in tumour cell height. Taking into account the changes in iatrogenic collapsed AIS histology, led to reclassification of 9 patients with small pulmonary adenocarcinoma (13.0%) to AIS, supported by the 100% recurrence-free survival rate. Furthermore, we described in detail revised classification criteria using elastin and keratin 7 immunohistochemistry in this study and recognized other intra-alveolar growth patterns, other than the monolayer like in AIS in the revised classification, that could be surrogate markers of invasion. 14
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