167 Elastin in pulmonary pathology Conclusion This proof-of-principle study shows that taking surgical collapse into account when scoring H&E and IHC-CK7 slides can enable re-classification of WHO invasive NSCLC cases into non-invasive AIS cases. In this study, the shift in recognition improved the prediction of survival outcomes, highlighting the need to recognize surgical collapse in pathological readings, as this may prevent underdiagnosing AIS. Introduction According to the 2015 WHO classification of non-mucinous lung adenocarcinoma, the predominant pattern present in any case is used for subtyping the tumors306.The concepts of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), first established in the 2015 WHO classification, are now recognized more frequently, particularly in patients taking part in lung cancer screening protocols. Both AIS and MIA are associated with 100% 5-years survival. The 8th edition of UICC/AJCC TNM classification system for non-small cell lung cancer (NSCLC) tumors recommends that the size measurement of the primary tumor be based solely on the invasive components307. The distinction between adenocarcinoma in situ (AIS) from other patterns, which are regarded as “invasive” is therefore of the utmost importance. Surgical collapse or compression of the alveolar structure/lepidic pattern was recognized recently as a frequent phenomenon in pulmonary resection specimen279. This pattern may affect the shape of normal alveoli as well as alveoli lined by tumor cells and can significantly modify the morphology of the tumor. Artefactual compression of alveolar structures lined by tumor cells may lead to folding or tufting in deflated lung parenchyma. As a consequence, it is possible that collapsed folds (alveolar walls) may mimic a papillary architecture when cross-sectioned90 308. Our assumption is that not all pathologists realize that collapse may mimic certain patterns of pulmonary adenocarcinoma classification such as papillary and acinar patterns. The clinical consequence is that some in-situ carcinomas are diagnosed as invasive lung cancer, with the implication of greater invasive tumor diameters leading to possible differences in staging or even neoadjuvant therapy. Our hypothesis is that cases with surgical collapse in AIS will have a favorable prognosis. For the interpretation of surgical collapse, the recognition of the pre-existing architecture is of utmost importance. Currently there is no information whether a cytokeratin stain is supportive for the recognition of the pre-existing architecture. Therefore, we performed a proof of principle study to examine the recognition of surgical collapse as a pseudo-invasive pattern in cases of AIS and the possible supportive role of CK7 in the recognition of these pseudo-invasive patterns, that should correlate to an excellent prognosis. 13
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