203 Reproducibility study on invasiveness of pulmonary AdC with a modified classification Conclusions There is significant interobserver variation in the measurements of invasive size and assignment of invasive patterns among pathologists. However, using refined morphological criteria along with CK7 and elastin staining can help improve recognition of collapsed AIS. The formal recognition of collapsed AIS can aid in identifying low-risk lesions that are wholly non-invasive. Introduction According to the 2015 WHO classification of non-mucinous lung adenocarcinoma, the predominant histological growth pattern present determines tumour subtype4. Furthermore, these patterns are used to assign tumour grade in recent IASLC recommendations252. The concepts of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), first established in the 2015 WHO classification, are being recognized increasingly frequently, particularly in lesions identified through lung cancer screening. When resected, both AIS and MIA show essentially 100% 5-years survival306 and their definitive identification is crucial to prevent overtreatment with, for example, adjuvant chemotherapy. 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 components19. The distinction between adenocarcinoma AIS from other patterns, which are all regarded as “invasive”, is therefore of utmost importance. The poor reproducibility of invasive pattern recognition in adenocarcinomas was shown by an IASLC pathology committee study in 201214. During surgical resection deflation is part of the procedure and specimens typically arrive at the pathology laboratory in a collapsed state, often being compressed to less than half of their in vivo width. This iatrogenic collapse changes the morphology of the resected adenocarcinoma as well as background tissue. In particular, the histological criteria of the WHO pattern classification, especially papillary and acinar subtypes, show overlap with iatrogenic collapsed adenocarcinoma in situ (IC-AIS). Our hypothesis is that the use of additional histopathological criteria may delineate IC-AIS from higher risk patterns currently designated as being invasive adenocarcinomas. The aim of the study was to examine if such additional histopathological criteria can improve the recognition of non-invasive growth, with or without iatrogenic collapse, in non-mucinous adenocarcinomas, and to determine the effect of these criteria on invasion measurements and subtype classification. To evaluate the potential of a revised classification, a group of 42 pathologists from different parts of the world were asked to interpret a series of adenocarcinomas twice. The first interpretation was based on the 2021 WHO classification, while in the second 15
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