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166 Chapter 13 Abstract Introduction The 8th edition of UICC/AJCC TNM classification system for non-small cell lung cancer (NSCLC) tumors recommends that size measurement of the primary tumor should be based solely on the invasive components. The distinction between adenocarcinoma in-situ (AIS) and other patterns, which are regarded as “invasive”, is of the utmost importance. In AIS, surgical collapse could alter architectural patterns, e.g., papillary, thus simulating invasive growth. The purpose of this study was: a) to examine the effect of surgical collapse in hematoxylin and eosin (H&E) stained slides on the WHO classification of pulmonary adenocarcinomas and b) to examine the additional value of cytokeratin 7 (CK7) immunohistochemical (IHC) staining for recognition of surgical collapse. Material and methods A retrospective, proof-of-principle study was performed, including early-stage NSCLC patients with resected primary adenocarcinomas, diagnosed between November 2007 and November 2010 at the Department of Pathology, Amsterdam UMC, location VUmc. H&E readings (using on average 2 slides (range 1-3)) without and with knowledge of surgical collapse were performed, blinded for clinical outcome. In a first scoring, pattern recognition according to the WHO was performed by one pathologist (HB). Subsequently, incorporating knowledge on surgical collapse, a second consensus scoring of the same slides was performed by two pathologists (HB & ET). An AIS with surgical collapse pattern was interpreted as non-invasive when a compressed preexisting alveolar pattern was recognizable. Additionally, CK7 immunohistochemical stained slides of the same block were independently scored based on recognition of a regular collapsed pattern and monolayer of tumor cells. For survival analysis, patients with more than one tumor were categorized as ‘invasive’ if at least one of the tumors was invasive. Results A total of 74 histological sections of 40 tumors from 33 patients were scored. After the first H&E scoring according to the WHO classification, the 5-year overall survival (OS) rate for patients with a non-invasive pattern (n=2) versus invasive pattern (n=31) was respectively 100% and 48% (p=0.18). When surgical collapse was considered, 5 invasive cases were downgraded to non-invasive AIS. The 5-year OS rate for all those non-invasive cases (n=7) remained 100% and for the invasive cases (n=26) became 39% (p=0.019). After CK7 staining the same 7 cases were scored as non-invasive. The CK7 reading was perceived as an easy tool. Noteworthy, this shift of cases to the non-invasive category did NOT affect the 100% 5-years overall survival of this non-invasive category.

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