14 Chapter 1 In part III with the chapters 12-16, we focus on iatrogenic and biological collapse as a possible pitfall in the assessment of invasion in small adenocarcinomas. In chapter 12 we describe the role of elastin in pulmonary pathology and its possible usefulness in the recognition of non-invasive patterns. Chapter 13 discusses a proof-of-principle study that explores the feasibility of considering surgical collapse when diagnosing non-invasive cases of lung cancer. This study examines whether the use of cytokeratin 7 as an immunohistochemical marker can facilitate the recognition of surgical collapse and enable the diagnosis of more non-invasive cases with excellent prognoses. Chapter 14 details the morphological characteristics of iatrogenic and biologic collapsed AIS, incorporating lessons learned from a mathematical model and utilizing cytokeratin 7 and elastin staining to assess invasiveness. Two independent cohorts of resected adenocarcinomas measuring 3 cm or smaller were examined to investigate these aspects and their relationship to recurrence-free and overall survival was analyzed. Chapter 15 concerns a large international interobserver study, determining whether incorporating iatrogenic and biological collapse in the assessment of lung adenocarcinoma invasion using elastin and cytokeratin 7 stainings could diagnose (collapsed) AIS and reduce the interobserver variation of invasive patterns in small pulmonary adenocarcinomas. According to the WHO for AIS has a maximum size limit of 3 cm. We wondered whether AIS may occur as a larger tumor. In Chapter 16, we examined in the nationwide subgroup of T3N0 NSCLC for the possible presence of AIS with a size larger than 7 cm.
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