Hans Blaauwgeers

79 Artifacts and histologic pitfalls in the lung measurement instruments. In a reproducibility study on the morphologic interpretation of transbronchial lung biopsies, the observer agreement was low for bronchiolitis obliterans111. Perhaps the contraction effect played a role here too. Artifactual knife carryover is a well-recognized phenom- enon. In fact, sometimes entire strips of mucosa are displaced into bronchiolar and alveolar spaces89. Interestingly, the 2015 World Health Organization classification of lung adenocarcinoma describes a pattern of lung cancer ‘‘spreading through the airways’’ (STAS)112. This STAS-like pattern had also been described previously under different names113–116. Subsequently, the association of STAS and poor prognosis has been reported for larger studies117 118. Warth and colleagues118 reported that the presence of STAS was tightly linked to specific growth patterns. In resected surgical specimens, STAS has been associated with reduced overall and disease-free survival, which was growth pattern, but not stage, independent. The study of Kadota and colleagues117 reports a higher risk of recurrence in patients with STAS-positive tumors than in patients with STAS- negative tumors in a limited resection group. In contrast to the study of Warth and colleagues118, in the lobectomy group the presence of STAS was not associated with recurrence. In STAS the underlying biologic assumption is that in an adenocarcinoma with a micropapillary, acinar, or solid component with dissociated tumor cells, tumor fragments can spread aerogenously well beyond the mass lesion and endanger the prospect of a complete resection if less than a lobectomy is performed112. The STAKS explanation for association between STAS and histologic patterns with poor prognosis lies in the fact that tumor cells have a tendency for dissociation. In the micropapillary pattern, the seemingly loose alveolar cells (partly dissociated tumor cells) in one section are connected to other tumor cells or to the basement membrane in the section above or below, but they are disconnected in another plane of sectioning. Moreover, the big (shovel-like) force applied during gross cutting (see Figure 8 for relative sizes) disconnects the cells or clusters of cells with a tendency to dissociate from their fixed connection, freeing them and allowing displacement, similar to the apple/ink phenomenon shown in Figure 6. 5

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