182 Chapter 14 multilayering were excluded. The measurements were performed on the two cohorts. The Milan set was used as a test set and the OLVG cases for validation. Criteria of iatrogenic collapsed adenocarcinoma in situ in a proposed modification of the adenocarcinoma classification Iatrogenic collapsed AIS was defined as a folded alveolar wall lined with a monolayer of non-mucinous adenocarcinoma cells. Within “the alveolar wall” in the elastin stain fragmented or linear elastin fibers should be present. Moreover, in CK7 staining, a regular pattern of collapsed alveolar septa is visible. In AIS with iatrogenic collapse without scar, the in vivo structure is altered from straight alveolar walls to an undulated, folded, focally pseudopapillary or wavy appearance. On low power view, the tumour growth in AIS respects the physiological contours of the bronchovascular bundles and interlobular septa. The lining tumour cells can focally overlap with mild stratification314 and this effect is even accentuated by tangential cutting (Figure 5). The tumour cells in (iatrogenic collapsed) AIS have usually low nuclear grade322. Figure 5. Illustration of the phenomenon of tangential cutting. In AIS with scar, two components are discerned: fibrosis with dense collagen, and biological collapse with increased elastin. The latter is recognized by the pre-existing pulmonary architecture, previously described as Noguchi 1995 type B10 or Type II by Goto et al, both concluded to be non-invasive323. In AIS, the area with collagen rich scar lacks invasive tumour cells in the H&E and CK7 stain.
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