184 Chapter 14 a) complete alveolar filling tumour growth is a solid pattern similar to the WHO; b) cribriform pattern is made of multiple small lumina visible within an alveolar space which fit in an invasive acinar pattern324 325 326; c) micropapillary growth shows tufting with discohesive tumour cells327 328 329; and d) a grey zone refers to an alveolar growth that exceeds the criteria of a monolayer of collapsed AIS but does not meet the criteria for options a-c. These alveolar growth patterns are surrogate markers of invasion, as opposed to true morphologic invasion which is frequently associated with desmoplastic stromal reaction. Examples of the latter are invasive growth of individual, small tumour cell clusters or glands, usually surrounded by desmoplastic stroma and lacking elastin. A summary is shown in table 1. Table 1. Revised adenocarcinoma classification based on evaluation of H&E, CK7 and elastin stainings. Revised adenocarcinoma classification*) Remarks AIS ± collapse Regular pattern, monolayer of tumour cells, elastin in alveolar wall Iatrogenic collapse is collapse of flexible parts of the parenchyma. Biological collapse is associated with an increase of elastin (Noguchi type B). Without increase of elastin is Noguchi type A10. Minor collagen fibers may be present in biological collapse between elastin and tumour cells. This observation needs further study. In CK7 stain a regular pattern of CK7 positive tumour cells. Borders of bronchovascular bundles and interlobular septa are respected. Any irregularity in the CK7 pattern should be scrutinized for focal true invasion. Tangential cutting of. a monolayer may lead to focal pseudo-stratification. This should not be interpreted as micropapillary or grey zone. Iatrogenic collapsed AIS has pseudo-papillary and pseudo-acinar appearance Carcinomas do not produce elastin. Segmented (or continuous) elastin fibers in relatively thin alveolar walls point to growth on alveolar wall. Luminal alveolar macrophages may vary in number. When abundantly present the iatrogenic collapse is less pronounced. True invasion in: Bronchovascular bundle Expansion in size, also visible in elastin staining Interlobular septum Delineated by elastin on both sides. Alveolar space, accompanied by desmoplastic stroma Desmoplastic stroma may be focal or very extensive (solid). The CK7 supports in the recognition of individual tumour cells. Some pulmonary adenocarcinomas lack or have reduced CK7 staining intensity330. Visceral pleura Elastin criteria, similar as in WHO 2021 Interstitium = stroma of alveolar walls When alveolar walls are lined with alveolar type II cells, think of metastases. Small acinar adenocarcinoma has glands <<200 μm and usually not surrounded by elastin.
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