142 Chapter 11 Figure 5. Lobectomy specimen with elevated pleura above the tumour and different moments of gross cutting. Photos made in Italy received with the courtesy of M. Papotti M.D. PhD. and Alessandra Pittaro, M.D. Note that with the intention to cut in the vertical direction only, the distance between two fingers of the left hand holding the tumor mass is getting progressively smaller, indicating increasing pressure on the tumor. In a third prospective study, Xie and colleagues examined 83 patients and collected an upper and a lower block225. In 45 patients STAS was noted, but only consistently present in upper and lower block in 60% of the cases. In the remaining 40% STAS was only present in the lower block. Remarkably, Xie and colleagues interpreted in these (inconsistent) cases the presence of STAS as an artifact: in patients with real STAS, the upper blocks still had fewer fields of STAS compared to lower blocks (p =0.016), emphasizing an effect of the cutting direction. In addition, EBUS needles may also displace tissue fragments226. In short, the prospective studies on sampling blocks related to the gross cutting direction at the pathology laboratory is still a matter of debate: beside the needle displacement two studies find more loose tumour fragments in the blocks after cutting through the tumour, while the other did not show this difference. Biology of loose tumour cells Wild type epithelial cells are attached to each other with adhesion molecules. Detachment will lead to apoptosis. Adhesion molecules play a role in the apoptotic process. In pulmonary adenocarcinoma downregulation of E-Cadherin is a frequent finding with increased risk for metastases, which is supported in model systems and leads to a reduction in cohesion, a characteristic of malignant cells, what is also recognized in other organs. For example, discohesion of tumor cells in cytological samples of breast cancer is used as a criterium for malignancy, not as a prove for invasion, as ductal carcinoma in situ may show the same dissociation. Remarkably, in the lung the discohesion of loose tumor cells is, if interpreted as STAS, in the WHO 2021 classification arbitrarily interpreted as invasive19. The discohesion is a clear morphological characteristic of the micropapillary pattern. Peculiar is in this context is that in the study of Yagi and colleagues E-cadherin
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