141 Editorial (PRO/) CON: is STAS an inducible artifact? Displacement during pathology handling The use of a knife during grossing has been reported as a possible cause of displaced tumour (and benign) cells in tissue120. As a reaction upon STAS appearing in the WHO classification19, a prospective study by Blaauwgeers et al. was performed about loose tumour cells and tissue sampling from a proximal and distal side from cutting direction162. The authors hypothesized that, if the grossing knife (blade thickness 250micron, blade holder thickness 2000 micron = 2 mm.) was a possible cause of STAS, the first block would have less displaced tumour cells (tumour cell size range around 20-40 micron) than the other three blocks in sequence when the same knife was used. They showed in this multi-institutional study significantly more displaced tumour cells in the other three blocks compared to the first sampled tissue fragment (i.e., tissue cut by the knife before the knife reaches the tumour). During grossing there was no obligation to clean or change the knife. Subsequently, a carefully designed study of Metovic and colleagues175 was published, where a new clean blade was used for each cut, and the sequential analysis of fresh and formalin-fixed specular samples containing the lung tumour and the peritumoural parenchyma performed. No difference was found between the proximal and distal samples in the cut of the fresh sample, nor in the cut after 24 hours fixation. One of the issues that does not cause a difference between studies of Blaauwgeers et al. and Metovic et al. is the method of counting. Metovic and colleagues used the method of Kadota as well as the method used by Blaauwgeers and colleagues and showed almost the same scores (correlation coefficient >0.90)224, indicating that the differences in reported STAS data from other studies cannot be attributed to differences in these counting methods. This study of Metovic and colleagues claims to perform vertical cuts only by the pathologist175 224. However, we have the experience that perfectly vertical cuts are practically impossible to perform because of resistances generated by entire cutting edge (a knife as a second kind of lever) and the soft consistency of lung parenchyma, preventing thin slices to obtain (it is not just like a paraffin block fixed on a microtome with moving blade in the same direction of cutting), since there is always a transversal movement necessary to sequentially reduce in single cutting lines the tumour mass as a whole, sometimes even accidental and imperceptible subjectively, which is thus inherent to cutting procedure by itself197. It is impossible to account for vertical and lateral-transversal cut, even if it is minimal and apparently controlled. It is likely that at the tumour edges the tumour cells have the soft consistency of a raw egg or like an amoeba, and are prone to be dissociated under minimal pressure while cutting or by unavoidable traumas even occurring during the preoperative biopsy process. In Metovic’s study another possible source of detachment is the manipulation by the pathologist itself while handling175, sampling or simply describing the sample (touch and palpation are commonly performed while grossing (Figure 5). Likely, interfering cut procedures are probably the last ones to intervene. 11
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