113 Letter: STAS, can artifact be excluded? To the Editor With great interest we read the study of Metovic et al175 “Gross specimen handling procedures do not impact the occurrence of spread through air spaces (STAS) in lung cancer” in search for scientific truth in the discussion about spread through air spaces (STAS), whether STAS is an artifact or a biological reality. The authors deserve a compliment for performing a more controlled prospective study then the study of Blaauwgeers et al162 also published in your journal, with respect to the use of a clean knife for every cut. Nevertheless, we have 2 questions about the interpretation of their data. The first one deals with the statement in the discussion “As it is against physical laws that the possibility of neoplastic cell clusters to be misplaced in the reverse direction of an acting physical force, as that produced by a cutting blade, it seems virtually impossible to interpret STAS images in the upper parenchymal portion as a knife-induced artifact.” The authors seem to think of only a vertical cut into the tissue without relevant mechanical force on the tissue. A possible confounder may, beside the downward displacement also be a slight sideward movement of an oblique knife. Moreover, using an ~800 μm thick knife there has to be a physical downward force at cellular level120. This force does not exclude a sideways and possibly upward wave in a tissue structure that consist of 70% water. Think about examples like a bow wave of a ship sailing in the water, the upward rain-drop image when it rains “cats and dogs” and, for example, the guillotine, with a vertical controlled, yet oblique knife. In these examples, there is besides a sideways also an even upward movement of water/blood. The second question deals with the extravasated erythrocytes around the loose displaced tumor cells (interpreted a “STAS”) present in all the figures. Of note, Pelosi et al174 interpreted the presence of such erythrocytes around the also displaced benign neuroendocrine cells as an artifact. On the basis of the confounder of hard to prove but not difficult to imagine crude cutting force (including the effect of extravasated erythrocytes) we think that the suggestion in the title “Gross specimen handling procedure do not impact the occurrence of spread through air spaces (STAS) in lung cancer” should be downsized. Future studies are warranted. 9
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