135 Editorial (PRO/) CON: is STAS an inducible artifact? F) The elephant in the room is in this context the erythrocyte: a benign cell that is present in practically all publications that contain microscopic examples of STAS, in the neighbourhood of the as STAS interpreted cells (Figure 2). Most pathologists will see these erythrocytes and immediately skip these for diagnostic purpose and mentally regard this as artifact. Recently, spreading of neuroendocrine epithelial cells and erythrocytes were regarded as an artifact174. The question is here: why are the erythrocytes interpreted as artifact and the adjacent loose tumour cells as STAS? In short, these considerations around the definition of STAS is actually based on topology of at least two “loose tumor cells”, which are on itself on morphological/ cytological grounds indistinguishable from what the leading authors call “artifacts”. In addition, inconsistency in interpretation of loose erythrocytes from adjacent tumour cells is arbitrary. Reproducibility of STAS in frozen section To be useful for pathology diagnosis in daily practice, the criteria for that diagnosis have to be clear allowing a pathologist to be consistent in time (intra-observer reproducibility) as well as lead to the same diagnosis between different pathologists (inter-observer variability). Studies on interobserver reproducibility can be divided in local and global approach: studies reporting on reproducibility between a few pathologists within an institute or within a region and studies involving pathologists from around the globe. The latter will be most informative. A possible application of STAS could be the use in frozen sections. The sensitivity for STAS in four studies ranged from 55 to 86%204 205 172. One study mentions a worrying lack of consistency in sampling: STAS was only consistently present in i) frozen section, ii) paraffin section of frozen section and iii) other tumor sections in 39% of the cases172. The reproducibility studies of STAS assessment in frozen sections revealed kappa scores of 0.51 and low 0.34, respectively204 205.The concerns of STAS analysis in frozen sections are clearly expressed in the summary of the paper by Villalba and colleagues, which are regional pathologists with specific interest in pulmonary pathology: “As current accepted definitions for STAS and artifactual clusters are variably interpreted by pathologists, more precise criteria should be established and standardized, before the assessment of STAS can be implemented globally in the intraoperative setting to aid surgical decision making”204. Alternative explanation for the occurrence of loose tumour cells Given the tendency of discohesion in malignant cells and the notion that the consistency of the cells is like a raw egg without a shell, other explanations for spreading of tumor cells may be the surgeon’s i) hand, ii) instrument (Figure 3 and 4), iii) (eventual) localization procedure, iv) tearing tissue through a pinhole in video assisted thoracic 11
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