310 Appendices adenocarcinoma variant may be similar to that for the pT2 category, while squamous cell carcinoma with multiple nodules may remain pT3. This population analysis of overall survival for the pT3N0 subcategory for NSCLC suggests that histological variant is a relevant description for the category of two or more nodules, provides no support for the shift of tumors larger than 7 cm to the pT4 category, and suggests that a combination of two pT3 descriptions (the mixed group) deserves migration to pT4. However, the TNM classification currently only uses anatomical locations in the classification. Adding orthogonal characteristics may further refine the prognostic classification. Part II focuses on the phenomenon of Spread Through Air Spaces (STAS). This has been described as a new way of metastases since the 2015 WHO classification, but it may be an artifact. Chapter 5 describes various histopathological artifacts related to tissue treatment after removal and upon receipt at the pathology department. It explains the effect of surgical collapse, which is the collapse of lung tissue after removal from the thoracic cavity. Additionally, spreading of tumor tissue by a knife during the cutting of the resection specimen is described as a possible explanation for the presence of loose tumor cells or cell clusters in alveolar spaces away from the tumor’s border. This finding is referred to as spread through a knife surface (STAKS) instead of STAS and is considered an artifact. In Chapter 6, a prospective multicenter study is described that suggests that STAS is an inducible phenomenon. In 44 resection specimens, the number of loose tumor cells and/or cell clusters was counted in four sections taken through the tumor without cleaning the preparation knife. The number of loose cells and/or clusters increased from the first section that was cut without going through the tumor to the last section where the knife had been used twice through the tumor. The number of cells was significantly greater between the first section and sections 2-4. Cells were also found in the alveoli originating from benign bronchial epithelium, also referred to as dragging by the knife. These findings were independent of the institution. Based on this study, it was concluded that it is highly likely that STAS is an inducible artifact. Chapter 7 is a critical evaluation of the STAS phenomenon, discussing the literature up until then and explaining alternative explanations for STAS, suggesting that it should be considered more as an artifact than a new way of metastasis. This chapter does not deny the association between STAS and prognosis, but rather suggests that it is a result of STAS being more common in high-grade tumors, such as micropapillary adenocarcinoma, where the cohesion between tumor cells is less. Chapters 8 and 9 provide commentary on this topic, related to a study on neuroendocrine tumors of the lung and the findings in a similar study as described in Chapter 6. This commentary emphasizes alternative explanations for finding loose tumor cells in alveoli other than the preparation knife during macroscopic processing at the pathology department, such as manipulation by the surgeon during lung lobe removal or manipulation by the pathologist.
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