85 A Prospective Study of Loose Tissue Fragments in resected NSCLC Introduction The 2015 World Health Organization (WHO) Classi cation of Lung Tumors considers “Spread Through Air Spaces (STAS)”112 a form of invasion in lung carcinoma. It is de ned as “spread of lung cancer cells into air spaces in the lung parenchyma beyond the edge of the main tumor.” The same morphologic nding was recently described as an artifact, namely the spread of loose tissue fragments attributed to lung specimen sectioning, and designated “Spreading Through A Knife Surface” (STAKS)120. Although this distinction has signi cant clinical importance regarding adequacy of resection and risk of local recurrence, this issue has only been addressed in retrospective studies. “STAKS” is considered an artifact secondary to one of the mechanical forces at play during specimen handling. A typical prosecting knife or scalpel blade is up to 30 times wider than a human cell, leading to carry over of cells along the knife’s path. This hypothesis implies that the direction of cutting in uences the number of free- oating tumor cells. Conceptually, a tissue block taken from a sample before tumor is reached should contain no or fewer loose tumor tissue fragments than a tissue block where the knife has already passed through the tumor. Generally, the information about cutting direction together with annotation of the tissue blocks is not included in pathology reports. Thus, retrospective studies cannot be used to prove or reject the hypothesis that these loose cell clusters are the result of mechanical forces and more importantly, artifactual. Furthermore, if this hypothesis holds, then it should occur in any pathology laboratory. To this end, we undertook a prospective multi-institutional study on lung resection specimens with systematic recording of cutting direction and tissue block annotation. Subsequently, the histologic sections were examined for the presence and frequency of loose tissue fragments. Materials and methods A prospective, multi-institutional study of non–small cell lung cancer (NSCLC) lobectomy and pneumonectomy resection specimens was performed from January 1 through July 1, 2016. Prosection, sampling, and scoring of displaced fragments was undertaken in a systematic manner. For prosection the specimen was either cut in a fresh unfixed state, or after formalin perfusion fixation. The first cut was made with a clean long knife; the second cut was made in a parallel plane to the first cut, without cleaning the knife. These 2 pieces were each divided into 2 sections without cleaning the knife such that 4 formalin-fixed paraffin-embedded tissue blocks were procured. Block 1 was the upper part of the first cut containing normal lung tissue and then tumor tissue; block 2: the lower part of the first cut, containing first tumor tissue and then normal lung tissue; block 3: the upper part of the second cut, identical to block 1; block 4: the lower part of the second cut, similar to block 2 (Fig. 1). 6
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