132 Chapter 11 Since the introduction of spread through air spaces (STAS) as a new invasive pattern in the 2015 WHO classification on non-small cell lung cancer (NSCLC)112, there has been a debate on whether STAS is a true biological phenomenon or mainly an artifact induced by surgical and pathological handling of the resected specimen173. The definition of STAS is blurred by semantics and imaginary interpretations and lack thereof. In morphological terms pathologists may recognize “loose tumor cells” as single cells or clusters in airspaces. The definition of STAS has several peculiarities and implications19. A) The actual definition of STAS has two components: a morphological and a topological component. In the identification of STAS three so called “patterns” are recognized: single cells, micropapillary and solid tumour cell clusters117. For the topological component one of these “patterns” of intra-alveolar tumor cells need to be demonstrated in a continuum of airspaces containing intraalveolar tumor cells back to the tumor edge (or viewed from the other direction “beyond the main tumor edge”). However, if the tumour cells fitting in this “pattern” description are localized at a distance from the main tumor (without the continuum), then these tumor cell “patterns” are regarded as an artifact. In other words, although there is no morphological or cytological difference between these “patterns” the topological distribution denotes whether they are interpreted as artifact or STAS. Of note: the term “pattern” is in the lung not synonymous for “morphology”. Beside the above definition other aspects are relevant of the distinction of STAS: B) Tumour floaters shown by the presence of clusters of cells often randomly scattered over tissue and at the edges of the tissue section are favoured to be interpreted as an artifact117. However, no diagnostic clues are provided how to make the distinction between when (a few) tumor cells close to the tumor, when they are randomly scattered or “real” STAS. In a more recent publication, the refinement of “more than one tumor cell nest involvement of at least one air space beyond the tumor edge, and continuous alveolar spread from the tumour edge to the furthest STAS.”171 was made. The minimum number should be two “cells or clusters”. C) The presence of “jagged edges” of tumour cell clusters suggested tumour fragmentation or edges of a knife cut during specimen processing. In practice the knife blade has a width of 250 micron and the blade holder a width of 2000 micron (2mm). The blade itself has a width of at least 10x the size of a tumor cell, while the blade holder is broader than 80 tumor cells in a row (Figure 1).
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