104 Chapter 7 studies STAS is correlated with other prognostically unfavorable factors, such as lymphovascular invasion, pleural invasion, high grade histology (such as micropapillary and solid patterns) and EGFR-negative status (see table 2), and associated with poorly differentiated features such as necrosis, higher grade, nuclear diameter and Ki67 labeling index. In daily practice the prognosis of patients diagnosed with lung cancer is guided by the TNM system. Pathology factors relevant in the TNM system are tumor size, lymph node metastases and pleural invasion. The value of another prognostic pathology factor based on an artifact may be appreciated in the context of more than 100 additional prognostic factors have been published, none of which have made it into the TNM168,169. After its rapid embrace by pathologists, the concept of aerogenous spread has been inhaled by the radiologists, starting with a radiological definition: intrapulmonary discontinuous spread of neoplastic cells through airspaces and airways, with the discontinuous foci seen close to the primary tumor as satellite foci or at distance, including in the contralateral lung170. Remarkably, the size of the tumor clusters seen microscopically defined STAS are below the current detection limit of CT scanning. There is sufficient evidence to support that tumor cell clusters or loose cells are an artifact caused by displacement from surgical manipulation and gross processing - particularly from a knife blade. Thus, tumor cell clusters or loose cells should neither be interpreted as “spread through air spaces” (aerogenic or pneumonic metastasis) or as a novel pattern of tumor invasion. The most compelling argument for recognition of this histologic finding is its correlation with poor survival. However, this prognostic association often loses its significance when high-grade histologic patterns are included in multivariate analyses. Despite this fact, the recognition of tumor cell clusters or loose cells is useful and should be a telltale sign for pathologists, that there is likely a high-grade neoplasm nearby. In conclusion, we believe that, while well-intentioned, the inclusion of STAS in the WHO classification for lung cancer as a pattern of invasion was premature. These loose tissue fragments are simply an artifact, that often reveal the presence of a high-grade neoplasm.
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