Significance of tumor spread through air spaces (STAS) in lung cancer from the pathologist perspective

Abstract

Airspace invasion in lung cancer has been known over the last 30 years, but it was only recently that WHO 2015 formally recognized it as a mechanism of invasion with the terminology of tumor spread through air spaces (STAS). Multiple studies have shown the association of STAS with lower survival and suggest that STAS is an independent prognostic factor across lung adenocarcinoma of all stages and in other histologic subtypes of lung cancer as well. Consequently, STAS is designated as an exclusion criterion of adenocarcinoma in situ and minimally invasive adenocarcinoma; thus, the presence of STAS impacts the diagnosis and staging of lung adenocarcinoma. Further, wedge resection and segmentectomy have been increasingly applied for small node negative tumors and the presence of STAS in those specimens may indicate the requirement of completion lobectomy. Given these significant clinical implications, we, pathologists, need to recognize and appropriately report STAS (possibly including at the time of intraoperative consultation). However, emerging data suggests that more work should be done to improve consensus and identification of STAS, including at frozen section. In this review, the evolution of our understanding of airspace invasion over the past decade, the clinical significance of STAS, and controversies and practical issues associated with the diagnosis of STAS are discussed.