Gross Specimen Handling Procedures Do Not Impact the Occurrence of Spread Through Air Spaces (STAS) in Lung Cancer

Abstract

Spread Through Air Spaces (STAS) is a form of invasion characterized by neoplastic cell dissemination in the lung parenchyma surrounding the outer edge of the tumor. Its possible artifactual origin is widely debated in the literature. The aim of this study is to investigate the potential impact of gross sampling procedures in causing STAS. A prospective series of 51 surgical lung specimens was collected (35 adenocarcinomas, 68.6%; 13 squamous cell carcinomas, 25.5%; 2 large-cell neuroendocrine carcinomas, 3.9%; 1 atypical carcinoid, 2%). The fresh tissue was sectioned with a new and clean blade for each cut, to obtain a tissue slice comprising the upper lung parenchyma, the tumor, and the lower parenchyma. This slice was cut in half and separately processed. The same procedure was repeated in the residual (specular) specimen after formalin fixation. STAS was identified in 33/51 (64.7%) cases, the predominant pattern being cluster formation (29 cases, 87.9%), the remaining 4 cases having single-cell invasion. Comparing STAS detection in upper and lower lung parenchyma areas (ie, before and after the blade crossed the tumor), no significant preferential STAS distribution was observed, indeed being almost overlapping (60.6% and 63.6% for fresh and 61.3% and 65.6% for fixed tissues, respectively). There was no difference between STAS occurrence in freshly cut and fixed corresponding samples. These findings indicate that STAS is not a pathologist-related artifactual event because of knife transportation of tumor cells during gross specimen handling and support the notion that it is a phenomenon preexisting to surgical tissue processing.

Impact of preoperative biopsy on tumor spread through air spaces in stage I non-small cell lung cancer: a propensity score-matched study

“…However, some scholars have questioned STAS, arguing that it is only the spread of tumor cell clusters caused by knife cutting during specimen processing, and called it "Spread Through a Knife Surface" [ 12 ]. Recently, more and more studies have shown that STAS is an in vivo phenomenon rather than an artifact caused by specimen handling procedures [ 13 , 23 , 24 ]. However, could this in vivo phenomenon be another manipulation artifacts, caused by preoperative invasive biopsy?…”

The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015

“…62 The occurrence of STAS does not seem to be affected by gross specimen-handling procedures. 63 STAS in adenocarcinoma is composed of three morphologic patterns, including micropapillary structures, solid nests, and discohesive single cells. 61 STAS is associated with worse clinical outcome in resected lung adenocarcinoma and all investigated major histologic lung cancer types.…”

Spread Through Air Spaces (STAS) in Non−Small Cell Lung Carcinoma

“…1,23 Furthermore, a recent series demonstrated that gross specimen handling procedures did not impact the incidence of STAS in lung carcinoma specimens, suggesting that STAS is not a pathologist induced artifact from knife translocation of tumor cells. 24 While concerns have been raised that individual STAS clusters can survive in the airway separate from the tumor, our observations that viable STAS cells, with no evidence of necrosis, in additional resection specimens up to 1 month after the initial procedure confirms that cell clusters can survive distant from the tumor. Whether the spread of tumor cells is introduced by surgical manipulation of the tumor at the time of surgery has also been questioned.…”