Spreading Through Air Spaces And Thinking About Lung Metastases

Spread through air spaces (STAS) is a novel pattern of invasion in primary lung cancers, which was introduced in the 2015 World Health Organization classification. Several studies have validated STAS to be a predictor of clinical outcome in lung adenocarcinoma. However, little is known about STAS as a mode of intraparenchymal diffusion of pulmonary metastases (PMs).

The aim of this study was to investigate the incidence of STAS among PMs and the association between STAS and clinicopathological characteristics of PMs.

From August 1, 2017 to July 31, 2022, 50 patients underwent pulmonary metastectomy in our center. Clinicopathological characteristics of patients were retrospectively evaluated. Continuous variables were compared by using unpaired Students t-test or MannWhitney test, as appropriate. Categorical variables were compared by using Qui-squared test or Fishers exact test as appropriate.

A total of 50 patients with PMs who underwent surgical resection were analyzed, 68% being male. The median age of the study population was 60 years (range 24-80). Most patients had primary cancer originating from epithelial tissue (n=45) and the remaing from mesenchymal tissue (n=5). Colorectal cancer was the most frequent primary site of PMs (n= 32), followed by kidney (n=4) and osteosarcoma (n=3). 60% of patients (n=30) underwent sublobar resection (wedge resection or anatomic segmentectomy). STAS was observed in 10 patients (20%): 7 patients with PMs from CRC, 1 with PM from palatine tonsil, 1 from kidney and 1 from uterus. STAS was more frequent in elder patients (62 years, SD=7.099 vs 60 years, SD= 13.889; p = 0.034). Notably, STAS was significantly more frequent in PMs with larger dimension (2.8 cm, SD=2.049 vs 2.03 SD=1.104; p = 0.010), patients with lymph node metastases (p = 0.004) and in patients who underwent lobectomy rather than sublobar resection (70% vs 32.5%; p = 0.03). Although without statistically significant difference, locorregional recurrence and mortality was higher in patients with STAS+ (40% vs 22.5% and 40% vs 20%, respectively).

VSTAS is nowadays considered to be a lung-specific tumour invasion pattern and is commonly observed in PMs of different origins.