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Review Article
- Spread through air spaces as a marker of nonlinear evolutionary trajectories in lung cancer: implications for the 9th edition TNM classification
- Jin-Haeng Chung
- J Pathol Transl Med. 2026;60(5):463-475. Published online September 15, 2026
- DOI: https://doi.org/10.4132/jptm.2026.06.16
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Abstract
PDF - Recent advancements in the diagnosis and therapeutic management of lung cancer have contributed to an evolution in pathological reporting standards. The 8th edition of the TNM classification of lung tumors has introduced the invasive size of adenocarcinoma—rather than total tumor size—as the primary determinant for staging. Concurrently, histological grading criteria proposed by the International Association for the Study of Lung Cancer (IASLC), based on predominant and highest-grade architectural patterns, appear to offer improved clinical utility over legacy systems. In addition, tumor spread through air spaces (STAS) has emerged as an actively investigated pattern of invasion, characterized by the presence of neoplastic cells beyond the main tumor mass within the adjacent pulmonary parenchyma. STAS is frequently observed in advanced-stage and node-positive non–small cell lung cancer and often correlates with distant metastasis. Recognizing its clinical relevance, the IASLC Staging Project recently recommended incorporating STAS as a histologic T descriptor in the 9th edition of the TNM classification. Expanding upon this framework, this review explores STAS not merely as a prognostic indicator, but as a potential reflection of divergent evolutionary trajectories influenced by underlying driver mutations. Accordingly, this review aims to comprehensively synthesize the prevailing controversies and recent academic milestones regarding STAS, the current limitations in preoperative STAS risk prediction, the logistical hurdles of intraoperative diagnosis, and critically evaluates the need for prospective clinical trials to validate STAS as a predictive biomarker for adjuvant systemic therapy.
Original Article
- Correlations and prognostic impacts of tumor spread through airspaces in surgically resected non–small cell lung cancer: a retrospective study from Jordan
- Ola Abu Al Karsaneh, Amani Al-Rousan, Sofian Al Shboul, Mohammed El-Sadoni, Anas Hayajneh, Moath Alrjoub, Sura Al-Rawabdeh, Tareq Saleh
- J Pathol Transl Med. 2026;60(1):92-106. Published online January 9, 2026
- DOI: https://doi.org/10.4132/jptm.2025.10.15
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Abstract
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Supplementary Material - Background
Spread through air spaces (STAS) has been identified as an invasion pattern in non–small cell lung cancer (NSCLC). This study evaluated the association between tumor STAS and various clinicopathological parameters of NSCLC, with emphasis on the prognostic role of STAS. Methods: We evaluated 96 cases of NSCLC for STAS. STAS-positive cases were graded according to the distance between the edge of the primary tumor and the furthest STAS, in millimeters, or the number of alveoli separating STAS from the tumor. Results: STAS was observed in 33 patients (34.4%). In 28 cases, STAS was located in airspaces >3 alveoli away from the primary tumor. In 18 cases, STAS was found in airspaces > 2.5 mm away from the edge of the primary tumor. Morphologically, 18 cases of STAS demonstrated a solid nest pattern, eight showed a micropapillary cluster pattern, and seven exhibited a single-cell pattern. In multivariate analysis, only high tumor grade (p = .001) was independently associated with STAS in NSCLC. The presence of STAS (p = .047), lymphovascular invasion (p = .001), positive surgical margin (p = .021), adenocarcinoma histology (p = .020), and postoperative therapy (p = .049) showed a statistically significant lower overall survival (OS). However, multivariate analyses showed that STAS is not an independent predictor of OS in NSCLC. In addition, STAS-positive cases with an extension of >2.5 mm had significantly lower disease-free survival (DFS) (p = .018). Conclusions: The findings demonstrated that STAS is independently associated with a higher tumor grade and appears to have an adverse impact on OS and DFS in the examined subpopulation.
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