How to refine a precise definition of spread through air spaces in lung adenocarcinoma?_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

SONG Tieniu ^1,2 , JIANG Lili ³ , LUO Jun ^1,2 ,  LIN Yidan ¹

1. Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;
2. West China School of Medicine, Sichuan University, Chengdu, 610041, P.R.China;
3. Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding author：

LIN Yidan, Email: linyidan.academy@foxmail.com

Keywords：

Spread through air spaces; lung adenocarcinoma; review

DOI：

10.7507/1007-4848.201902024

Video：

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It was a short time from the initial investigation of tumor islands to the concept of tumor spread through air spaces (STAS) being adopted as a pattern of invasion in lung adenocarcinoma. Generally, STAS was defined as "spread of lung cancer cells into air spaces in the lung parenchyma beyond the edge of the main tumor". More and more studies had demonstrated that STAS could increase recurrence rate and cause worse prognosis in lung adenocarcinoma. However, criteria of this definition were various in previous studies, and there is no unified criterion of STAS up to now. In addition, perioperative manipulations including specimen processing and surgery procedure could squeeze tumor cells into alveolar spaces which could affect the assessment of STAS. Obviously, we need a precise definition to reduce and quantify the impacts of confounding factors. We summarize recent developments and put forward some advice for further studies in this article.

Citation： SONG Tieniu, JIANG Lili, LUO Jun, LIN Yidan. How to refine a precise definition of spread through air spaces in lung adenocarcinoma?. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2020, 27(1): 97-100. doi: 10.7507/1007-4848.201902024 Copy

1.	Kadota K, Nitadori J, Sima CS, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small stageⅠlung adenocarcinomas. J Thorac Oncol, 2015, 10(5): 806-814.
2.	Warth A, Muley T, Kossakowski CA, et al. Prognostic impact of intra-alveolar tumor spread in pulmonary adenocarcinoma. Am J Surg Pathol, 2015, 39(6): 793-801.
3.	Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol, 2015, 10(9): 1243-1260.
4.	Onozato ML, Kovach AE, Yeap BY, et al. Tumor islands in resected early-stage lung adenocarcinomas are associated with unique clinicopathologic and molecular characteristics and worse prognosis. Am J Surg Pathol, 2013, 37(2): 287-294.
5.	Morimoto J, Nakajima T, Suzuki H, et al. Impact of free tumor clusters on prognosis after resection of pulmonary adenocarcinoma. J Thorac Cardiovasc Surg, 2016, 152(1): 64-72.
6.	Lu S, Tan KS, Kadota K, et al. Spread through air spaces (STAS) is an independent predictor of recurrence and lung cancer-specific death in squamous cell carcinoma. J Thorac Oncol, 2017, 12(2): 223-234.
7.	Yokoyama S, Murakami T, Tao H, et al. Tumor spread through air spaces identifies a distinct subgroup with poor prognosis in surgically resected lung pleomorphic carcinoma. Chest, 2018, 154(4): 838-847.
8.	Toyokawa G, Yamada Y, Tagawa T, et al. High frequency of spread through air spaces in resected small cell lung cancer. Anticancer Res, 2018, 38(3): 1821-1825.
9.	Thunnissen E, Blaauwgeers HJLG, de Cuba EM, et al. Ex vivo artifacts and histopathologic pitfalls in the lung. Arch Pathol Lab Med, 2016, 140(3): 212-220.
10.	Blaauwgeers H, Flieder D, Warth A, et al. A prospective study of loose tissue fragments in non-small cell lung cancer resection specimens: an alternative view to "spread through air spaces". Am J Surg Pathol, 2017, 41(9): 1226-1230.
11.	Zhao S, Guo T, Li J, et al. Expression and prognostic value of GalNAc-T3 in patients with completely resected small (≤2 cm) peripheral lung adenocarcinoma after IASLC/ATS/ERS classification. Onco Targets Ther, 2015, 8: 3143-3152.
12.	Zhang B, Zhang H. Metastasis-associated protein 2 (MTA2) promotes the metastasis of non-small-cell lung cancer through the inhibition of the cell adhesion molecule Ep-CAM and E-cadherin. Jpn J Clin Oncol, 2015, 45(8): 755-766.
13.	Blaauwgeers H, Russell PA, Jones KD, et al. Pulmonary loose tumor tissue fragments and spread through air spaces (STAS): Invasive pattern or artifact? A critical review. Lung Cancer, 2018, 123: 107-111.
14.	Warth A, Beasley MB, Mino-Kenudson M. Breaking new ground: the evolving concept of spread through air spaces (STAS). J Thorac Oncol, 2017, 12(2): 176-178.
15.	Shiono S, Yanagawa N. Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stageⅠlung adenocarcinoma. Interact Cardiovasc Thorac Surg, 2016, 23(4): 567-572.
16.	Liu L, Che G, Pu Q, et al. A new concept of endoscopic lung cancer resection: Single-direction thoracoscopic lobectomy. Surg Oncol, 2010, 19(2): e71-e77.
17.	Zhu Y, Pu Q, Liu L. Trans-inferior-pulmonary-ligament VATS basal segmentectomy: application of single-direction strategy in segmentectomy of left S9+10. J Thorac Dis, 2018, 10(11): 6266-6268.
18.	Zhu Y, Mei J, Liu L. The application of a single-direction strategy in VATS segmentectomy: left S3 segmentectomy. Ann Transl Med, 2018, 6(20): 410.
19.	Diaz LK, Wiley EL, Venta LA. Are malignant cells displaced by large gauge need core biopsy of the breast? AJR Am J Roentgenol, 1999, 173(5): 1303-1313.
20.	Uruga H, Fujii T, Fujimori S, et al. Semiquantitative assessment of tumor spread through air spaces (STAS) in early-stage lung adenocarcinomas. J Thorac Oncol, 2017, 12(7): 1046-1051.
21.	Morales-Oyarvide V, Mino-Kenudson M. Taking the measure of lung adenocarcinoma: towards a quantitative approach to tumor spread through air spaces (STAS). J Thorac Dis, 2017, 9(9): 2756-2761.
22.	Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/ American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol, 2011, 6(2): 244-285.
23.	Dai C, Xie H, Su H, et al. Tumor spread through air spaces affects the recurrence and overall survival in patients with lung adenocarcinoma >2 to 3 cm. J Thorac Oncol, 2017, 12(7): 1052-1060.
24.	Cha MJ, Lee HY, Lee KS, et al. Micropapillary and solid subtypes of invasive lung adenocarcinoma: clinical predictors of histopathology and outcome. J Thorac Cardiovasc Surg, 2014, 147(3): 921-928.
25.	American Joint Committee on Cancer, Lung, in: R. Rami-Porta, H. Asamura, W.D. Travis, V.W. Rusch (Eds.), AJCC Cancer Staging Manual, 8th ed. New York: Springer. 2017. 431-456.
26.	Ma K, Zhan C, Wang S, et al. Spread through air spaces(STAS): a new pathologic morphology in lung cancer. Clin Lung Cancer, 2019, 20(2): e158-e162.
27.	刘傲, 矫文捷. 气腔播散影响肺癌预后的研究进展. 中华胸心血管外科杂志, 2018, 34(9): 561-564.
28.	Hu SY, Hsieh MS, Hsu HH, et al. Correlation of tumor spread through air spaces and clinicopathological characteristics in surgically resected lung adenocarcinomas. Lung Cancer, 2018, 126: 189-193.
29.	Lee JS, Kim EK, Kim M, et al. Genetic and clinicopathologic characteristics of lung adenocarcinoma with tumor spread through air spaces. Lung Cancer, 2018, 123: 121-126.
30.	Toyokawa G, Yamada Y, Tagawa T, et al. Significance of spread through air spaces in resected pathological stageⅠlung adenocarcinoma. Ann Thorac Surg, 2018, 105(6): 1655-1663.

1. Kadota K, Nitadori J, Sima CS, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small stageⅠlung adenocarcinomas. J Thorac Oncol, 2015, 10(5): 806-814.
2. Warth A, Muley T, Kossakowski CA, et al. Prognostic impact of intra-alveolar tumor spread in pulmonary adenocarcinoma. Am J Surg Pathol, 2015, 39(6): 793-801.
3. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol, 2015, 10(9): 1243-1260.
4. Onozato ML, Kovach AE, Yeap BY, et al. Tumor islands in resected early-stage lung adenocarcinomas are associated with unique clinicopathologic and molecular characteristics and worse prognosis. Am J Surg Pathol, 2013, 37(2): 287-294.
5. Morimoto J, Nakajima T, Suzuki H, et al. Impact of free tumor clusters on prognosis after resection of pulmonary adenocarcinoma. J Thorac Cardiovasc Surg, 2016, 152(1): 64-72.
6. Lu S, Tan KS, Kadota K, et al. Spread through air spaces (STAS) is an independent predictor of recurrence and lung cancer-specific death in squamous cell carcinoma. J Thorac Oncol, 2017, 12(2): 223-234.
7. Yokoyama S, Murakami T, Tao H, et al. Tumor spread through air spaces identifies a distinct subgroup with poor prognosis in surgically resected lung pleomorphic carcinoma. Chest, 2018, 154(4): 838-847.
8. Toyokawa G, Yamada Y, Tagawa T, et al. High frequency of spread through air spaces in resected small cell lung cancer. Anticancer Res, 2018, 38(3): 1821-1825.
9. Thunnissen E, Blaauwgeers HJLG, de Cuba EM, et al. Ex vivo artifacts and histopathologic pitfalls in the lung. Arch Pathol Lab Med, 2016, 140(3): 212-220.
10. Blaauwgeers H, Flieder D, Warth A, et al. A prospective study of loose tissue fragments in non-small cell lung cancer resection specimens: an alternative view to "spread through air spaces". Am J Surg Pathol, 2017, 41(9): 1226-1230.
11. Zhao S, Guo T, Li J, et al. Expression and prognostic value of GalNAc-T3 in patients with completely resected small (≤2 cm) peripheral lung adenocarcinoma after IASLC/ATS/ERS classification. Onco Targets Ther, 2015, 8: 3143-3152.
12. Zhang B, Zhang H. Metastasis-associated protein 2 (MTA2) promotes the metastasis of non-small-cell lung cancer through the inhibition of the cell adhesion molecule Ep-CAM and E-cadherin. Jpn J Clin Oncol, 2015, 45(8): 755-766.
13. Blaauwgeers H, Russell PA, Jones KD, et al. Pulmonary loose tumor tissue fragments and spread through air spaces (STAS): Invasive pattern or artifact? A critical review. Lung Cancer, 2018, 123: 107-111.
14. Warth A, Beasley MB, Mino-Kenudson M. Breaking new ground: the evolving concept of spread through air spaces (STAS). J Thorac Oncol, 2017, 12(2): 176-178.
15. Shiono S, Yanagawa N. Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stageⅠlung adenocarcinoma. Interact Cardiovasc Thorac Surg, 2016, 23(4): 567-572.
16. Liu L, Che G, Pu Q, et al. A new concept of endoscopic lung cancer resection: Single-direction thoracoscopic lobectomy. Surg Oncol, 2010, 19(2): e71-e77.
17. Zhu Y, Pu Q, Liu L. Trans-inferior-pulmonary-ligament VATS basal segmentectomy: application of single-direction strategy in segmentectomy of left S9+10. J Thorac Dis, 2018, 10(11): 6266-6268.
18. Zhu Y, Mei J, Liu L. The application of a single-direction strategy in VATS segmentectomy: left S3 segmentectomy. Ann Transl Med, 2018, 6(20): 410.
19. Diaz LK, Wiley EL, Venta LA. Are malignant cells displaced by large gauge need core biopsy of the breast? AJR Am J Roentgenol, 1999, 173(5): 1303-1313.
20. Uruga H, Fujii T, Fujimori S, et al. Semiquantitative assessment of tumor spread through air spaces (STAS) in early-stage lung adenocarcinomas. J Thorac Oncol, 2017, 12(7): 1046-1051.
21. Morales-Oyarvide V, Mino-Kenudson M. Taking the measure of lung adenocarcinoma: towards a quantitative approach to tumor spread through air spaces (STAS). J Thorac Dis, 2017, 9(9): 2756-2761.
22. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/ American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol, 2011, 6(2): 244-285.
23. Dai C, Xie H, Su H, et al. Tumor spread through air spaces affects the recurrence and overall survival in patients with lung adenocarcinoma >2 to 3 cm. J Thorac Oncol, 2017, 12(7): 1052-1060.
24. Cha MJ, Lee HY, Lee KS, et al. Micropapillary and solid subtypes of invasive lung adenocarcinoma: clinical predictors of histopathology and outcome. J Thorac Cardiovasc Surg, 2014, 147(3): 921-928.
25. American Joint Committee on Cancer, Lung, in: R. Rami-Porta, H. Asamura, W.D. Travis, V.W. Rusch (Eds.), AJCC Cancer Staging Manual, 8th ed. New York: Springer. 2017. 431-456.
26. Ma K, Zhan C, Wang S, et al. Spread through air spaces(STAS): a new pathologic morphology in lung cancer. Clin Lung Cancer, 2019, 20(2): e158-e162.
27. 刘傲, 矫文捷. 气腔播散影响肺癌预后的研究进展. 中华胸心血管外科杂志, 2018, 34(9): 561-564.
28. Hu SY, Hsieh MS, Hsu HH, et al. Correlation of tumor spread through air spaces and clinicopathological characteristics in surgically resected lung adenocarcinomas. Lung Cancer, 2018, 126: 189-193.
29. Lee JS, Kim EK, Kim M, et al. Genetic and clinicopathologic characteristics of lung adenocarcinoma with tumor spread through air spaces. Lung Cancer, 2018, 123: 121-126.
30. Toyokawa G, Yamada Y, Tagawa T, et al. Significance of spread through air spaces in resected pathological stageⅠlung adenocarcinoma. Ann Thorac Surg, 2018, 105(6): 1655-1663.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

How to refine a precise definition of spread through air spaces in lung adenocarcinoma?

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