HHS Public Access Author manuscript Author Manuscript
J Thorac Cardiovasc Surg. Author manuscript; available in PMC 2017 July 01. Published in final edited form as: J Thorac Cardiovasc Surg. 2016 July ; 152(1): 73–74. doi:10.1016/j.jtcvs.2016.04.020.
Spread Through Alveolar Spaces (STAS): An Airborne Invasion in Pulmonary Adenocarcinomas Prasad S. Adusumilli, MD, FACS, FCCP1,2 1Thoracic
Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York,
NY
Author Manuscript
2Center
for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY
Author Manuscript
With the implementation of a new classification system for early-stage lung adenocarcinomas (ADCs) by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, tumors that were previously classified as either well- or poorly differentiated are now classified on the basis of their histological patterns: adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic, acinar, papillary, micropapillary (MIP), and solid.1 Of these patterns, the MIP-predominant pattern is a high-grade histological subtype with poor prognosis. Our group was the first to demonstrate that the presence of MIP pattern (≥5%) is independently associated with the risk of local recurrence in patients treated with limited resection (i.e., wedge resection) for small (≤2 cm) lung ADCs.2 The risk of recurrence was higher when the surgical margin was 3 clusters containing 3 mm from the main tumor, in patients with MIP-positive tumors (>5%). FTCs were associated with poor recurrence-free and overall survival and higher rates of locoregional recurrence.
Corresponding Author: Prasad S. Adusumilli, MD, FACS, FCCP, Deputy Chief, Translational and Clinical Research, Thoracic Service, Department of Surgery, Associate Attending, Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, Phone: (212) 639-8093; Fax: (646) 422-2340, [email protected]. Conflict of Interest: The author has no conflicts of interest to disclose.
Adusumilli
Page 2
Author Manuscript
The authors measured the distance from the FTCs to the main tumor—the distance did not exceed the diameter of the main tumor. They propose a provocative interpretation of their data: that the coexistence of FTCs should be considered a factor to upgrade the pathological T stage.
Author Manuscript
This study adds to the recent literature investigating the biological reasons for the higher rates of locoregional recurrence following curative-intent resection for lung ADC. The strengths of the study are its focus on MIP-positive lung ADCs; its careful approach, to include 3 clusters as an essential minimum to define FTCs, avoiding misinterpretation of any artifacts; and the choice to measure the distance between FTCs and the main tumor, which is of practical significance in determining the appropriate resection for small lung ADCs. The limitations of the study include the small cohort of patients with multiple pathological stages and the inclusion of patients who received adjuvant therapy, which might have influenced outcomes and resulted in shorter follow-up periods. More importantly, the authors’ suggestion that the presence of FTCs should lead to upgrading the T stage, on the basis of a very small number of patients, is speculative yet provocative and necessitates further investigation in a larger cohort. FTCs, a component of STAS, are unique to lung ADCs and hold significant prognostic implications for both recurrence and overall survival. Investigations focusing on the biological mechanisms of STAS, as well as the accurate identification of STAS in the resected specimen—or, even better, preoperatively—will change the management of earlystage lung ADCs, specifically small lung ADCs ≤2 cm in size.
Acknowledgments Author Manuscript
Funding Sources: Supported by grants from the National Institutes of Health (R21 CA164568-01A1, R21 CA164585-01A1, U54 CA137788, P30 CA008748, and P50 CA086438-13), the U.S. Department of Defense (PR101053, LC110202, and BC132124), the Mr. William H. Goodwin and Alice Goodwin, the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center.
Biography
Prasad S. Adusumilli, MD
Author Manuscript
References 1. Eguchi T, Kadota K, Park BJ, et al. The new IASLC-ATS-ERS lung adenocarcinoma classification: what the surgeon should know. Semin Thorac Cardiovasc Surg. 2014; 26:210–222. [PubMed: 25527015] 2. Nitadori J, Bograd AJ, Kadota K, et al. Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2cm or smaller. J Natl Cancer Inst. 2013; 105:1212–1220. [PubMed: 23926067]
J Thorac Cardiovasc Surg. Author manuscript; available in PMC 2017 July 01.
Adusumilli
Page 3
Author Manuscript
3. Kadota K, Nitadori JI, Sima CS, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences following limited resection for small stage I lung adenocarcinomas. J Thorac Oncol. 2015; 10:806–814. [PubMed: 25629637] 4. Warth A, Muley T, Kossakowski CA, et al. Prognostic impact of intra-alveolar tumor spread in pulmonary adenocarcinoma. Am J Surg Pathol. 2015; 39:793–801. [PubMed: 25723114]
Author Manuscript Author Manuscript Author Manuscript J Thorac Cardiovasc Surg. Author manuscript; available in PMC 2017 July 01.
Adusumilli
Page 4
Author Manuscript
Central Message Clusters of viable tumor cells identified at a distance from the tumor margin, within alveolar spaces, can negatively influence recurrence and prognosis in lung adenocarcinomas.
Author Manuscript Author Manuscript Author Manuscript J Thorac Cardiovasc Surg. Author manuscript; available in PMC 2017 July 01.
J Thorac Cardiovasc Surg. Author manuscript; available in PMC 2017 July 01. Published in final edited form as: J Thorac Cardiovasc Surg. 2016 July ; 152(1): 73–74. doi:10.1016/j.jtcvs.2016.04.020.
Spread Through Alveolar Spaces (STAS): An Airborne Invasion in Pulmonary Adenocarcinomas Prasad S. Adusumilli, MD, FACS, FCCP1,2 1Thoracic
Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York,
NY
Author Manuscript
2Center
for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY
Author Manuscript
With the implementation of a new classification system for early-stage lung adenocarcinomas (ADCs) by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, tumors that were previously classified as either well- or poorly differentiated are now classified on the basis of their histological patterns: adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic, acinar, papillary, micropapillary (MIP), and solid.1 Of these patterns, the MIP-predominant pattern is a high-grade histological subtype with poor prognosis. Our group was the first to demonstrate that the presence of MIP pattern (≥5%) is independently associated with the risk of local recurrence in patients treated with limited resection (i.e., wedge resection) for small (≤2 cm) lung ADCs.2 The risk of recurrence was higher when the surgical margin was 3 clusters containing 3 mm from the main tumor, in patients with MIP-positive tumors (>5%). FTCs were associated with poor recurrence-free and overall survival and higher rates of locoregional recurrence.
Corresponding Author: Prasad S. Adusumilli, MD, FACS, FCCP, Deputy Chief, Translational and Clinical Research, Thoracic Service, Department of Surgery, Associate Attending, Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, Phone: (212) 639-8093; Fax: (646) 422-2340, [email protected]. Conflict of Interest: The author has no conflicts of interest to disclose.
Adusumilli
Page 2
Author Manuscript
The authors measured the distance from the FTCs to the main tumor—the distance did not exceed the diameter of the main tumor. They propose a provocative interpretation of their data: that the coexistence of FTCs should be considered a factor to upgrade the pathological T stage.
Author Manuscript
This study adds to the recent literature investigating the biological reasons for the higher rates of locoregional recurrence following curative-intent resection for lung ADC. The strengths of the study are its focus on MIP-positive lung ADCs; its careful approach, to include 3 clusters as an essential minimum to define FTCs, avoiding misinterpretation of any artifacts; and the choice to measure the distance between FTCs and the main tumor, which is of practical significance in determining the appropriate resection for small lung ADCs. The limitations of the study include the small cohort of patients with multiple pathological stages and the inclusion of patients who received adjuvant therapy, which might have influenced outcomes and resulted in shorter follow-up periods. More importantly, the authors’ suggestion that the presence of FTCs should lead to upgrading the T stage, on the basis of a very small number of patients, is speculative yet provocative and necessitates further investigation in a larger cohort. FTCs, a component of STAS, are unique to lung ADCs and hold significant prognostic implications for both recurrence and overall survival. Investigations focusing on the biological mechanisms of STAS, as well as the accurate identification of STAS in the resected specimen—or, even better, preoperatively—will change the management of earlystage lung ADCs, specifically small lung ADCs ≤2 cm in size.
Acknowledgments Author Manuscript
Funding Sources: Supported by grants from the National Institutes of Health (R21 CA164568-01A1, R21 CA164585-01A1, U54 CA137788, P30 CA008748, and P50 CA086438-13), the U.S. Department of Defense (PR101053, LC110202, and BC132124), the Mr. William H. Goodwin and Alice Goodwin, the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center.
Biography
Prasad S. Adusumilli, MD
Author Manuscript
References 1. Eguchi T, Kadota K, Park BJ, et al. The new IASLC-ATS-ERS lung adenocarcinoma classification: what the surgeon should know. Semin Thorac Cardiovasc Surg. 2014; 26:210–222. [PubMed: 25527015] 2. Nitadori J, Bograd AJ, Kadota K, et al. Impact of micropapillary histologic subtype in selecting limited resection vs lobectomy for lung adenocarcinoma of 2cm or smaller. J Natl Cancer Inst. 2013; 105:1212–1220. [PubMed: 23926067]
J Thorac Cardiovasc Surg. Author manuscript; available in PMC 2017 July 01.
Adusumilli
Page 3
Author Manuscript
3. Kadota K, Nitadori JI, Sima CS, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences following limited resection for small stage I lung adenocarcinomas. J Thorac Oncol. 2015; 10:806–814. [PubMed: 25629637] 4. Warth A, Muley T, Kossakowski CA, et al. Prognostic impact of intra-alveolar tumor spread in pulmonary adenocarcinoma. Am J Surg Pathol. 2015; 39:793–801. [PubMed: 25723114]
Author Manuscript Author Manuscript Author Manuscript J Thorac Cardiovasc Surg. Author manuscript; available in PMC 2017 July 01.
Adusumilli
Page 4
Author Manuscript
Central Message Clusters of viable tumor cells identified at a distance from the tumor margin, within alveolar spaces, can negatively influence recurrence and prognosis in lung adenocarcinomas.
Author Manuscript Author Manuscript Author Manuscript J Thorac Cardiovasc Surg. Author manuscript; available in PMC 2017 July 01.
