Skip to main content

Advertisement

SpringerLink
Log in

Imaging Features Suggestive of Multiple Primary Lung Adenocarcinomas

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The tumor-node-metastasis classification system has proposed that lung cancers presenting as multifocal ground-glass nodules (multi-GGN) on computed tomography scan should be staged as multiple primaries instead of intrapulmonary metastases. However, the problem still exists for those synchronous multiple lung adenocarcinomas (SMLA) involving solid lesions. This study aimed to explore the distinct features of SMLA to better define the diagnosis and staging of this disease.

Methods

Between 2008 and 2016, consecutive patients with complete resection of SMLA were prospectively enrolled in the study. The patients were divided into three groups based on CT images as follows: multi-GGN, one solid nodule plus one or more GGNs (solid-GGN), and multiple solid lesions with or without GGN (multi-solid). Clinicopathologic features and survival outcomes were compared between these groups. Multivariate Cox proportional hazards analyses using bootstrap internal validation were performed to identify independent predictors for recurrence-free survival (RFS) and overall survival (OS).

Results

Of the 695 patients who met the inclusion criteria, 486 (69.9%) presented with multi-GGN tumor, 124 (17.9%) with solid-GGN tumor, and 85 (12.2%) with multi-solid tumor. The three groups had distinguished clinicopathologic features of gender, smoking history, nodal metastases, tumor size, subtype, and location (all P < 0.001). Multivariate analyses demonstrated that multi-solid tumor was an independent predictor for both decreased RFS [hazard ratio (HR) 2.941; 95% confidence interval (CI) 1.07–8.08; P = 0.036] and poor OS (HR 6.13; 95% CI 1.15–32.63; P = 0.034), but neither RFS (P = 0.384) nor OS (P = 0.811) differed between solid-GGN and multi-GGN tumors.

Conclusions

Both multi-GGN and solid-GGN tumors should be staged as multiple primaries, whereas multi-solid tumor was indicated to be advanced disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ishikawa Y, Nakayama H, Ito H, et al. Surgical treatment for synchronous primary lung adenocarcinomas. Ann Thorac Surg. 2014;98:1983–8.

    Article  Google Scholar 

  2. Zhang Y, Hu H, Wang R, et al. Synchronous non-small cell lung cancers: diagnostic yield can be improved by histologic and genetic methods. Ann Surg Oncol. 2014;21:4369–74.

    Article  Google Scholar 

  3. Martini N, Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg. 1975;70:606–12.

    Article  CAS  Google Scholar 

  4. Chung JH, Choe G, Jheon S, et al. Epidermal growth factor receptor mutation and pathologic-radiologic correlation between multiple lung nodules with ground-glass opacity differentiates multicentric origin from intrapulmonary spread. J Thorac Oncol. 2009;4:1490–5.

    Article  Google Scholar 

  5. Girard N, Deshpande C, Lau C, et al. Comprehensive histologic assessment helps to differentiate multiple lung primary non-small cell carcinomas from metastases. Am J Surg Pathol. 2009;33:1752–64.

    Article  Google Scholar 

  6. Girard N, Deshpande C, Azzoli CG, et al. Use of epidermal growth factor receptor/Kirsten rat sarcoma 2 viral oncogene homolog mutation testing to define clonal relationships among multiple lung adenocarcinomas: comparison with clinical guidelines. Chest. 2010;137:46–52.

    Article  CAS  Google Scholar 

  7. Warth A, Macher-Goeppinger S, Muley T, et al. Clonality of multifocal non-small cell lung cancer: implications for staging and therapy. Eur Respir J. 2012;39:1437–42.

    Article  CAS  Google Scholar 

  8. Murphy SJ, Aubry MC, Harris FR, et al. Identification of independent primary tumors and intrapulmonary metastases using DNA rearrangements in non-small cell lung cancer. J Clin Oncol. 2014;32(36):4050–8.

    Article  CAS  Google Scholar 

  9. Sun W, Liu Y, Liu XY, Lin DM, Lv N. Significance of nonmucinous lepidic component with mild nuclear atypia in the discrimination of multiple primary lung cancers from intrapulmonary metastases. Int J Clin Exper Pathol. 2014;7:7583–96.

    Google Scholar 

  10. Detterbeck FC, Nicholson AG, Franklin WA, et al. The IASLC Lung Cancer Staging Project: summary of proposals for revisions of the classification of lung cancers with multiple pulmonary sites of involvement in the forthcoming eighth edition of the TNM classification. J Thorac Oncol. 2016;11:639–50.

  11. Gu B, Burt BM, Merritt RE, et al. A dominant adenocarcinoma with multifocal ground glass lesions does not behave as advanced disease. Ann Thorac Surg. 2013;96:411–8.

    Article  Google Scholar 

  12. Ye T, Deng L, Wang S, et al. Lung adenocarcinomas manifesting as radiological part-solid nodules define a special clinical subtype. J Thorac Oncol. 2019;14:617–27.

    Article  Google Scholar 

  13. Fu F, Zhang Y, Wen Z, et al. Distinct prognostic factors in patients with stage I non-small cell lung cancer with radiologic part solid or solid lesions. J Thorac Oncol. 2019;14(12):2133–42.

    Article  Google Scholar 

  14. Ye T, Deng L, Xiang J, et al. Predictors of pathologic tumor invasion and prognosis for ground-glass opacity featured lung adenocarcinoma. Ann Thorac Surg. 2018;106:1682–90.

    Article  Google Scholar 

  15. Liu S, Wang R, Zhang Y, et al. Precise diagnosis of intraoperative frozen section is an effective method to guide resection strategy for peripheral small-sized lung adenocarcinoma. J Clin Oncol. 2016;34:307–13.

    Article  Google Scholar 

  16. Ettinger DS, Wood DE, Akerley W, et al. Non-small cell lung cancer, version 1.2015. JNCCN J Natl Comprehensive Cancer Network. 2014;12:1738–61.

  17. 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;6:244–85.

    Article  Google Scholar 

  18. Warth A, Muley T, Meister M, et al. The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol. 2012;30:1438–46.

    Article  Google Scholar 

  19. Hu H, Sun Z, Li Y, et al. The histologic classifications of lung adenocarcinomas are discriminable by unique lineage backgrounds. J Thorac Oncol. 2016;11(12):2161–72.

    Article  Google Scholar 

  20. Zhang Y, Wang R, Cai D, et al. A comprehensive investigation of molecular features and prognosis of lung adenocarcinoma with micropapillary component. J Thorac Oncol. 2014;9:1772–8.

    Article  CAS  Google Scholar 

  21. Zhang Y, Li J, Wang R, et al. The prognostic and predictive value of solid subtype in invasive lung adenocarcinoma. Sci Rep. 2014;4:7163.

    Article  CAS  Google Scholar 

  22. Tsao MS, Marguet S, Le Teuff G, et al. Subtype classification of lung adenocarcinoma predicts benefit from adjuvant chemotherapy in patients undergoing complete resection. J Clin Oncol. 2015;33:3439–46.

    Article  CAS  Google Scholar 

  23. Gazdar AF, Minna JD. Multifocal lung cancers: clonality vs field cancerization and does it matter? J Natl Cancer Institute. 2009;101:541–3.

    Article  Google Scholar 

  24. Detterbeck FC, Marom EM, Arenberg DA, et al. The IASLC Lung Cancer Staging Project: background data and proposals for the application of TNM staging rules to lung cancer presenting as multiple nodules with ground-glass or lepidic features or a pneumonic type of involvement in the forthcoming eighth edition of the TNM classification. J Thorac Oncol. 2016;11:666–80.

  25. Detterbeck FC, Franklin WA, Nicholson AG, et al. The IASLC Lung Cancer Staging Project: background data and proposed criteria to distinguish separate primary lung cancers from metastatic foci in patients with two lung tumors in the forthcoming eighth edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11:651–65.

  26. Detterbeck FC, Bolejack V, Arenberg DA, et al. The IASLC Lung Cancer Staging Project: background data and proposals for the classification of lung cancer with separate tumor nodules in the forthcoming eighth edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11:681–92.

  27. Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. The 8th-edition lung cancer stage classification. Chest. 2017;151(1):193–203.

    Article  Google Scholar 

  28. 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 stage I lung adenocarcinomas. J Thorac Oncol. 2015;10:806–14.

    Article  CAS  Google Scholar 

  29. Kim HK, Choi YS, Kim K, et al. Management of ground-glass opacity lesions detected in patients with otherwise operable non-small cell lung cancer. J Thorac Oncol. 2009;4:1242–6.

    Article  Google Scholar 

  30. Donington JS. An additional step toward personalization of surgical care for early-stage non-small cell lung cancer. J Clin Oncol. 2016;34:295–6.

    Article  Google Scholar 

  31. Baisi A, De Simone M, Raveglia F, Cioffi U. What really affects synchronous pulmonary adenocarcinoma management? Ann Thorac Surg. 2015;100:1506–7.

    Article  Google Scholar 

  32. Zhao Y, Wang R, Shen X, et al. Minor components of micropapillary and solid subtypes in lung adenocarcinoma are predictors of lymph node metastasis and poor prognosis. Ann Surg Oncol. 2016;23:2099–105.

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from The National Natural Science Foundation of China (81572253), the Shanghai Shenkang Hospital Development Center City Hospital Emerging Cutting-Edge Technology Joint Research Project (SHDC12017102), and the Shanghai Municipal Health Commission Key Discipline Project (2017ZZ02025 and 2017ZZ01019).

Author information

Author notes

  1. Yiliang Zhang and Guodong Li contributed equally to this study.

Authors and Affiliations

  1. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

    Yiliang Zhang MD, PhD, Yunjian Pan MD, Yang Zhang MD, Hong Hu MD, Yihua Sun MD, Yawei Zhang MD, Jiaqing Xiang MD & Haiquan Chen MD

  2. Department of Interventional Radiology, Fudan University Shanghai Cancer Center, Shanghai, China

    Guodong Li MD

  3. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

    Yuan Li MD, PhD

  4. Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China

    Quan Liu MD

  5. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Yiliang Zhang MD, PhD, Guodong Li MD, Yuan Li MD, PhD, Quan Liu MD, Yunjian Pan MD, Yang Zhang MD, Hong Hu MD, Yihua Sun MD, Yawei Zhang MD, Jiaqing Xiang MD & Haiquan Chen MD

  6. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark

    Yongfu Yu PhD

  7. Bioinformatics Center and Computational Core, Chinese Institute for Brain Science, Beijing, China

    Yuan Ma PhD

Authors
  1. Yiliang Zhang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guodong Li MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuan Li MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Quan Liu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yongfu Yu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuan Ma PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yunjian Pan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yang Zhang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hong Hu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yihua Sun MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yawei Zhang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jiaqing Xiang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Haiquan Chen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yuan Li MD, PhD or Haiquan Chen MD.

Ethics declarations

Disclosure

The author declares that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Li, G., Li, Y. et al. Imaging Features Suggestive of Multiple Primary Lung Adenocarcinomas. Ann Surg Oncol 27, 2061–2070 (2020). https://doi.org/10.1245/s10434-019-08109-w

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-019-08109-w

Search

Navigation