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A clinicopathological study of lung adenocarcinomas with pure ground-glass opacity > 3 cm on high-resolution computed tomography

  • Chest
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Abstract

Objectives

This study aimed to discuss whether a diameter of 3 cm is a threshold for diagnosing lung adenocarcinomas presenting with radiological pure ground-glass mass (PGGM, pure ground-glass opacity > 3 cm) as adenocarcinomas in situ or minimally invasive adenocarcinomas (AIS-MIAs). Another aim was to identify CT features and patient prognosis that differentiate AIS-MIAs from invasive adenocarcinomas (IACs) in patients with PGGMs.

Methods

From June 2007 to October 2015, 69 resected PGGMs with HRCT and followed up for ≥ 5 years were included in this study and divided into AIS-MIA (n = 13) and IAC (n = 56) groups. Firth’s logistic regression model was performed to determine CT characteristics that helped distinguish IACs from AIS-MIAs. The discriminatory power of the significant predictors was tested with the area under the receiver operating characteristics curve (AUC). Disease recurrence was also evaluated.

Results

Univariable and multivariable analyses identified that the mean CT attenuation (odds ratio: 1.054, p = 0.0087) was the sole significant predictor for preoperatively discriminating IACs from AIS-MIAs in patients with PGGMs. The CT attenuation had an excellent differentiating accuracy (AUC: 0.981), with the optimal cut-off value at −600 HU (sensitivity: 87.5%; specificity: 100%). Additionally, no recurrence was observed in patients manifesting with PGGMs > 3 cm, and the 5-year recurrence-free survival and overall survival rates were both 100%, even in cases of IAC.

Conclusions

This study demonstrated that PGGMs > 3 cm could still be AIS-MIAs. When PGGMs are encountered in clinical practice, the CT value may be the only valuable parameter to preoperatively distinguish IACs from AIS-MIAs.

Key Points

• Patients with pure ground-glass opacity > 3 cm in diameter are rare but can be diagnosed as adenocarcinomas in situ or minimally invasive adenocarcinomas.

• The mean CT attenuation is the sole significant CT parameter that differentiates invasive adenocarcinoma from adenocarcinoma in situ or minimally invasive adenocarcinoma in patients with pure ground-glass opacity > 3 cm.

• Lung adenocarcinoma with pure ground-glass opacity > 3 cm has an excellent prognosis, even in cases of invasive adenocarcinoma.

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Abbreviations

AAH:

Atypical adenomatous hyperplasia

AIS:

Adenocarcinomas in situ

AUC:

Area under the curve

DFS:

Disease-free survival

GGM:

Ground-glass mass

GGN:

Ground-glass nodule

GGO:

Ground-glass opacity

HRCT:

High-resolution computed tomography

HU:

Hounsfield unit

IAC:

Invasive adenocarcinomas

IASLC/ATS/ERS:

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society

LPA:

Lepidic-predominant adenocarcinomas

LVI:

Lymphatic/vascular invasion

MIA:

Minimally invasive adenocarcinomas

PGGM:

Pure ground-glass mass

ROC:

Receiver operating characteristic

ROI:

Region of interest

SD:

Standard deviation

TNM:

Tumor, node, and metastasis

VPI:

Visceral pleural invasion

References

  1. Naidich DP, Bankier AA, MacMahon H et al (2013) Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology 266:304–317

    Article  Google Scholar 

  2. Zhou QJ, Zheng ZC, Zhu YQ et al (2017) Tumor invasiveness defined by IASLC/ATS/ERS classification of ground-glass nodules can be predicted by quantitative CT parameters. J Thorac Dis 9:1190–1200

    Article  Google Scholar 

  3. Lee HY, Choi YL, Lee KS et al (2014) Pure ground-glass opacity neoplastic lung nodules: histopathology, imaging, and management. AJR Am J Roentgenol 202:W224–W233

    Article  Google Scholar 

  4. Jin X, Zhao SH, Gao J et al (2015) CT characteristics and pathological implications of early stage (T1N0M0) lung adenocarcinoma with pure ground-glass opacity. Eur Radiol 25:2532–2540

    Article  Google Scholar 

  5. Lim HJ, Ahn S, Lee KS et al (2013) Persistent pure ground-glass opacity lung nodules ≥ 10 mm in diameter at CT scan: histopathologic comparisons and prognostic implications. Chest 144:1291–1299

    Article  Google Scholar 

  6. Zhao Q, Wang JW, Yang L, Xue LY, Lu WW (2019) CT diagnosis of pleural and stromal invasion in malignant subpleural pure ground-glass nodules: an exploratory study. Eur Radiol 29:279–286

    Article  Google Scholar 

  7. Chang B, Hwang JH, Choi YH et al (2013) Natural history of pure ground-glass opacity lung nodules detected by low-dose CT scan. Chest 143:172–178

    Article  Google Scholar 

  8. Li W, Zhou F, Wan Z et al (2019) Clinicopathologic features and lymph node metastatic characteristics in patients with adenocarcinoma manifesting as part-solid nodule exceeding 3cm in diameter. Lung Cancer 136:37–44

    Article  Google Scholar 

  9. Travis WD, Brambilla E, Noguchi M et al (2011) International Association for the Study of Lung Cancer / American Thoracic Society / European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6(2):244–285

    Article  Google Scholar 

  10. Travis WD, Asamura H, Bankier AA et al (2016) The IASLC lung cancer staging project: proposals for coding T categories for subsolid nodules and assessment of tumor size in part-solid tumors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol 11:1204–1223

    Article  Google Scholar 

  11. Travis WD, Brambilla E, Nicholson AG et al (2015) The 2015 World Health Organization classification of lung tumors. J Thorac Oncol 10:1243–1260

    Article  Google Scholar 

  12. Kadota K, Villena-Vargas J, Yoshizawa A et al (2014) Prognostic significance of adenocarcinoma in situ, minimally invasive adenocarcinoma, and nonmucinous lepidic predominant invasive adenocarcinoma of the lung in patients with stage I disease. Am J Surg Pathol 38:448–460

    Article  Google Scholar 

  13. Borczuk AC, Qian F, Kazeros A (2009) Invasive size is an independent predictor of survival in pulmonary adenocarcinoma. Am J Surg Pathol 33:462–469

    Article  Google Scholar 

  14. Maeshima AM, Tochigi N, Yoshida A, Asamura H, Tsuta K, Tsuda H (2010) Histological scoring for small lung adenocarcinomas 2 cm or less in diameter: a reliable prognostic indicator. J Thorac Oncol 5:333–339

    Article  Google Scholar 

  15. Eguchi T, Kondo R, Kawakami S et al (2014) Computed tomography attenuation predicts the growth of pure ground-glass nodules. Lung Cancer 84:242–247

    Article  Google Scholar 

  16. Firth D (1993) Bias reduction of maximum likelihood estimates. Biometrika 80:27–38

    Article  Google Scholar 

  17. Heinze G, Schemper M (2002) A solution to the problem of separation in logistic regression. Stat Med 21:2409–2419

    Article  Google Scholar 

  18. Aoki T, Tomoda Y, Watanabe H et al (2001) Peripheral lung adenocarcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival. Radiology 220:803–809

    Article  CAS  Google Scholar 

  19. Yang ZG, Sone S, Takashima S et al (2001) High-resolution CT analysis of small peripheral lung adenocarcinomas revealed on screening helical CT. AJR Am J Roentgenol 176:1399–1407

    Article  CAS  Google Scholar 

  20. Noguchi M (2010) Stepwise progression of pulmonary adenocarcinoma--clinical and molecular implications. Cancer Metastasis Rev 29:15–21

    Article  Google Scholar 

  21. Eguchi T, Kadota K, Park BJ, Travis WD, Jones DR, Adusumilli PS (2014) The new IASLC-ATS-ERS lung adenocarcinoma classification: what the surgeon should know. Semin Thorac Cardiovasc Surg 26:210–222

    Article  Google Scholar 

  22. Yanagawa N, Shiono S, Abiko M, Ogata SY, Sato T, Tamura G (2013) New IASLC/ATS/ERS classification and invasive tumor size are predictive of disease recurrence in stage I lung adenocarcinoma. J Thorac Oncol 8:612–618

    Article  Google Scholar 

  23. Sasada S, Nakayama H, Miyata Y et al (2015) Comparison of malignant grade between pure and partially invasive types of early lung adenocarcinoma. Ann Thorac Surg 99:956–960

    Article  Google Scholar 

  24. Chao L, Yi-Sheng H, Yu C et al (2014) Relevance of EGFR mutation with micropapillary pattern according to the novel IASLC/ATS/ERS lung adenocarcinoma classification and correlation with prognosis in Chinese patients. Lung Cancer 86:164–169

    Article  Google Scholar 

  25. Sumiyoshi S, Yoshizawa A, Sonobe M et al (2013) Pulmonary adenocarcinomas with micropapillary component significantly correlate with recurrence, but can be well controlled with EGFR tyrosine kinase inhibitors in the early stages. Lung Cancer 81:53–59

    Article  Google Scholar 

  26. Ghaly G, Rahouma M, Kamel MK et al (2017) Clinical predictors of nodal metastases in peripherally clinical T1a N0 non-small cell lung cancer. Ann Thorac Surg 104:1153–1158

    Article  Google Scholar 

  27. Aokage K, Miyoshi T, Ishii G et al (2018) Influence of ground glass opacity and the corresponding pathological findings on survival in patients with clinical stage I non-small cell lung cancer. J Thorac Oncol 13:533–542

    Article  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge the help of Mr. Aijun You (Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine), who kindly provided statistical guidance for this manuscript.

Funding

The authors state that this work has not received any funding.

Author information

Author notes

  1. Ke Sun and Huikang Xie contributed equally to this study.

    Liping Zhang and Wei Li contributed equally to this study as co-corresponding authors.

Authors and Affiliations

  1. Department of Radiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China

    Ke Sun, Jiabi Zhao, Bin Wang, Xiao Bao & Wei Li

  2. Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China

    Huikang Xie & Liping Zhang

  3. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zheng Min Road, Shanghai, 200433, China

    Fei Zhou

Authors
  1. Ke Sun
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  4. Bin Wang
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Corresponding authors

Correspondence to Liping Zhang or Wei Li.

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Guarantor

The scientific guarantor of this publication is Wei Li.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

Aijun You kindly provided statistical advice for this manuscript.

Informed consent

Written informed consent was waived by the Institutional Review Board.

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Institutional Review Board approval was obtained.

Methodology

• retrospective

• cross-sectional study/diagnostic or prognostic study/observational /

• performed at one institution

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Sun, K., Xie, H., Zhao, J. et al. A clinicopathological study of lung adenocarcinomas with pure ground-glass opacity > 3 cm on high-resolution computed tomography. Eur Radiol 32, 174–183 (2022). https://doi.org/10.1007/s00330-021-08115-1

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  • DOI: https://doi.org/10.1007/s00330-021-08115-1

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