Subsolid lung adenocarcinoma with cystic airspaces (LACA) is a unique manifestation of lung cancer. This study was conducted to establish a radiologic disease progression model of LACA and to explore its association with the clinical course and clinicopathologic features of LACA.
Materials and Methods
Sixty patients with LACA who underwent surgery at our center between 2004 and 2017 were retrospectively reviewed. The morphological changes of LACA over time on 98 serial computed tomography scans from 27 of 60 patients were tracked to establish a radiologic disease progression model. Associations between this model and the clinicopathologic characteristics of LACA were investigated.
The following stepwise progression model of LACA was developed: in phase I, cystic airspaces (CAs) appear in the middle of non-solid nodules; in phase II, the CAs grow; in phase III, a solid component appears on the border of the CAs; and in phase IV, the solid component gradually surrounds the CAs and becomes thicker, and the CAs shrink. In total, 10 (17%), 33 (55%), and 17 (28%) LACA patients were classified as belonging to phases II, III, and IV at the time of surgery, respectively. More advanced phases were associated with higher pathologic T and N staging, lymphovascular invasion, visceral pleural invasion, spread through air spaces, and solid/micropapillary subtype. In the multivariate analysis, our model demonstrated a good discrimination capability for cancer recurrence risk.
The stepwise disease progression model of LACA based on radiologic findings developed in this study represented its natural clinical course and clinicopathologic features well.
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Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J clin. 2016;66(1):7–30.
Ujiie H, Kadota K, Chaft JE, et al. Solid predominant histologic subtype in resected stage I lung adenocarcinoma is an independent predictor of early, extrathoracic, multisite recurrence and of poor postrecurrence survival. J Clin Oncol. 2015;33(26):2877–84. https://doi.org/10.1200/jco.2015.60.9818.
Chen C-Y, Wang J-Y, Chien Y-C, et al. Lung cancer mimicking pulmonary tuberculosis in a TB-endemic country: the role of early invasive diagnostic procedures. Lung Cancer Manag. 2015;4(1):9–16.
Tomimaru Y, Higashiyama M, Okami J, et al. Surgical Results of Lung Cancer with Sarcoid Reaction in Regional Lymph Nodes. Jpn J Clin Oncol. 2007;37(2):90–95. https://doi.org/10.1093/jjco/hyl141.
Ichikawa T, Hattori A, Suzuki K, et al. Clinicopathological characteristics of lung cancer mimicking organizing pneumonia on computed tomography—a novel radiological entity of pulmonary malignancy. Jpn J Clin Oncol. 2016;46(7):681–86. https://doi.org/10.1093/jjco/hyw053.
Fintelmann FJ, Brinkmann JK, Jeck WR, et al. Lung cancers associated with cystic airspaces: natural history, pathologic correlation, and mutational analysis. J Thorac Imaging. 2017;32(3):176–88. https://doi.org/10.1097/rti.0000000000000265.
Farooqi AO, Cham M, Zhang L, et al. Lung cancer associated with cystic airspaces. Am J Roentgenol. 2012;199(4):781–86.
Cardinale L, Angelino V, Piacibello E, et al. The many faces of lung cancer. Int J Cancer Clin Res. 2016;3:050.
Kimura H, Saji H, Miyazawa T, et al. Worse survival after curative resection in patients with pathological stage I non-small cell lung cancer adjoining pulmonary cavity formation. J Thorac Dis. 2017;9(9):3038–44. https://doi.org/10.21037/jtd.2017.08.42.
Sheard S, Moser J, Sayer C, et al. Lung cancers associated with cystic airspaces: underrecognized features of early disease. RadioGraphics. 2018;38(3):704–17.
Mascalchi M, Attinà D, Bertelli E, et al. Lung cancer associated with cystic airspaces. J Comput Assis Tomogr. 2015;39(1):102–08.
Bankier AA, MacMahon H, Goo JM, et al. Recommendations for measuring pulmonary nodules at CT: a statement from the Fleischner Society. Radiology. 2017;285(2):584–600.
Detterbeck FC, Boffa DJ, Kim AW, et al. The eighth edition lung cancer stage classification. CHEST. 2017;151(1):193–203. https://doi.org/10.1016/j.chest.2016.10.010.
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 Thoracic Oncol. 2015;10(9):1243–60. https://doi.org/10.1097/JTO.0000000000000630.
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(3):210–22. https://doi.org/10.1053/j.semtcvs.2014.09.002.
Rahman MS, Sultana M. Performance of Firth-and logF-type penalized methods in risk prediction for small or sparse binary data. BMC Med Res Methodol. 2017;17(1):33.
Aoki T, Nakata H, Watanabe H, et al. Evolution of peripheral lung adenocarcinomas: CT findings correlated with histology and tumor doubling time. Am J Roentgenol. 2000;174(3):763–68.
Takashima S, Maruyama Y, Hasegawa M, et al. CT findings and progression of small peripheral lung neoplasms having a replacement growth pattern. Am J Roentgenol. 2003;180(3):817–26.
Min JH, Lee HY, Lee KS, et al. Stepwise evolution from a focal pure pulmonary ground-glass opacity nodule into an invasive lung adenocarcinoma: an observation for more than 10 years. Lung Cancer. 2010;69(1):123–26.
Soda H, Nakamura Y, Nakatomi K, et al. Stepwise progression from ground-glass opacity towards invasive adenocarcinoma: long-term follow-up of radiological findings. Lung Cancer. 2008;60(2):298–301.
Noguchi M. Stepwise progression of pulmonary adenocarcinoma—clinical and molecular implications. Cancer Metastasis Rev. 2010;29(1):15–21.
Xue X, Wang P, Xue Q, et al. Comparative study of solitary thin-walled cavity lung cancer with computed tomography and pathological findings. Lung Cancer. 2012;78(1):45–50. https://doi.org/10.1016/j.lungcan.2012.06.004
Ohdama S, Akagawa S, Matsubara O, et al. Primary diffuse alveolar septal amyloidosis with multiple cysts and calcification. Eur Respir J. 1996;9(7):1569–71.
Goncharova EA, Goncharov DA, James ML, et al. Folliculin controls lung alveolar enlargement and epithelial cell survival through E-cadherin, LKB1, and AMPK. Cell Rep. 2014;7(2):412–23. https://doi.org/10.1016/j.celrep.2014.03.025.
Kakinuma R, Ohmatsu H, Kaneko M, et al. Progression of focal pure ground-glass opacity detected by low-dose helical computed tomography screening for lung cancer. J Comput Assist Tomogr. 2004;28(1):17–23.
Watanabe Y, Kusumoto M, Yoshida A, et al. Cavity wall thickness in solitary cavitary lung adenocarcinomas is a prognostic indicator. Ann Thorac Surg. 2016;102(6):1863–71. https://doi.org/10.1016/j.athoracsur.2016.03.121.
Watanabe Y, Kusumoto M, Yoshida A, et al. Surgically resected solitary cavitary lung adenocarcinoma: association between clinical, pathologic, and radiologic findings and prognosis. Ann Thorac Surg. 2015;99(3):968–74.
Deng H, Zhang J, Zhao S, et al. Thin-wall cystic lung cancer: a study of 45 cases. Oncol Lett. 2018;16(1):755–60. https://doi.org/10.3892/ol.2018.8707.
Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med. 2012;18(7):1028–40. https://doi.org/10.1038/nm.2807.
Rybinski B, Franco-Barraza J, Cukierman E. The wound healing, chronic fibrosis, and cancer progression triad. Physiol Genom. 2014;46(7):223-44. https://doi.org/10.1152/physiolgenomics.00158.2013.
Hayashi Y, Tsujii M, Kodama T, et al. p53 functional deficiency in human colon cancer cells promotes fibroblast-mediated angiogenesis and tumor growth. Carcinogenesis. 2016;37(10):972–84.
The authors thank the Division of Statistics in the Medical Research Collaborating Center at SNUBH for assistance with the statistical analyses.
This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.
Woohyun Jung, Sukki Cho, Sungwon Yum, Jin-Haeng Chung, Kyung won Lee, Kwhanmien Kim, Choon Taek Lee, and Sanghoon Jheon have no conflicts of interest to declare.
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Electronic Supplementary Material
Flow chart summarizing the study methods: (1) search strategy for patients with lung adenocarcinoma with cystic airspaces (LACA) using our prospective collected database system, clinical data warehouse (CDW), and electronic medical records (EMR); (2) construction of the disease progression model; and (3) model verification.
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Jung, W., Cho, S., Yum, S. et al. Stepwise Disease Progression Model of Subsolid Lung Adenocarcinoma with Cystic Airspaces. Ann Surg Oncol 27, 4394–4403 (2020). https://doi.org/10.1245/s10434-020-08508-4