Ground-Glass Opacity Lung Nodules in the Era of Lung Cancer CT Screening: Radiology, Pathology, and Clinical Management.

The advent of computed tomography screening for lung cancer will increase the incidence of ground-glass opacity (GGO) nodules detected and referred for diagnostic evaluation and management. GGO nodules remain a diagnostic challenge; therefore, a more systematic approach is necessary to ensure correct diagnosis and optimal management. Here we present the latest advances in the radiologic imaging and pathology of GGO nodules, demonstrating that radiologic features are increasingly predictive of the pathology of GGO nodules. We review the current guidelines from the Fleischner Society, the National Comprehensive Cancer Network, and the British Thoracic Society. In addition, we discuss the management and follow-up of GGO nodules in the light of experience from screening trials. Minimally invasive tissue biopsies and the marking of GGO nodules for surgery are new and rapidly developing fields that will yield improvements in both diagnosis and treatment. The standard-of-care surgical treatment of early lung cancer is still minimally invasive lobectomy with systematic lymph node dissection. However, recent research has shown that some GGO lesions may be treated with sublobar resections; these findings may expand the surgical treatment options available in the future.

[1]  H. Asamura,et al.  Sublobar resection for early-stage lung cancer. , 2014, Translational lung cancer research.

[2]  Massimo Bellomi,et al.  CT Radiogenomic Characterization of EGFR, K-RAS, and ALK Mutations in Non-Small Cell Lung Cancer , 2015, European Radiology.

[3]  M. Okada,et al.  Appropriate sublobar resection choice for ground glass opacity-dominant clinical stage IA lung adenocarcinoma: wedge resection or segmentectomy. , 2014, Chest.

[4]  Y. Yatabe,et al.  Disproportionate representation of KRAS gene mutation in atypical adenomatous hyperplasia, but even distribution of EGFR gene mutation from preinvasive to invasive adenocarcinomas , 2007, The Journal of pathology.

[5]  Mathias Prokop,et al.  Pulmonary ground-glass nodules: increase in mass as an early indicator of growth. , 2010, Radiology.

[6]  Hiromasa Yamamoto,et al.  Sequential Molecular Changes during Multistage Pathogenesis of Small Peripheral Adenocarcinomas of the Lung , 2008, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[7]  Kenji Suzuki,et al.  Radiologic classification of small adenocarcinoma of the lung: radiologic-pathologic correlation and its prognostic impact. , 2006, The Annals of thoracic surgery.

[8]  Masahiko Kusumoto,et al.  Radiographically determined noninvasive adenocarcinoma of the lung: survival outcomes of Japan Clinical Oncology Group 0201. , 2013, The Journal of thoracic and cardiovascular surgery.

[9]  S. Lam,et al.  Probability of cancer in pulmonary nodules detected on first screening CT. , 2013, The New England journal of medicine.

[10]  Harry J de Koning,et al.  Management of lung nodules detected by volume CT scanning. , 2009, The New England journal of medicine.

[11]  Federico Davini,et al.  Thoracoscopic localization techniques for patients with solitary pulmonary nodule: hookwire versus radio-guided surgery. , 2007, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[12]  A. Dirksen,et al.  Lung Cancer Screening and Video-Assisted Thoracic Surgery , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[13]  Akihiko Yoshizawa,et al.  Prognostic Significance of Adenocarcinoma In Situ, Minimally Invasive Adenocarcinoma, and Nonmucinous Lepidic Predominant Invasive Adenocarcinoma of the Lung in Patients With Stage I Disease , 2014, The American journal of surgical pathology.

[14]  Takayuki Fukui,et al.  The association between baseline clinical-radiological characteristics and growth of pulmonary nodules with ground-glass opacity. , 2014, Lung cancer.

[15]  B. Meyers,et al.  Segmentectomy versus wedge resection for non-small cell lung cancer in high-risk operable patients. , 2013, The Annals of thoracic surgery.

[16]  Ning Wu,et al.  Early detection of lung cancer: Low-dose computed tomography screening in China , 2015, Thoracic cancer.

[17]  Michelle S. Ginsberg,et al.  Are There Imaging Characteristics Associated with Epidermal Growth Factor Receptor and KRAS Mutations in Patients with Adenocarcinoma of the Lung with Bronchioloalveolar Features? , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[18]  Jae Ho Lee,et al.  Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements in lung cancer with nodular ground-glass opacity , 2014, BMC Cancer.

[19]  C. Gatsonis,et al.  Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening , 2012 .

[20]  G. Feola,et al.  Methylene blue-stained autologous blood for needle localization and thoracoscopic resection of deep pulmonary nodules. , 2002, Journal of pediatric surgery.

[21]  I. Takeyoshi,et al.  Correlation between computed tomography findings and epidermal growth factor receptor and KRAS gene mutations in patients with pulmonary adenocarcinoma. , 2011, Oncology reports.

[22]  Tae Jung Kim,et al.  The long-term course of ground-glass opacities detected on thin-section computed tomography. , 2013, Respiratory medicine.

[23]  T. Kohno,et al.  Invasiveness and malignant potential of pulmonary lesions presenting as pure ground-glass opacities. , 2014, Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia.

[24]  Etsuo Miyaoka,et al.  Pulmonary Ground-Glass Opacity (GGO) Lesions–Large Size and a History of Lung Cancer are Risk Factors for Growth , 2008, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[25]  Matthijs Oudkerk,et al.  International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report. , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[26]  K. Kerr,et al.  Guidelines on the radical management of patients with lung cancer , 2010, Thorax.

[27]  H. Matsuda,et al.  Optimal distance of malignant negative margin in excision of nonsmall cell lung cancer: a multicenter prospective study. , 2004, The Annals of thoracic surgery.

[28]  M. Kalra,et al.  The 10 Pillars of Lung Cancer Screening: Rationale and Logistics of a Lung Cancer Screening Program. , 2015, Radiographics : a review publication of the Radiological Society of North America, Inc.

[29]  M. Okada,et al.  Oncologic outcomes of segmentectomy compared with lobectomy for clinical stage IA lung adenocarcinoma: propensity score-matched analysis in a multicenter study. , 2013, The Journal of thoracic and cardiovascular surgery.

[30]  T. Naruke,et al.  Evaluation of F-18 fluorodeoxyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images. , 2004, Lung cancer.

[31]  A. Duranceau,et al.  Thoracoscopic localization of intraparenchymal pulmonary nodules using direct intracavitary thoracoscopic ultrasonography prevents conversion of VATS procedures to thoracotomy in selected patients. , 2012, The Journal of thoracic and cardiovascular surgery.

[32]  A. Scarsbrook,et al.  Risk of malignancy in pulmonary nodules: A validation study of four prediction models. , 2015, Lung cancer.

[33]  W. Travis WHO classification of tumours of the lung, pleura, thymus and heart , 2015 .

[34]  W. De Wever,et al.  Computed Tomography of the Lung: A Pattern Approach , 2008, Journal of Nuclear Medicine.

[35]  Ho Yun Lee,et al.  Pure ground-glass opacity neoplastic lung nodules: histopathology, imaging, and management. , 2014, AJR. American journal of roentgenology.

[36]  D. Wood,et al.  National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Lung Cancer Screening. , 2015, Thoracic surgery clinics.

[37]  B. van Ginneken,et al.  Towards a close computed tomography monitoring approach for screen detected subsolid pulmonary nodules? , 2014, European Respiratory Journal.

[38]  Gwénaël Le Teuff,et al.  Subtype Classification of Lung Adenocarcinoma Predicts Benefit From Adjuvant Chemotherapy in Patients Undergoing Complete Resection. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  E. Duhig,et al.  Mitosis Trumps T Stage and Proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification for Prognostic Value in Resected Stage 1 Lung Adenocarcinoma , 2015, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[40]  Michael Thomas,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. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  V. Torri,et al.  Differential diagnosis and management of focal ground-glass opacities , 2009, European Respiratory Journal.

[42]  J. Austin,et al.  Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. , 2005, Radiology.

[43]  Colin Jacobs,et al.  Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial , 2015, European Radiology.

[44]  M. Masuda,et al.  Comparison between CT tumor size and pathological tumor size in frozen section examinations of lung adenocarcinoma. , 2014, Lung cancer.

[45]  Arman Kilic,et al.  Anatomic segmentectomy in the treatment of stage I non-small cell lung cancer. , 2007, The Annals of thoracic surgery.

[46]  Kyung Soo Lee,et al.  Natural history of pure ground-glass opacity lung nodules detected by low-dose CT scan. , 2013, Chest.

[47]  G. Veronesi,et al.  Positron emission tomography in the diagnostic work-up of screening-detected lung nodules , 2014, European Respiratory Journal.

[48]  O. Miettinen,et al.  Survival of Patients with Stage I Lung Cancer Detected on CT Screening , 2008 .

[49]  A. Yoshizawa,et al.  Validation of the IASLC/ATS/ERS Lung Adenocarcinoma Classification for Prognosis and Association with EGFR and KRAS Gene Mutations: Analysis of 440 Japanese Patients , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[50]  X. Chen,et al.  Comparative analysis of clinicoradiologic characteristics of lung adenocarcinomas with ALK rearrangements or EGFR mutations , 2015, European Radiology.

[51]  Iver Petersen,et al.  Reproducibility of histopathological subtypes and invasion in pulmonary adenocarcinoma. An international interobserver study , 2012, Modern Pathology.

[52]  M. Okada,et al.  Prognostic significance of using solid versus whole tumor size on high-resolution computed tomography for predicting pathologic malignant grade of tumors in clinical stage IA lung adenocarcinoma: a multicenter study. , 2012, The Journal of thoracic and cardiovascular surgery.

[53]  S. Toyooka,et al.  Clinical outcomes of short hook wire and suture marking system in thoracoscopic resection for pulmonary nodules. , 2009, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[54]  S. Lam,et al.  Preoperative computed tomography-guided microcoil localization of small peripheral pulmonary nodules: a prospective randomized controlled trial. , 2015, The Journal of thoracic and cardiovascular surgery.

[55]  Y. Yatabe,et al.  Genetic features of pulmonary adenocarcinoma presenting with ground-glass nodules: the differences between nodules with and without growth. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[56]  D. Libby,et al.  Outcomes of Unresected Ground-Glass Nodules with Cytology Suspicious for Adenocarcinoma , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[57]  M. Tsuboi,et al.  A phase III randomized trial of lobectomy versus limited resection for small-sized peripheral non-small cell lung cancer (JCOG0802/WJOG4607L). , 2010, Japanese journal of clinical oncology.

[58]  M. Callister,et al.  British Thoracic Society guidelines for the investigation and management of pulmonary nodules. , 2015 .

[59]  Kyung Soo Lee,et al.  Persistent pure ground-glass opacity lung nodules ≥ 10 mm in diameter at CT scan: histopathologic comparisons and prognostic implications. , 2013, Chest.

[60]  T. Naruke,et al.  Usefulness and complications of computed tomography-guided lipiodol marking for fluoroscopy-assisted thoracoscopic resection of small pulmonary nodules: experience with 174 nodules. , 2006, The Journal of thoracic and cardiovascular surgery.

[61]  S. Hirohashi,et al.  Mutations of the epidermal growth factor receptor gene in atypical adenomatous hyperplasia and bronchioloalveolar carcinoma of the lung. , 2005, Lung cancer.

[62]  D. Lynch,et al.  The National Lung Screening Trial: overview and study design. , 2011, Radiology.