The Pseudocavitation Sign of Lung Adenocarcinoma: A Distinguishing Feature and Imaging Biomarker of Lepidic Growth

Purpose: Our purpose was to evaluate whether pseudocavitation, characterized by round or oval areas of low attenuation in a lesion on computed tomography (CT), can help distinguish adenocarcinoma from other types of non–small cell lung cancer (NSCLC). We also sought to determine whether pseudocavitation is associated with lepidic growth on histopathology. Materials and Methods: This retrospective HIPAA-compliant study was approved by our institutional review board. The need for informed consent was waived. CT scans and pathology records from 158 NSCLCs in 149 patients were retrospectively reviewed. The frequency of pseudocavitation was compared among types of NSCLC, specifically adenocarcinoma versus other types of NSCLC. Subgroup analysis of adenocarcinomas was performed to identify any difference in the frequency of pseudocavitation between adenocarcinomas with reported lepidic growth and those without lepidic growth. Results: There was a significantly greater frequency of pseudocavitation in adenocarcinomas versus other types of NSCLC [19/86 (22.1%) vs. 4/72 (5.6%), P=0.007]. The sensitivity and specificity of the pseudocavitation sign for adenocarcinoma were 0.22 and 0.94, respectively. Among adenocarcinomas, the pseudocavitation sign was more frequent in tumors with lepidic growth versus those without lepidic growth [10/24 (41.7%) vs. 9/62 (14.5%), P=0.015]. Conclusions: Pseudocavitation at CT is more common in primary lung adenocarcinoma than in other types of NSCLC. It is also more common in adenocarcinomas with lepidic growth, suggesting a correlation between the imaging finding of pseudocavitation and the pathologic finding of lepidic growth. As the subtype of NSCLC guides treatment, predicting tumor pathology by imaging may improve diagnostic workup for patients with NSCLC.

[1]  P. Gevenois,et al.  Bronchioloalveolar carcinoma: computed tomography findings. , 1996, The European respiratory journal.

[2]  N. Müller,et al.  Solitary pulmonary nodule: high-resolution CT and radiologic-pathologic correlation. , 1991, Radiology.

[3]  T. Mok,et al.  Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. , 2009, The New England journal of medicine.

[4]  R. Wilson,et al.  EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  H. Hansen,et al.  Lung cancer. , 1990, Cancer chemotherapy and biological response modifiers.

[6]  V. Gebski,et al.  Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. , 2013, Journal of the National Cancer Institute.

[7]  A. Gazdar.  Personalized medicine and inhibition of EGFR signaling in lung cancer. , 2009, The New England journal of medicine.

[8]  Hiroto Hatabu,et al.  Imaging of lung cancer in the era of molecular medicine. , 2011, Academic radiology.

[9]  J. Stout,et al.  Cavitary Pulmonary Disease , 2008, Clinical Microbiology Reviews.

[10]  J. Mouroux,et al.  Should cavitated bronchopulmonary cancers be considered a separate entity? , 1996, The Annals of thoracic surgery.

[11]  E. Felip,et al.  Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. , 2012, The Lancet. Oncology.

[12]  S. Lippman,et al.  Lung cancer. , 2008, The New England journal of medicine.

[13]  Kenji Suzuki,et al.  Bronchioloalveolar Carcinoma (Lepidic Growth) Component Is a More Useful Prognostic Factor than Lymph Node Metastasis , 2009, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[14]  S. Gabriel,et al.  EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy , 2004, Science.

[15]  Michael Thomas,et al.  Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. , 2013, The New England journal of medicine.

[16]  Denise R. Aberle,et al.  Radiologic implications of the 2011 classification of adenocarcinoma of the lung. , 2013, Radiology.

[17]  Masahiro Tsuboi,et al.  International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma , 2011, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[18]  S. Thongprasert,et al.  A Prospective, Molecular Epidemiology Study of EGFR Mutations in Asian Patients with Advanced Non–Small-Cell Lung Cancer of Adenocarcinoma Histology (PIONEER) , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[19]  A. Shaw,et al.  Targeting Anaplastic Lymphoma Kinase in Lung Cancer , 2011, Clinical Cancer Research.

[20]  K S Lee,et al.  Bronchioloalveolar carcinoma: clinical, histopathologic, and radiologic findings. , 1997, Radiographics : a review publication of the Radiological Society of North America, Inc.

[21]  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.

[22]  Masahiro Tsuboi,et al.  Correlations of Thin-Section Computed Tomographic, Histopathological, and Clinical Findings of Adenocarcinoma With a Bubblelike Appearance , 2010, Journal of computer assisted tomography.

[23]  Joungho Han,et al.  Pathologic Review of Cystic and Cavitary Lung Diseases , 2012, Korean journal of pathology.

[24]  Hiroto Hatabu,et al.  State of the art: Response assessment in lung cancer in the era of genomic medicine. , 2014, Radiology.

[25]  Patricia L. Harris,et al.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. , 2004, The New England journal of medicine.

[26]  D. Lynch,et al.  Interobserver variability in the CT assessment of honeycombing in the lungs. , 2013, Radiology.

[27]  Robert Brian Jenkins,et al.  Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[28]  Masahiro Fukuoka,et al.  Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  N. Müller,et al.  Fleischner Society: glossary of terms for thoracic imaging. , 2008, Radiology.

[30]  Y. Sakao,et al.  Subtypes of peripheral adenocarcinoma of the lung: differentiation by thin-section CT , 2005, European Radiology.

[31]  Cystic Change (Pseudocavitation) Associated with Bronchioloalveolar Carcinoma: A Report of Four Patients , 1995, Journal of thoracic imaging.

[32]  Jun Ma,et al.  Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. , 2011, The Lancet. Oncology.