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Diagnostic Workup for Suspected Lung Cancer Confined to the Chest

Summary of Key Points In the context of disease confined to the chest, mediastinal staging is crucial for determining the best curative treatment strategy, especially for nonsmall cell lung cancer (NSCLC). Urgent referral for chest imaging is recommended for patients who present with hemoptysis or any of several symptoms or signs that are unexplained or persistent. Chest radiograph is the main radiographic investigation in the primary…

Positron Emission Tomography Imaging of Lung Cancer

Summary of Key Points 18 F-2-deoxy- d -glucose (FDG)-positron emission tomography–computed tomography (PET–CT) is routinely used clinically for diagnosis, staging, and radiation treatment planning and may have a role in prognosis and monitoring of treatment response. FDG-PET–CT is not optimal in determination of T descriptors (additional small lung nodules, locoregional invasion, etc.) as respiratory motion and or low-radiation-dose imaging degrade image quality. FDG-PET–CT has superior accuracy…

Conventional Imaging of Lung Cancer

Summary of Key Points Low-dose multidetector computed tomography (CT) screening of active and former heavy smokers has been shown to decrease lung cancer mortality. The malignant potential of solid pulmonary nodules depends on their size, with larger nodules more likely to represent tumor. Nevertheless, solid nodules have a low overall malignancy rate (7%). Ground-glass nodules and part-solid nodules have a higher chance of malignancy than completely…

Clinical Presentation and Prognostic Factors in Lung Cancer

Summary of Key Points Most people with lung cancer are symptomatic at the time of initial presentation; however, between 5% and 15% of people may be asymptomatic. Alarming symptoms for lung cancer like cough, hemoptysis, dyspnea, chest pain and weight loss should be timely recognized. No specific clinical manifestations exist to guide and help the physician distinguish between specific histologic subtypes. Increased awareness of cough, one…

Management of Small Histologic and Cytologic Specimens in the Molecular Era

Summary of Key Points Techniques for the optimal triage and preparation of small specimens for diagnosis and ancillary studies are provided. For optimal results, a standardized protocol and algorithm should be implemented in the laboratory. Various factors determine the decision to perform a core-needle biopsy or fine-needle aspiration, including operator and pathologist preference, availability of rapid onsite evaluation, risk of complications such as pneumothorax or hemorrhage,…

Molecular Testing in Lung Cancer

Summary of Key Points Of key importance is whether a prognostic marker is also a predictive marker for therapeutic benefit. As predictive biomarkers become integral in the use of targeted therapies to treat lung cancer, multidisciplinary and evidence-based guidelines for molecular testing are needed; the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association of Molecular Pathologists have published…

Classic Anatomic Pathology and Lung Cancer

Summary of Key Points A clinically relevant pathologic classification of lung cancer is essential for accurate diagnosis and for patients to receive appropriate therapy. Although classification of the majority of lung cancers is straightforward, areas of controversy and diagnostic challenges remain. The current lung cancer classification is applicable to surgically resected tumors and small biopsy specimens. Pathologists play a critical role in properly handling tissue and…

Humoral and Cellular Immune Dysregulation and Lung Cancer

Summary of Key Points Humoral and cellular immune dysregulation in the tumor microenvironment contributes to immune evasion, a key hallmark of lung cancer. Immunosuppressive mechanisms observed in lung cancer include defective antigen presentation, secretion of immunosuppressive tumor-derived soluble factors, and immunosuppressive cells infiltrating the tumors. Suppression of antigen-presenting machinery in lung cancer results from several mechanisms including deficiencies in expression of antigen-processing genes and haplotype loss…

MicroRNAs as Biomarkers for Lung Cancer

Summary of Key Points The biologic roles of microRNAs (miRNAs) in lung cancer indicate their correlation with disease status, prognosis, and therapeutic outcome. The discovery of miRNAs has opened a new avenue for individualized disease diagnosis and treatment. Dysfunctions of miRNAs are frequently found in lung cancer. These noncoding RNAs have been recognized as some of the main regulatory gatekeepers of coding genes in the human…

Microenvironment and Lung Cancer

Summary of Key Points There is untapped potential for targeted lung cancer prevention and therapy that requires, as a first step, a more clear delineation of the biology underlying the lung carcinogenesis process. The pulmonary microenvironment represents a unique milieu in which lung carcinogenesis proceeds in complicity with the four main components of the tumor microenvironment (TME): the field, cellular, soluble, and structural components. The literature…

Stem Cells and Lung Cancer: In Vitro and In Vivo Studies

Summary of Key Points The use of mouse models to study the initiation and evolution of lung cancers has been crucial in advancing the field through the identification of putative stem cell niches within the lung. Bronchoalveolar stem cells (BASCs) are the putative cell of origin for lung adenocarcinoma. The tumor suppressor gene phosphatase and tensin homolog (PTEN) exerts a brake on BASC transformation to adenocarcinoma.…

Epigenetic Events in Lung Cancer: Chromatin Remodeling and DNA Methylation

Summary of Key Points Distinct cellular phenotypes are based on differential gene expression, which is achieved through heritable epigenetic modifications that maintain active and inactive chromosomal regions. Epigenetic mechanisms include DNA methylation, histone modifications, regulatory DNA-binding proteins, regulatory RNAs, genome-organizing proteins, and chromatin remodeling complexes, all of which can be altered in lung cancer. Both genetic and epigenetic alterations can contribute to lung cancer and they…

Mutational Events in Lung Cancer: Present and Developing Technologies

Summary of Key Points Cancer genomes are characterized by the presence of a variety of alterations including base substitutions, copy-number alterations (amplifications or deletions), and structural rearrangements (translocations or chromosomal rearrangements). Among the early methods of DNA sequencing (now known as first-generation methods), the most successful has been the Sanger sequencing or chain termination reaction method. Despite its effectiveness, accuracy, and the substantial improvements since its…

Copy Number Abnormalities and Gene Fusions in Lung Cancer: Present and Developing Technologies

Summary of Key Points Lung cancers commonly have structural chromosome aberrations and aneuploidy, with many of them associated with carcinogenesis. Gene amplification is a common mechanism of oncogenic activation in nonsmall cell lung cancer (NSCLC) involving genes such as MYC , EGFR , ERBB 2, MET , PIK3CA, and FGFR1. Gene amplification is also associated with resistance to drugs, for instance, to epidermal growth factor receptor…

Chemoprevention of Lung Cancer and Management of Early Lung Cancer

Summary of Key Points Most chemoprevention research is focused on natural products and is not amenable to traditional pharmaceutical development. Robust research and development for lung cancer chemoprevention by the pharmaceutical industry is largely lacking. The traditional model of developing drugs for advanced disease and then backing successful agents into early disease application is not working. Safety is coequal to efficacy in developing a successful chemopreventive…

Preclinical Biomarkers for the Early Detection of Lung Cancer

Summary of Key Points This chapter provides a review of some of the most promising recent studies of diagnostic biomarkers in lung cancer. We discuss the challenges and the importance of biomarker validation. Current guidelines recommend a study design to include prospective collections of specimens and retrospective blinded evaluation. A novel multiomics approach to biomarker discovery has greatly advanced the field of early lung cancer detection.…

Screening for Lung Cancer

Summary of Key Points The National Lung Screening Trial has definitively shown a reduction in lung cancer mortality in a research setting but effective implementation of a lung cancer screening program needs to be evaluated in different health-care communities. Selection of high-risk participants for low-dose (radiation) computed tomography screening is improved by the use of multivariate risk prediction models. A range of recruitment strategies will be…

Genetic Susceptibility to Lung Cancer

Summary of Key Points While 85% to 90% of lung cancer is attributable to cigarette smoking, substantial evidence exists to support genetic susceptibility to this disease. A family history of lung cancer is associated with a 1.5 to 4-fold increased risk of lung cancer after adjustment for the clustering of smoking in families. A family-based linkage study has identified a region on chromosome 6q that segregates…

Gender-Related Differences in Lung Cancer

Summary of Key Points Epidemiology of lung cancer is still changing: in the last 10 years lung cancer became the first cause of cancer-related deaths in both men and women in many countries, while having previously been a rare disease in females. Smoking is the first cause of lung cancer also among women: no conclusive data are present in the literature about female smokers and their…

Lung Cancer in Never-Smokers: A Different Disease

Summary of Key Points The known or suspected etiologic factors for lung cancer arising in never-smokers are weak carcinogens or rare factors, which cannot explain the relatively high frequency of cancer in never-smokers. This also applies to environmental tobacco smoke. Genetic factors play an increasing role in the etiology of lung cancer in never-smokers. These include rare high penetrance mutations in crucial genes such as the…