Advances in molecular biology are improving the understanding of lung cancer and changing the approach to treatment. A satisfactory biopsy that allows for histologic characterization and mutation analysis is becoming increasingly important. Most patients with lung cancer are diagnosed at an advanced stage, and diagnosis is often based on a small biopsy or cytology specimen. Here, we review the techniques available for making a diagnosis of lung cancer, including bronchoscopy, ultrasound-guided bronchoscopy, mediastinoscopy, transthoracic needle aspiration, thoracentesis, and medical thoracoscopy. We also discuss the indications, complications, and tissue yields of those techniques, especially as they pertain to testing for molecular markers. KEY WORDSLung cancer, diagnosis, bronchoscopy, endobronchial ultrasonography, thoracoscopy, transthoracic needle aspiration, molecular markers, EGFR INTRODUCTIONDiscoveries in molecular biology are changing the approach to the treatment of patients with non-smallcell lung cancer (nsclc). In recent years, the histologic characterization of lung cancer has markedly advanced, moving beyond the simple distinction of small-cell or non-small-cell disease.The observation that certain histologic subtypes respond differently to particular chemotherapeutic agents and the increasing use of targeted therapies have created a need for precise histologic characterization of biopsy specimens. For example, several trials have shown that response rate and survival with pemetrexed are significantly better in patients with non-squamous histology [1][2][3] . Trials using tyrosine kinase inhibitors have observed that greater benefit from treatment with those agents is seen in patients with nsclc tumours harbouring EGFR mutations than in patients with wild-type tumours 4 . Ongoing clinical trials are examining the use of Alk inhibitors in patients with nsclc characterized by EML4-ALK gene translocations 5 . Those mutations are found almost exclusively in adenocarcinomas.Lung cancer remains the leading cause of cancer death in North America. In Canada in 2010, an estimated 25,300 Canadians were diagnosed with lung cancer, and 20,600 died of the disease 6 . At diagnosis, 75% of patients have either locally advanced or metastatic disease 7 . The goal in this latter group of patients is to establish the diagnosis and, ideally, to confirm the disease stage with the least invasive technique possible. As a result, biopsy specimens have become increasingly smaller. Of nsclc patients receiving chemotherapy for advanced disease, 80% will have only a small biopsy specimen or cytology samples available for diagnosis 8 .In this review, we discuss the minimally invasive and invasive techniques available for the diagnosis and staging of lung cancer, with their success rates and complications. We also discuss the size of the tissue samples obtained by the various techniques, as that size pertains to maximizing the histologic characterization of lung cancer in an era of personalized medicine. Lastly, we re...

BackgroundStudies have reported a high diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of sarcoidosis. We sought to review the yield of EBUS-TBNA for the diagnosis of sarcoidosis at our institution over time, and examine factors that may influence this yield.MethodsPatients who underwent EBUS-TBNA for suspected sarcoidosis between December 2008 and November 2011 were identified. EBUS was performed without rapid on-site evaluation (ROSE) of samples. The final diagnosis was based on the results of all invasive diagnostic procedures and/or clinical follow-up. Logistic regression analysis was used to examine the effect of various factors on yield.Results43 patients underwent 45 EBUS-TBNA procedures for suspected sarcoidosis. A total of 115 lymph nodes were sampled. The 21 G needle was used in 51% of procedures. The mean number of lymph node stations sampled was 2.6 (SD 0.7) and the mean number of needle passes per procedure was 7.8 (SD 2.0). Non-necrotising granulomatous inflammation was detected in EBUS-TBNA samples from 34/45 (76%) procedures. The overall diagnostic yield increased to 36/45 (80%) following a cytopathology review for this study. Needle gauge, number of lymph node stations sampled and number of needle passes were not associated with diagnostic yield. The yield of EBUS-TBNA increased significantly after the first 15 procedures performed for suspected sarcoidosis; the 2 additional cases diagnosed after the cytopathology review were part of this early experience.ConclusionsEBUS-TBNA is a valuable technique for the diagnosis of sarcoidosis when performed without ROSE. The yield of the procedure improved significantly over time, based on operator and cytopathologist experience.

Lung cancer has entered the era of personalized therapy with histologic subclassification and the presence of molecular biomarkers becoming increasingly important in therapeutic algorithms. At the same time, biopsy specimens are becoming increasingly smaller as diagnostic algorithms seek to establish diagnosis and stage with the least invasive techniques. Here, we review techniques used in the diagnosis of lung cancer including bronchoscopy, ultrasound-guided bronchoscopy, transthoracic needle biopsy, and thoracoscopy. In addition to discussing indications and complications, we focus our discussion on diagnostic yields and the feasibility of testing for molecular biomarkers such as epidermal growth factor receptor and anaplastic lymphoma kinase, emphasizing the importance of a sufficient tumor biopsy.