Snapshot A 65-year-old man with a 40 pack-year smoking history presents to his primary care physician for fatigue and cough. He reports that his symptoms began approximately 1 year ago and has progressively worsened. He has noticed a streak of blood when coughing into a napkin. He says that at times he wakes up from sleep drenched in sweat. Compared to his last visit 4 months ago he has lost 12 pounds which he states is unintentional. Physical examination is notable for finger clubbing. Radiography of the chest demonstrates a pulmonary nodule, and no prior imaging is available. A CT scan of the chest demonstrates an 11 mm pulmonary eccentric nodule located peripherally. Introduction Clinical definition malignancy that affects the lung parenchyma or airways most lung cancers can be divided into small cell lung cancer non-SCLC Small Cell Lung Cancer (SCLC) Type Location Associated Findings Histology SCLC (oat cell) Central MYC gene amplication May produce adrenocorticotropic hormone (ACTH) leads to Cushing syndrome excessive anti-diuretic hormone (ADH) leads to syndrome of inappropriate ADH (SIADH) presynaptic calcium channel antibodies leads to Lambert Eaton syndrome Kulchitsky cells Positive for neuron-specific enolase chromogranin A Non-Small Cell Lung Cancer (NSCLC) Type Location Associated Findings Histology Adenocarcinoma Peripheral Most common cause of lung cancer in non-smokers cause of lung cancer (excluding metastasis) Adenocarcinoma in situ tumor growth along alveolar structures lepidic growth pattern Patients may have hypertrophic osteoarthropathy Common gene mutations include KRAS EGFR ALK Typically mucin positive and has a glandular appearance Large cell carcinoma Peripheral Associated with a poor prognosis Highly associated with smoking Pleomorphic giant cells Squamous cell carcinoma of the lung Central Can arise from the bronchus Keratin pearls Intracellular bridges Bronchial carcinoid tumor - Carcinoid syndrome Better prognosis Neuroendocrine cells Chromogranin A positive Epidemiology incidence second most common cancer leading cause of cancer-related death risk factors cigarette smoking most important risk factor second-hand smoking asbestos radon Etiology tobacco smoke is the most common cause Prognosis depends on cancer type and severity Screening performed with a low-dose computerized tomography (CT) scan of the chest indicated in patients 55-80 years of age who have a 30 pack-year smoking history and currently smoke or has quit within the past 15 years Presentation Symptoms cough unintentional weight loss hemoptysis chest pain dyspnea hoarseness suggests involvement in the recurrent laryngeal nerve Imaging Radiography indication initial imaging modality when evaluating a patient with symptoms concerning for lung cancer it is highly important to review old chest imaging to assess for lesion properties and changes Computerized tomography (CT) scan indication perform with low-doses to screen for lung cancer (review "screening" in the introduction) to further evaluate pulmonary nodule found on radiography Studies Laboratory testing complete blood count liver function tests (e.g., alanine aminotransferase, aspartate aminotransferase, and total bilirubin) abnormalities may suggest liver metastasis alkaline phosphatase abnormalities may suggest liver or bone metastasis a gamma-glutamyl transpeptidase (GGT) should be obtained to differentiate between liver or bone involvement calcium abnormalities may suggest bone metastasis or paraneoplastic syndromes Pulmonary function tests Evaluation of an incidental solitary pulmonary nodule introduction benign features diffuse central popcorn concentric malignant features ground-glass eccentric chest CT should be obtained for all patients with an unclearly characterized solitary pulmonary nodule seen on radiography solitary pulmonary nodule < 8mm if there are or aren't risk factors, one typically does surveillance with a chest CT in a few months depending on the size of the lesion solitary pulmonary nodule > 8mm very low probability of malignancy CT surveillance low/moderate probability of malignancy positron emission tomography (PET) scan if absent or mild uptake CT surveillance if moderate or intense uptake biopsy or video-assisted thoracoscopic surgery high probability of malignancy staging evaluation with or without PET scan Differential Tuberculosis (Tb) differentiating factors abnormal quantiferon or purified protein derivative (PPD) test history of increased risk of exposure (e.g., household contact with someone with diagnosed Tb and travel to Tb endemic area) Treatment SCLC most cases are non-resectable and thus require chemotherapy (e.g., carboplatin and etoposide) NSCLC treatment includes surgical removal, lymph node sampling or dissection, radiation, and chemotherapy depends on the staging Complications Superior vena cava syndrome Pancoast tumor Metastasis Horner syndrome Pericardial effusion Pleural effusion Paraneoplastic syndromes Lambert-Eaton syndrome SIADH Cushing syndrome