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The diagnosis of lung cancer rests on examination of a tissue or cytology specimen Sputum cytology is highly specific but insensitive; the yield is highest when there are lesions in the central airways Thoracentesis (sensitivity 50 65%) can be used to establish a diagnosis of lung cancer in patients with malignant pleural effusions If cytologic examination of an adequate sample (50 100 mL) of pleural fluid is nondiagnostic, the procedure should be repeated once If results remain negative, thoracoscopy is preferred to blind pleural biopsy Fine-needle aspiration (FNA) of palpable supraclavicular or cervical lymph nodes is frequently diagnostic Serum tumor markers are neither sensitive nor specific enough to aid in diagnosis Fiberoptic bronchoscopy allows visualization of the major airways, cytology brushing of visible lesions or lavage of lung segments with cytologic evaluation of specimens, direct biopsy of endobronchial abnormalities, blind transbronchial biopsy of the pulmonary parenchyma or peripheral nodules, and FNA biopsy of mediastinal lymph nodes Diagnostic yield varies widely (10 90%) depending on the size of the lesion and its location Recent advances include fluorescence bronchoscopy, which improves the ability to identify early endobronchial lesions; and endoscopic ultrasound, which permits more accurate direction of FNA Transthoracic needle aspiration (TTNA) has a sensitivity between 50% and 97% Mediastinoscopy, video-assisted thoracoscopic surgery (VATS), and thoracotomy are necessary in cases where less invasive techniques fail to yield a diagnosis

Lung cancer is symptomatic at diagnosis in 75 90% of patients The clinical presentation depends on the type and location of the primary tumor, the extent of local spread, and the presence of distant metastases and any paraneoplastic syndromes

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Anorexia, weight loss, or asthenia occurs in 55 90% of patients presenting with a new diagnosis of lung cancer Up to 60% of patients have a new cough or a change in a chronic cough; 6 31% have hemoptysis; and 25 40% complain of pain, sometimes nonspecific chest pain but often referable to bony metastases to the vertebrae, ribs, or pelvis Local spread may cause endobronchial obstruction with atelectasis and postobstructive pneumonia, pleural effusion (12 33%), change in voice (compromise of the recurrent laryngeal nerve), superior vena cava syndrome (obstruction of the superior vena cava with supraclavicular venous engorgement), and Horner s syndrome (ipsilateral ptosis, miosis, and anhidrosis from involvement of the inferior cervical ganglion and the paravertebral sympathetic chain) Distant metastases to the liver are associated with asthenia and weight loss Brain metastases (10%; more common in adenocarcinoma) may present with headache, nausea, vomiting, seizures, or altered mental status Paraneoplastic syndromes are incompletely understood patterns of organ dysfunction related to immune-mediated or secretory effects of neoplasms These syndromes occur in 10 20% of lung cancer patients They may precede, accompany, or follow the diagnosis of lung cancer They do not necessarily indicate metastatic disease Fifteen percent of patients with small cell carcinoma will develop syndrome of inappropriate antidiuretic hormone (SIADH); 10% of patients with squamous cell carcinoma will develop hypercalcemia Digital clubbing is seen in up to 20% of patients at diagnosis Other common paraneoplastic syndromes include increased ACTH production, anemia, hypercoagulability, peripheral neuropathy, and the Eaton-Lambert myasthenia syndrome Their recognition is important because treatment of the primary tumor may improve or resolve symptoms even when the cancer is not curable

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Nearly all patients with lung cancer have abnormal findings on chest radiography or CT scan These findings are rarely specific for a particular diagnosis Interpretation of characteristic findings in isolated nodules is described in 9

1 Staging Accurate staging (see Additional Reading at the end of the chapter) is crucial (1) to provide the clinician with information to guide treatment, (2) to provide the patient with accurate information regarding prognosis, and (3) to standardize entry criteria for clinical trials to allow interpretation of results There are two essential principles of staging NSCLC First, the more extensive the disease, the worse the prognosis; second, surgical resection offers the best and perhaps the only realistic hope for cure Staging of NSCLC uses two integrated systems The TNM international staging system attempts a physical description of the neoplasm: T describes the size and location of the primary tumor; N describes the presence and location of nodal metastases; and M refers to the presence or absence of distant metastases These TNM stages are grouped into prognostic categories (stages I IV) using the results of clinical trials This classification is used to guide therapy Many patients with stage I and stage II disease are cured through surgery Patients with stage IIIB and stage IV disease do not benefit from surgery Patients with stage IIIA disease have locally invasive disease that may benefit from surgery in certain circumstances

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