Clinical Presentation of Lung Cancer
Matthew G. Blum
As one of the most common malignancies in the world, lung cancer presents with widely varied signs, symptoms, and syndromes. Some 93% of lung cancer patients present with symptoms. Unfortunately early-stage lung cancer is rarely symptomatic. Even when symptoms of early cancer are present, they are generally not specific and frequently mimic more common disease. Consequently most patients present in advanced stages with metastases and ultimately die of their disease. A recent study of the presentation of lung cancer in 1,154 patients found that 98% of symptomatic patients had stage III or IV disease (versus 46% of asymptomatic patients).52
Reports examining the prevalence of particular presenting symptoms vary widely owing to differing study designs, patient populations, and the time period studied. The most common symptoms from several recent series are cough and dyspnea (Table 107-1). However, the spectrum of lung cancer presentation remains extremely broad because it includes symptoms caused by local invasion, metastases, and paraneoplastic mechanisms. Paraneoplastic syndromes occur in only 2% of patients with lung cancer but cause the widest variety of symptoms and syndromes (Table 107-2). Much of the information about lung cancer presentation refers to data from the 1960s through 1980s, before computed tomography (CT) scanning. Since then there has been a shift in demographics to more elderly patients, women, and adenocarcinoma histology, which may be changing the relative proportions of presenting signs or symptoms. In a report detailing the presentation of 1,277 lung cancer patients between 1989 and 2002, fewer patients presented with cough or chest pain and more were asymptomatic in more recent periods.5 The increasing use of helical CT and high-resolution CT scanning as a lung cancer screening tool and in the evaluation of other medical conditions may account for the increase in asymptomatic lesions detected. Whether by clinical symptoms or radiographic imaging, diagnosing lung cancer relies on having a high index of suspicion in the appropriate setting.
Tobacco smoking is clearly recognized as the major cause of lung cancer, but a myriad of other exposures and patient characteristics have been related to the development of lung cancer. Environmental exposures to secondhand smoke,20 silica, creosotes, and mining of gold, nickel, asbestos, and uranium have all been associated with increased risk of lung cancer. Individuals with autoimmune diseases such as scleroderma and idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), and particular treatments such as chemotherapy for Hodgkin’s lymphoma are also at higher risk of developing lung cancer.51 A familial predilection to lung cancer, even in nonsmokers, suggests that genetics may also predispose some patients to lung cancer.
The incidence of lung cancer increases with age. As a result, young patients (<40 years of age), women, and nonsmokers are more likely to have their symptoms attributed to benign causes. This lower index of suspicion probably accounts for those <40 presenting with higher-stage disease.4,55 Lung cancers appearing <40 years of age are more common in women.23 Adenocarcinoma is also more frequently found in those <40 years of age.4,23,55 The increased use of cigarettes by women has resulted in a parallel increase in the prevalence of lung cancer in women.
Local Symptoms
Bronchopulmonary Symptoms
Cough
Cough is the most common presenting symptom of lung cancer (Table 107-1), but it is frequently overlooked because it is far more often associated with infections or chronic bronchitis. Cancer-associated cough is caused by airway irritation secondary to mass effect, inflammatory response to cancer, mucin production, or obstruction-causing pneumonia. Smokers frequently have a chronic cough, but changes in the character (sputum production, frequency) of the cough should prompt further evaluation. There are no particular characteristics that distinguish benign from malignant causes of cough. However, cough with associated symptoms (weight loss, anorexia, or hemoptysis) or laboratory abnormalities (spirometric or thrombocytosis) increases the likelihood of a cancer diagnosis.12
Hemoptysis
Hemoptysis is generally an alarming symptom that leads to rapid presentation to the medical system. Inflammatory diseases still account for most cases of hemoptysis, although the rising incidence of lung cancer makes it increasingly common as a cause of hemoptysis. Some 13% to 40% of patients presenting with hemoptysis have lung cancer.15,54 Hemoptysis may also be the earliest symptom of occult cancer, and a thorough evaluation should be undertaken to establish a cause. In a multivariate analysis of symptoms present 180 days or more prior to the diagnosis of lung cancer, hemoptysis was the symptom most likely to
be associated with cancer.8 Of 722 patients presenting to a pulmonologist for evaluation of hemoptysis who had no bleeding source found during the initial evaluation, 6% ultimately were diagnosed with lung cancer.9 Bronchoscopy and chest radiography should be used routinely to evaluate hemoptysis. A CT scan of the chest should follow a negative bronchoscopic examination and chest radiograph. If initial studies fail to determine a cause of hemoptysis, interval CT scans should be obtained.
be associated with cancer.8 Of 722 patients presenting to a pulmonologist for evaluation of hemoptysis who had no bleeding source found during the initial evaluation, 6% ultimately were diagnosed with lung cancer.9 Bronchoscopy and chest radiography should be used routinely to evaluate hemoptysis. A CT scan of the chest should follow a negative bronchoscopic examination and chest radiograph. If initial studies fail to determine a cause of hemoptysis, interval CT scans should be obtained.
Table 107-1 Common Symptoms of Lung Cancer Presentation | ||||||||||||||||||||||||
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Hemoptysis from lung cancer is generally small to moderate in volume (<500 mL/24 hours).17,39 Possible sources of hemoptysis include systemic supply from the bronchial arteries or collaterals and pulmonary supply from the pulmonary artery or veins. Severe systemic arterial bleeding may be controlled by embolization. Carcinoma-induced hemoptysis frequently has a multisource blood supply, and this, as compared with other causes of hemoptysis, has reduced the success of embolization.10,14,39,49 Survival after embolization for lung cancer–induced hemoptysis is less than 4 months.14 Erosion of tumor into pulmonary arteries or systemic vessels is often massive and fatal. Tumor erosion into the heart itself has been reported as a cause of fatal hemoptysis.30 Despite these reports, lung cancer is rarely a cause of massive hemoptysis.
Wheezing or Stridor
Lung cancer can cause airway obstruction and turbulent airflow, resulting in the harshness of stridor or musical wheezing. Both intrinsic obstruction by tumor mass and extrinsic airway compression by tumor or adenopathy may cause obstruction. Stridor generally indicates tracheal obstruction and occurs when >50% of the lumen is obstructed. Occasionally central mainstem bronchial tumors may create stridor. Wheezing caused by lung cancer (in contrast to polyphonic diffuse asthmatic wheezing) is often monophonic and localized around the area of obstruction. Both stridor and wheezing from tumors involving the trachea are occasionally diagnosed as adult-onset asthma. Stridor is an inspiratory noise and should not be mistaken for the expiratory wheezing of asthma. Neither stridor nor wheezing caused by cancer responds well to bronchodilators. Chest radiographs are often unrevealing, but CT scanning will usually show intraluminal mass or extrinsic compression by tumor or adenopathy. Bronchoscopy is usually diagnostic when symptomatic airway involvement is present.
Table 107-2 Paraneoplastic Syndromes in Lung Cancer Patients | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dyspnea
Lung cancer may cause dyspnea by multiple different mechanisms. Airway obstruction can cause atelectasis distal to the obstruction. The amount of lung parenchyma involved may vary from only a subsegmental area of lung parenchyma to an entire lung, depending on the site and degree of airway obstruction. Similarly, obstruction or compression of the pulmonary artery or branches may result in areas of defunctionalized lung secondary to hypoperfusion. Ventilation/perfusion mismatch in either case may cause dyspnea. Postobstructive pneumonia can similarly result in dyspnea. Additionally, tumor infiltration of lung parenchyma or increased lung water from inhibition of lymphatic drainage can result in increased alveolar thickness, less efficient gas diffusion, and relative shunting. Pleural effusions frequently cause dyspnea. Symptomatic effusions from lung cancer most commonly contain malignant cells. Less common causes of dyspnea are phrenic nerve paralysis and pericardial effusion.
Postobstructive Infectious Symptoms
Tumors that obstruct airways inhibit airway drainage, allowing colonization and overgrowth of bacteria. The resulting postobstructive pneumonia can cause fever and leukocytosis, malaise, and weight loss. Chest imaging may be unable to reliably distinguish tumor mass from a pneumonic process. Therefore patients treated with antibiotics should have a follow-up radiography to confirm complete resolution of infiltrates. Recurrent pneumonia in the same location should prompt CT scanning and bronchoscopy to exclude intraluminal tumor or an anatomic basis for recurrence.
Nonbronchopulmonary Symptoms
Pain
Chest wall pain may bring patients to medical attention. Pleural-based pain may be due to direct irritation of the parietal pleura by either inflammation from postobstructive pneumonia or direct invasion by tumor. Tumor invasion or metastasis to ribs may create bone pain. Additionally, sensory nerve invasion (intercostal or brachial plexus) can lead to neuropathic pain. Chest wall pain in the region of known tumor should raise the suspicion of chest wall invasion. Preoperative evaluation should include imaging of the region to define depth of invasion and involved structures. When complex neurovascular structures are involved (such as the apex of the chest or spine), magnetic resonance imaging (MRI) provides better anatomic definition than CT scanning. Operations on patients who have chest wall pain should include a strategy for en bloc chest wall resection. Diffuse facial pain from lung cancer may be caused by invasion of the ipsilateral vagus nerve and relieved by treatment of the primary tumor.1
Pancoast Syndrome
Superior sulcus tumors may invade the brachial plexus and stellate ganglion, presenting with a constellation of signs and symptoms known as Pancoast’s syndrome. These include ipsilateral Horner’s syndrome (facial anhydrosis, miosis, and ptosis) as well as neuritic pain and muscular atrophy in the arm and hand. Horner’s syndrome is caused by direct tumor invasion of the stellate ganglion. Tumor invasion of the lower brachial plexus cords (C7, C8, T1) leads to inner arm pain and wasting of intrinsic muscles of the hand. Vertebral body or rib destruction results in bone pain. Direct invasion of intercostal nerves can also cause chest wall and inner arm (via intercostobrachial branch) pain. Although locally invasive, Pancoast tumors are frequently amenable to treatment with multimodality therapy, including surgical resection.
Dysphagia
Dysphagia occurs rarely as a presenting complaint of lung cancer. When it does occur, it is usually due to esophageal compression, invasion from subcarinal nodal disease, or tension hydrothorax. Rarely, direct extension of tumor or involvement of paraesophageal nodes causes obstruction.
Other Local, Potentially Symptomatic Consequences of Lung Cancer Growth
Pleural Effusion
Patients with dyspnea from lung cancer frequently have a malignant pleural effusion. The typically one-sided effusions result from an imbalance of pleural fluid production and resorption. Cancer patients may develop effusions from any of the following:
Increased capillary permeability or hemorrhage from tumor implants
Decreased oncotic pressure from hypoproteinemia
Decreased absorption secondary to lymphatic obstruction by tumor
Pleural effusions associated with lung cancer can be reactive, especially in the setting of postobstructive atelectasis or pneumonia.
Thoracentesis and fluid cytology is indicated to establish the presence or absence of malignant cells prior to resection and in any cases where such staging would change the therapeutic plan. Occasionally, an effusion will be discovered incidentally as a radiographic abnormality and prompt additional evaluation that ultimately leads to the diagnosis of lung cancer. In a report of 860 pleural effusion specimens from patients without known lung cancer, cytology demonstrated lung cancer in 2%.31 All died within 19 months of diagnosis, attesting to the poor survival of patients presenting with malignant effusions. Mesothelioma frequently presents with malignant pleural effusion. Directed pleural biopsy, usually thoracoscopic, is encouraged to evaluate recurrent pleural effusions with nondiagnostic cytology.
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