Symptoms and signs of lung cancer are divided into those caused by local tumor growth and invasion, by metastatic spread, or by paraneoplastic syndromes. The symptoms and signs associated with growth and invasion vary with tumor location (Table 32.2).
Table 32.2Frequency ranges of initial symptoms and signs of lung cancer ||Download (.pdf) Table 32.2 Frequency ranges of initial symptoms and signs of lung cancer
|Symptom ||Frequency Range |
|Weight loss ||0%-68% |
|Dyspnea ||3%-60% |
|Chest pain ||20%-49% |
|Hemoptysis ||6%-35% |
|Bone pain ||6%-25% |
|Clubbing ||0%-20% |
|Fever ||0%-20% |
|Weakness ||0%-10% |
|Superior vena cava obstruction ||0%-4% |
|Dysphagia ||0%-2% |
|Wheezing and stridor ||0%-2% |
Tumors arising in a central location, that is, in and around large airways, are the most likely to cause cough and hemoptysis. Large airway involvement may also produce wheezing. Peripheral tumors that involve the pleura or chest wall may cause chest pain, as can central tumors that obstruct airways and subsequently collapse of a portion of the lung or the entire lung. Shortness of breath and dyspnea on exertion may result from large airway obstruction or from compromise of the pulmonary circulation by central tumors. Associated pleural or pericardial effusions can also cause dyspnea. Hoarseness can occur due to disruption of the recurrent laryngeal nerve, most commonly on the left. Horner syndrome is a clinical triad of ptosis, miosis, and anhidrosis that results from damage to sympathetic neurons transversing the lung apex, and is associated with superior sulcus tumors also known as Pancoast tumors (Fig. 32.10).
Superior sulcus tumors also can affect the brachial plexus, causing pain and weakness in the more distal upper extremity as well as shoulder pain. An elevated hemidiaphragm with paradoxical motion on inspiration suggests disruption of the ipsilateral phrenic nerve by a central tumor (Fig. 32.11). Finally, central tumors can compromise superior vena caval blood flow. Patients with superior vena cava syndrome report a sensation of fullness in the head and dyspnea. Physical exam may reveal edema of the head and neck with plethora and prominent superficial veins over the chest.
Elevated right hemidiaphragm as a result of disruption of the right phrenic nerve by a non-small cell lung cancer. Contributed by Dr. Hani Alasalam. From www.radiopaedia.org.
Nearly half of patients with lung cancer have metastatic disease at the time of initial diagnosis, and many more develop metastatic disease at a later time. Metastatic involvement of other organs can give rise to a wide range of symptoms and signs. The organs most commonly showing metastases are liver, adrenal glands, bones, and brain. Liver involvement is typically asymptomatic and discovered only upon imaging of the liver. More extensive involvement of the liver causes abdominal pain, jaundice, and elevated serum [transaminases]. Likewise, adrenal metastases are often asymptomatic and found upon imaging of the upper abdomen during the staging process. A small percentage of patients with adrenal metastases may develop adrenal insufficiency that is manifest as weakness, nausea, orthostatic hypotension, hyponatremia, and hyperkalemia. In contrast, bony metastases are usually symptomatic and associated with osteolytic lesions evident on radiographs; pathologic fractures may occur. Headaches, seizures, vomiting, cranial nerve deficits, and visual field loss in a patient with lung cancer should raise suspicion for brain metastasis. More subtle findings include personality changes, mood disturbance, cognitive difficulty, and memory loss.
Finally, symptoms and signs of lung cancer may be a result of paraneoplastic phenomena, that is, disorders mediated by secretory products of tumor cells or by anti-tumor antibodies that cross-react with other tissues (Table 32.3). Paraneoplastic syndromes occur in up to 20% of patients with lung cancer, with hypercalcemia leading to constipation, dehydration, lethargy, and confusion being common. Unlike most paraneoplastic syndromes that are associated with small cell lung cancers, hypercalcemia is most common among patients with squamous cell lung cancer.
Table 32.3Paraneoplastic syndromes associated with lung cancer ||Download (.pdf) Table 32.3 Paraneoplastic syndromes associated with lung cancer
|Skeletal and Systemic ||Hematologic |
|Hypertrophic osteoarthropathy ||Anorexia, cachexia ||Anemia |
|Clubbing ||Fever, malaise ||Leukocytosis |
|Renal, nephrotic syndromes ||Collagen-vascular syndromes ||Leukemoid reactions |
|Glomerulonephritis ||Dermatomyositis ||Thrombocytosis, TTP |
|Hypouricemia ||Polymyositis ||Coagulopathies, DIC |
|Metabolic syndromes ||Vasculitis ||Thrombophlebitis |
|Lactic acidosis ||Systemic lupus erythematosus ||Eosinophilia |
|Cutaneous || Endocrine ||Neurologic |
|Acquired hypertrichosis lanuginosa || SIADH production ||Sensory neuropathy |
|Erythema gyratum repens || Nonmetastatic hypercalcemia ||Mononeuritis multiplex |
|Erythema multiforme || Cushing syndrome ||Intestinal pseudo-obstruction |
|Tylosis || Gynecomastia ||Lambert-Eaton myasthenia |
|Erythroderma || Hypercalcitonemia ||Encephalomyelitis |
|Exfoliative dermatitis || Elevated [LSH], [FSH] ||Necrotizing myelopathy |
|Acanthosis nigricans || Hypoglycemia ||Cancer-associated retinopathy |
|Sweet syndrome || Hyperthyroidism || |
|Pruritus and urticaria || Carcinoid syndrome || |
The syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) is another common paraneoplastic entity. SIADH results in hyponatremia which may lead to confusion, seizures, and coma. Cushing syndrome due to tumor cell production of ACTH can lead to hypertension, hypokalemia, and hyperglycemia. Clubbing and hypertrophic pulmonary osteoarthropathy are paraneoplastic syndromes with skeletal manifestations (Fig. 32.12). Hypertrophic osteoarthropathy is characterized by painful proliferative periostitis most commonly involving the wrists, elbows, ankles, or knees. Neurologic paraneoplastic syndromes include Lambert-Eaton myasthenic syndrome (LEMS) characterized by limb weakness, autonomic dysfunction, and cranial nerve deficits. This syndrome displays a characteristic improvement in muscular response to repetitive nerve stimulation during neurophysiologic testing. A hypercoagulable state, thrombocytosis, cachexia, and malaise are all common paraneoplastic syndromes. Treatment of the underlying lung cancer is paramount in the treatment of the paraneoplastic syndromes, as many of these will improve if not completely resolved with effective treatment of the malignancy.
Representative example of clubbing of the fingers. Image courtesy of the University of Leeds. From www.sciencedaily.com