Non-Small Cell Lung Cancer Clinical Presentation

  • Author: Winston W Tan, MD; Chief Editor: Jules E Harris, MD   more...
 
Updated: Apr 12, 2012
 

History

Lung cancer is often insidious, and it may produce no symptoms until the disease is well advanced. Approximately 7-10% of patients with lung cancer are asymptomatic, and their cancers are diagnosed incidentally after a chest radiograph performed for other reasons.

Early recognition of symptoms may be beneficial to outcome. The symptoms manifested by lung cancers may be due to the primary tumor, locoregional spread, metastatic disease, or ectopic hormone production (see the image below).

Non–small cell lung cancer. Symptoms and signs of Non–small cell lung cancer. Symptoms and signs of lung cancer.

Symptoms due to primary tumor

The symptoms produced by the primary tumor depend on its location (ie, central, peripheral). Central tumors are generally squamous cell carcinomas (SCCs) and produce symptoms of cough, dyspnea, atelectasis, postobstructive pneumonia, wheezing, and hemoptysis.

Most peripheral tumors are adenocarcinomas or large cell carcinomas and, in addition to causing cough and dyspnea, can cause symptoms due to pleural effusion and severe pain as a result of infiltration of parietal pleura and the chest wall. Because of their peripheral location, adenocarcinomas may not call attention to themselves until they have developed extrathoracic metastases. For example, patients may present with clinical signs of bone spread or intracranial metastatic disease.

Symptoms due to locoregional spread

Symptoms due to locoregional spread can include superior vena cava obstruction, paralysis of the recurrent laryngeal nerve, and phrenic nerve palsy, causing hoarseness and paralysis of the diaphragm; pressure on the sympathetic plexus, causing Horner syndrome; dysphagia resulting from esophageal compression; and pericardial effusion.

Superior sulcus tumors (Pancoast tumors) can cause compression of the brachial plexus roots as they exit the neural foramina, resulting in intense, radiating neuropathic pain in the ipsilateral upper extremity.

Symptoms by location of cancer

Cough is reported to be the most common presenting symptom of lung cancer. Other respiratory symptoms include dyspnea, chest pain, and hemoptysis. Hemoptysis has been described as the one symptom often prompting more rapid presentation.[24] At initial diagnosis, 20% of patients have localized disease, 25% of patients have regional metastasis, and 55% of patients have distant spread of disease. Symptoms depend on the location of cancer.[25]

Endobronchial symptoms include the following:

  • Cough (45-75%)
  • Hemoptysis (57%)
  • Bronchial obstruction
  • Post obstructive complications (eg, pneumonitis, pneumonia, effusion)

Mediastinal symptoms include the following:

  • Dyspnea
  • Postprandial coughing (esophageal)
  • Wheezing
  • Stridor (upper airway obstruction, 2-18%)
  • Hoarseness (left vocal cord paralysis due to recurrent laryngeal nerve impingement, 2-18%)
  • Chylothorax (thoracic duct)
  • Palpitations (pericardial)
  • Dysphagia (enlargement of the subcarinal lymph nodes can cause dysphagia by compressing the middle third of the esophagus)

Pleural symptoms include the following:

  • Chest pain (27-49%)
  • Dyspnea (37-58%)
  • Cough (45-75%)

Neurologic symptoms include the following:

  • Arm weakness and paresthesias (brachial plexus impingement)
  • Miosis ptosis and anhidrosis (cervical sympathetic chain, Horner syndrome)
  • Dyspnea (secondary to phrenic nerve paralysis)

Metastatic (8-68%) symptoms include the following:

  • Weight loss
  • Cachexia

Central nervous system (CNS) symptoms include the following:

  • Headache
  • Altered mental status
  • Seizure
  • Meningismus
  • Ataxia
  • Nausea and/or vomiting

Vascular symptoms include the following:

  • Phlebitis
  • Thromboembolism (Trousseau syndrome)

Musculoskeletal symptoms include the following:

  • Bone pain (6-25%)
  • Spinal cord impingement

In addition, the patient’s history may clue the physician in on a specific paraneoplastic syndrome (10-20% of patients). Most paraneoplastic syndromes are caused by small cell lung cancer (SCLC). However many paraneoplastic syndromes also occur in non-small cell lung cancer (NSCLC) patients. Some examples include:

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Physical Examination

Systemic findings may include unexplained weight loss and low-grade fever. Extrapulmonary findings may include adenopathy and clubbing. Numerous signs may be associated with NSCLC (see the image below).

Non–small cell lung cancer. Symptoms and signs of Non–small cell lung cancer. Symptoms and signs of lung cancer.

In approximately two thirds to three fourths of patients, the cancer is not diagnosed until it has reached an advanced stage; patients may have lost weight and may have obvious respiratory distress. Subtle findings on physical examination may provide clues for early detection.

About one third of patients present with symptoms as a result of distant metastases. The most common sites of distant metastasis from lung cancer are the bones; liver; adrenal glands and intra-abdominal lymph nodes; brain and spinal cord; and lymph nodes and skin. Lung cancer can metastasize to virtually any bone, although the axial skeleton and proximal long bones are most commonly involved.

Head and neck

Commonly, no signs are found upon examination of the head and neck regions, but when the cancer has spread to the supraclavicular lymph nodes, careful examination may reveal enlargement of involved nodes, which helps in the clinical staging process.

Superior sulcus tumors (Pancoast tumors), because of their presence at the apex of the lung, can compress the cervical sympathetic plexus, causing classic Horner syndrome. Findings involve ipsilateral ptosis, miosis, enophthalmos, and anhidrosis (ie, lack of sweating).

The superior vena cava syndrome (SVCS) results from obstruction of blood flow to the heart from the head and neck regions and upper extremities as a consequence of compression of the superior vena cava, either from direct invasion by the primary tumor into the mediastinum or from lymphatic spread with enlarged right paratracheal metastatic lymph nodes. It is commonly caused by SCLC but can result from any centrally located tumor or mediastinal spread.

Signs of SVCS include the following:

  • Feeling of fullness in the head
  • Dyspnea
  • Cough
  • Dilated neck veins
  • Prominent venous pattern on the face and the chest
  • Upper extremity and facial edema
  • Papilledema
  • Facial cyanosis
  • Plethora
  • Conjunctival edema (possibly)

Respiratory system

Findings are variable and depend on location and spread. Centrally located obstructing tumors can cause collapse of the entire lung with an absence of breath sounds on the side of the lesion. Peripheral lesions can cause individual segments or lobes to collapse, leading to findings of dullness to percussion and/or decreased breath sounds.

Pleural effusions give rise to characteristic findings of dullness and decreased breath sounds, depending on the size.

Respiratory insufficiency is signaled by dyspnea and increased work of breathing, retractions, orthopnea, and cyanosis. Upper airway obstruction is manifested by stridor and wheezing. Lower airway obstruction is manifested by asymmetric breath sounds, pleural effusion, pneumothorax, infiltrate, and post obstructive processes.

Cardiovascular system

Cardiac findings are usually noted when the tumor causes an effusion. Findings can range from simple effusion to tamponade. Direct cardiac involvement may also occur.

Gastrointestinal tract

Ogilvie intestinal pseudo-obstruction may occur, as manifested by the following:

  • Nausea
  • Vomiting
  • Early satiety
  • Abdominal discomfort
  • Weight loss
  • Change in bowel habits

The most common site of metastatic spread is the liver, which may manifest as tender hepatomegaly.

Musculoskeletal system

The examination should include fist percussion of the spine to look for tender spots, which may suggest vertebral column metastases.

Bone is another common site of spread for lung carcinomas. Patients may report bone pain, and tender spots may be found during examination.

A Pancoast tumor may give rise to pain (eg, in the shoulder, medial forearm, arm, scapula), bone destruction, or hand muscle atrophy.

Central nervous system

A neurologic examination should be performed to look for focal neurological deficits caused by brain metastases and/or signs of spinal cord compression. Signs of acute spinal cord compression include the following:

  • Paraplegia
  • Sensory deficits
  • Urinary incontinence or retention
  • Vertebral pain

Paraneoplastic syndromes

Findings indicative of the following paraneoplastic syndromes may be noted[26] :

  • Cushing syndrome
  • Lambert-Eaton myasthenic syndrome - Gradual onset of proximal lower extremity weakness; proximal upper extremity weakness is usually less noticeable. The syndrome may be worse in the morning and improve during the day. Although extraocular muscle involvement is uncommon, ptosis is often found.
  • Hypercalcemia
  • Syndrome of inappropriate antidiuretic hormone secretion
  • Enlargement of the extremities, and painful, swollen joints (hypertrophic osteoarthropathy)

The American College of Chest Physicians (ACCP) updated its comprehensive set of lung cancer guidelines in 2007, including an executive summary of recommendations from all articles in the guideline set.[27]

Among the 2007 ACCP guidelines is a guideline for the initial evaluation of patients with lung cancer. This guideline states that paraneoplastic syndromes are unrelated to the size of the primary tumor. Sometimes paraneoplastic syndromes precede the diagnosis of a malignancy, sometimes they occur late in the disease, and sometimes they are the first signs of a recurrence. The guideline maintains that patients with lung cancer who have a paraneoplastic syndrome should nevertheless be considered for potentially curative therapy.[28]

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Complications

The skeletal system is a common site of spread of lung cancer. When cancer metastasizes to the axial skeleton, it may grow and compress the spinal cord.

Patients usually report back pain and neurological symptoms in the form of decreased sensation in the lower half of the body, decreased strength, loss of bowel control, and loss of bladder control. A careful neurologic examination usually localizes the level of compression.

Suspected spinal cord compression is an emergency. Patients should immediately receive an adequate dose of a corticosteroid (usually intravenous dexamethasone at 10 mg followed by 4 mg q6h) and should undergo an immediate MRI scan of the vertebral column. If documented, spinal cord compression should be treated emergently with radiation therapy, and steroids should be tapered slowly.

A study by Fadel et al found that en block resection can achieve good long-term survival in highly selected patients with NSCLC that invades the thoracic inlet and spine.[29]

The most common metabolic complication associated with NSCLC is hypercalcemia, which is usually associated with squamous cell carcinoma. Other findings can include hyponatremia, and syndrome of inappropriate secretion of antidiuretic hormone should be considered.

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Contributor Information and Disclosures
Author

Winston W Tan, MD  Assistant Professor of Medicine, Mayo Medical School; Consulting Staff, Mayo Group Practices

Winston W Tan, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Philippine Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Gino A Farina, MD, FACEP, FAAEM  Associate Professor of Clinical Emergency Medicine, Albert Einstein College of Medicine; Program Director, Department of Emergency Medicine, Long Island Jewish Medical Center

Gino A Farina, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Syed Huq, MD  Fellow, Division of Hematology-Oncology, Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Ellis Fischel Cancer Center

Syed Huq, MD is a member of the following medical societies: American Medical Informatics Association, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Irfan Maghfoor, MD  Consulting Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia

Irfan Maghfoor, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Michael Perry, MD, MS, MACP  Nellie B Smith Chair of Oncology Emeritus, Director, Division of Hematology and Medical Oncology, Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

Michael Perry, MD, MS, MACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, International Association for the Study of Lung Cancer, and Missouri State Medical Association

Disclosure: Nothing to disclose.

Mityanand Ramnarine, MD  Chief Resident Physician, Department of Emergency Medicine, Albert Einstein College of Medicine at Long Island Jewish Medical Center

Mityanand Ramnarine, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Edmond A Hooker II, MD, DrPH, FAAEM  Assistant Professor, Department of Emergency Medicine, University of Cincinnati College of Medicine; Associate Professor, Department of Health Services Administration, Xavier University

Edmond A Hooker II, MD, DrPH, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American Public Health Association, Society for Academic Emergency Medicine, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jeffrey L Arnold, MD, FACEP  Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP  Professor of Emergency Medicine, Professor of Internal Medicine, Program Director for Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Peter T Porrello, MD, and Tamas Peredy, MD, to the development and writing of a source article.

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Non–small cell lung cancer. Symptoms and signs of lung cancer.
Non–small cell lung cancer. Diagnostic approach for possible lung cancer.
Staging workup for non–small cell lung cancer.
Treatment recommendations and future research directions in the management of non–small cell lung cancer.
Non–small cell lung cancer. Performance status scales for patients with cancer.
Non–small cell lung cancer. Prognostic factors for lung cancer.
Non–small cell lung cancer. Bronchoscopy. A large central lesion was diagnosed as non–small cell carcinoma.
Non–small cell lung cancer. Left pleural effusion and volume loss secondary to non–small cell carcinoma of the left lower lobe. The pleural effusion was sampled and found to be malignant; therefore, the lesion is inoperable.
Non–small cell lung cancer. Left upper collapse is almost always secondary to endobronchial bronchogenic carcinoma.
Non–small cell lung cancer. Complete left lung collapse secondary to bronchogenic carcinoma of left mainstem bronchus.
Non–small cell lung cancer. A cavitating right lower lobe squamous cell carcinoma.
Non–small cell lung cancer. CT scan shows cavitation and air-fluid level.
Non–small cell lung cancer. Patient has right lower lobe opacity. This is not well circumscribed and was found to be a squamous cell carcinoma.
Lung cancer, small cell. Contrast-enhanced CT scan of the chest shows a large left lung and a hilar mass, with invasion of the left pulmonary artery.
Lung cancer, small cell. Coronal positron emission tomogram shows abnormal areas of increased metabolic activity in the left hilar and left adrenal regions consistent with a hilar tumor with left adrenal metastasis.
Lung cancer, small cell. Whole-body nuclear medicine bone scanning with anterior and posterior images reveal multiple abnormal areas of increased radiotracer activity in the pelvis, spine, ribs, and left scapula. These findings are consistent with bony metastatic disease. The bones are commonly affected in patients with small-cell lung cancer.
 
 
 
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