Non-Small Cell Lung Cancer (NSCLC) Clinical Presentation

Updated: Jun 07, 2023
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
  • Print


Lung cancer is often insidious, producing no symptoms until the disease is well advanced. In approximately 7-10% of cases, lung cancer is diagnosed in asymptomatic patients when a chest radiograph performed for other reasons reveals the disease. At initial diagnosis, 20% of patients have localized disease, 25% of patients have regional metastasis, and 55% of patients have distant spread of disease.

Signs and symptoms of lung cancers may be due to the primary tumor, locoregional spread, metastatic disease, or ectopic hormone production (see the image below). 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. [40]

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). [1] Central tumors are generally squamous cell carcinomas (SCCs) and produce 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 produced 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

Endobronchial cancers may produce the following signs:

  • Cough (45-75% of patients)
  • Hemoptysis (57%)
  • Bronchial obstruction
  • Postobstructive complications (eg, pneumonitis, pneumonia, effusion)

Mediastinal cancers may produce the following signs and symptoms:

  • 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 cancers may produce the following signs and symptoms:

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

Neurologic signs and 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 cancer may produce the following signs (8-68%):

  • Weight loss
  • Cachexia

Central nervous system (CNS) signs and symptoms include the following:

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

Vascular signs include the following:

  • Phlebitis
  • Thromboembolism (Trousseau syndrome)

Musculoskeletal manifestations include the following:

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

Paraneoplastic syndromes occur in 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:

  • Hypercalcemia due to parathyroid-like hormone production occurs most commonly in patients with SCCs

  • Clubbing and hypertrophic pulmonary osteoarthropathy and Trousseau syndrome of hypercoagulability are caused more frequently by adenocarcinomas

  • The syndrome of inappropriate antidiuretic hormone production (SIADH) is more common in SCLC but can also occur in NSCLC.

  • Cushing syndrome from ectopic adrenocorticotropic hormone (ACTH) production is more likely to occur in SCLC or bronchial carcinoid [41]


Physical Examination

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

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 as follows:

  • Bone
  • Liver
  • Adrenal glands and intra-abdominal lymph nodes
  • Brain and spinal cord
  • 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. However, 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 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 tumor 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 a pericardial effusion. Findings can range from simple effusion to tamponade. Direct cardiac involvement may also occur.

Gastrointestinal tract

The most common site of metastatic spread is the liver, which may manifest as tender hepatomegaly. In addition, Ogilvie intestinal pseudo-obstruction may occur, as manifested by the following:

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

Musculoskeletal system

Bone is another common site of spread for lung carcinomas. Patients may report bone pain, and tender spots may be found during examination.The examination should include fist percussion of the spine to look for tender spots, which may suggest vertebral column metastases.

A Pancoast tumor may give rise to any of the following:

  • Pain (eg, in the shoulder, medial forearm, arm, scapula)
  • Bone destruction
  • Hand muscle atrophy

Central nervous system

A neurologic examination should be performed to assess for focal neurological deficits caused by brain metastases and for signs of spinal cord compression. The skeletal system is a common site of spread of lung cancer, and metastatic lesions in the spine 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 urinary incontinence or retention. 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, 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 bloc resection can achieve good long-term survival in highly selected patients with NSCLC that invades the thoracic inlet and spine. Factors that independently affected survival were incomplete resection and subclavian artery involvement. [42]

Paraneoplastic syndromes

Paraneoplastic syndromes are more likely to occur in small cell lung cancer than in NSCLC. Nevertheless, findings indicative of the following paraneoplastic syndromes may be noted [43] :

  • 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 (SIADH)

  • Enlargement of the extremities, and painful, swollen joints (hypertrophic osteoarthropathy)

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.