Small Cell Lung Cancer Clinical Presentation

Updated: Oct 09, 2017
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Presentation

History

Fewer than 5% of patients with small cell lung cancer (SCLC) are asymptomatic at presentation. Common presenting signs and symptoms of the disease, which very often occur in advanced-stage disease, include the following:

  • Shortness of breath
  • Cough
  • Bone pain
  • Weight loss
  • Fatigue
  • Neurologic dysfunction

Most patients with this disease present with a short duration of symptoms, usually only 8-12 weeks before presentation. The clinical manifestations of SCLC can result from local tumor growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.

Local tumor growth

SCLCs are usually centrally located and may cause irritation and/or obstruction of the major airways. Common symptoms resulting from local tumor growth include cough, dyspnea, and hemoptysis. Squamous cell cancer also presents as a central lesion, but unlike SCLC, it frequently exhibits central cavitation.

Rapid tumor growth may lead to obstruction of major airways, with distal collapse leading to postobstructive pneumonitis, infection, and fever.

Intrathoracic spread

SCLCs usually grow rapidly and metastasize to mediastinal lymph nodes relatively early in the course of the disease. At presentation, patients may have very large intrathoracic tumors, and distinguishing the primary tumor from lymph node metastases may be impossible.

Pressure on mediastinal structures can cause various symptoms, including the following:

SCLC causes SVC obstruction more often than non-SCLC (NSCLC). Patients present with swelling of the face and upper extremities, and can develop stridor due to laryngeal edema or headache, dizziness, and other neurologic symptoms due to cerebral edema. Hoarseness of recent onset can be caused by compression of the left recurrent laryngeal nerve by a mediastinal mass involving the aortopulmonary window (ie, primary tumor or lymph node metastasis).

Compression of the phrenic nerve causes paralysis of the ipsilateral hemidiaphragm, contributing to shortness of breath. In addition, esophageal compression can lead to dysphagia and odynophagia, and compression of the mainstem bronchi and trachea can cause severe shortness of breath and stridor or wheezing.

Symptoms from distant spread

Common sites of hematogenous metastases include the brain, bones, liver, adrenal glands, and bone marrow. The symptoms depend upon the site of spread.

Neurologic dysfunction can occur due to brain metastases or spinal cord compression. Patients with symptomatic brain metastases may have raised intracranial pressure secondary to mass lesions and vasogenic edema. Common symptoms include the following:

  • Headache - Usually worse in the morning
  • Blurred vision
  • Photophobia
  • Nausea
  • Vomiting
  • Slurred speech
  • Confusion
  • Localizing symptoms - Such as extremity weakness

Suspected spinal cord compression is an oncologic emergency. Early recognition of vertebral and paraspinal metastases is important, because a delay in diagnosis and treatment frequently results in permanent loss of neurologic function. The initial symptom is usually back pain, with or without neurologic dysfunction. Once present, neurologic dysfunction can progress very rapidly (ie, within hours) to cause quadriplegia or paraplegia, depending upon the location of the lesion.

Other symptoms from distant metastasis may include pain from bone metastasis, as well as jaundice or abdominal/right upper quadrant pain due to liver metastasis.

Paraneoplastic syndromes

Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to a neoplasm or ectopic production of a hormone or cytokine. Table 1, below, shows some examples of the paraneoplastic syndromes affecting the endocrine and neurologic systems in patients with SCLC.

See  Paraneoplastic Diseases for more information.

Table 1. Paraneoplastic Syndromes Affecting Endocrine and Neurologic Function in SCLC (Open Table in a new window)

Organ System Syndrome Mechanism Frequency
Endocrine SIADH Antidiuretic hormone 15% [20]
Ectopic secretion of ACTH ACTH 2-5% [21]
     
Neurologic Eaton-Lambert reverse myasthenic syndrome   3% [22]
Subacute cerebellar degeneration    
Subacute sensory neuropathy    
Limbic encephalopathy Anti-Hu, anti-Yo antibodies  
ACTH = adrenocorticotropic hormone; SCLC = small cell lung cancer; SIADH = syndrome of inappropriate antidiuretic hormone.



Sources:  (1) Campling BG, Sarda IR, Baer KA, et al. Secretion of atrial natriuretic peptide and vasopressin by small cell lung cancer. Cancer. May 15, 1995;75(10):2442-51 [20] ; (2) Shepherd FA, Laskey J, Evans WK, et al. Cushing's syndrome associated with ectopic corticotropin production and small-cell lung cancer. J Clin Oncol. Jan 1992;10(1):21-7 [21] ; (3) Sher E, Gotti C, Canal N, et al. Specificity of calcium channel autoantibodies in Lambert-Eaton myasthenic syndrome. Lancet. Sep 16, 1989;2(8664):640-3. [22]



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Physical Examination

Physical findings in small cell lung cancer (SCLC) depend upon the extent of local and distant spread and the organ system involved.

Respiratory system

Patients usually experience shortness of breath; physical examination may reveal use of the accessory muscles of respiration (scalene muscles, intercostal muscles) and flaring of the nasal alae. In addition, by virtue of a central tumor location, patients may develop distal atelectasis and postobstructive pneumonia. With pleural effusion, the examination reveals dullness to percussion and decreased or absent breath sounds on the side of the effusion.

Cardiovascular system

Pericardial effusions may be asymptomatic when small, or they may result in tamponade if they are large or accumulate over a short period. Patients are usually short of breath and their heart sounds may be distant on auscultation. Jugular venous pulsation is elevated, and, paradoxically, it rises with inspiration.

Tamponade is an emergency and requires immediate decompression of the pericardium. Pulsus paradoxus is a classic sign of pericardial tamponade. If tamponade is suspected, an echocardiogram should be performed. The definitive diagnosis is established with cardiac catheterization, which reveals equalization of pressures in cardiac chambers. Definitive management may include chemotherapy and/or surgical creation of a pleuropericardial window.

Examination of the extremities may reveal clubbing, cyanosis, or edema. In the presence of superior vena cava (SVC) obstruction, the right upper extremity is usually edematous.

Central nervous system

Asymptomatic brain metastases occur in 5-10% of patients with SCLC (see Workup). Patients with symptomatic brain metastases may have raised intracranial pressure secondary to mass lesions and surrounding brain edema. The physical findings depend on the site of the brain lesions.

Perform funduscopy to look for signs of raised intracranial pressure, as well as a thorough neurologic examination and an evaluation of cerebellar function, coordination, and gait.

Gastrointestinal system

The liver is a common site of metastatic spread. Physical examination may reveal icterus (secondary to widespread liver metastasis or obstruction of biliary outflow) and/or hepatomegaly. However, most patients do not have any specific finding related to the gastrointestinal (GI) tract on examination. Very often patients are asymptomatic but may have mild elevation of liver enzyme levels.

Lymphatic system

Carefully perform a lymph node examination. Currently, enlarged ipsilateral supraclavicular lymph nodes are included in limited-stage disease, but enlarged axillary lymph nodes upstage the diagnosis to extensive-stage disease.

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Complications

Multiple complications may be noted, depending on the site of metastasis or the metabolic factor that the tumor affects. Hypercalcemia could initially be asymptomatic but in late stages could lead to weakness, fatigue, and sleepiness, and in extreme cases to severe constipation and lethargy.

Brain metastasis is often asymptomatic but could manifest as a unilateral eye abnormality, focal neurologic deficit, or at times with a new-onset headache that wakes the patient up. Seizures are a possible manifestation.

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