Small Cell Lung Cancer Clinical Presentation
- Author: Winston W Tan, MD; Chief Editor: Jules E Harris, MD more...
History
Patients with small cell lung cancer (SCLC) present with symptoms such as shortness of breath, chronic cough with rapid worsening of symptoms, bone pain, weight loss, fatigue, and even seizure if the patients has brain metastasis. Less than 5% of patients have a small, asymptomatic primary tumor at presentation. This disease typically presents with a relatively short duration of symptoms, usually within 8-12 weeks before presentation. The symptoms can result from local tumor growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes. Constitutional symptoms include fatigue, anorexia, and weight loss.
Local tumor growth
Small cell (oat cell) carcinomas are usually centrally located and may cause irritation, obstruction, or both 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 and sometimes as a cavitary lesion.
Patients give a short history of symptoms of recent onset, with rapid worsening. Rapid tumor growth may lead to obstruction of major airways, with distal collapse and consequent postobstructive pneumonitis. Fever may result from infections distal to the obstruction or from the tumor itself.
Intrathoracic spread
Small cell (oat cell) carcinomas rapidly grow in size and metastasize to the mediastinal lymph nodes relatively early in the course of the disease. At presentation, patients may have a very large intrathoracic tumor, and distinguishing a primary tumor from lymph node metastasis may be impossible. Pressure on mediastinal structures can cause various symptoms.
Symptoms due to intrathoracic spread include the following:
- Hoarseness (ie, palsy of the recurrent laryngeal nerve)
- Phrenic nerve palsy
- Dysphagia (ie, compression of esophagus)
- Stridor (ie, compression of the trachea mainstem bronchus)
Small cell lung cancer causes SVC obstruction more often than non-small-cell lung cancer (NSCLC) does. Patients present with swelling of the face and upper extremities. Headache, dizziness, and other neurologic symptoms are late occurrences.
Patients report hoarseness of recent onset. The recurrent laryngeal nerve may be compressed by a mediastinal mass (ie, primary tumor or lymph node metastasis) as it traverses up on the left to supply the vocal cords, causing paralysis of this nerve.
Compression of the phrenic nerve causes paralysis of the ipsilateral hemidiaphragm, contributing to respiratory symptoms. 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.
Symptoms from distant spread
Common sites of spread include brain, bones, liver, adrenals, and bone marrow. The symptoms depend upon the site of spread.
Neurologic dysfunction can occur with brain metastasis and spinal cord compression. Patients with symptomatic brain metastases may have raised intracranial pressure secondary to mass lesions, as well as surrounding brain edema. These individuals may experience headache (usually worse early in the morning), blurring of vision, photophobia, nausea, vomiting, and various localizing symptoms, such as extremity weakness.
The importance of early recognition of vertebral and paraspinal metastases is important because, if not detected early, these could potentially lead to permanent loss of neurologic function. This is an oncologic emergency. The initial symptom is usually back pain, with or without neurologic dysfunction.
The main objective is to establish the diagnosis early, before neurologic dysfunction is established. Once present, neurologic dysfunction can progress very rapidly (ie, within hours) to cause quadriplegia or paraplegia, depending upon the location.
Other symptoms from distant metastasis may include bone pain from bone metastasis, and abdominal/right upper quadrant pain may occur as a result of liver metastasis.
Paraneoplastic syndromes
Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to a neoplasm. Table 2 below shows some examples of the paraneoplastic syndromes affecting the endocrine and neurologic systems.
See the topic Paraneoplastic Diseases for more information.
Table 2. Paraneoplastic Syndromes (Open Table in a new window)
| Organ System | Syndrome | Mechanism | Frequency |
| Endocrine | SIADH | Antidiuretic hormone | 5-10% |
| Ectopic secretion of ACTH | Adrenocorticotropic hormone | 5% | |
| Atrial natriuretic factor | |||
| Neurologic | Eaton-Lambert reverse myasthenic syndrome | 5-6% | |
| Subacute cerebellar degeneration | |||
| Subacute sensory neuropathy | |||
| Limbic encephalopathy | Anti-Hu, Anti-Yo antibodies | ||
| ACTH = adrenocorticotropic hormone; SIADH = syndrome of inappropriate antidiuretic hormone. | |||
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 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; paradoxically, it rises with inspiration.
Pulsus paradoxus is a classic sign of pericardial tamponade. This should be recognized clinically based on examination findings. An echocardiogram should be performed. The definitive diagnosis is established with cardiac catheterization, which reveals equalization of pressures in cardiac chambers. Tamponade is an emergency and requires immediate decompression of the pericardium. 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 SVC obstruction, the right upper extremity is usually edematous.
Central nervous system
Patients with small cell lung cancer may have asymptomatic brain metastasis in 5-10% of cases, which may be picked up on staging workup (see Workup).
Patients with symptomatic brain metastases may have raised intracranial pressure secondary to mass lesions, as well as surrounding brain edema. The physical findings are dependent upon the site of the brain lesions. Perform funduscopy to look for signs of raised intracranial pressure, and perform a detailed neurologic examination, including evaluation of cerebellar function, coordination, and gait.
Gastrointestinal system
The liver is the common site of spread in the gastrointestinal (GI) system, and physical examination may reveal icterus (secondary to widespread liver metastasis or obstruction of biliary outflow) or hepatomegaly. However, most patients do not have any specific finding related to the GI tract on examination.
Lymphatic system
Lymph node examination should be carried out carefully. Currently, enlarged ipsilateral supraclavicular lymph nodes are included in limited stage, but enlarged axillary lymph nodes upstage the diagnosis to extensive-stage disease.
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| Newly Diagnosed Cases of Diagnosed Lung Cancer | Lung Cancer Deaths | |
| 2008 Estimates | ||
| Total (% of all cancers) | 215,020 (15%) | 161,840 (29%) |
| Men | 114, 690 | 90,810 |
| Women | 100,330 | 71,030 |
| 2009 Estimates | ||
| Total (% of all cancers) | 219,440 (15%) | 159,390 (28%) |
| Men | 116,090 | 88,900 |
| Women | 103,350 | 70,490 |
| 2010 Estimates | ||
| Total (% of all cancers) | 222,520 (15%) | 157,300 (28%) |
| Men | 116,750 | 86,220 |
| Women | 105,770 | 71,080 |
| Sources: American Cancer Society. Cancer facts & figures 2008,[15] 2009,[19] 2010.[20] | ||
| Organ System | Syndrome | Mechanism | Frequency |
| Endocrine | SIADH | Antidiuretic hormone | 5-10% |
| Ectopic secretion of ACTH | Adrenocorticotropic hormone | 5% | |
| Atrial natriuretic factor | |||
| Neurologic | Eaton-Lambert reverse myasthenic syndrome | 5-6% | |
| Subacute cerebellar degeneration | |||
| Subacute sensory neuropathy | |||
| Limbic encephalopathy | Anti-Hu, Anti-Yo antibodies | ||
| ACTH = adrenocorticotropic hormone; SIADH = syndrome of inappropriate antidiuretic hormone. | |||
| Regimen | Dose |
| “CAV” Regimen | |
| Cyclophosphamide | 1000 mg/m2 IV day 1 |
| Doxorubicin (Adriamycin) | 50 mg/m2 IV day 1 |
| Vincristine | 2 mg IV |
| “PE” Regimen | |
| Cisplatin | 25 mg/m2 IV days 1-3 |
| Etoposide | 100 mg/m2 IV days 1-3 |
| “CAVE” Regimen | |
| Cyclophosphamide | 1000 mg/m2 IV day 1 |
| Doxorubicin (Adriamycin) | 50 mg/m2 IV day 1 |
| Vincristine | 1.4 mg/m2 IV day 1 (maximum 2 mg) |
| Etoposide | 100 mg/m2 IV day 1 |
| “PEC” Regimen | |
| Paclitaxel | 200 mg/m2 IV day 1 |
| Etoposide | 50 mg/d PO alternating with 100 mg/d PO from days 1-10 |
| Carboplatin | AUC 6 IV day 1 |
| Single-Agent Regimens | |
| Topotecan | 1.5 mg/m2 IV day 1-5 |
| Etoposide | 50 mg PO bid days 1-14 |
| AUC = area under the concentration curve; bid = twice daily; IV = administered intravenously; PO = administered orally. | |
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