Small cell carcinoma of the lung overview: Difference between revisions
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Without treatment, small cell lung cancer (SCLC) has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2 to 4 months. Compared with other cell types of lung cancer, SCLC has a greater tendency to be widely disseminated by the time of diagnosis but is much more responsive to chemotherapy and radiation therapy. | Without treatment, small cell lung cancer (SCLC) has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2 to 4 months. Compared with other cell types of lung cancer, SCLC has a greater tendency to be widely disseminated by the time of diagnosis but is much more responsive to chemotherapy and radiation therapy. | ||
Because patients with small cell lung cancer tend to develop distant metastases, localized forms of treatment, such as surgical resection or radiation therapy, rarely produce long-term survival. With incorporation of current chemotherapy regimens into the treatment program, however, survival is unequivocally prolonged, with at least a 4- to 5-fold improvement in median survival compared with patients who are given no therapy. Furthermore, about 10% of the total population of patients remains free of disease during 2 years from the start of therapy, the time period during which most relapses occur. Even these patients, however, are at risk of dying from lung cancer (both small- and non-small cell types). The overall survival at 5 years is 5% to 10%. | Because patients with small cell lung cancer tend to develop distant metastases, localized forms of treatment, such as surgical resection or radiation therapy, rarely produce long-term survival. With the incorporation of current chemotherapy regimens into the treatment program, however, survival is unequivocally prolonged, with at least a 4- to 5-fold improvement in median survival compared with patients who are given no therapy. Furthermore, about 10% of the total population of patients remains free of disease during 2 years from the start of therapy, the time period during which most relapses occur. Even these patients, however, are at risk of dying from lung cancer (both small- and non-small cell types). The overall survival at 5 years is 5% to 10%. | ||
==Historical Perspective== | |||
Laennec first recognized lung cancer as a separate disease in 1815, in his work "Encephaloides" published in the Dictionnaire des sciences médicales. Azzopardi, in 1959, distinguished small cell lung cancer (SCLC) from anaplastic adenocarcinoma and squamous cell carcinoma and described the clinical and biological features that characterize it as a separate disease. | |||
==Pathophysiology== | |||
Small cell lung cancer is the most aggressive form of [[lung cancer]] and has the highest association with [[smoking]] of all lung cancers. Small cell lung cancer usually starts in the [[bronchi]] and expands through the [[bronchial]] [[mucosa]]. Small cell lung cancer often [[metastasize]]s rapidly to other parts of the body, including the [[brain]], [[liver]], and [[bone]]. A [[mutation]] in the [[p53]] [[gene]] is reported in 75%-100% of the cases. Other [[molecular]] abnormalities that contribute to the development of small cell lung cancer have been described. | |||
==Causes== | |||
Smoking [[cigarettes]] and other [[tobacco]] related products are the predominant worldwide cause of small cell carcinoma of the lung and it can be associated with other [[Small cell carcinoma of the lung risk factors|risk factors]] in its development. | |||
==Differentiating Small cell carcinoma of the lung from Other Diseases== | |||
Depending on the presentation, [[lung cancer]] should be differentiated from other lung diseases such as [[pulmonary tuberculosis]], lung [[abscess]], and [[respiratory tract]] infection and [[autoimmune]] diseases affecting the [[respiratory tract]]. Once [[lung cancer]] is confirmed, small cell carcinoma should be differentiated from other [[NSCLC|non-small cell carcinoma]] based on histopathological findings. | |||
==Epidemiology and Demographics== | |||
Small cell lung cancer (SCLC) represents 13.4% of all [[Lung cancer|lung cancers]] in the United States. The majority of small cell lung cancer occurs among patients > 65 years of age. The age-adjusted [[Incidence (epidemiology)|incidence]] of small cell lung cancer in the United States is reported to be 6.23 per 100,000 in 2011. | |||
==Risk Factors== | |||
[[Tobacco]] smoking is the leading [[risk factor]] of [[lung cancer]]. Other [[risk factors]] for lung cancer include environmental exposures, [[air pollution]], and certain host-related factors. | |||
==Screening== | |||
The [[United states preventive services task force recommendations scheme|USPSTF]] recommends annual [[Screening (medicine)|screening]] for lung cancer with low-dose [[computed tomography]] (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. [[Screening (medicine)|Screening]] should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. | |||
==Natural History, Complications, and Prognosis== | |||
The [[Natural history of disease|natural history]] of untreated small cell lung cancer (SCLC) is extremely poor, with a median survival of only 2 months for stage IV SCLC and less than 3 to 4 months for [[tumors]] confined to the [[thorax]]. With the current treatment modalities, the median survival of patients with limited stage disease ranges from 16 to 24 months while that of patients with extensive-stage disease ranges from 6 to 12 months. SCLC can be complicated by [[paraneoplastic syndrome]]s. Limited stage disease, absence of [[brain]] [[metastasis]], young age, and female sex are considered good [[prognostic]] factors. | |||
==Diagnosis== | |||
===Staging=== | |||
Staging schemes for small cell lung cancer (SCLC) have been developed by the Veterans Administration Lung Study Group (VALG), the American Joint Committee on Cancer (AJCC), and the National Comprehensive Cancer Network (NCCN). The Veterans Administration Lung Study Group (VALG) staging scheme is the oldest among the three staging schemes. Although the AJCC staging scheme is newer than that of the VALG, clinicians commonly use the VALG staging system because it has been referred to in most clinical trials. The NCNN combines the AJCC (TNM) staging scheme with the VALG staging scheme. | |||
===Diagnostic Study of Choice=== | |||
The confirmation of the diagnosis of SCLC relies on the histopathological findings of the tumor [[biopsy]]. All patients with confirmed diagnosis of SCLC by [[histopathological]] findings should undergo a [[CT scan]] of the [[abdomen]] for staging purposes. [[Computed tomography|CT scan]] of the [[abdomen]] helps identify [[metastasis]] to organs, such as the [[liver]] or the [[adrenal glands]]. | |||
===History and Symptoms=== | |||
Small cell lung cancer (SCLC) is characterized by a relatively rapid onset of symptoms. Patients usually present within 8 to 12 weeks of the onset of symptoms, which can be related either to the tumor growth in the [[thorax]] or to the distant spread of the [[tumor]]. In addition, SCLC is associated with the occurrence of [[paraneoplastic syndrome]]s such as the [[syndrome of inappropriate antidiuresis]] ([[SIADH]]). | |||
===Physical Examination=== | |||
Many authors have concluded that performing a complete assessment, with a detailed history and [[physical examination]], is useful for identifying patients with a higher likelihood of [[metastases]]. Fever is reported in 20% of the patients. Patient may present with [[Weight loss|weight loss,]] [[cachexia]] and [[anorexia]]. Upon [[auscultation]] unilateral decreased air entry, unilateral [[wheeze]], and decreased air entry in the bases of the [[lungs]] and/or [[crackles]] (suggestive of [[pleural effusion]]) may be present. The [[musculoskeletal system]] may show the signs of [[digital clubbing]], [[bone]] [[tenderness]], (suggestive of [[bone]] [[metastasis]]) and [[osteoarthropathy]] may be noted. | |||
===Laboratory Findings=== | |||
The initial evaluation of patients with small cell lung cancer (SCLC) confirmed by histopathological findings include a [[complete blood count]] with differential, [[electrolytes]], [[liver function test]], [[calcium]] level, [[LDH]], [[BUN]], and [[creatinine]]. These laboratory tests should also be performed to assess the response to the initial therapy. | |||
===Electrocardiogram=== | |||
===X-ray=== | |||
An [[x-ray]] may be helpful in the [[diagnosis]] of small cell lung cancer. Findings on an [[x-ray]] suggestive of small cell lung cancer include a hilar mass, lobular mass-like opacity, nodule in the [[lung]], [[mediastinal]] [[lymphadenopathy]], thickening of the paratracheal stripe and a [[mediastinal]] mass. | |||
===Echocardiography and Ultrasound=== | |||
===CT scan=== | |||
Chest [[CT scan]], preferably with [[intravenous]] [[contrast]] administration, may be helpful in the [[diagnosis]] of small cell carcinoma. Findings on [[CT scan]] suggestive of small cell carcinoma include [[Hilum|hilar]] mass, [[mediastinal]] involvement, numerous [[lymphadenopathy]], direct infiltration of adjacent structures, [[necrosis]] and [[hemorrhage]]. Small cell carcinoma of the lung is the most common cause of [[SVC obstruction]], due to both compression/[[thrombosis]] and/or direct infiltration 2. All patients with confirmed diagnosis of SCLC by [[histopathological]] findings should undergo a [[CT scan]] of the [[abdomen]] for staging purposes. [[Computed tomography|CT scan]] of the [[abdomen]] helps identify [[metastasis]] to organs, such as the [[liver]] or the [[adrenal glands]]. Brain imaging is also mandatory for staging; however, brain [[MRI]] is preferred over brain [[CT scan]] due to its superior [[sensitivity]] for the detection of brain [[metastasis]]. In addition, when limited stage small cell lung cancer is suspected, [[PET]] CT scan should be performed. | |||
===MRI=== | |||
There are no [[Magnetic resonance imaging|MRI]] findings associated with small cell carcinoma. However, a [[Magnetic resonance imaging|MRI]] may be helpful in the [[diagnosis]] of complications of small cell carcinoma, which include [[brain]] [[metastasis]]. [[Brain]] imaging is mandatory for staging purposes in all patients with small cell lung cancer. | |||
===Other Imaging Findings=== | |||
Patients with small cell lung cancer should undergo [[positron emission tomography]] ([[Positron emission tomography|PET]]) scan to evaluate for [[metastasis]]. PET-CT scan is preferred. If [[PET scan]] is unavailable, whole [[bone scan]] should be performed to detect whether [[cancer]] has [[metastasized]] to the [[bone]]s | |||
===Other Diagnostic Studies=== | |||
Among patients with small cell lung cancer (SCLC) who have [[pleural effusion]] large enough to be sampled, [[thoracentesis]] should be performed. The results of the analysis of the [[pleural effusion]] fluid should be considered in the staging of the patient. In addition, [[pathological]] [[mediastinal]] staging in selected patients should be performed through either [[mediastinoscopy]], video assisted [[thoracoscopy]], or endobronchial/[[esophageal]] guided [[ultrasound]] [[biopsy]]. Moreover, [[bone marrow biopsy]] is required among SCLC who have evidence on [[blood smear]] of nucleated [[red blood cells]], [[neutropenia]], or [[thrombocytopenia]]. | |||
==Treatment== | |||
===Medical Therapy=== | |||
Patients with small cell carcinoma of the lung (SCCL) have many treatment options.The selection of management depends on the stage of the [[tumor]], limited stage versus extensive stage. The options are [[Small cell carcinoma of the lung radiation therapy|radiation therapy]], [[chemotherapy]], [[Small cell carcinoma of the lung surgery|surgery]], or a combination of these methods. Because [[cancer]] treatments often damage healthy [[Cells (biology)|cells]] and [[tissues]], [[side effects]] are common. [[Side effects]] may not be the same for each person, and they may change from one treatment session to the next. SCLC patients are encouraged to participate in [[clinical trial]]s that investigate new regimens. In addition, SCLC patients should be strongly encouraged to discontinue [[smoking]]. | |||
===Surgery=== | |||
The feasibility of surgery depends on the stage of small cell lung carcinoma at diagnosis. In small cell lung carcinoma, surgery should only be considered among patients with clinical stage I (T1-2, N0). Postoperative chemotherapy with or without [[small cell carcinoma of the lung radiation therapy|radiation therapy]] is recommended based on the presence or absence of [[lymph node]] involvement. | |||
===Prevention=== | |||
Smoking cessation and avoidance of second-hand smoking are the most important measures for the [[Prevention (medical)|prevention]] of small cell lung cancer (SCLC) among other types of [[lung cancer]]. Lifestyle changes, such as a healthy diet rich in fruits and vegetables and regular exercise, might decrease the risk of developing cancer in general. | |||
==References== | ==References== | ||
Latest revision as of 19:51, 30 April 2018
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]
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Small Cell Carcinoma of the Lung Microchapters |
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Differentiating Small Cell Carcinoma of the Lung from other Diseases |
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Treatment |
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Overview
Small cell carcinoma of the lung is an anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. There are admixtures of small cell lung carcinoma with other types of lung cancer. Small cell carcinomas are distinguished by their distinctive biological features, response to chemotherapy and radiotherapy, and by their nearly universal tendency to develop overt or subclinical metastases, which frequently eliminates surgery in most patients.
Without treatment, small cell lung cancer (SCLC) has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2 to 4 months. Compared with other cell types of lung cancer, SCLC has a greater tendency to be widely disseminated by the time of diagnosis but is much more responsive to chemotherapy and radiation therapy.
Because patients with small cell lung cancer tend to develop distant metastases, localized forms of treatment, such as surgical resection or radiation therapy, rarely produce long-term survival. With the incorporation of current chemotherapy regimens into the treatment program, however, survival is unequivocally prolonged, with at least a 4- to 5-fold improvement in median survival compared with patients who are given no therapy. Furthermore, about 10% of the total population of patients remains free of disease during 2 years from the start of therapy, the time period during which most relapses occur. Even these patients, however, are at risk of dying from lung cancer (both small- and non-small cell types). The overall survival at 5 years is 5% to 10%.
Historical Perspective
Laennec first recognized lung cancer as a separate disease in 1815, in his work "Encephaloides" published in the Dictionnaire des sciences médicales. Azzopardi, in 1959, distinguished small cell lung cancer (SCLC) from anaplastic adenocarcinoma and squamous cell carcinoma and described the clinical and biological features that characterize it as a separate disease.
Pathophysiology
Small cell lung cancer is the most aggressive form of lung cancer and has the highest association with smoking of all lung cancers. Small cell lung cancer usually starts in the bronchi and expands through the bronchial mucosa. Small cell lung cancer often metastasizes rapidly to other parts of the body, including the brain, liver, and bone. A mutation in the p53 gene is reported in 75%-100% of the cases. Other molecular abnormalities that contribute to the development of small cell lung cancer have been described.
Causes
Smoking cigarettes and other tobacco related products are the predominant worldwide cause of small cell carcinoma of the lung and it can be associated with other risk factors in its development.
Differentiating Small cell carcinoma of the lung from Other Diseases
Depending on the presentation, lung cancer should be differentiated from other lung diseases such as pulmonary tuberculosis, lung abscess, and respiratory tract infection and autoimmune diseases affecting the respiratory tract. Once lung cancer is confirmed, small cell carcinoma should be differentiated from other non-small cell carcinoma based on histopathological findings.
Epidemiology and Demographics
Small cell lung cancer (SCLC) represents 13.4% of all lung cancers in the United States. The majority of small cell lung cancer occurs among patients > 65 years of age. The age-adjusted incidence of small cell lung cancer in the United States is reported to be 6.23 per 100,000 in 2011.
Risk Factors
Tobacco smoking is the leading risk factor of lung cancer. Other risk factors for lung cancer include environmental exposures, air pollution, and certain host-related factors.
Screening
The USPSTF recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery.
Natural History, Complications, and Prognosis
The natural history of untreated small cell lung cancer (SCLC) is extremely poor, with a median survival of only 2 months for stage IV SCLC and less than 3 to 4 months for tumors confined to the thorax. With the current treatment modalities, the median survival of patients with limited stage disease ranges from 16 to 24 months while that of patients with extensive-stage disease ranges from 6 to 12 months. SCLC can be complicated by paraneoplastic syndromes. Limited stage disease, absence of brain metastasis, young age, and female sex are considered good prognostic factors.
Diagnosis
Staging
Staging schemes for small cell lung cancer (SCLC) have been developed by the Veterans Administration Lung Study Group (VALG), the American Joint Committee on Cancer (AJCC), and the National Comprehensive Cancer Network (NCCN). The Veterans Administration Lung Study Group (VALG) staging scheme is the oldest among the three staging schemes. Although the AJCC staging scheme is newer than that of the VALG, clinicians commonly use the VALG staging system because it has been referred to in most clinical trials. The NCNN combines the AJCC (TNM) staging scheme with the VALG staging scheme.
Diagnostic Study of Choice
The confirmation of the diagnosis of SCLC relies on the histopathological findings of the tumor biopsy. All patients with confirmed diagnosis of SCLC by histopathological findings should undergo a CT scan of the abdomen for staging purposes. CT scan of the abdomen helps identify metastasis to organs, such as the liver or the adrenal glands.
History and Symptoms
Small cell lung cancer (SCLC) is characterized by a relatively rapid onset of symptoms. Patients usually present within 8 to 12 weeks of the onset of symptoms, which can be related either to the tumor growth in the thorax or to the distant spread of the tumor. In addition, SCLC is associated with the occurrence of paraneoplastic syndromes such as the syndrome of inappropriate antidiuresis (SIADH).
Physical Examination
Many authors have concluded that performing a complete assessment, with a detailed history and physical examination, is useful for identifying patients with a higher likelihood of metastases. Fever is reported in 20% of the patients. Patient may present with weight loss, cachexia and anorexia. Upon auscultation unilateral decreased air entry, unilateral wheeze, and decreased air entry in the bases of the lungs and/or crackles (suggestive of pleural effusion) may be present. The musculoskeletal system may show the signs of digital clubbing, bone tenderness, (suggestive of bone metastasis) and osteoarthropathy may be noted.
Laboratory Findings
The initial evaluation of patients with small cell lung cancer (SCLC) confirmed by histopathological findings include a complete blood count with differential, electrolytes, liver function test, calcium level, LDH, BUN, and creatinine. These laboratory tests should also be performed to assess the response to the initial therapy.
Electrocardiogram
X-ray
An x-ray may be helpful in the diagnosis of small cell lung cancer. Findings on an x-ray suggestive of small cell lung cancer include a hilar mass, lobular mass-like opacity, nodule in the lung, mediastinal lymphadenopathy, thickening of the paratracheal stripe and a mediastinal mass.
Echocardiography and Ultrasound
CT scan
Chest CT scan, preferably with intravenous contrast administration, may be helpful in the diagnosis of small cell carcinoma. Findings on CT scan suggestive of small cell carcinoma include hilar mass, mediastinal involvement, numerous lymphadenopathy, direct infiltration of adjacent structures, necrosis and hemorrhage. Small cell carcinoma of the lung is the most common cause of SVC obstruction, due to both compression/thrombosis and/or direct infiltration 2. All patients with confirmed diagnosis of SCLC by histopathological findings should undergo a CT scan of the abdomen for staging purposes. CT scan of the abdomen helps identify metastasis to organs, such as the liver or the adrenal glands. Brain imaging is also mandatory for staging; however, brain MRI is preferred over brain CT scan due to its superior sensitivity for the detection of brain metastasis. In addition, when limited stage small cell lung cancer is suspected, PET CT scan should be performed.
MRI
There are no MRI findings associated with small cell carcinoma. However, a MRI may be helpful in the diagnosis of complications of small cell carcinoma, which include brain metastasis. Brain imaging is mandatory for staging purposes in all patients with small cell lung cancer.
Other Imaging Findings
Patients with small cell lung cancer should undergo positron emission tomography (PET) scan to evaluate for metastasis. PET-CT scan is preferred. If PET scan is unavailable, whole bone scan should be performed to detect whether cancer has metastasized to the bones
Other Diagnostic Studies
Among patients with small cell lung cancer (SCLC) who have pleural effusion large enough to be sampled, thoracentesis should be performed. The results of the analysis of the pleural effusion fluid should be considered in the staging of the patient. In addition, pathological mediastinal staging in selected patients should be performed through either mediastinoscopy, video assisted thoracoscopy, or endobronchial/esophageal guided ultrasound biopsy. Moreover, bone marrow biopsy is required among SCLC who have evidence on blood smear of nucleated red blood cells, neutropenia, or thrombocytopenia.
Treatment
Medical Therapy
Patients with small cell carcinoma of the lung (SCCL) have many treatment options.The selection of management depends on the stage of the tumor, limited stage versus extensive stage. The options are radiation therapy, chemotherapy, surgery, or a combination of these methods. Because cancer treatments often damage healthy cells and tissues, side effects are common. Side effects may not be the same for each person, and they may change from one treatment session to the next. SCLC patients are encouraged to participate in clinical trials that investigate new regimens. In addition, SCLC patients should be strongly encouraged to discontinue smoking.
Surgery
The feasibility of surgery depends on the stage of small cell lung carcinoma at diagnosis. In small cell lung carcinoma, surgery should only be considered among patients with clinical stage I (T1-2, N0). Postoperative chemotherapy with or without radiation therapy is recommended based on the presence or absence of lymph node involvement.
Prevention
Smoking cessation and avoidance of second-hand smoking are the most important measures for the prevention of small cell lung cancer (SCLC) among other types of lung cancer. Lifestyle changes, such as a healthy diet rich in fruits and vegetables and regular exercise, might decrease the risk of developing cancer in general.