Small cell carcinoma of the lung overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]

Small Cell Carcinoma of the Lung Microchapters

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Patient Information

Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Small Cell Carcinoma of the Lung from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Radiation Therapy

Surgery

Prevention

Future or Investigational Therapies

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Case #1

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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.

References


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