Large cell carcinoma of the lung overview: Difference between revisions
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==Overview== | ==Overview== | ||
'''Large cell carcinoma of the lung''' ('''''LCC''''') is a type of non-small cell carcinoma of the lung, that accounts for 5% and 10% of all lung cancers. Large cell carcinoma of the lung has a moderate causal association with smoking. According to the World Health Organization (WHO), large cell carcinoma of the lung can be classified into 6 sub-types: giant-cell carcinoma of the lung, basaloid large cell carcinoma of the lung, clear cell carcinoma of the lung, lymphoepithelioma-like carcinoma of the lung, large-cell lung carcinoma with rhabdoid phenotype, and large cell neuroendocrine carcinoma of the lung. Large cell carcinoma of the lung arises from the epithelial cells of the lung, which are usually involved in the lining of the airways. The pathological irritation causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells to be replaced by stratified squamous epithelium. Large cell carcinoma of the lung has a peripheral location, and usually appears as a well-circumcised mass attached to the thoracic wall. Large cell carcinoma of the lung is a rapidly growing cancer. The histologic subtype of large cell neuroendocrine tumor is related with a more aggressive presentation. Genes involved in the pathogenesis of large cell carcinoma of the lung include: EGFR, EML-4, KRAS, HER2, and ALK. On gross pathology, large cell carcinoma of the lung is characterized by well-defined borders, spherical morphology, homogeneous gray-white surface, and bulging appearance. On microscopic pathology, hallmark features of large cell carcinoma of the lung, include: larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin. On immunohistochemistry characteristic features, include: loss of staining with CK5/6, and positive immunoreactivity to EGFR, PDGFR-alpha, and c-kit. | '''Large cell carcinoma of the lung''' ('''''LCC''''') is a type of non-small cell carcinoma of the lung, that accounts for 5% and 10% of all lung cancers. Large cell carcinoma of the lung has a moderate causal association with smoking. According to the World Health Organization (WHO), large cell carcinoma of the lung can be classified into 6 sub-types: giant-cell carcinoma of the lung, basaloid large cell carcinoma of the lung, clear cell carcinoma of the lung, lymphoepithelioma-like carcinoma of the lung, large-cell lung carcinoma with rhabdoid phenotype, and large cell neuroendocrine carcinoma of the lung. Large cell carcinoma of the lung arises from the epithelial cells of the lung, which are usually involved in the lining of the airways. The pathological irritation causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells to be replaced by stratified squamous epithelium. Large cell carcinoma of the lung has a peripheral location, and usually appears as a well-circumcised mass attached to the thoracic wall. Large cell carcinoma of the lung is a rapidly growing cancer and frequently has early metastasis. The histologic subtype of large cell neuroendocrine tumor is related with a more aggressive presentation. Genes involved in the pathogenesis of large cell carcinoma of the lung include: EGFR, EML-4, KRAS, HER2, and ALK. On gross pathology, large cell carcinoma of the lung is characterized by well-defined borders, spherical morphology, homogeneous gray-white surface, and bulging appearance. On microscopic pathology, hallmark features of large cell carcinoma of the lung, include: larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin. On immunohistochemistry characteristic features, include: loss of staining with CK5/6, and positive immunoreactivity to EGFR, PDGFR-alpha, and c-kit. | ||
==Historical Perspective== | ==Historical Perspective== | ||
Revision as of 14:48, 9 March 2016
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Large Cell Carcinoma of the Lung Microchapters |
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Differentiating Large Cell Carcinoma of the Lung from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]
Overview
Large cell carcinoma of the lung (LCC) is a type of non-small cell carcinoma of the lung, that accounts for 5% and 10% of all lung cancers. Large cell carcinoma of the lung has a moderate causal association with smoking. According to the World Health Organization (WHO), large cell carcinoma of the lung can be classified into 6 sub-types: giant-cell carcinoma of the lung, basaloid large cell carcinoma of the lung, clear cell carcinoma of the lung, lymphoepithelioma-like carcinoma of the lung, large-cell lung carcinoma with rhabdoid phenotype, and large cell neuroendocrine carcinoma of the lung. Large cell carcinoma of the lung arises from the epithelial cells of the lung, which are usually involved in the lining of the airways. The pathological irritation causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells to be replaced by stratified squamous epithelium. Large cell carcinoma of the lung has a peripheral location, and usually appears as a well-circumcised mass attached to the thoracic wall. Large cell carcinoma of the lung is a rapidly growing cancer and frequently has early metastasis. The histologic subtype of large cell neuroendocrine tumor is related with a more aggressive presentation. Genes involved in the pathogenesis of large cell carcinoma of the lung include: EGFR, EML-4, KRAS, HER2, and ALK. On gross pathology, large cell carcinoma of the lung is characterized by well-defined borders, spherical morphology, homogeneous gray-white surface, and bulging appearance. On microscopic pathology, hallmark features of large cell carcinoma of the lung, include: larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin. On immunohistochemistry characteristic features, include: loss of staining with CK5/6, and positive immunoreactivity to EGFR, PDGFR-alpha, and c-kit.
Historical Perspective
In 1976,"The Nurses Health Study" was the first epidemiological study to assess the risk of large cell lung carcinoma with a previous history of tobacco smoking
Classification
According to the World Health Organization (WHO), large cell carcinoma of the lung can be classified into 6 sub-types: giant-cell carcinoma of the lung, basaloid large cell carcinoma of the lung, clear cell carcinoma of the lung, lymphoepithelioma-like carcinoma of the lung, large-cell lung carcinoma with rhabdoid phenotype, and large cell neuroendocrine carcinoma of the lung.
Pathophysiology
Large cell carcinoma of the lung arises from the epithelial cells of the lung, which are usually involved in the lining of the airways. The pathological irritation causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells to be replaced by stratified squamous epithelium. Large cell carcinoma of the lung has a peripheral location, and usually appears as a well-circumcised mass attached to the thoracic wall. Large cell carcinoma of the lung is a rapidly growing cancer. The histologic subtype of large cell neuroendocrine tumor is related with a more aggressive presentation. Genes involved in the pathogenesis of large cell carcinoma of the lung, include: EGFR, EML-4, KRAS, HER2, and ALK. On gross pathology, large cell carcinoma of the lung is characterized by well-defined borders, spherical morphology, homogeneous gray-white surface, and bulging appearance. On micropathology, large cell carcinoma of the lung is characterized by the larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin. On immunohistochemistry characteristic features, include: loss of staining with CK5/6, and positive immunoreactivity to EGFR, PDGFR-alpha, and c-kit.
Causes
In general, causes of large cell carcinoma of the lung are those of non-small cell lung cancers. Common causes include precursor lesions, such as metaplasia or dysplasia induced by smoking, asbestos exposure, ionizing radiation, atmospheric pollution, and chronic interstitial pneumonitis. Less common causes of large cell carcinoma of the lung include chromium and nickel exposure, vinyl chloride exposure, and inorganic arsenic exposure.[1]
Differentiating Large Cell Carcinoma of the Lung from other Diseases
Large cell carcinoma of the lung must be differentiated from other diseases that cause non-productive cough, weight loss, fatigue, and dyspnea among adults such as tuberculosis, pulmonary fungal disease, lung abscess, and more importantly from other causes of non-small cell lung cancers, such as adenocarcinoma and squamous cell lung cancer.[2][3]
Epidemiology and Demographics
Large cell lung cancer accounts for 5% and 10% of all lung cancers. Other subtypes of large cell carcinoma of the lung, such as large cell neureoendocrine carcinoma and lymphoepithelioma-like carcinoma are rare, and represent only 1-3% of lung cancers. Large cell carcinoma of the lung accounts for less than 2% of all cancer deaths. The incidence of large cell carcinoma of the lung increases with age; the median age at diagnosis is approximately 60 years.[4] Large cell carcinoma of the lung is most frequently diagnosed among people among 55 to 65 years old. Males are more commonly affected with large cell carcinoma of the lung than females. Asian race has a higher incidence of lymphoepithelioma-like large lung cell carcinoma compared to the white race.
Risk Factors
The most important risk factor in the development of large cell carcinoma of the lung is cigarette smoking. Other common risk factors in the development of large cell carcinoma of the lung are family history of lung cancer, high levels of air pollution, radiation therapy to the chest, radon gas, asbestos, occupational exposure to chemical carcinogens, and previous history of lung disease.[5]
Screening
According to the U.S. Preventive Services Task Force (USPSTF), screening for large cell carcinoma of the lung by low-dose computed tomography is recommended every year among smokers who are between 55 to 80 years old and who have history of smoke 30 pack-years or more and either continue to smoke or have quit within the past 15 years (grade B recommendation).[6][7][8]
Natural History, Complications and Prognosis
If left untreated, large cell carcinoma of the lung progression occurs rapidly and is then followed by local invasion to chest wall and adjacent lymph nodes.[9] Large cell carcinoma of the lung is a locally aggressive tumor. Large cell carcinoma of the lung is a diagnosis of "exclusion", usually the tumor cells lack light microscopic characteristics that would classify the neoplasm as a small-cell carcinoma, squamous-cell carcinoma, adenocarcinoma, or other more specific histologic type of lung cancer. Large cell carcinoma of the lung commonly occurs in adult patients between 55 to 60 years. Common sites of metastasis include adrenal gland, bone, brain, and liver. Complications of large cell carcinoma of the lung, include: acute respiratory failure, malignant pleural effusion, metastases, and pneumonia. Features associated with worse prognosis are presence of lymphatic invasion, location of lesion, gene expression profile, performance status, presence of satellite lesions, and presence of regional or distant metastases. Prognosis is generally regarded as poor.
Diagnosis
Staging
Staging system classification for large cell carcinoma of the lung is same as the non-small cell lung cancer staging. The two main staging systems, include: American Joint Committee on Cancer (AJCC) staging system and International Union Against Cancer (UICC) staging system. According to both institutions, TNM system, which they now develop jointly, classifies cancer by several factors, T for tumor, N for nodes, M for metastasis, and then groups these TNM factors into overall stages.[10] There are 4 stages of large cell carcinoma of the lung: stage I, stage II, stage III, and stage IV [10] Each stage is assigned a letter and a number that designate T for tumor size, N for node invasion, and M for metastasis.
History and Symptoms
The hallmark of large cell carcinoma of the lung is non-productive chronic cough, weight loss, and fatigue. A positive history of smoking, exposure to asbestos, or a high risk occupation may be suggestive of large cell carcinoma of the lung. Symptoms related with large cell carcinoma of the lung will vary depending on the size and location of the tumor. Common symptoms of large cell carcinoma of the lung may also include: shortness of breath, fatigue, and chest pain.[11][12]
Physical Examination
Physical examination findings of large cell carcinoma of the lung will depend on the stage and size of the tumor. Large cell carcinoma of the lung with peripheral location may cause reduced chest expansion, tachypnea, and crackling sounds. Other common physical examination findings of patients with large cell carcinoma of the lung, may include: bubbling noises, decreased/absent breath sounds, and whispered pectoriloquy.[13]
Laboratory Findings
Laboratory findings associated with large cell carcinoma of the lung, include: elevation of LDH or serum tumor markers. Routine laboratory studies for large cell carcinoma of the lung, include: complete blood count, electrolytes, calcium, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, albumin, and lactate dehydrogenase.[14]
Chest X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Biopsy
Treatment
Medical Therapy
Chemotherapy
Radiation Therapy
Surgery
Primary Prevention
Secondary Prevention
References
- ↑ National Cancer Institute: PDQ® Non-Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified January 22. http://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq. Accessed February 23, 2015
- ↑ Bhatt M, Kant S, Bhaskar R (2012). "Pulmonary tuberculosis as differential diagnosis of non-small cell lung cancer". South Asian J Cancer. 1 (1): 36–42. doi:10.4103/2278-330X.96507. PMC 3876596. PMID 24455507.
- ↑ Singh VK, Chandra S, Kumar S, Pangtey G, Mohan A, Guleria R (2009). "A common medical error: lung cancer misdiagnosed as sputum negative tuberculosis". Asian Pac. J. Cancer Prev. 10 (3): 335–8. PMID 19640168.
- ↑ Meza R, Meernik C, Jeon J, Cote ML (2015). "Lung cancer incidence trends by gender, race and histology in the United States, 1973-2010". PLoS ONE. 10 (3): e0121323. doi:10.1371/journal.pone.0121323. PMC 4379166. PMID 25822850.
- ↑ Lung cancer. Canadian Cancer Society 2015. http://www.cancer.ca/en/cancer-information/cancer-type/lung/risks/?region=ab#Outdoor_air_pollution Accessed February 3, 2016
- ↑ Lung Cancer: Screening http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lung-cancer-screening. Accessed on February 3, 2016
- ↑ Davis AM, Cifu AS. Lung Cancer Screening. JAMA. 2014;312(12):1248-1249. doi:10.1001/jama.2014.12272.
- ↑ National Lung Screening Trial. Wikipedia. https://en.wikipedia.org/wiki/National_Lung_Screening_Trial Accessed on February 4,2016
- ↑ Soares M, Darmon M, Salluh JI, Ferreira CG, Thiéry G, Schlemmer B, Spector N, Azoulay E (2007). "Prognosis of lung cancer patients with life-threatening complications". Chest. 131 (3): 840–6. doi:10.1378/chest.06-2244. PMID 17356101.
- ↑ 10.0 10.1 Stages of non–small cell lung cancer. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/lung/staging/?region=ab
- ↑ Large cell carcinoma of the lung. Wikipedia. https://en.wikipedia.org/wiki/Non-small-cell_lung_carcinoma Accessed on February 24, 2016
- ↑ Raz DJ, Zell JA, Ou SH, Gandara DR, Anton-Culver H, Jablons DM (2007). "Natural history of stage I large cell carcinoma of the lung: implications for early detection". Chest. 132 (1): 193–9. doi:10.1378/chest.06-3096. PMID 17505036.
- ↑ Hyde L, Hyde CI (1974). "Clinical manifestations of lung cancer". Chest. 65 (3): 299–306. PMID 4813837.
- ↑ Spira A, Ettinger DS (2004). "Multidisciplinary management of lung cancer". N. Engl. J. Med. 350 (4): 379–92. doi:10.1056/NEJMra035536. PMID 14736930.