Small cell carcinoma
Encyclopedia
Small cell carcinoma is a type of highly malignant
cancer
that most commonly arises within the lung
, although it can occasionally arise in other body sites, such as the cervix
and prostate
.
Lambert-Eaton myasthenic syndrome (LEMS) is a well-known paraneoplastic condition linked to small cell carcinoma.
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When associated with the lung, it is sometimes called "oat cell carcinoma" due to the flat cell shape and scanty cytoplasm
.
It is thought to originate from neuroendocrine cell
s (APUD cell
s) in the bronchus
called Feyrter cells (named for Friedrich Feyrter
).
Hence, they express a variety of neuroendocrine markers, and may lead to ectopic production of hormones like ADH and ACTH that may result in paraneoplastic syndrome
s and Cushing's syndrome. Approximately half of all individuals diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) will eventually be found to have a small cell carcinoma of the lung.
Small cell carcinoma is most often more rapidly and widely metastatic
than non-small cell lung carcinoma (and hence staged differently). There is usually early involvement of the hilar and mediastinal lymph nodes.
, including extremely complex malignant tissue admixtures.
.
When it is found with one or more differentiated forms of lung cancer
, such as squamous cell carcinoma
or adenocarcinoma
, the malignant tumor is then diagnosed and classified as a combined small cell lung carcinoma
(c-SCLC). C-SCLC is the only currently recognized subtype of SCLC.
Although combined small cell lung carcinoma is currently staged and treated similarly to "pure" small cell carcinoma of the lung, recent research suggests surgery might improve outcomes in very early stages of this tumor type.
Smoking is a significant etiological
factor.
Symptoms and signs are as for other lung cancer
s. In addition, because of their neuroendocrine cell origin, small cell carcinomas will often secrete substances that result in paraneoplastic syndromes such as Lambert-Eaton myasthenic syndrome
.
(approx 1% of PC). Due to the fact that there is little variation in prostate specific antigen
levels, this form of cancer is normally diagnosed at an advanced stage, after metastasis.
It can metastasize to the brain.
In cases of LS-SCLC, combination chemotherapy (often including cyclophosphamide
, cisplatinum, doxorubicin
, etoposide
, vincristine
and/or paclitaxel
) is administered together with concurrent chest radiotherapy (RT).
Chest RT has been shown to improve survival in LS-SCLC.
Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using chemotherapy
alone, with between 45% and 75% of individuals showing a "complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. Unfortunately, relapse is the rule, and median survival is only 18 to 24 months.
Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to CT and/or RT, there has been little role for surgery in this disease since the 1970s. However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy.("adjuvant chemotherapy").
In ES-SCLC, combination chemotherapy is the standard of care, with radiotherapy added only to palliate symptoms such as dyspnea
, pain from liver or bone metastases, or for treatment of brain metastases, which, in small cell lung carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy.
Combination chemotherapy consists of a wide variety of agents, including cisplatin
, cyclophosphamide
, vincristine
and carboplatin
. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination chemotherapy
, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, however.
If complete response to chemotherapy
occurs in a subject with SCLC, then prophylactic cranial irradiation (PCI) is often used in an attempt to prevent the emergence of brain metastases. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.
All in all, small cell carcinoma is very responsive to chemotherapy
and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse, and median survival remains low.
The prognosis is far worse in extensive stage small cell lung carcinoma, with treatment, median survival is just 8–13 months, and only 1-5% of patients with extensive stage small cell lung carcinoma treated with chemotherapy live 5 years or longer.
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
that most commonly arises within the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
, although it can occasionally arise in other body sites, such as the cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...
and prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
.
Histopathology
Small cell carcinoma is an undifferentiated neoplasm composed of primitive-appearing cells.Paraneoplastic Syndromes
In a not-insignificant number of cases, small cell carcinomas can produce ectopic hormones, including adrenocorticotropic hormone (ACTH) and anti-diuretic hormone (ADH). Ectopic production of large amounts of ADH leads to syndrome of inappropriate production of anti-diuretic hormone (SIADH).Lambert-Eaton myasthenic syndrome (LEMS) is a well-known paraneoplastic condition linked to small cell carcinoma.
Lung
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
.
It is thought to originate from neuroendocrine cell
Neuroendocrine cell
Neuroendocrine cells are cells that receive neuronal input and, as a consequence of this input, release message molecules to the blood. In this way they bring about an integration between the nervous system and the endocrine system, a process known as neuroendocrine integration...
s (APUD cell
APUD cell
right|thumb|350px|Actions of the major digestive hormones secreted by APUD cellsAPUD cells constitute a group of apparently unrelated endocrine cells, which were named by the scientist A.G.E. Pearse, who developed the APUD concept in the early 60's. These cells share the common function of...
s) in the bronchus
Bronchus
A bronchus is a passage of airway in the respiratory tract that conducts air into the lungs. The bronchus branches into smaller tubes, which in turn become bronchioles....
called Feyrter cells (named for Friedrich Feyrter
Friedrich Feyrter
-References:...
).
Hence, they express a variety of neuroendocrine markers, and may lead to ectopic production of hormones like ADH and ACTH that may result in paraneoplastic syndrome
Paraneoplastic syndrome
A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors excreted by tumor cells or by an immune response against the tumor...
s and Cushing's syndrome. Approximately half of all individuals diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) will eventually be found to have a small cell carcinoma of the lung.
Small cell carcinoma is most often more rapidly and widely metastatic
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
than non-small cell lung carcinoma (and hence staged differently). There is usually early involvement of the hilar and mediastinal lymph nodes.
Combined small cell lung carcinoma (c-SCLC)
Small cell lung carcinoma can occur in combination with a wide variety of other histological variants of lung cancerLung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
, including extremely complex malignant tissue admixtures.
.
When it is found with one or more differentiated forms of lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
, such as squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
or adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
, the malignant tumor is then diagnosed and classified as a combined small cell lung carcinoma
Combined small cell lung carcinoma
Combined small cell lung carcinoma is a form of multiphasic lung cancer that is diagnosed when a malignant tumor arising from lung tissue contains a component of small cell lung carcinoma admixed with one components of non-small cell lung carcinoma .-Classification:Lung cancer is a large and...
(c-SCLC). C-SCLC is the only currently recognized subtype of SCLC.
Although combined small cell lung carcinoma is currently staged and treated similarly to "pure" small cell carcinoma of the lung, recent research suggests surgery might improve outcomes in very early stages of this tumor type.
Smoking is a significant etiological
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
factor.
Symptoms and signs are as for other lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
s. In addition, because of their neuroendocrine cell origin, small cell carcinomas will often secrete substances that result in paraneoplastic syndromes such as Lambert-Eaton myasthenic syndrome
Lambert-Eaton myasthenic syndrome
Lambert–Eaton myasthenic syndrome is a rare autoimmune disorder that is characterised by muscle weakness of the limbs...
.
Small cell carcinoma of the prostate
In the prostate, small cell carcinoma (SCCP) is a rare form of cancerProstate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
(approx 1% of PC). Due to the fact that there is little variation in prostate specific antigen
Prostate specific antigen
Prostate-specific antigen also known as gamma-seminoprotein or kallikrein-3 is a glycoprotein that in humans is encoded by the KLK3 gene. KLK3 is a member of the kallikrein-related peptidase family that are secreted by the epithelial cells of the prostate gland...
levels, this form of cancer is normally diagnosed at an advanced stage, after metastasis.
It can metastasize to the brain.
Treatment for small cell lung carcinoma
Small cell lung carcinoma has long been divided into two clinicopathological stages, including limited stage (LS) and extensive stage (ES). The stage is generally determined by the presence or absence of metastases, whether or not the tumor appears limited to the thorax, and whether or not the entire tumor burden within the chest can feasibly be encompassed within a single radiotherapy portal.In cases of LS-SCLC, combination chemotherapy (often including cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, cisplatinum, doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
, etoposide
Etoposide
Etoposide phosphate is an anti-cancer agent. It is known in the laboratory as a topoisomerase poison. Etoposide is often incorrectly referred to as a topoisomerase inhibitor in order to avoid using the term "poison" in a clinical setting...
, vincristine
Vincristine
Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
and/or paclitaxel
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
) is administered together with concurrent chest radiotherapy (RT).
Chest RT has been shown to improve survival in LS-SCLC.
Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
alone, with between 45% and 75% of individuals showing a "complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. Unfortunately, relapse is the rule, and median survival is only 18 to 24 months.
Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to CT and/or RT, there has been little role for surgery in this disease since the 1970s. However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy.("adjuvant chemotherapy").
In ES-SCLC, combination chemotherapy is the standard of care, with radiotherapy added only to palliate symptoms such as dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
, pain from liver or bone metastases, or for treatment of brain metastases, which, in small cell lung carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy.
Combination chemotherapy consists of a wide variety of agents, including cisplatin
Cisplatin
Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...
, cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, vincristine
Vincristine
Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
and carboplatin
Carboplatin
Carboplatin, or cis-Diammineplatinum is a chemotherapy drug used against some forms of cancer...
. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, however.
If complete response to chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
occurs in a subject with SCLC, then prophylactic cranial irradiation (PCI) is often used in an attempt to prevent the emergence of brain metastases. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.
All in all, small cell carcinoma is very responsive to chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse, and median survival remains low.
Prognosis
In limited stage disease, median survival with treatment is 14–20 months, and about 20% of patients with limited stage small cell lung carcinoma live 5 years or longer.The prognosis is far worse in extensive stage small cell lung carcinoma, with treatment, median survival is just 8–13 months, and only 1-5% of patients with extensive stage small cell lung carcinoma treated with chemotherapy live 5 years or longer.
See also
- Lung cancerLung cancerLung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
- Prostate cancerProstate cancerProstate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
- Brown-Sequard SyndromeBrown-Séquard syndromeBrown-Séquard syndrome, also known as Brown-Séquard's hemiplegia and Brown-Séquard's paralysis, is a loss of sensation and motor function that is caused by the lateral hemisection of the spinal cord...
- Cervical cancerCervical cancerCervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
- Combined small cell lung carcinomaCombined small cell lung carcinomaCombined small cell lung carcinoma is a form of multiphasic lung cancer that is diagnosed when a malignant tumor arising from lung tissue contains a component of small cell lung carcinoma admixed with one components of non-small cell lung carcinoma .-Classification:Lung cancer is a large and...
External links
- Neuroimmunology - by Abid R Karim, Birmingham UK, at University of Birmingham Medical SchoolUniversity of Birmingham Medical SchoolThe University of Birmingham Medical School is one of Britain's largest and oldest medical schools with over 400 Medics graduating each year. It is based at the University of Birmingham in Edgbaston, Birmingham, England...
- Image at Tulane UniversityTulane UniversityTulane University is a private, nonsectarian research university located in New Orleans, Louisiana, United States...