Small-cell carcinoma
Small-cell carcinoma, also known as oat 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, prostate, and gastrointestinal tract. Compared to non-small cell carcinoma, small cell carcinoma is more aggressive, with a shorter doubling time, higher growth fraction, and earlier development of metastases.
Small-cell carcinoma is a neuroendocrine tumor, meaning that the cells were originally part of the neuroendocrine system. As a result, small cell carcinomas often secrete various hormones, such as adrenocorticotropic hormone or vasopressin. The unpredictable hormone secretion of small-cell carcinoma adds additional symptoms and mortality to the aggressive course of the cancer.
Extensive stage small cell lung cancer is classified as a rare disorder. Ten-year relative survival rate is 3.5%. Survival can be higher or lower based on a combination of factors including stage, age, sex and race. While most lung cancers are associated with tobacco smoking, SCLC is very strongly associated with tobacco smoking.
Types
Lung cancer
Lung cancers are broadly divided into non-small cell lung carcinomas, which account for about 80% of cases, and small cell lung carcinomas,which contribute about 20% of cases. Small-cell lung carcinoma has long been divided into two clinicopathological stages, termed limited stage and extensive stage. 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 general, if the tumor is confined to one lung and the lymph nodes close to that lung, the cancer is said to be LS. If cancer has spread beyond that, it is said to be ES.Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for the highest mortality rates among both men and women. When associated with the lung, SCLC is sometimes called "oat cell carcinoma" due to the flat cell shape and scanty cytoplasm. Small cell mesothelioma – an extremely rare subtype of lung cancer – can be mistaken for small cell lung cancer.
Small-cell carcinoma is most often more rapidly and widely metastatic than non-small-cell lung carcinoma. There is usually early involvement of the hilar and mediastinal lymph nodes. The mechanisms of its metastatic progression are not well understood.
Combined
When SCLC 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. Small-cell lung carcinoma can occur in combination with a wide variety of other histological variants of lung cancer, including extremely complex malignant tissue admixtures.C-SCLC is the only currently recognized subtype of SCLC.
Extrapulmonary
Very rarely, the primary site for small-cell carcinoma is outside of the lungs and pleural space; in these cases, it is referred to as extrapulmonary small-cell carcinoma. Outside of the respiratory tract, small-cell carcinoma can appear in the cervix, prostate, liver, pancreas, gastrointestinal tract, or bladder. It is estimated to account for 1,000 new cases a year in the U.S. Histologically similar to small-cell lung cancer, therapies for small-cell lung cancer are usually used to treat EPSCC. First-line treatment is usually with cisplatin and etoposide. In Japan, first-line treatment is shifting to irinotecan and cisplatin. When the primary site is in the skin, it is referred to as a Merkel-cell carcinoma.Extrapulmonary localized in the lymph nodes
This is an extremely rare type of small cell, and there has been little information in the scientific community. It appears to occur in only one or more lymph nodes, and nowhere else in the body. Treatment is similar to small-cell lung cancer, but survival rates are much higher than other small-cell carcinomas.Prostate
Small-cell carcinoma of the prostate is a rare form of prostate cancer. Symptomatic metastasis of SCCP to the brain is rare, and carries a poor prognosis.Signs and symptoms
Small-cell carcinoma of the lung usually presents in the central airways and infiltrates the submucosa leading to the narrowing of bronchial airways. Common symptoms include cough, dyspnea, weight loss, and debility. Over 70% of patients with small-cell carcinoma present with metastatic disease; common sites include the liver, adrenals, bone, and brain.Due to its high grade neuroendocrine nature, small-cell carcinomas can produce ectopic hormones, including adrenocorticotropic hormone and anti-diuretic hormone. Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic hormone hypersecretion. Lambert–Eaton myasthenic syndrome is a well-known paraneoplastic condition linked to small-cell carcinoma. Approximately half of all individuals diagnosed with Lambert–Eaton myasthenic syndrome will eventually be found to have a small-cell carcinoma of the lung.
Genetics
is mutated in 70 to 90% of SCLCs. RB1 and the retinoblastoma pathway are inactivated in most SCLCs. PTEN is mutated in 2 to 10%. MYC and MYC family member amplifications are found in 30% of SCLCs. Loss of heterozygosity on chromosome arm 3p is found in more than 80% of SCLCs, including the loss of FHIT. One hundred translocations have been reported in SCLCs.Diagnosis
Small-cell carcinoma is an undifferentiated neoplasm composed of primitive-appearing cells. As the name implies, the cells in small-cell carcinomas are smaller than normal cells and barely have room for any cytoplasm. Some researchers identify this as a failure in the mechanism that controls the size of the cells.At the time of diagnosis, 60–70% of people already have metastases.
LS-SCLC
are typically the first step to evaluate someone for any type of lung cancer. If images show suspicious spots on the patient's lung, a healthcare provider may order chest CT, PET, needle biopsy or bronchoscopy for further check.It is possible to use bronchoscopic biopsy to diagnose Lung small-cell carcinoma. However, small-cell carcinoma tissue obtained through bronchoscopy is prone to tissue compression and unclear morphology. However, pathologists can stain lesions with immunohistochemistry Ki-67, CD56, TTF-1, CgA, Syn, P63, CK5/6, LCA, and 34βE12 to help, in order to make a differential diagnosis.
ES-SCLC
The common metastasis sites of SCLC include the lung, brain, bone, adrenal gland, liver, colorectum, and lymph nodes.If the tumor metastasises to the brain, It is necessary to comprehensively evaluate the patient's condition in combination with PET/CT and MRI. In patients with brain metastases from small cell lung cancer, MRI has specificity and sensitivity of 75% to 90% and 70% to 85%, respectively. In MRI, T1- and T2-weighted images had medium-to-high signal intensity. Presently, brain metastasis diagnosis by FDG-PET/CT often uses TBR ≥1.6 of increased absorption as the appropriate diagnostic index for positive brain metastasis. Researchers also found cerebellum is the risk site with a high incidence of metastasis. In patients with SCLC brain metastasis, the general manifestation on plain CT is of low and medium density, and high-density signals of lesions are rare. However, the imaging with enhanced CT is more clear, showing obvious enhanced signals of cancer lesions. The extensive low-density edema zone of finger edema can be observed. What's more, it is difficult to detect small metastasis in the brain <0.5 cm, which contributes to the high false-positive rate of brain CT.
Treatment
LS-SCLC
In cases of LS-SCLC, combination chemotherapy is administered together with concurrent chest radiotherapy. Chest radiotherapy has been shown to improve survival in LS-SCLC. Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s. However, in cases of small, asymptomatic, node-negative SCLC's, surgical excision may improve survival when used prior to chemotherapy.ES-SCLC
In ES-SCLC, platinum-based combination chemotherapy is the standard of care.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 a combination chemotherapy, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, and the evidence surrounding the risk of treatment compared to the potential benefit of chemotherapy for people who have extensive SCLC is not clear.
Chemotherapy
Small-cell lung cancer is most commonly treated with chemotherapy in a combination of two drugs, which is more effective than one drug alone.- Cisplatin and etoposide,
- Carboplatin and etoposide.
Cisplatin-resistance
Immunotherapy
The FDA has approved three immunotherapies for small cell lung cancer:- Nivolumab, a PD-1 inhibitor
- Atezolizumab, a PD-L1 inhibitor
- Tarlatamab, a bi-specific T-cell engager