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Small Cell Lung Cancer

Pathology || Signs and Symptoms || Diagnosis || Treatment || Overview ||
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Pathology





Small cell lung cancer is believed to arise from neuroendocrine cells. The reasons for this belief are that when viewed under the microscope this cancer has neither a glandular nor squamous architecture. Additionally, a significant proportion of cells have secretory granules similar to those seen in the neuroendocrine cells that line the bronchi (aka: Kulchitsky cells), which are capable of secreting a variety of hormone like molecules.

Small cell lung cancer is associated with numerous genetic mutations that likely occur after years of exposure to carcinogens, most notably those found in cigarette smoke. The genetic mutations frequently involve genes that encode proteins which normally suppress abnormal cellular growth. These genes are known collectively as "tumor suppressors". In small cell lung cancer mutations in the tumor suppressor genes p53 and retinoblastoma are common, although many other genetic abnormalities are also seen.

Unlike squamous cell carcinoma, which tends to occur proximally in the lung (ie: closer to the heart) or adenocarcinoma, which tends to occur distally (ie: further from the heart), small cell cancer can be found in either location. It is highly malignant and commonly metastasizes to distant organs.

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Signs and Symptoms

Patients with small cell cancer often present with signs and symptoms consistent with many other types of cancer. Significant weight loss, fatigue, recurrent infections, and malaise are nonspecific signs of cancer. However, due to the fact that it originates in the lung, patients also often have cough and shortness of breath. Hemoptysis (ie: coughing up blood) may be seen in some patients if the cancer has invaded blood vessels. Co-existent pneumonias may also complicate the clinical picture.

Several paraneoplastic processes are associated with small cell cancer. Due to its neuroendocrine origin, the tumor can secrete a molecule similar to anti-diuretic hormone. The result is syndrome of inappropriate anti-diuretic hormone (SIADH). In this syndrome patients retain wate. This can lead to a decreased serum sodium level and possibly weakness, seizures, or coma.

The tumor can also secrete adrenocorticotropin hormone (ACTH), which stimulates the adrenal glands to produce cortisol (a steroid). The excess steroid secretion causes Cushing's syndrome, which may manifest as obesity, purple striae on the abdomen, development of diabetes mellitus, and fragile skin with easy bruising.

Finally, a paraneoplastic syndrome known as Lambert-Eaton syndrome can occur. This causes weakness that improves with repeated muscle contraction.

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Diagnosis

Diagnosis is based on both non-invasive and invasive testing. Most patients who are suspected to have small cell cancer get a contrast enhanced CT scan of their chest, abdomen, and pelvis. This will not only show the primary lung tumor, but will also show evidence of metastatic disease elsewhere in the body.

Once imaging is complete, the patient is usually referred for biopsy of the tumor (ie: "no meat, no treat"). If the tumor is near the larger conducting airways in the center of the chest, a procedure known as bronchoscopy is commonly used to directly visualize and biopsy the tumor.

Ultimately, small cell lung cancer can only be officially diagnosed by looking at a sample of the tumor under a microscope.

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Treatment

Treatment for small cell lung cancer involves both radiation and chemotherapy. Early stage disease responds well to chemoradiaton treatment, but the overall prognosis remains poor with life expectancy usually measured in months. The most commonly used chemotherapies include platinum based medications like cisplatin and carboplatin. Alkylating agents including ifosfamide and cyclophosphamide, as well as the anthracyclines doxorubicin and epirubicin are also used. Generally two or more chemotherapeutic medicines are used at the same time.

Surgical resection is not usually an option for small cell cancer because it is highly malignant, and by the time it presents has often spread to other areas of the body.

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Overview

Small cell lung cancer is a tumor derived from neuroendocrine cells. It occurs most commonly after years of cigarette smoking, which causes mutations in genes that normally suppress tumor growth. Weight loss, fatigue, coughing, and shortness of breath may occur, but many other signs and symptoms may also be present, especially with metastatic disease (ie: seizures if brain mets are present). Diagnosis is based on imaging and biopsy with evaluation of the tissue by a pathologist under a microscope. Treatment is with chemoradiation. Unfortunately, regardless of treatment, prognosis remains poor.

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Related Articles

- Chronic obstructive pulmonary disease

- Mechanical ventilation

- Pulmonary embolism

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References and Resources

(1) Miller CW, Simon K, Aslo A, et al. p53 mutations in human lung tumors. Cancer Res 1992 Apr 1;52(7):1695-8.

(2) Helin K, Holm K, Niebuhr A, et al. Loss of the retinoblastoma protein-related p130 protein in small cell lung carcinoma. Proc Natl Acad Sci U S A 1997 Jun 24;94(13):6933-8.

(3) Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Seventh Edition. Philadelphia: Elsevier Saunders, 2004.

(4) Flynn JA. Oxford American Handbook of Clinical Medicine (Oxford American Handbooks of Medicine). First Edition. Oxford University Press, 2007.

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