eMedicine Specialties > Oncology > Carcinomas of the Lung and Other Intrathoracic Carcinomas

Lung Cancer, Oat Cell (Small Cell): Differential Diagnoses & Workup

Author: Irfan Maghfoor, MD, Consulting Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia
Coauthor(s): Michael Perry, MD, MS, MACP, Nellie B Smith Chair of Oncology Emeritus, Professor, Department of Internal Medicine, Division of Hematology and Oncology, University of Missouri/Ellis Fischel Cancer Center
Contributor Information and Disclosures

Updated: May 22, 2009

Differential Diagnoses

Lung Cancer, Non-Small Cell
Lymphoma, Mediastinal

Workup

Laboratory Studies

A full staging workup for small cell lung cancer (SCLC) is described in Staging.

Investigations are performed to identify limited-stage disease (ie, potentially curable and requiring the addition of radiotherapy to its management), as well as to assess organ function before starting therapy.

• CBC count: In 5-10% of patients, the disease may have spread to bone marrow at presentation. Bone marrow examination is not routinely performed unless abnormalities are identified in the CBC count or peripheral smear examination, raising the possibility of bone marrow spread. These may include variable degrees of cytopenias; the presence of immature white and red blood cells (a leukoerythroblastic blood picture) raises the possibility of myelophthisic anemia. Additionally, the absolute neutrophil count should be >1000 x 10³/µL, hemoglobin >10 g/dL, and platelet count >100 x 10³/µL before instituting initial full-dose combination chemotherapy.
• Serum chemistries: Elevated serum calcium and alkaline phosphatase raise the suspicion of bone metastasis, and bone scan should be ordered even in the absence of symptoms. Serum electrolytes should be obtained to look for paraneoplastic syndromes, as already discussed. The presence of hyponatremia is considered an adverse prognostic indicator. Elevated serum lactate dehydrogenase (LDH) indicates increased tumor mass and cell turnover and is an adverse prognostic indicator. Abnormal liver function findings raise the possibility of hepatic metastasis and may provide a clue to the cause (eg, biliary outflow obstruction versus parenchymal liver metastasis).

Imaging Studies

• CT scans: The patient in whom lung cancer is suspected or diagnosed should undergo imaging of the thorax and all common sites of metastasis to stage the disease adequately. In the United States, CT scans of the chest and upper abdomen to include the liver and adrenal glands are standard. Even though some controversy exists regarding routine pretreatment CT/MRI scanning of the brain in asymptomatic patients, most authors consider it prudent to obtain a baseline scan of the brain in all patients.
• Magnetic resonance imaging: MRI scans are not part of the routine staging workup of small cell lung cancer, even though they have been shown to detect abnormal bone marrow signal in patients with bone marrow metastasis. MRI scans have an increased ability to detect disease in proximity to neurovascular structures. MRI examination is considered standard in the workup of patients in whom spinal cord compression is suspected.
• Radionuclide imaging: Bone metastases from small cell lung cancer are predominantly osteoblastic, and a bone scan is superior to plain radiographs in detecting osteoblastic lesions. Bone scans should be obtained in all patients with small cell lung cancer at diagnosis or during follow-up if new bone symptoms develop or if serum calcium or alkaline phosphatase level is elevated.
• Positron emission tomography: Positron emission tomography (PET) scanning still is under evaluation for lung cancers and, to date, has had its greatest application in non-small-cell lung cancer, in which it is used to more accurately stage patients prior to anticipated surgery.

Other Tests

• Sputum cytology is a noninvasive test, and, if positive, usually allows more invasive diagnostic tests to be averted. The highest yield of this test is with large, central tumors. However, because small cell lung cancer cells involve the submucosal layer of the bronchi with little or no exophytic endobronchial extension sputum cytology may be uncommonly positive. This may be true as well of bronchial washings.
• Bronchoscopy: Small cell lung cancer is usually centrally located and can be approached easily with a bronchoscope. The advantage of endoscopy is direct visualization of the tumor, allowing direct biopsy as well as cytologic examination of bronchial washings.
• Transthoracic percutaneous fine-needle aspiration: For accessible tumors, this test is less invasive than bronchoscopy and is carried out under CT scan guidance.

Procedures

• Thoracentesis: The presence of malignant pleural effusion upstages the disease to extensive stage. For adequate staging, pleural effusions should be aspirated and examined for malignant cells if no other sites of distant spread are identified. If a large symptomatic pleural effusion is present, therapeutic thoracentesis provides symptomatic relief. In patients with resistant, relapsed, or nonresponding disease, thoracentesis can be combined with pleurodesis to prevent recurrence. The preferred agent is currently sterilized talc, which can be instilled either as a slurry or as a powder during pleuroscopy. A large randomized study conducted by Cancer and Leukemia Group B will likely answer the question of whether slurry or poudrage is superior.
• Bone marrow aspiration and biopsy: Bone marrow examination is necessary in patients in whom myelophthisic anemia (leukoerythroblastic peripheral blood) is suspected.

Histologic Findings

Small cell lung cancer is typically centrally located, arising in peribronchial locations. They are thought to arise from Kulchitsky cells.

• The tumor is composed of sheets of small, round cells with dark nuclei, scant cytoplasm, fine granular nuclear chromatin, and indistinct nucleoli.
• Crush artifact leading to nuclear molding is a common finding, but it is not considered diagnostic.
• Very high rates of cell division are observed, and necrosis, sometimes extensive, may be seen. Because of the central location, the cells exfoliate in sputum and bronchial washings.
• Neurosecretory granules can be identified on electron microscopy, and the neuroendocrine nature of the neoplasm is suggested by its frequent association with paraneoplastic syndromes caused by peptide hormones.
• Immunohistochemical stains for chromogranin, neuron-specific enolase, and synaptophysin are usually positive.
• Approximately 5% of small cell lung cancers exhibit features of mixed small cell and large cell components and, less frequently, may exhibit mixed small cell and squamous cell components.
• The World Health Organization (WHO) classified small cell lung cancers into 3 subcategories: oat cell carcinoma, intermediate cell type, and combined oat cell carcinoma. This subclassification has been difficult to reproduce, however, even by expert lung cancer pathologists, and in 1988, the International Association for the Study of Lung Cancer recommended dropping the intermediate cell type from the classification and adding the category of mixed small cell carcinoma and large cell carcinoma.

Staging

The 2-stage system used for small cell lung cancer initially was proposed by the Veterans Administration Lung Group. Patients with disease confined to one hemithorax, with or without mediastinal, contralateral hilar, or ipsilateral supraclavicular or scalene lymph nodes are considered to have limited-stage disease, while those with disease involvement at any other location are considered to have extensive-stage disease. (The involvement of supraclavicular nodes and the presence of cytologically positive pleural effusion subsequently have been placed in different stage groupings in slightly revised staging classifications.) The key variable in this purposely vague staging definition is the ability to encompass the entire disease within one radiation therapy port. A slight modification of this system is used currently and is as follows:

• Limited stage: Disease confined to one hemithorax; includes involvement of mediastinal, contralateral hilar, and/or supraclavicular and scalene lymph nodes. Malignant pleural effusion is excluded.
• Extensive stage: Disease has spread beyond the definition of limited stage, or malignant pleural effusion is present.

The purpose of the staging workup is to determine the prognosis and management of small cell lung cancer. Patients with limited-stage disease are offered combined chemoradiotherapy, while those with extensive-stage disease are usually treated with chemotherapy alone.

• Staging workup of small cell lung cancer is as follows:
  • Complete history and physical examination
  • Chest radiograph
  • CT scans of chest and abdomen
  • CT scan/MRI of brain
  • Bone scan
  • CBC count with differential
  • Bone marrow aspiration and biopsy if abnormalities in CBC count or peripheral smear
  • Serum electrolytes, including calcium
  • Liver function tests
  • Renal function tests
  • Serum LDH
  • Serum alkaline phosphatase
• History and physical examination: A thorough history and physical examination usually provide clues to the organ systems involved and are used to guide further workup.
• Chest roentgenogram: Good posteroanterior and lateral radiographs are useful in identifying the primary tumor as well as concurrent parenchymal abnormalities. Mediastinal widening may be noticed as well.
• CT scans of chest and abdomen: Evaluation via CT scan of thorax (lungs and mediastinum) and commonly involved abdominal viscera (ie, liver, adrenals) is the minimum requirement in standard staging workup of small cell lung cancer.
• Bone scan: Bone is a common site of metastasis for small cell lung cancer, and a radionuclide bone scan should be obtained to identify bone metastases. Since some benign etiologies can also cause abnormalities on bone scan, obtaining plain radiographs of abnormal areas for radiographic correlation is important.
• CT scan/MRI of brain: Brain metastasis may be present in as many as 10% of patients at diagnosis and may be occult in 5% of patients. Even though obtaining imaging scans of brain in all patients at diagnosis is controversial, the policy of most authors is to obtain a scan of the brain at diagnosis for adequate staging.
• Bone marrow examination: Even though some authorities recommend a bone marrow examination in patients in whom no other site of spread is identified (ie, in cases in which detection of bone marrow involvement would change the staging from limited to extensive disease), the majority of authors recommend bone marrow examination only in patients in whom bone marrow involvement is suspected owing to abnormal findings on CBC count or peripheral smear.
• Blood workup
  • CBC count with differential, serum electrolytes, renal function studies, and liver function tests are all are part of the routine staging workup, and in some cases they may identify the site of metastasis, for instance elevated serum calcium level with bone metastasis. These tests are also important to assess organ function prior to starting therapy.
  • Serum LDH and sodium levels also provide prognostic information. Increased uric acid levels may indicate the possibility of rapid tumor lysis syndrome with therapy.

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