A 72-year-old man is brought to the hospital due to a 1-week history of progressive confusion and lethargy. He has also had a persistent cough for the past several weeks with 2 episodes of blood in the sputum. The patient has hyperlipidemia, well-controlled hypertension, and a 48-pack-year smoking history. On examination, mucous membranes are moist. Lung auscultation reveals wheezing in the left lung. Serum sodium is 123 mEq/dL. Chest x-ray reveals a mass in the upper lobe of the left lung. A bronchoscopic biopsy of the mass is performed, and light microscopy of the tissue confirms an aggressive lung cancer. Which of the following is most likely to be present on further analysis of the patient's biopsy sample?
Small cell carcinoma of the lung | |
Clinical features |
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Histology |
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Associated paraneoplastic syndromes |
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NCAM = neural cell adhesion molecule; SIADH = syndrome of inappropriate antidiuretic hormone. | |
This patient with an aggressive lung cancer has symptomatic hyponatremia (eg, confusion, lethargy) despite appearing euvolemic (moist mucous membranes). This presentation suggests small cell carcinoma of the lung complicated by paraneoplastic syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Small cell carcinoma, the most aggressive type of lung cancer, typically occurs in patients with a history of heavy smoking. It is characterized by a rapid doubling time and early distant spread; most patients have metastatic disease at the time of diagnosis. Although small cell carcinoma is sensitive to chemotherapy and radiation, most patients relapse within months, and the 5-year survival rate is very low. This malignancy frequently synthesizes hormones or hormone-like substances, resulting in paraneoplastic syndromes (eg, vasopressin resulting in SIADH, adrenocorticotropic hormone resulting in Cushing syndrome).
Small cell carcinomas show evidence of neuroendocrine differentiation. These tumors stain for neuroendocrine markers, such as neural cell adhesion molecule (CD56), neuron-specific enolase, chromogranin, and synaptophysin. Neurosecretory granules can be identified in the cytoplasm of the tumor cells on electron microscopy.
(Choice A) Epidermal growth factor receptor gene mutations are present in some non-small cell lung cancers (NSCLCs), most commonly in adenocarcinoma in nonsmokers. This mutation can predict responsiveness to tyrosine kinase inhibitor drugs (eg, erlotinib, afatinib). It is not present in small cell lung cancer.
(Choice B) Glial fibrillary acidic protein-positive fibrils are seen with some astrocytomas.
(Choice C) KRAS is an activating mutation that is present in up to 25% of lung adenocarcinomas and is associated with smoking. It is also frequently seen in colorectal and pancreatic cancer.
(Choice D) Mucin is a glycoprotein that frequently provides a protective barrier to epithelial cells. However, the MUC gene is overexpressed in a variety of malignancies (eg, breast, NSCLC, pancreatic) and is a marker for poor prognosis.
(Choice F) Vimentin is an intermediate filament found within cells of mesenchymal origin and is used in diagnosing sarcomas.
Educational objective:
Small cell carcinoma of the lung is the most aggressive type of lung cancer and is commonly associated with paraneoplastic syndromes (eg, SIADH, Cushing syndrome). It is thought to have a neuroendocrine origin; tumor cells express neuroendocrine markers (eg, neural cell adhesion molecule, chromogranin, synaptophysin) and contain neurosecretory granules in the cytoplasm.