43: Lung Cancer

Key Points

• Disease summary:

  • Lung cancer is the leading cause of cancer mortality in the United States.

  • Approximately 85% of lung cancers are nonsmall cell lung cancer (NSCLC), and about 15% small cell lung cancer (SCLC). Among NSCLC, the incidence of adenocarcinoma is rising to surpass that of squamous cell carcinoma.

  • Presenting symptoms may include shortness of breath, cough, weight loss, or symptoms from a metastatic site such as headache or seizure from a brain metastasis or pain from a bony metastasis. Clinical symptoms typically present late in the course of disease and most patients are diagnosed with advanced lung cancer.

  • NSCLC staging uses the TNM system, in which T stage describes tumor size and location, N stage describes nodal status, and M stage describes metastases—the overall TNM defines if the cancer is stage I, II, III, or IV.

  • SCLC is staged as either limited stage or extensive stage, depending on the extent of the tumor and whether it can fit within a radiation port (limited) or not (extensive).

• Differential diagnosis:

  • It includes infection, metastatic cancer from another primary site, lymphoma, among others.

• Monogenic forms:

  • No single genetic cause of lung cancer is known to exist.

• Family history:

  • Some studies have suggested a slight increase in risk among first-degree relatives, but studies are confounded by smoking and exposure to secondhand smoke.

• Environmental factors:

  • Cigarette smoking is the leading cause of lung cancer and accounts for approximately 90% of all lung cancer cases in the United States. Both duration of smoking and number of cigarettes per day are directly correlated with lung cancer risk.

  • Environmental tobacco smoke, radon, occupational exposures to tar and soot, asbestos, and metals such as arsenic, chromium, and nickel, have also been associated with increased lung cancer risk.

• Genome-wide associations:

  • Recent genome-wide association studies (GWAS) have identified a region in the long arm of chromosome 15 (15q25) as being highly associated with lung cancer risks. This region on chromosome 15 contains several genes, including three that encode subunits of nicotinic acetylcholine receptor (nAChR): CHRNA5, CHRNA3, and CHRNB4, as well as other potential candidate genes including IREB2 and PSMA4. It remains unclear whether the association is primarily related to the genetic variation in chromosome 15 affecting smoking behavior, or whether there is truly an independent association with lung cancer risk independent of the confounding effects of smoking behavior. Other potential lung cancer susceptibility loci identified by these GWAS studies mapped to 5q15.33 and 6p21.33.

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria

• Histologically or cytologically confirmed tissue biopsy showing lung cancer.

• Evaluation should include a full staging workup to assess for common sites of metastatic disease including chest computed tomography (CT) extending down through the liver and adrenals, positron emission tomography (PET) scan, and brain magnetic resonance imaging (MRI).