PROBLEM The patient is a 59-year-old male smoker who presents to the office with fever and cough. The chest x-ray film reveals no infiltrates, but the radiologist notes a 9-mm nodule in the right lower lobe.

APPROACH A solitary pulmonary nodule (SPN) is defined as a lung parenchymal lesion less than 3 cm in diameter. These nodules, identified in approximately 150,000 patients each year, are malignant in 10% to 70% of cases. If an SPN is malignant, the physician must make an early, accurate diagnosis because the 5-year prognosis after resection is 70% (compared with a 5-year prognosis of 10%-15% for all patients with lung cancer).

TABLE 1.Solitary pulmonary nodule: Differential diagnosis

Many factors influence the probability that a lung nodule is malignant: size, change in size, calcification appearance, age, smoking history, airflow obstruction, and certain occupations. Increasing size favors cancer. A lesion that doubles (increases its diameter by 25%) in less than a month is less likely to be benign. Eccentric calcification or a spiculated appearance on chest radiographs is more consistent with malignancy. Asbestos workers have a 3 to 5 times greater risk of lung cancer than the population at large—a risk that is greatly magnified by smoking. Chronic obstructive pulmonary disease poses an additional risk. In addition to malignancy, there are many other diagnoses to consider (see Table 1).

EVALUATION AND MANAGEMENT The first step is to determine whether the SPN is definitely located in the lung parenchyma. Is it a nipple shadow, a soft tissue mass, or an object of clothing? Once the nodule is determined to be intraparenchymal, the next step is to figure out whether the nodule is old or new by reviewing previous x-ray films. If a nodule has not changed in 2 years, it is almost always benign. The next question to ask is whether the nodule is single or multiple. CT evaluation will provide the answer. The presence of more than 6 nodules suggests granulomatous disease; the presence of 2 to 6 nodules is worrisome for metastatic disease.

Once a true, solitary nodule is identified, the diagnostic approach involves consideration of the patient's risk factors for cancer, comorbid conditions, surgical risk, patient preference, and the skills of the surgeon and radiologist. Nodule size is also a significant factor. Nodules less than 5 mm in diameter are not commonly associated with cancer. However, uncertainty exists in the literature regarding the best approach to these small nodules. Patients with the greatest risk for lung cancer may require follow-up CT scans. Nodules larger than 1 cm, especially in moderate- to high-risk patients, should be considered for transthoracic needle aspiration or surgical resection. Nodules of 5 to 9 mm in diameter are usually too small to aspirate. Ordering serial CT scans every 3 months for 1 year, and then every 6 months for the following year, is a reasonable approach for these nodules. Nodules that increase in size require aspiration or resection.

Positron-emission tomography (PET) is becoming increasingly available for the evaluation of lung nodules. PET imaging involves the uptake of 18F-fludeoxyglucose (cancer cells have greater metabolic activity and thus have greater uptake of this molecule). PET may be useful in patients who refuse needle aspiration or in the evaluation of nodules that are difficult to biopsy. PET can also identify occult mediastinal metastases in the presence of a normal CT scan of the mediastinum. PET is not useful, however, in nodules smaller than 1 cm. False-positive results can occur with infection and inflammation (PET sensitivity is approximately 97% and its specificity, 78%).