 Diagnosis and management of the indeterminate pulmonary nodule Peter D. Kaplan, M.D., Co-director, Allegheny Center for Lung and Thoracic Disease The finding of a "new" indeterminate pulmonary nodule on a patient's chest roentgenogram raises important diagnostic questions for the primary physician. By definition, a pulmonary nodule is characterized as a mass lesion circumscribed by the lung substance with a diameter of 4 cm or less (Figure 1). More than 150,000 patients are identified with such pulmonary lesions in the United States each year. In most cases, the detection of a solitary pulmonary nodule (SPN) is unexpected and found on a routine chest X-ray. Pulmonary or constitutional symptoms are rarely associated with the nodule, and, if present, may be related to another cause. For example, hemoptysis is not a common presenting complaint and might indicate the presence of an unrelated endobronchial lesion. The decision to either resect the lesion or to follow the nodule with serial films depends upon multiple factors, including the patient's age, the radiographic appearance and size, and history of a prior malignancy.
The initial approach to the patient includes a complete history, physical exam and review of prior chest X-rays. There are several parameters the clinician caring for the patient with a new lung lesion can use to assist in weighing the risk of malignancy in any particular lung lesion Table 1. The importance of locating prior films for comparison cannot be overstated. A nodule that does not grow over a two-year period or is densely calcified likely is benign; no further investigation is required. Age is an important factor, as a small nodule found in a patient less than 35 years old likely is benign and careful radiographic follow-up is the only monitoring required (unless the patient has a prior history of malignancy). In contrast, older patients identified with a new noncalcified pulmonary nodule - particularly individuals with a history of smoking - are more likely to have a malignant lesion. This premise also holds true for older nonsmoking patients (older than 70 years of age) with new pulmonary nodules.
The importance of locating prior films for comparison cannot be overstated. A nodule that does not grow over a two-year period or is densely calcified likely is benign; no further investigation is required. A computed tomograph (CT) scan, especially a high-resolution, thin-cut CT scan of the chest, can be helpful in determining the presence of calcification. Central, diffuse, laminated or popcorn patterns of calcification indicate a benign process; an eccentric location of calcification in the nodule should raise the concern that the lesion may be cancerous. Besides the size and the presence or absence of calcification, other characteristics can be helpful to differentiate between benign and malignant lesions. Benign lesions tend to have smooth edges, for example; malignant nodules may have blurred, stellate or lobulated margins. Spiculation of a nodule is suggestive of malignancy. Only characteristic calcification (as mentioned above) or fat within the lesion (pathognomonic of hamartoma), are definitive indicators of benignity. CT reference phantom scanning and CT contrast enhancement are promising techniques that may help distinguish a benign from a malignant nodule. MRI generally does not provide additional information in evaluating a solitary pulmonary nodule. The decision to proceed with a biopsy of the nodule depends on multiple other factors. For example, a nodule larger than 3 cm is likely to be malignant, and a nonspecific diagnosis on biopsy still does not exclude malignancy. Although transthoracic needle aspiration (TTNA) may be successful in identifying a malignant etiology among large (>3 cm in diameter) peripheral pulmonary nodules in the majority of cases, the success rate in determining the etiology of smaller lesions with this technique is less reliable. The complications related to this procedure (pneumothorax and hemothorax) may approach 25 percent. The risk of pneumothorax from TTNA, however, especially in patients with emphysema, approaches 40 percent with one-half requiring chest tube insertion. Fiberoptic bronchoscopy yields a diagnosis in only about 20 percent of peripheral nodules 2 cm or smaller. However, larger lesions are more likely to be accessible by fiberoptic bronchoscopy, particularly if performed under fluoroscopy guidance.
Although the success rate in identifying a malignant lesion is high (78 percent), the next therapeutic step involves surgical resection in the good-risk patient. In this case, percutaneous biopsy is a costly, superlative maneuver. When a negative biopsy result is obtained, the risk of missing representative tumor cells is too great (-40 percent) to allow for continued observation. The complication rate (25 percent) associated with this costly and diagnostically equivocal procedure (<15 percent patients with calcified nodules ultimately avoid thoracotomy) warrants the limited use of this approach to those patients who are absolutely unresectable or with such impairment in functional status that pulmonary resection is contra-indicated. Prior to surgery, routine bronchoscopy in an asymptomatic patient may not be necessary, as recent studies suggest bronchoscopy rarely identifies any other lesions or affects the surgical staging of the nodule. However, the surgeon should examine the airway at the time of surgery to help ensure that surgical resection is reasonable. Preoperative bronchoscopy does have a role in selected circumstances. For example, if a patient has symptoms of cough or hemoptysis, bronchoscopy is mandatory to determine the presence of an endobronchial lesion (even in the contralateral lung) that may be undetected by chest X-ray or CT scanning. One approach to the nodule is a "wait and watch" strategy to see if the nodule enlarges over time. Malignant nodules tend to double between 30 and 400 days. Although the magnitude of the hazard of delaying surgery in a given patient is unknown, we generally disagree with this "wait and watch" strategy, as the five-year survival rate is inversely proportional to the size of the lesion. It is always prudent, however, to wait a few weeks and repeat the chest film because a subclinical chest infection may present as a spherical lesion and resolve within this time. Pulmonary function studies should be performed routinely prior to surgery to assess the patient's functional reserve, as well as to identify the degree of reversible bronchospasm. On occasion, more extensive resection than anticipated is required to properly remove the tumor. In some patients with severe functional impairment, measuring the response to exercise (maximum oxygen uptake, gas exchange) can be extremely useful in assessing safe limits of resectability. Prior to surgery, cessation of smoking along with treatment of bronchitis and bronchospasm effectively decrease postoperative complications. Bronchodilators and judicious use of corticosteroids also prove valuable in this regard.
The surgical modalities available for biopsy are open surgical excisional biopsy through a standard thoracotomy and a closed thoracoscopic excisional biopsy. Because percutaneous biopsy approaches are associated with an unacceptable false negative rate (approximately 35 percent), procedural-related morbidity, and unnecessary delays in definitive treatment for primary lung cancers, we prefer surgical excisional biopsy as the primary diagnostic modality for patients who can undergo a general anesthetic and wedge resection of the lung. Surgical biopsy is effective in diagnosing the lesion in nearly all these patients. Definitive management of lesions found to be primary lung cancers can be performed under the same anesthetic management. Our tendency to move directly to the surgical biopsy approach to evaluate the good-risk patient has been enhanced by the effectiveness of minimally invasive, video-assisted thoracoscopic approaches to excisional wedge resection biopsy of pulmonary lesions (Figure 2). This approach is usually accomplished via three 1-inch incisions through which the video camera/thoracoscope and appropriate instrumentation are introduced to accomplish resection of the pulmonary lesion. In many instances, the biopsy approach can be accomplished with only two intercostal incisions by alternating the position of the thoracoscope/camera and the endosurgical resective instrumentation. Our clinical experience with more than 500 thoracoscopic excisional biopsies of peripheral indeterminate pulmonary nodule has been gratifying. The average hospital stay has been less than three days and postoperative complications have been minimal. When a benign or metastatic lesion is diagnosed, the morbidity of thoracotomy is avoided. When a primary lung cancer is determined, conversion to open thoracotomy to accomplish a formal anatomic resection of the lobe affected by the pulmonary lesion can be performed immediately. Alternatively, a video-assisted approach to lobar resection can be utilized in lieu of thoracotomy to perform lobectomy in patients with favorable lobar anatomy. The nature of the indeterminate pulmonary nodule can be determined with certainty in the majority of patients by combining a careful clinical history and physical examination, appropriate roentgenographic assessment and minimally invasive approaches to lesional biopsy. Such comprehensive management should provide the greatest opportunity for cure of the patient with early stage lung cancer, as well as avoid unnecessary extensive surgical interventions in patients with benign or metastatic pulmonary nodules.
References
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