I. Solitary Pulmonary Nodule

Introduction

The term “solitary pulmonary nodule” (SPN) describes a well-circumscribed, rounded, smooth edged, dense pulmonary lesion, 3 cm or less in diameter. The older term “coin lesion” has been replaced by SPN since these lesions are spherical, not flat. Many solitary pulmonary nodules are malignant. Because lung cancer is the leading cause of cancer death for both men and women in the United States, with an overall five year survival rate of only 12%-15%, the thorough evaluation and careful selection for operative removal of those SPNs that are malignant is especially important. If a malignant solitary pulmonary nodule is resected early, the prognosis is excellent, with five year survival rates as high as 70%-80%.

Etiology

Solitary pulmonary nodules are a frequent diagnostic challenge. Features associated with non-malignant etiologies include age younger than 30 years, no smoking history, no evidence of obstructive lung disease, calcification within the lesion, and no radiographic change over two years. By contrast, the incidence of lung cancer is as high as 80% in patients with SPN who are older than 50 years, have chronic obstructive pulmonary disease (COPD), a smoking history, and a non-calcified lesion which is new or has grown within a two-year interval. The overall chance of a SPN being malignant is about 40%.

Benign Lesions

A benign pulmonary nodule is usually the result of an inflammatory response to a previous granulomatous infection, tuberculosis, coccidioidomycosis, histoplasmosis or atypical mycobacteria. Those due to histoplasmosis and tuberculosis commonly calcify, but nodules due to coccidioidomycosis usually do not. Fungal granulomas are typically caused by Coccidioides immitis in the southwestern United States, Histoplasma capsulatum in the upper Mississippi region, and less commonly by cryptococcus or blastomycosis.

The most common presentation of a SPN as a benign neoplasm is a hamartoma, which can be recognized by its classic pattern of diffuse or “popcorn” calcification, when present. Other causes of benign SPNs include: anthracosilicosis, rheumatoid arthritis with fibrosing alveolitis, bronchogenic cysts or sequestration, hemangiomas, lymph node hyperplasia (Castleman’s disease), and rarely pulmonary embolism with infarction or Wegener’s granulomatosis.

A solitary pulmonary nodule in a tropical region may be a parasitic infection, most commonly a helminthic infection caused by the animal filarial parasite Dirofilaria, the intestinal ascarid, Toxocara, or the human filarial parasite, Wuchereria or Brugia. These infections are prevalent in certain temperate, tropical and subtropical regions of the world. Most cases are diagnosed after a lung resection for a solitary pulmonary nodule presumed to be malignant. Although patients with pulmonary dirofilariasis are typically asymptomatic, patients with toxocariasis or visceral larva migrans are more likely to complain of symptoms of cough, asthma, pneumonia and have persistent eosinophilia.

Malignant Lesions

The likelihood that a SPN is malignant increases with the patient’s age and cigarette smoking history. Unfortunately, only a small proportion of lung cancer patients, about 16%-18%, present with “early stage” disease. A SPN in a patient under the age of 35 has less than a 1% chance of being malignant, contrasted with up to a 60% incidence in patients age 50 years or older. In specialty referral settings, up to 90% of patients evaluated for SPN will have malignancy. Although all lung cancer cell types can present as a SPN, most malignant nodules are adenocarcinoma or squamous cell carcinoma. About 5% of small cell lung cancer present as a SPN. A SPN may also present as metastatic cancer from a known or unknown primary lesion.

X-ray Characteristics of SPN

The characteristics on chest x-rays that help to differentiate between benign and malignant nodules are outlined in Table 9-1. The most important characteristic of a benign nodule is the presence of calcification, which can be a diffuse speckled, or “popcorn,” pattern, typical of a hamartoma, or a large central nidus or concentric calcification typical of a granuloma. Occasionally, however, a malignant nodule has a small “fleck” of calcification present or it engulfs a nearby small granuloma during its growth and a metastatic osteogenic sarcoma may calcify, so the presence of a very small amount of calcification does not ensure benignity.

The second important factor distinguishing a malignant from a benign nodule is the growth rate. Since the “doubling time” of a lung cancer ranges from 15 to 450 days, the nodule that does not increase in diameter over a two year period can be considered benign. Any lesion that increases in size over a two year period of observation, or less, must be considered malignant until proven otherwise. One exception is a nodule doubling in less than 20 days, which usually suggests an acute inflammatory process.

The third important characteristic is the appearance of the nodule’s edge. Benign lesions have smooth rounded edges, whereas the incidence of neoplasm increases dramatically in lesions with irregular, spiculated borders. An increasing incidence of malignancy occurs, ranging from 20-93%, depending on the degree of border irregularity (Table 18).

Clinical circumstances may suggest a benign explanation for a “new” nodule, such as the development of a nodule during resolution of a pneumonia, pulmonary contusion, or pulmonary embolism with infarction. Other radiologic findings, such as small size, increased density, smooth borders, or vessels entering the lesion suggesting an arteriovenous fistula, increase the likelihood of a benign condition.

Diagnosis

The first step in evaluating a SPN is to try to obtain old chest x-rays for comparison. If this is not possible, and the nodule does not have a classic, calcified appearance typical of a granuloma or hamartoma, then further testing or a period of careful observation must be undertaken. A CT scan can help distinguish the pattern of calcification, and classify lesions as “indeterminate” based on the presence of stippled or eccentric calcification and medium density, or “benign” based on the presence of fat density typical of a hamartoma. The most common CT finding in early stage adenocarcinoma and squamous cell carcinoma of the lung is that of a solitary pulmonary nodule which enhances after administration of IV contrast. In small cell carcinoma, however, hilar and mediastinal adenopathy secondary to metastases is the most common CT presentation. The presence of irregular margins, associated air bronchogram, convergence of the surrounding structure, or the involvement of three or more blood vessels is more likely in malignant lesions. Because of the difficulty with noninvasive diagnosis of the SPN, new radiologic techniques are being studied, including positron emission tomography imaging (PET), which is able to distinguish benign from malignant pulmonary nodules by measuring 18-fluorodeoxyglucose (FDG), and by showing increased FDG uptake and retention in malignant cells. PET scanning is a valuable, noninvasive tool with a 95% sensitivity for identifying malignancy and a specificity of 85% or greater. However, false positive results may be obtained in lesions containing an active inflammatory process, and this diagnostic modality is not generally available.

If a period of observation is chosen, chest x-rays, and possibly serial CT scans, should be done at 3-month intervals over at least a two year period to determine if any change in the size of the nodule has occurred. An increase in the diameter of the nodule by 25% indicates a doubling of the mass volume.

When to Refer

Once the decision has been made that the patient’s SPN may represent a malignancy, a histologic diagnosis is needed. If the patient’s SPN has characteristics strongly suggesting malignancy, and there are no contraindications to surgery, refer to a thoracic surgeon. In most other circumstances refer to a pulmonologist for further workup. Diagnostic procedures may include: fiberoptic bronchoscopy aided by fluoroscopy, or CT-guided transthoracic fine needle aspiration. The yield of these procedures in the diagnosis of the small solitary pulmonary nodule (< 1.5 cm in diameter) is about 40% for fiberoptic bronchoscopy, and 50% for fine needle aspiration. The incidence of pneumothorax requiring chest tube insertion from bronchoscopic transbronchial biopsy is about 5% and from needle aspiration about 25%, depending on patient characteristics and variation of local physician technique. Thoracoscopic resection or thoracotomy is needed for diagnosis in about 20% of patients, in whom the less invasive techniques were not successful.

Medicolegal Aspects

Physicians should discuss the possibility of lung cancer presenting as a SPN in those patients who have lesions that cannot be confirmed to be benign based on their presence on old films with over 2 years of stability, or classic calcification typical of a benign lesion. Patients should play an active role in the decision to remove, evaluate with invasive procedures, or observe their SPN. The pros and cons of pulmonary resection should be discussed and a recommendation made. This should be carefully documented in the patient record, and if observation is chosen, advice for follow up given. Then, it is important for the physician to insure that follow up actually occurs.

Summary

The overall probability that a solitary pulmonary nodule is malignant is approximately 40%. Aggressive efforts are needed to establish whether the lesion is benign or malignant. This chapter gives an approach for estimating malignancy versus benignity. The evaluation of a solitary pulmonary nodule should be systematic and appropriate for the individual patient. There is an increasing frequency of malignancy occurring in lesions with irregular edges, without calcification, occurring in patients over the age of 50 years, whose lesions double within a 2 year period. The decision for operative removal versus electing a period of observation of the nodule can be made based on nodule characteristics, patient age and rate of growth of the lesion.

References

Dewan N, Shehan C, Reeb S. Likelihood of malignancy in a solitary pulmonary nodule. Chest 1997; 112: 416-422. A description of the possible role of PET scanning in the evaluation of the solitary pulmonary nodule.

Hartman T, Swensen S, Muller N. Cigarette smoking: CT and pathologic findings of associated pulmonary diseases. Radiographics 1997; 17:377-390. A description of the most common CT findings in smoking related diseases of the lung with special attention to the most common CT presentations of lung cancer.

Libby D, Henschke C, Yankelevitz D. The solitary pulmonary nodule: Update 1995. JAMA 1995; 99: 491-496. A good review of the characteristics of benign versus malignant pulmonary nodules, with an analysis of the evaluation and treatment of the SPN in patients referred to a pulmonary specialist’s office.

Lillington GA. Solitary pulmonary nodules. Postgrad Medicine 1997;101:145-150. An excellent review article summarizing the evaluation and treatment of the solitary pulmonary nodule.

Shaffer K. Radiologic evaluation in lung cancer. Chest 1997;112(Suppl): 235S-237S. A summary of the risk of a solitary nodule being malignant in the overall context of cancer with comments on the diagnosis and staging of lung cancer.

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