Pulmonary Nodules

A thorough workup in primary care can help determine risk.

Solitary pulmonary nodules are a frequently encountered clinical finding in outpatient and inpatient settings, and it can be daunting for many clinicians.1 This finding is seen in approximately 1 in 500 chest x-rays.2 With increasing use of chest computed tomography (CT) and chest CT angiography (CTA) for cardiac evaluation and diagnosing pulmonary embolism, the number of identified pulmonary nodules is on the rise.3,4

A solitary pulmonary nodule (SPN) is a focal, round or oval area of increased opacity within the lung parenchyma that is less than 3 cm.3 If the area is greater than 3 cm, it is referred to as a lung mass.2

This article focuses on malignant pulmonary nodules. Diagnosis of these lesions is of extreme importance because early detection of lung cancers improves patient outcomes. Lung carcinoma is the No. 1 cause of cancer-related deaths, and 5-year survival rates are as high as 85% when treatment begins in stage I of the disease.3,5

Nodule Characteristics

After an SPN has been identified, the first step is to obtain previous films to determine stability of the lesion.However, this may be the patient’s first chest x-ray, or prior imaging studies may not be accessible. In such cases, a chest CT can help differentiate between benign and malignant etiologies.6 Radiographic features that provide clues to the diagnosis include the following:

  • Nodule size
  • Presence of calcifications
  • Nodule density
  • Rate of growth

A benign etiology is more common in lesions that are smaller than 2 cm, have diffuse, uniform calcification or “popcorn” calcification, have increased density (i.e., unable to visualize normal parenchymal structures) and/or have remained unchanged in size. Larger lesions with a spiculated appearance that have increased in size are more likely to be malignant.2,6

Differential Diagnoses

Benign Findings. Commonly, an SPN is evidence of an old infection known as a granuloma. Mycobacterial infections, both tuberculous and non-tuberculous, should be included in the differential diagnosis. Infection by the fungus Histoplasma capsulatum is frequently encountered in the southeastern United States and is associated with bird fecal matter, especially in areas near chicken coops. Approximately 80% of people living in this region have evidence of exposure with pulmonary granulomas or fibrosis.6Many patients are asymptomatic throughout the course of this infection.7

Another common fungal infection is Coccidioidomycosis or “San Joaquin Valley Fever,” which is endemic to the southwestern United States and parts of Central and South America. Causative agents includeCoccidioides immitis and Coccidioides posadasii. It can present as systemic illness or lower respiratory symptoms with pneumonia and respiratory failure.8 Other fungal infections can be caused by Blastomyces dermatitidis, Aspergillus species and Cryptococcus species.7 Medications in the triazole class of antifungals (e.g. fluconazole [Diflucan], itraconazole [Sporanox] and ketoconazole) are effective against the aforementioned fungal infections.9 Infection with the dog heartworm Dirofilaria immitis can manifest as granulomatous disease.1 This finding is rare and the only effective treatment of D immitis is surgical excision.10

Pulmonary hamartomas are benign tumors found in the lung. Areas of fat within the nodule can point to the diagnosis of a hamartoma. Lipomas and fibromas are also seen within the lung parenchyma.6

Primary lung cancer causes more deaths than breast, colon and prostate cancers combined, so prompt diagnosis is crucial to arrange appropriate treatment.5 Diagnosing lung cancer at an early stage gives the patient the best opportunity to receive curative treatment.11 The lungs are also a common site for metastasis of malignant melanoma, sarcomas and other primary cancers including breast, colon, kidney and testicle. Carcinoid tumors may be present in peripheral lung parenchyma.6,11

Risk Factors

Knowing your patient and his or her risk factors can provide clues to the diagnosis. Risk factors associated with an increased likelihood of malignancy are as follows: growing nodule size, increasing patient age, smoking history, family history of lung carcinoma, history of other malignancies, or chemical or biological exposure history (e.g., asbestos, fumes, toxins). Of course, malignancy cannot be excluded in young patients if other risk factors exist.2,6

Some patients, upon further questioning, may express signs and symptoms that increase the suspicion of lung carcinoma. Patients can have vague and nonspecific symptoms such as fatigue, weight loss, swollen lymph nodes, anorexia and generalized weakness; other more specific symptoms include chest discomfort, cough with or without hemoptysis, dyspnea or hoarseness.12

Diagnostic Imaging

Chest CT is the next best step in further evaluation of an SPN.2,13 While chest x-rays are cost-effective for routine examinations and initial testing for many pulmonary and cardiac conditions,14 CT scans can provide more detailed imaging to distinguish specific features of the nodule. A CT can more accurately identify smaller nodules and can detect changes as small as 0.3 mm. In comparison, radiographic changes on a standard chest x-ray must be 3.0 mm to 5.0 mm.

Despite the increased cost of computed tomography, it is being used more often for routine surveillance of pulmonary nodules.2,5 No standard protocols to use CT scans for lung cancer screening exist.5 A chest CT may also reveal multiple nodules, not seen previously on the chest x-ray, and this information may alter the differential diagnosis.3

Referral to a pulmonologist or thoracic surgeon is indicated at this point. Based on the CT scan findings and the patient’s personal and family history, watchful waiting may be appropriate. Many specialists use the Fleischner Society guidelines for management of these nodules. The Fleischner Society Guidelines (http://www.med.umich.edu/rad/res/Fleischner-nodule.htm), developed to provide guidance for followup of small nodules, do not apply to patients who are younger than 35, have known or suspected carcinoma outside the lungs, or who have unexplained fever.6,15

The pulmonologist may also decide to obtain a positron emission tomography (PET) scan if the CT raises suspicion for malignancy. PET imaging uses a radioactively tagged glucose molecule, fluorine-18-labeled fluoro-2-deoxyglucose (FDG), to determine metabolic activity of various tissues. Lesions with higher uptake are more commonly malignant, whereas lesions with low uptake are likely benign. Uptake of FDG is noted with a standardized uptake value (SUV). Generally, an SUV lower than 2.0 is considered benign. However, benign conditions can also cause an increased SUV. For example, inflammatory and infectious processes such as histoplasmosis, sarcoidosis, Wegener’s granulomatosis and pneumonia can cause a high SUV.2,3 FDG-PET scans have a limited value for nodules less than 1 cm in size.5 FDG-PET scans are relatively expensive and thus should be reserved for patients in whom the CT strongly suggests malignancy.2

Diagnostic Testing

Obtaining a sample of tissue from the nodule can provide an exact diagnosis. Several methods to obtain tissue for pathology evaluation exist, including bronchoscopy with lavage or washings of the airway to obtain cells. Advances in bronchoscopy include endobronchial ultrasound (EBUS), which allows visualization of lesions for biopsy through the bronchial tissue, and electromagnetic navigational bronchoscopy (ENB), which uses a special probe in the flexible bronchoscope that guides the catheter directly to the lesion. Electromagnetic navigational bronchoscopy is especially useful for lesions that cannot be seen with a regular bronchoscope. However, both EBUS and ENB are operator dependent and are not available at all institutions.6

Lung biopsy, either with fine-needle aspiration or core biopsy, is the diagnostic tool of choice for definitive diagnosis of an SPN. CT is used for guidance, and both are relatively safe procedures. The most common complication is a pneumothorax that requires a thoracostomy tube.11 Fine-needle aspiration (FNA) samples the nodule for cytology. It does not provide a core piece of tissue; this is obtained through a core biopsy.6 Relative contraindications include bleeding disorders, severe bullous emphysema and contralateral pneumonectomy.4 Diagnostic yields are higher with core biopies, larger nodules (greater than 1.5 cm) and a more skillful interventionist.4,6,11

Treatment of Malignancy

For an SPN nodule that is diagnosed as a malignancy, several treatment options exist. Surgical resection with a complete lobectomy is the standard of care.16 This is accomplished through minimally invasive video-assisted thoracoscopic surgery or a muscle-sparing thoracotomy incision.16,17 Minimally invasive techniques offer less pain and quicker recovery. They often are better tolerated in elderly patients. Robotic surgery is also emerging as an option for thoracic surgery.17

Some patients cannot tolerate anatomic resection of an entire lobe; thus a wedge resection of the nodule is another option.16 Because the population is living longer, patients are presenting with comorbid conditions that hinder surgery, including poor cardiopulmonary status. For these patients, noninvasive procedures are better tolerated. Conventional fractionated radiotherapy is given in small doses over several sessions.18

One of the newer treatments is radiofrequency ablation, which uses electrodes placed into the nodule or mass under CT guidance. Electrical current is delivered, causing irreversible tissue destruction and tumor necrosis.16 Stereotactic body radiotherapy (SBRT) is safe for patients with severely compromised lung function, emphysema or chronic obstructive pulmonary disease. SBRT uses high doses of radiation in large amounts over a short period of time. A special body frame is used to minimize movement, thus more specifically targeting abnormal tissue and sparing normal lung parenchyma.18

Systematic Examination Needed

Incidental pulmonary nodules are a common radiologic finding that can be intimidating. However, PAs and NPs can systematically examine the patient and consider his or her risk factors to help determine if a malignancy is possible. Because the structure of healthcare is ever-changing, NPs and PAs are often seeing a patient more often than his or her primary care physician. Referral to a specialist such as a pulmonologist or thoracic surgeon can assist in the initiation of testing and interventions that can improve overall outcomes.

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