A lung nodule is a small growth in the lung tissue, typically measuring less than three centimeters in diameter. These common findings are frequently discovered incidentally during chest imaging, such as a CT scan, performed for other reasons. The primary concern is determining whether the nodule is benign (non-cancerous) or malignant (cancer). Positron Emission Tomography (PET) scanning is an important diagnostic tool that helps differentiate between these possibilities based on the nodule’s metabolic activity.
Defining Lung Nodules and Their Prevalence
A pulmonary nodule is defined as a discrete, well-defined spot on the lung, completely surrounded by lung tissue. Lesions exceeding three centimeters are classified as masses and are considered highly suspicious for malignancy. The vast majority of these nodules—estimated to be around 95%—are benign, often representing scars from previous infections or inflammation.
Benign nodules commonly result from infectious granulomas, which are clusters of immune cells that have walled off an infection. Conditions like fungal infections or tuberculosis are frequent causes of these benign growths. Noninfectious causes, such as inflammatory diseases like rheumatoid arthritis or sarcoidosis, can also lead to nodule formation.
While most are harmless, a small percentage are malignant, meaning they are early-stage lung cancers. Features such as irregular margins, a larger size, or a rapid growth rate increase the probability that a nodule is cancerous. The challenge lies in distinguishing the minority of malignant nodules from the large number of benign ones without resorting to invasive procedures.
The Mechanism of the PET Scan and FDG
The PET scan provides a unique window into the body’s metabolic activity, rather than just its structure. This capability is achieved through the use of a specialized radioactive tracer called Fluorodeoxyglucose (FDG). FDG is a glucose analog that mimics simple sugar, which is the primary fuel source for most cells.
Once injected into the bloodstream, the FDG travels throughout the body and is taken up by cells actively consuming glucose. Cancer cells are highly metabolically active due to their rapid, uncontrolled growth and often display a preference for glucose consumption. They typically have an increased number of glucose transporters on their surface, allowing them to rapidly absorb the FDG tracer.
After the cell takes in the FDG, an enzyme called hexokinase phosphorylates it. Unlike normal glucose, the FDG is unable to be fully metabolized and becomes trapped inside the cell. The radioactive fluorine atom within the trapped FDG then decays, emitting positrons that are detected by the PET scanner. Areas of high glucose metabolism, such as a growing tumor, accumulate more of the tracer and “light up” brightly on the resulting image.
Interpreting the Results: The SUV Score
While a visual assessment provides initial information, determining if a nodule is benign or malignant on a PET scan is primarily quantitative. This measure is called the Standardized Uptake Value (SUV). The SUV is calculated based on the radiotracer concentration in the tissue, and the maximum SUV value (SUVmax) is widely used to characterize the lesion’s metabolic rate.
Generally, a low SUV score suggests that a lung nodule is benign, as non-cancerous tissue is not as metabolically active as malignant tissue. Physicians often use an established threshold of 2.5 as a cutoff value. A nodule with an SUVmax below 2.5 is considered more likely to be benign, while a score above this value strongly suggests malignancy.
This threshold is not absolute. Some low-grade cancers, such as certain types of adenocarcinoma or carcinoid tumors, may exhibit low SUV scores, leading to a false-negative result. Conversely, certain benign conditions can cause a high SUV score, resulting in a false-positive finding. Therefore, the SUV score is always considered alongside the nodule’s size, shape, growth rate, and the patient’s overall clinical history.
Causes of False Positives
A benign lung nodule can “light up” brightly on a PET scan, leading to a false-positive result, because high metabolic activity is not exclusive to cancer cells. The FDG tracer is taken up by any cell type with an increased need for glucose, including rapidly proliferating immune cells. When the body is fighting an infection or dealing with active inflammation, immune cells rush to the site and become metabolically hyperactive.
Several common benign conditions in the lungs can cause this intense FDG uptake, making them mimic cancer. These include active infections such as acute pneumonia, abscesses, and chronic fungal infections. Granulomatous diseases, like sarcoidosis or active tuberculosis, are also well-known causes of false positives because the collections of immune cells consume large amounts of glucose.
In regions where fungal diseases are endemic, the rate of false-positive PET scans due to these benign causes can be significantly higher. When a nodule displays a high SUV score, a doctor must carefully consider the patient’s symptoms and history, such as recent illness or travel, to correctly interpret the PET scan results. Integrating the functional information from the PET scan with the structural details from a CT scan helps physicians distinguish between a malignant tumor and a benign inflammatory process.