What are Lung Nodules? What is Done in Treatment?

Anadolu Health Center Chest Diseases Specialist Assoc. Prof. Dr. Tayfun Çalışkan provided information about lung nodules.

What is a Lung Nodule?

A lung nodule is a round or irregular white lesion (opacity) on radiological imaging that is surrounded by aerated lung tissue, with a diameter of ≤ 3 cm, and has well-defined or indistinct edges. Nodules that are in contact with the pleura (lung lining) are also included in this definition, but those associated with lymphadenopathy (enlarged lymph nodes) or pleural disease are not. Nodules smaller than 3 mm should be referred to as micronodules. Nodules typically measuring between 3-10 mm are defined as millimetric nodules.

How is a Nodule Detected in the Lung?

The diagnosis of lung nodules is primarily made through computed tomography (CT) scans of the lungs. However, nodules can also be detected using standard chest X-rays, depending on their size and location. Small nodules may not be visible on chest X-rays. Solitary (single) pulmonary nodules are incidentally found in approximately 0.1-0.2% of chest X-rays and about 13% of lung CT scans.

Is Every Lung Nodule Cancerous? What are the Other Causes?

Not every nodule is cancerous. Nearly 95% of nodules detected in the lungs are benign. Causes of benign nodules include infections (such as tuberculosis, bacterial pneumonia) and inflammatory diseases (like sarcoidosis and rheumatic diseases, as well as rare congenital conditions). The size of the nodules, the individual’s risk of cancer, and the growth rate of the nodule are key determinants. Some morphological (structural) features of the nodule can also provide insights. In terms of morphological characteristics, the presence of small size, widespread, central, laminated, or popcorn-like calcifications, as well as fat tissue density and peripheral fissural location, are considered indicators of benign lesions.

Is Follow-Up Necessary for All Detected Lung Nodules?

In the presence of a lung nodule, the main goal for doctors is to identify any suspicious nodules that would require further testing (advanced investigation) as early as possible, thereby avoiding unnecessary diagnostic or therapeutic procedures. Early diagnosis of lung cancer in cases of malignant nodules can provide a safe and definitive solution. According to recent guidelines, the nodule size threshold (diameter or volume) is used to determine the need for follow-up. Currently, risk assessment tools like the Brock University risk assessment tool used in British Thoracic Society (BTS) guidelines may be more frequently used in future guidelines. The thresholds have been increased to 5 mm or 80 mm³ for BTS guidelines and 6 mm or 100 mm³ for the Fleischner Society. Routine follow-up is not required for nodules below certain sizes (National Comprehensive Cancer Network (NCCN), <4 mm; American College of Chest Physicians (ACCP) and British Thoracic Society (BTS), <5 mm; Fleischner Society, International Early Lung Cancer Action Program (IELCAP), and Lung CT Screening Reporting and Data System (Lung-RADS), <6 mm). However, nodules that are <6 mm, located in the upper lobes, and have suspicious morphology may be monitored based on the presence of additional diseases and the patient's preferences. The follow-up decision should be made on a personal basis by your doctor.

How is Follow-Up Performed for Lung Nodules?

The size, number, structure, and growth rate of a nodule are the most commonly used determinants to assess the likelihood of malignancy and to guide nodule management according to international guidelines.

The follow-up indications outlined in the guidelines are based on the existence of a direct proportional relationship between the initial size of the nodules, their number, growth rate, and the risk of malignancy. Lung nodules can be assessed by calculating their diameter, area, or volume using manual or semi-automated/automated methods. Most pulmonary nodule guidelines include common components such as risk factor assessment, nodule size, and nodule structure. The initial and annual re-evaluation protocols in screening programs differ. Risk factors include age, smoking history, family history, previous cancer history, occupational exposures, etc.

The latest version of the Fleischner Society (Radiology Society) guidelines, published in 2017, recommends calculating the average nodule diameter between the long and short axes, regardless of the plane in which the maximum size of the nodule is displayed (axial, coronal, or sagittal). Different follow-up approaches are recommended depending on the number and structure of the nodules, whether they are solid, subsolid (partially solid), or ground glass nodules.

How Often and for How Long Should Nodules in the Lung be Followed Up?

What are Solid, Subsolid, and Ground Glass Nodules?

Lung nodules are classified into three groups based on their structure: solid, subsolid, and ground glass nodules. For solid nodules, the minimum diameter threshold requiring follow-up has been raised to 6 mm to reduce false positives, and a follow-up time interval has been established to decrease the number of examinations performed on stable nodules. However, due to their indolent nature when cancerous, longer follow-up periods are recommended for managing subsolid nodules after the initial follow-up. Current guidelines indicate that ground glass nodules with a diameter of ≥ 6 mm should be followed for 5 years with 2-year screening intervals, while partially solid nodules with a solid component of <6 mm should be evaluated annually for 5 years. Partially solid nodules with a solid component of ≥ 6 mm should be assessed for Positron Emission Tomography-Computed Tomography (PET-CT), biopsy, or resection based on other nodule characteristics (such as morphological features and growth) and clinical risk after the initial follow-up.

Is Further Investigation (such as PET-CT or Biopsy) Required for All Detected Lung Nodules?

As previously mentioned, approximately 95% of lung nodules detected are benign. These can be due to infections, benign tumors such as hamartomas, vascular structures like arteriovenous malformations, developmental bronchogenic cysts, rheumatoid arthritis-related nodules, inflammatory diseases such as sarcoidosis, or round atelectasis. However, in patients with a known history of cancer outside the lungs, there is a 25% chance that the detected lung nodules may be malignant. The most common types include breast, colon, head and neck cancers, kidney, testicular, malignant melanoma, and sarcomas.

Clinical risk scoring systems have been developed based on the characteristics of the detected nodule and the patient, which can help in making decisions regarding further investigation and follow-up. For example, in Brock University's cancer risk scoring system, a risk percentage is calculated based on factors such as age, gender, family history of cancer, presence of emphysema, nodule size, type of nodule (solid/subsolid/ground glass), location in the upper lobe, number of nodules, and whether the nodule's outer margin shows spiculated features. According to this system, a probability of <5% is considered low, 5%-65% is moderate, and >65% is high. For patients with moderate probability or high-risk patients who cannot undergo surgery, the option of biopsy should be considered. In high-probability patients or moderate-probability patients whose biopsy results are inconclusive or suspicious for malignancy, surgical intervention should be contemplated. The likelihood of false negatives with PET-CT is particularly high for nodules smaller than 8 mm; therefore, its use may be considered for nodules larger than 8 mm. As the size increases, the results become more valuable; for instance, the sensitivity for detecting cancer in nodules larger than 2 cm is reported to be 91%. If the nodule increases in size within less than 20 days or remains stable for 2 years, the likelihood of it being benign is higher. However, it should be noted that subsolid nodules, particularly of the adenocarcinoma type, may exhibit slow growth; hence, follow-up for subsolid nodules is recommended for up to 5 years. After all these evaluations, a decision for further investigation should be made.

What Should Patients with Detected Lung Nodules Do?

Patients with detected lung nodules should consult a pulmonologist. Bringing previous thoracic CT images, if available, can facilitate the comparison and evaluation alongside old images. The decision on whether to follow up on the nodule should be made by the pulmonologist based on the characteristics of the nodule and the patient.

If There is a Diagnosis of Lung Cancer in My Family, Does My Risk Increase?

Clinical factors such as advanced age, heavy smoking/current smoking history, exposure to other inhaled carcinogens (asbestos, radon, or uranium), as well as the presence of emphysema or fibrosis and a family history of lung cancer have been shown to be determinants of malignancy and increase the risk.

How Much Does Smoking Increase the Risk of Cancer in Lung Nodules?

When examining the risk factors for lung cancer, smoking ranks first. Among all lung cancer patients, it is observed that 90% are smokers. For long-term smokers, the risk of developing lung cancer is 10 to 30 times higher compared to individuals who have never smoked. In heavy smokers, the cumulative risk of lung cancer can rise to 30%, while in non-smokers, this rate is below 1%.

I Had COVID-19, and a Nodule Was Detected in My Lung. Could This Be Related?

A study evaluating various research on findings detected in the lungs after COVID-19 found that 32% of patients had a nodule or mass in the lungs. However, it is not known whether these findings are related to COVID-19. Therefore, it would be appropriate to evaluate the nodules detected in individuals who have had COVID-19 according to the recommendations of the Fleischner Society guidelines.

Doctors Previously Told Me That There Was a Spot in My Lung. Is There a Relationship with This Nodule Appearance?

There may be differences in how the physician conveys the abnormality detected in the patient's CT scan in a manner that the patient can understand. Here, it is important to clarify what is meant by "spot." Generally, sequelae of previously experienced benign conditions are thought to be expressed as spots. For instance, in a patient who has had pulmonary tuberculosis, the CT scan may show healed sequelae along with calcified nodules. Your physician may have referred to this appearance as a spot in the lungs. I recommend obtaining more detailed information from your doctor and retaining as many old test results (especially lung CT scans) as possible.

What Does Growth in a Lung Nodule Mean?

The latest BTS (British Thoracic Society) guidelines indicate that an increase of ≥2 mm in maximum diameter strongly predicts malignancy. Other guidelines have reported that an increase of 1.5 mm is also considered growth.

What Should Be Done If There Is Growth in a Lung Nodule?

If there is growth in the nodule, PET/CT and biopsy (either surgical or non-surgical methods) are recommended. In high-probability patients, although PET/CT may not be necessary as a priority, it can be beneficial for staging and assessing regions outside the lungs where biopsy may be more easily obtained.

What Procedures Are Used for Diagnostic Tissue Sampling in Lung Nodules?

Non-surgical methods such as bronchoscopy or transthoracic needle biopsy (biopsy guided by imaging from the chest wall) can be used. For large and centrally located tumors, bronchoscopic techniques (flexible bronchoscopy/endobronchial ultrasound [EBUS]) are appropriate, while transthoracic approaches are suitable for small and peripheral tumors. Additionally, navigational techniques (virtual bronchoscopy, electromagnetic navigation, radial EBUS, and robotic bronchoscopy) can also be utilized for peripheral nodules.

What Is the Role of Surgery in Lung Nodules?

Surgical removal of the nodule is the gold standard method for diagnosis and can also be curative in some cancers. In patients identified as high probability and those with intermediate probability who cannot be diagnosed through non-surgical methods, video-assisted thoracoscopic surgery (VATS) is preferred for nodule removal. Lesions that can be visualized from outside the lungs can be excised directly via VATS. However, for nodules that are not visible, they may be removed via open thoracotomy with palpation; in VATS surgery, auxiliary methods such as wire placement or staining with methylene blue may also be used prior to the procedure. Rapid pathological assessment (frozen section analysis) can identify patients with non-small cell lung carcinoma, allowing for mediastinal lymph node sampling and VATS lobectomy/segmentectomy to be performed in the same session, thus achieving diagnosis and surgical treatment simultaneously. Evaluating patients with detected nodules in the lungs and who are recommended for surgery through multidisciplinary thoracic tumor boards will be the most optimal approach.