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Authors: Samuel Copeland, MD; Ebtesam Islam, MD, PhD
Pulmonary nodules are small, generally spherical abnormalities, commonly noted incidentally on chest radiography or computed tomography1. Ground glass opacifications (GGO) are a subset of pulmonary nodules or masses with non-uniformity and less density than solid nodules. GGO are usually described as either pure ground glass or part solid (subsolid) nodules. This discussion focuses on the management of incidental GGO discovered on CT scans.
Management of GGO focuses on identifying those ground glass opacities that are or will become cancers. Serial CT imaging is the preferred modality for this purpose. Over time, most cancerous GGO will enlarge, develop solid components, or both. Serial CT scanning can identify these changes and thus GGO malignancies at an early, curable stage.
The most common cancer manifesting with ground glass opacity on CT is adenocarcinoma in situ, also known as minimally invasive adenocarcinoma, formerly known as bronchioloalveolar carcinoma (BAC). Multiple tumor types can also coexist or develop inside complex GGO, with solid or subsolid components.
The natural history of cancerous GGO such as adenocarcinoma in situ is typically a more indolent course with a lower risk of invasion, compared to solid lung cancers. In a recent study published in CHEST, 226 patients with pure GGO nodules that were enrolled in a study from 2000-2005 were reexamined in March of 2015. Tumor growth noted by CT scan was slow and invasive disease was uncommon. Nevertheless, resection rates were high2.
These features pose a challenge for physicians and patients managing GGO over time. As with management of solid nodules, the goal is to identify and cure (usually through resection) all dangerous cancers, and to avoid resection in all benign tumors. With GGO, the risks of observation with serial imaging are usually lower, but the observation epochs significantly longer, in order to achieve these goals.
Infection must also be considered as a possible etiology for GGO / subsolid nodules, moreso than with solid nodules. The microbiology of infections manifesting as GGO is beyond the scope of this discussion.
The Fleischner Society released its first major guidelines on GGO and subsolid pulmonary nodules in 2013. Since that time, new research has shed light on GGO, prompting a revision released in 2017 along with the new guidelines for solid pulmonary nodules.
The new guidelines allow for more variability based upon physician and patient discussion as well as tailoring repeat scans based upon individual patient risk. In general, GGO’s should be followed with repeat CT scans less frequently but for longer periods of time, accounting for the slow or nonexistent growth of these nodules.
The classification of GGO for purposes of follow-up is based on size of the nodule, and is not based on morphologic risk assessment as with solid nodules. Instead, clinical experience and patient factors (age, life expectancy, comorbidities, and value preferences) should inform discussion of subsequent imaging decisions.
Recommended Management of Ground Glass Opacity / Subsolid Nodules
Recommendations suggest GGO’s be categorized into less than or equal to 5 mm and greater than 5 mm with measurements not to include tenths of a millimeter (IE: 5.9 mm is a 5 mm nodule).
The following is a limited summary of the 2017 Fleischner guidelines for GGO and subsolid pulmonary nodules3.
Pure GGO Pulmonary Nodules
Nodules ≤5 mm diameter
- No routine follow up is suggested for pure GGO’s less than or equal to 5 mm (Grade 1B; strong recommendation, moderate quality of evidence).
- For suspicious pure GGO’s less than or equal to 5 mm a CT can be obtained at 2 and 4 years (No graded recommendation).
- Suspicious morphology
- High risk patient due to comorbidities
- Data based on Asian populations, malignant transformation was less than 1%. 4 5
Nodules >5 mm diameter
- A CT scan between 6 and 12 months should be obtained to confirm persistence and then a CT scan every 2 years until the 5 year mark. At that time, the physician and patient can stop following the nodule, assuming benignity and stability (Grade 1B; strong recommendation, moderate quality evidence).
Part Solid (Subsolid) Pulmonary Nodules
A general rule is that GGO cannot truly be defined as part solid until after the nodule is larger than 6 mm diameter.
≤5 mm Subsolid Nodules
- No routine follow up is recommended for part solid GGO’s less than 6mm (Grade 1C: strong recommendation, low or very low quality evidence).
- As with pure GGO’s, a suspicious nodule can be followed with a 2 and 4 year CT scan.
>5mm Subsolid Nodules
- Part solid GGO greater than 5 mm should have a CT scan between 3 and 6 months to confirm persistence. If the overall nodule size is unchanged and the solid component remains less than 6 mm, an annual CT scan should be performed for 5 years at which time the physician can stop following the nodule assuming stability (Grade 1B; strong recommendation, moderate quality evidence).
- Part solid nodules have a much higher risk of malignancy, however part solid GGO with a solid component less than 6 mm typically represent either adenocarcinoma in situ or minimally invasive adenocarcinoma with low risk of malignant transformation.
- Persistence of the part solid nodule is confirmed with a 3-6 month follow up, as many GGO and part solid GGO represent infectious or inflammatory etiologies and have a reasonable chance at resolution on relatively short term follow up imaging.
- For part solid nodules with particularly suspicious morphology, a growing solid component, or a solid component larger than 8 mm a PET/CT, biopsy, or resection is recommended (Grade 1B; strong recommendation, moderate quality evidence).
- A solid component larger than 5 mm correlates with a substantial likelihood of local invasion.
- The larger the solid component, the greater the risk of local invasion and metastasis.
Multiple Subsolid Nodules or GGO
The category of multiple subsolid nodules includes both pure GGO and part solid GGO. Multiple subsolid nodules represent a special category as they often represent infectious or inflammatory processes.
Multiple subsolid nodules ≤5 mm diameter
- In patients with multiple subsolid nodules smaller than 6 mm, an initial follow up scan is recommended at 3-6 months, with the consideration of follow up at approximately 2 and 4 years to confirm stability depending on the clinical setting (Grade 1C; strong recommendation, low or very low quality of evidence).
Multiple subsolid nodules >5 mm diameter
- In patients with multiple subsolid nodules with at least one nodule that is 6 mm or larger, management decisions should be based on the most suspicious nodule. If persistence is confirmed on CT scan after 3-6 months, then subsequent CT scans should follow the recommendations from the category of the most suspicious nodule (Grade 1C; strong recommendation, low or very low quality of evidence).
- If multiple nodules are 6 mm or larger than the one that is determined to be most suspicious should guide timing of future scans.
The Fleischner Society recommendations on radiographic management of incidentally discovered pulmonary nodules has defined the standard of care. The current guidelines put more emphasis on the physician patient relationship, allowing more flexibility in management styles pending patient preferences. In addition, the number of follow up CT scans should decrease with the cessation of routine follow up for nodules less 6 mm.
- Shen KR, Meyers BF, Larner JM, Jones DR, American COCP. Special treatment issues in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132, 290S-305S.
- Lim HJ, Ahn S, Lee KS et al. Persistent pure ground-glass opacity lung nodules ≥ 10 mm in diameter at CT scan: histopathologic comparisons and prognostic implications. Chest 2013; 144, 1291-1299.
- MacMahon H, Naidich DP, Goo JM et al. Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017. Radiology 2017; 284, 228-243.
- Kakinuma R, Muramatsu Y, Kusumoto M et al. Solitary Pure Ground-Glass Nodules 5 mm or Smaller: Frequency of Growth. Radiology 2015; 276, 873-882.
- Yankelevitz DF, Yip R, Smith JP et al. CT Screening for Lung Cancer: Nonsolid Nodules in Baseline and Annual Repeat Rounds. Radiology 2015; 277, 555-564.