Ground-glass nodules of the lung in never-smokers and smokers: clinical and genetic insights

Pulmonary ground-glass nodules (GGNs) are hazy radiological findings on computed tomography (CT). GGNs are detected more often in never-smokers. Retrospective and prospective studies have revealed that approximately 20% of pure GGNs and 40% of part-solid GGNs gradually grow or increase their solid components, whereas others remain stable for years. Most persistent or growing GGNs are lung adenocarcinomas or their preinvasive lesions. To distinguish GGNs with growth from those without growth, GGNs should be followed for at least 5 years. Lesion size and smoking history are predictors of GGN growth. Genetic analyses of resected GGNs have suggested that EGFR mutations are also predictors for growth but a subset of KRAS- or BRAF-mutated GGNs may undergo spontaneous regression because the frequencies of KRAS or BRAF mutations decrease with the advance of pathological invasiveness. Although lobectomy is the standard surgical procedure for lung cancer, limited surgery such as wedge resection or segmentectomy for lung cancers ≤2 cm with consolidation/tumor ratio ≤0.25 can be a viable alternative based on the recent clinical trial. Further genetic analyses and clinical trials can contribute to elucidation of the biological aspects of preinvasive adenocarcinoma and the development of less invasive management strategies for patients with GGNs.