In this review, we have updated recent data on GGNs in terms of smoking and genetic alterations to gain insights into the biological features of lung cancer progression and to suggest clinical management strategies for GGNs.Īlthough GGNs often remain stable without growth for years, about 20% of pure GGNs and 40% of part-solid GGNs gradually grew or increased their solid components in our recent review summarizing four reports ( 3). Thus, GGN can be regarded as one of the features of lung cancer in never-smokers. Although there is some inconsistency regarding the incidence of smoking status, 8 of 9 articles reported that GGNs are detected more often in never-smokers. In total, approximately 60% of GGNs are found in never-smokers. We collected recent reports analyzing more than 100 GGNs with information on smoking history ( 7- 15) ( Table 1). Some GGNs exhibit gradual growth, but others remain unchanged for years. Typically, AAH and AIS present as pure GGNs on CT, whereas minimally invasive adenocarcinoma (MIA) and lepidic invasive adenocarcinoma present as part-solid GGNs. Solid components of GGN on CT often contain pathologically invasive parts when analyzed under a microscope. Empirically, C/T ratio ≤0.5 has been suggested as a benchmark for pathological invasiveness because the incidence of lymph node metastasis in ≤3 cm GGNs with C/T ratio >0.5 ranges from 21% to 26% ( 4- 6). The longest diameter of consolidation/longest diameter of tumor ratio (C/T ratio) is commonly used to evaluate the proportion of ground-glass components ( Figure 1B). The proportion of solid components of GGNs is closely related to pathological invasive lesions. We previously reviewed the pathological features and natural history of the GGN ( 3). Representative computed tomography images of pure and part-solid GGN and the definition of the consolidation/tumor (C/T) ratio. 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. 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. 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. Lesion size and smoking history are predictors of GGN growth. To distinguish GGNs with growth from those without growth, GGNs should be followed for at least 5 years. Most persistent or growing GGNs are lung adenocarcinomas or their preinvasive lesions. 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. GGNs are detected more often in never-smokers. Pulmonary ground-glass nodules (GGNs) are hazy radiological findings on computed tomography (CT).
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