Clinical Outcomes of Resected Pure Ground-Glass, Heterogeneous Ground-Glass, and Part-Solid Pulmonary Nodules

Abstract

BACKGROUND. Increased (but not definitively solid) attenuation within pure ground-glass nodules (pGGNs) may indicate invasive adenocarcinoma and the need for resection rather than surveillance. OBJECTIVE. The purpose of this study was to compare the clinical outcomes among resected pGGNs, heterogeneous ground-glass nodules (GGNs), and part-solid nodules (PSNs). METHODS. This retrospective study included 469 patients (335 female patients and 134 male patients; median age, 68 years [IQR, 62.5-73.5 years]) who, between January 2012 and December 2020, underwent resection of lung adenocarcinoma that appeared as a subsolid nodule on CT. Two radiologists, using lung windows, independently classified each nodule as a pGGN, a heterogeneous GGN, or a PSN, resolving discrepancies through discussion. A heterogeneous GGN was defined as a GGN with internal increased attenuation not quite as dense as that of pulmonary vessels, and a PSN was defined as having an internal solid component with the same attenuation as that of the pulmonary vessels. Outcomes included pathologic diagnosis of invasive adenocarcinoma, 5-year recurrence rates (locoregional or distant), and recurrence-free survival (RFS) and overall survival (OS) over 7 years, as analyzed by Kaplan-Meier and Cox proportional hazards regression analyses, with censoring of patients with incomplete follow-up. RESULTS. Interobserver agreement for nodule type, expressed as a kappa coefficient, was 0.69. Using consensus assessments, 59 nodules were pGGNs, 109 were heterogeneous GGNs, and 301 were PSNs. The frequency of invasive adenocarcinoma was 39.0% in pGGNs, 67.9% in heterogeneous GGNs, and 75.7% in PSNs (for pGGNs vs heterogeneous GGNs, p < .001; for pGGNs vs PSNs, p < .001; and for heterogeneous GGNs vs PSNs, p = .28). The 5-year recurrence rate was 0.0% in patients with pGGNs, 6.3% in those with heterogeneous GGNs, and 10.8% in those with PSNs (for pGGNs vs heterogeneous GGNs, p = .06; for pGGNs vs PSNs, p = .02; and for heterogeneous GGNs vs PSNs, p = .18). At 7 years, RFS was 97.7% in patients with pGGNs, 82.0% in those with heterogeneous GGNs, and 79.4% in those with PSNs (for pGGNs vs heterogeneous GGNs, p = .02; for pGGNs vs PSNs, p = .006; and for heterogeneous GGNs vs PSNs, p = .40); OS was 98.0% in patients with pGGNs, 84.6% in those with heterogeneous GGNs, and 82.9% in those with PSNs (for pGGNs vs heterogeneous GGNs, p = .04; for pGGNs vs PSNs, p = .01; and for heterogeneous GGNs vs PSNs, p = .50). CONCLUSION. Resected pGGNs had excellent clinical outcomes. Heterogeneous GGNs had relatively worse outcomes, more closely resembling outcomes for PSNs. CLINICAL IMPACT. The findings support surveillance for truly homogeneous pGGNs versus resection for GGNs showing internal increased attenuation even if not having a true solid component.

Keywords: ground-glass nodule; heterogeneous ground-glass nodule; part-solid nodule; pure ground-glass nodule.

Figure 1.

Flowchart showing patient selection process.

Figure 2.

Characterization of subsolid nodules on axial chest CT images in different patients. (A) 82-year-old woman. Pure ground glass nodule (pGGN) is present in right upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. No recurrence occurred at follow-up of 45 months. (B) 73-year-old woman. Heterogeneous ground glass nodule is present in right lower lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. At 42 months, patient presented with thoracic lymphadenopathy, consistent with regional recurrence (not shown). (C) 75-year-old man. Heterogeneous GGN is present in left upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. At 39 months, surveillance FDG PET/CT showed FDG-avid soft tissue thickening along surgical margin (not shown), consistent with local recurrence. (D) 48-year-old woman. Part-solid nodule (PSN) is present in left upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. Solid component within nodule (white arrows) is as dense as pulmonary vessels (blue arrows). At 18 months, patient presented with progressive headache and was subsequently diagnosed with leptomeningeal carcinomatosis, consistent with distant recurrence. Heterogeneous GGNs in (B) and (C) shows internal density greater than that of pGGN in (A), but that is not quite as dense as pulmonary vessels (blue arrow, B and C). PSN in (D) shows density similar to that of pulmonary vessel (blue arrow).

Figure 2.

Characterization of subsolid nodules on axial chest CT images in different patients. (A) 82-year-old woman. Pure ground glass nodule (pGGN) is present in right upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. No recurrence occurred at follow-up of 45 months. (B) 73-year-old woman. Heterogeneous ground glass nodule is present in right lower lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. At 42 months, patient presented with thoracic lymphadenopathy, consistent with regional recurrence (not shown). (C) 75-year-old man. Heterogeneous GGN is present in left upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. At 39 months, surveillance FDG PET/CT showed FDG-avid soft tissue thickening along surgical margin (not shown), consistent with local recurrence. (D) 48-year-old woman. Part-solid nodule (PSN) is present in left upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. Solid component within nodule (white arrows) is as dense as pulmonary vessels (blue arrows). At 18 months, patient presented with progressive headache and was subsequently diagnosed with leptomeningeal carcinomatosis, consistent with distant recurrence. Heterogeneous GGNs in (B) and (C) shows internal density greater than that of pGGN in (A), but that is not quite as dense as pulmonary vessels (blue arrow, B and C). PSN in (D) shows density similar to that of pulmonary vessel (blue arrow).

Figure 2.

Characterization of subsolid nodules on axial chest CT images in different patients. (A) 82-year-old woman. Pure ground glass nodule (pGGN) is present in right upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. No recurrence occurred at follow-up of 45 months. (B) 73-year-old woman. Heterogeneous ground glass nodule is present in right lower lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. At 42 months, patient presented with thoracic lymphadenopathy, consistent with regional recurrence (not shown). (C) 75-year-old man. Heterogeneous GGN is present in left upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. At 39 months, surveillance FDG PET/CT showed FDG-avid soft tissue thickening along surgical margin (not shown), consistent with local recurrence. (D) 48-year-old woman. Part-solid nodule (PSN) is present in left upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. Solid component within nodule (white arrows) is as dense as pulmonary vessels (blue arrows). At 18 months, patient presented with progressive headache and was subsequently diagnosed with leptomeningeal carcinomatosis, consistent with distant recurrence. Heterogeneous GGNs in (B) and (C) shows internal density greater than that of pGGN in (A), but that is not quite as dense as pulmonary vessels (blue arrow, B and C). PSN in (D) shows density similar to that of pulmonary vessel (blue arrow).

Figure 2.

Characterization of subsolid nodules on axial chest CT images in different patients. (A) 82-year-old woman. Pure ground glass nodule (pGGN) is present in right upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. No recurrence occurred at follow-up of 45 months. (B) 73-year-old woman. Heterogeneous ground glass nodule is present in right lower lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. At 42 months, patient presented with thoracic lymphadenopathy, consistent with regional recurrence (not shown). (C) 75-year-old man. Heterogeneous GGN is present in left upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. At 39 months, surveillance FDG PET/CT showed FDG-avid soft tissue thickening along surgical margin (not shown), consistent with local recurrence. (D) 48-year-old woman. Part-solid nodule (PSN) is present in left upper lobe. Resection yielded pathologic diagnosis of invasive adenocarcinoma. Solid component within nodule (white arrows) is as dense as pulmonary vessels (blue arrows). At 18 months, patient presented with progressive headache and was subsequently diagnosed with leptomeningeal carcinomatosis, consistent with distant recurrence. Heterogeneous GGNs in (B) and (C) shows internal density greater than that of pGGN in (A), but that is not quite as dense as pulmonary vessels (blue arrow, B and C). PSN in (D) shows density similar to that of pulmonary vessel (blue arrow).

Figure 3.

Kaplan-Meier analysis of recurrence-free survival (RFS) through 7 years of follow-up after resection of subsolid nodules. pGGN = pure ground glass nodule; hGGN = heterogeneous ground glass nodule; PSN = part-solid nodule.

Figure 4.

Kaplan-Meier analysis of overall survival (OS) through 7 years of follow-up after resection of subsolid nodules. pGGN = pure ground glass nodule; hGGN = heterogeneous ground glass nodule; PSN = part-solid nodule.

Figure 5.

Cumulative probability of recurrence through 7 years of follow-up after resection of subsolid nodules. pGGN = pure ground glass nodule; hGGN = heterogeneous ground glass nodule; PSN = part-solid nodule.