What are ground glass opacities?

Ground Glass Opacities: Definition and Clinical Significance

Ground glass opacity (GGO) is a radiographic finding on chest CT characterized by hazy increased lung density where bronchial and vascular margins remain visible, distinguishing it from consolidation where these structures become obscured. 1

Radiographic Definition

GGO appears as a diffuse homogeneous increase in lung density on high-resolution CT (HRCT), with persistent visibility of vessels and bronchial walls. 1, 2 This is the key distinguishing feature—if vascular structures are obscured, the term "consolidation" should be used instead. 2, 3

Pathophysiologic Basis

GGO results from several underlying processes at the histopathologic level: 3, 4

• Partial filling of alveolar spaces with fluid, cells, or other material 3, 4
• Thickening of alveolar walls or septal interstitium from inflammation or fibrosis 3, 4
• Increased capillary blood volume in the pulmonary vasculature 3
• Combinations of the above processes occurring simultaneously 4

Clinical Significance and Interpretation

When GGO occurs with reticular lines and traction bronchiectasis/bronchiolectasis, it indicates lung fibrosis. 1 Conversely, isolated GGO without fibrotic features typically represents inflammatory cells in the alveolar septum or lumen (alveolitis). 1

The extent of GGO on CT correlates with physiologic impairment and can predict response to treatment. 1 In fibrotic processes, GGO may progress to reticular opacity or honeycombing on follow-up imaging, while in inflammatory conditions like desquamative interstitial pneumonitis, areas of GGO may regress with treatment. 1

Common Causes by Category

Interstitial Lung Diseases

• Nonspecific interstitial pneumonia (NSIP) frequently presents with GGOs without basal or peripheral predominance 5, 1
• Desquamative interstitial pneumonitis (DIP) typically shows extensive GGOs 5, 1
• Idiopathic pulmonary fibrosis (IPF) may show GGOs, though extensive ground glass opacity (>30% of lung involvement) should prompt consideration of alternative diagnoses 5, 1
• Respiratory bronchiolitis-interstitial lung disease demonstrates GGOs often with centrilobular nodules 5

Inflammatory and Infectious Patterns

Various interstitial pneumonia patterns can present as GGOs, including organizing pneumonia (OP), diffuse alveolar damage (DAD), hypersensitivity pneumonitis (HP), and pulmonary eosinophilia. 6, 5 The specific pattern helps narrow the differential:

• Organizing pneumonia shows patchy consolidation or GGO in predominantly peripheral or peribronchovascular distribution 6, 7
• Hypersensitivity pneumonitis demonstrates small, poorly defined centrilobular nodules with widespread GGO 6, 5
• Diffuse alveolar damage presents with extensive bilateral GGO and dependent consolidation with traction bronchiectasis 6

Drug-Related and Radiation Causes

Drug-related pneumonitis from molecular targeting agents (EGFR-TKIs, mTOR inhibitors) and immune checkpoint inhibitors commonly presents with GGO patterns. 6, 5 Radiation pneumonitis typically shows GGOs within the radiation portal, appearing 3-12 weeks after exposure. 5

Other Important Causes

• Pulmonary edema causes expansion of connective tissue space around airways and vessels, presenting with hazy opacities and Kerley lines 5
• Alveolar hemorrhage presents with bilateral patchy GGOs in middle and lower lung zones 5
• COVID-19 pneumonia characteristically shows multiple, patchy, sub-segmental or segmental ground-glass density shadows in both lungs, often with "paving stone-like" changes from interlobular septal thickening 6

Diagnostic Approach: Key Distinguishing Features

Distribution Pattern Analysis

Evaluate whether GGO is diffuse, patchy, peripheral, basal, or peribronchovascular—this significantly narrows the differential. 5, 7

• Peribronchovascular distribution suggests organizing pneumonia, hypersensitivity pneumonitis, or drug-related pneumonitis 7
• Subpleural distribution is characteristic of COVID-19 pneumonia and organizing pneumonia 6
• Centrilobular GGO with septal lines and mediastinal adenopathy has 100% specificity for pulmonary veno-occlusive disease in patients with pulmonary hypertension 7

Associated Imaging Findings

Look for specific accompanying features that provide diagnostic clues: 5, 1

• "Three-density pattern" (hypoattenuating, normal, and hyperattenuating lobules in close proximity) is highly specific for fibrotic hypersensitivity pneumonitis 5, 1
• "Reversed halo sign" (GGO surrounded by a ring of consolidation) suggests organizing pneumonia or fungal infection 7, 1
• "Paving stone-like" appearance (GGO with interlobular septal thickening) is characteristic of COVID-19 pneumonia 6
• Reticular opacities, honeycombing, and traction bronchiectasis indicate fibrotic disease 5, 1

Critical Clinical Correlation

Always correlate imaging with clinical history: 4

• Recent drug exposure (especially targeted cancer therapies or immune checkpoint inhibitors) 6, 5
• Radiation therapy history (look for GGO within radiation portal) 5
• Chronicity of symptoms (acute vs. chronic presentation) 4
• Immune status (immunocompromised patients have different differential) 4

Common Pitfalls to Avoid

Do not confuse GGO with mosaic attenuation from small airway disease or vascular abnormalities—evaluate vessel caliber and perform expiratory scans to assess for air trapping. 3 Physiological processes like poor ventilation of dependent lung areas can also mimic GGO. 8

Extensive GGO (>30% of lung involvement) in a patient with suspected IPF should prompt reconsideration of the diagnosis, as this is atypical for IPF and suggests alternative diagnoses like NSIP or hypersensitivity pneumonitis. 5, 1