What is the differential diagnosis for a cavitary lesion in the lung?

Differential Diagnosis of Cavitary Lung Lesions

The differential diagnosis for cavitary lung lesions is broad and includes infectious causes (tuberculosis, non-tuberculous mycobacteria, fungal infections, bacterial pneumonia), malignancy (primary lung cancer, metastases), and autoimmune/inflammatory conditions (granulomatosis with polyangiitis, rheumatoid nodules), with the specific diagnosis guided by cavity characteristics, patient demographics, and clinical context. 1

Infectious Etiologies

Mycobacterial Infections

• Tuberculosis and non-tuberculous mycobacteria (NTM) are the predominant infectious causes of cavitary disease, particularly in upper lobe locations 1
• NTM characteristically presents with nodular/bronchiectatic patterns that progress to cavitation over months to years 1
• Mycobacterial infection is the usual differential diagnosis for chronic pulmonary aspergillosis and may precede, follow, or occur simultaneously with fungal infection 2
• Cavities are more common in tuberculosis during earlier stages of HIV disease when cellular immunity is relatively preserved 3

Fungal Infections

• Aspergillus species cause cavitary lesions through three distinct mechanisms: aspergillomas forming within pre-existing cavities, chronic cavitary pulmonary aspergillosis (CCPA) creating new expanding cavities, and subacute invasive aspergillosis in immunocompromised patients 1
• CCPA develops most commonly in pre-existing cavities from prior TB, NTM infection, COPD, or treated lung cancer 1
• The hallmark features of CCPA include new and/or expanding cavities of variable wall thickness with or without intracavitary fungal ball formation, often with pleural thickening and marked parenchymal destruction 1
• Aspergillomas present as upper-lobe, solid, round or oval intracavitary masses with the characteristic "air-crescent" sign that is mobile on prone positioning 1
• Chronic cavitary histoplasmosis, paracoccidioidomycosis, and coccidioidomycosis present similarly to CCPA depending on geographical location and travel history 2
• Invasive pulmonary aspergillosis frequently produces cavitation, particularly in immunocompromised patients 3

Bacterial Infections

• Pseudomonas aeruginosa causes cavitation in 4-15% of severe pneumonia cases and requires specific antimicrobial coverage 1
• Lung abscesses from septic emboli often involve mixed anaerobic flora and require cultures specifically for anaerobes 1
• Bacterial pneumonia complicated by cavitation is especially common with Pseudomonas aeruginosa, Nocardia asteroides, and Rhodococcus equi 3
• Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, and Haemophilus influenzae are common organisms causing cavitary lesions 4

Malignant Causes

• Malignancy is a leading cause of cavitary lesions in adults, particularly in patients with thick cavity walls, older age, smoking history, and hemoptysis 1, 5
• Necrotic lung carcinoma can mimic aspergilloma radiographically 2
• Multiple lesions of varying size are most likely malignant, particularly in patients with known primary tumors 1
• Metastases should be considered in the differential, especially with multiple cavitary nodules 1
• Cavitary lesions from pulmonary Kaposi's sarcoma and non-Hodgkin's lymphoma have been reported in HIV-infected patients 3

Autoimmune and Inflammatory Causes

• Granulomatosis with polyangiitis (Wegener's granulomatosis) causes cavitary nodules as part of systemic vasculitis 1
• Rheumatoid nodules can cavitate and may be pure rheumatoid nodules or contain Aspergillus superinfection 1
• Other granulomatous diseases, including sarcoidosis (particularly fibrocystic sarcoidosis), predispose to cavity formation 1

Pre-existing Structural Lung Disease

• COPD, prior pneumothorax, bronchiectasis, and ankylosing spondylitis create structural abnormalities that predispose to secondary infection and cavitation 1
• Pneumoconiosis and progressive massive fibrosis in silicosis provide substrate for cavity development 1

Critical Diagnostic Clues Based on Imaging Characteristics

Cavity Wall Characteristics

• Thick-walled cavities with irregular margins suggest malignancy, while thin-walled cavities with air-fluid levels suggest infection 1
• Findings suggestive of malignancy include thick walls, irregular margins, and associated mass lesions 6
• Findings suggestive of infection include air-fluid levels, surrounding consolidation, and multiple cavities 6

Location and Distribution

• Upper lobe predominance suggests tuberculosis, NTM, or aspergillosis 1
• Multiple cavities with surrounding consolidation suggest bacterial infection or septic emboli 1

Temporal Considerations

• Chronic cavitary lesions present for >3 months require evaluation for chronic pulmonary aspergillosis, especially with positive Aspergillus serology 1, 6

Important Clinical Pitfalls

• Cavitating lesions are usually caused by tumors or abscesses, and the clinical picture often helps distinguish between these diagnoses 5, 6
• Patients with dual infection (e.g., CMV and Pneumocystis jiroveci) may have more severe disease and worse outcomes 2
• The presence of a fungal ball within a cavity can be identified on CT imaging 5
• Necrotic lung carcinoma can mimic infectious causes like aspergilloma, requiring tissue diagnosis for definitive differentiation 2