Causes of Pulmonary Nodules
Malignant Causes
Lung cancer represents the most critical malignant cause of pulmonary nodules, with up to 30-40% of solitary pulmonary nodules being malignant. 1, 2
Primary lung cancer is the most important malignant etiology, particularly in patients with risk factors including advanced age, current or former smoking (odds ratio 2.2-7.9), family history of lung cancer, and hemoptysis 1
Metastatic disease from extrapulmonary cancers can present as pulmonary nodules, with breast cancer being a notable example where metastases must be differentiated from other concurrent lung pathology 3
Lymphoma rarely presents as multiple tracheobronchial nodules 4
Infectious Causes
Infectious etiologies are a major cause of false-positive findings on PET scans and must be considered in the differential diagnosis of pulmonary nodules. 5
Tuberculosis (TB) is a significant infectious cause, presenting as granulomas that can appear as solitary or multiple nodules, and may show increased metabolic activity on PET scan mimicking malignancy 5, 3, 4
Endemic mycoses (histoplasmosis, coccidioidomycosis, blastomycosis) commonly cause pulmonary nodules, with coccidioidomycosis notably causing nodules that may have increased metabolic activity on PET scan even without clinical symptoms of active infection 5
Fungal infections can present as multiple tracheobronchial nodules 4
Inflammatory and Granulomatous Causes
Sarcoidosis causes pulmonary nodules and can produce false-positive PET scan results due to active inflammation 5, 4
Rheumatoid nodules in patients with rheumatoid arthritis can present as pulmonary nodules with increased FDG uptake 5
Granulomas of unknown etiology are frequently identified on biopsy of multiple tracheobronchial nodules 4
Chronic inflammation accounts for a significant proportion of nodules found on bronchoscopy 4
Benign Neoplastic Causes
- Hamartomas are benign tumors characterized by the presence of intranodular fat, diffuse or "popcorn" calcification, and combination of round shape with smooth margins 1
Other Benign Causes
Tracheobronchopathia osteochondroplastica presents as multiple tracheobronchial nodules (21.8% of cases in one series) 4
Pulmonary lymph nodes, fibrosis, and other inflammatory lesions represent common benign etiologies 6
Rare Causes
- Familial hemophagocytic lymphohistiocytosis can rarely present with recurrent pulmonary nodules as the primary symptom, though this is often not considered in the differential diagnosis 6
Key Diagnostic Considerations
Concomitant pathology is possible—patients may have multiple distinct diseases simultaneously, such as both tuberculosis and metastatic cancer presenting as separate nodules 3
PET scan limitations must be recognized: false-positives occur with infections and inflammatory conditions, while false-negatives occur with less metabolically active tumors including lepidic-predominant adenocarcinomas, mucinous adenocarcinomas, and carcinoid tumors 5
Nodule characteristics help differentiate etiology: malignant nodules typically show spiculated margins, size >8 mm, upper lobe location, and volume doubling time <400 days, while benign nodules show diffuse/central/laminated/"popcorn" calcification, smooth margins, and stability for ≥2 years 1, 7