Multiple Pulmonary Nodules

Eva Ilse Rubio, MD

DIFFERENTIAL DIAGNOSIS

Common

Fungal Infection
Mycoplasma Infection

Less Common

Tuberculosis (TB)
Viral Infection
Septic Emboli
Metastatic Disease
Lymphoproliferative Disease
Post-Transplant Lymphoproliferative Disorder
Langerhans Cell Histiocytosis, Pulmonary
Wegener Granulomatosis
Sarcoid

Rare but Important

Hypersensitivity Pneumonitis
Thoracic Lymphoma

ESSENTIAL INFORMATION

Key Differential Diagnosis Issues

Location within pulmonary parenchyma
- Centrilobular vs. random
- Upper vs. lower lobe predominant
Tendency to present as cavitary lesions
- Septic emboli, Aspergillus, Wegener, papillomatosis
Patient demographic/clinical considerations
- High risk TB population?
- Regional endemic fungal infections?
- Immunocompromised patient?
Many primary neoplasms metastasize to lungs; usually there is known primary when lung metastases are detected

Helpful Clues for Common Diagnoses

Fungal Infection
- Histoplasmosis
  - Common in midwestern USA
  - Variable appearance: Multiple nodules, alveolar, ill-defined peripheral opacities
  - Coarsely calcified mediastinal/hilar lymph nodes are common
  - Pulmonary nodules often calcify
- Candida
  - Typically seen in patients with multiple underlying medical conditions
  - Variable parenchymal pattern: Nodules, segmental consolidation, ± cavitation
  - Look for other systemic disease: Spleen, liver, bloodstream, sinuses
- Aspergillus
  - Allergic: Typically seen in asthma or cystic fibrosis patients; ill-defined consolidation or branching mucoid plugs
  - Saprophytic: Preexisting architectural abnormality (bronchiectasis, cavity); classic fungus ball
  - Mildly invasive: Chronically ill patients; focal infiltrate or fungus ball in cavity
  - Frankly invasive: Immunocompromised patients; variable appearance of peripheral consolidation, “halo” sign, cavitary lesions
- Coccidiomycosis
  - Imaging appearance compared to TB
  - Highly variable appearance: Nodules, infiltrates, or thin-walled cavities
  - Pleural effusions, adenopathy possible
- Blastomycosis
  - Rare in children
  - More severe infection/multiorgan involvement if immunocompromised
  - Variable pattern: Nodules, peripheral consolidation, interstitial opacities
Mycoplasma Infection
- Wide spectrum of radiologic and clinical presentations
  - May manifest as bronchopneumonia, atelectasis, or interstitial opacities
  - Typical in older school-aged children

Helpful Clues for Less Common Diagnoses

Tuberculosis (TB)
- Secondary tuberculosis may present as diffuse bilateral < 3 mm nodular opacities
  - May be associated with pleural effusions, lymphadenopathy
  - Consider concomitant solid visceral or CNS involvement
Viral Infection
- Cytomegalovirus
  - Typically seen after bone marrow transplant
  - Bilateral, diffusely distributed, small nodular opacities
- Human papillomavirus
  - Endobronchial spread of laryngeal papillomatosis
  - Bilateral nodules of varying size, may cavitate
Septic Emboli
- Common organisms: Staphylococcus aureus, Streptococcus
- Search for underlying source: Soft tissue infection, osteomyelitis, central line infection, endocarditis
- Imaging
  - Multiple, basilar-predominant, nodular or ill-defined opacities
  - Eventual cavitation common
  - Source vessel may be identified
Metastatic Disease
- Wilms tumor
  - Lungs are most common site of mets
  - Pulmonary: Multiple pulmonary nodules, masses
  - Cardiovascular: Tumor extension into renal vein, IVC, right atrium
- Ewing sarcoma
  - Lungs are most common site of metastatic disease; metastases may be seen at diagnosis or years later
- Rhabdomyosarcoma
  - Common tumor in children arising from GU tract, orbits, chest wall
  - Lungs are most common site of metastatic disease
- Osteosarcoma
  - Most common malignant bone tumor in children
  - Lungs are most common site of metastases: Nodules that may be ossified; spontaneous pneumothorax; hemothorax
Lymphoproliferative Disease, Post-Transplant Lymphoproliferative Disorder
- Variable appearance: Infiltrates or nodules
- Hilar/mediastinal adenopathy may be seen
Langerhans Cell Histiocytosis, Pulmonary
- Parenchymal findings: Nodule that cavitates; thick- or thin-walled cysts
- Other thoracic features: Pneumothorax, adenopathy, fibrosis
Wegener Granulomatosis
- Vasculitis, cavitating nodules (basilar predominant), ± ground-glass halo
- Other respiratory/thoracic manifestations: Rhinorrhea, epistaxis, mucosal ulcerations, airway stenosis, pleural effusions, pulmonary hemorrhage
- Other visceral manifestations: Glomerulonephritis, splenic lesions
Sarcoid
- Pulmonary: Small reticulonodular opacities
- Thoracic: Hilar, paratracheal adenopathy

Helpful Clues for Rare Diagnoses

Hypersensitivity Pneumonitis
- Variable pattern of fine nodules, alveolar or interstitial opacities
Thoracic Lymphoma
- Pulmonary nodules more common in Hodgkin vs. non-Hodgkin
- Typically seen with mediastinal/hilar adenopathy
- Variable pattern of round nodules or ill-defined opacities