Lymphatic Distribution, Centrilobular Nodules

Eric J. Stern, MD

DIFFERENTIAL DIAGNOSIS

Common

Sarcoidosis, Pulmonary
Silicosis/Coal Worker’s Pneumoconiosis
Lymphangitic Carcinomatosis

Less Common

Lymphoma, Non-Hodgkin or Hodgkin
Bronchiolitis, Follicular
Amyloidosis
Berylliosis

Rare but Important

Lymphocytic Interstitial Pneumonia

ESSENTIAL INFORMATION

Key Differential Diagnosis Issues

Definition of lymphatic pattern
- Predominant abnormality is nodules (< 1 cm diameter) in pulmonary lymphatics
- Often called “perilymphatic” (pathology, however, usually in lymphatics)
Lymphatic compartments
- Axial: Follows bronchi and arteries to level of terminal bronchioles in secondary pulmonary lobule
- Peripheral: Follows veins, septa, and pleura
- Alveoli and respiratory bronchioles devoid of lymphatics
- Same disease process may sometimes preferentially involve axial lymphatics, sometimes peripheral lymphatics
Pathophysiology of disease
- Inhalational: Especially from rounded dust particles
- Hematogenous less common, implies migration into adjacent lymphatics (lymphohematogenous dissemination)
Lymphatic vs. hematogenous pattern
- Lymphatic nodules
  - Clustered like grapes, unlike dispersion in random distribution pattern
  - May be focal and localized; random is usually diffuse
- Lymphatic pattern
  - Nodules arranged in rays along bronchovascular pathways
  - Usually associated with subpleural and fissural nodules that comprise > 10% of total number of nodules
  - Often more severe in upper lung zones, random pattern often more severe in lower lung zones
  - Often associated with hilar and mediastinal adenopathy
Lymphatic vs. bronchovascular pattern
- Bronchovascular pattern nodules less common along fissure and subpleural lung (< 10% of total number of nodules)
  - Associated with small airways disease: Mosaic attenuation, air-trapping, tree-in-bud opacities
  - May be focal (from aspiration) or diffuse (from inhalation disorders)
- Some diseases start as bronchovascular pattern (from acute-semiacute reaction from inhaled pathogen) and evolve into lymphatic pattern (as pathogen migrates to draining lymphatics)
- Lymphatic pattern often associated with hilar and mediastinal adenopathy

Helpful Clues for Common Diagnoses

Sarcoidosis, Pulmonary
- Focal aggregation of nodules along bronchovascular bundles
- Nodules may be clustered into large masses (called alveolar sarcoid)
  - Galaxy sign: Coalescent mass surrounded by its constituent smaller nodules
- Nodules more profuse in upper lung zones
- Symmetric hilar and mediastinal adenopathy common
  - Nodes may contain chalky-smudgy or eggshell pattern calcification
Silicosis/Coal Worker’s Pneumoconiosis
- Work history of occupational exposure to silica particles or coal
- Nodules more profuse in upper lung zones
- Nodules tend to aggregate in dorsal aspect of lung; right lung usually more severely involved than left
- Severity and time results in progressive massive fibrosis (PMF)
- Hilar and mediastinal lymphadenopathy may show “eggshell” calcification (5%)
- Inhalational talcosis and siderosis give identical findings (reflects lung’s ability to chronically handle small rounded dusts)
Lymphangitic Carcinomatosis
- Seen primarily with adenocarcinomas
- Frequency of involvement: Axial lymphatics (75%), axial + peripheral (20%), peripheral (5%)
- Characteristically spares whole lobe or even whole lung
- Lung architecture preserved, unlike sarcoidosis and silicosis, which show architectural distortion
- Pleural effusion(s) common (unusual in sarcoidosis or silicosis)
- May have adenopathy

Helpful Clues for Less Common Diagnoses

Lymphoma, Non-Hodgkin or Hodgkin
- Pulmonary involvement in Hodgkin (40%) and non-Hodgkin (25%) disease
  - Primarily involves axial lymphatics
  - Pulmonary nodules, usually > 1 cm (often with air-bronchograms)
- Associated with bulky lymphadenopathy, effusion(s) also common
Bronchiolitis, Follicular
- Synonym: Lymphoid hyperplasia of bronchus-associated lymphoid tissue (BALT)
- Pathology: Similar to lymphocytic interstitial pneumonia (LIP)
  - Follicular bronchiolitis: Centered on airway lymphatics
- Interlobular septal thickening, bronchiolectasis, thin-walled cysts
- Associated with collagen vascular diseases (rheumatoid arthritis, Sjögren syndrome), AIDS, infections, hypersensitivity reaction
Amyloidosis
- Primary (associated with myeloma) and secondary (associated with chronic inflammatory disease)
- Wide spectrum findings: Tracheobronchial thickening and nodularity, centrilobular nodules, septal thickening
- Diffuse septal form more commonly has nodules in subpleural lung
- Nodules may calcify
Berylliosis
- Gives identical findings, occupational history important
- Beryllium lightweight metal with high melting point, used in wide variety of industries
- Latent period after exposure of 1 month to 40 years
- Incites hypersensitivity reaction with granulomas

Helpful Clues for Rare Diagnoses

Lymphocytic Interstitial Pneumonia
- Also associated with viral infection: HIV and Epstein-Barr virus, dysproteinemias, or Sjögren syndrome
- Thin-walled cysts distinctive (80%)
- Usually associated with nonspecific ground-glass opacities (100%)
- Diffuse distribution