What further investigations are recommended after identifying hilar lymphadenopathy on a chest X-ray (CXR)?

Diagnostic Approach to Hilar Lymphadenopathy on Chest X-ray

After identifying hilar lymphadenopathy on chest X-ray, a high-resolution CT scan should be performed as the next investigation to better characterize the lymphadenopathy and guide further diagnostic workup. 1

Initial Evaluation

• High-resolution CT (HRCT) is essential to:

  • Better characterize the lymphadenopathy (size, distribution, symmetry)
  • Assess for additional lung parenchymal abnormalities
  • Help narrow the differential diagnosis 1

• Complete clinical assessment focusing on:

  • Symptoms suggestive of sarcoidosis (erythema nodosum, fever, arthralgia)
  • Constitutional symptoms suggesting lymphoma or tuberculosis (fever, weight loss, night sweats)
  • Occupational exposures (beryllium, silica) 1, 2

Laboratory Testing

• Pulmonary function tests (spirometry and diffusion capacity) to assess for restrictive physiology and impaired gas exchange 1
• Tuberculosis testing (interferon-gamma release assay or tuberculin skin test) 1
• Serum tests based on clinical suspicion:
  • Angiotensin-converting enzyme (ACE) for suspected sarcoidosis
  • IgG4 levels if IgG4-related disease is suspected 1

Diagnostic Algorithm Based on Clinical Presentation

For Bilateral Symmetric Hilar Lymphadenopathy:

• High suspicion for sarcoidosis, especially with:
  • Classic Löfgren's syndrome (erythema nodosum, fever, arthralgia)
  • Other characteristic clinical features (lupus pernio, Heerfordt's syndrome) 1
• Consider observation with close follow-up if classic presentation 1

For Unilateral or Asymmetric Hilar Lymphadenopathy:

• Higher suspicion for malignancy or infection
• Tissue sampling is more strongly indicated 3, 2

For Hilar Lymphadenopathy with Parenchymal Abnormalities:

• Consider hypersensitivity pneumonitis, infection, or malignancy
• Multidisciplinary discussion is recommended to guide further testing 4

Tissue Sampling Methods When Indicated

• EBUS-guided lymph node sampling:

  • Diagnostic yield of approximately 87%
  • Minimal complications (<0.1%)
  • First-line approach for accessible lymph nodes 1

• Mediastinoscopy:

  • Higher diagnostic yield (98%) but more invasive
  • Consider when EBUS is non-diagnostic or not feasible 1

• Surgical lung biopsy:

  • Consider when all available clinical, laboratory, and radiologic findings along with bronchoscopic results do not yield a confident diagnosis
  • Results may help guide management decisions 4

• Core needle biopsy is preferred over fine-needle aspiration to enable histological examination 4, 1

Common Causes of Hilar Lymphadenopathy

• Infectious: Tuberculosis, fungal infections (histoplasmosis, coccidioidomycosis), atypical mycobacteria 5, 2
• Inflammatory: Sarcoidosis, silicosis, beryllium disease 5, 2
• Neoplastic: Lymphoma, lung cancer with metastasis to hilar nodes 5, 2
• Others: Amyloidosis, drug reactions, heart failure, IgG4-related disease 5

Special Considerations

• For suspected hypersensitivity pneumonitis with typical HRCT findings and compelling exposure history, BAL fluid analysis may not be routinely needed 4
• In patients with suspected interstitial lung disease, multidisciplinary discussion should be considered before proceeding to invasive procedures 4
• Rare causes of hilar lymphadenopathy should be considered in appropriate clinical contexts (e.g., COVID-19) 6, 7

Follow-up Recommendations

• Close clinical follow-up is essential for patients with asymptomatic bilateral hilar lymphadenopathy where sampling is deferred 1
• Follow-up imaging at appropriate intervals based on the suspected diagnosis and clinical course 1
• Repeat pulmonary function tests regularly if interstitial lung disease is suspected 1