What investigations should be done after finding hilar lymphadenopathy on chest X-ray (CXR)?

Investigations for Hilar Lymphadenopathy on Chest X-ray

When hilar lymphadenopathy is detected on chest X-ray, a high-resolution CT (HRCT) scan should be performed as the initial investigation, followed by appropriate diagnostic procedures based on clinical suspicion and CT findings.

Initial Evaluation

• High-resolution CT scan should be performed to better characterize the lymphadenopathy, assess for additional abnormalities, and help narrow the differential diagnosis 1
• Complete clinical assessment focusing on symptoms suggestive of specific etiologies:
  • Erythema nodosum, fever, and arthralgia (Löfgren's syndrome) suggesting sarcoidosis 1
  • Constitutional symptoms (fever, weight loss, night sweats) suggesting lymphoma or tuberculosis 1, 2
  • Occupational history (silica, beryllium exposure) 3

Diagnostic Algorithm Based on Clinical Presentation

For patients with high clinical suspicion for sarcoidosis:

• If classic presentation of Löfgren's syndrome, lupus pernio, or Heerfordt's syndrome is present, lymph node sampling is not recommended 1
• Close clinical follow-up is required if biopsy is deferred 1

For patients with asymptomatic bilateral hilar lymphadenopathy:

• The American Thoracic Society makes no firm recommendation for or against lymph node sampling 1
• Consider the following factors:
  • Sarcoidosis is confirmed in 85% of patients with suspected stage 1 disease 1
  • Alternative diagnoses (found in only 1.9% of cases) include tuberculosis (38%) and lymphoma (25%) 1

For patients with unilateral hilar lymphadenopathy or concerning features:

• Diagnostic sampling is recommended, especially for:
  • Unilateral hilar mass following negative bronchoscopy 1
  • Patients with risk factors for malignancy 1
  • Atypical radiographic patterns 2

Sampling Methods When Indicated

• EBUS-guided lymph node sampling has a diagnostic yield of 87% with minimal complications (<0.1%) 1
• Mediastinoscopy has a higher diagnostic yield (98%) but is more invasive 1
• Core needle biopsy is preferred over fine-needle aspiration to enable histological examination 1

Laboratory and Additional Testing

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

Special Considerations

• In patients with suspected lymphoma, routine thoracic CT is justified for all patients 4
• For suspected interstitial lung disease with hilar lymphadenopathy, pulmonary function tests are essential for monitoring disease progression 1
• Rare causes of hilar lymphadenopathy include infections (Mycoplasma pneumoniae, COVID-19) that should be considered in appropriate clinical contexts 5, 6

Follow-up Recommendations

• For patients with asymptomatic bilateral hilar lymphadenopathy where sampling is deferred, close clinical follow-up is essential 1
• Follow-up imaging should be performed at appropriate intervals based on the suspected diagnosis and clinical course 1
• Pulmonary function tests should be repeated regularly if interstitial lung disease is suspected 1

Pitfalls to Avoid

• Assuming all bilateral hilar lymphadenopathy represents sarcoidosis without considering other diagnoses 1, 2
• Failing to recognize that 10% of patients with bilateral hilar lymphadenopathy may have lymphoma 1
• Underestimating the value of CT in detecting mediastinal lymphoma, which is detected by CT in 95% of cases versus only 56% by conventional chest radiography 4