What is the initial workup for a patient presenting with mediastinal lymphadenopathy and suspected sarcoidosis?

Workup for Mediastinal Lymphadenopathy with Suspected Sarcoidosis

The workup should begin with high-resolution CT imaging to characterize the lymphadenopathy, followed by a risk-stratified approach to tissue sampling based on clinical presentation—avoiding biopsy in classic sarcoidosis syndromes while pursuing EBUS-guided sampling when diagnosis is uncertain or alternative diagnoses must be excluded. 1, 2

Initial Clinical Assessment

Identify high-probability clinical syndromes that may obviate the need for biopsy:

• Löfgren's syndrome (bilateral hilar lymphadenopathy + erythema nodosum + arthralgia + fever) strongly suggests sarcoidosis and does NOT require tissue confirmation 3
• Lupus pernio or Heerfordt's syndrome (parotid enlargement, uveitis, facial nerve palsy, fever) similarly indicate sarcoidosis without need for sampling 3
• Constitutional symptoms (fever, night sweats, weight loss) raise concern for lymphoma or tuberculosis and mandate tissue diagnosis 1

The American Thoracic Society explicitly recommends against lymph node sampling in patients with these classic sarcoidosis presentations 3.

Imaging Strategy

• High-resolution CT chest is essential to characterize lymph node distribution, assess for parenchymal abnormalities, and narrow the differential diagnosis 1, 2
• Bilateral symmetric hilar and right paratracheal lymphadenopathy with normal lung parenchyma has 85% probability of sarcoidosis, but alternative diagnoses include tuberculosis (38% of non-sarcoid cases) and lymphoma (25% of non-sarcoid cases) 3

Laboratory Testing

Obtain the following based on clinical suspicion:

• Tuberculosis testing (interferon-gamma release assay or tuberculin skin test) is mandatory given TB represents 38% of alternative diagnoses in suspected stage I sarcoidosis 3, 1, 2
• Serum ACE level for suspected sarcoidosis (though not diagnostic) 1, 2
• IgG4 levels if IgG4-related disease is in the differential 1, 2
• Pulmonary function tests (spirometry and DLCO) to assess for restrictive physiology and impaired gas exchange 1, 2

Tissue Sampling Decision Algorithm

When to AVOID sampling:

• Classic Löfgren's syndrome, lupus pernio, or Heerfordt's syndrome present 3
• Asymptomatic bilateral hilar lymphadenopathy in appropriate clinical context—the ATS makes no firm recommendation for or against sampling in this scenario, allowing clinical judgment 3

When sampling IS indicated:

• Absence of classic sarcoidosis syndromes 3
• Constitutional symptoms suggesting malignancy or infection 1
• Atypical radiographic patterns (unilateral, asymmetric, or with concerning features) 4
• Need to exclude alternative diagnoses with serious mortality implications 3

Sampling Method Selection

EBUS-guided transbronchial needle aspiration is the preferred first-line approach:

• Diagnostic yield: 87% with 98% of diagnostic samples confirming sarcoidosis 3
• Complication rate: <0.1% (minimal risk) 3
• Identifies alternative diagnoses (lymphoma, TB, lung cancer) in 2% of cases 3

Mediastinoscopy should be reserved for:

• Non-diagnostic EBUS results requiring definitive diagnosis 3
• Higher diagnostic yield (98%) but more invasive with greater complication risk including vocal cord damage 3

Transbronchial needle aspiration (TBNA) during flexible bronchoscopy:

• Diagnostic yield of 72% for stage I sarcoidosis 5
• When combined with transbronchial lung biopsy, increases diagnostic yield to 87% 5

Critical Pitfalls to Avoid

• Do not assume bilateral hilar lymphadenopathy equals sarcoidosis: 10% have lymphoma and 7.7% have other serious diagnoses (malignancy, silicosis, amyloidosis) 3
• Do not rely on fine-needle aspiration alone: Core needle biopsy is preferred to enable histological examination of granuloma architecture 1, 2
• Do not skip TB testing: Tuberculosis accounts for 38% of alternative diagnoses in suspected stage I sarcoidosis 3
• Do not forget cultures: All tissue samples must have fungal and mycobacterial cultures sent 4

Follow-Up Requirements

If biopsy is deferred in suspected sarcoidosis:

• Close clinical follow-up is mandatory with serial imaging and symptom monitoring 3
• Repeat pulmonary function tests regularly if interstitial lung disease develops 1, 2
• Follow-up imaging at appropriate intervals based on clinical course 1, 2

The key principle: While 85% of suspected stage I sarcoidosis cases are confirmed, the 15% with alternative diagnoses include life-threatening conditions (lymphoma, TB) that require early identification to reduce mortality 3.