Mediastinal & Hilar Lymphadenopathy: Differential Diagnosis & Workup

Mediastinal/hilar lymphadenopathy = enlarged lymph nodes in central chest (mediastinum) and lung hila. "Multiple sites" implies multifocal involvement – narrows differential toward systemic processes.

Anatomic Context

• Mediastinum: Superior, anterior, middle, posterior compartments.
• Hila: Right/left – pulmonary vessels, bronchi, nodes.
• Station mapping: IASLC lymph node map (Stations 1-14) standard for staging/communication.

Major Etiologic Categories

Category	Key Examples	Typical Pattern
Infectious	TB, histoplasmosis, coccidioidomycosis, MAC, fungal, bacterial	Often hilar + mediastinal; may calcify
Malignancy	Lung Ca (N2/N3), lymphoma (HL/NHL), metastatic (breast, melanoma, renal), thymoma	Asymmetric, progressive; may have primary mass
Sarcoidosis	Non-caseating granulomas	Bilateral hilar (BHL) + right paratracheal (1-2-3 sign); symmetric
Autoimmune	RA, SLE, Sjögren's, IgG4-related disease	Often with other systemic features
Other	Silicosis/coal worker's, Castleman's, amyloidosis, drug reaction	Occupational history, specific serologies

Diagnostic Workup

1. CT Chest with contrast: Characterize nodes (size, necrosis, calcification), assess lung parenchyma, search primary.
2. PET-CT: Metabolic activity – malignancy/sarcoid vs. benign.
3. Labs: ACE (sarcoid), AFB/culture (TB), fungal serologies, ANCA, RF, IgG4, SPEP, HIV.
4. Tissue diagnosis (if needed):
   • EBUS-TBNA (stations 2,4,7,10,11) – first-line, minimally invasive.
   • Mediastinoscopy (stations 5,6,8,9) – surgical, higher yield for some.
   • CT-guided percutaneous (anterior/posterior).
   • VATS (station 5,6, aorticopulmonary window).

Multifocal mediastinal/hilar nodes = think systemic (sarcoid, lymphoma, TB, metastatic) before local. EBUS-TBNA is diagnostic cornerstone.