What are the infectious causes of mediastinal masses in patients with varying immune status, age, and geographic location?

Infectious Causes of Mediastinal Masses

Primary Infectious Etiologies

The most common infectious causes of mediastinal masses are histoplasmosis (manifesting as mediastinal lymphadenitis or granuloma), tuberculosis (particularly in endemic areas and high-risk populations), and less commonly other endemic mycoses and bacterial mediastinitis. 1

Histoplasmosis

Histoplasmosis is the most well-documented infectious cause of mediastinal masses, presenting in two distinct forms:

Mediastinal Lymphadenitis:

• Results from inflammatory enlargement of mediastinal lymph nodes following acute pulmonary histoplasmosis 1
• Presents with chest pain, cough, atelectasis from bronchial compression, or dysphagia from esophageal compression 1
• Children are more likely than adults to develop airway obstruction 1
• Treatment is usually unnecessary in most cases 1
• For symptoms lasting ≥4 weeks or requiring corticosteroids: itraconazole 200 mg three times daily for 3 days, then 200 mg once or twice daily for 6-12 weeks 1
• Prednisone (0.5-1.0 mg/kg daily, maximum 80 mg, tapered over 1-2 weeks) is reserved for severe cases with obstruction or compression of contiguous structures 1

Mediastinal Granuloma:

• Represents a large (3-10 cm in adults, smaller in children), mostly caseous mass of coalesced mediastinal lymph nodes forming a single encapsulated lesion 1
• Asymptomatic cases require no treatment 1
• Symptomatic cases warrant itraconazole 200 mg three times daily for 3 days, then once or twice daily for 6-12 weeks 1

Tuberculosis

Geographic and Population Considerations:

• In high-prevalence TB areas, chronic cough should be defined as 2-3 weeks duration (per WHO PAL program) rather than the typical longer timeframe 1
• High-risk populations include prisoners, nursing home residents, and elderly patients who may present atypically (less fever, sweating, hemoptysis, and more lower lung lesions with less cavitation) 1
• Sputum smears and cultures for acid-fast bacilli plus chest radiograph should be obtained whenever TB is suspected 1
• Special surveillance and early diagnostic programs are mandatory in prisons and nursing homes to prevent outbreaks 1

Other Endemic Mycoses

Geographic Distribution Matters:

• Endemic mycoses are restricted to discrete geographic regions and acquired by inhalation of fungal spores 1
• Can produce latent pulmonary infection or progressive acute/subacute disease 1
• Disseminated histoplasmosis can present with extensive mediastinal and cervical lymphadenopathy, even in immunocompetent patients, though this is unusual 2
• Rare fungal pathogens like Bipolaris australiensis can cause mediastinal masses with lymphadenopathy and pericardial effusion, typically requiring amphotericin B and itraconazole 3

Acute Bacterial Mediastinitis

Clinical Context:

• Most commonly results from esophageal perforation, penetrating trauma, or poststernotomy infection (the most common cause today) 4
• Can also result from direct extension from adjacent infections or hematogenous spread 4
• Associated with high morbidity and mortality, requiring aggressive treatment directed at the primary pathology 4

Critical Diagnostic Pitfalls

Age and Immune Status Influence Differential:

• While infections can cause mediastinal masses, remember that thymomas (28%), benign cysts (20%), and lymphomas (16%) are more common causes of anterior mediastinal masses overall 5
• In immunocompromised patients (especially AIDS), latent endemic fungal infections can progress to disseminated disease with mediastinal involvement 1
• Elderly patients with infectious mediastinal masses may lack typical fever and constitutional symptoms 1

Geographic History is Essential:

• Always obtain detailed travel and residence history, as endemic mycoses (histoplasmosis in Ohio/Mississippi River valleys, coccidioidomycosis in Southwest US, paragonimiasis in Southeast Asia) have specific geographic distributions 1
• Immigration patterns may bring endemic infections to non-endemic areas 1

Imaging Cannot Definitively Distinguish Infection from Malignancy:

• CT chest with contrast is the primary imaging modality for mediastinal masses but cannot reliably differentiate infectious from neoplastic etiologies 6
• Tissue diagnosis through EBUS-guided TBNA, CT-guided biopsy, or surgical sampling is often necessary 7
• Histological examination with special stains (Grocott-silver for fungi, acid-fast stains for mycobacteria) is critical 2