What infections can cause a mediastinal mass with lymphadenopathy?

Infections Causing Mediastinal Mass with Lymphadenopathy

Histoplasmosis is the most common infectious cause of mediastinal mass with lymphadenopathy in endemic areas, presenting as granulomatous mediastinitis or mediastinal lymphadenitis that can mimic malignancy. 1

Primary Infectious Etiologies

Histoplasmosis (Most Common)

• Histoplasma capsulatum causes mediastinal lymphadenitis as a complication of acute pulmonary infection, with persistent inflammation of mediastinal lymph nodes that can present as a mass-like lesion 1
• Granulomatous mediastinitis from histoplasmosis results from active inflammation of mediastinal lymph nodes, causing symptoms including chest pain, cough, hemoptysis, and dyspnea due to compression of airways, superior vena cava, or pulmonary vessels 1
• In children with histoplasmosis presenting with mediastinal lymphadenopathy, 84% become asymptomatic within 1-2 months, indicating this is typically a self-limiting disease 2
• Histoplasmosis can rarely present as an actual pulmonary artery mass with mediastinal lymphadenopathy, not just lymph node enlargement 3

Tuberculosis (Second Most Common)

• Mycobacterium tuberculosis is a major cause of mediastinal lymphadenopathy, particularly in adults where it accounts for >90% of culture-proven mycobacterial lymphadenitis 1
• Tuberculous mediastinitis can develop chronically and is one of the most frequent infections resulting in mediastinal lymphadenopathy 4, 5
• Mediastinal lymph node involvement may occur with or without active pulmonary disease 1

Nontuberculous Mycobacteria

• Mycobacterium avium complex (MAC) causes approximately 80% of culture-proven nontuberculous mycobacterial lymphadenitis, though primarily cervical rather than mediastinal 1
• Mediastinal node involvement can occur, particularly in immunocompromised patients 1
• Other species including M. scrofulaceum, M. malmoense, and M. haemophilum can cause lymphadenitis 1

Fungal Infections (Endemic and Opportunistic)

• Coccidioidomycosis is a frequent cause of mediastinal lymphadenopathy in endemic regions 4
• Bipolaris australiensis (dematiaceous fungus) can cause disseminated infection with mediastinal lymphadenopathy and mass formation, even in immunocompetent hosts 6
• Other fungal infections including mucormycosis can rarely cause mediastinal masses 3

Clinical Approach and Diagnostic Considerations

Key Distinguishing Features

• Geographic history is critical: Histoplasmosis predominates in Ohio and Mississippi River valleys; coccidioidomycosis in southwestern United States 1, 4
• Immune status matters: In HIV-positive patients, opportunistic infections (MAC, CMV, tuberculosis) and lymphoma must be excluded when lymphadenopathy is present 1
• Age and presentation: In children, histoplasmosis with mediastinal lymphadenopathy is usually self-limiting; in adults, tuberculosis becomes more likely 1, 2

Diagnostic Workup

• Tuberculin skin testing should be performed, though histoplasmosis can cause positive reactions (up to one-third show ≥10mm induration) 1
• Acid-fast bacilli staining and mycobacterial culture of any tissue or fluid obtained 1
• Histoplasma antigen testing in urine and serum, plus complement fixation titers 1
• Tissue biopsy (when obtained) should include fungal stains and cultures, though biopsies are rarely diagnostic in histoplasmosis-related mediastinal lymphadenopathy and invasive procedures should be avoided when clinical picture is consistent 2

Critical Pitfalls to Avoid

• Do not assume malignancy without excluding infectious causes, particularly in endemic areas for histoplasmosis or in patients with tuberculosis risk factors 1, 4
• Avoid unnecessary biopsies in children with suspected histoplasmosis and mediastinal lymphadenopathy, as the disease is typically self-limiting and biopsies are rarely diagnostic 2
• In HIV-positive patients, always perform infectious disease workup for lymphadenopathy before attributing findings to malignancy, as nonmalignant causes are more common with higher viral loads and lower CD4+ counts 1

Treatment Considerations

• Asymptomatic mediastinal lymphadenopathy from histoplasmosis does not require antifungal treatment 1
• Granulomatous mediastinitis with obstructive symptoms warrants amphotericin B 0.7-1.0 mg/kg/day initially, transitioning to itraconazole 200mg once or twice daily 1
• Fibrosing mediastinitis (chronic fibrotic complication) is not expected to respond to antifungal therapy, though a 12-week trial of itraconazole may be considered if acute inflammatory features are present 1
• Tuberculous mediastinitis requires standard multi-drug antituberculous therapy 1