Can Histoplasma (a type of fungus) cause masses outside of the lung, especially in immunocompromised individuals?

Can Histoplasma Cause Masses Outside of the Lung?

Yes, Histoplasma can definitively cause masses and lesions outside the lungs, particularly in immunocompromised patients through hematogenous dissemination, affecting multiple organ systems including the gastrointestinal tract, adrenal glands, liver, spleen, bone marrow, and central nervous system. 1

Mechanism of Extrapulmonary Involvement

Hematogenous dissemination from the lungs to other tissues occurs in virtually all infected individuals during the first 2 weeks of infection before specific immunity develops. 1 In most immunocompetent hosts, this dissemination is nonprogressive and leads only to calcified granulomas in the liver and/or spleen. 1 However, progressive dissemination occurs primarily in those with underlying immunosuppressive disorders or those at the extremes of age. 1

Common Extrapulmonary Sites

Gastrointestinal Tract

• Colonic involvement can occur as polypoid lesions or infiltrative disease, even as isolated findings without pulmonary symptoms. 2, 3
• The ileum is the most frequently affected gastrointestinal site, though any part of the digestive system can be involved. 2
• Gastrointestinal disease typically manifests with diarrhea, fever, abdominal pain, and weight loss. 1

Adrenal Glands

• Adrenal involvement can present as adrenal insufficiency with bilateral adrenal masses. 4
• This presentation can occur even in immunocompetent hosts, though it is more common in disseminated disease. 4

Liver and Spleen

• Hepatosplenomegaly is a common manifestation of disseminated histoplasmosis. 1, 3
• Liver lesions can mimic metastatic disease on imaging, causing diagnostic confusion with primary malignancies. 5

Central Nervous System

• CNS histoplasmosis typically presents with fever, headache, and if brain involvement is present, seizures, focal neurological deficits, and changes in mental status. 1
• For CNS disease, CSF testing shows 70-90% sensitivity for antibody and 40-70% sensitivity for antigen. 6

Other Sites

• Bone marrow involvement can cause pancytopenia. 3, 5
• Skin, bone, and genitourinary tract can be affected. 1
• Lymphadenopathy is common in disseminated disease. 1

Risk Factors for Extrapulmonary Disease

Progressive dissemination occurs primarily in patients with CD4+ counts <150 cells/µL, organ transplant recipients, and those at extremes of age. 1 The disease is accelerated and can be life-threatening in immunosuppressed patients. 1

Diagnostic Approach for Extrapulmonary Masses

Antigen Testing (First-Line)

• Histoplasma antigen detection in urine has 95% sensitivity and serum has 85% sensitivity for disseminated histoplasmosis in AIDS patients. 1
• This is the diagnostic method of choice for disseminated disease in immunocompromised patients. 6

Tissue Biopsy

• Histopathologic examination of biopsy material from involved tissues (adrenal, colon, liver, bone marrow) can demonstrate organisms and confirm diagnosis. 4, 2, 3
• In severe disseminated histoplasmosis, peripheral blood smears can show organisms engulfed by white blood cells. 1

Antibody Testing Limitations

• Sensitivity drops dramatically in immunocompromised patients: only 18% in organ transplant recipients and 45% in HIV/AIDS patients. 6
• Do not rely on antibody testing alone in immunocompromised patients—combine with antigen testing for optimal diagnostic yield. 6

Critical Clinical Pitfall

The most dangerous pitfall is assuming histoplasmosis is limited to the lungs or requires pulmonary symptoms. 3 Disseminated histoplasmosis can present with prominent extrapulmonary involvement and minimal or absent respiratory symptoms, particularly in immunocompromised patients. 3 Extrapulmonary masses can mimic malignancy on imaging, leading to delayed diagnosis and treatment. 5

Treatment Implications

• Disseminated histoplasmosis requires antifungal treatment regardless of symptom severity. 1
• Amphotericin B (0.7 mg/kg/day) is indicated for severe manifestations, followed by itraconazole for maintenance therapy. 1
• Mortality in histoplasmosis is estimated at 5% in children and 8% in adults, making rapid diagnosis essential. 6