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Granulomatous Hepatitis: Fungal Infections

The liver is affected by many non-viral, fungal, and infectious agents. In the United States, fungal infections are commonly limited to patients that are immunosuppressed. Common fungal infections found in liver biopsies involve Histoplasma, Candida, and Aspergillus. Other fungal infections that may appear as a result of disseminated (wide spread) disease are Cryptococcus, Blastomyces, and Coccidioides.
Histoplasma causes the most commonly seen fungal infection in the general population of the United States. The common histologic finding in Histoplasmosis is the presence of granulomas. With the application of the Gomori methenamine silver (GMS) stain, 2-5 µm narrow based budding yeast forms can be visualized. Histoplasma can be distinguished from other fungal organisms by the size and shape of the yeast.
Candida of the liver is commonly seen in immunocompromised patients. Candida is difficult to diagnose on a small needle biopsy because of its focal nature and is better visualized with a larger wedge biopsy. The presence of Candida organisms may be plentiful or rare and visualized best with the GMS stain. In abundance, Candida can also be visualized with application of the periodic acid-Schiff (PAS) or hematoxylin and eosin (H&E) stains. The characteristic histologic finding with Candida is a mixture of yeast forms and pseudohyphae (incomplete budding or branching).
Aspergillus may be rarely diagnosed on a liver needle core biopsy. A characteristic histologic finding of Aspergillus is hemorrhagic necrosis, as opposed to granuloma formation with Histoplasma. The presence of Aspergillus is characterized by organisms that are 8-10 µm long with branching septate hyphae. They are visible with both H&E and GMS stains.