• Liver involvement is almost always part of disseminated infection
Patients often immunocompromised
Liver is involved in up to 90% of cases of disseminated disease
• With treatment, mortality rate is < 10%
• Most infections in immunocompetent persons are self-limited and often clinically unrecognized
Microscopic
• Portal and lobular lymphohistiocytic inflammation is typical
• Discrete granulomas variable present and often absent in immunocompromised patients
May have little or no inflammatory response in severely immunocompromised patients
• Large numbers of yeast are present in portal and sinusoidal macrophages
• Yeast are 2-4 μm, oval, with narrow-based budding
GMS and PAS/diastase positive
Top Differential Diagnoses
• Sarcoidosis: Similar epithelioid discrete granulomas
• Leishmaniasis: Kinetoplast and GMS negative
• Candidiasis: Larger yeast, more budding
• Penicilliosis: Pill capsule forms; different geographic distribution
Granulomas This liver biopsy in a patient with disseminated histoplasmosis contains large, coalescent, epithelioid granulomas.
Lymphohistiocytic Inflammation Immunocompromised patients with disseminated histoplasmosis may have only necrosis along with lymphocytes and histiocytes that are filled with organisms , rather than well-formed granulomas.
Intracellular Organisms This high-power view shows macrophages that are distended with Histoplasma. Note the pale “halo” surrounding the fungi, which is a helpful clue on H&E staining.
GMS, High Power Histoplasma are uniformly small with narrow-based buds at the more pointed end of the organism.
TERMINOLOGY
Definitions
• Infection by the fungus Histoplasma capsulatum
ETIOLOGY/PATHOGENESIS
Histoplasma capsulatum
• Dimorphic fungus
Found in soil, particularly when contaminated with bird or bat droppings
• Exists as mycelial form at room temperature and as yeast form at body temperature
• Mechanism of infection
Aerosolized microconidia are inhaled
– Survive within macrophages as yeast form
– Organism disseminates throughout reticuloendothelial cell system
– In immunocompetent patients, sensitized T cells activate macrophages, which then are able to kill organism
CLINICAL ISSUES
Epidemiology
• Geographic distribution
Variety of endemic areas around globe
– Ohio, Missouri, and Mississippi River valleys and parts of eastern United States
Most common endemic mycosis in United States
– Central and South America
– Parts of southern Europe, Africa, and southeastern Asia
• Conditions associated with infection/outbreaks
Demolition of buildings
Moving soil contaminated with bird or bat droppings
Uprooting trees where birds roost
Spelunking in caves where bats live
Presentation
• Acute disseminated infection
Usually occurs in immunosuppressed patients
– Disseminated histoplasmosis occurs in ∼ 55% of infected immunocompromised patients and 4% of infected immunocompetent patients
Liver is involved in up to 90% of cases of disseminated disease
Patients may present with signs of liver/GI involvement rather than pulmonary involvement
Typically symptomatic
– Chills/fever
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, rather than well-formed granulomas.
