Diagnosis and Discussion: Hepatosplenic Candidiasis in a Patient With Leukemia
Figure 1. Abdominal computed tomogram. Multiple low-attenuation foci are visible within the spleen.
Figure 2. Cut surface of the spleen showing numerous well-demarcated, cheesy-appearing nodules.
Figure 3. Histological appearance of the nodules; a central stellate abscess surrounded by epithelioid cells.
Figure 4. Budding yeast and pseudohyphae demonstrated in the center of the abscess (methenamine silver, original magnification ×200).
The patient had hepatosplenic candidiasis, a disseminated fungal infection that manifests itself as focal hepatic and splenic abscesses. It is an increasingly recognized complication of chemotherapy for malignant neoplasms. The patient with leukemia receiving intensive chemotherapy is rendered susceptible to these infections for a variety of reasons, including prolonged episodes of neutropenia and impaired gut mucosal integrity. Furthermore, the use of broad-spectrum antibiotics in febrile neutropenic patients promotes fungal overgrowth, leading to its dissemination through the blood and across the damaged enteric mucosa.1
The diagnosis of hepatosplenic candidiasis is often difficult to make owing to its nonspecific clinical presentation and variable laboratory and radiologic findings. The most common scenario involves persistence or recurrence of fever in a patient who has recently received broad-spectrum antibiotics for fever with neutropenia and whose neutrophil count has now recovered. One review of 68 adult and pediatric cases found fever as a presenting sign in 85%, with 56% having associated abdominal pain.2,3 Liver function test results commonly show an elevated alkaline phosphatase level, while transaminase levels are often normal or mildly elevated. An additional review of 30 pediatric cases revealed a similar clinical picture.4
Computed tomography and abdominal ultrasonography often aid in the diagnosis of hepatosplenic candidiasis. Both modalities may reveal multiple small hypolucent lesions, which may evolve into multilayered "bull's-eye" lesions. It is important to realize that imaging studies may be negative early in the course of the disease, especially during the patient's neutropenic phase. It is believed that a neutrophil-mediated inflammatory response is necessary to produce the characteristic lesions. The pathological characteristics are usually straightforward, although the striking similarity of the granulomas to those seen in cat-scratch disease warrants a word of caution when the pseudohyphae do not stain well. This may lead to an erroneous diagnosis of cat-scratch disease.
Once the diagnosis is established, extended treatment with systemic antifungal medications is indicated. Amphotericin B, either alone or in combination with 5-flucytosine, is the most commonly prescribed regimen. Newer studies have examined the role of fluconazole. Despite these therapies, the disease may have a mortality rate of approximately 20%.
Accepted for publication January 20, 1998.
Reprints: Jean-Pierre de Chadarevian, MD, Department of Pathology, St Christopher's Hospital for Children, Erie Avenue at Front Street, Philadelphia, PA 19134-1095.
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