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Pathological Case of the Month
David M. Fleece, MD;
Eric N. Faerber, MD;
Jean-Pierre de Chadarévian, MD, MD
From the Departments of Pediatrics (Dr Fleece), Radiology (Dr Faerber) and Pathology (Dr de Chadarévian), St Christopher's Hospital for Children; Temple University School of Medicine (Dr Fleece); and Allegheny University of the Health Sciences, MCP Hahnemann School of Medicine (Drs Faerber and de Chadarévian), Philadelphia, Pa.
Arch Pediatr Adolesc Med. 1998;152:1033-1034.
A 5-YEAR-OLD boy with acute lymphoblastic leukemia presented with a 2-day history of fever and chills. The child had been treated with vincristine and L-asparaginase. He was receiving trimethoprim-sulfamethoxazole for Pneumocystis carinii prophylaxis, which was his only medication. Physical examination results were normal except for a mild left upper quadrant tenderness, but no organomegaly or masses.
Laboratory data included a hemoglobin level of 107 g/L, platelet count of 376x109/L, and white blood cell count of 10.3x109/L, with a normal differential cell count. Serum electrolytes, serum urea nitrogen, creatinine, serum transaminase, and amylase levels were all within normal limits. The chest radiograph revealed diffuse mild interstitial disease. Abdominal ultrasonography showed multiple small hypoechogenic foci within a normal-sized spleen and a normal-appearing liver, kidney, and pancreas. Abdominal computed tomography showed multiple small low-attenuation foci within the spleen, left lobe of the liver, and both kidneys (Figure 1).
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Figure 1.
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The patient remained febrile despite treatment with cefuroxime and amphotericin. Daily cultures of blood and urine remained negative for organisms. On hospital day 5, the patient underwent splenectomy. Fever subsequently resolved and the patient was discharged 10 days postoperatively.
The resected spleen weighed 300 g. It had a bosselated surface caused by the presence of numerous subcapsular whitish nodules, better seen when the organ was serially cross-sectioned. This revealed a cut surface studded with discretely demarcated nodules measuring up to 0.7 cm in diameter (Figure 2). They were firm and whitish yellow with necrotic, cheesy-appearing centers. Each nodule was histologically a stellate-shaped granuloma made of epithelioid cells surrounding a central abscess, very reminiscent of the abscesses seen in cat-scratch disease (Figure 3). Staining for acid-fast bacilli, bacteria, and spirochetes (Warthin-Starry stain) remained negative, but the periodic acid–Schiff and the methenamine silver stains demonstrated the presence of aggregates of budding yeast and pseudohyphae in the center of the abscesses (Figure 4).
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Figure 2.
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Figure 3.
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Figure 4.
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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 x200).
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%.
AUTHOR INFORMATION
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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.
REFERENCES
1. Freifeld AG, Walsh TJ, Pizzo PA. Infectious complications in the pediatric cancer patient. In: Pizzo P, Poplack D, eds. Principles and Practice of Pediatric Oncology. 3rd ed. Philadelphia, Pa: JB Lippincott Co; 1997:1097-1098.
2. Thaler M, Pastakia B, Shawker TH, O'Leary T, Pizzo PA. Hepatic candidiasis in cancer patients: the evolving picture and the syndrome. Ann Intern Med. 1988;108:88-100.
3. Walsh TJ, Whitcomb PO, Revankar SG, Pizzo PA. Successful treatment of hepatosplenic candidaiasis through repeated cycles of chemotherapy and neutropenia. Cancer. 1995;76:2357-2362.
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4. Carstensen H, Widding E, Storm K, Østergaard E, Herlin T. Hepatosplenic candidiasis in children with cancer: three cases in leukemic children and a literature review. Pediatr Hematol Oncol. 1990;7:3-12.
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SECTION EDITOR: ENID GILBERT-BARNESS, MD
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