Disseminated histoplasmosis diagnosed by peripheral blood film in a patient with chronic lymphocytic leukaemia

A 72-year-old Caucasian female had been diagnosed with chronic lymphocytic leukaemia (CLL) 4 years earlier and received the most recent dose of oral chlorambucil 1 month before presentation. She was admitted to a local hospital for treatment of febrile neutropenia with a blood culture positive for Klebsiella pneumoniae. Ten days later, she was transferred to a tertiary care hospital intensive care unit (ICU) for further diagnosis and treatment. She had fever, fluctuating loss of consciousness and clinical manifestations consistent with septic shock. Laboratory investigations showed a pancytopenia with a normocytic anaemia, haemoglobin concentration 93 g/l, thrombocytopenia (platelet count <10 9 10/l) and severe neutropenia (neutrophil count below detectable limits). Lactate dehydrogenase (LDH) was significantly elevated at 2134 iu/l (reference 100–205 iu/l). Chest radiography showed moderate to severe pulmonary oedema with bibasal atelectasis. A computerized tomography scan of the abdomen and pelvis demonstrated hepatosplenomegaly and lymphadenopathy consistent with the known diagnosis of CLL, and multiple small hypodense lesions in the spleen suggestive of lymphomatous deposits or splenic abscesses (left). The patient was treated with piperacillin-tazobactam, vancomycin, fluconazole and filgrastim. Microscopic evaluation of a peripheral blood film revealed rare neutrophils, a relative but not absolute lymphocytosis, smear cells and lymphocytes with clumped chromatin, compatible with CLL. A giant reactive monocyte with multiple intracellular yeast-like organisms was discovered at the feather-edge of the film. These organisms were about 2–4 lm in diameter and were eccentric within a typical clear pseudocapsule, findings diagnostic of Histoplasma capsulatum (right). Careful scrutiny of the whole film demonstrated a neutrophil with one organism inside the cytoplasm, which had the same morphological features. Only 10 neutrophils and/or monocytes were observed in the film, and of these, 3 (30%) contained 1–9 intracellular organisms per cell. Following the diagnosis of disseminated histoplasmosis, liposomal amphotericin was added to the treatment regimen. Additional histoplasmosis-specific workup was implemented, including fungal culture from both blood and tracheal aspirate and serological tests. Next day, the patient displayed evidence of respiratory failure and required urgent intubation. She deteriorated quickly and died 3 d after admission to ICU. Fungal culture from both blood and tracheal aspirate isolated Histoplasma capsulatum, confirming that patient had disseminated histoplasmosis. Disseminated histoplasmosis is a progressive haematogenous extra-pulmonary infection. It may occur in patients during the acute infection before cellular immunity develops or by reactivation in immunocompromised patients. In our patient, the clinical presentation of histoplasmosis, including lymphadenopathy and hepatosplenomegaly, was somewhat masked by the underlying CLL and febrile neutropenia that could be attributed to Klebsiella pneumoniae infection. But several clues existed for the diagnosis of histoplasmosis besides the peripheral blood film examination. One clue was the multiple hypodense areas in the spleen, which may have represented histoplasma abscesses. This case emphasizes the importance of microscopic examination of peripheral blood films. Zhaodong Xu, Greg German, Peter Jessamine, Janis Bormanis, Antonio Giulivi and Ruth Padmore Division of Hematopathology, Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON, and Division of Medical Microbiology, Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON, Canada. E-mail: zxu@toh.on.ca images in haematology