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Disseminated Cunninghamella bertholletiae infection with septic pulmonary embolism after allogeneic bone marrow transplantation K. Matsumoto, W. Yamamoto, E. Ohgusa, M. Tanaka, A. Maruta, Y. Ishigatsubo, H. Kanamori. Disseminated Cunninghamella bertholletiae infection with septic pulmonary embolism after allogeneic bone marrow transplantation. Transpl Infect Dis 2014: 16: 304–306. All rights reserved Abstract: Mucormycosis in immunocompromised patients is often reported. We report a patient who developed non-thrombotic pulmonary embolism due to Cunninghamella bertholletiae after allogeneic stem cell transplantation.

K. Matsumoto1, W. Yamamoto1, E. Ohgusa1, M. Tanaka2, A. Maruta1, Y. Ishigatsubo3, H. Kanamori1 1

Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan, 2Department of Hematology, Yokohama City University Yokohama Medical Center, Yokohama, Japan, 3Department Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan Key words: pulmonary embolism; mucormycosis stem cell transplantation; Cunninghamella Correspondence to: Heiwa Kanamori, MD, Department of Hematology, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan Tel: +81 45 391 5761 Fax: +81 45 361 4692 E-mail: [email protected]

Received 28 March 2013, revised 30 June 2013, 8 September 2013, accepted for publication 22 September 2013 DOI: 10.1111/tid.12190 Transpl Infect Dis 2014: 16: 304–306

Mucormycosis is an opportunistic fungal infection that can invade the internal organs of immunocompromised patients. Here, we report a patient who developed non-thrombotic pulmonary embolism (NTPE) due to Cunninghamella bertholletiae after allogeneic stem cell transplantation (SCT). A 61-year-old man with acute myeloid leukemia received SCT from an unrelated matched donor in January 2011. Engraftment was successful and he was discharged in April 2011 without acute graft-versus-host disease. However, the patient was re-admitted to our hospital in August with high-grade fever and dry cough. He had been treated with fluconazole for fungal infection at this time. On admission, laboratory tests revealed a white blood cell count of 1.8 9 109/L,

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hemoglobin of 5.2 g/dL, and platelet count of 1.0 9 109/L. The bone marrow aspirate showed severely hypocellular marrow with 96.8% lymphocytes. Blood cultures were positive for Klebsiella pneumoniae, while those for fungi were negative. Furthermore, serological examinations including b-D glucan and galactomannan antigen were negative. He was diagnosed as having secondary graft failure and sepsis without relapse of his acute myeloid leukemia. Although he was treated with granulocyte colonystimulating factor, antibiotics, and an antifungal agent (micafungin), his symptoms and neutropenia did not improve. The patient suddenly complained of anterior chest pain on day 10 after re-admission, and chest x-ray films

Matsumoto et al: Mucormycosis and pulmonary embolism

and computed tomography scans revealed infiltration with a nodular lesion in the right lung (Fig. 1A). No halo sign, multiple lesions, or pleural effusion was seen. Fungal infection including mucormycosis was suspected on the basis of his clinical and laboratory findings, and therefore liposomal amphotericin B was administered promptly at a dose of 3 mg/kg/day. However, he died of acute respiratory failure at 14 days after admission without any improvement. Autopsy revealed pulmonary embolism (Fig. 1B) with a mass in the enlarged right atrium. Inflammatory lesions were detected around the right bronchus, but other findings were not confirmed by evidence in the lungs. Arterial emboli were also found in the intestines and kidneys. Histological examination showed broad, non-septate, branching hyphae within the arterial emboli (Fig. 1C). The fungal pathogen was identified as C. bertholletiae by culture. NTPE is commonly defined as partial or total occlusion of the pulmonary circulation by a variety of nonthrombotic embolic agents. The main causes of NTPE include cancer, fat, infectious agents, amniotic fluid, foreign materials, and gases (1). This life-threatening

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complication is often underestimated because of the lack of specific symptoms and signs, and retrospective studies based on autopsy data have revealed a much higher incidence of NTPE than expected (2). It is well known that patients with hematological malignancies, such as leukemia or lymphoma, have a high risk of developing septic pulmonary embolism due to fungal infection. Sakuma et al. (3) reported that septic pulmonary embolism was detected in 247 patients (2.2%) among 11,367 patients with pulmonary embolism, and 173 cases of fungal embolism (36 Aspergillus, 31 Mucor, and 18 Candida) were found in a large-scale study based on autopsy findings. Although we could not identify the cause of NTPE before his death, it is noteworthy that fungal embolisms sometimes occur in patients with hematological malignancy. With regard to fungal infection in patients with hematological malignancies, zygomycosis is uncommon and its frequency was reported to be 1.9% in an autopsy study (4). The major pathogens described in previous reports were Rhizopus, Rhizomucor, Mucor, and Absidia, which belong to the order Mucorales, as does Cunninghamella species (5). Although the most frequent site of mucormycosis in

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Fig. 1. Important findings in this patient with non-thrombotic pulmonary embolism. A: Computed tomography of the chest revealed a nodular lesion with obstructive bronchus in the right lung. B: Pulmonary involvement included occlusion of the main pulmonary artery by a large mass. C: Histopathologic examination showed non-septate hyphae in the pulmonary artery (hematoxylin and eosin staining).

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patients with hematological malignancies is the lung (6), and various pulmonary complications can occur after SCT (7), NTPE due to C. bertholletiae (as in our case) seems to be extremely rare. NTPE has a wide spectrum of clinical manifestations, ranging from complete absence of symptoms to death. In general, clinical and laboratory findings are insufficient for making a reliable diagnosis of acute NTPE. Although our patient received liposomal amphotericin B therapy after lung infiltration was detected, he died of disseminated mucormycosis with acute respiratory failure due to fungal NTPE. Prolonged severe neutropenia was suspected to be the main reason for fungal dissemination and poor outcome. Physicians should consider NTPE due to mucormycosis in patients with prolonged neutropenia who present with fever and lung infiltrate and develop acute respiratory failure, although unfortunately no curative strategy exists for this lifethreatening complication.

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References 1. Jorens PG, Van Marck E, Snoeckx A, Parizel PM. Nonthrombotic pulmonary embolism. Eur Respir J 2009; 34: 452–474. 2. Montagnana M, Cervellin G, Franchini M, Lippi G. Pathophysiology, clinics and diagnostics of non-thrombotic pulmonary embolism. J Thromb Thrombolysis 2011; 31: 436–444. 3. Sakuma M, Sugimura K, Nakamura M, et al. Unusual pulmonary embolism: septic pulmonary embolism and amniotic fluid embolism. Circ J 2007; 71: 772–775. 4. Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KV. Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis 2000; 30: 851–856. 5. Prabhu RM, Patel R. Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect 2004; 10: 31–47. 6. Pagano L, Ricci P, Tonso A, et al. Mucormycosis in patients with haematological malignancies: a retrospective clinical study of 37 cases. Br J Haematol 1997; 99: 331–336. 7. Sharma S, Nadrous HF, Peters SG, et al. Pulmonary complications in adult blood and bone marrow transplant recipients: autopsy findings. Chest 2005; 128: 1385–1392.

Transplant Infectious Disease 2014: 16: 304–306

Disseminated Cunninghamella bertholletiae infection with septic pulmonary embolism after allogeneic bone marrow transplantation.

Mucormycosis in immunocompromised patients is often reported. We report a patient who developed non-thrombotic pulmonary embolism due to Cunninghamell...
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