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Mycotic pulmonary artery aneurysm due to Aspergillus infection in a patient with leukemia: Case report and review of the literature
Leukemia Research 34 (2010) e133–e136
Contents lists available at ScienceDirect
Leukemia Research journal homepage: www.elsevier.com/locate/leukres
Letter to the Editor Mycotic pulmonary artery aneurysm due to Aspergillus infection in a patient with leukemia: Case report and review of the literature
a r t i c l e
i n f o
Keywords: Pulmonary aneurysm Aspergillus Leukemia
a b s t r a c t We present a case of a patient with hairy cell leukemia and pulmonary aspergillosis who developed a cycotic pulmonary artery aneurysm despite prolonged antifungal therapy. A review of the literature in regards to incidence, etiology, clinical manifestations and treatment options is included. © 2009 Elsevier Ltd. All rights reserved.
1. Introduction Pulmonary artery aneurysms secondary to pulmonary infection are infrequent and usually occur in patients with infective endocarditis or congenital heart disease. Staphylococcus aureus and Streptococcus spp. are generally the most often isolated causative microorganisms. Mycotic pulmonary aneurysms due to invasive fungal infection (IFI) are rare and occur as a result of direct extension from the lung in patients with pneumonia or due to septic emboli [1,2]. The causative organisms are usually Aspergillus spp., Mucorales, and Candida spp. and infection typically occur in patients with congenital heart disease [3,4], hematologic malignancies [5], and diabetes mellitus [6] or after invasive percutaneous procedures [7]. The mortality rate in patients with mycotic pulmonary aneurysms is high and early diagnosis and prompt intervention are important in preventing life-threatening hemorrhage [8]. We report a case of a patient with hairy cell leukemia and pulmonary aspergillosis who developed a mycotic pulmonary artery aneurysm despite prolonged antifungal therapy and review the literature to provide an overview of the incidence, etiology, clinical manifestations and treatment of this entity. 2. Case report A 49-year-old man with a medical history significant for mitral valve prolapse presented with a 1-year history of easy bruising and a 6-month history of generalized malaise and abdominal fullness. Laboratory studies revealed a white blood cell count of 4.8 × 109 L−1 , with 49% unclassified cells, 48% lymphocytes, and 3% neutrophils; a hemoglobin level of 7 g/dL; and a platelet count of 52 × 109 L−1 . A bone marrow biopsy showed 90% cellularity and the presence of hairy leukemic cells expressing CD103, CD25, CD22, CD11, CD20 and CD19 markers. The decision was made to treat the patient with standard chemotherapy for hairy cell leukemia: cladribine 0.1 mg/kg intravenously over 2 h daily for 5 days. On admission to the hospital for chemotherapy, the patient was found to have a dental abscess and was treated with clindamycin. A chest radiograph showed bilateral pulmonary opacities consistent with pneumonia. Blood cultures were negative. Levofloxacin, vala-
0145-2126/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2009.11.010
cyclovir hydrochloride, and fluconazole (200 mg by mouth daily) were added for bacterial, viral, and fungal prophylaxis, respectively. A follow-up chest X-ray on day 14 from the start of chemotherapy showed clear lungs; at that time, the patient’s white blood cell count was 0.3 × 109 L−1 , and he was started on therapy with granulocyte colony-stimulating factor (GM-CSF) to expedite recovery of the bone marrow. The patient was discharged home day 4 from the start of chemotherapy on clindamycin, levofloxacin, and valacyclovir. He was readmitted 9 days later because of neutropenic fever. Clindamycin was discontinued, and treatment with ceftazidine, vancomycin, and fluconazole was begun for antifungal prophylaxis. He became afebrile and 2 days later he was discharged home. Four days after discharge, the patient was readmitted to the hospital for recurrent neutropenic fever, dry cough, and pleuritic chest pain. A chest radiograph revealed an ill-defined opacity in the middle lobe of the right lung associated with a small pleural effusion. The patient was started on meropenem and liposomal amphotericin B (5 mg/kg/day). One week later, however, chest computed tomography (CT) revealed bilateral pleural effusions and ground-glass opacities and scattered mass-like opacities in both lungs. Antifungal therapy was changed to caspofungin acetate (70 mg intravenously on day 1, then 50 mg intravenously daily) and voriconazole (200 mg by mouth twice a day) (Fig. 1A). A CT-guided biopsy of a mass-like opacity in the right lung was performed. Grocott’s methenamine silver staining revealed numerous fungal hyphae consistent with Aspergillus sp.; fungal cultures were negative. Treatment with caspofungin and voriconazole was continued. Over the next week, the patient’s white blood cell count and differential count recovered to normal levels, and his pulmonary symptoms markedly improved. A bone marrow biopsy revealed normal findings, and the patient was declared to be in complete remission from hairy cell leukemia. Treatment with caspofungin and voriconazole was continued over the next 2 months, and the patient was periodically given GM-CSF to maintain his neutrophil level at high normal level. Additional chest radiographs obtained approximately every 2 weeks during these 2 months showed waxing and waning of the pulmonary opacities but never complete clearance.
e134
Letter to the Editor / Leukemia Research 34 (2010) e133–e136
Fig. 1. (A) Bilateral pleural effusions and ground-glass opacities and scattered mass-like opacities in both lungs. (B) 14-Week chest CT scan revealed a new 3.5 cm saccular/focal aneurysm of the right interlobar artery pulmonary artery.
Unfortunately, the patient was readmitted to the hospital 4 months after the admission for recurrent neutropenic fever with hemoptysis, bilateral rhonci, and shortness of breath. A chest radiograph showed progression of bilateral opacities in the right lower lung and bilateral pleural effusions. Bronchoscopy with bronchoalveolar lavage was performed and revealed several thick mucous plugs in the bronchi with no other abnormalities. Pathologic examination of one of the thick mucous plugs revealed necrotic tissue, acute inflammation, and numerous fungal hyphae consistent with Aspergillus sp. Voriconazole was changed to amphotericin B lipid complex (7.5 mg/kg/day), and caspofungin was continued at the same dose. Three weeks later, CT of the chest showed persistence and progression of some nodular lesions and improvement of others. Because of these findings, the previous antifungal therapy was discontinued, and the patient was started on posaconazole (200 mg 4 times a day). Although two subsequent chest CT scans (obtained at 4 and 14 weeks after his admission for hemoptysis) showed decrease in the consolidative and nodular opacities, the 14-week chest CT scan revealed a new 3.5 cm saccular/focal aneurysm of the right interlobar artery pulmonary artery (Fig. 1B). Because of the risk of massive hemoptysis, the patient underwent thoracotomy and middle and right lower lobe resection. The
pathologic examination confirmed an aneurysm of the interlobar pulmonary artery and revealed thrombus containing numerous fungal organisms consistent with Aspergillus sp. infection and an abscess in the adjacent lung parenchyma Aspergillus sp. (Fig. 2A and B). The patient continued antifungal therapy with posaconazole for the following 2 years. He remained clinically stable, without clinical or imaging findings of recurrent infection or leukemia. Unfortunately, the patient died two and a half years after the surgery due to progressive emphysema and pulmonary hypertension. 3. Discussion Invasive fungal infections (IFI) are a frequent complication in patients with hematologic malignancies and in patients undergoing stem cell transplantation. The most common fungal infections in these high-risk patients are due to Candida spp. and Aspergillus. Although new tests have been developed for early diagnosis of fungal infections [9,10] and the armamentarium of antifungal drugs has increased substantially in the last decade, the mortality rate due to IFI continues to be high. In this regard, IFI can manifest as pulmonary artery aneurysms. However, the development of mycotic pulmonary artery aneurysm as a complication of IFI of
Fig. 2. (A) Lung tissue with a fungal ball composed of a tangled mass of fungal hyphae (H&E stains). (B) Higher magnification image demonstrating fungal hyphae without apparent septations.
Lobectomy and posa-
32
62
49
F
M
M
Died 28 months after diagnosis of aneurysm due to pulmonary hypertension
12 F
Surgery for insertion of prosthetic tricuspid valve Hairy cell leukemia
Filamentous fungi with septate pseudohyphae and budding yeast Aspergillus spp.
Hemoptysis and shortness of breath
Died due to massive hemoptysis Died due to massive bleeding after bronchoscopy Antibiotics Mucormycosis
Fever, cough, rinorrhea, and chest pain Shortness of breath and cough with hemoptysis
None
Died due to massive bleeding Tricuspid valve replacement Fever and intermittent back pain Aspergillus spp.
5 months F
Surgery for ventricular septal defect and ventriculoarterial discordance with dextroposition of the aorta Surgery for insertion of porcine pulmonary valve and partial tricuspid annuloplasty Diabetes
Aspergillus spp.
Tachypnea, fever, and hemoptysis
Excision and fluconazole
Died due to massive bleeding during bronchoscopy Alive None Left total pneumothorax Aspergillus fumigatus 53 M
Acute myelogenous leukemia
Age (years) Sex
e135
the lung is rare: a search of the English literature in PubMed using the search terms “pulmonary artery mycotic aneurysm” and “Aspergillus” revealed only five published cases [3–7]. The main clinical features of these cases are shown in Table 1. The most frequently reported underlying organism was Aspergillus (3 cases); 1 patient developed fungal aneurysm due to Candida spp. and another developed fungal aneurysm due to Mucormycosis. Three of the previously reported cases occurred in patients with a history of cardiac surgery [3,4,7]; only one occurred in a patient with a history of acute leukemia [5]. Thus, our patient is the second reported patient with leukemia and pulmonary aneurysm due to Aspergillus spp. The most common symptoms of pulmonary artery aneurysm are cough, dyspnea, and chest pain [11]. The clinical presentations of the five previously reported patients were remarkable for fever (3 of 5 patients) and respiratory symptoms, such as cough, hemoptysis, and/or shortness of breath. In contrast, at the moment of diagnosis of the aneurysm, the patient we report had only mild cough and described no other symptoms. Possible explanations for this lack of symptoms are partial improvement of the pulmonary disease due to leukemia remission and the prolonged time on antifungal treatment. Mycotic aneurysm of the pulmonary artery may be impossible to differentiate from inflammatory or malignant processes of the lung. If the aneurysm originates proximally, it may be confused with mediastinal lymphadenopathy due to tuberculosis or lymphoma; if the aneurysm develops in a more peripheral branch, it may be confused with numerous other causes of pulmonary lesions [12]. In our patient, the extensive parenchymal disease revealed on previous CT may have masked the aneurysm, which was evident after the pulmonary opacities improved. The gold standard for diagnosis of pulmonary aneurysm is angiography, which allows determination of whether other structures are involved and assessment of rightside cardiac pressures [11]. Magnetic resonance imaging is useful for estimating the size of the lesion and assessing the severity of the aneurysm [13]. In the previously reported cases of fungal pulmonary artery aneurysm, the mortality rate was 80% (4 of 5 patients). In 2 of the patients, death was a complication of bronchoscopy; the other 2 died of massive bleeding due to rupture of the aneurysm. The only patient who survived, like our patient, had thoracotomy with excision of the aneurysm. Medical treatment alone may not prevent rupture of the pulmonary artery. Surgical repair of the mycotic pulmonary aneurysm is vital. Different approaches at repair have been described, such as arterioplasty, pericardial patch reconstruction, and interposition grafting with allografts or synthetic textile grafts [14,15]. The type of procedure depends on the site of involvement. For aneurysms of the main pulmonary trunk, aneurysmorrhaphy is performed. In the case of distal involvement, a lobectomy is performed, and in the case of multiple aneurysms, a pulmonectomy is performed. Removal of lesser amounts of pulmonary parenchyma has been also successfully employed. Over the last few years, minimally invasive transcatheter embolization with steel coils or detachable balloons is increasingly being used as a safe method of preventing aneurysm rupture [15,16].
Conazole
Present case (2009)
[6] (1988)
[5] (1982)
[2] (2000)
[3]
[4] (2005)
4. Conclusion Reference (year)
Table 1 Previously reported cases of mycotic pulmonary artery aneurysm.
Predisposing factor
Organism
Clinical presentation
Treatment
Outcome
Letter to the Editor / Leukemia Research 34 (2010) e133–e136
Mycotic aneurysms of the pulmonary artery are a rare and potentially life-threatening complication of pulmonary fungal infection. Our case demonstrates that despite the development of new and broad-spectrum antifungal medication, complications associated with IFI can still occur. In particular, chronic antifungal treatment does not preclude the development of a mycotic
e136
Letter to the Editor / Leukemia Research 34 (2010) e133–e136
aneurysm of the pulmonary arteries. Accordingly, vigilance and early diagnosis remain important as prompt surgical treatment can decrease morbidity and mortality. Conflict of interest There are no conflict of interests to disclose. Role of funding source There are no funding sources to disclose. Acknowledgement All authors met the criteria for authorship. References [1] Coffey MJ, Fantone 3rd J, Stirling MC, Lynch 3rd JP. Pseudoaneurysm of pulmonary artery in mucormycosis. Radiographic characteristics and management. Am Rev Respir Dis 1992;145(6):1487–90. [2] Loevner LA, Andrews JC, Francis IR. Multiple mycotic pulmonary artery aneurysms: a complication of invasive mucormycosis. AJR 1992;158(4):761–2. [3] Choyke PL, Edmonds PR, Markowitz RI, Kleinman CS, Laks H. Mycotic pulmonary artery aneurysm: complication of Aspergillus endocarditis. AJR 1982;138(6):1172–5. [4] Talwar S, Sharma R, Das B, Bhan A, Ray R, Saxena A, et al. Multiple fungal mycotic pulmonary artery aneurysms in an infant. Indian Heart J 2000;52(3):343–5. [5] Greillier L, Barlesi F, Fraticelli A, Gimenez C, Chetaille B, Gaubert JY, et al. Fatal pulmonary haemorrhage from a mycotic pulmonary artery aneurysm. Int J Tuberc Lung Dis 2005;9(6):702–3. [6] Vaideeswar P. Fatal haemoptysis due to mucormycotic intrapulmonary arterial aneurysm. Int J Cardiol 2002;83(3):273–4. [7] Roush K, Scala-Barnett DM, Donabedian H, Freimer EH. Rupture of a pulmonary artery mycotic aneurysm associated with candidal endocarditis. Am J Med 1988;84(1):142–4. [8] Navarro C, Dickinson PC, Kondlapoodi P, Hagstrom JW. Mycotic aneurysms of the pulmonary arteries in intravenous drug addicts. Report of three cases and review of the literature. Am J Med 1984;76(6):1124–31. [9] De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46(12):1813–21.
[10] Caillot D, Couaillier JF, Bernard A, Casasnovas O, Denning DW, Mannone L, et al. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J Clin Oncol 2001;19(1):253–9. [11] Garcia A, Byrne JG, Bueno R, Flores RM. Aneurysm of the main pulmonary artery. Ann Thorac Cardiovasc Surg 2008;14(6):399–401. [12] Jaffe RB, Condon VR. Mycotic aneurysms of the pulmonary artery and aorta. Radiology 1975;116(02):291–8. [13] Lopez-Candales A, Kleiger RE, Aleman-Gomez J, Kouchoukos NT, Botney MD. Pulmonary artery aneurysm: review and case report. Clinical cardiology 1995;18(12):738–40. [14] Hamawy AH, Cartledge RG, Girardi LN. Graft repair of a pulmonary artery aneurysm. Heart Surg Forum 2002;5(4):396–8. [15] Caralps JM, Bonnin JO, Oter R, Aris A. True aneurysm of the main pulmonary artery: surgical correction. Ann Thorac Surg 1978;25(6):561–3. [16] Pelage JP, El Hajjam M, Lagrange C, Chinet T, Vieillard-Baron A, Chagnon S, et al. Pulmonary artery interventions: an overview. Radiographics 2005;25(6):1653–67.
Matjaz Sever a Srdan Verstovsek a Jeremy Erasmus Jr. b Gloria N. Mattiuzzi a,∗ a Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA b Department of Diagnostic Radiology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA ∗ Corresponding author at: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe, Unit 428, Houston, TX 77030, USA. Tel.: +1 713 745 2723; fax: +1 713 745 5372. E-mail address: [email protected] (G.N. Mattiuzzi)
9 October 2009 10 November 2009 13 November 2009 Available online 4 January 2010
Contents lists available at ScienceDirect
Leukemia Research journal homepage: www.elsevier.com/locate/leukres
Letter to the Editor Mycotic pulmonary artery aneurysm due to Aspergillus infection in a patient with leukemia: Case report and review of the literature
a r t i c l e
i n f o
Keywords: Pulmonary aneurysm Aspergillus Leukemia
a b s t r a c t We present a case of a patient with hairy cell leukemia and pulmonary aspergillosis who developed a cycotic pulmonary artery aneurysm despite prolonged antifungal therapy. A review of the literature in regards to incidence, etiology, clinical manifestations and treatment options is included. © 2009 Elsevier Ltd. All rights reserved.
1. Introduction Pulmonary artery aneurysms secondary to pulmonary infection are infrequent and usually occur in patients with infective endocarditis or congenital heart disease. Staphylococcus aureus and Streptococcus spp. are generally the most often isolated causative microorganisms. Mycotic pulmonary aneurysms due to invasive fungal infection (IFI) are rare and occur as a result of direct extension from the lung in patients with pneumonia or due to septic emboli [1,2]. The causative organisms are usually Aspergillus spp., Mucorales, and Candida spp. and infection typically occur in patients with congenital heart disease [3,4], hematologic malignancies [5], and diabetes mellitus [6] or after invasive percutaneous procedures [7]. The mortality rate in patients with mycotic pulmonary aneurysms is high and early diagnosis and prompt intervention are important in preventing life-threatening hemorrhage [8]. We report a case of a patient with hairy cell leukemia and pulmonary aspergillosis who developed a mycotic pulmonary artery aneurysm despite prolonged antifungal therapy and review the literature to provide an overview of the incidence, etiology, clinical manifestations and treatment of this entity. 2. Case report A 49-year-old man with a medical history significant for mitral valve prolapse presented with a 1-year history of easy bruising and a 6-month history of generalized malaise and abdominal fullness. Laboratory studies revealed a white blood cell count of 4.8 × 109 L−1 , with 49% unclassified cells, 48% lymphocytes, and 3% neutrophils; a hemoglobin level of 7 g/dL; and a platelet count of 52 × 109 L−1 . A bone marrow biopsy showed 90% cellularity and the presence of hairy leukemic cells expressing CD103, CD25, CD22, CD11, CD20 and CD19 markers. The decision was made to treat the patient with standard chemotherapy for hairy cell leukemia: cladribine 0.1 mg/kg intravenously over 2 h daily for 5 days. On admission to the hospital for chemotherapy, the patient was found to have a dental abscess and was treated with clindamycin. A chest radiograph showed bilateral pulmonary opacities consistent with pneumonia. Blood cultures were negative. Levofloxacin, vala-
0145-2126/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2009.11.010
cyclovir hydrochloride, and fluconazole (200 mg by mouth daily) were added for bacterial, viral, and fungal prophylaxis, respectively. A follow-up chest X-ray on day 14 from the start of chemotherapy showed clear lungs; at that time, the patient’s white blood cell count was 0.3 × 109 L−1 , and he was started on therapy with granulocyte colony-stimulating factor (GM-CSF) to expedite recovery of the bone marrow. The patient was discharged home day 4 from the start of chemotherapy on clindamycin, levofloxacin, and valacyclovir. He was readmitted 9 days later because of neutropenic fever. Clindamycin was discontinued, and treatment with ceftazidine, vancomycin, and fluconazole was begun for antifungal prophylaxis. He became afebrile and 2 days later he was discharged home. Four days after discharge, the patient was readmitted to the hospital for recurrent neutropenic fever, dry cough, and pleuritic chest pain. A chest radiograph revealed an ill-defined opacity in the middle lobe of the right lung associated with a small pleural effusion. The patient was started on meropenem and liposomal amphotericin B (5 mg/kg/day). One week later, however, chest computed tomography (CT) revealed bilateral pleural effusions and ground-glass opacities and scattered mass-like opacities in both lungs. Antifungal therapy was changed to caspofungin acetate (70 mg intravenously on day 1, then 50 mg intravenously daily) and voriconazole (200 mg by mouth twice a day) (Fig. 1A). A CT-guided biopsy of a mass-like opacity in the right lung was performed. Grocott’s methenamine silver staining revealed numerous fungal hyphae consistent with Aspergillus sp.; fungal cultures were negative. Treatment with caspofungin and voriconazole was continued. Over the next week, the patient’s white blood cell count and differential count recovered to normal levels, and his pulmonary symptoms markedly improved. A bone marrow biopsy revealed normal findings, and the patient was declared to be in complete remission from hairy cell leukemia. Treatment with caspofungin and voriconazole was continued over the next 2 months, and the patient was periodically given GM-CSF to maintain his neutrophil level at high normal level. Additional chest radiographs obtained approximately every 2 weeks during these 2 months showed waxing and waning of the pulmonary opacities but never complete clearance.
e134
Letter to the Editor / Leukemia Research 34 (2010) e133–e136
Fig. 1. (A) Bilateral pleural effusions and ground-glass opacities and scattered mass-like opacities in both lungs. (B) 14-Week chest CT scan revealed a new 3.5 cm saccular/focal aneurysm of the right interlobar artery pulmonary artery.
Unfortunately, the patient was readmitted to the hospital 4 months after the admission for recurrent neutropenic fever with hemoptysis, bilateral rhonci, and shortness of breath. A chest radiograph showed progression of bilateral opacities in the right lower lung and bilateral pleural effusions. Bronchoscopy with bronchoalveolar lavage was performed and revealed several thick mucous plugs in the bronchi with no other abnormalities. Pathologic examination of one of the thick mucous plugs revealed necrotic tissue, acute inflammation, and numerous fungal hyphae consistent with Aspergillus sp. Voriconazole was changed to amphotericin B lipid complex (7.5 mg/kg/day), and caspofungin was continued at the same dose. Three weeks later, CT of the chest showed persistence and progression of some nodular lesions and improvement of others. Because of these findings, the previous antifungal therapy was discontinued, and the patient was started on posaconazole (200 mg 4 times a day). Although two subsequent chest CT scans (obtained at 4 and 14 weeks after his admission for hemoptysis) showed decrease in the consolidative and nodular opacities, the 14-week chest CT scan revealed a new 3.5 cm saccular/focal aneurysm of the right interlobar artery pulmonary artery (Fig. 1B). Because of the risk of massive hemoptysis, the patient underwent thoracotomy and middle and right lower lobe resection. The
pathologic examination confirmed an aneurysm of the interlobar pulmonary artery and revealed thrombus containing numerous fungal organisms consistent with Aspergillus sp. infection and an abscess in the adjacent lung parenchyma Aspergillus sp. (Fig. 2A and B). The patient continued antifungal therapy with posaconazole for the following 2 years. He remained clinically stable, without clinical or imaging findings of recurrent infection or leukemia. Unfortunately, the patient died two and a half years after the surgery due to progressive emphysema and pulmonary hypertension. 3. Discussion Invasive fungal infections (IFI) are a frequent complication in patients with hematologic malignancies and in patients undergoing stem cell transplantation. The most common fungal infections in these high-risk patients are due to Candida spp. and Aspergillus. Although new tests have been developed for early diagnosis of fungal infections [9,10] and the armamentarium of antifungal drugs has increased substantially in the last decade, the mortality rate due to IFI continues to be high. In this regard, IFI can manifest as pulmonary artery aneurysms. However, the development of mycotic pulmonary artery aneurysm as a complication of IFI of
Fig. 2. (A) Lung tissue with a fungal ball composed of a tangled mass of fungal hyphae (H&E stains). (B) Higher magnification image demonstrating fungal hyphae without apparent septations.
Lobectomy and posa-
32
62
49
F
M
M
Died 28 months after diagnosis of aneurysm due to pulmonary hypertension
12 F
Surgery for insertion of prosthetic tricuspid valve Hairy cell leukemia
Filamentous fungi with septate pseudohyphae and budding yeast Aspergillus spp.
Hemoptysis and shortness of breath
Died due to massive hemoptysis Died due to massive bleeding after bronchoscopy Antibiotics Mucormycosis
Fever, cough, rinorrhea, and chest pain Shortness of breath and cough with hemoptysis
None
Died due to massive bleeding Tricuspid valve replacement Fever and intermittent back pain Aspergillus spp.
5 months F
Surgery for ventricular septal defect and ventriculoarterial discordance with dextroposition of the aorta Surgery for insertion of porcine pulmonary valve and partial tricuspid annuloplasty Diabetes
Aspergillus spp.
Tachypnea, fever, and hemoptysis
Excision and fluconazole
Died due to massive bleeding during bronchoscopy Alive None Left total pneumothorax Aspergillus fumigatus 53 M
Acute myelogenous leukemia
Age (years) Sex
e135
the lung is rare: a search of the English literature in PubMed using the search terms “pulmonary artery mycotic aneurysm” and “Aspergillus” revealed only five published cases [3–7]. The main clinical features of these cases are shown in Table 1. The most frequently reported underlying organism was Aspergillus (3 cases); 1 patient developed fungal aneurysm due to Candida spp. and another developed fungal aneurysm due to Mucormycosis. Three of the previously reported cases occurred in patients with a history of cardiac surgery [3,4,7]; only one occurred in a patient with a history of acute leukemia [5]. Thus, our patient is the second reported patient with leukemia and pulmonary aneurysm due to Aspergillus spp. The most common symptoms of pulmonary artery aneurysm are cough, dyspnea, and chest pain [11]. The clinical presentations of the five previously reported patients were remarkable for fever (3 of 5 patients) and respiratory symptoms, such as cough, hemoptysis, and/or shortness of breath. In contrast, at the moment of diagnosis of the aneurysm, the patient we report had only mild cough and described no other symptoms. Possible explanations for this lack of symptoms are partial improvement of the pulmonary disease due to leukemia remission and the prolonged time on antifungal treatment. Mycotic aneurysm of the pulmonary artery may be impossible to differentiate from inflammatory or malignant processes of the lung. If the aneurysm originates proximally, it may be confused with mediastinal lymphadenopathy due to tuberculosis or lymphoma; if the aneurysm develops in a more peripheral branch, it may be confused with numerous other causes of pulmonary lesions [12]. In our patient, the extensive parenchymal disease revealed on previous CT may have masked the aneurysm, which was evident after the pulmonary opacities improved. The gold standard for diagnosis of pulmonary aneurysm is angiography, which allows determination of whether other structures are involved and assessment of rightside cardiac pressures [11]. Magnetic resonance imaging is useful for estimating the size of the lesion and assessing the severity of the aneurysm [13]. In the previously reported cases of fungal pulmonary artery aneurysm, the mortality rate was 80% (4 of 5 patients). In 2 of the patients, death was a complication of bronchoscopy; the other 2 died of massive bleeding due to rupture of the aneurysm. The only patient who survived, like our patient, had thoracotomy with excision of the aneurysm. Medical treatment alone may not prevent rupture of the pulmonary artery. Surgical repair of the mycotic pulmonary aneurysm is vital. Different approaches at repair have been described, such as arterioplasty, pericardial patch reconstruction, and interposition grafting with allografts or synthetic textile grafts [14,15]. The type of procedure depends on the site of involvement. For aneurysms of the main pulmonary trunk, aneurysmorrhaphy is performed. In the case of distal involvement, a lobectomy is performed, and in the case of multiple aneurysms, a pulmonectomy is performed. Removal of lesser amounts of pulmonary parenchyma has been also successfully employed. Over the last few years, minimally invasive transcatheter embolization with steel coils or detachable balloons is increasingly being used as a safe method of preventing aneurysm rupture [15,16].
Conazole
Present case (2009)
[6] (1988)
[5] (1982)
[2] (2000)
[3]
[4] (2005)
4. Conclusion Reference (year)
Table 1 Previously reported cases of mycotic pulmonary artery aneurysm.
Predisposing factor
Organism
Clinical presentation
Treatment
Outcome
Letter to the Editor / Leukemia Research 34 (2010) e133–e136
Mycotic aneurysms of the pulmonary artery are a rare and potentially life-threatening complication of pulmonary fungal infection. Our case demonstrates that despite the development of new and broad-spectrum antifungal medication, complications associated with IFI can still occur. In particular, chronic antifungal treatment does not preclude the development of a mycotic
e136
Letter to the Editor / Leukemia Research 34 (2010) e133–e136
aneurysm of the pulmonary arteries. Accordingly, vigilance and early diagnosis remain important as prompt surgical treatment can decrease morbidity and mortality. Conflict of interest There are no conflict of interests to disclose. Role of funding source There are no funding sources to disclose. Acknowledgement All authors met the criteria for authorship. References [1] Coffey MJ, Fantone 3rd J, Stirling MC, Lynch 3rd JP. Pseudoaneurysm of pulmonary artery in mucormycosis. Radiographic characteristics and management. Am Rev Respir Dis 1992;145(6):1487–90. [2] Loevner LA, Andrews JC, Francis IR. Multiple mycotic pulmonary artery aneurysms: a complication of invasive mucormycosis. AJR 1992;158(4):761–2. [3] Choyke PL, Edmonds PR, Markowitz RI, Kleinman CS, Laks H. Mycotic pulmonary artery aneurysm: complication of Aspergillus endocarditis. AJR 1982;138(6):1172–5. [4] Talwar S, Sharma R, Das B, Bhan A, Ray R, Saxena A, et al. Multiple fungal mycotic pulmonary artery aneurysms in an infant. Indian Heart J 2000;52(3):343–5. [5] Greillier L, Barlesi F, Fraticelli A, Gimenez C, Chetaille B, Gaubert JY, et al. Fatal pulmonary haemorrhage from a mycotic pulmonary artery aneurysm. Int J Tuberc Lung Dis 2005;9(6):702–3. [6] Vaideeswar P. Fatal haemoptysis due to mucormycotic intrapulmonary arterial aneurysm. Int J Cardiol 2002;83(3):273–4. [7] Roush K, Scala-Barnett DM, Donabedian H, Freimer EH. Rupture of a pulmonary artery mycotic aneurysm associated with candidal endocarditis. Am J Med 1988;84(1):142–4. [8] Navarro C, Dickinson PC, Kondlapoodi P, Hagstrom JW. Mycotic aneurysms of the pulmonary arteries in intravenous drug addicts. Report of three cases and review of the literature. Am J Med 1984;76(6):1124–31. [9] De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46(12):1813–21.
[10] Caillot D, Couaillier JF, Bernard A, Casasnovas O, Denning DW, Mannone L, et al. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J Clin Oncol 2001;19(1):253–9. [11] Garcia A, Byrne JG, Bueno R, Flores RM. Aneurysm of the main pulmonary artery. Ann Thorac Cardiovasc Surg 2008;14(6):399–401. [12] Jaffe RB, Condon VR. Mycotic aneurysms of the pulmonary artery and aorta. Radiology 1975;116(02):291–8. [13] Lopez-Candales A, Kleiger RE, Aleman-Gomez J, Kouchoukos NT, Botney MD. Pulmonary artery aneurysm: review and case report. Clinical cardiology 1995;18(12):738–40. [14] Hamawy AH, Cartledge RG, Girardi LN. Graft repair of a pulmonary artery aneurysm. Heart Surg Forum 2002;5(4):396–8. [15] Caralps JM, Bonnin JO, Oter R, Aris A. True aneurysm of the main pulmonary artery: surgical correction. Ann Thorac Surg 1978;25(6):561–3. [16] Pelage JP, El Hajjam M, Lagrange C, Chinet T, Vieillard-Baron A, Chagnon S, et al. Pulmonary artery interventions: an overview. Radiographics 2005;25(6):1653–67.
Matjaz Sever a Srdan Verstovsek a Jeremy Erasmus Jr. b Gloria N. Mattiuzzi a,∗ a Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA b Department of Diagnostic Radiology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA ∗ Corresponding author at: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe, Unit 428, Houston, TX 77030, USA. Tel.: +1 713 745 2723; fax: +1 713 745 5372. E-mail address: [email protected] (G.N. Mattiuzzi)
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