VOLUME
33
䡠
NUMBER
10
䡠
APRIL
1
2015
JOURNAL OF CLINICAL ONCOLOGY
D I A G N O S I S
I N
O N C O L O G Y
Isolated Renal Mucormycosis in a Transplantation Recipient Case Report A 30-year-old patient with a relapsed primary mediastinal germ cell tumor with pulmonary and brain metastases enrolled onto a trial of tandem cycles of bevacizumab with high-dose chemotherapy (HDC) with autologous stem-cell support (NCT00936936). His first cycle, using voriconazole as antifungal prophylaxis, proceeded uneventfully. After engraftment, he was readmitted for fever and right flank pain. There were no skin lesions, and the patient had no prior history of mold infection. Blood work showed WBC of 10.9 ⫻ 109/L and absolute neutrophil count of 8.4 ⫻ 109/L. Blood cultures showed negative results for fungi and bacteria. Urinalysis revealed WBC 50 to 100/hpf and RBC greater than 100/hpf without bacteria. A white string-like structure was noticed in his urine. Cytologic examination revealed tangles of fungal hyphae consistent with Mucor-RhizopusAbsidia in a background of acute inflammation and degenerated cells (Fig 1A). A computed tomography (CT) scan of the abdomen revealed an enlarged kidney with hypodense parenchymal regions suggestive of areas of infarction and abscess formation (Fig 2). Chest CT scan showed pre-existing pulmonary metastases and no infection. Treatment was initiated with liposomal amphotericin B (3 mg/kg per day intravenously) and posaconazole (200-300 mg/four times per day orally based on blood levels). CT scans of the sinus and brain did not show lesions suspicious for Mucor involvement. After 2 weeks of treatment, follow-up CT scan of abdomen and pelvis showed slight improvement in the right pyelonephritis. Because of his aggressive tumor, the patient was then admitted for his second planned course of HDC 49 days after his prior HDC cycle. He received both antifungals throughout his second transplantation with liposomal amphotericin B discontinued on day 36. On day 50, he underwent laparoscopic right nephrectomy (Fig 3). Histopathologic examination showed zygomycosis in renal tissue with necrotizing granulomatous inflammation
A
Fig 2.
(Fig 1B). Five months after his second cycle of HDC the patient continues on posaconazole with no evidence of active zygomycosis. Discussion Mucormycosis is a rare opportunistic infection frequently associated with immunosuppressed states. This mold belongs to the order Mucorales, which includes Mucor, Rhizopus, and Absidia. Mucormycosis occurs in less than 2% of hematopoietic stem-cell transplantation recipients1,2 with an overall 1-year survival of less than 20%.3,4 Renal involvement is infrequently encountered and almost exclusively in disseminated forms of mucormycosis.5 In contrast, isolated renal mucormycosis is extremely rare.6,7 The clinical manifestations and radiographic findings of isolated renal mucormycosis are typical of subacute pyelonephritis.8,9 The diagnosis is usually established by microscopic examination and culture of involved fluid or tissues.10-12 On histopathologic examination,
B
Fig 1. e50
© 2014 by American Society of Clinical Oncology
Journal of Clinical Oncology, Vol 33, No 10 (April 1), 2015: pp e50-e51
Diagnosis in Oncology
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES
Fig 3.
fungi appear as large, ribbon-like, aseptate hyphae with irregular ramifications (Fig 1). The pathogenic mechanisms of mucormycosis are not completely understood. Phagocytosis, which remains defective for several months after allogeneic stem-cell transplantation, is the major cellmediated defense against Mucorales.12 The pulmonary tract is the most common organ involved. Mucormycosis usually begins in sinopulmonary tract following inhalation of sporangiospores. Mucorales have a special tendency to interact with endothelial cells, invade blood vessels, and spread hematogenously.12,13 The pathological hallmark is tissue infarction and necrosis due to angioinvasion, which can prevent access of leukocytes and antifungal agents to the site of infection. Surgery is the mainstay of treatment,6,7,9,12,14 along with effective antifungal therapy. Voriconazole, widely used as prophylaxis and primary treatment for Candida and Aspergillus in transplantation patients, has been associated with increased incidence of mucormycosis in this population.2,15 In vitro studies showed that amphotericin B and posaconazole are the only antifungals with good activity against Mucorales.16,17 To our knowledge, this is the first report of a transplantation patient diagnosed with isolated renal mucormycosis. While renal preservation is an important consideration in transplantation patients, the aggressive biology and poor survival associated with this condition necessitated complete nephrectomy.
Amir Hamdi, Victor E. Mulanovich, Surena F. Matin, Gene Landon, Kanishka Sircar, Shi-Ming Tu, and Yago Nieto The University of Texas MD Anderson Cancer Center, Houston, TX
1. Maertens J, Demuynck H, Verbeken EK, et al: Mucormycosis in allogeneic bone marrow transplant recipients: Report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transplant 24:307-312, 1999 2. Marty FM, Cosimi LA, Baden LR: Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med 350:950-952, 2004 3. Marr KA, Carter RA, Crippa F, et al: Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 34:909-917, 2002 4. Kontoyiannis DP, Marr KA, Park BJ, et al: Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) database. Clin Infect Dis 50:1091-1100, 2010 5. Raghavan R, Date A, Bhaktaviziam A: Fungal and nocardial infections of the kidney. Histopathology 11:9-20, 1987 6. Gupta KL, Joshi K, Sud K, et al: Renal zygomycosis: An under-diagnosed cause of acute renal failure. Nephrol Dial Transplant 14:2720-2725, 1999 7. Goel S, Carter JE, Culpepper M, et al: Primary renal zygomycotic infarction mimicking renal neoplasia in an immunocompetent patient. Am J Med Sci 338:330-333, 2009 8. Chugh KS, Sakhuja V, Gupta KL, et al: Renal mucormycosis: Computerized tomographic findings and their diagnostic significance. Am J Kidney Dis 22:393397, 1993 9. Jianhong L, Xianliang H, Xuewu J: Isolated renal mucormycosis in children. J Urol 171:387-388, 2004 10. Roden MM, Zaoutis TE, Buchanan WL, et al: Epidemiology and outcome of zygomycosis: A review of 929 reported cases. Clin Infect Dis 41:634-653, 2005 11. Kontoyiannis DP, Lewis RE: Invasive zygomycosis: Update on pathogenesis, clinical manifestations, and management. Infect Dis Clin North Am 20:581607, 2006 12. Spellberg B, Edwards J Jr, Ibrahim A: Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 18:556569, 2005 13. Langston C, Roberts DA, Porter GA, et al: Renal phycomycosis. J Urol 109:941-944, 1973 14. Chakrabarti A, Das A, Sharma A, et al: Ten years’ experience in zygomycosis at a tertiary care centre in India. J Infect 42:261-266, 2001 15. Kontoyiannis DP, Lionakis MS, Lewis RE, et al: Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: A case-control observational study of 27 recent cases. J Infect Dis 191:13501360, 2005 16. Sun QN, Fothergill AW, McCarthy DI, et al: In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrob Agents Chemother 46:1581-1582, 2002 17. Sabatelli F, Patel R, Mann PA, et al: In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother 50:2009-2015, 2006
DOI: 10.1200/JCO.2013.49.1969; published online ahead of print at www.jco.org on May 19, 2014 ■ ■ ■
www.jco.org
© 2014 by American Society of Clinical Oncology
e51
33
䡠
NUMBER
10
䡠
APRIL
1
2015
JOURNAL OF CLINICAL ONCOLOGY
D I A G N O S I S
I N
O N C O L O G Y
Isolated Renal Mucormycosis in a Transplantation Recipient Case Report A 30-year-old patient with a relapsed primary mediastinal germ cell tumor with pulmonary and brain metastases enrolled onto a trial of tandem cycles of bevacizumab with high-dose chemotherapy (HDC) with autologous stem-cell support (NCT00936936). His first cycle, using voriconazole as antifungal prophylaxis, proceeded uneventfully. After engraftment, he was readmitted for fever and right flank pain. There were no skin lesions, and the patient had no prior history of mold infection. Blood work showed WBC of 10.9 ⫻ 109/L and absolute neutrophil count of 8.4 ⫻ 109/L. Blood cultures showed negative results for fungi and bacteria. Urinalysis revealed WBC 50 to 100/hpf and RBC greater than 100/hpf without bacteria. A white string-like structure was noticed in his urine. Cytologic examination revealed tangles of fungal hyphae consistent with Mucor-RhizopusAbsidia in a background of acute inflammation and degenerated cells (Fig 1A). A computed tomography (CT) scan of the abdomen revealed an enlarged kidney with hypodense parenchymal regions suggestive of areas of infarction and abscess formation (Fig 2). Chest CT scan showed pre-existing pulmonary metastases and no infection. Treatment was initiated with liposomal amphotericin B (3 mg/kg per day intravenously) and posaconazole (200-300 mg/four times per day orally based on blood levels). CT scans of the sinus and brain did not show lesions suspicious for Mucor involvement. After 2 weeks of treatment, follow-up CT scan of abdomen and pelvis showed slight improvement in the right pyelonephritis. Because of his aggressive tumor, the patient was then admitted for his second planned course of HDC 49 days after his prior HDC cycle. He received both antifungals throughout his second transplantation with liposomal amphotericin B discontinued on day 36. On day 50, he underwent laparoscopic right nephrectomy (Fig 3). Histopathologic examination showed zygomycosis in renal tissue with necrotizing granulomatous inflammation
A
Fig 2.
(Fig 1B). Five months after his second cycle of HDC the patient continues on posaconazole with no evidence of active zygomycosis. Discussion Mucormycosis is a rare opportunistic infection frequently associated with immunosuppressed states. This mold belongs to the order Mucorales, which includes Mucor, Rhizopus, and Absidia. Mucormycosis occurs in less than 2% of hematopoietic stem-cell transplantation recipients1,2 with an overall 1-year survival of less than 20%.3,4 Renal involvement is infrequently encountered and almost exclusively in disseminated forms of mucormycosis.5 In contrast, isolated renal mucormycosis is extremely rare.6,7 The clinical manifestations and radiographic findings of isolated renal mucormycosis are typical of subacute pyelonephritis.8,9 The diagnosis is usually established by microscopic examination and culture of involved fluid or tissues.10-12 On histopathologic examination,
B
Fig 1. e50
© 2014 by American Society of Clinical Oncology
Journal of Clinical Oncology, Vol 33, No 10 (April 1), 2015: pp e50-e51
Diagnosis in Oncology
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES
Fig 3.
fungi appear as large, ribbon-like, aseptate hyphae with irregular ramifications (Fig 1). The pathogenic mechanisms of mucormycosis are not completely understood. Phagocytosis, which remains defective for several months after allogeneic stem-cell transplantation, is the major cellmediated defense against Mucorales.12 The pulmonary tract is the most common organ involved. Mucormycosis usually begins in sinopulmonary tract following inhalation of sporangiospores. Mucorales have a special tendency to interact with endothelial cells, invade blood vessels, and spread hematogenously.12,13 The pathological hallmark is tissue infarction and necrosis due to angioinvasion, which can prevent access of leukocytes and antifungal agents to the site of infection. Surgery is the mainstay of treatment,6,7,9,12,14 along with effective antifungal therapy. Voriconazole, widely used as prophylaxis and primary treatment for Candida and Aspergillus in transplantation patients, has been associated with increased incidence of mucormycosis in this population.2,15 In vitro studies showed that amphotericin B and posaconazole are the only antifungals with good activity against Mucorales.16,17 To our knowledge, this is the first report of a transplantation patient diagnosed with isolated renal mucormycosis. While renal preservation is an important consideration in transplantation patients, the aggressive biology and poor survival associated with this condition necessitated complete nephrectomy.
Amir Hamdi, Victor E. Mulanovich, Surena F. Matin, Gene Landon, Kanishka Sircar, Shi-Ming Tu, and Yago Nieto The University of Texas MD Anderson Cancer Center, Houston, TX
1. Maertens J, Demuynck H, Verbeken EK, et al: Mucormycosis in allogeneic bone marrow transplant recipients: Report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transplant 24:307-312, 1999 2. Marty FM, Cosimi LA, Baden LR: Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med 350:950-952, 2004 3. Marr KA, Carter RA, Crippa F, et al: Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 34:909-917, 2002 4. Kontoyiannis DP, Marr KA, Park BJ, et al: Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) database. Clin Infect Dis 50:1091-1100, 2010 5. Raghavan R, Date A, Bhaktaviziam A: Fungal and nocardial infections of the kidney. Histopathology 11:9-20, 1987 6. Gupta KL, Joshi K, Sud K, et al: Renal zygomycosis: An under-diagnosed cause of acute renal failure. Nephrol Dial Transplant 14:2720-2725, 1999 7. Goel S, Carter JE, Culpepper M, et al: Primary renal zygomycotic infarction mimicking renal neoplasia in an immunocompetent patient. Am J Med Sci 338:330-333, 2009 8. Chugh KS, Sakhuja V, Gupta KL, et al: Renal mucormycosis: Computerized tomographic findings and their diagnostic significance. Am J Kidney Dis 22:393397, 1993 9. Jianhong L, Xianliang H, Xuewu J: Isolated renal mucormycosis in children. J Urol 171:387-388, 2004 10. Roden MM, Zaoutis TE, Buchanan WL, et al: Epidemiology and outcome of zygomycosis: A review of 929 reported cases. Clin Infect Dis 41:634-653, 2005 11. Kontoyiannis DP, Lewis RE: Invasive zygomycosis: Update on pathogenesis, clinical manifestations, and management. Infect Dis Clin North Am 20:581607, 2006 12. Spellberg B, Edwards J Jr, Ibrahim A: Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 18:556569, 2005 13. Langston C, Roberts DA, Porter GA, et al: Renal phycomycosis. J Urol 109:941-944, 1973 14. Chakrabarti A, Das A, Sharma A, et al: Ten years’ experience in zygomycosis at a tertiary care centre in India. J Infect 42:261-266, 2001 15. Kontoyiannis DP, Lionakis MS, Lewis RE, et al: Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: A case-control observational study of 27 recent cases. J Infect Dis 191:13501360, 2005 16. Sun QN, Fothergill AW, McCarthy DI, et al: In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrob Agents Chemother 46:1581-1582, 2002 17. Sabatelli F, Patel R, Mann PA, et al: In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother 50:2009-2015, 2006
DOI: 10.1200/JCO.2013.49.1969; published online ahead of print at www.jco.org on May 19, 2014 ■ ■ ■
www.jco.org
© 2014 by American Society of Clinical Oncology
e51
