© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
J Cutan Pathol 2014: 41: 483–486 doi: 10.1111/cup.12337 John Wiley & Sons. Printed in Singapore
Journal of Cutaneous Pathology
Cover Quizlet Jayne Bird MD, Gladys Telang MD and Leslie Robinson-Bostom MD Figure 1 and 2 are depicted on the journal cover.
Figure 3.
Figure 4.
Figure 5.
Your diagnosis? Discussion follows on page 484
483
Cover Quizlet
Two Pink Nodules in a Patient with Acute Myeloid Leukemia Jayne Bird MD, Gladys Telang MD and Leslie Robinson-Bostom MD The Warren Alpert School of Brown University email: [email protected]
Keywords: fungal infection, infectious diseases, leukemia Accepted for publication March 9, 2014
Primary cutaneous mucormycosis, a sub-type of mucormycosis, is an infection caused by fungi from the order Mucorales.1 It was previously known as zygomycosis. Cutaneous infection is the third most common sub-type of mucormycosis, preceded by pulmonary and rhino-cerebral involvement. Herein, we present a patient with primary cutaneous mucormycosis, in the setting of acute myeloid leukemia, type M3, with t(15;17), whose biopsy demonstrated mucormycosis mimicking pancreatic panniculitis. An 84-year-old Caucasian woman with recently diagnosed acute myeloid leukemia (type M3, with t(15;17), also known as acute promyelocytic leukemia) developed two discrete 0.9 cm × 0.9 cm nodules with central eschar and well-demarcated pink-violaceous rims on her left upper back while being hospitalized for, and recovering from, disseminated intravascular coagulation (Figure 3). The tender nodules, which appeared several weeks after admission, developed overnight, though no systemic signs of infection were noted. Blood cultures were obtained and were negative for growth. Two punch biopsies were performed; one was for pathologic evaluation with hematoxylin-eosin staining and one was for culture. Routinely-stained sections revealed epidermal ulceration as well as dermal and subcutaneous necrosis. The subcutaneous tissue showed prominent suppurative lobular panniculitis with cystic spaces rimmed by granular basophilic material, resembling ghost cells (Figure 1). Higher magnification demonstrated numerous branching aseptate hyphae throughout the tissue with focal invasion of the vessels, consistent with mucormycosis. Supporting this histopathologic diagnosis were a wet mount
484
Fig. 1. There is a suppurative lobular panniculitis with cystic spaces resembling ghost cells, and numerous branching aseptate hyphae are also present (hematoxylin/eosin, 40x).
(Figure 2), the calcofluor (Figure 5), and a fungal tissue culture (Figure 4), which demonstrated 1+ mold with aseptate hyphae consistent with a Rhizopus species. Upon confirmation of the fungal etiology, the patient was immediately started on lipophilic amphotericin B and surgery was consulted for wide local excision of the two nodules. Later in her hospital course, the patient underwent bronchoalveolar lavage for acute respiratory distress; however, the bronchial specimens were negative for fungal growth. Though her primary cutaneous fungal infection was effectively treated, she later succumbed to acute respiratory distress secondary to congestive heart failure. Primary cutaneous mucormycosis, a sub-type of mucormycosis (previously known as zygomycosis), is
Cover Quizlet
Fig. 2. A wet mount obtained from the tissue culture reveals aseptate hyphae.
an infection caused by fungi from the order Mucorales.1 Cutaneous infection is the third most common subtype. Unlike pulmonary or rhinocerebral involvement, 50% of cases of cutaneous mucormycosis are found in immunocompetent patients, while the other 50% occur in patients with underlying hematologic malignancy, organ transplantation, or diabetes mellitus.2 The ubiquitous fungi causing mucormycosis are found living throughout nature in the soil, decaying matter, wood, cotton, bread, fruits, and vegetables. Most commonly, primary cutaneous infection is caused by direct inoculation and has been reported after insulin injections, intravenous cannulation, arthropod stings, or major trauma.3,4 The clinical presentation of primary cutaneous mucormycosis varies widely and includes strikingly erythematous nodules with central necrotic eschar, large necrotic plaques several centimeters in size, indurated nodules, and bull’s-eye lesions.5,6 Confirmation of the fungal causation is obtained with punch biopsies for culture and conventional microscopy. The tissue culture will demonstrate characteristic fungal growth, which will allow for speciation of the pathologic fungus. In routinelystained sections, the aseptate hyphae and 90-degree branching of mucormycosis are visualized, often with the aid of special fungal staining.
Our case is exceptional because only fourteen cases, in two previously published case reports, have described a cutaneous fungal infection mimicking pancreatic panniculitis. In the article by Requena et al, thirteen cases of cutaneous and mucosal mucormycosis revealed ‘ghost’ adipocytes histopathologically, closely resembling those seen in pancreatic panniculitis or in our case.7 In response to the Requena article, Colmenero et al report a case of cutaneous aspergillosis also imitating pancreatic panniculitis.8 The mechanism behind the development of a lobular panniculitis resembling the ghost cells of pancreatic panniculitis is thought to stem from the large amount of extracellular lipase produced by fungi of the family Mucoraceae, of which Rhizopus and Mucor are members, as well as other fungi such as Aspergillus, Candida, and Penicillium.9,10 We posit that whenever a panniculitis with ‘ghost’ lipocytes is encountered, both fungal infection and pancreatic panniculitis should be considered in the differential diagnosis. Treatment of cutaneous mucormycosis involves both surgical and medical management. While no consensus exists on surgical guidelines, it is considered standard of care to combine debridement with medical therapy, and often multiple debridements are necessary.11,12 First-line medical management involves starting liposomal amphotericin B or amphotericin B lipid complex at dosages ranging from 3 to 5 mg/kg/day for 6 to 8 weeks.3 If amphotericin B is not tolerated, second-line therapy with posaconazole or hyperbaric oxygen can be used.12 Despite aggressive treatment, mortality is estimated to be 31% with cutaneous mucormycosis, though this number improves to 10% with localized infection.11,12 Fig. 3. Two discrete 0.9 cm round nodules with central eschar were observed on the left upper back. Fig. 4. A plated culture grew 1+ mold. Fig. 5. Calcufluor obtained from the tissue culture is depicted.
References 1. Sun H-Y, Singh N. Mucormycosis: its contemporary face and management strategies. Lancet Infect Dis 2011; 11: 301. 2. Roden MM, Zaoutis TE, Buchanan WL, et al. Epidermiology and outcome of zygomycosis: a report of 929 reported cases. Clin Infect Dis 2005; 41: 634. 3. Skiada A, Petrikkos G. Cutaneous mucormycosis. SKINmed 2013; 11: 155.
4. Miyamoto H, Hayashi H, Nakajima H. Cutaneous Mucormycosis in a Patient with Acute Lymphocytic Leukemia. J Dermatol 2005; 32: 273. 5. Burdick L, Hamrock D, Mawhorter S, Tuthill R, Karai L, Regula C, Clarke J, Maher I, Langer J, and Chung C. Asymptomatic necrotic ulcer on leg. J Am Acad Dermatol 2009; 61: 172-4.
6. Rubin A, Grossman M. Bull’s-eye cutaneous infarct of zygomycosis: A bedside diagnosis confirmed by touch preparation. J Am Acad Dermatol 2004; 51: 996. 7. Requena L, Sitthinamsuwan P, Santonja C, et al. Cutaneous and mucosal mucormycosis mimicking pancreatic panniculitis and gouty panniculitis. J Am Acad Dermatol 2012; 66: 975.
485
Cover Quizlet 8. Colmenero I, Alonso-Sanz M, Casco F, Hern´andez-Martín A, Torrelo A. Cutaneous aspergillosis mimicking pancreatic and gouty panniculitis. J Am Acad Dermatol 2012; 67: 789. 9. Singh AK, Mukhopadhyay M. Overview of fungal lipase: a review. Appl Biochem Biotechnol 2012; 166: 486.
486
10. Yike I. Fungal proteases and their pathophysiological effects. Mycopathologia 2011; 171: 299. 11. Lossee JE, Selber J, Vega S, Hall C, Scott G, Serletti JM. Primary cutaneous mucormycosis: guide to surgical management. Ann Plast Surg 2002 Oct; 49: 385.
12. Ledgard JP, van Hal S, and Greenwood JE. Primary cutaneous zygomycosis in a burns patient: a review. J Burn Care Res 2008; 29: 286-90.
J Cutan Pathol 2014: 41: 483–486 doi: 10.1111/cup.12337 John Wiley & Sons. Printed in Singapore
Journal of Cutaneous Pathology
Cover Quizlet Jayne Bird MD, Gladys Telang MD and Leslie Robinson-Bostom MD Figure 1 and 2 are depicted on the journal cover.
Figure 3.
Figure 4.
Figure 5.
Your diagnosis? Discussion follows on page 484
483
Cover Quizlet
Two Pink Nodules in a Patient with Acute Myeloid Leukemia Jayne Bird MD, Gladys Telang MD and Leslie Robinson-Bostom MD The Warren Alpert School of Brown University email: [email protected]
Keywords: fungal infection, infectious diseases, leukemia Accepted for publication March 9, 2014
Primary cutaneous mucormycosis, a sub-type of mucormycosis, is an infection caused by fungi from the order Mucorales.1 It was previously known as zygomycosis. Cutaneous infection is the third most common sub-type of mucormycosis, preceded by pulmonary and rhino-cerebral involvement. Herein, we present a patient with primary cutaneous mucormycosis, in the setting of acute myeloid leukemia, type M3, with t(15;17), whose biopsy demonstrated mucormycosis mimicking pancreatic panniculitis. An 84-year-old Caucasian woman with recently diagnosed acute myeloid leukemia (type M3, with t(15;17), also known as acute promyelocytic leukemia) developed two discrete 0.9 cm × 0.9 cm nodules with central eschar and well-demarcated pink-violaceous rims on her left upper back while being hospitalized for, and recovering from, disseminated intravascular coagulation (Figure 3). The tender nodules, which appeared several weeks after admission, developed overnight, though no systemic signs of infection were noted. Blood cultures were obtained and were negative for growth. Two punch biopsies were performed; one was for pathologic evaluation with hematoxylin-eosin staining and one was for culture. Routinely-stained sections revealed epidermal ulceration as well as dermal and subcutaneous necrosis. The subcutaneous tissue showed prominent suppurative lobular panniculitis with cystic spaces rimmed by granular basophilic material, resembling ghost cells (Figure 1). Higher magnification demonstrated numerous branching aseptate hyphae throughout the tissue with focal invasion of the vessels, consistent with mucormycosis. Supporting this histopathologic diagnosis were a wet mount
484
Fig. 1. There is a suppurative lobular panniculitis with cystic spaces resembling ghost cells, and numerous branching aseptate hyphae are also present (hematoxylin/eosin, 40x).
(Figure 2), the calcofluor (Figure 5), and a fungal tissue culture (Figure 4), which demonstrated 1+ mold with aseptate hyphae consistent with a Rhizopus species. Upon confirmation of the fungal etiology, the patient was immediately started on lipophilic amphotericin B and surgery was consulted for wide local excision of the two nodules. Later in her hospital course, the patient underwent bronchoalveolar lavage for acute respiratory distress; however, the bronchial specimens were negative for fungal growth. Though her primary cutaneous fungal infection was effectively treated, she later succumbed to acute respiratory distress secondary to congestive heart failure. Primary cutaneous mucormycosis, a sub-type of mucormycosis (previously known as zygomycosis), is
Cover Quizlet
Fig. 2. A wet mount obtained from the tissue culture reveals aseptate hyphae.
an infection caused by fungi from the order Mucorales.1 Cutaneous infection is the third most common subtype. Unlike pulmonary or rhinocerebral involvement, 50% of cases of cutaneous mucormycosis are found in immunocompetent patients, while the other 50% occur in patients with underlying hematologic malignancy, organ transplantation, or diabetes mellitus.2 The ubiquitous fungi causing mucormycosis are found living throughout nature in the soil, decaying matter, wood, cotton, bread, fruits, and vegetables. Most commonly, primary cutaneous infection is caused by direct inoculation and has been reported after insulin injections, intravenous cannulation, arthropod stings, or major trauma.3,4 The clinical presentation of primary cutaneous mucormycosis varies widely and includes strikingly erythematous nodules with central necrotic eschar, large necrotic plaques several centimeters in size, indurated nodules, and bull’s-eye lesions.5,6 Confirmation of the fungal causation is obtained with punch biopsies for culture and conventional microscopy. The tissue culture will demonstrate characteristic fungal growth, which will allow for speciation of the pathologic fungus. In routinelystained sections, the aseptate hyphae and 90-degree branching of mucormycosis are visualized, often with the aid of special fungal staining.
Our case is exceptional because only fourteen cases, in two previously published case reports, have described a cutaneous fungal infection mimicking pancreatic panniculitis. In the article by Requena et al, thirteen cases of cutaneous and mucosal mucormycosis revealed ‘ghost’ adipocytes histopathologically, closely resembling those seen in pancreatic panniculitis or in our case.7 In response to the Requena article, Colmenero et al report a case of cutaneous aspergillosis also imitating pancreatic panniculitis.8 The mechanism behind the development of a lobular panniculitis resembling the ghost cells of pancreatic panniculitis is thought to stem from the large amount of extracellular lipase produced by fungi of the family Mucoraceae, of which Rhizopus and Mucor are members, as well as other fungi such as Aspergillus, Candida, and Penicillium.9,10 We posit that whenever a panniculitis with ‘ghost’ lipocytes is encountered, both fungal infection and pancreatic panniculitis should be considered in the differential diagnosis. Treatment of cutaneous mucormycosis involves both surgical and medical management. While no consensus exists on surgical guidelines, it is considered standard of care to combine debridement with medical therapy, and often multiple debridements are necessary.11,12 First-line medical management involves starting liposomal amphotericin B or amphotericin B lipid complex at dosages ranging from 3 to 5 mg/kg/day for 6 to 8 weeks.3 If amphotericin B is not tolerated, second-line therapy with posaconazole or hyperbaric oxygen can be used.12 Despite aggressive treatment, mortality is estimated to be 31% with cutaneous mucormycosis, though this number improves to 10% with localized infection.11,12 Fig. 3. Two discrete 0.9 cm round nodules with central eschar were observed on the left upper back. Fig. 4. A plated culture grew 1+ mold. Fig. 5. Calcufluor obtained from the tissue culture is depicted.
References 1. Sun H-Y, Singh N. Mucormycosis: its contemporary face and management strategies. Lancet Infect Dis 2011; 11: 301. 2. Roden MM, Zaoutis TE, Buchanan WL, et al. Epidermiology and outcome of zygomycosis: a report of 929 reported cases. Clin Infect Dis 2005; 41: 634. 3. Skiada A, Petrikkos G. Cutaneous mucormycosis. SKINmed 2013; 11: 155.
4. Miyamoto H, Hayashi H, Nakajima H. Cutaneous Mucormycosis in a Patient with Acute Lymphocytic Leukemia. J Dermatol 2005; 32: 273. 5. Burdick L, Hamrock D, Mawhorter S, Tuthill R, Karai L, Regula C, Clarke J, Maher I, Langer J, and Chung C. Asymptomatic necrotic ulcer on leg. J Am Acad Dermatol 2009; 61: 172-4.
6. Rubin A, Grossman M. Bull’s-eye cutaneous infarct of zygomycosis: A bedside diagnosis confirmed by touch preparation. J Am Acad Dermatol 2004; 51: 996. 7. Requena L, Sitthinamsuwan P, Santonja C, et al. Cutaneous and mucosal mucormycosis mimicking pancreatic panniculitis and gouty panniculitis. J Am Acad Dermatol 2012; 66: 975.
485
Cover Quizlet 8. Colmenero I, Alonso-Sanz M, Casco F, Hern´andez-Martín A, Torrelo A. Cutaneous aspergillosis mimicking pancreatic and gouty panniculitis. J Am Acad Dermatol 2012; 67: 789. 9. Singh AK, Mukhopadhyay M. Overview of fungal lipase: a review. Appl Biochem Biotechnol 2012; 166: 486.
486
10. Yike I. Fungal proteases and their pathophysiological effects. Mycopathologia 2011; 171: 299. 11. Lossee JE, Selber J, Vega S, Hall C, Scott G, Serletti JM. Primary cutaneous mucormycosis: guide to surgical management. Ann Plast Surg 2002 Oct; 49: 385.
12. Ledgard JP, van Hal S, and Greenwood JE. Primary cutaneous zygomycosis in a burns patient: a review. J Burn Care Res 2008; 29: 286-90.
