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Mycosis fungoides–associated follicular mucinosis after bone-marrow transplantation
e240 Letters
children.2,4,5 There are also data suggesting that outcome might be better in those patients lacking cutaneous lesions, although comparisons between different groups might be confounded by differences in treatment regimens.2,4 An aggressive initial therapy that includes hematopoietic stem-cell transplantation may improve the patients’ prognosis. Although it is generally accepted that initial high-dose chemotherapy is essential in all age groups, it is still debated if hematopoietic stemcell transplantation should be reserved for children who relapse and achieve a second remission2 or should be performed after the first complete remission as is recommended for adults and as was done in our case.4 Additional studies are needed to identify the optimal therapeutic regimen. These patients should be expeditiously admitted to a tertiary oncologic pediatric center that has expertise in hematopoietic stem-cell transplantation. opez-Lerma, Carla Ferr a ndiz-Pulido, MD,a Ingrid L MD, PhD,a Constantino S abado, MD,b Berta Ferrer, MD,c Sandra Pisa, MD,b and Vicente Garcıa-Patos, MD, PhDa Departments of Dermatology,a Pediatric b Oncology, and Pathology,c Hospital Universitari Vall d’Hebron, Universitat Aut onoma de Barcelona, Spain Funding sources: None. Conflicts of interest: None declared. Correspondence to: Carla Ferr a ndiz-Pulido, MD, Department of Dermatology, Hospital Universitari Vall d’Hebron, Passeig Vall d’Hebron 119129, 08035 Barcelona, Spain E-mail: [email protected] REFERENCES 1. Facchetti F, Jones DM, Petrella T. Blastic plasmacytoid dendritic cell neoplasm. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al, editors. WHO classification of tumors of hematopoietic and lymphoid tissues. Lyon: IARC; 2008. pp. 145-9. 2. Jegalian AG, Buxbaum NP, Facchetti F, Raffeld M, Pittaluga S, Wayne AS, et al. Blastic plasmacytoid dendritic cell neoplasm in the pediatric population: diagnostic features and clinical implications. Haematologica 2010;95:1873-9. 3. Cota C, Vale E, Viana I, Requena L, Ferrara G, Anemona L, et al. Cutaneous manifestations of blastic plasmacytoid dendritic cell neoplasmemorphologic and phenotypic variability in a series of 33 patients. Am J Surg Pathol 2010;34:75-87. 4. Dalle S, Beylot-Barry M, Bagot M, Lipsker D, Machet L, Joly P, et al. Blastic plasmacytoid dendritic cell neoplasm: is transplantation the treatment of choice? Br J Dermatol 2010;162:74-9. 5. Bekkenk MW, Jansen PM, Meijer CJ, Willemze R. CD561 hematological neoplasms presenting in the skin: a retrospective
J AM ACAD DERMATOL
JUNE 2012
analysis of 23 new cases and 130 cases from the literature. Ann Oncol 2004;15:1097-108. doi:10.1016/j.jaad.2011.07.016
Mycosis fungoideseassociated follicular mucinosis after bone-marrow transplantation To the Editor: A 32-year-old woman with acute myelogenous leukemia presented with a 2-month history of subtle papules on her cheeks and forehead 100 days after allogenic bone-marrow transplantation (Fig 1). She was on cyclosporine for graft-versus-host disease prophylaxis. A punch biopsy specimen from her cheek revealed a dermal folliculocentric infiltrate with exocytosis of atypical lymphocytes into the follicular epithelium and mucin deposition (Fig 2, A). The infiltrate was positive for CD3 and CD4 and negative for CD7, CD8, and myeloperoxidase (Fig 2, B). Histologic features of graft-versus-host disease were not present. T-cell receptor gene rearrangements were detected by polymerase chain reaction analysis. These findings suggested a diagnosis of mycosis fungoideseassociated follicular mucinosis. Peripheral blood smear for Sezary cells and flow cytometry were negative. A bone-marrow biopsy specimen 200 days after transplantation was consistent with complete sustained remission and blood chimerism studies suggested 100% engraftment of donor cells. Bexarotene gel resulted in some improvement, however, 6 months later, her cutaneous disease flared and new violaceous plaques developed on her neck, temples, and legs. A biopsy specimen from her neck revealed epidermotropism (without folliculotropism) of CD41, CD7e T cells consistent with mycosis fungoides (myeloperoxidase stain was negative on this specimen). The violaceous plaques on her temple, however, showed a superficial and deep
Fig 1. Subtle and discrete pink to erythematous follicular papules (black arrows) on temple and cheek. White arrow, Biopsy site.
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Letters e241
VOLUME 66, NUMBER 6
Fig 2. A, Perifollicular lymphocytic infiltrate with spongiosis and mucin deposition within follicular epithelium. (Hematoxylin-eosin stain; original magnification: 3100.) B, Prominent exocytosis of lymphocytes within follicular epithelium. (CD3 immunoperoxidase; original magnification: 3200.)
nodular infiltrate of large, atypical myeloperoxidasepositive mononuclear cells with minimal epidermotropism in addition to background CD41, CD7e folliculotropic lymphocytes suggesting concomitant leukemia cutis. A repeated bone-marrow biopsy specimen was markedly hypercellular with immature myeloid cells. Genetics reports and fluorescent in situ hybridization demonstrated clonal abnormalities similar to those noted during her initial diagnosis indicating recurrence of the leukemia. She declined a second transplantation and died a few months later from sepsis. In 1990, Habboush et al1 described a patient with mycosis fungoideseassociated follicular mucinosis who subsequently developed acute myelomonocytic leukemia. In our review of the literature, all other cases describing follicular mucinosis in a patient with leukemia did not involve mycosis fungoides. For example, in 1998, Sumner et al2 reported a case of follicular mucinosis not accompanied by mycosis fungoides in a patient with transplantation and acute myeloblastic leukemia. In 2004, Lee et al3 reported similar findings in a patient with acute lymphoblastic leukemia. Our case is unusual in that it combines all 3 features of leukemia, mycosis fungoideseassociated follicular mucinosis, and a preceding bone-marrow transplantation in the same patient. This distinct clinical scenario raises a few unique questions. Were the aberrant T cells of the mycosis fungoides of donor or recipient origin? We sought to answer this question by performing T-cell chimerism studies on skin biopsy specimens. Unfortunately, although her initial bone-marrow chimerism studies suggested that all circulating cells were of donor origin, studies from the skin were inconclusive. Other unanswered
questions include whether or not the mycosis fungoides might represent a reactive process in which the T cells developed clonality secondary to immunosuppressive therapy. Could her initial cutaneous disease have been prevented or anticipated by screening of the donor? Ultimately, it is important to closely monitor immunocompromised patients with transplantation for the most subtle of skin changes as these may be clues to alterations in underlying disease status. Faith A. Stewart, MD,a Aleodor Andea, MD,b and Lauren C. Hughey, MDa Departments of Dermatologya and Pathology,b University of Alabama at Birmingham Funding sources: None. Conflicts of interest: None declared. Correspondence to: Lauren C. Hughey, MD, Department of Dermatology, University of Alabama at Birmingham, 1530 Third Ave S, EFH 414, Birmingham, AL 35294-0009 E-mail: [email protected] REFERENCES 1. Habboush HW, Lucie NP, Mackie RM, Ashworth J, Turbitt M. Follicular mucinosis, mycosis fungoides, and acute myeloid leukemia. J Clin Pathol 1990;43:347. 2. Sumner WT, Grichnik JM, Shea CR, Moore JO, Miller WS, Burton CS. Follicular mucinosis as a presenting sign of acute myeloblastic leukemia. J Am Acad Dermatol 1998;39:803-5. 3. Lee KK, Lee JY, Tsai Y, Chiou SC. Follicular mucinosis occurring after bone marrow transplantation in a patient with acute lymphoblastic leukemia. J Formos Med Assoc 2004;103:63-6. doi:10.1016/j.jaad.2011.07.017
children.2,4,5 There are also data suggesting that outcome might be better in those patients lacking cutaneous lesions, although comparisons between different groups might be confounded by differences in treatment regimens.2,4 An aggressive initial therapy that includes hematopoietic stem-cell transplantation may improve the patients’ prognosis. Although it is generally accepted that initial high-dose chemotherapy is essential in all age groups, it is still debated if hematopoietic stemcell transplantation should be reserved for children who relapse and achieve a second remission2 or should be performed after the first complete remission as is recommended for adults and as was done in our case.4 Additional studies are needed to identify the optimal therapeutic regimen. These patients should be expeditiously admitted to a tertiary oncologic pediatric center that has expertise in hematopoietic stem-cell transplantation. opez-Lerma, Carla Ferr a ndiz-Pulido, MD,a Ingrid L MD, PhD,a Constantino S abado, MD,b Berta Ferrer, MD,c Sandra Pisa, MD,b and Vicente Garcıa-Patos, MD, PhDa Departments of Dermatology,a Pediatric b Oncology, and Pathology,c Hospital Universitari Vall d’Hebron, Universitat Aut onoma de Barcelona, Spain Funding sources: None. Conflicts of interest: None declared. Correspondence to: Carla Ferr a ndiz-Pulido, MD, Department of Dermatology, Hospital Universitari Vall d’Hebron, Passeig Vall d’Hebron 119129, 08035 Barcelona, Spain E-mail: [email protected] REFERENCES 1. Facchetti F, Jones DM, Petrella T. Blastic plasmacytoid dendritic cell neoplasm. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al, editors. WHO classification of tumors of hematopoietic and lymphoid tissues. Lyon: IARC; 2008. pp. 145-9. 2. Jegalian AG, Buxbaum NP, Facchetti F, Raffeld M, Pittaluga S, Wayne AS, et al. Blastic plasmacytoid dendritic cell neoplasm in the pediatric population: diagnostic features and clinical implications. Haematologica 2010;95:1873-9. 3. Cota C, Vale E, Viana I, Requena L, Ferrara G, Anemona L, et al. Cutaneous manifestations of blastic plasmacytoid dendritic cell neoplasmemorphologic and phenotypic variability in a series of 33 patients. Am J Surg Pathol 2010;34:75-87. 4. Dalle S, Beylot-Barry M, Bagot M, Lipsker D, Machet L, Joly P, et al. Blastic plasmacytoid dendritic cell neoplasm: is transplantation the treatment of choice? Br J Dermatol 2010;162:74-9. 5. Bekkenk MW, Jansen PM, Meijer CJ, Willemze R. CD561 hematological neoplasms presenting in the skin: a retrospective
J AM ACAD DERMATOL
JUNE 2012
analysis of 23 new cases and 130 cases from the literature. Ann Oncol 2004;15:1097-108. doi:10.1016/j.jaad.2011.07.016
Mycosis fungoideseassociated follicular mucinosis after bone-marrow transplantation To the Editor: A 32-year-old woman with acute myelogenous leukemia presented with a 2-month history of subtle papules on her cheeks and forehead 100 days after allogenic bone-marrow transplantation (Fig 1). She was on cyclosporine for graft-versus-host disease prophylaxis. A punch biopsy specimen from her cheek revealed a dermal folliculocentric infiltrate with exocytosis of atypical lymphocytes into the follicular epithelium and mucin deposition (Fig 2, A). The infiltrate was positive for CD3 and CD4 and negative for CD7, CD8, and myeloperoxidase (Fig 2, B). Histologic features of graft-versus-host disease were not present. T-cell receptor gene rearrangements were detected by polymerase chain reaction analysis. These findings suggested a diagnosis of mycosis fungoideseassociated follicular mucinosis. Peripheral blood smear for Sezary cells and flow cytometry were negative. A bone-marrow biopsy specimen 200 days after transplantation was consistent with complete sustained remission and blood chimerism studies suggested 100% engraftment of donor cells. Bexarotene gel resulted in some improvement, however, 6 months later, her cutaneous disease flared and new violaceous plaques developed on her neck, temples, and legs. A biopsy specimen from her neck revealed epidermotropism (without folliculotropism) of CD41, CD7e T cells consistent with mycosis fungoides (myeloperoxidase stain was negative on this specimen). The violaceous plaques on her temple, however, showed a superficial and deep
Fig 1. Subtle and discrete pink to erythematous follicular papules (black arrows) on temple and cheek. White arrow, Biopsy site.
J AM ACAD DERMATOL
Letters e241
VOLUME 66, NUMBER 6
Fig 2. A, Perifollicular lymphocytic infiltrate with spongiosis and mucin deposition within follicular epithelium. (Hematoxylin-eosin stain; original magnification: 3100.) B, Prominent exocytosis of lymphocytes within follicular epithelium. (CD3 immunoperoxidase; original magnification: 3200.)
nodular infiltrate of large, atypical myeloperoxidasepositive mononuclear cells with minimal epidermotropism in addition to background CD41, CD7e folliculotropic lymphocytes suggesting concomitant leukemia cutis. A repeated bone-marrow biopsy specimen was markedly hypercellular with immature myeloid cells. Genetics reports and fluorescent in situ hybridization demonstrated clonal abnormalities similar to those noted during her initial diagnosis indicating recurrence of the leukemia. She declined a second transplantation and died a few months later from sepsis. In 1990, Habboush et al1 described a patient with mycosis fungoideseassociated follicular mucinosis who subsequently developed acute myelomonocytic leukemia. In our review of the literature, all other cases describing follicular mucinosis in a patient with leukemia did not involve mycosis fungoides. For example, in 1998, Sumner et al2 reported a case of follicular mucinosis not accompanied by mycosis fungoides in a patient with transplantation and acute myeloblastic leukemia. In 2004, Lee et al3 reported similar findings in a patient with acute lymphoblastic leukemia. Our case is unusual in that it combines all 3 features of leukemia, mycosis fungoideseassociated follicular mucinosis, and a preceding bone-marrow transplantation in the same patient. This distinct clinical scenario raises a few unique questions. Were the aberrant T cells of the mycosis fungoides of donor or recipient origin? We sought to answer this question by performing T-cell chimerism studies on skin biopsy specimens. Unfortunately, although her initial bone-marrow chimerism studies suggested that all circulating cells were of donor origin, studies from the skin were inconclusive. Other unanswered
questions include whether or not the mycosis fungoides might represent a reactive process in which the T cells developed clonality secondary to immunosuppressive therapy. Could her initial cutaneous disease have been prevented or anticipated by screening of the donor? Ultimately, it is important to closely monitor immunocompromised patients with transplantation for the most subtle of skin changes as these may be clues to alterations in underlying disease status. Faith A. Stewart, MD,a Aleodor Andea, MD,b and Lauren C. Hughey, MDa Departments of Dermatologya and Pathology,b University of Alabama at Birmingham Funding sources: None. Conflicts of interest: None declared. Correspondence to: Lauren C. Hughey, MD, Department of Dermatology, University of Alabama at Birmingham, 1530 Third Ave S, EFH 414, Birmingham, AL 35294-0009 E-mail: [email protected] REFERENCES 1. Habboush HW, Lucie NP, Mackie RM, Ashworth J, Turbitt M. Follicular mucinosis, mycosis fungoides, and acute myeloid leukemia. J Clin Pathol 1990;43:347. 2. Sumner WT, Grichnik JM, Shea CR, Moore JO, Miller WS, Burton CS. Follicular mucinosis as a presenting sign of acute myeloblastic leukemia. J Am Acad Dermatol 1998;39:803-5. 3. Lee KK, Lee JY, Tsai Y, Chiou SC. Follicular mucinosis occurring after bone marrow transplantation in a patient with acute lymphoblastic leukemia. J Formos Med Assoc 2004;103:63-6. doi:10.1016/j.jaad.2011.07.017