Case Report

A Case of Mycosis Fungoides Transmitted From Donor to Recipient, and Review of Literature of T-Cell Malignancies After Transplantation John C. Loh,1 David S. Cassarino,2 Wayne W. Grody,1,3 Melvin W. Chiu,1,4 Lauren C. Pinter-Brown1,5 Clinical Practice Points  Transmission of hematologic malignancy during bone

 To our knowledge, this case represents the first clearly

marrow transplantation has been previously reported for acute myeloid leukemia, chronic myeloid leukemia, and subcutaneous panniculitis-like T-cell lymphoma.  We present a case of mycosis fungoides appearing after bone marrow transplantation, which was clinically manifested in the donor at the time of bone marrow donation.

documented case of likely transmission of mycosis fungoides described in the english-language literature.  In this case report, we review the literature on T-cell malignancies after transplantation, and discuss the implications of our unusual case on ensuring the safety of bone marrow transplantation.

Clinical Lymphoma, Myeloma & Leukemia, Vol. -, No. -, --- ª 2014 Elsevier Inc. All rights reserved. Keywords: Allogeneic bone marrow transplantation, Cutaneous T-cell lymphoma, Exposure to Agent Orange, Screening of bone marrow donors, transmission of donor malignancy

Introduction Disease transmission is a rare, but well documented complication of bone marrow transplantation (BMT).1 Transmissible donor diseases include infections, congenital disorders, autoimmune diseases, and hematological and nonhematological malignancies.2 We present a case of mycosis fungoides developing after BMT, which was clinically manifested in the donor at the time of bone marrow donation. To our knowledge, this report represents the first case of likely transmission of mycosis fungoides described in the englishlanguage literature. We also review the literature on T-cell malignancies arising after transplantation.

Case A 52-year-old man with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) refractory to alpha interferon 1

David Geffen School of Medicine at University of California, Los Angeles, CA Department of Pathology, Kaiser Permanente, Southern California, Los Angeles, CA Departments of Pathology and Laboratory Medicine, Pediatrics and Human Genetics, University of California, Los Angeles, CA 4 Division of Dermatology, University of California, Los Angeles, CA 5 Division of Hematology-Oncology, University of California, Los Angeles, CA 2 3

Submitted: Nov 15, 2013; Revised: Jan 30, 2014; Accepted: Feb 11, 2014 Address for correspondence: Lauren C. Pinter-Brown, MD, University of California, Los Angeles, 10945 Le Conte Avenue, Suite 2333, Los Angeles, CA 90095 E-mail contact: [email protected]

2152-2650/$ - see frontmatter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clml.2014.02.005

underwent allogeneic peripheral stem cell transplantation using a matched-related donor in 1998. He was a Vietnam veteran, who was otherwise healthy at the time of transplantation. The patient’s histocompatible sister served as his stem cell donor. She was noted to be in relatively good health at the time of donation with a history of arthritis, hypertension, and fibromyalgia. However, photographs taken from that time show that she also had a skin rash (Fig. 1A). The patient was conditioned with busulfan and cyclophosphamide, and his course after transplantation was largely uneventful. There was no evidence of acute graft versus host disease (GvHD). GvHD prophylaxis consisted of cyclosporine and 4 doses of methotrexate. Immunosuppression was discontinued in 2000. Subsequently, the patient developed asymptomatic liver enzyme increases that were deemed to be chronic GvHD, which was successfully managed with prednisone. The patient was first seen for an erythematous plaque arising on his left axilla in 2006. The differential diagnosis at the time included granuloma annulare, ringworm infection, or contact dermatitis. On learning that his donor sister had recently been diagnosed with mycosis fungoides, the patient was sent for a skin biopsy, which was diagnosed as consistent with mycosis fungoides. Further staging evaluation was negative, resulting in a diagnosis of mycosis fungoides, stage IA. The patient’s disease initially responded well to clobetasol and narrow band UVB phototherapy 2 to 3 times per week. In 2012,

Clinical Lymphoma, Myeloma & Leukemia Month 2014

-1

Transmission of Mycosis Fungoides Figure 1 Clinical and Histopathological Characteristics of Mycosis Fungoides in Donor and Recipient. (A) Self-Photograph of Donor Sister in 1998, Showing Multiple Lesions of Presumed Mycosis Fungoides. (B) Clinical Examination of the Patient’s Left Preauricular Lesion Demonstrating Mycosis Fungoides, Stage IIB With Gross Tumors. (C) Histologic Examination of the Patient’s Left Preauricular Lesion Demonstrating Mycosis Fungoides, With Dense Sheets of Atypical Lymphoid Cells in the Dermis, Consistent With Tumor Stage Mycosis Fungoides (Magnification 310)

a left preauricular lesion of mycosis fungoides appeared that was thickened and was rebiopsied, which showed tumor stage mycosis fungoides with large cell transformation (Fig. 1B and C). The patient has since been given desatinib and oral bexarotene to treat his advanced stage of disease. Review of the self-photographs of the patient’s donor sister taken from the time of peripheral stem cell donation in 1998 show a rash that was consistent with mycosis fungoides (Fig. 1A). However, she was not diagnosed until 2006, at which time she had progressed to stage IVA mycosis fungoides with axillary lymph node involvement, and had a rapid demise thereafter.

Discussion

2

-

Exposure to dioxin-containing herbicides such as Agent Orange has multisystem effects, including an increased risk of certain malignancies.3 This might occur by a variety of carcinogenic mechanisms including increased oxidative stress, DNA damage, chromosome rearrangement, and upregulation of antiapoptotic mRNA. Our patient, a Vietnam veteran, developed CML 30 years after being exposed to Agent Orange. Unlike lymphomas, Agent Orange has not been strongly linked to the development of CML. A recent survey of 67 photopheresis centers identified 7 Vietnam veterans who had developed cutaneous T-cell lymphoma 27 to 35 years after their exposure.4 However, our case demonstrates that mycosis fungoides appearing in a similar time frame after exposure to Agent Orange might not be exposure-related.

Clinical Lymphoma, Myeloma & Leukemia Month 2014

Lymphoproliferative disorders that occur after transplant (PTLD) not associated with the Epstein-Barr virus are increasingly recognized.5 These PTLD are considered ‘late’ appearing (> 1 year) and are associated with a poorer prognosis. PTLD are classified as T-cell in origin (T-PTLD) when they meet the criteria for a T-cell lymphoma or leukemia.6-8 Knowledge of these rare forms of PTLD is based predominantly on case reports and small series.7 Like PTLD of B-cell origin, T-PTLD are thought to occur because of chronic immunosuppression resulting in dysregulation of lymphogenesis. However, most T-PTLD do not appear to be driven by the EpsteinBarr virus. T-PTLD have been reported to occur 2 to 43 months after BMT, with a median of 5 months.7 Extranodal sites are usually involved. However, the skin is a less common site of involvement, with only 25 cases reported to have occurred after solid organ transplantation, and a single case reported after BMT.9 Our patient developed mycosis fungoides 7 years after BMT, which does not fit within the timeline of reported T-PTLD. Furthermore, he had not been taking immunosuppressive drugs for some years before developing clinical manifestations of his mycosis fungoides. Case reports of transmission of donor malignancy in BMT are extremely rare in the literature.2 Malignancies reported to be transmitted include acute myeloid leukemia, chronic myeloid leukemia, and lymphoma.10-12 Stewart et al. first raised the possibility of transmission of mycosis fungoides during BMT with a case of mycosis fungoides-associated follicular mucinosis appearing after allogeneic BMT.13 However, they were not able to demonstrate disease manifestation in the donor, nor the origin of cells from

John C. Loh et al presumed mycosis fungoides lesions. Our patient’s donor sister had lesions consistent with mycosis fungoides on her abdomen and torso at the time of bone marrow donation per self-photograph. We were able to obtain diagnostic skin biopsies from our bone marrow donor and recipient. Polymerase chain reaction analysis of both specimens showed identical clonal peaks at the T-cell receptor gamma locus (Fig. 2). As such, we consider transmission of circulating malignant cells via this bone marrow transplant to be the likely etiology of our patient’s mycosis fungoides.14 The donor’s appearance at the time of donor evaluation raises the question of appropriate screening for bone marrow donors. Use of bone marrow aspirates to screen for occult hematologic malignancies in older donors has recently been discussed.1 At our

institution, prospective donors must undergo a full medical evaluation including a physical exam. However, the components of the exam are left to the discretion of the examiner. Among diseases manifesting in the skin, vitiligo, psoriasis, and alopecia areata have also been proposed to be transmitted through BMT, and melanoma is considered to have a high transmission rate and associated mortality in the setting of solid organ transplantation.15-19 Our patient’s donor sister passed away from mycosis fungoides, and our patient has recently been diagnosed with transformed mycosis fungoides, which will likely shorten his lifespan. In a recent retrospective analysis of 100 cases of mycosis fungoides with large cell transformation, Benner et al. found a median survival of 24 months, with a 5-year disease-specific survival and overall survival of 38%

Figure 2 Molecular Pathology of Donor and Recipient Specimens. (A) Molecular Pathology of Recipient Clone (top 2 Panels) at the T-cell Receptor Gamma Locus Showing Peaks at 68 to 70 Base Pairs and 248 to 250 Base Pairs. Negative Control is Represented in the Bottom 2 Panels. (B) Molecular Pathology of Donor Clone Showing Clonal Peaks Identical to the Recipient

Clinical Lymphoma, Myeloma & Leukemia Month 2014

-3

Transmission of Mycosis Fungoides and 33%, respectively.20 Despite the rarity of our case, our bone marrow recipient has been tremendously affected by transmission of his donor’s disease, which we believe heightens the need for appropriate screening of bone marrow donors before transplantation. In conclusion, our case demonstrates that mycosis fungoides without overt blood involvement might be transmitted via bone marrow transplant. This occurs via malignant cells that have lost their dependence on the skin microenvironment.21 We believe that our case highlights an additional cutaneous disease that might be transmitted by BMT.

Disclosure The authors have stated that they have no conflicts of interest.

References 1. Tilson MP, Jones RJ, Sexauer A, et al. Targeted pathologic evaluation of bone marrow donors identifies previously undiagnosed marrow abnormalities. Biol Blood Marrow Transplant 2013; 19:1254-9. 2. Niederwieser D, Gentilini C, Hegenbart U, et al. Transmission of donor illness by stem cell transplantation: should screening be different in older donors? Bone Marrow Transplant 2004; 34:657-65. 3. Institute of Medicine. Veterans and Agent Orange: Update 2010 (Eighth Biennial Update). Washington, DC: The National Academies Press, 2011. 4. Meyer KM. Incidence of CTCL in Vietnam veterans. Dermatol Nurs 2002; 14:42, 45, 52. 5. Leblond V, Davi F, Charlotte F, et al. Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity? J Clin Oncol 1998; 16:2052-9. 6. Swerdlow S. T-cell and NK-cell posttransplantation lymphoproliferative disorders. Am J Clin Pathol 2007; 127:887-95. 7. Tiede C, Maecker-Kolhoff B, Klein C, Kreipe H, Hussein K. Risk factors and prognosis in T-cell posttransplantation lymphoproliferative diseases: reevaluation of 163 cases. Transplantation 2013; 95:479-88.

4

-

Clinical Lymphoma, Myeloma & Leukemia Month 2014

8. Herreman A, Dierickx D, Morscio J, et al. Clinicopathological characteristics of posttransplant lymphoproliferative disorders of T-cell origin: single-center series of nine cases and meta-analysis of 147 reported cases. Leuk Lymphoma 2013; 54: 2190-9. 9. Santos-Briz A, Romo A, Antúnez P, et al. Primary cutaneous T-cell lymphoproliferative disorder of donor origin after allogeneic haematopoietic stem-cell transplantation. Clin Exp Dermatol 2009; 34:e778-81. 10. Niederwieser DW, Appelbaum FR, Gastl G, et al. Inadvertent transmission of a donor’s acute myeloid leukemia in bone marrow transplantation for chronic myelocytic leukemia. N Engl J Med 1990; 322: 1794-6. 11. Baron F, Dresse MF, Beguin Y. Transmission of chronic myeloid leukemia through peripheral-blood stem-cell transplantation. N Engl J Med 2003; 349: 913-4. 12. Berg KD, Brinster NK, Huhn KM, et al. Transmission of a T-cell lymphoma by allogeneic bone marrow transplantation. N Engl J Med 2001; 345: 1458-63. 13. Stewart FA, Andea A, Hughey LC. Mycosis fungoides-associated follicular mucinosis after bone-marrow transplantation. J Am Acad Dermatol 2012; 66: e240-1. 14. Robert C, Kupper TS. Inflammatory skin diseases, T cells, and immune surveillance. N Engl J Med 1999; 341:1817-28. 15. Alajlan A, Alfadley A, Pedersen KT. Transfer of vitiligo after allogeneic bone marrow transplantation. J Am Acad Dermatol 2002; 46:606-10. 16. Gardembas-Pain M. Psoriasis after allogeneic bone marrow transplantation. Arch Dermatol 1990; 126:1523. 17. Strauss DC, Thomas JM. Transmission of donor melanoma by organ transplantation. Lancet Oncol 2010; 11:790-6. 18. Neumeister P, Strunk D, Apfelbeck U, Sill H, Linkesch W. Adoptive transfer of vitiligo after allogeneic bone marrow transplantation for non-Hodgkin lymphoma. Lancet 2000; 355:1334-5. 19. Nadeem S, Hymes S, Kebriaei P, Abruzzo L, Curry JL, Duvic M. Alopecia areata after HLA-identical BMT from an affected, sibling donor. Bone Marrow Transplant, Published online January 20, 2014; http://dx.doi.org/10.1038/bmt. 2013.212. 20. Benner MF, Jansen PM, Vermeer MH, Willemze R. Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood 2012; 119: 1643-9. 21. Girardi M, Heald PW, Wilson LD. The pathogenesis of mycosis fungoides. N Engl J Med 2004; 350:1978-88.

A case of mycosis fungoides transmitted from donor to recipient, and review of literature of T-cell malignancies after transplantation.

A case of mycosis fungoides transmitted from donor to recipient, and review of literature of T-cell malignancies after transplantation. - PDF Download Free
858KB Sizes 0 Downloads 2 Views