Iman Almasry1,2*, Mohammed Taha2, Rawan Al Mohammad3, Atlal Allafi2
1Lecturer of Dermatology, Venereology and Andrology, Faculty of Medicine, Menoufia University, Egypt
2Consultant dermatology; As’ad Al-Hamad Dermatology Center, Kuwait
3Assistant dermatologist, As’ad Al-Hamad Dermatology Center, Kuwait
*Correspondence author: Iman Almasry, Lecturer of Dermatology, Venereology and Andrology, Faculty of Medicine, Menoufia University, Egypt and Consultant dermatology; As’ad Al-Hamad Dermatology Center, Kuwait;
Email: [email protected]
Published Date: 09-06-2023
Copyright© 2023 by Almasry I, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Mycosis fungoides is fairly common type of cutaneous T-cell lymphoma with prolonged indolent course. Early-stage MF patch/plaque stage disease (T1/T2) can be treated safely and effectively by Phototherapy. Systemic PUVA and Narrowband UVB widely used with considerable result in MF. Topical PUVA is rarely considered as a phototherapy line in MF. We represent in our patient complete clearance of MF plaque after topical PUVA phototherapy without relapse.
Keywords: MF; CTCL; Phototherapy; PUVA; Adult Patient
Introduction
Mycosis Fungoides (MF) is the most common form of cutaneous T-cell lymphoma. The incidence of Cutaneous T-Cell Lymphomas (CTCL) has been increasing in recent years [1]. MF represents approximately 75% of primary CTCL which are T-cell derived [2]. The precise etiology of MF is still unknown, even epidemiological studies have failed to identify any environmental or virally associated risk factors for most CTCL subtypes, except for HTLV-1 infection in adult T-cell leukemia/ lymphoma [3]. Recent studies have suggested that medications like hydrochlorothiazide may induce an antigen-driven T-cell lymphoproliferation or dyscrasia [4]. Phototherapy is one of helpful therapies in early-stage MF especially narrowband UVB which has demonstrated efficacy in patients with patch/plaque stage disease (T1/T2) [5,6]. Another alternative phototherapy is PUVA (8-methoxypsoralen plus ultraviolet A), which is recommended by National comprehensive cancer in thick plaques MF [7].
History of the Case
A gentleman of 45-year-old previously healthy presented in 2015 to our center with 35×20 cm scaly hyperpigmented patch in the right side of anterior chest for six years. A new lesion one month ago over right gluteal area was developed. It was hyperpigmented scaly skin patch about 15× 10 cm. MF was highly suspected, so skin biopsy was taken from the chest lesion (and it confirmed the clinical suspicion of MF) (Fig. 1).
Figure 1: A: H&E showed: epidermal thinning with loss of the rete ridges, epidermotropism and lichenoid infiltration of the upper dermis with lymphocytic infiltration having large nuclei; B: A higher power of same findings.
Figure 2: A: The patch lesion over chest became worsen after oral PUVA; B: Closer view to same lesion.
A new biopsy was done, which showed more extensive epidermotropism and cellular infiltration, with also thickened collagen bundles (Fig. 3). Immunohistochemical staining was done (Fig. 4) for CD markers and showed negative CD20, CD30 and CD 7, while positive pan staining for CD3 and CD4 and focal staining for CD8 specific pattern for MF Image. The second biopsy confirmed the persistence and progression of MF lesion, as it became plaque rather than patch with nodular infiltration.
Figure 3: A: H&E showed more extensive epidermotropism and cellular infiltration, with also thickened collagen bundles; B: Showed higher magnification of same findings.
Figure 4: A,B: Negative immunostaining for CD2O and CD30; C: CD7 negative; D: CD8 negative with focal positivity; E,F: Positive for CD3 andCD4.
Topical PUVA was an option which is rarely used for mycosis fungoides [15]. Our patient started on topical UVA three times a week. Topical psoralens (methoxsalen solution 0.1%) was administered 60 minutes before the session Ultraviolet A phototherapy (315-400 nm) was started with 0.5 J/cm2 and was increased by 0.5 J/cm2 every third day until 10.5 J/cm2 was reached (Fig. 5). Total 96 sessions, the cumulative dose was 660 J/cm2 in the affected area while the remaining skin was covered. Regular clinical follow-up for patient showed a complete remission for 2 years, without any recurrence in same site neither in other skin sites. Patient has electronic file and came for other dermatology complain (pityriasis versicolor) this year 2023, examination for skin which is completely free. The patient if free for 8 years till now.
Figure 5: Complete clearance of MF plaque lesion after topical PUVA.
Discussion
MF is a primary cutaneous lymphoma, a variant of heterogeneous group of extra-nodal non-Hodgkin lymphomas started primarily in the skin. Non-Hodgkin lymphomas are mainly T-cell derived [9]. The incidence CTCL has been increasing and is currently, even in children and young adults specially the histopathologic variant MF [10]. The malignant lymphocytes in MF/SS are usually CD3+CD4+ and CD8-, but frequently lose the expression of other pan-T-cell antigens. Therefore, demonstration of a significant population of CD4+ cells lacking CD2, CD5 and/or CD7 expression is highly specific (specificity >90%) for MF in most reported series [11]. Phototherapy is one of selective therapies in early-stage MF, either NBUVB, or oral PUVA. Narrow band UVB is used in early-stage patch and plaque MF, in other hand PUVA in skin of color MF patients has demonstrated efficacy in many retrospective and prospective studies [12-14]. Both phototherapy types have a significant efficacy in early-stage MF. NBUVB is widely used because it has limited local skin effect low potential carcinogenic role [16]. Phototherapy PUVA exerts a systemic action, unfortunately might have adverse potential carcinogenic effect this might be an explanation which had happened in our patient of exacerbation of his MF chest plaque over chest after given him systemic PUVA [17]. It induces neoplastic T lymphocyte death by forming singlet oxygen and directly damaging DNA [18]. Our patient is early-stage MF at time of presentation (stage IA). Patient was stared on NBUVB which is considered effective and safe options in early-stage MF [5,6]. The patch lesion over gluteal lesion completely cleared. The other patch lesion over the shoulder unfortunately did not improve and became worse as it progressed to a plaque (stage IA). Patient shifted to oral PUVA, that it is more effective and recommended in MF in adult, the shoulder plaque increase in size and infiltrated by multiple nodular lesions [19-21]. Topical PUVA was our last option for this patient with excellent outcome and complete clear of shoulder plaque which was resistant to NB-UVB and progress in systemic PUVA. Topical PUVA it is uncommonly used in MF and mostly tried in children in cases report study [22]. Although phototherapy is mainstay therapy in early-stage MF with efficacy and safety in most of patients, it is reported the contrary in retrospective review [23]. Progression of MF resumed to UV-induced p53 mutations in advanced MF suggest that phototherapy may contribute to disease progression [24]. Topical PUVA is good alternative optional phototherapy in case of non-tolerated or contraindicated systemic PUVA as in children or patients with hepatic impairment, or in patients rarely show paradoxical unexplained response as in our case.
Limitation of Study
Prephototherapy treatment photography had not taken for patient as he had refused at that time to take one for gluteal area.
Conflict of Interest
The authors have no conflict of interest to declare.
References
- Criscione VD, Weinstock MA. Incidence of cutaneous T-cell lymphoma in the United States, 1973-2002. Arch Dermatol. 2007;143:854-9.
- Willemze R, Jaffe ES, Burg G. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105:3768-85.
- Whittemore AS, Holly EA, Lee IM. Mycosis fungoides in relation to environmental exposures and immune response: a casecontrol study. J Natl Cancer Inst. 1989;81:1560.
- Jahan-Tigh RR, Huen AO, Lee GL, Pozadzides JV, Liu P, Duvic M. Hydrochlorothiazide and cutaneous T-cell lymphoma: prospective analysis and case series. Cancer. 2013;119:825-31.
- Dereure O, Picot E, Comte C, Bessis D, Guillot B. Treatment of early stages of mycosis fungoides with narrowband ultraviolet B. A clinical, histological and molecular evaluation of results. Dermatol. 2009;218:1-6.
- Almasry MI, Albathali AA, Alajmi H, Al-Lafi A, Sadek A, Lazarevic V, et al. Efficacy and safety of narrowband-UVB in early-stage cutaneous t-cell lymphoma in Kuwaiti patients. J Clin Exp Dermatol Res. 2020;11:536.
- Olsen EA, Hodak E, Anderson T. Guidelines for phototherapy of mycosis fungoides and Sezary syndrome: A consensus statement of the United States Cutaneous Lymphoma Consortium. J Am Acad Dermatol. 2016;74:27-58.
- Olsen E, Vonderheid E, Pimpinelli N. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a pro posal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110:1713-22.
- Willemze R, Cerroni L, Kempf W. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133(16):1703-14.
- Pope E, Weitzman S, Ngan B. Mycosis fungoides in the pediatric, population: report from an international childhood registry of cutaneous lymphoma. J Cutan Med Surg. 2010;14:1-6.
- Ormsby A, Bergfeld WF, Tubbs RR, Hsi ED. Evaluation of a new paraffin-reactive CD7 T-cell deletion marker and a polymerase chain reaction-based T-cell receptor gene rearrangement assay: implications for diagnosis of mycosis fungoides in community clinical practice. J Am Acad Dermatol. 2001;45:405-13.
- Olsen EA, Hodak E, Anderson T. Guidelines for phototherapy of mycosis fungoides and Sezary syndrome: A consensus statement of the United States cutaneous lymphoma consortium. J Am Acad Dermatol. 2016;74:27-58.
- Dereure O, Picot E, Comte C, Bessis D, Guillot B. Treatment of early stages of mycosis fungoides with narrowband ultraviolet B: A clinical, histological and molecular evaluation of results. Dermatol. 2009;218:1-6.
- Gathers RC, Scherschun L, Malick F, Fivenson DP, Lim HW. Narrowband UVB phototherapy for early-stage mycosis fungoides. J Am Acad Dermatol. 2002;47:191-7.
- Pabsch H, Rütten A, Von Stemm A, Meigel W, Sander CA, Schaller J. Treatment of childhood mycosis fungoides with topical PUVA. Acad Dermatol. 2002;47:557-61.
- Amitay-Laish I, Davidovici B, Moyal L, Gurevich M, Akerman L, Hodak E. Lack of detectable effect of narrow-band ultraviolet B on peripheral blood mononuclear cell cytokine expression in early-stage Mycosis Fungoides. Photodermatol Photoimmunol Photomed. 2018;34(5):350-3.
- Karamova AE, Verbenko DA, Vorontsova AA, Zhilova MB, Nikonorov AA, Gatiatulina ER, et al. Effect of PUVA and NB-UVB therapy on profile in patients with mycosis fungoides. J Oncol. 2022;2022:3149293-7.
- Jung JM, Lim DJ, Won CH, Chang SE, Lee MW, Lee WJ. Mycosis fungoides in children and adolescents: a systematic review. JAMA Dermatol. 2021;157(4):431-8.
- Harvey NT, Spagnolo DV, Wood BA. Could it be mycosis fungoides? An approach to diagnosing patch stage mycosis fungoides. J Hematopathol. 2015;8:209-23.
- Hristov AC, Tejasvi T, Wilcox RA. Mycosis fungoides and Sézary syndrome: 2019 update on diagnosis, risk‐stratification and management. Am J Hematol. 2019;94(9):1027-41.
- Cerroni L. Mycosis fungoides-clinical and histopathologic features, differential diagnosis and treatment. Semin Cutan Med Surg. 2018;37(1):2-10.
- Pabsch H, Rütten A, Von Stemm A, Meigel W, Sander CA, Schaller J. Treatment of childhood mycosis fungoides with topical PUVA. J Am Acad Dermatol. 2002;47(4):557-61.
- Hoot JW, Wang L, Kho T, Akilov OE. The effect of phototherapy on progression to tumors in patients with patch and plaque stage of mycosis fungoides. J Dermatological Treatment. 2018;29(3):272-6.
- Benjamin CL, Ananthaswamy HN. p53 and the pathogenesis of skin cancer. Toxicology Appl Pharmacol. 2007;224(3):241-8.
Article Type
Case Report
Publication History
Received Date: 05-05-2023
Accepted Date: 02-06-2023
Published Date: 09-06-2023
Copyright© 2023 by Almasry I, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation: Almasry I, et al. Successful Treatment of Early-Stage Mycosis Fungoides With Topical PUVA in Adult Patient: Case Report. J Dermatol Res. 2023;4(2):1-7.
Figure 1: A: H&E showed: epidermal thinning with loss of the rete ridges, epidermotropism and lichenoid infiltration of the upper dermis with lymphocytic infiltration having large nuclei; B: A higher power of same findings.
Figure 2: A: The patch lesion over chest became worsen after oral PUVA; B: Closer view to same lesion.
Figure 3: A: H&E showed more extensive epidermotropism and cellular infiltration, with also thickened collagen bundles; B: Showed higher magnification of same findings.
Figure 4: A,B: Negative immunostaining for CD2O and CD30; C: CD7 negative; D: CD8 negative with focal positivity; E,F: Positive for CD3 andCD4.
Figure 5: Complete clearance of MF plaque lesion after topical PUVA.
