Dermatology Online Journal

Mycosis fungoides with depigmentation secondary to treatment
Bahar Firoz MD, Olympia I Kovich MD, Jo-Ann M Latkowski MD
Dermatology Online Journal 13 (1): 18

New York University Department of Dermatology

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Abstract

A 51-year-old man presented with itchy, erythematous patches and plaques on his trunk, arms, and legs. A skin biopsy specimen showed mycosis fungoides. Initially the patient did not respond to PUVA photochemotherapy but later improved on NB-UVB phototherapy combined with bexarotene and interferon-alpha. The lesions progressed from erythematous patches and plaques to hyperpigmented patches with central depigmentation and localized areas of follicular repigmentation. The development of depigmentation after PUVA photochemotherapy for mycosis fungoides has been described in the literature and does not have associated prognostic implications. It is important to be cognizant of phototoxicity associated with PUVA photochemotherapy or NB-UVB phototherapy in patients with mycosis fungoides, who may be taking photosensitizing medications or have depigmented patches which renders them more sensitive to lower doses of ultraviolet light.

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Clinical synopsis

A 57-year-old Jamaican man presented to the Charles C. Harris Skin and Cancer Pavilion for the evaluation of multiple, itchy, erythematous plaques on his back, which gradually spread to cover his face, chest, extremities, and scalp over 18 months. He had been treated 4 years earlier with psoralen and ultraviolet A (PUVA) photochemotherapy with little improvement. A skin biopsy specimen was consistent with mycosis fungoides, and narrow-band ultraviolet B (NB-UVB) phototherapy was started. In 3 months, some of his lesions began to thicken and ulcerate, and lymphadenopathy was noted. Interferon α-2b and bexarotene were started in addition to NB-UVB phototherapy. The plaques resolved with depigmented patches appearing in the areas of prior involvement. On two separate occasions, the patient developed erythema and tense bullae in some of the depigmented patches although he was on no new medications or photosensitizing agents. The NB-UVB protocol was modified with a maximum treatment dose of 600 mJ/cm², owing to the bullous reactions to higher doses. Many of the depigmented patches showed signs of repigmentation with follicular, skin-colored macules centrally.

Scattered, hyperpigmented patches with central hypopigmentation or depigmentation were present on the arms, legs, and trunk. Many of the depigmented patches contained skin-colored, follicular macules. A few, ill-defined, firm, subcutaneous nodules were noted on the anterior aspects of the upper thighs. There is neither cervical, axillary, or inguinal lymphadenopathy nor hepatosplenomegaly.

Figure 1	Figure 2

The hemoglobin was 12.9 g/dL , hematocrit 37.5 percent, and lactate dehydrogenase 295 U/L. A basic metabolic panel, liver function tests, lipid panel, thyroid function tests, and cholesterol panel were normal. Flow cytometry analysis of the peripheral blood showed a normal percentage of B and T lymphocytes, a normal CD4/CD8 ratio, and no evidence of a malignant lymphoproliferative disorder by cell-marker analysis. A computed tomography scan of the chest, abdomen, and pelvis failed to demonstrate lymphadenopathy or evidence of metastatic disease.

Histopathology reveals melanophages in the papillary dermis and a sparse lymphocytic infiltrate. Epidermal hyperplasia, hypergranulosis, and melanocytes are present at the basal layer.

Comment

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and accounts for approximately 50 percent of all cases. The malignant cells in MF are CD4+ T cells, which have encountered antigen and thus express CD45RO [1]. These T cells home to the skin via the interaction between a cell-surface marker, cutaneous leukocyte antigen (CLA), and E-selectin, which is expressed on vascular endothelial cells [2].

There are many clinical variants of MF. The most common clinical presentation is erythematous patches and plaques with fine scale that are distributed in sun-protected areas. Patients also may present with erythroderma or tumors. Less common clinical presentations include poikilodermatous, hypopigmented, folliculotropic, and granulomatous MF.

The diagnosis of MF is established with a skin biopsy. The most characteristic histopathologic feature of mycosis fungoides is lymphocytic epidermotropism with minimal spongiosis. Pautrier microabscesses of intraepidermal lymphocytes singly or in groups may be present. The lymphocytes usually have hyperchromatic, cerebriform, or convoluted nuclei.

The staging of a patient with MF is performed at initial diagnosis and depends on the type and extent of skin lesions and the presence or absence of nodal, visceral, and peripheral blood involvement. A physical examination that includes evaluation for adenopathy, a skin biopsy, a complete blood cell count with differential analysis, liver function tests, lactate dehydrogenase (LDH) level, flow cytometry analysis of blood, and computed tomography (CT) scans of chest, abdomen, and pelvis are recommended. LDH is a nonspecific marker but may suggest extracutaneous involvement, if elevated. Flow cytometry analysis of blood is used to assess blood involvement and immunocompetence of the patient. Elevation of the CD4/CD8 ratio or an increased percentage of CD45RO T-cells may portend a poorer prognosis and identifies patients in whom gene rearrangement polymerase chain reaction studies should be obtained to seek a malignant T-cell clonal population [2].

Prognosis is related to the stage of disease at the initial diagnosis and to the presence of extracutaneous disease. According to one study, the ten-year survival of patients with mycosis fungoides in stage I disease was equivalent to the normal age-matched population [3]. However, 10-year survival decreased for all other stages, namely 67.4 percent for stage II, 39.2 percent for stage III, and 41 percent for stage IV. Lymphadenopathy was correlated with a poorer prognosis.

Successful treatment of mycosis fungoides often depends on the stage of the disease at diagnosis [1]. For patch-stage disease limited to the skin (stage IA), topical glucocorticoids and topical nitrogen mustard have shown complete response rates of 60 percent [4, 5]. PUVA photochemotherapy and both broad-band UVB and NB-UVB phototherapy have shown complete response rates of 79 percent in stage I mycosis fungoides [6, 7, 8]. For more extensive disease, systemic therapy is necessary. Oral retinoids and vitamin A analogues alter gene expression via the retinoic acid receptor to modulate cell growth and division. Interferon alpha is used to inhibit the proliferative capacity of malignant T cells by altering the cytokine profile. Interferon α also may enhance the antitumor immune response by augmenting cell-mediated cytotoxicity. Combination therapy, such as oral retinoids and interferon α, has shown appreciable responses in otherwise refractory cases [9].

Our patient developed depigmented patches in response to therapy, which is a rare complication. One case series described four patients with MF, who developed vitiligo-like patches after PUVA photochemotherapy [10]. Biopsy specimens showed no evidence of MF; however, there was a complete loss of melanocytes that was confirmed with S100 staining. All of the areas of depigmentation were limited to skin which had previous involvement with MF prior to treatment. Partial repigmentation subsequently occurred in only two patients. The authors suggested that photochemotherapy may have activated cell-mediated immunity that lead to destruction of melanocytes [10]. Vitiligo associated with PUVA photochemotherapy was described in two mycosis fungoides patients and one psoriasis patient [11]. These patients developed depigmentation in areas that were not previously involved with psoriasis or MF. Again, these areas did not completely repigment.

References

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2. Latkowski, J, et al. Cutaneous T-cell Lymphomas. In: Freedberg IM, et al, eds. Fitzpatrick's Dermatology In General Medicine, 6th edition. New York: McGraw Hill, 2003: 1537

3. Kim YH, et al. Clinical stage IA (limited patch and plaque) mycosis fungoides: a longterm outcome analysis. Arch Dermatol 1999;135:26

4. Zackheim HS, et al. Topical corticosteroids for mycosis fungoides: experience in 79 patients. Arch Dermatol 1998;134:949

5. Ramsay D, et al. Topical mechlorethamine therapy for early stage mycosis fungoides. J Am Acad Dermatol 1988;14:527

6. Ramsay D, et al. Ultraviolet-B phototherapy for early-stage cutaneous T-cell lymphoma. Arch Dermatol 1992;128:931

7. Abel EA, et al. PUVA treatment of erythrodermic and plaque-type mycosis fungoides: ten-year follow-up study. Arch Dermatol 1987;123:897

8. Samson YS, et al. Narrow-band ultraviolet B treatment for vitiligo, pruritus, and inflammatory dermatoses. Photodermatol Photoimmunol Photomed 2003;19:164

9. McGinnis KS, et al. Low-dose oral bexarotene in combination with low-dose interferon alfa in the treatment of cutaneous T-cell lymphoma: clinical synergism and possible immunologic mechanisms. J Am Acad Dermatol 2004;50:375

10. Mimouni D, et al. Vitiligo-like leucoderma during photochemotherapy for mycosis fungoides. Br J Dermatol 2001;145:1008

11. Todes-Taylor N, et al. The occurrence of vitiligo after psoralens and ultraviolet a therapy. J Am Acad Dermatol 1983;9:526

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