Efficacy of narrowband UVB vs. PUVA in patients with early‐stage mycosis fungoides

Introduction Mycosis fungoides (MF) is a non‐Hodgkin’s T‐cell lymphoma of the skin that often begins as limited patches and plaques with slow progression to systemic involvement. Narrowband ultraviolet (UV) B therapy has been proven to be an effective short‐term treatment modality for clearing patch‐stage MF. The effect of psoralen plus long‐wave ultraviolet A (PUVA) in the treatment of patch‐ and plaque‐type MF has also been thoroughly documented. Objectives The purpose of this study was to compare the efficacy and safety of narrowband UVB and PUVA in patients with early‐stage MF. Methods We analysed the response to treatment, relapse‐free survival and irradiation dose in 114 patients with histologically confirmed early‐stage MF (stage IA, IB and IIA). Results A total of 95 patients were treated with PUVA (83.3%) and 19 with narrowband UVB (16.7%). With PUVA, 59 patients (62.1%) had a complete response (CR), 24 (25.3%) had a partial response (PR) and 12 (12.6%) had a failed response. Narrowband UVB led to CR in 12 (68.4%) patients, PR in 5 (26.3%) patients and a failed response in 1 (5.3%) patient. There were no differences in terms of time to relapse between patients treated with PUVA and those treated with narrowband UVB (11.5 vs. 14.0 months respectively; P = 0.816). No major adverse reactions were attributed to the treatment. Conclusions Our results confirm that phototherapy is a safe, effective and well‐tolerated, first‐line therapy in patients with early‐stage cutaneous T‐cell lymphoma, with prolonged disease‐free remissions being achieved. It suggests that narrowband UVB is at least as effective as PUVA for treatment of early‐stage MF.     

Phototherapy of mycosis fungoides

Background/purpose: Among the primary cutaneous T‐cell lymphomas, mycosis fungoides (MF) is the most common disease entity. Recently, an improved understanding of the pathology, clinical presentation, and prognosis of MF has lead to the development of new and practically useful classification and staging systems. In most patients, MF presents with patches and plaques and remains confined to the skin for years and decades, making it an ideal target for phototherapy. However, treatment schedules vary widely and this review describes the current knowledge about phototherapy of MF focusing mainly on narrow‐ and broadband UVB and 8‐methoxypsoralen plus UVA, its indications, practical aspects, and clinical outcome. Methods: Review and summary of the pertinent literature. Results and conclusions: Since 1976, when the first report on phototherapy for MF was published, sufficient evidence has accumulated to make narrowband UVB and PUVA safe and effective treatment options for early stages of the disease. In refractory cases or more advanced stages, combination of phototherapy with systemic treatments including mainly interferons and retinoids might be valuable. Additional research is required to further define the optimal treatment schedules and the role of maintenance.     

Narrowband UVB phototherapy for early-stage mycosis fungoides: evaluation of clinical and histopathological changes

Background Early‐stage (IA, IB, IIA) mycosis fungoides (MF) has long been treated with various agents including topical potent steroids, nitrogen mustard, carmustine, oral psoralen plus UVA (PUVA), broadband UVB, electron‐beam radiotherapy, interferon‐α and retinoids. However, each of these modalities is associated with various side‐effects. Narrowband UVB (NB‐UVB) therapy has the same effect but is safer to use than the other methods. Objective Our purpose in this prospective study was to determine the effects of NB‐UVB in early‐stage MF both clinically and histopathologically. Materials and methods Twenty‐three patients (20 men, three women, aged 27–78 years) with clinically and histologically confirmed MF were enrolled. Patients received NB‐UVB therapy three times a week. Clinical and histological responses, cumulative doses, total number of treatments, side‐effects and duration of remission period were noted. Results Six patients had stage IA MF, 15 patients stage IB and two patients stage IIA. Eighteen patients had patch stage and five patients had plaque stage histopathologically. All of the patients in the patch group had a complete response (CR). In the plaque group, three patients (60%) had a CR and two (40%) had partial (PR) or no clinical response (NR). The clinical response between patch and plaque groups was statistically significant. Regarding the histopathological findings, 17 (94.4%) had complete clearing and only one (5.6%) patient had a partial improvement in the patch group. In the plaque group, one (20%) patient had complete clearing and four (80%) patients had partial or no improvement. The difference between the two groups was statistically significant. In the patch group, the mean cumulative dose was 90.15 J/cm² and the mean number of treatments was 35.33. In the plaque group, the mean cumulative dose was 90.67 J/cm² and the mean total number of treatments was 39.40. The differences were not statistically significant, either between the mean cumulative dose or the mean number of treatments. The mean duration of follow‐up was 10.87 months (range 1–25 months). Only one of the patients had a relapse. Conclusions NB‐UVB therapy for patients with early‐stage MF is an effective and safe treatment with the effect lasting for months. We suggest that clinical clearance correlates with histological improvement except for patients in the plaque stage.     

Treatment of pruritus in early‐stage hypopigmented mycosis fungoides with aprepitant

Pruritus is a symptom that significantly affects the patient's quality of life in cutaneous T cell lymphoma (CTCL). The most effective treatments are those that address the condition itself; however, it is often not possible to control this symptom. Lymphoma‐related pruritus normally becomes more severe as CTCL progresses, constituting an important factor for quality of life in these patients. Substance P is a neuromodulator which appears to play a key role in pruritus. Aprepitant is a neurokinin‐1 receptor antagonist affecting the substance P receptor. So far, several cases have been documented with an antipruritic response to the drug aprepitant in advanced‐stage mycosis fungoides (MF). In this paper, we describe an excellent response to aprepitant in a female patient with severe pruritus secondary to hypopigmented stage I MF. We would also like to stress the absence of nausea and vomiting of this combined therapy of interferon and aprepitant. Aprepitant could improve tolerance to interferon.     

Bexarotene and narrowband ultraviolet B phototherapy combination treatment for mycosis fungoides

Combination therapy for mycosis fungoides (MF) has the potential to be synergistic, improve therapeutic efficacy and reduce toxicities. We present a patient with MF who improved on combination therapy with bexarotene and narrowband ultraviolet B (NB-UVB) therapy. The patient is an 81-year-old Caucasian male who initially presented with stage IB MF. After temporary improvement with NB-UVB phototherapy, he progressed to develop plaques and tumors. Psoralen and ultraviolet A therapy was contraindicated because of ophthalmologic disease. Addition of bexarotene 300 mg daily led to rapid clinical improvement in combination with NB-UVB. Interruption of NB-UVB during a prolonged hospitalization led to a clinical flare of lesions, despite continued treatment with bexarotene. Reinitiating NB-UVB was associated with clinical improvement. This report demonstrates that combination treatment with oral bexarotene and NB-UVB therapy may represent a safe alternative for the treatment of plaque-stage MF.     

Etoposide as a single agent in the treatment of mycosis fungoides: A retrospective analysis

Several chemotherapy agents have shown efficacy in the treatment of mycosis fungoides (MF). In the literature, there is limited data on the use of single agent etoposide for MF. We aimed to retrospectively review our experience with single agent etoposide in the treatment of advanced‐stage or refractory early‐stage MF with focus on analyzing its efficacy and safety. We included 13 MF patients who were treated with single agent etoposide. Patients were identified through the Cutaneous T Cell Lymphoma Database of Indiana University that involves patients treated from 2006 to 2016. Overall nine patients (69%) responded to treatment. No complete response was identified. Median time to response was 12.5 weeks (range: 6–25.4). Median duration of response was 43 weeks (range: 5–60) and median time to treatment failure was 31.3 weeks (range: 12.4–230). Hematological toxicity was observed in eight patients including two patients with grade 4 neutropenia and/or lymphopenia leading to sepsis. Higher doses of etoposide were significantly correlated with higher grades of anemia, neutropenia or lymphopenia (p < .05). Our study demonstrates that etoposide is an effective treatment for MF and may be considered in selected patients with progressive MF who have failed other treatments.     

Extracorporeal photopheresis for the treatment of early‐stage mycosis fungoides

Extracorporeal photopheresis (ECP) has been used for nearly 30 years in the treatment of cutaneous T‐cell lymphoma. However, current clinical practice largely reserves ECP for patients with late‐stage mycosis fungoides (MF) or Sézary syndrome or for those who are refractory to other therapies. We briefly describe a 48‐year‐old male who experienced long‐term complete remission of his patch MF disease with ECP, and we suggest a role for ECP in the treatment of early‐stage MF given evidence of its efficacy, safety, and tolerability.     

Hypopigmented mycosis fungoides in childhood and adolescence: a long‐term retrospective study

Patients with hypopigmented mycosis fungoides (HMF) present at a younger age than those with classic MF. Our goal was to describe the clinical presentation, histopathologic features and long‐term outcome in patients who developed HMF before the age of 21. It was observed that among 69 pediatric patients diagnosed with MF between 1992 and 2010, 50 had HMF. Thirty‐five patients had clinical follow‐up. There were 37 males and 32 females with a mean age of 13.6 years. Most patients were African American or Hispanic and presented with multiple hypopigmented patches. All biopsies showed epidermotropism of T‐lymphocytes, whereas fibroplasia and lichenoid infiltrate were variable. All specimens tested were CD8+. Treatment modalities included topical steroids, narrow band ultraviolet B and psoralen and ultraviolet A. HMF patients were followed for <1–12 years. Most children responded to treatment, but recurrence rates were high. One patient progressed to plaque/tumor stage. Others did not progress; however, many were lost to follow‐up. We present a large cohort of children with HMF and report on the features of disease and progression. A major difference in histology of HMF was lack of fibroplasia and lichenoid infiltrate, probably because of presentation in the early patch stage. Most patients have a waxing‐and‐waning course and relapse after discontinuation of therapy, requiring repetitive treatment.     

Disseminated CD8‐positive,CD30‐positive cutaneous lymphoproliferative eruption with overlapping features of mycosis fungoides and primary cutaneous anaplastic large cell lymphoma following remote solitary lesional presentation

CD8‐positive, CD30‐positive cutaneous lymphoproliferative disorders constitute a rare subset of T‐cell lymphoproliferative conditions, including variants of primary cutaneous anaplastic large cell lymphoma (ALCL), mycosis fungoides, lymphomatoid papulosis type D, cutaneous gamma‐delta T‐cell lymphoma and cutaneous peripheral T‐cell lymphoma. These entities share overlapping clinical, histopathologic and immunophenotypic features, presenting both a clinical and pathological diagnostic challenge. Presented here is a 73‐year‐old man with a disseminated, indolent CD30+, CD8+ cutaneous lymphoproliferative disorder with overlapping clinical and histopathological features of both mycosis fungoides and primary cutaneous ALCL, as well as features of lymphomatoid papulosis. To our knowledge, this is the first case of a generalized CD8+, CD30+ eruption with features of both mycosis fungoides and primary cutaneous ALCL arising following an episode of solitary primary cutaneous CD8‐positive ALCL.     

Juvenile mycosis fungoides with large‐cell transformation: Successful treatment with psoralen with ultraviolet A light,interferon‐alfa,and localized radiation

Mycosis fungoides with large‐cell transformation is historically associated with a poor prognosis. Pediatric cases of mycosis fungoides with large‐cell transformation are rare, with only three other cases reported in the literature. We present the first case of a child with almost complete remission of his mycosis fungoides with large‐cell transformation shortly after administration of psoralen plus ultraviolet A, interferon‐alfa, and localized radiation.     

Hypopigmented interface T‐cell dyscrasia: A form of cutaneous T‐cell dyscrasia distinct from hypopigmented mycosis fungoides

Hypopigmentation in cutaneous T‐cell lymphoproliferative disease should not always be equated with hypopigmented mycosis fungoides (MF). A form of hypopigmented pre‐lymphomatous T‐cell dyscrasia falling under the designation of the so‐called hypopigmented interface variant of T‐cell dyscrasia has recently been proposed. The aim of the present study was to establish hypopigmented interface T‐cell dyscrasia as its own entity apart from other T‐cell dyscrasias and MF using a patient case series. Twenty four cases of hypopigmented interface T‐cell dyscrasia were identified in the dermatopathology database of Weill Medical College of Cornell University. There were 17 females and seven males (mean age, 36 years). In children and adolescents, the patients were most commonly of African American extraction. Truncal photo‐protected areas manifesting as large solitary patches or multiple smaller macules were characteristic; disease progression to MF occurred in only one patient. The lesions responded to topical steroids and light therapy. The pathology was defined by a cell poor interface associated with degeneration of keratinocytes and melanocytes, and by lymphocytes whose nuclei showed low‐grade cerebriform atypia, and which expressed a significant reduction in CD7 and CD62L expression. In 50% of the cases, the implicated cell type was of the CD8 subset. Clonality was not identified. Hypopigmented interface T‐cell dyscrasia is a distinct entity separate from and rarely progressive to MF.     

Tumor‐stage mycosis fungoides in palmoplantar localization with large‐cell transformation and partial CD30 expression shows complete response to brentuximab vedotin

Mycosis fungoides in palmoplantar localization (MFPP) is a rare variant of MF that is confined to the hands and feet. Patients commonly receive treatment over many years for suspected palmoplantar dermatitis before the diagnosis is made. Most MFPP patients remain at patch or plaque stage, and often respond to treatment with radiotherapy. Herein, we describe a 77‐year‐old man who suffered 6 years of hand and foot dermatitis that failed multiple treatments, most notably TNF‐α inhibitors and mycophenolate mofetil. He eventually developed a tumor on the hand, which was biopsied to reveal a dense dermal infiltrate of large lymphocytes (CD3+/CD4‐/CD8‐/TCR‐BetaF1+/partial CD30+). A subsequent biopsy of an eczematous patch from his hand revealed an epidermotropic and syringotropic infiltrate comprised of smaller lymphocytes with a concordant immunophenotype and matching clonal peak with TCR gene rearrangement. He was diagnosed with MFPP and started on radiotherapy with a modest response; therefore, a decision was made to start brentuximab vedotin, which resulted in a complete response. MFPP is an exceedingly rare variant of MF that can show large‐cell transformation and progress in stage. We highlight a possible association between disease progression and immunosuppressants and the potential role for treatment with brentuximab.     

Double‐positive CD4/CD8 mycosis fungoides: a rarely reported immunohistochemical profile

Mycosis fungoides (MF) represents the most common epidermotropic cutaneous T‐cell lymphoma (CTCL), and tumor cells typically express a mature T‐helper memory phenotype. A minority of MF patients display an unusual phenotype, which may be either CD4(?)/CD8(+) or double negative. Herein, we report a case of biopsy‐proven MF in a 31‐year‐old woman who presented with infiltrated plaques involving photoprotected areas of the skin. Immunohistochemical study combined with confocal microscopy revealed co‐expression of CD4 and CD8 in a subset of atypical T lymphocytes. To our knowledge, this is the second report of a CD4/CD8 dual‐positive MF.     

Poikilodermatous mycosis fungoides with CD30‐positive large cell transformation successfully treated by brentuximab vedotin

We present a patient with a 33‐year history of poikilodermatous mycosis fungoides (MF) who subsequently developed CD30‐positive large cell transformation. After 6 years of conventional MF treatment, side effects of therapy and/or concomitant diseases prevented the previously applied treatment modalities. The CD30‐directed antibody‐cytotoxic drug conjugate (brentuximab vedotin) was introduced and followed by quick and excellent therapeutic response.     

miR‐155 is involved in tumor progression of mycosis fungoides

Biopsy specimens from 23 early stage and 19 tumor‐stage mycosis fungoides (MF) patients were evaluated for miR‐155 expression by real‐time qualitative PCR and compared with 15 biopsy specimens from patients with T‐cell‐rich inflammatory skin diseases. Significant upregulation of miR‐155 was found in MF tumors compared with both early‐stage MF lesions and controls. There was no difference in miR‐155 expression between early‐stage and inflammatory dermatoses. Using laser capture microdissection, it was found that miR‐155 was significantly higher in the lymphoma cells in tumor stage compared with the intraepidermal lymphocytes in early stage. In contrast, there was no difference in miR‐155 expression between the intraepidermal lymphocytes and the dermal lymphocytes in early‐stage MF. These findings suggest that although miR‐155 expression cannot serve to discriminate early‐stage MF from inflammatory dermatoses; however, it is involved in the switch from the indolent early stage into the aggressive tumor stage of the disease.