Early-stage Mycosis Fungoides Research Articles

Standardization of regimens in Narrowband UVB and PUVA in early stage mycosis fungoides: position paper from the Italian Task Force for Cutaneous Lymphomas.

UV-based (PUVA and narrowband UVB) phototherapy is broadly and commonly used in the treatment of Cutaneous T-cell Lymphomas (CTCL), yet unfortunately, the evidence for the efficacy of these treatments is based only on case series or prospective but non-randomized studies. Therefore, no internationally approved guidelines exist and no standardization of schedules has been proposed. Recently, consensus guidelines have been published by the United States Cutaneous Lymphoma Consortium. The aim of this study was to review the biological and clinical evidences on PUVA and NB-UVB in CTCL and to critically evaluate acceptability and feasibility of these guidelines in the real-life setting from the perspective of the Cutaneous Lymphoma Task Force of the Italian Lymphoma Foundation (Fondazione Italiana Linfomi, FIL).

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.

Clinical and epidemiological profile of patients with early stage mycosis fungoides

Background:Mycosis fungoides is the most common form of primary cutaneous lymphoma, with an indolent, slowly progressive course and 88% five-year survival rate. The diagnosis is challenging, especially in the early stages, and usually relies on a good clinical-histopathological correlation. Objective:The aim was to establish the clinical and epidemiological profile of patients with early-stage mycosis fungoides. Methods:This was a retrospective cross-sectional observational study with an exploratory analysis. Outcome variables were disease progression and mycosis fungoides-related death. Results:One hundred and two patients were included. The majority were white males, with a mean age of 55.6 years. Mean time from onset of lesions to diagnosis was 51.08 months. The majority of patients were classified as IB stage according to TNMB. Mean follow-up time was 7.85 years. Disease progression was seen in 29.4% of the patients. Death related to the disease occurred in 7.9% of patients. Plaque lesions, involvement of more than 10% of the body surface, altered lactate dehydrogenase and beta-2-microglobulin, and stage IB were significantly associated with disease progression, and altered lactate dehydrogenase and beta-2-microglobulin also correlated with higher frequency of deaths. Study limitations:Small sample and retrospective design. Conclusions:The clinical and epidemiological profile of patients with early-stage mycosis fungoides in our sample corroborates reports in the literature. Diagnostic delay in our series is also consistent with previous findings, but the rate of disease progression, despite treatment, was higher than reported in the literature.

Evaluation of the Cutaneous Lymphoma International Prognostic Index in patients with early stage mycosis fungoides

BackgroundMycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. TNMB system is the staging method used in MF, and it not only guides therapeutic management, but represents the main prognostic factor. In order to improve the prognostic evaluation, the Cutaneous Lymphoma International Prognostic Index (CLIPi) was proposed.ObjectiveTo evaluate the performance of CLIPi score for prognostic analysis in patients with early stage MF.MethodsThis is a retrospective cross-sectional observational study, with exploratory analysis. The outcome variables were disease progression and related death.ResultsOne hundred and two patients were stratified according to CLIPi score, being the majority classified as low risk. Patients with intermediate or high risk presented disease progression more frequently than those with low risk (PR: 1.2 / p = 0.004 / 95%CI: 1.0 - 1.6). The same did not occur with the variable related death. In addition, survival rates were not consistent with risk stratification.Study LimitationsSmall sample and its retrospective analysis.ConclusionsSince CLIPi score was proposed, four other studies that we could consult showed conflicting results, similar to the present study. Further studies are necessary for a recommendation of its use.

Therapeutic and prognostic significance of PARP-1 in advanced mycosis fungoides and Sezary syndrome.

While mycosis fungoides (MF) is typically an indolent malignancy, it may infrequently undertake an aggressive course. We used proteomic analyses to identify a biomarker of the aggressive course of MF. Results of this investigation demonstrated that PARP-1, heat-shock protein family A (Hsp70) member 1 like (HSAP1L), Hsp70 member 1A (HSPA1A), ATP-depending RNA helicase (DDX17) and the α-isoform of lamina-associated polypeptide 2 (TMPO) had higher expression in aggressive disease versus non-aggressive. Moreover, PARP-1 was overexpressed in patients with early stage of MF who developed later an aggressive disease. PARP-1 was evaluated as a new target for therapy, demonstrating the selective dose-dependent cytotoxic effect of PARP inhibitors on Sézary cells in comparison with non-malignant lymphocytes. In conclusion, we believe that PARP-1 may serve not only as a biomarker at initial biopsies for a disease that may become aggressive but also as a new therapeutic target of advanced MF and Sézary syndrome.

Cutaneous lymphomas in Taiwan: A review of 118 cases from a medical center in southern Taiwan

Abstract Background Cutaneous lymphomas (CLs) have not been well characterized in Taiwan. Methods We retrospectively reviewed the clinical and pathologic findings of cases of CLs of our department diagnosed from January 2001 to December 2010. The final diagnosis was made according to the 2008 World Health Organization (WHO) classification and its 2016 update. Results Our series consisted of 91 primary CLs, 27 secondary CLs. The primary CLs consisted of 84 cases of mature T-cell and NK-cell lymphomas (CTCLs) and 7 cases of B-cell lymphomas, including mycosis fungoides (MF) (57.1%), lymphomatoid papulosis (LyP) (14.3%), anaplastic large cell lymphoma (7.7%), extranodal NK/T cell lymphoma, nasal type (4.4%), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (3.3%), and diffuse large B-cell lymphoma (4.4%). Most MF (82.6%) cases were early MF (stage I–IIA) and were treated successfully, mainly with ultraviolet B (UVB) 311. The overall 5-year survival rate was 90.7% for early stage MF, 37.5% for stage late MF and 74.9% for all MF cases. Conclusion Compared to other larger Western and Asian series of primary CLs, our series showed higher proportions of CTCLs and MF. Over 80% of MF was early MF, a finding consistent with the trend in early diagnosis of MF in recent decades. A nation-wide study is warranted to further characterize CLs in Taiwan.

Radiotherapy for Mycosis Fungoides: Review of the Literature

Apart from systemic or nodal lymphomas, cutaneous lymphomas present a heterogeneous group of relatively infrequent non-Hodgkin lymphomas with distinct clinical characteristics. Among cutaneous lymphomas, primary cutaneous T cell lymphomas account for the majority of cases with Mycosis Fungoides (MF) being the most prevalent subtype. Skin-directed treatment constitutes the principal mode of management for early stage MF, and systemic therapies or combination of modalities are typically employed in more advanced stages. Radiation therapy including Total Skin Electron Beam Therapy (TSEBT) is a viable skin-directed tratment modality in the management of patients suffering from MF. Radiotherapy may be used alone or as part of multidisciplinary management with excellent complete response rates.

Bath Psoralen-ultraviolet A and Narrowband Ultraviolet B Phototherapy as Initial Therapy for Early-stage Mycosis Fungoides: A Retrospective Cohort of 267 Cases at the University of Toronto.

Phototherapy is used frequently to treat early-stage mycosis fungoides (MF). The effectiveness of bath psoralen-ultraviolet A (bath PUVA) and narrowband ultraviolet B (nbUVB) in MF is well established. However, evidence is limited comparing the effectiveness of the 2 modalities for early-stage MF. The objective of the present study was to compare the responses between the study participants receiving bath PUVA versus nbUVB phototherapy. The study included a retrospective cohort of stage 1A and 1B MF patients treated with bath PUVA or nbUVB at their initial presentation. The primary outcome was the response to treatment. The secondary outcome was disease-free survival. The cohort included 267 patients (158 treated with bath PUVA and 109 treated with nbUVB) with a mean age of 45.22 years. The mean follow-up period was 59.58 months for bath PUVA and 22.27 months for nbUVB. Overall, 88.61% of the bath PUVA group and 88.07% of the nbUVB group had complete responses (P= .89). The median number of treatments to achieve a complete response was 55 for bath PUVA and 55.5 for nbUVB (P= .63). The median disease-free survival was 43.25 months for bath PUVA and 14.9 months for nbUVB (P< .0001). The study was limited by its retrospective nature. Bath PUVA and nbUVB are both effective treatments. The use of bath PUVA resulted in significantly greater disease-free survival.

Recommendations for treatment in folliculotropic mycosis fungoides: report of the Dutch Cutaneous Lymphoma Group.

Folliculotropic mycosis fungoides (FMF) is an aggressive variant of mycosis fungoides (MF) and generally less responsive to standard skin-directed therapies (SDTs). Recent studies distinguished indolent (early-stage FMF) and more aggressive (advanced-stage FMF) subgroups. The optimal treatment for both subgroups remains to be defined. To evaluate initial treatment results in patients with early- and advanced-stage FMF. A study was undertaken of 203 patients (84 early-stage, 102 advanced-stage, 17 extracutaneous FMF) included in the Dutch Cutaneous Lymphoma Registry between 1985 and 2014. Type and results of initial treatment were retrieved from the Dutch Registry. Main outcomes were complete remission (CR); sustained complete remission; partial remission (PR), > 50% improvement; and overall response (OR; CR + PR). Patients with early-stage FMF were treated with nonaggressive SDTs in 67 of 84 cases resulting, respectively, in CR and OR of 28% and 83% for monotherapy topical steroids, 0% and 83% for ultraviolet B (UVB), and 30% and 88% for psoralen plus ultraviolet A (PUVA). In patients with advanced-stage FMF these SDTs were less effective (combined CR and OR 10% and 52%, respectively). In patients with advanced-stage FMF local radiotherapy (CR 63%; OR 100%), total skin electron beam irradiation (CR 59%; OR 100%) and PUVA combined with local radiotherapy (CR 5%, OR 75%) were most effective. The results of the present study demonstrate that not all patients with FMF should be treated aggressively. Patients with early-stage FMF may benefit very well from standard SDTs also used in early-stage classic MF and have an excellent prognosis.

ALK Expression is a Rare Finding in Mycosis Fungoides.

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. Although indolent in its early stages, MF is more aggressive in advanced stages, particularly if large cell transformation occurs. Histologically, transformed MF is similar to primary cutaneous anaplastic large cell lymphoma (pcALCL) and nodal ALCL (nALCL). MF had not been associated with immunohistochemical expression of anaplastic lymphoma kinase (ALK) until we previously reported a case documenting the presence of ALK by immunohistochemistry in a patient with stage IA MF and concurrent nALCL. This is a unique finding due to the fact that ALK positivity is usually found in nALCL. The goal of this study is to examine the extent to which ALK may be expressed in the different morphologic lesions of MF. One hundred three biopsies from 96 patients, including the patient from the original case, with confirmed MF representing various lesion stages and subtypes, were tested for ALK by immunohistochemical staining. Out of the 103 biopsies, only the original index case of Stage IA MF with concurrent nALCL expressed ALK. From these results, we conclude that ALK is not routinely present in MF in any lesion stage or variant type. Routine staining of ALK is therefore of no additional benefit for the workup of known early stage MF; however, its use may be beneficial in the initial workup of unspecified large cell lymphomas of the skin.

Psoralen with ultraviolet A-induced apoptosis of cutaneous lymphoma cell lines is augmented by type I interferons via the JAK1-STAT1 pathway.

Photochemotherapy with psoralen and ultraviolet A (PUVA), with or without adjuvant interferon-α (IFN-α), is a first-line therapy for early-stage mycosis fungoides and other forms of cutaneous T-cell lymphoma (CTCL). However, the mechanism by which PUVA with IFN-α work in CTCL is poorly understood. To develop a model to investigate the mechanisms of PUVA and PUVA with IFN-α in CTCL cells. An invitro model to study the molecular mechanisms of PUVA was created using two different CTCL cell lines, MyLa, which has functional p53, and HuT-78, in which p53 is inactivated due to a homozygous nonsense mutation. PUVA caused G2/M cell cycle block and apoptosis of MyLa and HuT-78 accompanied by increase in the expression of the mitochondrial pro-apoptotic genes Bax, BAK, and PUMA and a downregulation in anti-apoptotic Bcl-2. p53 was induced and c-Myc was repressed by PUVA, but neither were essential for PUVA-induced apoptosis. IFN-α augmented PUVA-induced apoptosis via the JAK1 pathway, and this activity could be inhibited by ruxolitinib. PUVA induces p53-independent apoptosis in CTCL cell lines, and this process is augmented by type I interferons via the JAK1 pathway.

250 CADM1 is a diagnostic marker in early-stage mycosis fungoides

250 CADM1 is a diagnostic marker in early-stage mycosis fungoides

Periorbital Involvement in Early Stage Mycosis Fungoides.

Periorbital Involvement in Early Stage Mycosis Fungoides.

The cellular microenvironment and neoplastic population in mycosis fungoides skin lesions: a clinicopathological correlation.

The cellular microenvironment has been proven to play a crucial role in solid tumours and seems to be important in haematologic malignancies, however, it has not been adequately investigated in primary cutaneous Tcell lymphomas. The aim of this study was to register the composition of the cellular microenvironment in mycosis fungoides skin lesions and correlate the composing parameters with the clinical data and follow-up results. The presence of eosinophilic polymorphonuclear leukocytes, Blymphocytes, CD68+ macrophages, and CD1a+ epidermal Langerhans and antigen-presenting dermal dendritic cells, as well as their relation to clinicopathological parameters, were studied in 16 mycosis fungoides cases of different disease stages. The presence and nature of the participating Tcell populations was also investigated. CD8+ tumour infiltrating Tcells and CD56+ cells were found among neoplastic CD4+ Tcells in the lesions. Generally, eosinophils and Blymphocytes were absent or in low numbers, regardless of clinical presentation, contrary to tumourous lesions. Macrophages and CD1a+ cells were constantly present, even in early-stage mycosis fungoides. The reduced presence of the CD1a+ population was associated with resistance to therapy (x2; p=0.012). There is a striking difference in cellular microenvironment composition between early and advanced mycosis fungoides lesions.

Expression of langerhans cells, dermal dendritic cells and plasmacytoid dendritic cells in early stage mycosis fungoides: Case control study

Expression of langerhans cells, dermal dendritic cells and plasmacytoid dendritic cells in early stage mycosis fungoides: Case control study

Identified early stage mycosis fungoides from psoriasis and atopic dermatitis by using non-invasive color contrast enhancement

Identified early stage mycosis fungoides from psoriasis and atopic dermatitis by using non-invasive color contrast enhancement

Expression of CD31 in Mycosis Fungoides

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL) characterized by malignant proliferation of mature T lymphocytes and primary skin involvement. Recent reports suggest that angiogenesis may play a role in the growth and spread of this malignancy. Cluster of differentiation 31 (CD31) is a protein classified into the Ig-superfamily of cell adhesion molecules, expressed on endothelial cells and majority of hematopoietic non-erythroid cells. The aim of our study was to explore the role of angiogenesis in MF. We evaluated the expression of CD31 in relation to clinicopathological data and potential impact on patients' outcome in MF utilizing immunohistochemistry (IHC) and western blot (WB) techniques in 73 and 19 MF and 21 and 4 control samples, respectively. In the IHC study, statistical analysis revealed significantly higher CD31 expression in MF compared to the controls (p<0.0001) with highest expression in advanced stages vs. early ones and controls (p<0.0001 for both). In regard to skin involvement, expression was also elevated in more infiltrative (T3, tumors) and in more extensive (T4, erythroderma) cutaneous lesions compared to less infiltrative and limited skin lesions (T1, T2, patches and/or plaques) (p<0.01 for both). Regarding the extracutaneous spread, higher CD31 expression correlated with nodal involvement (N1-3 vs. N0; p<0.0001). In the WB study, statistical analysis revealed significantly higher CD31 expression only in advanced vs. early stage of MF (p<0.05). In regard to skin involvement, expression was also elevated in T3 and T4 as compared T1+T2 (p=0.08, p<0.05; respectively). Higher CD31 expression correlated with nodal involvement (N1-3 vs. N0; p<0.01). A strong significant correlation between CD31 expression at the protein level analyzed by IHC and WB was noticed (r=0.802, p<0.0001). Moreover, strong positive correlations between IHC expression of CD31 and podoplanin (PDPN; r=0.582, p<0.0001), vascular endothelial growth factor C (VEGFC; r=0.332, p<0.01) and Ki-67 (r=0.330, p<0.01) were disclosed. Expression of CD31 in MF skin biopsies provides new evidence for the role of angiogenesis in the progression of MF. Additionally, the new data revealed prompts for further research on potential use of CD31 as a new marker of the disease advancement, as well as the target of new therapeutic strategies.

Correlation between mycosis fungoides and pregnancy.

Objectives:To evaluate the effect of pregnancy on the natural course of Mycosis fungoides (MF) and compare the obtained results with previous reports.Methods:The medical records of 140 patients with cutaneous T-cell lymphoma (CTCL) treated at the University Hospital of Isfahan (the academic referral center for CTCL) Isfahan, Iran. Between 2000 and 2013 were retrospectively reviewed to retrieve all cases of pregnancy during the course of MF disease.Results:A total of 8 pregnancies were recorded. The median age of patients at the time of diagnosis was 26.7 (range 21-30 years) and pregnancy 29.4 (range 27-31 years). Most of patients had early-stage MF (Ia and Ib). All patients experienced aggravation of disease during pregnancy or immediately postpartum. Mycosis fungoides did not cause any complications during pregnancy.Conclusion:Pregnancy appears to have a negative impact on the course of MF, probably due to immune system deteriorations during the pregnancy. Further studies are needed to clarify the interplay between pregnancy and MF.

Evaluation of neutrophil–lymphocyte ratio in patients with early-stage mycosis fungoides

Neutrophil-lymphocyte ratio (NLR), an indicator of inflammation, has been lately demonstrated as a prognostic factor and an indicator of disease activity in various diseases. However, the effects of NLR have not been investigated in mycosis fungoides (MF) patients yet. The aim of this study is to investigate the relationship between the NLR and treatment demand (systemic PUVA and/or chemotherapy), time to treatment, progression in stage, and time to progression in stage in MF patients. The data of 117 patients, who were followed with the diagnosis of MF at the Department of Dermatology in Istanbul Training and Research Hospital between April 2006 and January 2016, were analyzed retrospectively. The cutoff score for NLR was determined as 2 according to the median NLR level which was 1.96. At the time of diagnosis, the median age of patients was 54years (range, 21-90) with 62 (53%) female and 55 (47%) male. Seventy-seven (65.8%) patients required treatment during follow-up. Sixty-three (53.8%) patients showed progression in disease stage. There was no significant difference in treatment demand, time to treatment, progression in stage, and time to progression in stage in patients with a NLR ≥ 2 and NLR < 2 (p = 0.331, 0.987, 0.065, and 0.119, respectively). It seems that there is no association between the NLR and treatment demand, time to treatment, progression in stage, and time to progression in stage in MF patients.

Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma.

Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sézary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL.