Stage Mycosis Fungoides Research Articles

Narrowband Ultraviolet B Phototherapy of Early Stage Mycosis Fungoides in Korean Patients

BackgroundNarrowband UVB (NBUVB) is currently used to treat early mycosis fungoides (MF). There are a number of reports on the efficacy and safety of NBUVB in Caucasians, but little data is available for Asians.ObjectiveThis study was designed to evaluate the effectiveness and safety of NBUVB for early stage MF in Korean patients.MethodsWe enrolled 14 patients (12 men, 2 women; age range, 10~64 years) with clinically and histologically proven MF. Three patients were stage IA, and the others were stage IB. The patients received NBUVB phototherapy three times a week. The starting dose was 70% of the minimal erythema dose and was increased in 20 percent increments if the previous treatment did not cause erythema. Clinical response, total number of treatments, total cumulative dose, duration of remission and side effects were investigated.ResultsEleven of 14 patients (78.6%) achieved complete remission within a mean of 15.36±5.71 weeks (range, 5~27 weeks), 31.0±7.4 treatments (range, 16~39 treatments) and a mean cumulative UVB dose of 31.31±12.16 J/cm2 (range, 11.4~46.8 J/cm2). Three of the 14 patients (21.4%) achieved a partial remission. After discontinuation of treatment, 6 of 11 patients (54.5%) with complete remission relapsed after a mean of 8.5±4.09 months. No serious adverse effects were observed except for hyperpigmentation (7/14, 50%).ConclusionOur data suggest that NBUVB therapy is safe and effective for the treatment of early stage MF in Korean patients.

EORTC 21012: Phase II Multicentre Study of Caelyx™ Monotherapy In Patients with Advanced Mycosis Fungoides Stage IIb, Iva and IVb with or without Previous Chemotherapy.

AbstractAbstract 2823 Background:Cutaneous lymphomas consist of a heterogeneous group of diseases that are characterized by a clonal accumulation of lymphocytes in the skin. The estimated incidence is 1–2/100.000 per year. The more advanced stages have a poor prognosis and treatments are usually palliative, such as combination of PUVA with retinoids or recombinant interferon alpha. CHOP or COPBLAM are widely used in analogy to other peripheral T-cell lymphomas, but have severe, sometimes lethal infectious complications and short response duration. Some studies indicated response rates after CHOP chemotherapy regimen are between 40% and 70% in cutaneous T-cell lymphoma (CTCL). However, these studies include patients in various disease stages, that might not necessarily need aggressive treatment and without precise information concerning the CTCL subtype. Therefore, there is an urgent need for multicenter trials designed to test a clearly defined patient population. Pegylated liposomal doxorubicin (PLD, Caelyx™) is an antineoplastic antibiotic with pharmacologic actions similar to those of daunorubicin. PLD provides a longer circulation time and a higher drug concentration in tumors than in normal tissue that could lead to reduced side effects in particular life-threatening cardiotoxicity and neutropenia with infectious complications. Material and methods:Eligible patients had histologically confirmed Mycosis Fungoides stage IIb, IVa, or IVb, WHO performance status (PS) 0–2, no systemic treatment with steroids and refractory or recurrent disease after at least 2 or more previous therapies. Caelyx 20 mg/m2 was administered on days 1 and 15 in a 28-day cycle for a maximum of 6 cycles. The primary endpoint was response rate (RR), defined as patients achieved either complete clinical response (CCR) or partial response (PR). Using the Fleming design with α= 0.1 and β= 0.05 and aiming at a RR = 45% and powered to rule out a RR < 25%, 48 patients who are eligible and started treatment are required. To declare success, a 1-sided 90% confidence interval (CI) for RR should exclude 25% (the rate used in the null hypothesis). Results:Between November 22, 2003 and July 3, 2009, 9 centers registered 49 patients. All of them were eligible and started treatment. The majority of patients were male (67%), had PS 0, 1 (43%, 53%) and were between 56–65 and 66–75 year old (33% and 31%). The median (range) number of chemotherapy cycles received was 5(1-6) and the majority of patients had relative dose intensity of 90–110% and 70–90% (53% and 35%). Eighty eight percents of patients received prophylactic antiemetics; 84% had PS 0–1 during treatment. There was no Grade 3–4 hematological toxicity; only grade 2 neutropenia (4%), leukopenia (4%) and anemia (4%) were observed during treatment. Grade 3/4 non-hematologic/non biochemical toxicities were cardiac (2%), allergy (2%), constitutional symptom (4%), hand foot reaction (2%), other dermatologic toxicity (6%), other gastro intestinal toxicity (4%) and other infection (4%). One patient (2%) had grade 4 cardiac ischemia. Of 49 patients who were eligible and started treatment, 20 (40.8%) were responders: 3 (6.1%) CCR and 17 (34.7%). The 1-sided 90% CI for the RR is: (31.2%, 100%). Conclusion:The primary RR endpoint of the study was reached (ie, 1-sided 90% CI excludes 25%). We conclude that Caelyx™ should be considered for further investigation. Caelyx™ has an acceptable safety profile with only a few toxicities and no sepsis observed in this patient population of advanced age. Its efficacy appears promising. Disclosures:Dummer:Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cephalon: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dhome: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Transgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Schering Plough: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Becker:SheringPlough International: Consultancy. Weichenthal:Schering-Plough : Honoraria, Research Funding.

In Situ Vaccination with TLR9 Agonist Combined with Local Radiation In Mycosis Fungoides: Analysis of Phase I/II Study

AbstractAbstract 286 Background:In a murine model, our in situ vaccination therapy combining tumor antigens with TLR9 agonist cured mice of lymphoma. Our phase I/II study in indolent B-cell lymphoma demonstrated that this in situ vaccination maneuver utilizing local radiation to expose tumor antigens combined with CpG ODN was well-tolerated without treatment limiting toxicities. It induced meaningful systemic clinical responses and tumor-reactive memory CD8 T-cells. In parallel, we explored this in situ vaccination strategy in cutaneous T-cell lymphoma (CTCL), specifically mycosis fungoides (MF). Our objectives were to determine the feasibility and safety and to assess the local and systemic antitumor effects in MF. Methods:Patients with MF stages IA-IVA who failed ≥1 standard therapy were eligible. Immunization site was treated with low-dose radiation (2 Gy × 2 d), bracketed by intratumoral injection of CpG followed by weekly intratumoral CpG × 8. Local (immunized site) and systemic antitumor responses were assessed at wk 0, 2, 4, 8, 12, then monthly until PD/off-study. Clinical response was evaluated by assessing skin disease burden at sites not treated with immunization procedure. Results:Study enrollment was completed with total of 15 patients. Median age was 57 yrs (range 18–71 yrs), 12 of 15 were male. Six patients had stage IB and 9 with stage IIB (3 with large-cell transformation). Median number of prior therapies was 5 with range of 2–9. After the initial 6 patients, a second immunization site was added at wk 4 to enhance systemic response. Total of 5 partial responses were observed (30% OR); 2 of 6 treated with single immunization and 3 of 9 with dual immunization. Median time to response was 8 wks (range 4–12 wks), duration of response 7 wks (range 4–44 wks), and time to progression 20+ wks (range 3–44+ wks). Patients with large-cell transformed MF did not respond. Common toxicities were injection site and flu-like symptoms; mostly grade 1–2 and all transient. No clinical or laboratory findings of any autoimmune disorder were observed. Local tissue tumor/immune responses were assessed by immunostaining. CpG + local radiation treated immunization site showed a significant reduction of CD25+, Foxp3+ T-cells (p<0.01) consisting of MF cells and tumor-infiltrating lymphocytes. Similar reduction in S100+, CD1a+ dendritic cells (DCs) was observed post immunization (p < 0.025). A qualitative analysis suggested more remarkable reduction of CD25+ T-cells and skin DCs in clinical responders vs. non-responders (p= 0.058, 0.121). CpG dose-responsive activation of peripheral blood pDCs was observed in vitro. Conclusions:Our novel in situ vaccination strategy using a combination of intratumoral CpG ODN and low-dose radiation is feasible in CTCL/MF with acceptable toxicities. Depletion of tissue T-regs may be observed at immunized sites. Reduction of skin DCs may suggest cross-priming and migration of DCs to regional lymph nodes. Clinical responses in subset of patients and CpG responsiveness of pDCs may warrant further study with modifications to augment therapeutic effects. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Thymus and activation-regulated chemokine in different stages of mycosis fungoides: Tissue and serum levels

Thymus and activation-regulated chemokine (CCL17) is a member of the CC chemokines known to attract T-helper 2 type memory T cells and to participate in different T-helper 2 diseases. The aim of this study is to determine both serum and tissue levels of thymus and activation-regulated chemokine in patients with different stages of mycosis fungoides. Thirty-two patients with different stages of mycosis fungoides and 10 controls were included in the study. Skin biopsies and blood samples were taken to evaluate both tissue and serum levels of thymus and activation-regulated chemokine using the enzyme-linked immunosorbent assay method. The mean tissue level of thymus and activation-regulated chemokine in 10 tumour-stage patients was significantly higher (P = 0.002) than in the controls. The mean serum level of thymus and activation-regulated chemokine in all stages of mycosis fungoides patients was not significantly elevated (P = 0.131, 0.725 and 0.622) compared with controls. Both tissue and serum levels of thymus and activation-regulated chemokine correlated significantly with both the disease extent and duration in the three different stages of mycosis fungoides. Thymus and activation-regulated chemokine may be a marker for disease activity of mycosis fungoides, and may have a role in monitoring disease progression.

A large scale analytical study on efficacy of different photo(chemo)therapeutic modalities in the treatment of psoriasis, vitiligo and mycosis fungoides

Psoriasis, vitiligo, and mycosis fungoides (MF) are among the most frequently treated dermatological diseases by photo(chemo)therapy. The objectives are to determine which photo (chemo) therapeutic modality could achieve the best response in the treatment of psoriasis, vitiligo, and MF. The design used in this study is retrospective analytical study. The study included 745 patients' records; 293 with psoriasis, 309 with vitiligo, and 143 with early MF, treated in the Phototherapy Unit, Dermatology Department, Kasr El-Aini Hospital, Cairo University by either psoralen and ultraviolet A (PUVA), narrow band ultraviolet B (NB-UVB), psoralen and narrow band UVB (P-NBUVB), broad band UVB (BB-UVB), or broad band UVA (BetaBeta-UVA). Data were retrieved from the computer database of the unit and statistically analyzed. In psoriasis, oral and topical PUVA and NB-UVB were found to be equally effective, whereas oral PUVA had significantly better results than both UVA and BB-UVB at the end of therapy. In generalized vitiligo, PUVA and P-NBUVB had significantly better results than NB-UVB alone. In early MF, there was no statistically significant difference between the response to oral PUVA and NB-UVB. PUVA and NB-UVB are good choices in patients with psoriasis and early stage MF, whereas PUVA appears the best choice in the treatment of vitiligo.

P99 Broadband UVA versus PUVA in the treatment of early stage mycosis fungoides: a comparative study

Background Mycosis fungoides (MF) is the most common type of cutaneous-T-cell lymphoma, with no established consensus for its treatment [1]. The standard treatment for early stage MF is PUVA [2]. UVA1 phototherapy was found to induce marked improvement in skin lesions of patients with stages IA and IB MF. Broad band UVA is composed of 80.1% UVA1, with similar mechanisms of action [3]. Aim of work The aim of the present work was to compare the efficacy of PUVA versus broad band UVA as a substitute to UVA1 in the treatment of early stage MF (IA, IB, IIA). Patients and methods; Thirty patients with early stage MF (IA and IB) were included in this prospective, randomized clinical trial. They were randomly divided into two equal groups; group A (15 patients receiving PUVA) and group B (15 patients receiving BBUVA at 20 J/cm2/session). The patients received three sessions/week for 13 weeks i.e. forty sessions. The patients were compared regarding clinical, histopathological, immunohistochemical (By measuring the bcl-2 level) and overall responses. Results Among each of the two groups, there was statistically significant improvement in the clinical, histopathological, immunohistochemical and overall responses. However there was no statistically significant difference between both groups in any of the aspects with comparable overall success rates; (93.3%) in the PUVA group and (80%) in the BBUVA group. Excellent overall response rates was higher in the BB-UVA group (41.7%) versus (14.3%) in the PUVA group, but still with no statistically significant difference (P=0.117). As regards the side effects encountered in both groups; there was no statistically significant difference in the rates of tanning, pruritus, appearance of new lesions, photosensitivity or dryness. However discomfort was significantly higher among the BB-UVA group (P=0.032) and nausea was significantly higher among the PUVA group (P=0.003). Conclusion BB-UVA is a new, yet promising therapeutic modality in the treatment of early stage MF, as it is comparable to PUVA, as regards both the efficacy and safety. It could substitute the use of UVA1 in the treatment of early stage MF.

Histopathological Changes Seen in Mycosis Fungoides Patients After Phototherapy

Early stage (IA, IB, IIA) mycosis fungoides (MF) has long been treated with various agents including oral psoralen plus UVA (PUVA), broadband and narrowband. The histopathological changes seen after phototherapy have not been clearly described. Twenty-three skin biopsy specimens of MF patients treated with phototherapy both UVA and UVB were evaluated before and 3 months after phototherapy. The clinical and histomorphological response were evaluated. Various types of epidermotropism: such as single cells, haloed cells, linearly arranged single cells, pagetoid spread, and Pautrier microabscesses were noted. Stratum corneum was classified as normal, hyperkeratotic, and parakeratotic. The epidermal thickness was noted as normal, atrophic, and hypertrophic. Spongiotic microvesiculation, presence of dilated dermal vessels, was investigated. Papillary dermis fibrosis, the presence of plasma cells, eosinophils, and extravasated erythrocytes were also examined. Epidermal hyperplasia, dermal fibrosis, loss of parakeratotic pattern, and inflammatory infiltrate were frequently observed after therapy. After phototherapy, the atypical cells rarely formed "Pautrier microabscess" or made a "linear pattern" at the base of epidermis. The cells other than lymphocytes (plasma cells, eosinophils, and erythrocytes) should also be considered regarding the phototherapy effect. A pathology report of a MF patient who has undergone successful phototherapy would describe changes resulting from phototherapy-such as fibrosis or "lack of dermal inflammation" and the absence of active epidermal cellular changes such as "Pautrier microabscess" or "linearly arranged cells."

Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Immunohistochemical Study of the Expression of Matrix Metalloproteinase-9 in Skin Lesions of Mycosis Fungoides

Matrix metalloproteinase-9 (MMP-9) has been correlated with poor clinical outcome in various malignancies and is associated with enhanced tumor growth and dissemination through its role in angiogenesis. This study was carried out to review the immunohistological staining of MMP-9 in skin lesions of different stages of mycosis fungoides (MF). The study was carried on 22 patients with MF and 10 healthy controls. Immunohistochemical staining using MMP-9 monoclonal anti-human antibodies was performed to determine the intensity of expression and distribution pattern of MMP-9 in MF lesions and in normal control skin. The general intensity of expression of MMP-9 was found to be significantly higher in cases with MF than in controls, and it increased in direct proportion to the increase in disease severity, being greatest in the tumor stages. A significantly greater number of blood vessels were found in cases with MF when compared with controls, and the MMP-9 expression by endothelial cells was significantly higher in endothelial cells within tumor cell aggregates than in endothelial cells outside the tumor cell aggregates. This study raises the possibility that MMP-9 may play an important role in the development of MF lesions, and its significantly higher expression in tumor stages may point to a possible role in disease progression. Further studies are needed to validate these findings and to assess the possible therapeutic role of drugs targeting MMP-9 in the treatment of MF.

Bcl-2 expression in mycosis fungoides before and after PUVA therapy

PUVA is the first therapeutic choice in early stages of mycosis fungoides (MF). In this study the effect of PUVA on bcl-2 expression in MF was assessed in 15 patients (three stage Ia and 12 stage Ib) and 10 controls. Two biopsies were taken from each patient before and after 24 sessions of PUVA therapy. Histopathological assessment and immunohistochemical staining for bcl-2 was performed and showed positive bcl-2 staining of lymphocytes in 53% of MF cases (8/15) before PUVA, with no statistically significant difference in the bcl-2 level before and after PUVA therapy (P value 0.3). A statistically significant difference was found in the bcl-2 level between control samples and MF patients' biopsies before (P value 0.02) and after PUVA therapy (P value 0.011). In conclusion, a lack of decline in the bcl-2 level and the absence of clinical or histopathological correlation with the bcl-2 level before and after PUVA therapy in MF patients suggest that PUVA-induced apoptosis in MF cases may occur through pathways other than bcl-2 inhibition.

Treatment of Early Stages of Mycosis Fungoides with Narrowband Ultraviolet B: A Clinical, Histological and Molecular Evaluation of Results

Treatment of Early Stages of Mycosis Fungoides with Narrowband Ultraviolet B: A Clinical, Histological and Molecular Evaluation of Results

Primary cutaneous T-cell lymphoma: Two rare presentations

Cutaneous T-Cell Lymphoma (CTCL) is a subset of non-Hodgkin's T-cell lymphomas which presents with malignant lymphocytic infiltration of the skin. The disease spectrum is characterized by clonal proliferation of helper T-cells of the CD4 phenotype in the skin. Mycosis Fungoides (MF), the commonest variant of CTCL, is characterized clinically by an indolent clinical course with subsequent evolution of patches, plaques andtumours and histologically by the infiltration of the epidermis by medium-sized to large atypical T-cells with cerebriform nuclei [1]. Although not very rare worldwide, it is commonest among Africans and relatively uncommon among Asians. Hypopigmented MF is a rare variant of patch stage MF in the dark skinned. Folliculotropic MF is an uncommon variant characterized by folliculotropic T-cell infiltrates with or without mucinous degeneration of the hair follicles.

Somatostatin receptor scintigraphy in primary cutaneous T‐ and B‐cell lymphomas

Monitoring and repeated staging is of substantial importance in many patients with primary cutaneous T-cell lymphomas (CTCL). For primary cutaneous B-cell lymphomas (CBCL), extensive initial staging is the mainstay for correct diagnosis. To evaluate the value of somatostatin receptor scintigraphy using the radiolabeled somatostatin analog (111)In-pentetreotide in comparison to conventional imaging methods for the staging of patients with primary CTCL and primary CBCL. Twenty-two patients (15 patients with histologically verified CTCL and 7 patients with histologically verified CBCL) were included. Stage of disease was established by physical examination, laboratory screening, skin inspection, palpation of superficial lymph nodes, sonography and computed tomography (CT) in patients with advanced clinical stage. Focally elevated tracer uptake of (111)In-pentetreotide was compared to common imaging modalities, physical aspect and digital photographs of the respective skin lesions. Of the 15 patients with CTCL, only 4 (27%) showed positive scintigraphic results, but not in all sites of lymphomatous involvement. None of the five patients with mycosis fungoides in stage I, nor any of the four patients with Sézary syndrome, had a positive (111)In- pentetreotide scan. Of the seven patients with CBCL three positive scintigraphic results (43%) could be obtained: in two patients with a follicular center lymphoma and one patient with a diffuse large B-cell lymphoma - leg type, but again not in all apparent sites of lymphoma. Based on our results, we do not recommend the use of somatostatin receptor scintigraphy for routine staging of patients with CTCL and CBCL. As our series includes only 22 patients, and the number of patients with rarer variants of CTCL was rather small, it might be too premature to abandon SST-R in the staging of patients with cutaneous lymphomas.

T-plastin (PLS3 ) gene expression differentiates Sézary syndrome from mycosis fungoides and inflammatory skin diseases and can serve as a biomarker to monitor disease progression

Background Cutaneous T-cell lymphoma (CTCL) is a group of lymphoproliferative disorders that includes mycosis fungoides (MF) and Sezary syndrome (SS). T-Plastin (PLS3) is an actin-bundling protein that has been found to be highly expressed in Sezary cells but not in normal PBMCs. Here, we describe the value of using PLS3 as a sensitive molecular marker for differentiating stages of MF from SS, and for monitoring development of SS from MF.

Diagnosis of mycosis fungoides with different algorithmic approaches

Algorithmic scoring approaches for evaluating early cases of mycosis fungoides (MF) provide a degree of diagnostic standardization. At the UWMC, biopsies from clinically concerning cases for MF are individually reviewed by a panel of pathologists and an average score is assigned to each biopsy reflecting the degree of suspicion for a diagnosis of MF; however, such an approach may not be practical outside of an academic center. 78 cases characterized in our institution, with the diagnosis confirmed by clinicopathologic correlation/clinical follow-up were evaluated with two different algorithms, based entirely on histologic evaluation (Guitart algorithm) and partial implementation of the ISCL algorithm evaluating histology, immunohistochemistry and T-cell clonality. A receiver operating characteristic curve comparing the results of the two approaches in early MF cases showed no statistical difference between the areas under the two curves. Increased stages of MF showed variable loss of T-cell antigens by immunohistochemistry and higher rates of detectable clonality. We could not document a statistically significant advantage of adding ancillary immunohistochemical and molecular testing to careful histologic evaluation in the workup of suspected cases of early MF. A systemic approach to histologic diagnosis by a single pathologist correlated favorably to the MF panel diagnosis.

Different Applications of Monochromatic Excimer Light in Skin Diseases

Ultraviolet radiation has been used for curative purposes in dermatologic conditions, especially in the last 30 years. We analyzed the efficacy of monochromatic excimer light in psoriasis, palmoplantar pustulosis, vitiligo, mycosis fungoides and alopecia areata, and to examine potential new indications. Two hundred seventy-nine patients with common and persistent skin diseases were enrolled in an open prospective study: 152 patients with stable and localized plaque psoriasis, 47 with palmoplantar psoriasis, 7 with palmoplantar pustulosis, 32 with vitiligo, 11 with prurigo nodularis, 9 with mycosis fungoides stage Ia, 8 with alopecia, 5 with localized scleroderma, 5 with genital lichen sclerosus, and 3 with granuloma annulare. The 308 nm excimer light was used at a power density of 48 mW/cm(2). An average of 12 sessions (range, 6-18), one session per week, was performed and yielded a total dose range of 4-12.5 J/cm(2). Clinical response was assessed using photos, biopsies, and specific clinical scores. Patients were monitorized for 6 and 12 months for psoriasis, 12 months for mycosis fungoides, and 4 months for the remaining conditions. We observed complete remission in more than 50% of patients with plaque psoriasis and palmoplantar dermatoses, respectively, complete remission in all patients affected by mycosis fungoides, excellent repigmentation in one third of vitiligo patients, hair regrowth in three patients with alopecia areata, an overall improvement in prurigo nodularis, a partial remission in patients affected by localized scleroderma, and a complete remission in most of the patients with genital lichen sclerosus and granuloma annulare. Our study confirms the use of monochromatic excimer light as a valid choice for the treatment of psoriasis, vitiligo, and mycosis fungoides; we also observed and report for the first time that monochromatic excimer light produces a therapeutic response in prurigo nodularis, localized scleroderma, genital lichen sclerosus, and granuloma annulare.

Evaluation of the role of human herpes virus 6 and 8 in parapsoriasis

The aetiology of mycosis fungoides and parapsoriasis (which may be considered as an early stage of mycosis fungoides) remains debated. Previous recent studies have suspected the involvement of viral agents and particularly human herpes viruses (HHV).The aim of the present study was to screen for the presence of HHV-6 and HHV-8 genome in parapsoriasis samples. Fifty paraffin-embedded samples from skin biopsies of parapsoriasis were retrospectively collected from archival files in our Dermatology department. Total DNA was extracted from samples using the phenol-chloroform method and the presence of viral genomes was screened using real-time PCR. Forty nine out of the fifty tissue samples of parapsoriasis were interpretable, they were all found negative for HHV-6 and HHV-8. This study does not confirm the suspected role of HHV-6 or -8 in parapsoriasis. HHV-8 has been the most studied virus in parapsoriasis and more widely in cutaneous lymphoproliferative diseases and our results are in agreement with most of the studies which found none or few HHV-8 in more advanced stages of cutaneous lymphoproliferative diseases. Concerning HHV-6, our study is the first one investigating the presence of this virus in lesional tissue samples of patients with parapsoriasis. In conclusion, parapsoriasis does not seem to be associated with either HHV-6 or HHV-8.

The conundrum of parapsoriasis versus patch stage of mycosis fungoides

Terminological confusion with benign dermatosis, such as parapsoriasis en plaques, makes it difficult to diagnose mycosis fungoides in the early patch stage. Early diagnosis of mycosis fungoides (MF) is important for deciding on type of therapy, prognosis and for further follow-up. However, until recently, there has been no consensus on criteria that would help in diagnosing the disease early. Some believe that large plaque parapsoriasis (LPP) should be classified with early patch stage of MF and should be treated aggressively. However, there is no firm clinical or laboratory criteria to predict which LPP will progress to MF and we can only discuss about statistical probability. Moreover, long-term outcome analysis of even patch stage of MF is similar to that of control population. We therefore believe that LPP should be considered as a separate entity at least to prevent the patient from being given a frightening diagnosis. We also feel that patients need not be treated with aggressive therapy for LPP and will need only a close follow-up. This article emphasizes the criteria for diagnosing early MF and has highlighted the importance of considering LPP as a distinct benign entity.

Psoralen plus ultraviolet A ± interferon-α treatment resistance in mycosis fungoides: the role of tumour microenvironment, nuclear transcription factor-κB and T-cell receptor pathways

Interferon (IFN)-alpha is widely used in the treatment of mycosis fungoides (MF) and when used in combination with photochemotherapy (psoralen plus ultraviolet A, PUVA) both improved response and duration of complete remission have been reported. However, in spite of encouraging results of the initial studies, currently there is no information available on specific prognostic factors enabling prediction of patients' resistance to PUVA +/- IFN-alpha treatment. To identify factors responsible for resistance to PUVA +/- IFN-alpha treatment in MF patients. The gene expression profiling of pretreatment samples from 29 patients diagnosed as IA, IB or IIA stage of MF enrolled in a randomized PUVA vs. PUVA + IFN-alpha clinical trial was analysed using cDNA microarrays. A Cox model (SAM) and gene set enrichment analysis (GSEA) were used for identification of genes and biologically significant pathways related to resistance to treatment. Genes involved in NF-kappaB signalling, T-cell receptor (TCR) signalling, cytokine signalling and proliferation were differentially expressed between responders and nonresponders. Interestingly, expression of markers representative of those pathways was found not only in the tumoral cells, but also in specific subpopulations of macrophages, dendritic cells and other non-neoplastic cell types constituting the tumour microenvironment, likely involved in the promotion of survival and proliferation of cutaneous T-cell lymphoma. Gene expression changes in both the tumour and the tumour microenvironment are an important determinant of treatment outcome in early-stage MF patients. Some proinflammatory factors such as NF-kappaB, inflammatory cytokines and their receptors in addition to TCR-associated molecules could be promising targets for MF treatment.

Treatment of Early Stages of Mycosis Fungoides with Narrowband Ultraviolet B

Background: Narrowband ultraviolet B (UVB) phototherapy is increasingly used in mycosis fungoides (MF). Objective: We report on the results obtained in a prospective series of early MF patients receiving this therapeutic regimen. Methods: In total, 22 patients were treated. Therapeutic results were evaluated on clinical, histological and molecular levels. Patients were then submitted to a clinical follow-up. Results: The cumulative number of treatments ranged from 22 to 48 (mean: 29). A complete clinical remission (CCR) was obtained in 18/22 patients, and a partial clinical remission in 4 cases. Complete or partial histological responses were achieved in 9/15 (all in CCR) and 4/15 patients, respectively. The molecular response was evaluated in 12 patients, and a disappearance of the dominant T cell clone in the skin was obtained in only 3 cases. After 4–48 months of follow-up (mean 20.1 months), 7/18 patients in CCR (39%) relapsed. Conclusion: Narrowband UVB phototherapy is a well-tolerated treatment of early-stage MF, and its efficiency is maximal in very early stages (Ia). Even though clinical results seem very similar to PUVA through indirect and tentative comparisons with historical series, relapses tend to occur earlier than with PUVA, especially when an incomplete histological or molecular response was achieved.