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Mycosis fungoides is the most common primary cutaneous T-cell lymphoma, characterized by skin-homing CD4+ T cells derivation, indolent course, and low-grade of malignancy. Mycosis fungoides’s classic type typically onsets with cutaneous erythematous patches, plaque, and tumor. In WHO-EORTC classification, folliculotropic mycosis fungoides, pagetoid reticulosis, and granulomatous slack skin are recognized as distinct variants of mycosis fungoides, because of their clinical and histological features, behavior, and /or prognosis. Mycosis fungoides often shows diagnostic difficulties, due to its absence of specific features and lesional polymorphism. A patient’s treatment requires staging. In about 10% of cases, mycosis fungoides can progress to lymph nodes and internal organs. Prognosis is poor at advanced stage and management needs a multidisciplinary team approach. Advanced stage disease including tumors, erythroderma, and nodal, visceral, or blood involvement needs skin directed therapy associated with systemic drugs. Skin directed therapy includes steroids, nitrogen mustard, bexarotene gel, phototherapy UVB, and photochemiotherapy, i.e., total skin electron radiotherapy. Systemic therapies include retinoids, bexarotene, interferon, histone deacetylase inhibitors, photopheresis, targeted immunotherapy, and cytotoxic chemotherapy. Complexity of mycosis fungoides associated with long-term chronic evolution and multiple therapy based on disease stage need a multidisciplinary team approach to be treated.

Mycosis fungoides (MF) is a disease almost impossible to cure. In the context of heavily pretreated patients, the anti-programmed cell death protein 1 (anti-PD-1) pembrolizumab is a valid therapeutic option. The alteration of the PD-1-PD ligand 1 (PD-L1) axis is often present in MF, and this aspect explains the feasibility of this therapy. We report the case of a 60-year-old woman diagnosed with MF in 2003, Olsen stage IA (T1M0NXBO). Since the moment of the diagnosis, she received 10 lines of therapy, with a short duration of response after each one of them. In April 2020, our patient started pembrolizumab 2 mg/kg every 3 weeks, and she achieved a partial response after the 4th cycle, consistent with the modified severity assessment tool (mSWAT) 1, which she is still maintaining after 10 cycles. No grade ≥3 adverse events were recorded. We conclude that pembrolizumab can induce extremely rapid responses in MF, with very low toxicity.

Objectives Several studies suggested that CD30 expression is a favorable prognostic marker in transformed mycosis fungoides (tMF). However, evidence in this field is still unclear. This systematic review and meta-analysis aimed to evaluate the prognostic significance of CD30 in tMF. Methods Electronic databases were searched from their inception to June 2020 for all studies assessing the prognostic value of CD30 in tMF. Pooled hazard ratio (HR) for death was calculated; a P value less than .05 was considered significant. Inconsistency index (I2) was used to assess statistical heterogeneity among studies. Results Seven studies with 323 patients were included. CD30 expression in tMF was significantly associated with a decreased hazard of death both on univariate (HR, 0.459; 95% confidence interval [CI], 0.319-0.660; P < .001) and multivariate analysis (HR, 0.503; 95% CI, 0.345-0.734; P < .001), and the statistical heterogeneity among studies was null in all analyses (I2 = 0%). Conclusions tMF cases with CD30 expression in large cells have a hazard of death two times lower than CD30-negative cases.

Primary cutaneous T-cell lymphomas (PCTCL) are the most common types of cutaneous lymphomas, with Mycosis fungoides as the most frequent subtype. Besides early stages which usually have a good prognosis, advanced stages remain a great therapeutic challenge with low survival rates. To date, none of the currently available therapeutic options have significantly improved the outcomes of advanced cutaneous lymphomas. Recent studies have demonstrated that immune-checkpoint molecules, such as PD-1 and CTLA-4, play part in the proliferation pathways of neoplastic T-cells, as well as in other tumors. Hence, the potential role of immune-checkpoint-inhibitors in treating cutaneous lymphomas has been investigated in the last years. Herein, we outline the current knowledge regarding the role of immune-checkpoint molecules in PCTCL, their signaling pathways, microenvironment and therapeutic inhibition rationale. Moreover, we review the published data on immunotherapies in PCTCL and summarize the currently ongoing clinical trials in this field.

Patients with mycosis fungoides (MF) and Sezary syndrome (SS) often require multiple lines of systemic therapy. In the phase 3 MAVORIC study (NCT01728805), mogamulizumab demonstrated superiority to vorinostat in median progression-free survival (PFS) and confirmed overall response rate (ORR) in patients with MF/SS. This post hoc analysis examined the effects of number and type of prior systemic therapies on mogamulizumab response. MAVORIC patients randomized to mogamulizumab (1.0 mg/kg intravenously weekly) or vorinostat (400 mg orally daily) were grouped by number of prior therapies and immunomodulatory activity of immediate prior systemic therapy while also considering time elapsed since treatment. ORR, PFS, and duration of response (DOR) did not vary with number of prior therapies. ORR and DOR remained consistent regardless of immediate prior therapy type. Additionally, immunomodulatory activity of the last prior therapy and time from prior treatment generally did not affect the ORR or PFS observed in response to mogamulizumab.

INTRODUCTION: Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, can lead to disfiguring lesions, debilitating pruritus and frequent skin infections. This study assessed response to brentuximab vedotin in patients with MF in the phase III ALCANZA study. METHODS: Baseline CD30 levels and large-cell transformation (LCT) status were centrally reviewed in patients with previously-treated CD30-positive MF using ≥2 skin biopsies obtained at screening; eligible patients required ≥1 biopsy with ≥10% CD30 expression. Patients were categorised as CD30min

RC is a consultant for Kyowa Kirin and served on an advisory board for Helsinn. JJS is a consultant for Kyowa Kirin, Takeda, Recordat, 4SC, Innate Pharma and Helsinn. She received a 1-year educational grant from Kyowa Kirin for work on quality of life in CTCL. She also has membership on an entity’s Board of Directors or advisory committees for Kyowa Kirin, Takeda, 4SC, Innate Pharma, Miragen and Helsinn. PLZ has received honoraria from MSD, Celltrion, Gilead, Janssen-Cilag, BMS and TG Therapeutics. He is also a consultant for MSD, EUSA Pharma, Sanofi and Verastem. He also has membership on an entity’s Board of Directors or advisory committees for MSD, Eusa Pharma, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, Immune Design, Celgene, Portola, Roche, Kyowa Kirin, TG Therapeutics, and Verastem. He has also been on a Speakers Bureau for MSD, EUSA Pharma, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Immune Design, Celgene, Portola, Roche, Kyowa Kirin and Verastem. JPN has received honoraria from Pharmaceutical Industries, TEVA, Novartis AG, Biogen GmbH, Almirall Hermal AG, Actelion Pharmaceuticals, UCB Pharma, LaRoche Posay, Takeda Pharmaceuticals and Kyowa Kirin. He is also a consultant for Novartis AG, Biogen GmbH, Almirall Hermal AG, Actelion Pharmaceuticals, Innate Pharma, Kyowa Kirin and Takeda Pharmaceuticals. He has also received grants and personal fees from Pharmaceutical Industries outside of the submitted work. LS is a consultant for Dren Bio and served on an advisory board for Kyowa Kirin, Kymera Therapeutics and EUSA Pharma. LP-B has been an advisory board for Epizyme, Morphosys, Helsinn, Verastem and Actelion. She is also a consultant for Acrotech. PQ has received honoraria from Actelion, Innate Pharma, Takeda, Kyowa Kirin, Helsinn and Therakos. He also been on an advisory board for Actelion, Innate Pharma, Takeda, Kyowa Kirin, Helsinn and Therakos. LI has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Janssen-Cilag, Kyowa Kirin, LEO Pharma, MSD, Novartis, Pfizer, Sun Pharma and UCB. RD is a consultant for Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym and Second Genome. AM is an investigator for Menlo, Soligenix, Pfizer, Elorac and miRagen. She has also received honoraria from Kyowa Kirin. She also has a membership on an entity’s Board of Directors or advisory committees for Helsinn. FF has received honoraria from Seagen, Mallinckrodt and Kyowa Kirin. She is also a consultant for Miragen. She had also served on a Data Safety Monitoring Board for Celgene. She was also the President of the US Cutaneous Lymphoma Consortium. TI is an employee of Kyowa Kirin, Inc. J-PR is an employee of Kyowa Kirin, Inc. MCM is an employee of Kyowa Kirin, Inc.

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. In the majority of patients, the disease has a slow evolution and a protracted course; however, a subset of patients shows poor oncologic outcomes. Unfortunately, there are no reliable prognostic markers for MF, and the currently available treatments are only effective in a minority of patients. This study aimed to evaluate the expression and clinical significance of PARP-1 and CAF-1/p60 in MF. Sixty-four MF representatives of the different stages of disease were assessed by immunohistochemistry for PARP-1 and CAF-1/p60. The association of PARP-1 and CAF-1/p60 with the MF stage and outcome was assessed by using Fisher’s exact test and Kaplan-Meier survival analysis with the Log-rank test; a p value II (p = 0.034) but not with the risk of death (p = 0.237). CAF-1/p60 was overexpressed in 26.8% of MF and was significantly associated with decreased overall survival (p p = 1). A significant association was found between PARP-1 overexpression and CAF-1/p60 overexpression (p = 0.0025). Simultaneous overexpression of PARP-1 and CAF-1/p60 was significantly associated with decreased overall survival (p χ2 = 14.916 vs 21.729, respectively). In MF, PARP-1 is overexpressed in advanced stages, while CAF-1/p60 is overexpressed in the cases with shorter overall survival, appearing as a significant prognostic marker. A role for PARP-1 inhibitors and anti-CAF-1/p60 targeted therapy may be reasonably hypothesized in MF.

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Dermoscopy and trichoscopy are non-invasive methods used as auxiliary tools in diagnostics of different dermatoses. To date, no systematic review concerning the utility of dermoscopy and trichoscopy in the diagnostics of primary cutaneous lymphomas has been published. The aim of this study was to summarize the current state of knowledge on this topic based on systematic search of PubMed database and related references published before 8th of August 2020. Besides dermoscopic features, type of dermoscope, polarization mode, magnification, number of cases and histopathological correlation were analysed. A total of 34 records were included into the final analysis, evaluating 141 patients diagnosed with primary cutaneous T-cell lymphomas and 70 patients with primary cutaneous B-cell lymphomas. Most of the analysed records evaluated dermoscopic features (n = 206); trichoscopy was analysed in only 5 cases. Structures most commonly observed in classical mycosis fungoides (n = 108) were fine short linear vessels/linear vessels, spermatozoa-like vessels and orange-yellow patchy areas. In folliculotropic mycosis fungoides (n = 12), most frequently observed were comedonal lesions/comedo openings/central keratotic plugs and white halo around hair follicles/perifollicular accentuation. Primary cutaneous marginal zone B-cell lymphoma (n = 42) and primary cutaneous follicle centre lymphoma (n = 20) most commonly presented with salmon-coloured background and fine short/linear irregular/serpentine vessels. For other PCL, with less than 10 cases reported in the analysed records, details have been provided in the article. Most observations analysed in this systematic review rely on findings from case reports/case series (with the level of evidence V) and lack a control group. A few studies provided information concerning technical aspects of dermoscopic/trichoscopic examination. The role of dermoscopy/trichoscopy in diagnostics of cutaneous lymphomas requires further studies, especially in entities where dermoscopic features have been described in only single or a few cases. However, it seems that this practical, accessory tool in future may provide additional clues during clinical assessment.

Background: Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. It has been hypothesized that the interaction between the immune system, cutaneous cells, and neoplastic elements may play a role in MF/SS pathogenesis and progression. Methods: This paper aims to revise in a narrative way our current knowledge of the microenvironment’s role in MF/SS. Results and Conclusions: Literature data support a possible implication of microenvironment cells in MF/SS pathogenesis and progression, opening up new therapeutic avenues.

Background Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. Aims The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. Materials & methods E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. Results Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). Conclusions Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.

In this paper, we present a review of critical concepts, and produce recommendations on management issues in cutaneous T-cell lymphomas (CTCLs) of adults. A panel of nine experts was selected for their expertise in research and clinical practice of CTCLs. During an initial meeting, the areas of major concern in the management of CTCLs were selected by generating and rank-ordering clinical key questions using the criterion of clinical relevance, through group discussion. Recommendations were achieved by multiple-step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. The panel produced recommendations on how to facilitate the clinical suspicion of CTCL; indication of cutaneous biopsy; optimal histological diagnosis, immunohistochemistry and genetic markers; and staging pathway and up-to-date therapeutics (with particular focus on new treatments). The critical concept of integration of the different medical expertise in the management of the patients with CTCL was thoroughly examined. These recommendations are intended for use not only by expert centers but above all by "not experienced" dermatologists and hematologists as well as general practitioners.

Background Photodynamic therapy (PDT) is a well-known and effective treatment for non-melanoma skin-cancer. Numerous studies have also shown its effectiveness in mycosis fungoides. The aim of the study was to analyse MF patients treated with PDT at the Dermatology Unit of Bologna University. Methods We retrospectively analysed MF patients treated with PDT over the last ten years. Each PDT protocol consisted of the appliance for 3 h under an occlusive film dressing on each lesion of a one-mm-thick layer of 16% methyl aminolaevulinate (MAL) 160 mg/g cream (Metvix ® , Galderma, Paris, France). The cream was then removed and the skin was exposed to 630 nm red light from a diode lamp (Aktilite ® , Galderma Benelux, Rotterdam, the Netherlands), with a total radiation dose of 37 J/cm2 for 9 mins. A protocol of one session every month was scheduled. The treated lesions were clinically examined, before each treatment. Results Four cases, three male and one female, had been treated with PDT. Two patch lesions on the plantar area, one leg and the pubic area were treated. The number of PDT sessions ranged from 4 to 9. Two complete remissions and two partial remissions were observed. A low-to-mild burning sensation was reported during the treatment, and persisted over the next day; no further side effects were observed. Conclusions Our series shows that PDT can be considered an effective second-line treatment in patients characterised by a disease located in difficult-to-treat anatomical areas such as the feet and the pubic area.

Nous rapportons le résumé de la PEAUse « Hématologie et peau » organisée en février 2018 par le service de dermatologie des Cliniques universitaires Saint-Luc et consacrée aux lymphomes cutanés. Le professeur E. Van Den Neste nous a présenté les lymphomes cutanés les plus fréquents, leurs traitements suivis de quelques cas cliniques issus du service d’hématologie. Le Professeur A. Camboni nous a parlé plus précisément des aspects histologiques. [Hematology & dermatology] We here briefly summarize the “PEAUse dermatologique” meeting organized in February 2018 by the Department of Dermatology of the Saint-Luc University Clinics and dedicated to cutaneous lymphomas. Professor E. Van Den Neste presented the most frequent cutaneous lymphomas, their treatments, as well as several clinical cases from the Department of Hematology. Professor A. Camboni focused on the histological aspects.

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Primary cutaneous T-cell lymphomas (CTCLs), such as mycosis fungoides and Sézary syndrome, are a rare group of non-Hodgkin lymphomas, usually treated using a multimodal approach. Unfortunately, many patients go on to develop relapsed/refractory disease. Systemic treatment for relapsed/refractory CTCL has historically relied on chemotherapies and interferons, and while active, responses are often short-lived. Three drugs are now approved in the US to treat relapsed/refractory CTCL including the oral retinoid, bexarotene, and histone deacetylase inhibitors, romidepsin and vorinostat. Although response rates are typically

Accentuation of the follicle is an easily recognized dermoscopic sign that can be found in patients who do not exhibit clinical signs of folliculotropic MF. It represents a very early sign that allows us to choose a proper biopsy site, predict histology even at an early stage of MF, select more complex treatment and, finally, to predict the group of MF patients who will have a poor response to the standard treatment

SummaryBackground Mycosis fungoides (MF) is the major subtype of cutaneous T-cell lymphomas (CTCL). It usually has a prolonged indolent clinical course with a minority of cases acquiring a more aggressive biological profile and resistance to conventional therapies, partially attributed to the persistent activation of Nuclear Factor-kappa B (NF-κB) pathway. In the last decade, several papers suggested an important role for the FK506-binding protein 51 (FKBP51), an immunophilin initially cloned in lymphocytes, in the control of NF-κB pathway in different types of human malignancies. Objectives We aimed to investigate the possible value of FKBP51 expression as a new reliable marker of outcome in MF patients. Methods We assessed by immunohistochemistry (IHC) FKBP51 expression in 44 patients with MF, representative of different stages of the disease. Immunohistochemical results were subsequently confirmed at mRNA level with quantitative PCR (qPCR) in a subset of enrolled patients. In addition, IHC and qPCR served to study the expression of some NF-κB target genes, including the tumour necrosis factor receptor-associated factor 2 (TRAF2). Results Our results show that FKBP51 was expressed in all evaluated cases, with the highest level of expression characterizing MFs with the worst prognosis. Moreover, a significant correlation subsisted between FKBP51 and TRAF2 IHC expression scores. Conclusions we hypothesize a role for FKBP51 as a prognostic marker for MF and suggest an involvement of this immunophilin in deregulated NF-κB pathway of this CTCL. This article is protected by copyright. All rights reserved.

Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

BACKGROUND: Erythroderma is a serious medical condition characterized by inflamed red skin involving over 90% of the body. It can be the common presentation of different diseases, therefore clinical diagnosis can be problematic. Controversial data are reported regarding the diagnostic value of histological examination in erythroderma subjects. METHODS: A retrospective study was performed, investigating histological skin specimens of patients with a clinical diagnosis of erythroderma admitted to the Department of Dermatology of State Pediatric Medical University, Saint Petersburg, from 2001 to 2014. Histopathology examination was performed in each case by a pathologist with a special interest in the skin disease who was blind to any clinical information as well as to final diagnosis. RESULTS: Blinded histopathology examination alone was able to give the correct diagnosis in 61% (n = 50/82) of cases when compared to final diagnosis. A diagnosis of psoriasis was made in 23.2% (n = 19/82) of subjects, spongiotic dermatitis/eczema in 20.7% (n = 17/82), mycosis fungoides in 8.5% (n = 7/82), and drug eruption in 8.5%; histological diagnosis was inconclusive or not matching the final diagnosis when available in the remaining 39.1% of cases (n = 32/82). CONCLUSION: Erythroderma remains a condition difficult to study and treat. We showed that a correct judgment about its cause can be based on objective histopathological criteria in up to 60% of cases. More studies are needed to try to find out further histological and/or immunohistochemical markers that could help the clinician with the erythroderma etiology diagnostic process.

Mycosis fungoides (MF) is characterized by a switch from indolent behaviour in the early stages to a worse clinical outcome in the advanced ones. Recently, various studies have investigated the role the microenvironment might play in such a switch. We have analysed the distribution of Langerhans cells, plasmacytoid dendritic cells and myeloid-derived suppressor cells in 46 MF cases in various stages, aiming to assess whether changes occur from early to advanced stage. We have investigated the number of langerin, CD303 and arginase-1 positive cells and their distribution at high power. Data were analysed using t test for continuous variables, χ 2 tests or Fisher’s exact test for categorical variables, as well as analysis of covariance. In comparing stages IA/B to IIB, we observed a significant decrease in Langerhans cells (p value 0.03) and a significant increase in CD303 and arginase-1 positive cells (p value

Background Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. We previously reported that the prognosis of MF patients is not only related on clinical variables but it is also associated with peculiar HLA alleles. Until today, the association of HLA ligands for KIR with the prognosis of the disease has not yet been analysed. Objective We investigated the frequency of HLA ligands for killer cell Immunoglobulin-like receptors (KIRs) in MF patients, evaluating if the presence of particular HLA alleles that are ligands for KIR may have prognostic value. Methods The study includes 46 Caucasian MF patients that, between 1993 and 1997, underwent HLA genomic typing. All patients were diagnosed and followed up from 1977 to 2012 (mean follow-up of 11 years). Results MF patients have been divided into two groups (long survivors and dead patients). We noticed that the HLA-Bw6/Bw6 specificity increased among the group of seven dead patients compared to the group of 39 long survivors (71.4% vs. 41.0%, P = ns, OR = 3.59), while in the long survivors group the HLA- Bw4/Bw4 specificity increased when compared to dead patients (23.0% vs. 0%, P = ns). Moreover, we observed that six of the seven dead patients had HLA-DQB1*05; the phenotypic frequency of this HLA allele, in dead and long survivors patients, was 85.7% and 23.0% respectively (P = 0.004; OR = 20). Conclusion Our observations suggest that the presence of the HLA-DQB1*05 alleles characterizes the patients with the poorest prognosis in MF. In addition, absence of the KIR-ligand epitope HLA-B Bw4 showed a trend of being more prominent in MF patients with the poorest prognosis.

Background: Primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma (CD4+ PCSM-TCL) is a rare lymphoproliferative disorder with a favorable prognosis. Distinguishing it from other cutaneous lymphomas is often a challenge. Methods: We retrospectively collected CD4+PCSM-TCL cases from two centers (MD Anderson Cancer Center, USA and University of Milan, Italy) and evaluated their clinicopathological features. Array-comparative genomic hybridization (aCGH) analysis was performed on 11 cases. Results: A total of 62 patients were identified. Single lesions were the most common clinical presentations (79%). Five patients (8%) showed multiple MF-like plaques. All patients' disease had an indolent course. The infiltrate was nodular and diffuse, multinodular or superficial but in all cases, it was characterized by small/medium pleomorphic CD4+/CD279(PD1+) lymphocytes grouped in clusters and ‘pseudorosettes’ around B-cells. aCGH analysis showed no significant genomic abnormalities. Single lesions were mainly treated with surgical excision (91%) and/or radiotherapy (95%) with low rate of relapse (12%). For multiple lesions, topical steroids, nitrogen mustard and phototherapy were mainly used but the rate of relapse was high (69%). Conclusions: CD4+PCSM-TCL is characterized by heterogeneous clinical presentations. The arrangement of atypical cells in clusters or pseudorosettes is a useful criterion for diagnosis. The absence of significant genomic alterations is in agreement with its indolent behavior.

BACKGROUND: Mycosis fungoides (MF) is an indolent primary cutaneous T-cell lymphoma. To the authors' knowledge, no data currently are available regarding the evolution over time of the risk of developing specific pathways of disease progression. METHODS: This retrospective study analyzed 1422 patients with MF who were diagnosed and followed from 1975 through 2010 in 27 Italian Study Group for Cutaneous Lymphoma centers. The primary objectives were to ascertain the time course, pathways, and hazards risk trends of cutaneous/extracutaneous disease progression; to evaluate whether different tumor-lymph node-metastasis-blood (TNMB) stages have different pathways of disease progression; and to analyze differences between tumor-stage and erythrodermic MF with regard to clinical onset, disease evolution, and prognosis. The secondary objective was to provide a further validation for the revised International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. RESULTS: The median follow-up was 14.5 years; stage progression occurred in 29.7% of patients and blood involvement was the most frequent extracutaneous site of disease progression. Patients with stage IA to stage IB disease demonstrated a steady low annual incidence of disease progression to tumor-stage (1%-2%); patients with stage IIA disease had a higher risk within the first years (up to 9.4%). Erythroderma evolved with a significantly higher frequency from patches/plaques (13.9%/28.2%) than tumors (P = .028 and P = .013, respectively). Hazards rates of extracutaneous involvement were low (< 1%). The T-score was found to be associated with extracutaneous involvement site, tumor-stage disease with lymph node/visceral lesions, and erythroderma with blood involvement. TNMB classification and stage progression resulted as independent prognostic variables being detected on multivariate analysis; the type of extracutaneous involvement was found to affect survival . CONCLUSIONS: The data from the current study support the need for a stage-tailored follow-up, suggest that the classification of tumor-stage disease at a stage below erythroderma could be modified, and offer a further validation for the revised TNMB classification. Cancer 2012. © 2012 American Cancer Society.

AIMS: Aggressive epidermotropic cutaneous CD8+ lymphoma is currently afforded provisional status in the WHO classification of lymphomas. An EORTC Workshop was convened to describe in detail the features of this putative neoplasm and evaluate its nosological status with respect to other cutaneous CD8+ lymphomas.METHODS & RESULTS: Sixty-one CD8+ cases were analysed at the workshop; clinical details, often with photographs, histological sections, immunohistochemical results, treatment and patient outcome were discussed & recorded. Eighteen cases had distinct features and conformed to the diagnosis of aggressive epidermotropic cutaneous CD8+ lymphoma. The patients typically present with widespread plaques and tumours, often ulcerated and haemorrhagic, and have striking pagetoid epidermotropism histologically. A CD8+ CD45RA+ CD45RO- CD2- CD5- CD56- phenotype, with 1 or more cytotoxic markers was found in 7/18 with a very similar phenotype in the remainder.. The tumours seldom involve lymph nodes but mucosae and central nervous system involvement are not uncommon. The prognosis is poor, with a median survival of 12 months. Examples of CD8+ mycosis fungoides, lymphomatoid papulosis and Woringer-Kolopp presented the typical features well documented in the CD4+ forms of those diseases.CONCLUSIONS: Aggressive Epidermotropic Cutaneous CD8+ Lymphoma is a distinct lymphoma that warrants inclusion as a distinct entity in future revisions of lymphoma classifications. This article is protected by copyright. All rights reserved.

Early stage mycosis fungoides (MF) is difficult to be clinically differentiated from chronic dermatitis (CD) in a high proportion of patients. Dermoscopy is a rapid, cheep, non-invasive and widely used method for the evaluation of skin tumours and, recently, of inflammatory skin diseases, as well.To describe the dermoscopic pattern of early stage MF and compare it with the dermoscopic features observed in CD.This was a retrospective study. Dermoscopic images of lesions that were clinically equivocal between MF and CD were evaluated for the presence of predefined morphologic criteria. Diagnosis had been histopathologically and immunohistochemically confirmed in all cases. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for predefined dermoscopic criteria in relation to the diagnosis of mycosis fungoides.A total of 67 dermoscopic images were selected for dermoscopic evaluation. Mycosis fungoides lesions exhibited a characteristic dermoscopic pattern consisting of fine short linear vessels (sensitivity 93.7%, specificity 97.1%) and orange-yellowish patchy areas (sensitivity 90.6%, specificity 99.7%). A characteristic vascular structure resembling spermatozoa was also found to be highly specific for the diagnosis of mycosis fungoides. CD was typified by a different dermoscopic pattern, usually consisting of dotted vessels.These observations provide a first indication that early stage MF exhibits a characteristic dermoscopic pattern which is different from CD. Prospective studies with long term follow-up are needed to determine the value of these dermoscopic criteria in the differentiation between the two entities in the daily routine.

Mycosis fungoides following pityriasis lichenoides: An exceptional event or a potential evolution

We present a case of interstitial mycosis fungoides showing pseudodovascular clefts with "free-floating'' collagen fibers surrounded by neoplastic T lymphocytes. Such a finding further expands the histopathologic spectrum of mycosis fungoides and could be taken into account in its differential diagnosis from granuloma annulare, inflammatory morphea, and interstitial granulomatous drug reaction.

Mycosis fungoides (MF) constitutes the most frequent cutaneous T-cell lymphoma. Sezary syndrome is considered by some authors to be an erythrodermic leukemic variant of MF, but is classified separately in the new WHO-EORT classification of cutaneous lymphomas. MF usually occurs in old adults with a 2:1 male to female ratio. Its prognosis is variable and strongly conditioned by the extent and type of skin involvement and presence of extracutaneous disease. Patients with stage IA-disease have an excellent prognosis with an overall long-term life expectancy that is similar to an age-, sex-, and race-matched control population. Almost all patients with stage IA MF will die from causes other than MF, with a median survival >33 years. Only 9% of these patients will progress to more extended disease. Patients with stage IB or IIA have a median survival greater than 11 years. These patients with T2 disease have a likelihood of disease progression of 24% and nearly 20% die of MF. Subgroups with stage IB or IIA have similar prognosis. Patients with cutaneous tumors or generalized erythroderma have a median survival of 3 and 4.5 years, respectively. The majority of these patients will die of MF. Extracutaneous dissemination is observed in less than 10% of patients with patch or plaque disease and in 30-40% of patients with tumors or generalized erythrodermatous involvement. Extracutaneous involvement is directly correlated to the extent of cutaneous disease. The most commonly involved organs are lung, spleen, liver, and gastrointestinal tract. Patients with extracutaneous disease at presentation involving either lymph nodes or viscera have a median survival of 33 years. Only 9% of these patients will progress to more extended disease. Patients with stage IB or IIA have a median survival greater than 11 years. These patients with T2 disease have a likelihood of disease progression of 24% and nearly 20% die of MF. Subgroups with stage IB or IIA have similar prognosis. Patients with cutaneous tumors or generalized erythroderma have a median survival of 3 and 4.5 years, respectively. The majority of these patients will die of MF. Extracutaneous dissemination is observed in less than 10% of patients with patch or plaque disease and in 30-40% of patients with tumors or generalized erythrodermatous involvement. Extracutaneous involvement is directly correlated to the extent of cutaneous disease. The most commonly involved organs are lung, spleen, liver, and gastrointestinal tract. Patients with extracutaneous disease at presentation involving either lymph nodes or viscera have a median survival of

The purpose of this report is to describe a further distinctive cause of crazy-paving pattern on thin-section computed tomography in a patient affected by pulmonary granulomatous mycosis fungoides. It was possible to reconcile the crazy-paving appearance on thin-section computed tomography scan with the histopathologic pattern termed acute fibrinous organizing pneumonia pattern.

Mycosis fungoides (MF) is the most frequently found cutaneous T-cell lymphoma with an unknown aetiology. Several aetiopathogenetic mechanisms have been postulated, including persistent viral or bacterial infections. We looked for evidence of Borrelia burgdorferi (Bb), the aetiologic agent of Lyme disease (LD), in a case study of MF patients from Northeastern Italy, an area with endemic LD. Polymerase chain reaction for the flagellin gene of Bb was used to study formalin-fixed paraffin-embedded lesional skin biopsies from 83 patients with MF and 83 sex- and age-matched healthy controls with homolocalised cutaneous nevi. Borrelia burgdorferi-specific sequence was detected in 15 out of 83 skin samples of patients with MF (18.1%), but in none out of 83 matched healthy controls (P

Lettera all'Editore- no abstract available

Given the poor prognosis of patients with advanced cutaneous T-cell lymphoma and the high transplant-related mortality associated with conventional allogeneic bone marrow transplantation, we performed nonmyeloablative transplantation of allogeneic stem cells (ASCT) from HLA-identical siblings in three patients with this disease. All patients achieved full donor engraftment, clearance of clonal T cells leading to durable complete remissions but experienced high incidence of infections, which proved fatal in one case. These results suggest that nonmyeloablative ASCT is a novel and potentially curative therapy for patients with advanced T-cell lymphomas who have a histocompatible sibling.

The Authors describe a case of a 69-year-old woman who presented by two years erythematous, markedly hyperkeratotic and pruritic plaques with sharp borders on the palms and soles. Were also presents in these plaques deep vesicopustolar lesions. The patient was evaluated by other dermatologists that diagnosticated allergic contact dermatitis: patch tests confirmed theirs diagnosis (positivity for nickel and other substances). Fungal culture was negative. The lesions were treated with daily topical applications of a corticosteroid treaitment having a partial resolution. In consequence of the interruption of the therapy, the dermatosis flared up again. The clinical features gave evidence for psoriasis. A biopsy specimen taken from the right palm showed marked parakeratosis, acanthosis and diffuse infiltrate in the papillary dermis. The dermal bandlike infiltrate was composed of lymphocites and cells with hyperchromatic irregurarly shaped nuclei (mycosis cells). Immunohistochemistry confirmed diagnosis of mycosis fungoides. Further examinations excluded visceral involvement. The patient was treated with daily topical applications of mechlorethamine (nitrogen mustard). Before establishing the diagnosis of mycosis fungoides palmoplantaris (MFPP) has been diagnosed as dermatophyte infection, contact dermatitis and palmoplantar psoriasis. In summary, MFPP is an expression of MF that sometime initially presents and mimics many common palmoplantar dermatoses. A biopsy is recommended in the evaluation of unresponsive, chronic palmoplantar lesions.