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Alejandro A Gru, Jinah Kim, Melissa Pulitzer, Joan Guitart, Maxime Battistella, Gary S Wood, Lorenzo Cerroni, Werner Kempf, Rein Willemze, Joya Pawade, Christiane Querfeld, Andras Schaffer, Laura Pincus, Michael Tetzlaff, Madeleine Duvic, Julia Scarisbrick, Pierluigi Porcu, Aaron R Mangold, David J Dicaudio, Michi Shinohara, Eric K Hong, Bethany Horton, Youn H Kim
This pathology PILOT study aims to define the role and feasibility of centralized pathology review in a cohort of 75 patients from different centers in the United States and Europe using digital slide scanning. The pathologic material from 75 patients who had been diagnosed with mycosis fungoides/Sézary syndrome and were clinically staged as IIb or above was retrieved from 11 participating centers. Each pathology reviewer was provided with the pathologic diagnosis (by the referring pathologist), and the following list of histopathologic criteria (presence or absence) from the initial report: epidermotropism, folliculotropism (FT), large cell transformation, syringotropism, and granulomas...
March 14, 2018: American Journal of Surgical Pathology
Taku Fujimura, Kayo Tanita, Yota Sato, Yumi Kambayashi, Sadanori Furudate, Akira Tsukada, Akira Hashimoto, Setsuya Aiba
Mogamulizumab induces cytotoxicity against CCR4+ lymphoma cells by antibody-dependent cell-mediated cytotoxicity in advanced cutaneous T-cell lymphoma patients. Since the efficacy of mogamulizumab in mycosis fungoides (28.6%) is lower than that in Sézary syndrome (47.1%), reagents that enhance the antitumor immune response induced by mogamulizumab are needed to further optimize its use for the treatment of erythrodermic mycosis fungoides. In this report, we present a case of erythrodermic mycosis fungoides successfully treated with mogamulizumab followed by etoposide monotherapy...
January 2018: Case Reports in Oncology
Fernando Gallardo, Joan Bertran, Erika López-Arribillaga, Jéssica González, Silvia Menéndez, Ignacio Sánchez, Luis Colomo, Mar Iglesias, Marta Garrido, Luis Francisco Santamaría-Babí, Ferran Torres, Ramon M Pujol, Anna Bigas, Lluís Espinosa
Cutaneous T-cell lymphomas (CTCLs) represent different subtypes of lymphoproliferative disorders with no curative therapies for the advanced forms of the disease (namely mycosis fungoides and the leukemic variant, Sézary syndrome). Molecular events leading to CTCL progression are heterogeneous, however recent DNA and RNA sequencing studies highlighted the importance of NF-κB and β-catenin pathways. We here show that the kinase TAK1, known as essential in B-cell lymphoma, is constitutively activated in CTCL cells, but tempered by the MYPT1/PP1 phosphatase complex...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Julia J Scarisbrick, Emmilia Hodak, Martine Bagot, Rene Stranzenbach, Rudolf Stadler, Pablo L Ortiz-Romero, Evangelia Papadavid, Felicity Evison, Robert Knobler, Pietro Quaglino, Maarten H Vermeer
Our current mycosis fungoides (MF) and Sézary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sézary counts but results from our EORTC survey confirm these are rarely performed in patch/plaque/tumour MF, and there is a trend towards using flow cytometry to measure blood-class. Accurately assigning blood-class effects overall stage and the 'global response' used to measure treatment responses in MF/SS and hence impacts management...
February 21, 2018: European Journal of Cancer
Mahsa Khanlari, Juan Carlos Ramos, Sandra Patricia Sanchez, Jeong Hee Cho-Vega, Alexandra Amador, German Campuzano-Zuluaga, Francisco Vega, Jennifer R Chapman
Adult T-cell leukemia/lymphoma, an aggressive T-cell neoplasm, is causally linked to human T-cell lymphotropic virus type 1 and based on this association has a distinct geographic distribution. In our United States-based practice, whose population is enriched for immigrants from human T-cell lymphotropic virus type 1 endemic areas, we have identified that a subset of adult T-cell leukemia/lymphoma, in the absence of human T-cell lymphotropic virus type 1 identification, are indistinguishable from other more common T-cell neoplasms...
February 15, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Marina Passos Torrealba, Kelly Cristina Manfrere, Denis R Miyashiro, Josenilson F Lima, Luana de M Oliveira, Nátalli Z Pereira, Jade Cury-Martins, Juliana Pereira, Alberto J S Duarte, Maria N Sato, José A Sanches
Sézary syndrome (SS) is a leukemic variant of cutaneous T cell lymphoma (CTCL), and the neoplastic CD4+ T cells of SS patients undergo intense clonal proliferation. Although Sézary cells have been studied extensively, studies on adaptive immunity regarding CD8+T cells are scarce. This study aimed to investigate activation marker expression in CD8+ T cells according to the differentiation stages and IL-7/IL7Rα axis responses of patients with SS. Moreover, this study aimed to verify the soluble forms of CD38, sCD127 and IL-7 in serum...
January 9, 2018: Oncotarget
Massimiliano Bergallo, Paolo Fava, Ilaria Galliano, Mauro Novelli, Paola Montanari, Valentina Daprà, Marco Rassu, Pietro Quaglino, Maria Teresa Fierro
Mycosis fungoides (MF) is characterized by longstanding, scaly patch lesions preferentially involving the buttocks and body areas infrequently exposed to sunlight and by a slow evolution over years from patches to plaques and eventually tumors or erythroderma. Lymph node and visceral involvement, as well as large cell transformation, frequently occur in the late stages of the disease [1]. Sézary syndrome (SS) is an erythrodermic cutaneous T-cell lymphoma (CTCL) with leukemic involvement, an aggressive clinical behavior and poor prognosis [2]...
February 6, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Yang Li, Jin Wang, Minghang Yu, Yang Wang, Huilai Zhang, Jie Yin, Zexing Li, Ting Li, Han Yan, Fajin Li, Xi Wang
SNF5, is a core member of the SWI/SNF chromatin remodeling complex. It's deficiency leads to multiple types of aggressive cancer. Sézary syndrome, a leukemic variant of cutaneous T-cell lymphoma, is characterized by its resistance to apoptosis. Although the cause of apoptosis resistance is still poorly understood, recent evidence has revealed the importance of SATB1 in the apoptosis resistance of Sézary syndrome. In this study, we show that SNF5 is an upstream regulator of SATB1 in several conditions and that both are deficient in Sézary cells...
January 16, 2018: Leukemia & Lymphoma
T Numata, T Nagatani, K Shirai, T Maeda, K Mae, M Nakasu, M Saito, T Usuda, R Tsuboi, Y Okubo
A 70-year-old man presented to our clinic with a 10-year history of recurrent pruritic erythema and plaques on his trunk and limbs. Based on the pathological findings and monoclonal rearrangement of the T-cell receptor (TCR)-Cβ1 gene, mycosis fungoides (T2N0M0B0 stage IB) was diagnosed. Despite combination therapy including histone deacetylase inhibitor (vorinostat), the symptoms slowly evolved into Sézary syndrome (SS; T4N1M0B2) over 4 years, with dense infiltrates due to atypical lymphocytes expressing CCR4 developing in the entire dermis...
April 2018: Clinical and Experimental Dermatology
Sayaka Otobe, Makoto Sugaya, Rina Nakajima, Tomonori Oka, Naomi Takahashi, Miyoko Kabasawa, Tomomitsu Miyagaki, Yoshihide Asano, Shinichi Sato
Interleukin (IL)-36γ is expressed by keratinocytes and functions as a key initiator of inflammation in the skin. IL-36γ expression is enhanced by tumor necrosis factor-α and IL-17A, having a strong association with psoriasis. In this study, we examined the role of IL-36γ in atopic dermatitis (AD) and mycosis fungoides (MF)/Sézary syndrome (SS). Serum levels of IL-36γ in AD patients and MF/SS patients were elevated compared with those of healthy controls. Importantly, serum IL-36γ levels in AD patients positively correlated with Eczema Area and Severity Index and those of MF/SS patients positively correlated with serum soluble IL-2 receptor levels...
January 3, 2018: Journal of Dermatology
Jenna Janiga, Jonathan Kentley, Chadi Nabhan, Farah Abdulla
Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common cutaneous T-cell lymphomas (CTCLs). Both lack curative options, and advanced-stage carries a poor prognosis. Whilst there are a number of treatments available, achieving and maintaining a durable remission remains challenging. We review current systemic treatment options as monotherapy for advanced-stage MF (IIB-IV), appraising their mechanism of action, analyzing their efficacy, and describing toxicities. Individually, reported overall response rates (ORR) vary widely in the literature and duration of responses are typically short, ranging from 7...
January 8, 2018: Leukemia & Lymphoma
Maria Estela Martinez-Escala, Alba L Posligua, Heather Wickless, Audrey Rutherford, Kimberly A Sable, Belen Rubio-Gonzalez, Xiaolong A Zhou, Jason B Kaplan, Barbara Pro, Jaehyuk Choi, Christiane Querfeld, Steven T Rosen, Joan Guitart
BACKGROUND: Cutaneous lymphoma (CL) diagnosed after anti-tumor necrosis factor (TNF)α therapy has been reported in the literature, yet a clear link between both events remains elusive. OBJECTIVE: To review our experience with CL diagnosed during or after the use of anti-TNFα therapies. METHODS: This is a multicenter retrospective study and a literature review. RESULTS: Twenty-two cases, including 20 cutaneous T-cell lymphomas (CTCL) and 2 cutaneous B-cell lymphomas (CBCL), were identified...
January 4, 2018: Journal of the American Academy of Dermatology
R Nakajima, T Miyagaki, T Oka, N Takahashi, M Hirakawa, H Suga, A Yoshizaki, H Fujita, Y Asano, M Sugaya, S Sato
BACKGROUND: Interleukin (IL)-25 is a member of the IL-17 family which can promote and augment T-helper type (Th) 2 responses. The expression of IL-25 and its cognate receptor, IL-25 receptor (IL-25R), is upregulated and correlated with disease activity in Th2-associated diseases. OBJECTIVE: To examine the expression and function of IL-25 in cutaneous T-cell lymphoma (CTCL). METHODS: Expression and localization of IL-25 in lesional skin was investigated using immunohistochemistry...
December 13, 2017: British Journal of Dermatology
Elena Netchiporouk, Jennifer Gantchev, Matthew Tsang, Philippe Thibault, Andrew K Watters, John-Douglas Matthew Hughes, Feras M Ghazawi, Anders Woetmann, Niels Ødum, Denis Sasseville, Ivan V Litvinov
HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV-1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells...
November 10, 2017: Oncotarget
David Lemchak, Swati Banerjee, Shaunak S Digambar, Brian L Hood, Thomas P Conrads, Jaroslaw Jedrych, Larisa Geskin, Oleg E Akilov
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...
February 2018: Experimental Dermatology
Larisa J Geskin, Oleg E Akilov, Soonyou Kwon, Michael Schowalter, Simon Watkins, Theresa L Whiteside, Lisa H Butterfield, Louis D Falo
Tumor progression is associated with progressive immunosuppression mediated in part by T regulatory cell(s) (Treg) and/or myeloid-derived suppressor cell(s) (MDSC). Development of strategies to reduce populations of immune cells with suppressive function in cancer patients may enable the induction or recovery of immunity against tumor cells, which may limit or reverse disease progression. With a goal of developing Treg and MDSC neutralizing strategies to treat mycosis fungoides (MF) and Sézary syndrome (SzS), we determined the association between disease stage and suppressor cell populations in patients with MF/SzS, including those responding to therapy...
March 2018: Cancer Immunology, Immunotherapy: CII
Kelly C G ManfrereC, Marina P Torrealba, Denis R Miyashiro, Nátalli Z Pereira, Fabio S Y Yoshikawa, Luana de M Oliveira, Jade Cury-Martins, Alberto J S Duarte, José A Sanches, Maria N Sato
Sézary syndrome (SS), an aggressive and leukemic form of cutaneous T-cell lymphoma, usually results in shortened survival. Improving innate immunity in SS by targeting natural killer (NK) cells with Toll-like receptor (TLR) agonists could be an interesting modulatory strategy. We evaluated the NK cell populations in SS patients assessing activating and inhibitory receptors expression and profiled the differential expression of TLR signaling pathway genes in unstimulated NK cells and after TLR7/8 stimulation...
November 3, 2017: Oncotarget
Ryo Yokota, Yuki Kaminaga, Tetsuya J Kobayashi
Inter-sample comparisons of T-cell receptor (TCR) repertoires are crucial for gaining a better understanding of the immunological states determined by different collections of T cells from different donor sites, cell types, and genetic and pathological backgrounds. For quantitative comparison, most previous studies utilized conventional methods in ecology, which focus on TCR sequences that overlap between pairwise samples. Some recent studies attempted another approach that is categorized into Poisson abundance models using the abundance distribution of observed TCR sequences...
2017: Frontiers in Immunology
Martina Maurelli, Gianpaolo Tessari, Chiara Colato, Donatella Schena, Giampiero Girolomoni
BACKGROUND: Primary cutaneous lymphomas (PCLs) are a rare group of extranodal non-Hodgkin lymphomas, and epidemiological data in Mediterranean countries are scarce. OBJECTIVE: To investigate the incidence and characteristics of PCL in a single tertiary referral centre in Italy. MATERIALS & METHODS: A total of 141 PCL patients, seen over a 10-year follow-up period, were investigated. RESULTS: Incidence rate of PCL was 0...
November 24, 2017: European Journal of Dermatology: EJD
Mariah Giberson, Ahmed Mourad, Robert Gniadecki
BACKGROUND: Folliculotropic mycosis fungoides (FMF) is a distinct subtype of mycosis fungoides (MF) with unique clinicopathological features. The medical literature suggests that FMF has a more aggressive course and worse survival than classic MF. Previous studies do not use standardized treatment, and no studies have reported an association between treatment response and overall survival (OS). OBJECTIVE: To compare OS for MF, FMF, and Sézary syndrome (SS) patients...
November 24, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
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