Sézary syndrome—clinical and histopathologic features, differential diagnosis, and treatment

Spicknall, Kerith E.

doi:10.12788/j.sder.2018.005

Cited by 22 publications

(25 citation statements)

References 56 publications

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“…Thus, there is an urgent need for novel effective and well-tolerated modalities. 2,3 New insight into CTCL pathophysiology has led to a better understanding of disease mechanisms followed by identification of novel therapeutic targets. [4][5][6] In particular, it has been shown that the malignant behavior of CTCL cells is rather caused by cell-death resistance than by hyperproliferation.…”

Section: Introductionmentioning

confidence: 99%

Combined inhibition of Bcl-2 and NFκB synergistically induces cell death in cutaneous T-cell lymphoma

Froehlich

Müller‐Decker²,

Braun

et al. 2019

Blood

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Therapeutic options for cutaneous T-cell lymphoma (CTCL) are limited and curative treatment regimens are not available. Thus, new targeted and well-tolerated therapeutic approaches are urgently needed. In this respect, we have recently shown that dimethyl fumerate (DMF) inhibits NF-κB acting as a survival factor in CTCL. Similarly, inhibition of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) has been shown to induce cell death in CTCL especially when combined with histone deacetylase inhibitors. Therefore, we hypothesized that inhibition of Bcl-2 should potentiate NF-κB inhibition in a novel combination treatment of CTCL. We show that, in vitro, the Bcl-2 inhibitors ABT-199 and ABT-263 induced specific cell death in primary CD4+ cells from CTCL patients as well as in the CTCL cell line SeAx, but not in T cells of healthy donors nor in the CTCL cell line HH, which lacks Bcl-2. Combined treatment with ABT-199 and DMF caused synergistic cell death specifically in CTCL cells engaging 2 independent signaling pathways. To verify these findings in vivo, we performed combined ABT-199 and DMF treatment in a xenograft mouse model for CTCL. The combined treatment effectively reduced tumor growth and increased overall survival via synergistic induction of CTCL cell death and suppression of tumor cell proliferation. Essentially, the combination treatment was superior to ABT-199 monotherapy with respect to both efficacy and tolerability. To sum up, our data provide proof of principle for the therapeutic potential of combining Bcl-2 and NF-κB inhibitors in treating CTCL. Next, this potential should be explored further in a clinical study.

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Section: Introductionmentioning

confidence: 99%

Combined inhibition of Bcl-2 and NFκB synergistically induces cell death in cutaneous T-cell lymphoma

Froehlich

Müller‐Decker²,

Braun

et al. 2019

Blood

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“…Early-stage MF has an excellent prognosis, and 90% of patients do not progress to the tumour stage [ 2 , 3 ]. The incidence of SS, an aggressive and leukemic variant of CTCL, is 0.1–0.3 cases per million persons, accounting for only 2.5% of all CTCLs [ 4 ]. MF affects African Americans more often than Caucasians, while the incidence rate of SS is higher in Caucasians than in African Americans.…”

Section: Introductionmentioning

confidence: 99%

“…MF affects African Americans more often than Caucasians, while the incidence rate of SS is higher in Caucasians than in African Americans. However, the 2:1 male-to-female ratio is the same in both lymphomas [ 3 , 4 ]. Both SS and MF were shown to be closely related; the clinical features of the late-stage MF might resemble those of SS.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Heterogeneity of Cutaneous T-Cell Lymphomas Revealed Using RNA-Seq Technologies

Rassek

Iżykowska

2020

Cancers

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Cutaneous T-cell lymphomas (CTCLs) represent a large, heterogeneous group of non-Hodgkin lymphomas that primarily affect the skin. Among multiple CTCL variants, the most prevalent types are mycosis fungoides (MF) and Sézary syndrome (SS). In the past decade, the molecular genetics of CTCL have been the target of intense study, increasing the knowledge of CTCL genomic alterations, discovering novel biomarkers, and potential targets for patient-specific therapy. However, the detailed pathogenesis of CTCL development still needs to be discovered. This review aims to summarize the novel insights into molecular heterogeneity of malignant cells using high-throughput technologies, such as RNA sequencing and single-cell RNA sequencing, which might be useful to identify tumour-specific molecular signatures and, therefore, offer guidance for therapy, diagnosis, and prognosis of CTCL.

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“…Generalized erythroderma of progressive onset is associated with Sézary syndrome and MF with secondary peripheral blood involvement. 87 However, generalized erythroderma is more frequently associated with other common benign dermatoses; these include pityriasis rubra pilaris, psoriasis, eczem-atous eruptions, papuloerythroderma of Ofuji, and numerous other causes. Erythroderma is not unique to MF; as previously stated, there is marked clinical and histopathologic overlap between MF and cases of ATLL.…”

mentioning

confidence: 99%

A Systematic Approach to the Cutaneous Lymphoid Infiltrates: A Clinical, Morphologic, and Immunophenotypic Evaluation

Gru

McHargue

Salavaggione

2019

Archives of Pathology &Amp; Laboratory Medicine

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Context.— The evaluation of cutaneous lymphoid infiltrates, both neoplastic and inflammatory, occurs very frequently in routine dermatopathologic examination and consultation practices. The “tough” cutaneous lymphoid infiltrate is feared by many pathologists; skin biopsies are relatively small, whereas diagnostic possibilities are relatively broad. It is true that cutaneous lymphomas can be difficult to diagnose and that in many circumstances multiple biopsies are required to establish a correct diagnostic interpretation. As a reminder, one should understand that low-grade cutaneous lymphomas are indolent disorders that usually linger for decades and that therapy does not result in disease cure. It is also important to remember that in most circumstances, those patients will die from another process that is completely unrelated to a diagnosis of skin lymphoma (even in the absence of specific therapy). Objective.— To use a clinicopathologic, immunophenotypic, and molecular approach in the evaluation of common lymphocytic infiltrates. Data Sources.— An in-depth analysis of updated literature in the field of cutaneous lymphomas was done, with particular emphasis on updated terminology from the most recent World Health Organization classification of skin and hematologic tumors. Conclusions.— A diagnosis of cutaneous lymphoid infiltrates can be adequately approached using a systematic scheme following the proposed ABCDE system. Overall, cutaneous T- and B-cell lymphomas are rare and “reactive” infiltrates are more common. Evaluation of lymphoid proliferations should start with a good sense of knowledge of the clinical presentation of the lesions, the clinical differential considerations, and a conscientious and appropriate use of immunohistochemistry and molecular tools.

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Sézary syndrome—clinical and histopathologic features, differential diagnosis, and treatment

Cited by 22 publications

References 56 publications

Combined inhibition of Bcl-2 and NFκB synergistically induces cell death in cutaneous T-cell lymphoma

Combined inhibition of Bcl-2 and NFκB synergistically induces cell death in cutaneous T-cell lymphoma

Single-Cell Heterogeneity of Cutaneous T-Cell Lymphomas Revealed Using RNA-Seq Technologies

A Systematic Approach to the Cutaneous Lymphoid Infiltrates: A Clinical, Morphologic, and Immunophenotypic Evaluation

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