Management of cutaneous T cell lymphoma: new and emerging targets and treatment options

Cutaneous T cell lymphomas (CTCL) clinically and biologically represent a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the most common subtypes. Over the last decade, new immunological and molecular pathways have been identified that not only influence CTCL phenotype and growth, but also provide targets for therapies and prognostication. This review will focus on recent advances in the development of therapeutic agents, including bortezomib, the histone deacetylase inhibitors (vorinostat and romidepsin), and pralatrexate in CTCL

Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas.

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αβ T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αβ/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases

Correction. "The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms" Leukemia. 2022 Jul;36(7):1720-1748

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms

A Rare Case of Cutaneous Plasmacytosis in a Korean Male

Cutaneous and systemic plasmacytosis are reactive disease processes that occur in middle-aged Japanese and Chinese men. Systemic plasmacytosis, defined by plasmacytic infiltration of two organ systems, might rarely progress to lymphoma. Cutaneous plasmacytosis, however, is chronic and benign and is characterized by the development of multiple plasma cell-rich infiltrates in the skin. We present a case of cutaneous plasmacytosis in a 46-year-old Korean male. The patient demonstrated classic features of the disease entity, including disseminated red-brown plaques, differentiated plasmacytoid infiltrates on biopsy, hypergammaglobulinemia, and the absence of systemic disease

Authors reply to the letter to editor with regard to the article titled “Sézary syndrome and mycosis fungoides: An overview, including the role of immunophenotyping”

We have read with interest the letter to editor by M. Roelens et al. in response to our article on Sézary syndrome (SS) and mycosis fungoides (MF) and the role of immunophenotyping for diagnosis. We appreciate their comments on the potential utility of CD158k (KIR3DL2) for the diagnosis of SS and MF, which certainly complement the data on SS immunophenotyping we report. The authors cite their published work about the role of CD158k for the precise identification of Sézary cells (SCs). Based on their observations, they recommend introducing KIR3DL2/CD158k as a positive marker for the accurate identification of SCs using flow cytometry (Roelens, de Masson, Ram-Wolff, Bagot, & Moins-Teisserenc, 2020). We agree that CD158k is a promising marker, particularly because it would allow “positive” selection of SCs (instead of focusing on downregulated molecules, such as CD7 and CD26) while being negative in normal residual CD4+ T cells, as stated by Roelens et al. However, it should be noted that unequivocal expression of CD158k on SCs from most SS cases has been reported only by this group (though consistently over a long time), using an antibody obtained from a therapeutic antibody manufacturer and not commercially available as a flow-cytometry reagent. Unfortunately, other authors could not reproduce these results using the same clones and fluorochrome (Boonk et al., 2016, and personal observations), possibly due to issues with the reagent, such as lot-to-lot variability and stability for a product that most likely does not currently meet the quality standards to be sold as an analyte specific reagent (ASR) or even a research use only (RUO) antibody. Therefore, to definitively establish the precise utility of CD158k for SS (and MF) immunophenotyping in a standardized way, the exact antibody products used by M. Roelens et al (i.e., clone AZ158k or more recently clone 13E4, both conjugated to phycoerythrin, provided by Innate Pharma, Marseille, France) should be used and offered as a standard quality flow cytometry product (i.e., guaranteeing lot-to-lot stability, effective and stable dye-to-antibody ratio, etc.) available for purchase. This would allow different groups of experts to reach reproducible and comparable results, before recommending the systematic inclusion of CD158k in consensus/standardized panels for SS/MF immunophenotyping

Sézary syndrome and mycosis fungoides: An overview, including the role of immunophenotyping

This review discusses the definition and major categories of cutaneous T‐cell lymphoma, Sézary syndrome and mycosis fungoides, and the role of immunophenotyping in their diagnosis. The following key points are raised: (a) Sézary syndrome and mycosis fungoides cells most often have a characteristic CD3+ CD4+ CD7− and/or CD26− immunophenotype. (b) This immunophenotype is not specific, but can assist in the distinction from non‐neoplastic T cells and other subtypes of mature T‐cell neoplasm. (c) However, small subsets of normal and reactive T‐cells can have an overlapping immunophenotype, and can be distinguished by evaluating for additional changes in antigen expression.Peer reviewe