Cutaneous T-cell lymphomas: modern data of pathogenesis, clinics and therapy

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are characterized by skin infiltration with malignant monoclonal T lymphocytes. More common in adults aged 55 to 60 years, the annual incidence is about 0.5 per 100 000 people. Mycosis fungoides, Sézary syndrome and CD30+ lymphoproliferative diseases are the main subtypes of CTCL. To date, CTCL have a complex concept of etiopathogenesis, diagnosis, therapy and prognosis. The article presented summary data on these issues.

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An overview of cutaneous T cell lymphomas

F1000Research ◽

10.12688/f1000research.8829.1 ◽

2016 ◽

Vol 5 ◽

pp. 1882 ◽

Cited By ~ 26

Author(s):

Nooshin Bagherani ◽

Bruce R. Smoller

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Mycosis Fungoides ◽

Annual Incidence ◽

Heterogeneous Group ◽

Not Otherwise Specified ◽

T Cell Lymphomas ◽

Hodgkin's Lymphomas ◽

Diagnosis Therapy ◽

Peripheral T Cell Lymphomas

Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are characterized by a cutaneous infiltration of malignant monoclonal T lymphocytes. They typically afflict adults with a median age of 55 to 60 years, and the annual incidence is about 0.5 per 100,000. Mycosis fungoides, Sézary syndrome, and primary cutaneous peripheral T cell lymphomas not otherwise specified are the most important subtypes of CTCL. CTCL is a complicated concept in terms of etiopathogenesis, diagnosis, therapy, and prognosis. Herein, we summarize advances which have been achieved in these fields.

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The expression of CD26 and CD40 ligand is mutually exclusive in human T- cell non-Hodgkin's lymphomas/leukemias

Blood ◽

10.1182/blood.v86.12.4617.bloodjournal86124617 ◽

1995 ◽

Vol 86 (12) ◽

pp. 4617-4626 ◽

Cited By ~ 59

Author(s):

A Carbone ◽

A Gloghini ◽

V Zagonel ◽

D Aldinucci ◽

V Gattei ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

T Lymphocytes ◽

Mycosis Fungoides ◽

Cell Lines ◽

Critical Role ◽

Cd40 Ligand ◽

T Cell Lymphomas ◽

Human T Cell ◽

Hodgkin's Lymphomas

CD26 and CD40 ligand (CD40L) are surface molecules on human activated T lymphocytes that play a critical role in the regulation of lymphopoiesis. Both molecules are expressed on a restricted fraction of human T-cell non-Hodgkin's lymphomas (NHL)/leukemias; however, little is known about their functional and/or clinical significance in these disorders. In this study, the pattern of expression of CD40L was compared with that of the CD26 molecule. A series of 67 human T-cell NHL/leukemias and a panel of leukemia/lymphoma T-cell lines were evaluated by immunohistochemistry, flow cytometry, and RNA studies. The overall frequency of CD26+ and CD40L+ samples was rather similar (25/67 [37%] v 18/67 [27%]). However, the majority of CD26-expressing cases clustered in the lymphoblastic lymphomas (LBL)/T-acute lymphoblastic leukemias (ALL; 12/23) and CD30+ anaplastic large-cell (ALC) lymphomas (5/8), whereas CD40L+ lymphomas included a large fraction of mycosis fungoides (11/21 [52%]). CD26 and CD40L coexpression was found only in 2 myocosis fungoides cases and 1 small lymphocytic lymphoma. Thus, the expression of the two antigens was mutually exclusive in almost all T- cell lymphomas/leukemias. Accordingly, lymphoma cell lines expressed either one of the molecules or the relative amounts of CD26 and CD40L were inversely proportional. In contrast, reactive T lymphocytes from patients with non-neoplastic T-cell expansions and in vitro activated CD3+ or CD4+ normal T cells were found to coexpress CD40L and CD26. Results of a multivariate analysis showed that the expression of CD26 in T-cell LBL/ALL patients was associated to a worse outcome in terms of survival, as compared with patients with CD26- tumors (P < or = .0001). Based on our results, it can be concluded that, (1) as opposed to activated or reactive normal T cells, the expression of CD26 and of CD40L is mutually exclusive in human T-cell lymphomas/leukemias; (2) expression of CD26 is restricted to aggressive pathologic entities, such as T-cell LBL/ALL and T-cell CD30+ ALC lymphomas, whereas CD40L is expressed on slow progressing diseases such as mycosis fungoides; and (3) within the T-cell LBL/ALL group of tumors, CD26 may identify a subset of poor prognosis patients.

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Modern concepts of the mycosis fungoides pathogenesis

Oncohematology ◽

10.17650/1818-8346-2018-13-3-39-46 ◽

2018 ◽

Vol 13 (3) ◽

pp. 39-46

Author(s):

A. A. Vorontsova ◽

A. E. Karamova ◽

L. F. Znamenskaya

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Mycosis Fungoides ◽

Cell Lymphoma ◽

Epigenetic Mechanisms ◽

Cutaneous T Cell Lymphoma ◽

Cellular Composition ◽

Review Of The Literature ◽

Lymphoproliferative Diseases

Mycosis fungoides – the most common form of cutaneous T-cell lymphoma. The pathogenesis of this disease is complex and remains unclear. The article contains a review of the literature devoted to the main mechanisms of T-lymphocytes malignant proliferation, known to date. Data on dysregulation of immune, genetic and epigenetic mechanisms, as well as the role of microenvironment cells in the proliferation of T lymphocytes, are given. Immunophenotypic characteristics and cellular composition of the infiltrate in patients with mycosis fungoides, are described depending on the stage of the disease. Prospective directions in studying molecular-biological predictors of malignant lymphoproliferative diseases development are highlighted.

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Expression and activity of IL-17 in cutaneous T-cell lymphomas(mycosis fungoides and sezary syndrome)

International Journal of Cancer ◽

10.1002/ijc.20373 ◽

2004 ◽

Vol 112 (1) ◽

pp. 113-120 ◽

Cited By ~ 71

Author(s):

Arnaud Cirée ◽

Laurence Michel ◽

Sophie Camilleri-Bröet ◽

Francette Jean Louis ◽

Michèle Oster ◽

...

Keyword(s):

T Cell ◽

Mycosis Fungoides ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

T Cell Lymphomas ◽

Expression And Activity

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Non–Mycosis Fungoides Cutaneous T-Cell Lymphomas

American Journal of Clinical Pathology ◽

10.1309/ajcp83aoqtmlojtm ◽

2013 ◽

Vol 139 (4) ◽

pp. 491-514 ◽

Cited By ~ 48

Author(s):

Leticia Quintanilla-Martinez ◽

Patty M. Jansen ◽

Marsha C. Kinney ◽

Steven H. Swerdlow ◽

Rein Willemze

Keyword(s):

T Cell ◽

Mycosis Fungoides ◽

T Cell Lymphomas

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Staging and Treatment of the Cutaneous T Cell Lymphomas (Mycosis Fungoides and the Sézary Syndrome) at the National Cancer Institute (USA)

Lymphoproliferative Diseases of the Skin ◽

10.1007/978-3-642-68363-3_35 ◽

1982 ◽

pp. 270-282 ◽

Cited By ~ 1

Author(s):

P. A. Brunn ◽

A. B. Fishman ◽

E. Glatstein

Keyword(s):

T Cell ◽

Mycosis Fungoides ◽

National Cancer Institute ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

T Cell Lymphomas

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HOXC4, HOXC5, and HOXC6 Expression in Non-Hodgkin's Lymphoma: Preferential Expression of the HOXC5 Gene in Primary Cutaneous Anaplastic T-Cell and Oro-Gastrointestinal Tract Mucosa-Associated B-Cell Lymphomas

Blood ◽

10.1182/blood.v90.10.4116 ◽

1997 ◽

Vol 90 (10) ◽

pp. 4116-4125 ◽

Cited By ~ 13

Author(s):

Janet J. Bijl ◽

Johan W. van Oostveen ◽

Jan M.M. Walboomers ◽

Anja Horstman ◽

Adriaan J.C. van den Brule ◽

...

Keyword(s):

Gene Expression ◽

T Cell ◽

B Cell ◽

Expression Pattern ◽

Gene Expression Pattern ◽

Lymphoid Cells ◽

B Cell Lymphomas ◽

Preferential Expression ◽

T Cell Lymphomas ◽

Hodgkin's Lymphomas

Abstract Most of the 39 members of the homeobox (HOX) gene family are believed to control blood cell development. HOXC4 and HOXC6 gene expression levels increase with differentiation of lymphoid cells. In contrast, HOXC5 is not expressed in the lymphoid lineage, but was found in lymphoid cell lines, representing the neoplastic equivalents of various differentiation stages of T and B lymphocytes. In the present study, we investigated the HOXC4, HOXC5, and HOXC6 gene expression pattern in 89 non-Hodgkin's lymphomas (NHLs) of different histologic subtypes and originating from different sites. Using RNA in situ hybridization and semiquantitative reverse transcription-polymerase chain reaction, we found expression of HOXC4 in 83 of 88 and HOXC6 in 77 of 88 NHLs and leukemias investigated. In contrast, HOXC5 expression was found in only 26 of 87 NHLs and appeared to be preferentially expressed by two specific subsets of lymphomas, ie, primary cutaneous anaplastic T-cell lymphomas (9 of 9) and extranodal marginal zone B-cell lymphomas (maltomas; 7 of 9). These results indicate that, in contrast to HOXC4 and HOXC6, HOXC5 shows a type- and site-restricted expression pattern in both T- and B-cell NHLs.

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Granzyme B-expressing peripheral T-cell lymphomas: neoplastic equivalents of activated cytotoxic T cells with preference for mucosa- associated lymphoid tissue localization

Blood ◽

10.1182/blood.v84.11.3785.bloodjournal84113785 ◽

1994 ◽

Vol 84 (11) ◽

pp. 3785-3791 ◽

Cited By ~ 80

Author(s):

PC de Bruin ◽

JA Kummer ◽

P van der Valk ◽

P van Heerde ◽

PM Kluin ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Tumor Cells ◽

Lymphoid Tissue ◽

Cytotoxic T Cells ◽

Granzyme B ◽

Clinical Behavior ◽

T Cell Lymphomas ◽

Hodgkin's Lymphomas ◽

Peripheral T Cell Lymphomas

T-cell non-Hodgkin's lymphomas can be considered the neoplastic equivalents of immunologically functional, site-restricted T lymphocytes. Little is known about the occurrence and clinical behavior of T-cell lymphomas that are the neoplastic equivalents of different functional T-cell subsets. Here, we investigated the prevalence, preferential site, immunophenotype, and clinical behavior of the neoplastic equivalents of activated cytotoxic T cells (CTLs) in a group of 140 nodal and extranodal T-cell lymphomas. Activated CTLs were shown immunohistochemically with a monoclonal antibody against granzyme B, a major constituent of the cytotoxic granules of activated T cells. Granzyme B-positive T-cell lymphomas were mainly found in mucosa- associated lymphoid tissue (MALT; nose, 63% of the cases; gastrointestinal tract, 46%; and lung, 33%). Granzyme B-positive cases with primary localization in MALT were more often associated with angioinvasion (P = .005), necrosis (P = .002), and histologic characteristics of celiac disease in adjacent mucosa not involved with lymphoma. Eosinophilia was more often observed in granzyme B-negative cases (P = .03). Most cases belonged to the pleomorphic medium- and large-cell group of the Kiel classification. CD30 expression was more often found in granzyme B-positive lymphomas of MALT (P = .04), whereas CD56 expression was exclusively found in nasal granzyme B-positive lymphomas. Immunophenotypically, most of the cases should be considered as neoplastic equivalents of activated CTLs based on the presence of T- cell markers on tumor cells. In two cases of nasal lymphoma, tumor cells probably were the neoplastic counterparts of natural killer cells. The prognosis of the granzyme B-positive gastrointestinal T-cell lymphomas was poor but did not differ from granzyme B-negative gastrointestinal T-cell lymphomas. This indicates that, in peripheral T- cell lymphomas, site of origin is more important as a prognostic parameter than derivation of activated CTLs.

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