CD4/CD8 Double Negative Mycosis Fungoides With PD-1 (CD279) Expression—A Disease of Follicular Helper T-Cells?

Kempf, Werner; Kazakov, Dmitry V.; Cipolat, Claudio; Kutzner, Heinz; Roncador, Giovanna; Tomasini, Dario

doi:10.1097/dad.0b013e31825b26d1

Cited by 28 publications

(21 citation statements)

References 29 publications

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“…As opposed to AITL, these cases show a clinical presentation typical for MF, the infiltrate was epidermotropic (a feature not present in any case of AITL), and there was absence of CD10 and EBV. More recently some authors have described CD4 and CD8 negative cases of MF with T FH phenotype (a pattern also seen by the authors personal experience) 64,65 .…”

Section: Discussionsupporting

confidence: 71%

Extranodal Marginal Zone Lymphoma–like Presentations of Angioimmunoblastic T-Cell Lymphoma

Kaffenberger

Haverkos

Tyler

et al. 2015

The American Journal of Dermatopathology

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Angioimmunoblastic T-cell lymphoma (AITL) is the second most common type of peripheral T-cell lymphoma (PTCL) worldwide, and in some countries the most common form. Clinically, AITL usually presents with systemic symptoms, diffuse lymphadenopathy, hepatosplenomegaly and common laboratory abnormalities such as hypergammaglobulinemia. Skin rashes are seen in 50–80% of patients. AITL derives follicular T-helper cells (TFH), that express germinal center markes and produces hyperactivation of B-cell seen in AITL. Although the histologic features of AITL in the skin could be similar to pathologic findings present in lymph node biopsies, we present herein 2 cases of AITL with histologic and immunophenotypic features that were somewhat suggestive of extranodal marginal zone lymphoma (MALT).Caution is urged to exclude the possibility of a systemic T-cell lymphoma such as AITL in cutaneous and lymph node B-cell proliferations.

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Section: Discussionsupporting

confidence: 71%

Extranodal Marginal Zone Lymphoma–like Presentations of Angioimmunoblastic T-Cell Lymphoma

Kaffenberger

Haverkos

Tyler

et al. 2015

The American Journal of Dermatopathology

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“…Cutaneous proliferations of T cells may express markers of TFH cells. Accordingly, PD-1 is expressed by the tumor cells of patients with Sézary syndrome [73], primary cutaneous CD4+ small/medium T-cell lymphoma [74], and a rare type of CD4/CD8 double-negative mycosis fungoides [75]. Additionally, PD-L1 is overexpressed by anaplastic lymphoma kinase positive (ALK + ) anaplastic large cell lymphoma cells in a chimeric nucleophosmin/ALK-STAT3–dependent manner [76].…”

Section: Expression and Clinical Significance Of Pd-1 And Its Ligamentioning

confidence: 99%

Signaling pathway and dysregulation of PD1 and its ligands in lymphoid malignancies

Xia

Medeiros

Young

2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Tumor cells evade immune destruction, at least partially, by upregulating inhibitory signals to limit effector T cell activation. Programmed death 1 (PD-1) is one of the most critical co-inhibitory molecules limiting the T-cell antitumor response. PD-1 and its ligands, PD-L1 and PD-L2, are overexpressed by various types of tumors as well as reactive cells in the tumor microenvironment. A growing body of evidence has shown the clinical efficiency and minimal toxicity of PD-1 pathway inhibitors in patients with solid tumors, but the role of these inhibitors in lymphoid malignancies is much less well studied. In this review, we review the pathologic role of the PD-1 pathway in most common lymphoid malignancies and we organize the clinical data from clinical trials of PD-1 pathway inhibitors. Several anti–PD-1 regimens have shown encouraging therapeutic effects in patients with relapsed/refractory Hodgkin lymphoma, follicular lymphoma, and diffuse large B cell lymphoma. Additional progress is needed to foster an improved understanding of the role of anti–PD-1 therapy in reconstituting antitumor immunity in patients with lymphoid malignancies. Upcoming trials will explore the clinical efficiency of combining PD-1 pathway inhibitors and various agents with diverse mechanisms of action and create more therapeutic possibilities for afflicted patients.

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“…Different immunohistochemical variants of otherwise classical MF showing either a CD4−/CD8− (double negative) mature T-cell phenotype 9 or CD45RA expression with a high incidence of immunopathologic abnormalities have been reported. 10 Recently, Kempf et al 11 described a patient with a CD4/CD8 double negative variant of MF characterized by annular lesions confined to the left lower leg with the intraepidermal CD4/CD8 double negative clonal T-lymphocytes (CD2+, CD42, CD82, CD302, beta-F1+) expressing PD1-CD279 antigen, and negative for CXCL-13 and cytotoxic molecules (TIA-1, granzyme-B, perforin). Such cases have the same clinical behavior and prognosis as classic MF and are histopathologically characterized by a perivascular or band-like dermal lymphoid infiltrate with a moderate to marked epidermotropism of small-to medium-sized, highly indented and sometimes hyperchromatic convoluted lymphoid cells.…”

Section: Discussionmentioning

confidence: 98%

Pagetoid reticulosis tumor cells with double expression of TCRγδ and TCRαβ: an off‐target phenomenon or genuine expression?

2015

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Pagetoid reticulosis (PR) is a low-grade primary cutaneous T-cell lymphoma showing localized patches or plaques with an intrapeidermal proliferation of neoplastic T-cells with heterogeneous immunophenotype. We describe a 73-year-old woman with a 8-year history of gluteal lesions of PR, whom large blast cells were CD4/CD8 double negative T-cells with an activated cytotoxic profile. The case was investigated using a broad panel of monoclonal antibodies including TCRγM1, a new available antibody that recognizes the γ chain subunit of the T-cell receptor (TCR) in formalin-fixed paraffin-embedded tissue. Large blast cells were simultaneously positive for TCRαβ and TCRγδ with an activated cytotoxic phenotype. It is worldwide accepted the mutual exclusive expression of TCRαβ and TCRγδ but six different studies, dealing with TCRγδ expression in various types of extra-nodal lymphomas, reported cases whom tumor cells expressed simultaneously TCRαβ and TCRγδ. Our data and those of similar reports, suggest the possibility of existence of a subset of extra-nodal T-cell lymphomas showing simultaneous expression by tumor cells of TCRγδ and TCRαβ with an immunoprofile consistent with an origin from TCRγδ+ T lymphocytes. This unusual subset has preferential, but not exclusive, skin localization and variable epidermotropism.

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CD4/CD8 Double Negative Mycosis Fungoides With PD-1 (CD279) Expression—A Disease of Follicular Helper T-Cells?

Cited by 28 publications

References 29 publications

Extranodal Marginal Zone Lymphoma–like Presentations of Angioimmunoblastic T-Cell Lymphoma

Extranodal Marginal Zone Lymphoma–like Presentations of Angioimmunoblastic T-Cell Lymphoma

Signaling pathway and dysregulation of PD1 and its ligands in lymphoid malignancies

Pagetoid reticulosis tumor cells with double expression of TCRγδ and TCRαβ: an off‐target phenomenon or genuine expression?

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