Leu-8/CD7 antigen expression by CD3+ T cells: Comparative analysis of skin and blood in mycosis fungoides/Sézary syndrome relative to normal blood values

Thymidine phosphorylase may be overexpressed in both neoplastic cells and tumor stromal cells in a variety of malignancies. Our study explores thymidine phosphorylase expression in lymph nodes (LNs) from patients with mycosis fungoides (MF) or Sézary syndrome (SS). In MF/SS, the LNs may have a pathologic diagnosis of either dermatopathic lymphadenopathy (LN-DL) or involvement by MF/SS (LN-MF). We performed immunohistochemical staining on MF/SS lymph nodes using antibodies to thymidine phosphorylase, CD68, CD21, CD3, and CD4. In both LN-DL and benign nodes, thymidine phosphorylase staining was noted only in macrophages, dendritic cells, and endothelial cells. In LN-MF, thymidine phosphorylase expression was also noted in subsets of intermediate to large neoplastic T cells. Concurrent CD68, CD21, CD3, and CD4 staining supported the above observations. Similar results were noted in the skin and in LN-MF with large cell transformation. Other T-cell lymphomas were also examined (total 7 cases); only enteropathy-type T-cell lymphoma (1 case) showed TP positivity in neoplastic T lymphocytes. We demonstrated that thymidine phosphorylase staining is present in neoplastic T cells in mycosis fungoides. The exact mechanism needs further investigation.

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FoxP3-Positive T-Regulatory Cells in Lymph Nodes with Mycosis Fungoides and Sézary Syndrome

Lymphoma ◽

10.1155/2014/597908 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Rekha Bhat ◽

Bhavna Khandpur ◽

Eric C. Vonderheid ◽

J. Steve Hou

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Lymph Nodes ◽

Mycosis Fungoides ◽

Cox Proportional Hazards Model ◽

Cell Phenotype ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Malignant T Cells

Mycosis fungoides and Sézary syndrome are indolent cutaneous T-cell lymphomas, with skin-associated peripheral lymph nodes being the most frequent extracutaneous site of involvement. Acquisition of functional properties of regulatory T-cells by malignant T-cells in advanced disease may contribute to immunosuppression. Whereas previous studies examining FoxP3 protein expression in mycosis fungoides and Sézary syndrome have focused on skin specimens, little data are available on lymph nodes from patients with these conditions. In this study we examined FoxP3+ regulatory T-cells in lymph nodes from 26 patients with mycosis fungoides and Sézary syndrome and correlated the findings with clinical data, molecular assays for T-cell clonality, and flow cytometry. Except for one case of Sézary syndrome in which malignant T-cells expressed FoxP3 protein, a significantly lower number of FoxP3-expressing cells occurred in lymph nodes that were clearly involved with lymphoma as compared to uninvolved nodes. Cox proportional hazards model showed that lymph node rating and histological evidence of transformation, but not number of FoxP3+ cells, were factors significantly associated with adverse prognosis. We speculate that modulation of FoxP3+ cells in lymph nodes involved with lymphoma might play a role in disease progression. Attainment of a regulatory T-cell phenotype by a subset of lymphoma cells might signal a poor prognosis.

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Comparative analysis of histologicai and immunohistological features in mycosis fungoides and Sezary syndrome

Journal of Cutaneous Pathology ◽

10.1111/j.1600-0560.1998.tb01766.x ◽

1998 ◽

Vol 25 (8) ◽

pp. 407-412 ◽

Cited By ~ 48

Author(s):

J. Kamarashev ◽

G. Burg ◽

W. Kempf ◽

M. Hess Schmid ◽

R. Dummer

Keyword(s):

Comparative Analysis ◽

Mycosis Fungoides ◽

Sézary Syndrome ◽

Sezary Syndrome

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Differential expression of CD24-related epitopes in mycosis fungoides/Sezary syndrome: a potential marker for circulating Sezary cells

Blood ◽

10.1182/blood.v76.11.2343.2343 ◽

1990 ◽

Vol 76 (11) ◽

pp. 2343-2347 ◽

Cited By ~ 11

Author(s):

SJ Pirruccello ◽

MS Lang

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Mycosis Fungoides ◽

Peripheral Blood ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Low Density ◽

Circulating T Cells ◽

Sézary Cells

Abstract In the hematopoietic system, the B-cell associated antigen CD24 is expressed at high density on B cells, B-cell precursors, and B-cell malignancies as well as at low density on peripheral blood polymorphonuclear leukocytes. The 42-Kd sialoglycoprotein has not been previously demonstrated to be expressed on T cells, thymocytes, or T- cell malignancies. We identified three patients with mycosis fungoides/Sezary syndrome that showed low density expression of the CD24-related epitope recognized by antibody BA-1 on circulating T cells. All three patients had Sezary cells by morphologic assessment and clonal T-cell populations in the peripheral blood by gene rearrangement studies. In two of these patients, indirect immunofluorescence with a panel of six anti-CD24 monoclonal antibodies demonstrated reactivity for two of six antibodies in one case and only one of six antibodies in the other. The biologic significance of CD24- related epitope expression on circulating T cells in mycosis fungoides/Sezary syndrome is unclear. However, these findings suggest that differential, low density expression of CD24-related epitopes (BA- 1+, OKB2-) may be a useful phenotypic marker for identifying circulating Sezary cells.

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Photodynamic Therapy with the Silicon Phthalocyanine Pc 4 Induces Apoptosis in Mycosis Fungoides and Sezary Syndrome

Advances in Hematology ◽

10.1155/2010/896161 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Minh Lam ◽

YooJin Lee ◽

Min Deng ◽

Andrew H. Hsia ◽

Kelly A. Morrissey ◽

...

Keyword(s):

T Cells ◽

Photodynamic Therapy ◽

T Cell ◽

T Lymphocytes ◽

Mycosis Fungoides ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Silicon Phthalocyanine

Our current focus on the effects of Photodynamic Therapy (PDT) using silicon phthalocyanine Pc 4 photosensitizer on malignant T lymphocytes arose due to preclinical observations that Jurkat cells, common surrogate for human T cell lymphoma, were more sensitive to Pc 4-PDT-induced killing than epidermoid carcinoma A431 cells. Mycosis fungoides (MF) as well as Sezary syndrome (SS) are variants of cutaneous T-cell lymphoma (CTCL) in which malignant T-cells invade the epidermis. In this study, we investigated the cytotoxicity of Pc 4-PDT in peripheral blood cells obtained from patients with SS and in skin biopsies of patients with MF. Our data suggest that Pc 4-PDT preferentially induces apoptosis of CD4+CD7−malignant T-lymphocytes in the blood relative to CD11b+monocytes and nonmalignant T-cells.In vivoPc 4-PDT of MF skin also photodamages the antiapoptotic protein Bcl-2.

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Sézary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors

Blood ◽

10.1182/blood-2009-11-251926 ◽

2010 ◽

Vol 116 (5) ◽

pp. 767-771 ◽

Cited By ~ 260

Author(s):

James J. Campbell ◽

Rachael A. Clark ◽

Rei Watanabe ◽

Thomas S. Kupper

Keyword(s):

T Cells ◽

T Cell ◽

Mycosis Fungoides ◽

Memory T Cells ◽

Central Memory ◽

Effector Memory ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Central Memory T Cells ◽

Effector Memory T Cells

Abstract Cutaneous T-cell lymphoma (CTCL) encompasses leukemic variants (L-CTCL) such as Sézary syndrome (SS) and primarily cutaneous variants such as mycosis fungoides (MF). To clarify the relationship between these clinically disparate presentations, we studied the phenotype of T cells from L-CTCL and MF. Clonal malignant T cells from the blood of L-CTCL patients universally coexpressed the lymph node homing molecules CCR7 and L-selectin as well as the differentiation marker CD27, a phenotype consistent with central memory T cells. CCR4 was also universally expressed at high levels, and there was variable expression of other skin addressins (CCR6, CCR10, and CLA). In contrast, T cells isolated from MF skin lesions lacked CCR7/L-selectin and CD27 but strongly expressed CCR4 and CLA, a phenotype suggestive of skin resident effector memory T cells. Our results suggest that SS is a malignancy of central memory T cells and MF is a malignancy of skin resident effector memory T cells.

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