scholarly journals A puzzling diagnosis: mycosis fungoides masquerading as pyoderma gangrenosum

2020 ◽  
Vol 6 (6) ◽  
pp. 784
Author(s):  
Neil K. Jairath ◽  
Ruple Jairath ◽  
Krislyn Porter ◽  
Jon C. Davis
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycosis Fungoides ◽  
Pyoderma Gangrenosum ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Inflammatory Cell Infiltrate ◽  
Clonal Proliferation ◽  
Positron Emission ◽  
Metastatic Involvement

<p class="abstract">Mycosis fungoides (MF) is a form of cutaneous T cell lymphoma that initially affects the epidermis, and is characterized by the clonal proliferation of mature cluster of differentiation (CD4)+T cells. We report a 73-year old male presenting with chin and right axillary skin lesions that had ulceration and granulating areas. Initial biopsy revealed mixed inflammatory cell infiltrate, which suggested an initial diagnosis of pyoderma gangrenosum. Despite treatment, the progressive worsening of the skin lesions prompted multiple repeat biopsies, which eventually revealed a predominance of T cells within the infiltrate. A T cell receptor rearrangement resulted in elevated monoclonal T cell populations, confirming a diagnosis of MF. Subsequent positron emission tomography (PET) scans revealed metastatic involvement of the disease, which ultimately led to the patient’s death. Clinical presentations of MF can mimic several different clinical entities, including pyoderma gangrenosum. This report highlights the importance of a multimodal approach to the diagnosis of unidentified skin lesions.</p>

scholarly journals T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2580-2586 ◽  
Author(s):  
BJ Nickoloff ◽  
FO Nestle ◽  
XG Zheng ◽  
LA Turka
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mycosis Fungoides ◽  
Skin Diseases ◽  
Family Members ◽  
Chinese Hamster ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Epidermal Keratinocytes

The activation of T cells requires two distinct signals. One signal involves interaction of the antigen-specific T-cell receptor with major histocompatibility complex molecules plus antigenic peptide; a second signal, which is antigen nonspecific, is the interaction of CD28 with its natural ligands B7–1 and B7–2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and binds to B7 gene-family members, found on antigen-presenting cells. Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides. By immunostaining cryostat sections of skin, CD28 was found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7–1 was also found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. B7–1 expression was confirmed on CD3+ T lymphocytes using flow cytometry of single cell suspensions of fresh, unfixed psoriatic lesional tissue. To exclude the possibility that this result was caused by a second reagent contaminating the monoclonal antibody (MoAb) preparation, two different lots were used, and the MoAb was absorbed onto Chinese hamster ovary (CHO) transfectants expressing B7–1, or vector-only transfected CHO cells. These procedures confirmed that a B7- 1-like epitope was being recognized on psoriatic lesional T cells. In contrast to B7–1 expression on lymphocytes, B7–3, as defined by anti-BB- 1 MoAb reactivity, was found primarily on epidermal keratinocytes in both skin diseases and was not found on T cells. These results indicate that within two common skin disorders, lesional T cells accumulate in the dermis and epidermis, which express B7–1. Such expression may permit self-costimulation involving the CD28-mediated activation pathway, and thereby contribute to the ongoing T-cell proliferation present in these chronic, benign, and malignant skin diseases.

scholarly journals T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2580-2586 ◽  
Author(s):  
BJ Nickoloff ◽  
FO Nestle ◽  
XG Zheng ◽  
LA Turka
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mycosis Fungoides ◽  
Skin Diseases ◽  
Family Members ◽  
Chinese Hamster ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Epidermal Keratinocytes

Abstract The activation of T cells requires two distinct signals. One signal involves interaction of the antigen-specific T-cell receptor with major histocompatibility complex molecules plus antigenic peptide; a second signal, which is antigen nonspecific, is the interaction of CD28 with its natural ligands B7–1 and B7–2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and binds to B7 gene-family members, found on antigen-presenting cells. Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides. By immunostaining cryostat sections of skin, CD28 was found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7–1 was also found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. B7–1 expression was confirmed on CD3+ T lymphocytes using flow cytometry of single cell suspensions of fresh, unfixed psoriatic lesional tissue. To exclude the possibility that this result was caused by a second reagent contaminating the monoclonal antibody (MoAb) preparation, two different lots were used, and the MoAb was absorbed onto Chinese hamster ovary (CHO) transfectants expressing B7–1, or vector-only transfected CHO cells. These procedures confirmed that a B7- 1-like epitope was being recognized on psoriatic lesional T cells. In contrast to B7–1 expression on lymphocytes, B7–3, as defined by anti-BB- 1 MoAb reactivity, was found primarily on epidermal keratinocytes in both skin diseases and was not found on T cells. These results indicate that within two common skin disorders, lesional T cells accumulate in the dermis and epidermis, which express B7–1. Such expression may permit self-costimulation involving the CD28-mediated activation pathway, and thereby contribute to the ongoing T-cell proliferation present in these chronic, benign, and malignant skin diseases.

scholarly journals Demonstration of Frequent Occurrence of Clonal T Cells in the Peripheral Blood of Patients With Primary Cutaneous T-Cell Lymphoma

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1636-1642 ◽  
Author(s):  
J. Marcus Muche ◽  
Ansgar Lukowsky ◽  
Khusru Asadullah ◽  
Sylke Gellrich ◽  
Wolfram Sterry
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Systemic Disease ◽  
Cell Receptor ◽  
Skin Lesions ◽  
T Cell Lymphomas ◽  
Gradient Gel Electrophoresis ◽  
Advanced Stages ◽  
Temperature Gradient Gel Electrophoresis

Abstract Clonal T cells have been demonstrated in skin lesions of all stages of cutaneous T-cell lymphomas (CTCLs). However, there are conflicting data regarding the CTCL stage at which dissemination of clonal cells into peripheral blood occurs. Although the multifocal occurrence of cutaneous CTCL lesions and T-cell recirculation suggest an early appearance of neoplastic cells in the blood, circulating clonal T cells have only been detected in advanced stages. We investigated their occurrence by a highly sensitive polymerase chain reaction (PCR) assay amplifying T-cell receptor γ rearrangements and subsequent heteroduplex temperature gradient gel electrophoresis (HD-TGGE) of the amplification products. Circulating clonal T cells were found in 26 of 45 patients with mycosis fungoides (MF ), six of seven with Sezary's syndrome (SS), 10 of 13 pleomorphic CTCLs, and three of four unclassified CTCLs. Corresponding skin specimens carried clonal T cells in 29 of 40 MF, three of four SS, 12 of 12 pleomorphic, and two of two unclassified CTCL patients. Except for the blood specimen of a psoriatic patient, all samples of 60 controls (psoriasis vulgaris, atopic dermatitis, and healthy volunteers) revealed polyclonal amplification products. In 30 of 32 CTCL patients carrying a clonal rearrangement in blood and skin, identity of both clones was indicated by HD-TGGE and confirmed by sequencing six of these cases. We found an unexpected high frequency of identical clonal T cells in peripheral blood and skin of CTCL patients, including early stages of MF. This supports the concept of an early systemic disease in CTCL and raises new questions concerning the pathogenesis.

Flow Cytometric Detection of Neoplastic T Cells in Patients with Mycosis Fungoides Based on Levels of T-Cell Receptor Expression

1994 ◽  
Vol 102 (6) ◽  
pp. 856-860 ◽  
Author(s):  
Miroslaw Kuchnio ◽  
Edward A. Sausville ◽  
Elaine S. Jaffe ◽  
Timothy Greiner ◽  
Francine M. Foss ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycosis Fungoides ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Expression ◽  
Flow Cytometric

scholarly journals Evidence for in vivo clonal proliferation of unique population of blood CD4-/CD8- T cells bearing T-cell receptor alpha and beta chains in two normal men

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2965-2972 ◽  
Author(s):  
Y Kusunoki ◽  
Y Hirai ◽  
S Kyoizumi ◽  
M Akiyama
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Nk Cell ◽  
Cell Receptor ◽  
Cell Markers ◽  
Clonal Proliferation ◽  
Alpha Beta

Abstract Rare T lymphocytes bearing CD3 surface antigen and T-cell receptor (TCR) alpha and beta chains, but lacking both CD4 and CD8 antigens, viz, TCR alpha beta+CD4–8- cells, appear at a frequency of 0.1% to 2% in peripheral blood TCR alpha beta+ cells of normal donors. Here we report two unusual cases, found among 100 healthy individuals studied, who showed an abnormally elevated frequency of these T cells, ie, 5% to 10% and 14% to 19%. Southern blot analyses of the TCR alpha beta+CD4–8- clones all showed the identical rearrangement patterns for each individual, demonstrating that these are derivatives of a single T cell. The same rearrangement patterns were also observed for the freshly isolated lymphocytes of TCR alpha beta+CD4-CD8- fraction, which excludes the possible bias in the processes of in vitro cloning. These TCR alpha beta+CD4–8- T cells were found to express other mature T-cell markers such as CD2, CD3, and CD5 antigens, as well as natural killer (NK) cell markers (CD11b, CD16, CD56, and CD57 antigens) for both individuals. Further, although lectin-dependent or redirected antibody- dependent cell-mediated cytotoxicities were observed for both freshly sorted lymphocytes of TCR alpha beta+CD4–8- fraction and in vitro established clones, NK-like activity was not detected.

Expression of T-Cell Receptor Antigens in Mycosis Fungoides and Inflammatory Skin Lesions

1989 ◽  
Vol 93 (1) ◽  
pp. 116-120 ◽  
Author(s):  
Sara A. Michie ◽  
Elizabeth A. Abel ◽  
Richard T. Hoppe ◽  
Roger A. Warnke ◽  
Gary S. Wood
Keyword(s):  
T Cell ◽  
Mycosis Fungoides ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Inflammatory Skin

scholarly journals Evidence for clonal selection of gamma/delta T cells in response to a human pathogen.

1991 ◽  
Vol 174 (3) ◽  
pp. 683-692 ◽  
Author(s):  
K Uyemura ◽  
R J Deans ◽  
H Band ◽  
J Ohmen ◽  
G Panchamoorthy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clonal Selection ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Intraepithelial Lymphocytes ◽  
Gamma Delta T Cells ◽  
Antigen Receptors ◽  
Gamma Delta ◽  
Selection Of

T cells bearing gamma/delta antigen receptors comprise a resident population of intraepithelial lymphocytes in organs such as skin, gut, and lungs, where they are strategically located to contribute to the initial defense against infection. An important unsolved question about antigen-driven gamma/delta T cell responses regards the breadth of their T cell receptor (TCR) repertoire, since many specific epithelial compartments in mice display limited diversity. We have examined the diversity of TCR delta gene expression among human gamma/delta T cells from skin lesions induced by intradermal challenge with Mycobacterium leprae. We show that the vast majority of gamma/delta cells from M. leprae lesions use either V delta 1-J delta 1 or V delta 2-J delta 1 gene rearrangements and, within a given region of the lesion, display limited junctional diversity. This contrasts markedly with the extensive diversity of gamma/delta T cells from peripheral blood of these same individuals, as well as skin from normal donors. These results indicate that the gamma/delta response to M. leprae involves the selection of a limited number of clones from among a diverse repertoire, probably in response to specific mycobacterial and/or host antigens.

scholarly journals Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2440-2445 ◽  
Author(s):  
Kei-ichi Yamanaka ◽  
Rachael Clark ◽  
Benjamin Rich ◽  
Rebecca Dowgiert ◽  
Kazuki Hirahara ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Normal Skin ◽  
Neutralizing Antibody ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Interleukin 7 ◽  
Receptor Repertoire ◽  
T Cell Lymphomas ◽  
Skin Homing

AbstractCutaneous T-cell lymphomas (CTCLs) are malignancies of T cells that have a special affinity for the skin. We have previously reported that much of the T-cell receptor repertoire is altered in CTCL, and both malignant and nonmalignant clones are numerically expanded, presumably in response to T-cell trophic cytokines. We therefore examined levels of the T-cell trophic cytokines IL-2, IL-4, IL-7, IL-12, IL-13, and IL-15 in plasma in 93 CTCL patients and healthy controls. Only IL-7 levels were elevated in CTCL. We next looked at lesional skin from patients with CTCL and found elevated levels of IL-7 mRNA. Explant cultures of normal and lesional CTCL skin biopsies revealed significantly more IL-7 protein production in CTCL skin. Additionally, cultures of CTCL skin released greater numbers of T cells than normal skin; this was blocked by the addition of an IL-7 neutralizing antibody. Finally, these cultures induced proliferation of normal peripheral skin-homing T cells that were added to the cultures. These observations led us to postulate that IL-7 produced by skin cells contributes to the survival and proliferation of T cells within skin lesions and is likely the source of elevated circulating IL-7 in CTCL. (Blood. 2006;107:2440-2445)

scholarly journals The Feature of Distribution and Clonality of TCRγ/δSubfamilies T Cells in Patients with B-Cell Non-Hodgkin Lymphoma

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Liang Wang ◽  
Meng Xu ◽  
Chunyan Wang ◽  
Lihua Zhu ◽  
Junyan Hu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Distribution Patterns ◽  
Cell Receptor ◽  
Non Hodgkin Lymphoma ◽  
Clonal Proliferation

Restricted T-cell receptor (TCR) Vα/Vβrepertoire expression and clonal expansion ofαβT cells especially for putative tumor-associated antigens were observed in patients with hematological malignancies. To further characterize theγδT-cell immune status in B-cell non-Hodgkin lymphoma (B-NHL), we investigated the distribution and clonality of TCR Vγ/Vδrepertoire in peripheral blood (PB), bone marrow (BM), and lymph node (LN) from patients with B-NHL. Four newly diagnosed B-NHL cases, including three with diffuse large B-cell lymphoma (DLBCL) and one with small lymphocytic lymphoma (SLL), were enrolled. The restrictive expression of TCR Vγ/Vδsubfamilies with different distribution patterns could be detected in PB, BM, or LN from all of four patients, and partial subfamily T cells showed clonal proliferation. At least one clonally expanded Vδsubfamily member was found in PB from each patient. However, the expression pattern and clonality of TCR Vγ/Vδchanged in different immune organs and showed individual feature in different patients. The clonally expanded Vδ5, Vδ6, and Vδ8 were detected only in PB but neither in BM nor LN while clonally expanded Vδ2 and Vδ3 could be detected in both PB and BM/LN. In conclusion, the results provide a preliminary profile of distribution and clonality of TCRγ/δsubfamilies T cells in PB, BM, and LN from B-NHL; similar clonally expanded Vδsubfamily T cells in PB and BM may be related to the same B-cell lymphoma-associated antigens, while the different reactive clonally expanded Vγ/VδT cells may be due to local immune response.

scholarly journals Single-Cell RNA Sequencing Reveals Tissue Compartment-Specific Plasticity of Mycosis Fungoides Tumor Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Katharina Rindler ◽  
Wolfgang M. Bauer ◽  
Constanze Jonak ◽  
Matthias Wielscher ◽  
Lisa E. Shaw ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Rna Sequencing ◽  
Mycosis Fungoides ◽  
Cell Receptor ◽  
Skin Tumor ◽  
Single Cell Rna Sequencing

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. While initially restricted to the skin, malignant cells can appear in blood, bone marrow and secondary lymphoid organs in later disease stages. However, only little is known about phenotypic and functional properties of malignant T cells in relationship to tissue environments over the course of disease progression. We thus profiled the tumor micromilieu in skin, blood and lymph node in a patient with advanced MF using single-cell RNA sequencing combined with V-D-J T-cell receptor sequencing. In skin, we identified clonally expanded T-cells with characteristic features of tissue-resident memory T-cells (TRM, CD69+CD27-NR4A1+RGS1+AHR+). In blood and lymph node, the malignant clones displayed a transcriptional program reminiscent of a more central memory-like phenotype (KLF2+TCF7+S1PR1+SELL+CCR7+), while retaining tissue-homing receptors (CLA, CCR10). The skin tumor microenvironment contained potentially tumor-permissive myeloid cells producing regulatory (IDO1) and Th2-associated mediators (CCL13, CCL17, CCL22). Given their expression of PVR, TNFRSF14 and CD80/CD86, they might be under direct control by TIGIT+CTLA4+CSF2+TNFSF14+ tumor cells. In sum, this study highlights the adaptive phenotypic and functional plasticity of MF tumor cell clones. Thus, the TRM-like phenotype enables long-term skin residence of MF cells. Their switch to a TCM-like phenotype with persistent skin homing molecule expression in the circulation might explain the multi-focal nature of MF.

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