1/35. Mainly unmutated V(H) genes rearranged in B cells forming germinal centers in a cutaneous pleomorphic T-cell lymphoma.B cells in skin lesions of a pleomorphic cutaneous T-cell lymphoma with reactive germinal center hyperplasia were analyzed for their immunoglobulin V(H)DJ(H) gene rearrangements by micromanipulation and single cell polymerase chain reaction (PCR) analysis. In B lymphocytes located in germinal center-like structures, we found in 11/16 different V(H)DJ(H) rearrangements completely unmutated VH genes, suggesting that those cells did not undergo antigen-driven selection. Two V(H) genes showed more than 98% germ-line identity. In only three cells V(H) segments were somatically mutated to a higher extent, but two of these rearrangements were non-productive. These results differ markedly from what we have previously detected in B cells present in mycosis fungoides, another entity of cutaneous T-cell lymphomas where the Ig gene repertoire resembles the situation in peripheral blood with a significantly higher proportion of mutated V(H) genes. When investigating the large atypical B cells strongly expressing CD30 which were detected within the T-cell zone outside the germinal centers, we found again, in most cases, that the rearranged VH genes were completely unmutated. The B cells were of polyclonal origin. Due to this comparable Ig gene repertoire and mutational pattern, we suggest that these cells descend from the germinal center centroblasts which migrated into the T-cell zone and obviously became stimulated to express the CD30 marker. The micromanipulation technique and molecular analysis on the single cell level may provide an important input into our understanding of the mechanisms of immune regulation in cutaneous lymphomas.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/35. A case of natural killer/T cell lymphoma of the subcutis resembling subcutaneous panniculitis-like T cell lymphoma.A case of nasal type natural killer (NK)/T cell lymphoma of the subcutis showing clinical and morphological features that resemble subcutaneous panniculitis-like T cell lymphoma (SPTCL) is presented. A 73-year-old man presented with swelling of the left arm and was diagnosed with panniculitis by a dermatologist. It was concluded from a skin biopsy specimen that the patient had non-Hodgkin's lymphoma of the large cell, NK/T cell type because the neoplastic cells showed polyclonal CD3 immunoreactivity. Treatment with interferon-gamma was initiated, but the patient died of disseminated intravascular coagulation and multiple organ failure 2 months after the initial symptoms appeared. However, involvement of additional organs by the lymphoma was not apparent clinically. An autopsy was not performed. A routinely stained section of the biopsy skin specimen revealed massive necrosis of the subcutaneous fat, karyorrhexis admixed with reactive histiocytes, and large atypical lymphoid cells. Immunoreactivity for polyclonal CD3 was present in the perinuclear region, but absent in the neoplastic cell membranes. CD56, CD45RO (UCHL-1), CD43 (MT1), CD45 (leukocyte common antigen), and the cytotoxic molecules perforin, granzyme B and TIA-1 were positive, but CD20 (L26), CD4, CD8, and betaF1 were negative. Epstein-Barr virus (EBV) mRNA was detected in the nuclei of neoplastic cells by in situ hybridization. Subcutaneous panniculitis-like T cell lymphoma is reported to be an EBV-negative, clonal T cell neoplasm. Although this case showed clinical and morphological features that resembled SPTCL, perinuclear polyclonal CD3 staining and membranous CD56 reactivity seen in neoplastic cells were suggestive of NK cells. Furthermore, the neoplastic cells were positive for EBV. This case is considered to be a NK/T cell lymphoma of the subcutis resembling SPTCL. It is believed that it is important to recognize such a tumor because patients may undergo a fulminant clinical course, despite the tumor being localized in the subcutaneous adipose tissue.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/35. Subcutaneous panniculitis by Epstein-Barr virus-infected natural killer (NK) cell proliferation terminating in aggressive subcutaneous NK cell lymphoma.We describe here a case involving a patient presenting initially with subcutaneous panniculitis, which developed after 12 years into aggressive subcutaneous natural killer (NK) cell lymphoma with peripheral blood involvement and hemophagocytosis. The surface marker of lymphoid cells in peripheral blood was CD2 3-7 8-16 56 . skin biopsies were taken in May 1986 and June 1998. The initial biopsy revealed a diffuse proliferation of atypical lymphoid cells in the subcutaneous tissue with panniculitis, while the second biopsy revealed the presence of large lymphoid cells in the subcutaneous tissue with necrotic changes, consistent with a diagnosis of malignant lymphoma (diffuse pleomorphic type). The lymphoid cells from these two specimens were positive for CD56 and such cytotoxic molecules as T-cell intracellular antigen-1 (TIA-1), granzyme B, and, interestingly, also positive for Epstein-Barr (EB) virus by in situ hybridization. This suggests that chronic EB virus infections play an important role in the early stages of tumorigenesis and in the progression of NK cell lymphoproliferative disorders.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/35. Cutaneous T cell lymphoma reactive CD4 cytotoxic T lymphocyte clones display a Th1 cytokine profile and use a fas-independent pathway for specific tumor cell lysis.We have previously described two cytotoxic T lymphocyte clones isolated from lymphocytes infiltrating a human major histocompatibility complex class II-/class I , CD4 cutaneous T cell lymphoma. These clones displayed a CD4 CD8dim (TC5) and CD4 CD8- (TC7) phenotype and mediated a specific major histocompatibility complex class I-restricted cytotoxic activity toward Cou-LB autologous tumor cell line. Our studies were performed to elucidate the mechanism involved in T-cell-clone-mediated cytotoxicity and to determine the cytokine profile of both the lymphoma cell line and specific cytotoxic T lymphocyte clones. The results indicate that, despite surface expression of Fas receptor on Cou-LB and Fas ligand induction on TC5 and TC7 cell membranes, the CD4 cytotoxic T lymphocyte clones do not use this cytotoxic mechanism to lyse their specific target. The TC7 clone uses instead a granzyme-perforin-dependent pathway. Furthermore, quantitative analysis of Th1 and Th2 cytokine mRNA expression in the cutaneous T cell lymphoma cell line as well as in TC5 and TC7 clones indicated that, whereas the tumor cells display a Th2-type profile (interleukin-4, interleukin-6, and interleukin-10), the cytotoxic T lymphocyte clones express Th1-type cytokines (interferon-gamma, granulocyte macrophage colony stimulating factor, and interleukin-2). In addition, preincubation of the tumor-infiltrating lymphocyte clones with autologous tumor cells induced their activation and subsequent amplification of the Th1-type response. These results indicate a direct contribution of the malignant cells in the Th1/Th2 imbalance observed frequently in cutaneous T cell lymphoma patients and suggest their potential role in depressed cell-mediated immunity. Identification of CD4 Th1-type cytotoxic T lymphocyte clones, the tumor antigen they recognize, and optimization of their cytokine expression profile should be useful for the design of new immunotherapy protocols in cutaneous T cell lymphoma.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/35. Functional inhibitory receptors expressed by a cutaneous T cell lymphoma-specific cytolytic clonal T cell population.Inhibitory receptors on natural killer cells and on a minority of T lymphocytes are major histocompatibility complex class Ia or Ib specific. We have previously reported several tumor-specific cytotoxic T cell clones infiltrating a CD4( ) V beta 13( ) cutaneous T cell lymphoma. These clones mediated a specific major histocompatibility complex class I-restricted cytotoxic activity toward the uncultured tumor cells and autologous long-term tumor T cell lines. In this study, we cultured with interleukin-2 the peripheral blood lymphocytes of the same patient a few weeks before invasion of the blood by tumor cells. We report the rapid and selective expansion of a CD8( ) V beta 13( ) lymphoid population. This population was clonal, as it expressed a unique T cell receptor-V beta junctional region. V beta 13( ) tumor cells and V beta 13( ) reactive T cells were shown to have different junctional sequences. The CD8( ) reactive clone was functional, as it had a specific autologous tumor-specific, human leukocyte antigen-A2 restricted, cytotoxic activity. This clone coexpressed high levels of CD158a, CD158b, p70, and CD94/NKG2A inhibitory receptors. Interestingly, we found that anti-CD158a and anti-CD158b monoclonal antibodies could inhibit anti-CD3 redirected cytotoxicity mediated by the reactive clonal population. Further, an anti-human leukocyte antigen-B/C monoclonal antibody enhanced the specific cytotoxic activity of the clone against autologous tumor cells. These results are the first evidence that inhibitory receptor expression can lead to the inhibition of cutaneous T cell lymphoma-specific T cell responses.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
6/35. Posttransplant primary cutaneous T-cell lymphoma.A patient with posttransplant cutaneous lymphoma is described. Although most posttransplant lymphomas are of B-cell origin, this patient's lymphoma is a primary cutaneous lymphoma of T-cell origin. Another report exists of the first case of posttransplant primary cutaneous T-cell lymphoma localized to the lower extremities. Our patient's involvement was generalized with tumor nodules on the face and anterior chest. Reduced immune surveillance, chronic antigenic stimulation caused by transplant grafts, and the direct oncogenic effects of immunosuppressive drugs have all been suggested as mechanisms. Prompt recognition of this condition and initiation of appropriate therapy with reduction of high-dose immunosuppression can lead to better patient outcomes.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
7/35. Gene expression profile in a case of primary cutaneous CD30-negative large T-cell lymphoma with a blastic phenotype.A 65-year-old Japanese woman presented with disseminated erythematous patches, plaques, and nodules on the trunk and limbs. Histological examination showed diffuse and dense infiltrates located in the dermis and subcutis, composed of large pleomorphic T lymphocytes. Immunohistochemically, neoplastic cells were positive for blastic T-cell markers, but negative for CD30 (Ki-1) antigen. Based on the clinicopathological findings, a diagnosis of primary cutaneous large T-cell lymphoma was made. Despite systemic chemotherapy, the patient died 7 months after diagnosis. gene expression profiling using complementary dna microarrays indicated significantly increased expression of an apoptosis-inhibitory protein and certain cyokines and cytokine receptors (e.g. MCP-1, MCP-2, IP-10, and IL-2R gamma) in the tumour-indurated skin. Comprehensive gene expression patterning in additional cases may provide useful information regarding the biological and clinical behaviour of aggressive cutaneous lymphomas such as CD30-negative large T-cell lymphoma.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
8/35. T cells engrafted with a recombinant anti-CD30 receptor target autologous CD30( ) cutaneous lymphoma cells.T cells can be directed to antigen-specific, MHC-independent target cell lysis by grafting with a recombinant receptor with antibody-like specificity. Here, we asked whether T cells from the peripheral blood of a patient with cutaneous T cell lymphoma can be recruited for an immune response against autologous tumor cells. lymphoma cells with a CD3(-) CD4( ) CD30( ) phenotype and clonal TCR-Vbeta7 rearrangement were isolated from a cutaneous lesion. The lymphoma lesion additionally harbored CD3( ) CD25( ) activated normal T cells despite ongoing tumor progression. Peripheral blood-derived T cells from the lymphoma patient were retrovirally engrafted with a recombinant anti-CD30-scFv-gamma receptor. Upon cocultivation with autologous CD30( )lymphoma cells, grafted T cells increase IFN-gamma secretion and lyse specifically lymphoma cells with high efficiency, even at an effector to target cell ratio of as low as 1:20. Our data demonstrate that the recombinant anti-CD30-gamma receptor overcomes T cell tolerance for tumor cells and directs T cells specifically against autologous lymphoma cells.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
9/35. Cutaneous natural killer/T-cell lymphoma.Lymphomas are classified as either Hodgkin's or non-Hodgkin's. The 2 subtypes of non-Hodgkin's lymphoma that can present primarily in the skin are cutaneous T-cell lymphoma and cutaneous B-cell lymphoma, both of which tend to be low-grade malignant neoplasms. Recently another distinct subtype of lymphoma was discovered, the natural killer (NK)/T-cell lymphoma, which can involve the skin in a primary or secondary fashion. The NK/T-cell subtype of lymphoma is characterized by the expression of the NK-cell antigen CD56. These CD56( ) lymphomas are further subdivided into nasal NK/T-cell lymphomas that commonly present as midfacial destructive disease and non-nasal NK/T-cell lymphomas that often arise in extranodal locations, including the skin. We report a case of aggressive NK-cell leukemia/lymphoma with numerous secondary cutaneous lesions and review the clinical and histopathologic spectrum of non-nasal CD56( ) lymphomas, with an emphasis on the dermatologic findings.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/35. An ultrastructural study of cutaneous panniculitis-like T-cell lymphoma: cytoplasmic granules and active cellular and cell-to-matrix interaction mimic cytotoxic T-cells.Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare type of peripheral T-cell-derived lymphoma. A 30-year-old Japanese woman presented, complaining of skin lesions on her left hip. The cellular constituents in this SPTCL were of a mixed population. Not only tumor lymphoid cells, but also many macrophages, endothelial, fibroblasts, and fat cells were seen. The tumor cells immunostained positive for CD3 and CD8, but negative for CD4. Cytotoxic injury granule-related antigens of TIA-1 and granzyme B were positive in tumor cells. CD30. CD56, EBNA-2, LMP-1, CD20cy, and CD68 were all negative in the tumor cells. An ultrastructural study revealed that the lymphoma cells showed primitive cellular contacts with the neighboring tumor cells, interacted with the short villous dendrites of the opposing macrophage and fibroblast cellular membranes, and were associated with the vascular constituents, fat cells, and the extracellular matrix. Small aggregations of the granules were frequently seen in the cytoplasm. It was speculated that the tumor cells to some extent preserve the cytotoxic T-cell structure and function, have active cellular and cell-to-matrix interaction, contain characteristic cytoplasmic granules, and reveal unique histology like panniculities.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
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