Epstein-Barr Virus–Associated B-Cell Lymphoproliferative Disorders in Angioimmunoblastic T-Cell Lymphoma and Peripheral T-Cell Lymphoma, Unspecified

Zettl, Andreas; Lee, Seung Sok; Rüdiger, Thomas; Starostik, Petr; Marino, Mirella; Kirchner, Thomas; Ott, Michaela; Müller‐Hermelink, Hans Konrad; Ott, German

doi:10.1309/6utx-gvc0-12nd-jjeu

Cited by 187 publications

(170 citation statements)

References 26 publications

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“…Two recent studies reported the expression of IL-21 and its receptor by Hodgkin-Reed/ Sternberg cells (35,36). IL-21 could be responsible for the EBNA-2-negative, LMP-1-positive viral gene expression seen also in the EBV-positive B cell proliferations in the angioimmunoblastic T cell lymphomas (11). These malignant T cells are believed to originate from the T FH cells of GCs (37, 38), and therefore they probably produce IL-21.…”

Section: Resultsmentioning

confidence: 99%

IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter

Kis

Salamon

Persson

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Epstein-Barr virus (EBV) is associated with a variety of human tumors. Although the EBV-infected normal B cells in vitro and the EBV-carrying B cell lymphomas in immunodeficient patients express the full set of latent proteins (type III latency), the majority of EBVassociated malignancies express the restricted type I (EBNA-1 only) or type II (EBNA-1 and LMPs) viral program. The mechanisms responsible for these different latent viral gene expression patterns are only partially known. IL-21 is a potent B cell activator and plasma cell differentiation-inducer cytokine produced by CD4 + T cells. We studied its effect on EBV-carrying B cells. In type I Burkitt lymphoma (BL) cell lines and in the conditional lymphoblastoid cell line (LCL) ER/ EB2-5, IL-21 potently activated STAT3 and induced the expression of LMP-1, but not EBNA-2. The IL-21-treated type I Jijoye M13 BL line ceased to proliferate, and this was paralleled by the induction of IRF4 and the down-regulation of BCL6 expression. In the type III LCLs and BL lines, IL-21 repressed the C-promoter-derived and LMP-2A mRNAs, whereas it up-regulated the expression of LMP-1 mRNAs. The IL-21-treated type III cells underwent plasma cell differentiation with the induction of Blimp-1, and high levels of Ig and Oct-2. IL-21 might be involved in the EBNA-2-independent expression of LMP-1 in EBV-carrying type II cells. In light of the fact that IL-21 is already in clinical trials for the treatment of multiple malignancies, the in vivo modulation of EBV gene expression by IL-21 might have therapeutic benefits for the EBV-carrying malignancies.Epstein-Barr virus | IL-21 | lymphoma | STAT3

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Section: Resultsmentioning

confidence: 99%

IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter

Kis

Salamon

Persson

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…It should be noted that rare cases of B-cell lymphoma after angioimmunoblastic T-cell lymphoma and concurrent angioimmunoblastic T-cell lymphoma and large B-cell lymphoma have been reported. [8][9][10][11] Definitive classification of the B-cell process may be difficult, but it is most important not to overlook the underlying T-cell malignancy.…”

Section: Discussionmentioning

confidence: 99%

CD10 expression in peripheral T-cell lymphomas complicated by a proliferation of large B-cells

et al. 2006

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CD10 expression by the neoplastic T cells in angioimmunoblastic T-cell lymphoma was recently described. As cases of peripheral T-cell lymphoma, unspecified, fail to show similar CD10 expression, this feature helps discriminate between these two entities, particularly in cases exhibiting morphologic overlap. Given these findings, we studied CD10 expression in a subtype of peripheral T-cell lymphoma known as peripheral T-cell lymphoma complicated by a proliferation of large B cells and compared it with angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation. A total of 33 cases were identified including peripheral T-cell lymphoma complicated by a proliferation of large B cells (10), angioimmunoblastic T-cell lymphoma (10) and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (13). Diagnoses were established by hematoxylin and eosin (H&E) stain, immunohistochemistry and/or molecular findings (polymerase chain reaction for T-cell receptor-gamma gene rearrangement). Two of 10 cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells showed aberrant CD10 expression (20%) compared to 9/10 cases of angioimmunoblastic T-cell lymphoma (90%) and 8/13 of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (62%). One case each of angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation showed a rare, but not unequivocal, CD10( þ ) atypical cell. Four cases of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation were CD10 negative. Of the 2 CD10( þ ) peripheral T-cell lymphoma complicated by a proliferation of large B cells, one had no H&E or IHC features of angioimmunoblastic T-cell lymphoma and showed only a rare positive cell. The second case, a lung biopsy, exhibited diffuse CD10 tumor cell positivity. The predominant staining pattern in the CD10( þ ) cases was characterized by scattered, mostly individual, morphologically neoplastic cells. A rare case showed clusters of positive cells. Our data indicate that only 20% of cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells show CD10 expression by the neoplastic T cells in contrast to angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation which exhibit CD10 staining in 90 and 62% of cases, respectively. This finding does not reach statistical significance with a P-value of 0.57 (Fisher's exact test). As these entities appear to be biologically distinct and may portend different overall survivals, CD10 expression may serve as an additional discriminating criterion.

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“…She had previously undergone an autologous stem cell transplant. Unlike solid organ transplants these do not involve prolonged use of immunosuppressants and are not associated with EBV lymphoproliferative disorders.High rates of EBV infected lymphocytes have been reported in patients with angioimmunoblastic lymphoma [9]. At diagnosis a few patients with angioimmunoblastic lymphoma have been reported to also have a coexisting EBV lymphoproliferative disorder [9].…”

mentioning

confidence: 99%

“…High rates of EBV infected lymphocytes have been reported in patients with angioimmunoblastic lymphoma [9]. At diagnosis a few patients with angioimmunoblastic lymphoma have been reported to also have a coexisting EBV lymphoproliferative disorder [9].…”

mentioning

confidence: 99%

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Secondary Epstein‐Barr virus associated lymphoproliferative disorder developing in a patient with angioimmunoblastic T cell lymphoma on vorinostat

et al. 2012

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Ebstein-Barr Virus (EBV)-related lymphoproliferative disorders primarily occur in the setting of immunosuppression, most commonly after solid organ transplantation [1]. The frequency depends on the degree of immunosuppression and the specific organ transplanted, but can be as high as 3-9% in heart or lung transplant patients [2]. Less frequent outside of the transplant setting, EBV-related lymphoproliferative disorders classified as other iatrogenic immunodeficiency associated lymphoproliferative disorders in the WHO Classification, which are different than iatrogenically related lymphomas supervening on hematological malignancies, have been associated with other immunosuppressive therapies such as 6-Mercaptopurine, azathioprine, or alemtuzumab [3][4][5][6]. These disorders have also been reported to develop spontaneously in patients with T cell lymphomas (angioimmunoblastic and peripheral T cell NOS) [7]. Here we report the case of a patient with an angioimmunoblastic T cell lymphoma on therapy with vorinostat who developed an EBV related B-cell lymphoproliferative disorder involving bilateral adrenal glands. Angioimmunoblastic T cell lymphoma is associated with severe immunodeficiency and risk for opportunistic infections [7]. This immune dysregulation has been implicated in its association with EBV related lymphoproliferative disorders [8]. In this patient, vorinostat therapy also appears to be linked to the development of an EBV-related lymphoproliferative disorder.A 59-year-old female presented two years ago with unexplained skin nodules and palpable lymphadenopathy. An excisional lymph node biopsy demonstrated T cells with moderately abundant pale cytoplasm that were positive for CD3, CD4, CD5, as well as C10 and CD279. Also present were CD20 positive B cells and immunoblasts with a mild increase in EBV positive lymphocytes. These features including a positive T cell gene rearrangement were consistent with a diagnosis of angioimmunoblastic T cell lymphoma. On a PET scan there were enlarged and FDG avid axillary, subpectoral and femoral lymph nodes. Bone marrow biopsy and aspirate were negative for lymphoma involvement.She received six cycles of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone). PET imaging after the second and fourth cycles demonstrated a complete remission. The patient subsequently underwent an autologous stem cell transplant with BEAM conditioning in first remission. She tolerated this without complications. Follow-up examinations and imaging confirmed complete remission for fourteen months.The patient subsequently developed eosinophilia with eosinophilic dermatitis. PET imaging demonstrated multiple enlarged avid lymph nodes in the axillary, clavicular, hilar, porta hepatitis, peri-aortic, and inguinal region. An axillary lymph node biopsy confirmed recurrent angioimmunoblastic T cell lymphoma. She was treated with 400 mg daily of vorinostat. Interval PET scan after 2 months showed partial response. After five months of therapy her repeat PET imaging showed ...

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Epstein-Barr Virus–Associated B-Cell Lymphoproliferative Disorders in Angioimmunoblastic T-Cell Lymphoma and Peripheral T-Cell Lymphoma, Unspecified

Cited by 187 publications

References 26 publications

IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter

IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter

CD10 expression in peripheral T-cell lymphomas complicated by a proliferation of large B-cells

Secondary Epstein‐Barr virus associated lymphoproliferative disorder developing in a patient with angioimmunoblastic T cell lymphoma on vorinostat

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