Biphenotypic Gamma-Delta T-Cell Leukemia/Lymphoma with Coexpression of Pax-5 and Other B-Cell Specific Antigens.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4549-4549
Author(s):  
Henry Y. Dong ◽  
Patti Cohen ◽  
Po-Shing Lee
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Clinical Information ◽  
T Cell Lymphoma ◽  
Double Negative ◽  
Cell Antigen ◽  
T Cell Antigens ◽  
Cytogenetic Analyses

Abstract Lineage commitment of B- and T-lymphocytes occurs in early stages of normal differentiation. Pax-5 promotes commitment of B-cell and blocks early development of T-cell. Under neoplastic conditions, aberrant expression of less specific T-cell antigens (CD2, CD5 and CD8) has been detected in certain B-cell lymphomas, and B-cell antigens CD20 and CD79a have been seen in rare cases of T-cell lymphomas. However, coexpression of true lineage specific B-cell antigens Pax-5 and CD19 in T-cells with surface CD3 and T-cell receptors has not been reported in either normal or neoplastic T-cells. We report 4 cases of aggressive T-cell lymphoma/leukemia with a consistent but unusual immunophenotype, which was determined by immunohistochemistry (IHC) in all four cases with paraffin embedded tissue and by flow cytometry (FCM) in 2/4 cases. Molecular and cytogenetic analyses were also attempted in two patients and clinical information will be provided. All patients were male aged 21-79 years. Three patients, including 2 cases of T-ALL, presented with generalized lymphadenopathy and bone marrow involvement (clinical stage IV); 1/3 also had splenic involvement. A distinct mediastinal mass was not identified in any of the patients. Two patients undergoing therapy received the hyper-CVAD regimen and had a poor response to early treatment. One of the two was subsequently treated with Campath without success. The 4th patient presented with an isolated chest wall mass. Detailed clinical information is currently unavailable for 2 patients. In all cases, the neoplastic cells were characterized by blastic morphology and coexpression of bilineage lymphoid antigens. The neoplastic cells in 3 cases with systemic disease were immunoreactive with T-cell antigens CD3, CD5, CD7, CD43, and B-cell antigens CD79a and Pax-5; 2/3 cases that had FCM data both showed expression of CD19 and surface γ/δ-TCR, as well as myeloid antigens CD11c and CD33. The case without FCM data lacked βF1 (α/β-TCR) expression by IHC. In addition, 2/3 cases also had immunophenotypic features of typical T-lymphoblastic leukemia or lymphoma (T-ALL) (CD34+ and TdT+). All three cases lacked NK cell antigen CD56 and T-cell antigen CD2, and were double negative for CD4 and CD8. The tumor cells from the 4th case were positive for all pan-T cell antigens (CD2, CD3, CD7, CD43) except CD5 by IHC, and were double negative for CD4 and CD8. These features were phenotypically consistent with a γ/δ-T cell lymphoma, which was also supported by lack of detectable βF1 expression. Similar to other cases, however, these cells were also positive for B cell antigens Pax-5 and CD79a, as well as CD20. The only patient who had successful molecular and cytogenetic analyses had isochromosome 9 and clonal TCR gamma gene rearrangement. In summary, T-cell lymphoma or leukemia with bi-lineage lymphoid antigens is associated with Pax-5 expression, which may account for the upregulation of CD19. It appears to be a rare disease of γ/δ-T-cell origin with a unique phenotypic profile. Further study is needed to determine if the observed i(9) involves disruption of the Pax-5 locus at 9q13.

A Nationwide Prospective Multicenter Study of Clinical Features and Outcomes of Non-Hodgkin Lymphoma in Thailand: An Analysis of 939 Cases

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2064-2064 ◽  
Author(s):  
Udomsak Bunworasate ◽  
Noppadol Siritanaratanakul ◽  
Archrop Khuhapinant ◽  
Arnuparp Lekhakula ◽  
Pairaya Rujirojindakul ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Clinical Features ◽  
Cell Lymphoma ◽  
Elevated Serum ◽  
Clinical Information ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
T Cell Lymphoma ◽  
Nk T Cell

Abstract Abstract 2064 OBJECTIVE: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in Thailand. The objective of the study was to evaluate clinical features, histopathology, treatment outcomes and prognostic factors in Thai adult patients with NHL. METHODS: Using web-based registry system, we prospectively collected clinical information of newly diagnosed NHL patients from eleven major medical centers situated in various geographic regions of Thailand. All histopathological diagnoses were reviewed by consensus meeting of panels of 6 expert hematopathologists and classified according to the 2008 WHO classification of the lymphoid neoplasms. Clinical features and treatment outcomes were analyzed using STATA program. RESULTS: Between January 2007 and May 2009, there were a total of 939 NHL patients whose clinical information including follow-up data and tissue samples were readily available for analysis. The median age was 58 years (range, 15–99). Forty six percent of the patients were ≥60 years of age. Male:female was 1.18:1. The six leading subtypes were diffuse large B-cell lymphoma (67%), extranodal marginal zone lymphoma of MALT type (7%), follicular lymphoma (6%), mantle cell lymphoma (4%), peripheral T-cell lymphoma, not otherwise specified (NOS) (3%) and extranodal NK/T-cell lymphoma, nasal type (3%). T-cell lymphoma constituted 10% of all NHL. The three most common subtypes in T-cell lymphomas were peripheral T-cell lymphoma, NOS (26%), extranodal NK/T-cell lymphoma, nasal type (25%) and angioimmunoblastic T-cell lymphoma (15%). Fifty-eight percent of all patients had advanced disease (stage III, IV), 42% had B symptoms and 54% had elevated serum LDH. The IPI risk groups were 23% low, 30% low-intermediate, 30% high-intermediate and 17% high-risk. HIV-associated NHL was seen in 4.4% of the patients. Of the 801 patients who received chemotherapy, 90% were treated with anthracycline-containing regimen. Twenty-five percent of the patients received rituximab. Of the 663 evaluable patients, the rate of objective tumor response was 75% (CR+CRu, 59%). At a median follow-up time of 13 months, the 4-year projected overall survival (OS) was 73% (95% CI 69–77%). The OS of patients with T-cell lymphoma was inferior to B-cell lymphoma (58% vs. 74%, p = 0.04). With multivariate analysis, the independent adverse prognostic factors for OS in B-cell lymphoma were poor performance status (HR 2.4, 95% CI 1.7–3.5), elevated serum LDH (HR 2.1, 95% CI 1.4–3.1), stage III/IV (HR 1.6, 95% CI 1.1–2.3), WHO subtype (HR 1.1, 95% CI 1.0–1.2), no chemotherapy (HR 3.1, 95% CI 1.9–5.1) and no rituximab treatment (HR 1.7, 95% CI 1.1–2.6). The independent adverse factors for OS in T-cell lymphoma were elevated serum LDH (HR 3.7, 95% CI 1.2–11.1) and male sex (HR 3.4, 95% CI 1.3–8.8). CONCLUSIONS: This study confirmed the characteristic features of NHL among Thai population, i.e., a preponderance of diffuse large B-cell lymphoma and a low incidence of follicular lymphoma within B-cell lymphoma; a relatively high incidence of nasal NK/T-cell lymphoma within T-cell lymphoma. The IPI risk-groups and survival outcomes were comparable to most previously published reports. Disclosures: Bunworasate: Novartis Pharmaceutical: Research Funding. Off Label Use: Nilotinib is a safe and effective treatment for patients with CML. Chuncharunee:Novartis: Research Funding.

scholarly journals 3D investigation shows walls and wall-like structures around human germinal centres, probably regulating T- and B-cell entry and exit

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242177
Author(s):  
Miguel Thomos ◽  
Patrick Wurzel ◽  
Sonja Scharf ◽  
Ina Koch ◽  
Martin-Leo Hansmann
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Selection Process ◽  
Lymphoid Cells ◽  
T Cell Lymphoma ◽  
Tissue Slices ◽  
Angioimmunoblastic T Cell Lymphoma ◽  
Germinal Centres

This study deals with 3D laser investigation on the border between the human lymph node T-zone and germinal centre. Only a few T-cells specific for antigen selected B-cells are allowed to enter germinal centres. This selection process is guided by sinus structures, chemokine gradients and inherent motility of the lymphoid cells. We measured gaps and wall-like structures manually, using IMARIS, a 3D image software for analysis and interpretation of microscopy datasets. In this paper, we describe alpha-actin positive and semipermeable walls and wall-like structures that may hinder T-cells and other cell types from entering germinal centres. Some clearly defined holes or gaps probably regulate lymphoid traffic between T- and B-cell areas. In lymphadenitis, the morphology of this border structure is clearly defined. However, in case of malignant lymphoma, the wall-like structure is disrupted. This has been demonstrated exemplarily in case of angioimmunoblastic T-cell lymphoma. We revealed significant differences of lengths of the wall-like structures in angioimmunoblastic T-cell lymphoma in comparison with wall-like structures in reactive tissue slices. The alterations of morphological structures lead to abnormal and less controlled T- and B-cell distributions probably preventing the immune defence against tumour cells and infectious agents by dysregulating immune homeostasis.

scholarly journals Leukemia and lymphoma in ataxia telangiectasia

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 423-438 ◽  
Author(s):  
AM Taylor ◽  
JA Metcalfe ◽  
J Thick ◽  
YF Mak
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Cell Tumor ◽  
T Cell Lymphoma ◽  
Lymphoid Malignancy ◽  
Cell Clones ◽  
Tumor Types ◽  
Age Range

There is a large increase in lymphoid malignancy in A-T patients and a total absence of myeloid tumors. Penetrance of the tumor phenotype is about 10% to 15% by early adulthood. The increase in lymphoid malignancy includes both B- and T-cell tumors. However, young A-T patients do not show an increased susceptibility to cALL, and the UK data suggest that B-cell lymphoma occurs in older A-T children. T-cell tumors may occur at any age and may be T-ALL, T-cell lymphoma, or T-PLL; most strikingly, there may be a fourfold to fivefold increased frequency of T-cell tumors compared with that of B-cell tumors in these patients. If this is correct, it is possible that a significant proportion of all T-ALL/T-cell lymphoma in infants might be associated with undiagnosed A-T. The age range and sex predominance for T-ALL may be different for A-T and non-A-T patients and the age range for T-PLL may also be different in A-T and non-A-T patients. There is clearly some uncertainty concerning the ratio of T-cell to B-cell tumors in A-T, but this could be clarified by the publication of all tumors that occur in the disorder. In contrast, 8 of 9 tumors reported in NBS, which shows the same cellular features as A-T, were lymphomas and none was a leukemia. There are several indicators of genetic heterogeneity in A-T that suggest that not all patients are equally susceptible to all T-cell tumor types. Concordance for tumor type within individual families suggests that particular gene defects may be associated with particular tumor types. The logical extrapolation of this argument is that some patients may not have any increased risk for B-cell tumors at all or even to all T-cell types but only to a particular type of T-cell tumor. What is the cause of the increased predisposition to leukemia/lymphoma in A-T patients? There is no evidence that the immunodeficiency in A-T is related to this predisposition. One of the major findings in all A-T patients is the increase in V(D)J-mediated chromosome rearrangement observed in T lymphocytes. Particular chromosome translocations in T cells, involving a break in a TCR gene, are characteristically associated with either T-ALL or T-PLL in non-A-T patients. The majority of T-cell tumors in A-T are T-ALL and T-cell lymphoma, about which virtually nothing is known chromosomally, and the assumption is that the increased number of translocations leads to the increased level of these tumors. In older T patients, the expansion of specific translocation T-cell clones has been followed to the point to which they develop into T-PLL. All the evidence, therefore, suggests that the A-T mutation in the homozygous state allows a large increase in production of translocations formed at the time of V(D)J recombination, and this leads to the increased predisposition to leukemia. The general increased predisposition to T-cell tumors compared with B-cell tumors in A-T patients may be related to a preferential occurrence of translocations in T cells. Relatively little is known about translocations in circulating B lymphocytes in normal individuals, but A-T siblings have been shown to have clonal chromosome rearrangements of both B and T cells, simultaneously, although in these siblings the T-cell clones occupied all the T-cell compartment and the B-cell clones were small. An important inference from these facts is that the A-T defect preferentially affects immune system gene recombination in T cells rather than B cells. Recent evidence suggests that the V(D)J recombination machinery is not identical or is not regulated identically in T- and B-cell progenitors. This finding is consistent with the hypothesis that V(D)J rejoining in the majority, at least, of A-T patients may be preferentially deficient in T cells compared with B cells giving rise to the greatly increased number of translocations and T-cell tumors. Carbonari et al proposed that the recombination defect in A-T cells affected both Ig isotype switching and TCR rearrangeme

P53 Prevents TCR-Dependent Peripheral T-Cell Lymphomagenesis From Chronically Stimulated T Cells.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2401-2401
Author(s):  
Emmanuel Bachy ◽  
Alexandra Traverse-Glehen ◽  
Sophie Gazzo ◽  
Baseggio Lucile ◽  
Martine Ffrench ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Transformation Process ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Deficient Mice

Abstract Abstract 2401 Background. Compelling evidence suggests that chronic infections by various pathogens are linked to lymphoma development. The transformation process is supposed to be either direct (eg for EBV) or indirect. The association between Helicobacter pylori chronic infection and gastric marginal zone lymphoma (MZL) is the best characterized example for an indirect transformation. Several other pathogens such as hepatitis C virus, Campylobacter jejuni or Streptococcus Pneumoniae (Spn) are also suspected to promote B-cell lymphoma development through repeated stimulations of the BCR and/or inflammation. However, except for gastric MZL, animal models are lacking to study potential correlations between chronic infections and lymphoma development. Methods. To amplify and precipitate lymphomagenesis by precluding repair of DNA lesions potentially generated during chronic immune response, p53-deficient mice were used as a permissive model. Given the suspected role of carbohydrates from encapsulated bacteria such as Spn in promoting chronic lymphocytic leukemia, p53−/− (n=15) and p53+/− (n=53) mice were chronically injected with heat-killed Spn until disease development. P53-deficient mice chronically injected with PBS were used as control. Results. Unexpectedly, chronic injections of Spn promoted T-cell rather than B-cell lymphomagenesis in both p53−/− and p53+/− mice and shortened survival in p53+/− mice (P=.004). Whereas mostly thymic CD4+CD8+ double positive T-cell lymphomas have been described in p53-deficient mice, a vast majority of lymphomas observed following chronic Spn injections were of peripheral origin (TdT−) and exhibited an effector memory phenotype (CD44hiCD62LloCCR7−CD25−). Clonality and transferability of those peripheral T-cell lymphomas (PTCL) were established. Furthermore, lymphoma cells showed features of chronically stimulated T cells such as TCR, CD3 or CD4/CD8 co-receptor down-regulations along with PD-1 up-regulation. Several lines of evidence suggested a contribution of the TCR to the development of these PTCL: 1/all PTCL following Spn injections exhibited a Vß repertoire usage bias (Vß8 in 100%) consistent with a transformation process originating from a chronically-stimulated T cell by a pathogen-specific immunodominant peptide; 2/cyclosporin A, a strong TCR signaling inhibitor, decreased cell survival in vitro, and prolonged mice survival following transfer of lymphoma cells into recipient mice; 3/engraftment of CD8+ PTCL in MHC class I KO mice was significantly reduced compared to wild type mice (P<.0001). Finally in vitro survival of PTCL was strongly dependent on the addition of γc cytokines (IL-7 and IL-15) in agreement with the expression of CD122 and CD127 and their potential memory origin. The absence of B-cell lymphoma development in p53−/− mice and its very late onset in p53+/− mice (ie >450 days) compared to T-cell lymphoma prompted us to dissect the potential role of p53 in mature T-cell response in a context of chronic stimulation. WT and p53−/− negatively selected CD4+ and CD8+ T cells were repeatedly (ie every 7–10 days) stimulated in vitro using anti-CD3/anti-CD28-coated beads. In agreement with previous reports, no significant difference of cell viability was observed after the first or the second stimulation confirming the minor role of p53 in initial activation and proliferation as well as in activation-induced cell death. Nonetheless, a dramatic increase in cell viability was observed 48h after the third stimulation of p53−/− T cells, indicating a crucial function of p53 in deletion of chronically activated T cells. Conclusion. Chronic stimulations with heat-killed Spn unexpectedly increased peripheral T-cell lymphoma development in p53-deficient mice. Phenotypic characterization was consistent with a transformation process occurring in a pathogen-specific chronically-stimulated T cell. The incidence of p53 mutations is higher in T-cell than in B-cell mature malignancies in humans and the p53 pathway is functionally impaired in virtually all enteropathy-associated T-cell lymphomas, which are supposed to be a key model for an antigen-driven process. Therefore, aside from its known role in immature T-cell lymphoma development and in progression of B-cell malignancies, our work sheds light on a previously unsuspected physiopathological role of the p53 pathway in peripheral T-cell lymphomagenesis. Disclosures: No relevant conflicts of interest to declare.

Peripheral T-cell Lymphoma, NOS With Epstein-Barr Virus Positivity in an Elderly Patient With Myelodysplastic Syndrome: An Autopsy Case Report

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S81-S81
Author(s):  
J Lanceta ◽  
W Xue ◽  
M Hurford ◽  
H Wu
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

Abstract Casestudy Epstein-Barr virus (EBV)-associated peripheral T-cell lymphomas are a group of aggressive neoplasms with a geographic predilection for South America and Asia, but are very rare in Western populations. Results We report a case of a 74-year-old Caucasian female who presented with pancytopenia and B symptoms with EBV-IgG detected on admission. Past medical history included: ITP, chronic urticaria, and recently diagnosed myelodysplastic syndrome (MDS) on bone marrow biopsy one month prior to admission. Excisional biopsies of an enlarged right neck lymph node (repeated within 6 months) and right axillary lymph node five years ago were negative for a lymphoproliferative disorder at the time. Repeated bone marrow biopsy, performed during the current admission, confirmed the diagnosis of MDS, with scattered T-cells without aberrant immunophenotype. Despite aggressive treatment from multiple specialties, the patient deteriorated and expired four weeks later from complications of MDS. At autopsy, there was diffuse lymphadenopathy involving the mediastinum, axilla, pelvis and peripancreatic fat. Lymph node sections demonstrated nodal architecture effacement by diffuse, vaguely nodular lymphoid infiltrates. Histologically, the infiltrates were composed of medium to large lymphocytes with round to slight irregular nuclei, rare Reed-Sternberg-like multinucleated cells, clumped chromatin, and indistinct nucleoli. Individual cell necrosis was abundant with mitotic figures readily identifiable. Immunohistochemistry revealed CD2+ CD3+ neoplastic T-cells that co-express MUM1 and a subset of CD30, while negative for CD4, CD5, CD8, CD56, ALK1, and TDT. EBV-encoded RNA in-situ hybridization was focally positive. The final postmortem diagnosis was peripheral T-cell lymphoma, not otherwise specified (NOS), with focal EBV positivity. Conclusion Co-existence of a de-novo MDS and non-Hodgkin lymphoma without any prior chemotherapeutic exposure is a highly unusual finding, although MDS-like presentations can occur with EBV-associated lymphomas. Peripheral T-cell lymphoma, NOS is an aggressive lymphoma and EBV positivity has been found correlated with a poor prognosis. This case demonstrates how postmortem examination remains an important tool in clinical- pathological correlation and highlights the potential pathogenetic role EBV plays in MDS and T-cell lymphoma.

scholarly journals Use of immune repertoire sequencing to resolve discordant microscopic and immunochemical findings in a case of T cell-rich large B cell lymphoma in a young dog

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Gary Kwok Cheong Lee ◽  
Dorothee Bienzle ◽  
Stefan Matthias Keller ◽  
Mei-Hua Hwang ◽  
Nikos Darzentas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Repertoire ◽  
Large B Cell Lymphoma ◽  
Repertoire Sequencing ◽  
Reactive Lymphocytes ◽  
Large B Cell

Abstract Background Lymphocytic neoplasms with frequent reactive lymphocytes are uncommonly reported in dogs, and can pose a diagnostic challenge. Different diagnostic modalities such as cytology, flow cytometry, histopathology, immunohistochemistry, and clonality testing, are sometimes required for a diagnosis. This report illustrates the value of using a multi-modal diagnostic approach to decipher a complex lymphocytic tumor, and introduces immune repertoire sequencing as a diagnostic adjunct. Case presentation A 10-month-old Great Dane was referred for marked ascites. Cytologic analysis of abdominal fluid and hepatic aspirates revealed a mixed lymphocyte population including numerous large lymphocytes, yielding a diagnosis of lymphoma. Flow cytometrically, abdominal fluid lymphocytes were highly positive for CD4, CD5, CD18, CD45, and MHC II, consistent with T cell lymphoma. Due to a rapidly deteriorating clinical condition, the dog was euthanized. Post mortem histologic evaluation showed effacement of the liver by aggregates of B cells surrounded by T cells, suggestive of hepatic T cell-rich large B cell lymphoma. Immune repertoire sequencing confirmed the presence of clonal B cells in the liver but not the abdominal fluid, whereas reactive T cells with shared, polyclonal immune repertoires were found in both locations. Conclusions T cell-rich large B cell lymphoma is a rare neoplasm in dogs that may be challenging to diagnose and classify due to mixed lymphocyte populations. In this case, the results of histopathology, immunohistochemistry and immune repertoire sequencing were most consistent with a hepatic B cell neoplasm and reactive T cells exfoliating into the abdominal fluid. Immune repertoire sequencing was helpful in delineating neoplastic from reactive lymphocytes and characterizing repertoire overlap in both compartments. The potential pitfalls of equating atypical cytomorphology and monotypic marker expression in neoplasia are highlighted.

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