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Ahmet Dogan - One of the best experts on this subject based on the ideXlab platform.
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molecular genetic analysis with flow cytometry sorting identifies Angioimmunoblastic t cell Lymphoma and concomitant de novo myelodysplastic syndrome arising from the same hematopoietic progenitor
Journal of hematology, 2020Co-Authors: Ken Naganuma, Ahmet Dogan, Natasha Lewis, Masahiro Kizaki, Alexander Chan, Yanming Zhang, Wenbin Xiao, Mikhail Roshal, Mariko YabeAbstract:A 75-year-old man with no prior history of cytotoxic therapy presented with increasing fatigue and shortness of breath. He was found to have a new onset of pancytopenia, and chest X-ray showed severe pneumonia. Additional radiology exam revealed pan-lobar pneumonia, pleural effusion, generalized lymphadenopathy and mild splenomegaly. Bone marrow and mediastinal lymph node biopsy from the bilateral level 4 lymph nodes were performed to evaluate the cause of pancytopenia and generalized lymphadenopathy, respectively. Histologic sections of lymph nodes were consistent with Angioimmunoblastic T-Cell Lymphoma (AITL), and bone marrow biopsy showed low level involvement by AITL. Background trilineage hematopoiesis showed features suggestive of myelodysplastic syndrome (MDS) with karyotyping showing deletion 20q; however, interpretation of dysplasia and exclusion of reactive process was difficult due to the presence of severe infection, administration of multiple medications and multiorgan failure. Therefore, to further evaluate the possibility of concomitant myeloid neoplasm, we performed flow cytometry sorting of bone marrow aspirate to isolate the myeloid cell population from the abnormal T-Cell population, and comprehensive genomic profiling was performed in each population separately. Flow-sorted myeloid population showed three somatic mutations involving DNMT3A and BCORL1, supporting the diagnosis of MDS in conjunction with the presence of deletion 20q. Flow sorted abnormal T-Cell population showed six somatic mutations consistent with AITL, involving Ras homolog gene family member A (RHOA), TET2, DNMT3A, NOTCH2 and XPO1. These two sorted populations shared the DNMT3A p.N612Rfs*26 mutation, and the variants unique to one sorted population were confirmed to be completely absent in another sorted population by manual review of the sample. These findings suggested that the two neoplasms were clonally related and were sharing a common hematopoietic progenitor precursor, but underwent clonal divergence over time, leading to the development of two distinct neoplastic processes of T and myeloid lineages. This illustrates a rare case of concurrent diagnosis of AITL and de novo MDS and reliable genomic assessment was performed at the time of diagnosis to detect mutations in each neoplastic process without contamination. Further studies are needed to assess hypomethylating agents as potential therapy options for these patients.
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romidepsin activity in t follicular helper tfh phenotype ptcl versus non tfh treated on the same clinical trials
Journal of Clinical Oncology, 2018Co-Authors: Paola Ghione, Ahmet Dogan, Neval Ozkaya, Alison J. Moskowitz, Neha Mehtashah, Matthew A Lunning, Jia Ruan, Promie Faruque, Natasha Galasso, Steven M HorwitzAbstract:7509Background: Histone-deacetylase inhibitors are active agents for peripheral T-Cell Lymphomas (PTCL). Anecdotally, Angioimmunoblastic T-Cell Lymphoma (AITL) may respond better to romidepsin than...
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Histologic Evolution of Angioimmunoblastic T-Cell Lymphoma in Consecutive Biopsies: Clinical Correlation and Insights Into Natural History and Disease Progression
2015Co-Authors: Ayoma D Attygalle, T C Diss, Jehan Dupuis, Charalampia Kyriakou, Karen Lynne Z Grogg, Andrew Charles Wotherspoon, Peter Gershon Isaacson, Ahmet DoganAbstract:Abstract: Angioimmunoblastic T-Cell Lymphoma (AITL) is an uncommon, but aggressive nodal peripheral T-Cell Lymphoma. Little is known of its biology and its natural history has been poorly studied. We report the first comprehensive study on the natural history/histologic progression of AITL by reviewing consecutive biopsies in 31 cases. Immunostaining for CD3, CD20, CD10 and CD21, CD23, CNA-42, CD4, CD8, and Ki 67, in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA and polymerase chain reaction for T-clonality and B-clonality were performed. Histologic progression from AITL with limited nodal involvement and hyperplastic follicles (pattern I) to typical AITL with or without regressed follicles (patterns II and III) was observed in 7 cases, one of which relapsed subsequently as pattern I. Thirteen cases showed typical AITL at presentation and follow-up. Eleven cases where polymerase chain reaction results for T-Cell receptor-g gene rearrangement were directly compared showed an identical band-size in the initial and follow-up biopsies. Seven cases (23%) developed EBV-associated B-cell Lymphomas [5 diffuse large B-cell Lymphoma (DLBCL) and 2 classic Hodgkin Lymphoma]. In 4 cases, a dominant B-cell clone was observed in biopsies lacking evidence of DLBCL. A single case was complicated by EBV-negative DLBCL, whereas another with large cell transformation had a T-Cell phenotype. In conclusion, AITL represents a clonal T-Cell proliferation with a stable T-Cell clone throughout the disease. Partial nodal involvement with hyperplastic follicles is seen in early AITL and at relapse. When ‘‘morphologic high-grade transformation’ ’ occurs, it is usually due to a secondary (often EBV-associated) B-cell Lymphoma, rather than a T-Cell neoplasm. Key Words: Angioimmunoblastic T-Cell Lymphoma, progression, natural histor
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distinguishing Angioimmunoblastic t cell Lymphoma from peripheral t cell Lymphoma unspecified using morphology immunophenotype and molecular genetics
Histopathology, 2007Co-Authors: Ayoma D Attygalle, S S Chuang, T C Diss, P G Isaacson, Ahmet DoganAbstract:Distinguishing Angioimmunoblastic T-Cell Lymphoma from peripheral T-Cell Lymphoma, unspecified, using morphology, immunophenotype and molecular genetics Aims: To identify distinguishing histological, immunophenotypic and molecular genetic features between Angioimmunoblastic T-Cell Lymphoma (AITL) and peripheral T-Cell Lymphoma (PTL). Methods: Nodal T-Cell Lymphomas examined (n =137), included AITL (n = 89), PTL (n = 22), anaplastic large cell Lymphoma (n = 16) and 'AITL/PTL indeterminate' (n = 10) with overlapping features between AITL and PTL, showing morphology typical of AITL but lacking follicular dendritic cell expansion. Immunohistochemistry for CD3, CD20, CD21 and CD10, in situ hybridization for Epstein-Barr virus encoded RNA (EBER) and polymerase chain reaction for T-Cell and B-cell clonality analysis were performed. Results: Of the AITLs, 74/89 showed typical morphology, whereas 15/89 showed hyperplastic follicles. AITL and 'AITL/PTL indeterminate' showed a polymorphous infiltrate and prominent vascularity in all cases. In both groups, CD10 was present in the majority and clear cells and EBER positivity were specific (but not universal) features lacking in PTL. Detection of T-Cell clonality was significantly higher in AITL (90%) compared with PTLu (59%). Conclusions: Clear cells and EBV infection (when present) are useful distinguishing features and CD10 a sensitive and specific marker of AITL. Hyperplastic follicles are present in a significant minority of AITL. AITL/PTL indeterminate probably falls within the spectrum of AITL rather than PTL.
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expression of cxcl13 a chemokine highly upregulated in germinal center t helper cells distinguishes Angioimmunoblastic t cell Lymphoma from peripheral t cell Lymphoma unspecified
Modern Pathology, 2006Co-Authors: Karen L Grogg, Ayoma D Attygalle, William R Macon, Ellen D Remstein, Paul J Kurtin, Ahmet DoganAbstract:The germinal center T-helper cell has been proposed as the cell of origin for Angioimmunoblastic T-Cell Lymphoma. Our recent report of expression of CXCL13, a chemokine critical for germinal center formation and one of the most highly upregulated genes in the germinal center T-helper cell subset, in the majority of Angioimmunoblastic T-Cell Lymphoma cases, provided further support for this theory. To determine the specifity of this marker for Angioimmunoblastic T-Cell Lymphoma, we evaluated CXCL13 expression in 26 nodal-based peripheral T-Cell Lymphomas and 14 lymph nodes showing paracortical lymphoid hyperplasia. No significant paracortical CXCL13 staining was seen in the reactive lymph nodes. By WHO classification criteria, 20 of the Lymphoma cases were considered peripheral T-Cell Lymphoma, unspecified, and six were reclassified as Angioimmunoblastic T-Cell Lymphoma after immunohistochemical detection of disorganized follicular dendritic cell meshworks. Combining the results of our studies, 31 of 35 Angioimmunoblastic T-Cell Lymphoma cases (89%) showed CXCL13 expression, in contrast to two out of 20 peripheral T-Cell Lymphoma, unspecified cases (10%). The two peripheral T-Cell Lymphoma, unspecified cases that were positive for CXCL13 showed a Lennert Lymphoma-like histology. While these cases did not meet all histologic criteria for Angioimmunoblastic T-Cell Lymphoma, they did show an increase in EBV-positive B cells, suggesting they may be histologic variants of Angioimmunoblastic T-Cell Lymphoma. In conclusion, CXCL13 expression is a distinctive feature of Angioimmunoblastic T-Cell Lymphoma, providing further support for the germinal center T-helper cell as the cell of origin for this neoplasm. Given its specificity when compared to cases of peripheral T-Cell Lymphoma, unspecified as well as paracortical lymphoid hyperplasia, it may be a useful marker in the diagnosis of Angioimmunoblastic T-Cell Lymphoma.
Shiyong Li - One of the best experts on this subject based on the ideXlab platform.
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peripheral blood polyclonal plasmacytosis mimicking plasma cell leukemia in patients with Angioimmunoblastic t cell Lymphoma report of 3 cases and review of the literature
International Journal of Clinical and Experimental Pathology, 2011Co-Authors: Arshad N Ahsanuddin, Russell K. Brynes, Shiyong LiAbstract:Angioimmunoblastic T-Cell Lymphoma (AITL) is a unique type of peripheral T-Cell Lymphoma. Patients with AITL may have occasional reactive plasma cells present in the peripheral circulation. Prominent peripheral blood polyclonal plasmacytosis mimicking plasma cell leukemia, however, is distinctly uncommon. Here we describe 3 such cases from two large tertiary medical centers and discuss the role of ancillary studies in the differential diagnosis of peripheral blood plasmacytosis.
Jehan Dupuis - One of the best experts on this subject based on the ideXlab platform.
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Histologic Evolution of Angioimmunoblastic T-Cell Lymphoma in Consecutive Biopsies: Clinical Correlation and Insights Into Natural History and Disease Progression
2015Co-Authors: Ayoma D Attygalle, T C Diss, Jehan Dupuis, Charalampia Kyriakou, Karen Lynne Z Grogg, Andrew Charles Wotherspoon, Peter Gershon Isaacson, Ahmet DoganAbstract:Abstract: Angioimmunoblastic T-Cell Lymphoma (AITL) is an uncommon, but aggressive nodal peripheral T-Cell Lymphoma. Little is known of its biology and its natural history has been poorly studied. We report the first comprehensive study on the natural history/histologic progression of AITL by reviewing consecutive biopsies in 31 cases. Immunostaining for CD3, CD20, CD10 and CD21, CD23, CNA-42, CD4, CD8, and Ki 67, in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA and polymerase chain reaction for T-clonality and B-clonality were performed. Histologic progression from AITL with limited nodal involvement and hyperplastic follicles (pattern I) to typical AITL with or without regressed follicles (patterns II and III) was observed in 7 cases, one of which relapsed subsequently as pattern I. Thirteen cases showed typical AITL at presentation and follow-up. Eleven cases where polymerase chain reaction results for T-Cell receptor-g gene rearrangement were directly compared showed an identical band-size in the initial and follow-up biopsies. Seven cases (23%) developed EBV-associated B-cell Lymphomas [5 diffuse large B-cell Lymphoma (DLBCL) and 2 classic Hodgkin Lymphoma]. In 4 cases, a dominant B-cell clone was observed in biopsies lacking evidence of DLBCL. A single case was complicated by EBV-negative DLBCL, whereas another with large cell transformation had a T-Cell phenotype. In conclusion, AITL represents a clonal T-Cell proliferation with a stable T-Cell clone throughout the disease. Partial nodal involvement with hyperplastic follicles is seen in early AITL and at relapse. When ‘‘morphologic high-grade transformation’ ’ occurs, it is usually due to a secondary (often EBV-associated) B-cell Lymphoma, rather than a T-Cell neoplasm. Key Words: Angioimmunoblastic T-Cell Lymphoma, progression, natural histor
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Peripheral T-Cell Lymphomas with a follicular growth pattern are derived from follicular helper T cells (TFH) and may show overlapping features with Angioimmunoblastic T-Cell Lymphomas.
American Journal of Surgical Pathology, 2009Co-Authors: Yenlin Huang, Jehan Dupuis, Berthold Streubel, Anne Moreau, Barbara Petit, Steven Le Gouill, Nadine Martin-garcia, Christiane Copie-bergman, Fanny Gaillard, Marwan QubajaAbstract:Rare cases of peripheral T-Cell Lymphomas with follicular growth pattern (PTCL-F) have been recently reported, and their association with t(5;9)(q33;q22) involving ITK and SYK has been suggested. However, the clinicopathologic aspects of PTCL-F are poorly described and the normal cell counterpart of this subgroup of Lymphoma is still unknown. Therefore, we analyzed the pathologic, phenotypic, and cytogenetic features of a series of 30 patients (range: 33 to 88 y) that showed histopathologic features of PTCL-F in at least 1 biopsy (n=30), either at initial presentation (n=26) or at relapse (n=4). Neoplastic cells were medium-sized clear cells that were CD4+ (24/27, 89%), CD10+ (21/29, 72%), BCL-6+ (14/19, 74%), and expressed programed death-1 (27/27, 100%), CXCL13 (23/27, 85%), and ICOS (11/11, 100%), markers of follicular helper T cells (TFH). Four of 22 patients (18%) had t(5;9)(q33;q22) detected by fluorescence in situ hybridization. Patients with clinical data available had multiple lymphadenopathies (25/28, 89%), stage III to IV diseases (17/26, 65%), B symptoms (7/27, 26%), and skin lesions (6/23, 26%). Three patients with sequential biopsies disclosed clinical and histopathologic features of Angioimmunoblastic T-Cell Lymphoma at initial presentation. Our results show that this rare form of PTCL-F (1) has an immunophenotype indicative of derivation from TFH cells, (2) is associated with t(5;9) in a proportion of cases, and (3) shows some overlapping features with Angioimmunoblastic T-Cell Lymphoma, raising the question of a possible relationship.
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characterization of cxcl13 neoplastic t cells in cutaneous lesions of Angioimmunoblastic t cell Lymphoma aitl
The American Journal of Surgical Pathology, 2007Co-Authors: N Ortonne, Jehan Dupuis, Nadine Martin, Christiane Copiebergman, Anne Plonquet, Corinne Haioun, Mariehelene Delfaularue, M Bagot, Alain Gaulier, J WechslerAbstract:Skin manifestations of Angioimmunoblastic T-Cell Lymphoma (AITL) are frequent, sometimes as first manifestations of the disease. In the absence of a specific marker for neoplastic cells, diagnosis of AITL in skin biopsies is often difficult. CD10 and CXCL13 have been recently recognized as characteristic markers of AITL, but have not been yet investigated in the skin. We analyzed 15 skin biopsies from 8 patients with AITL having skin manifestations and compared them to 14 skin biopsies from patients with various cutaneous lymphocytic infiltrates. A few CD10 lymphocytes were found in only 2 samples of the AITL group, the identification of which was hampered by the presence of a dermal CD10 cell population with dendritic features. By contrast, CXCL13 lymphoid cells were identified in most AITL cutaneous biopsies (n=12, 80%), whereas, absent in all samples from control cases. Among 12 biopsies with CXCL13 cells, cutaneous involvement by AITL was suspected in only 5 on the basis of light microscopy and classic immunophenotyping. In another case, a diagnosis of cutaneous marginal zone B-cell Lymphoma had been proposed. In conclusion, this study shows that neoplastic AITL CXCL13 T cells localize in the skin and that accurate diagnosis of AITL lesions can be done in skin specimens using CXCL13 immunostaining on paraffin-embedded tissues.
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histologic evolution of Angioimmunoblastic t cell Lymphoma in consecutive biopsies clinical correlation and insights into natural history and disease progression
The American Journal of Surgical Pathology, 2007Co-Authors: Ayoma D Attygalle, Peter G Isaacson, T C Diss, Karen L Grogg, Jehan Dupuis, Charalampia Kyriakou, Andrew Wotherspoon, Shih Sung Chuang, Jose Cabecadas, Philippe GaulardAbstract:Angioimmunoblastic T-Cell Lymphoma (AITL) is an uncommon, but aggressive nodal peripheral T-Cell Lymphoma. Little is known of its biology and its natural history has been poorly studied. We report the first comprehensive study on the natural history/histologic progression of AITL by reviewing consecutive biopsies in 31 cases. Immunostaining for CD3, CD20, CD10 and CD21, CD23, CNA-42, CD4, CD8, and Ki 67, in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA and polymerase chain reaction for T-clonality and B-clonality were performed. Histologic progression from AITL with limited nodal involvement and hyperplastic follicles (pattern I) to typical AITL with or without regressed follicles (patterns II and III) was observed in 7 cases, one of which relapsed subsequently as pattern I. Thirteen cases showed typical AITL at presentation and follow-up. Eleven cases where polymerase chain reaction results for T-Cell receptor-gamma gene rearrangement were directly compared showed an identical band-size in the initial and follow-up biopsies. Seven cases (23%) developed EBV-associated B-cell Lymphomas [5 diffuse large B-cell Lymphoma (DLBCL) and 2 classic Hodgkin Lymphoma]. In 4 cases, a dominant B-cell clone was observed in biopsies lacking evidence of DLBCL. A single case was complicated by EBV-negative DLBCL, whereas another with large cell transformation had a T-Cell phenotype. In conclusion, AITL represents a clonal T-Cell proliferation with a stable T-Cell clone throughout the disease. Partial nodal involvement with hyperplastic follicles is seen in early AITL and at relapse. When "morphologic high-grade transformation" occurs, it is usually due to a secondary (often EBV-associated) B-cell Lymphoma, rather than a T-Cell neoplasm.
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expression of cxcl13 by neoplastic cells in Angioimmunoblastic t cell Lymphoma aitl a new diagnostic marker providing evidence that aitl derives from follicular helper t cells
The American Journal of Surgical Pathology, 2006Co-Authors: Jehan Dupuis, Karine Boye, Nadine Martin, Christiane Copiebergman, Anne Plonquet, Bettina Fabiani, Annecatherine Baglin, Corinne Haioun, Mariehelene Delfaularue, Philippe GaulardAbstract:Angioimmunoblastic T-Cell Lymphoma (AITL) represents a distinct entity among peripheral T-Cell Lymphomas (PTCLs). The cellular origin of AITL remains unknown, although a possible derivation from follicular helper T cells (TFH) has been suggested based on the CD4/Bcl-6 phenotype. It has been recently
Philippe Gaulard - One of the best experts on this subject based on the ideXlab platform.
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histologic evolution of Angioimmunoblastic t cell Lymphoma in consecutive biopsies clinical correlation and insights into natural history and disease progression
The American Journal of Surgical Pathology, 2007Co-Authors: Ayoma D Attygalle, Peter G Isaacson, T C Diss, Karen L Grogg, Jehan Dupuis, Charalampia Kyriakou, Andrew Wotherspoon, Shih Sung Chuang, Jose Cabecadas, Philippe GaulardAbstract:Angioimmunoblastic T-Cell Lymphoma (AITL) is an uncommon, but aggressive nodal peripheral T-Cell Lymphoma. Little is known of its biology and its natural history has been poorly studied. We report the first comprehensive study on the natural history/histologic progression of AITL by reviewing consecutive biopsies in 31 cases. Immunostaining for CD3, CD20, CD10 and CD21, CD23, CNA-42, CD4, CD8, and Ki 67, in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA and polymerase chain reaction for T-clonality and B-clonality were performed. Histologic progression from AITL with limited nodal involvement and hyperplastic follicles (pattern I) to typical AITL with or without regressed follicles (patterns II and III) was observed in 7 cases, one of which relapsed subsequently as pattern I. Thirteen cases showed typical AITL at presentation and follow-up. Eleven cases where polymerase chain reaction results for T-Cell receptor-gamma gene rearrangement were directly compared showed an identical band-size in the initial and follow-up biopsies. Seven cases (23%) developed EBV-associated B-cell Lymphomas [5 diffuse large B-cell Lymphoma (DLBCL) and 2 classic Hodgkin Lymphoma]. In 4 cases, a dominant B-cell clone was observed in biopsies lacking evidence of DLBCL. A single case was complicated by EBV-negative DLBCL, whereas another with large cell transformation had a T-Cell phenotype. In conclusion, AITL represents a clonal T-Cell proliferation with a stable T-Cell clone throughout the disease. Partial nodal involvement with hyperplastic follicles is seen in early AITL and at relapse. When "morphologic high-grade transformation" occurs, it is usually due to a secondary (often EBV-associated) B-cell Lymphoma, rather than a T-Cell neoplasm.
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expression of cxcl13 by neoplastic cells in Angioimmunoblastic t cell Lymphoma aitl a new diagnostic marker providing evidence that aitl derives from follicular helper t cells
The American Journal of Surgical Pathology, 2006Co-Authors: Jehan Dupuis, Karine Boye, Nadine Martin, Christiane Copiebergman, Anne Plonquet, Bettina Fabiani, Annecatherine Baglin, Corinne Haioun, Mariehelene Delfaularue, Philippe GaulardAbstract:Angioimmunoblastic T-Cell Lymphoma (AITL) represents a distinct entity among peripheral T-Cell Lymphomas (PTCLs). The cellular origin of AITL remains unknown, although a possible derivation from follicular helper T cells (TFH) has been suggested based on the CD4/Bcl-6 phenotype. It has been recently
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expression of cxcl13 by neoplastic cells in Angioimmunoblastic t cell Lymphoma aitl a new diagnostic marker providing evidence that aitl derives from follicular helper t cells
The American Journal of Surgical Pathology, 2006Co-Authors: Jehan Dupuis, Karine Boye, Nadine Martin, Christiane Copiebergman, Anne Plonquet, Bettina Fabiani, Annecatherine Baglin, Corinne Haioun, Mariehelene Delfaularue, Philippe GaulardAbstract:Angioimmunoblastic T-Cell Lymphoma (AITL) represents a distinct entity among peripheral T-Cell Lymphomas (PTCLs). The cellular origin of AITL remains unknown, although a possible derivation from follicular helper T cells (TFH) has been suggested based on the CD4/Bcl-6 phenotype. It has been recently shown that expression of CXCL13, a chemokine critically involved in B-cell migration into germinal centers, is characteristic of TFH cells, as compared with other T helper subsets. We compared CXCL13 expression in 29 AITLs, 20 PTCLs, unspecified, 10 anaplastic large cell Lymphomas (ALCL), and 4 other PTCLs. We showed that CXCL13 is expressed by AITL (29 of 29, 100%) and a subset of PTCL, unspecified (6 of 20, 30%), which all showed borderline features with AITL, but in only 1 of 10 (10%) ALCLs, and 0 of 4 other PTCLs. Two-color immunostainings further showed that CXCL13 was found in the cytoplasm of atypical CD5-positive T cells that expressed CD10. We conclude that CXCL13 expression is a common characteristic of AITL, which can help to delineate the morphologic spectrum of the disease, and further supports its derivation from TFH cells. CXCL13 expression may also provide an additional useful tool for the diagnosis of AITL.
Ayoma D Attygalle - One of the best experts on this subject based on the ideXlab platform.
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Histologic Evolution of Angioimmunoblastic T-Cell Lymphoma in Consecutive Biopsies: Clinical Correlation and Insights Into Natural History and Disease Progression
2015Co-Authors: Ayoma D Attygalle, T C Diss, Jehan Dupuis, Charalampia Kyriakou, Karen Lynne Z Grogg, Andrew Charles Wotherspoon, Peter Gershon Isaacson, Ahmet DoganAbstract:Abstract: Angioimmunoblastic T-Cell Lymphoma (AITL) is an uncommon, but aggressive nodal peripheral T-Cell Lymphoma. Little is known of its biology and its natural history has been poorly studied. We report the first comprehensive study on the natural history/histologic progression of AITL by reviewing consecutive biopsies in 31 cases. Immunostaining for CD3, CD20, CD10 and CD21, CD23, CNA-42, CD4, CD8, and Ki 67, in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA and polymerase chain reaction for T-clonality and B-clonality were performed. Histologic progression from AITL with limited nodal involvement and hyperplastic follicles (pattern I) to typical AITL with or without regressed follicles (patterns II and III) was observed in 7 cases, one of which relapsed subsequently as pattern I. Thirteen cases showed typical AITL at presentation and follow-up. Eleven cases where polymerase chain reaction results for T-Cell receptor-g gene rearrangement were directly compared showed an identical band-size in the initial and follow-up biopsies. Seven cases (23%) developed EBV-associated B-cell Lymphomas [5 diffuse large B-cell Lymphoma (DLBCL) and 2 classic Hodgkin Lymphoma]. In 4 cases, a dominant B-cell clone was observed in biopsies lacking evidence of DLBCL. A single case was complicated by EBV-negative DLBCL, whereas another with large cell transformation had a T-Cell phenotype. In conclusion, AITL represents a clonal T-Cell proliferation with a stable T-Cell clone throughout the disease. Partial nodal involvement with hyperplastic follicles is seen in early AITL and at relapse. When ‘‘morphologic high-grade transformation’ ’ occurs, it is usually due to a secondary (often EBV-associated) B-cell Lymphoma, rather than a T-Cell neoplasm. Key Words: Angioimmunoblastic T-Cell Lymphoma, progression, natural histor
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histologic evolution of Angioimmunoblastic t cell Lymphoma in consecutive biopsies clinical correlation and insights into natural history and disease progression
The American Journal of Surgical Pathology, 2007Co-Authors: Ayoma D Attygalle, Peter G Isaacson, T C Diss, Karen L Grogg, Jehan Dupuis, Charalampia Kyriakou, Andrew Wotherspoon, Shih Sung Chuang, Jose Cabecadas, Philippe GaulardAbstract:Angioimmunoblastic T-Cell Lymphoma (AITL) is an uncommon, but aggressive nodal peripheral T-Cell Lymphoma. Little is known of its biology and its natural history has been poorly studied. We report the first comprehensive study on the natural history/histologic progression of AITL by reviewing consecutive biopsies in 31 cases. Immunostaining for CD3, CD20, CD10 and CD21, CD23, CNA-42, CD4, CD8, and Ki 67, in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA and polymerase chain reaction for T-clonality and B-clonality were performed. Histologic progression from AITL with limited nodal involvement and hyperplastic follicles (pattern I) to typical AITL with or without regressed follicles (patterns II and III) was observed in 7 cases, one of which relapsed subsequently as pattern I. Thirteen cases showed typical AITL at presentation and follow-up. Eleven cases where polymerase chain reaction results for T-Cell receptor-gamma gene rearrangement were directly compared showed an identical band-size in the initial and follow-up biopsies. Seven cases (23%) developed EBV-associated B-cell Lymphomas [5 diffuse large B-cell Lymphoma (DLBCL) and 2 classic Hodgkin Lymphoma]. In 4 cases, a dominant B-cell clone was observed in biopsies lacking evidence of DLBCL. A single case was complicated by EBV-negative DLBCL, whereas another with large cell transformation had a T-Cell phenotype. In conclusion, AITL represents a clonal T-Cell proliferation with a stable T-Cell clone throughout the disease. Partial nodal involvement with hyperplastic follicles is seen in early AITL and at relapse. When "morphologic high-grade transformation" occurs, it is usually due to a secondary (often EBV-associated) B-cell Lymphoma, rather than a T-Cell neoplasm.
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distinguishing Angioimmunoblastic t cell Lymphoma from peripheral t cell Lymphoma unspecified using morphology immunophenotype and molecular genetics
Histopathology, 2007Co-Authors: Ayoma D Attygalle, S S Chuang, T C Diss, P G Isaacson, Ahmet DoganAbstract:Distinguishing Angioimmunoblastic T-Cell Lymphoma from peripheral T-Cell Lymphoma, unspecified, using morphology, immunophenotype and molecular genetics Aims: To identify distinguishing histological, immunophenotypic and molecular genetic features between Angioimmunoblastic T-Cell Lymphoma (AITL) and peripheral T-Cell Lymphoma (PTL). Methods: Nodal T-Cell Lymphomas examined (n =137), included AITL (n = 89), PTL (n = 22), anaplastic large cell Lymphoma (n = 16) and 'AITL/PTL indeterminate' (n = 10) with overlapping features between AITL and PTL, showing morphology typical of AITL but lacking follicular dendritic cell expansion. Immunohistochemistry for CD3, CD20, CD21 and CD10, in situ hybridization for Epstein-Barr virus encoded RNA (EBER) and polymerase chain reaction for T-Cell and B-cell clonality analysis were performed. Results: Of the AITLs, 74/89 showed typical morphology, whereas 15/89 showed hyperplastic follicles. AITL and 'AITL/PTL indeterminate' showed a polymorphous infiltrate and prominent vascularity in all cases. In both groups, CD10 was present in the majority and clear cells and EBER positivity were specific (but not universal) features lacking in PTL. Detection of T-Cell clonality was significantly higher in AITL (90%) compared with PTLu (59%). Conclusions: Clear cells and EBV infection (when present) are useful distinguishing features and CD10 a sensitive and specific marker of AITL. Hyperplastic follicles are present in a significant minority of AITL. AITL/PTL indeterminate probably falls within the spectrum of AITL rather than PTL.
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expression of cxcl13 a chemokine highly upregulated in germinal center t helper cells distinguishes Angioimmunoblastic t cell Lymphoma from peripheral t cell Lymphoma unspecified
Modern Pathology, 2006Co-Authors: Karen L Grogg, Ayoma D Attygalle, William R Macon, Ellen D Remstein, Paul J Kurtin, Ahmet DoganAbstract:The germinal center T-helper cell has been proposed as the cell of origin for Angioimmunoblastic T-Cell Lymphoma. Our recent report of expression of CXCL13, a chemokine critical for germinal center formation and one of the most highly upregulated genes in the germinal center T-helper cell subset, in the majority of Angioimmunoblastic T-Cell Lymphoma cases, provided further support for this theory. To determine the specifity of this marker for Angioimmunoblastic T-Cell Lymphoma, we evaluated CXCL13 expression in 26 nodal-based peripheral T-Cell Lymphomas and 14 lymph nodes showing paracortical lymphoid hyperplasia. No significant paracortical CXCL13 staining was seen in the reactive lymph nodes. By WHO classification criteria, 20 of the Lymphoma cases were considered peripheral T-Cell Lymphoma, unspecified, and six were reclassified as Angioimmunoblastic T-Cell Lymphoma after immunohistochemical detection of disorganized follicular dendritic cell meshworks. Combining the results of our studies, 31 of 35 Angioimmunoblastic T-Cell Lymphoma cases (89%) showed CXCL13 expression, in contrast to two out of 20 peripheral T-Cell Lymphoma, unspecified cases (10%). The two peripheral T-Cell Lymphoma, unspecified cases that were positive for CXCL13 showed a Lennert Lymphoma-like histology. While these cases did not meet all histologic criteria for Angioimmunoblastic T-Cell Lymphoma, they did show an increase in EBV-positive B cells, suggesting they may be histologic variants of Angioimmunoblastic T-Cell Lymphoma. In conclusion, CXCL13 expression is a distinctive feature of Angioimmunoblastic T-Cell Lymphoma, providing further support for the germinal center T-helper cell as the cell of origin for this neoplasm. Given its specificity when compared to cases of peripheral T-Cell Lymphoma, unspecified as well as paracortical lymphoid hyperplasia, it may be a useful marker in the diagnosis of Angioimmunoblastic T-Cell Lymphoma.
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neoplastic t cells in Angioimmunoblastic t cell Lymphoma express cd10
Blood, 2002Co-Authors: Ayoma D Attygalle, Peter G Isaacson, T C Diss, Rajai Aljehani, P Munson, Hongxiang Liu, Ahmet DoganAbstract:Angioimmunoblastic T-Cell Lymphoma (AITL) is a systemic disease involving lymph nodes, spleen, and bone marrow. Although the histologic features have been well described, the diagnosis is often challenging, as there are no specific phenotypic or molecular markers available. This study shows that the neoplastic cells of AITL can be identified by aberrant CD10 expression. Archival material from 30 cases of AITL, 10 cases of peripheral T-Cell Lymphoma unspecified (PTL), and 10 cases of reactive lymphoid hyperplasia were reviewed. Single and double immunostaining for CD3, CD4, CD8, CD20, CD21, CD10, BCL6, Ki67, and LMP-1 in situ hybridization for Epstein-Barr early region and polymerase chain reaction (PCR) for T-Cell receptor gamma chain gene and immunoglobulin heavy chain gene were performed. Three overlapping histologic patterns with hyperplastic follicles, depleted follicles, or without follicles were identified in AITL. Of the 30 cases of AITL, 27 contained CD10 + T cells. No CD10 + T cells were present in the cases of PTL or reactive hyperplasia. PCR confirmed a monoclonal or oligoclonal T-Cell population in 29 of 30 cases of AITL and a monoclonal B-cell population in 6 cases. Analysis of microdissected CD10 + single cells showed that they belonged to the neoplastic clone. In conclusion CD10 is a phenotypic marker that specifically identifies the tumor cells in 90% of AITL, including the early cases. The presence of these cells distinguishes AITL from other PTLs. This finding provides an objective criterion for accurate and early diagnosis of AITL.