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Ahmet Dogan - One of the best experts on this subject based on the ideXlab platform.
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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.
Joanne Ngeow - One of the best experts on this subject based on the ideXlab platform.
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comparative analysis of extra nodal nk t cell Lymphoma and peripheral t cell Lymphoma significant differences in clinical characteristics and prognosis
European Journal of Haematology, 2007Co-Authors: Soon Thye Lim, Siew Wan Hee, Richard Quek, Lay Cheng Lim, Swee Peng Yap, Erli Loong, Ivy Sng, Leonard Tan, Meikim Ang, Joanne NgeowAbstract:Aim: We aimed to compare the frequencies, clinical characteristics, and prognostic factors of peripheral T-Cell Lymphoma (PTCL) vs. extra-nodal natural killer (NK)/T-Cell Lymphoma and to characterize the subtypes of extra-nodal NK/T-Cell Lymphoma. Methods: We reviewed 97 consecutive patients with PTCL and extra-nodal NKT Lymphoma from 2000 to 2006. During this period, a total of 780 patients with malignant Lymphomas were treated in our center. The diagnostic criteria used were based on the WHO classification system of malignant Lymphomas. Results: Extra-nodal-NK/T-Cell Lymphoma and PTCL comprised 5.0% (39/780) and 7.4% (58/780) of all cases. Of the PTCL cases, histology was PTCL-NOS in 25, anaplastic large cell in 11, angioimmunoblastic T cell in 18 and other subtypes in four patients. Compared with PTCL, extra-nodal NK/T-Cell Lymphoma was associated with a significantly inferior rates of complete remission (33% vs. 53%, P = 0.05) and 3 yr overall survival (29.5% vs. 47.5%, P = 0.003). On multivariate analysis, extra-nodal NK/T-Cell histology was independently associated with decreased survival. Further analysis into this subtype showed the nasal variant (n = 25) differed significantly from extra-nasal variant (n = 14) in terms of stage at presentation (stages III/IV, 36% vs. 79%), international prognostic index scores (high intermediate or high IPI scores, 24% vs. 64%), complete remission rates (48% vs. 7%), and median survival (10 months vs. 1 month, P < 0.0001). Conclusions: Extra-nodal NK/T-Cell Lymphoma was associated with a poorer prognosis compared with PTCL and is likely to comprise two distinct variants with different clinical behavior and prognosis.
Yusuke Okuno - One of the best experts on this subject based on the ideXlab platform.
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somatic rhoa mutation in angioimmunoblastic t cell Lymphoma
Nature Genetics, 2014Co-Authors: Mamiko Sakatayanagimoto, Terukazu Enami, Kenichi Yoshida, Yuichi Shiraishi, Ryohei Ishii, Yasuyuki Miyake, Hideharu Muto, Naoko Tsuyama, Aiko Satootsubo, Yusuke OkunoAbstract:Shigeru Chiba and colleagues report exome sequencing of angioimmunoblastic T cell Lymphoma (AITL) and other peripheral T cell Lymphomas and identify a recurrent somatic RHOA mutation encoding a p.Gly17Val alteration in 68% of AITL samples.
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somatic rhoa mutation in angioimmunoblastic t cell Lymphoma
Nature Genetics, 2014Co-Authors: Mamiko Sakatayanagimoto, Terukazu Enami, Kenichi Yoshida, Yuichi Shiraishi, Ryohei Ishii, Yasuyuki Miyake, Hideharu Muto, Naoko Tsuyama, Aiko Satootsubo, Yusuke OkunoAbstract:Angioimmunoblastic T cell Lymphoma (AITL) is a distinct subtype of peripheral T cell Lymphoma characterized by generalized lymphadenopathy and frequent autoimmune-like manifestations. Although frequent mutations in TET2, IDH2 and DNMT3A, which are common to various hematologic malignancies, have been identified in AITL, the molecular pathogenesis specific to this Lymphoma subtype is unknown. Here we report somatic RHOA mutations encoding a p.Gly17Val alteration in 68% of AITL samples. Remarkably, all cases with the mutation encoding p.Gly17Val also had TET2 mutations. The RHOA mutation encoding p.Gly17Val was specifically identified in tumor cells, whereas TET2 mutations were found in both tumor cells and non-tumor hematopoietic cells. RHOA encodes a small GTPase that regulates diverse biological processes. We demonstrated that the Gly17Val RHOA mutant did not bind GTP and also inhibited wild-type RHOA function. Our findings suggest that impaired RHOA function in cooperation with preceding loss of TET2 function contributes to AITL-specific pathogenesis.
Thomas Rüdiger - One of the best experts on this subject based on the ideXlab platform.
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clinicopathologic characteristics of angioimmunoblastic t cell Lymphoma analysis of the international peripheral t cell Lymphoma project
Journal of Clinical Oncology, 2013Co-Authors: Massimo Federico, Elaine S Jaffe, Nancy Lee Harris, Thomas Rüdiger, Stefano Pileri, Bharat N. Nathwani, Monica Bellei, Stefano Luminari, Bertrand Coiffier, Kerry J. SavageAbstract:Purpose The International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-Cell and natural killer (NK) ‐cell Lymphomas. Patients and Methods Angioimmunoblastic T-Cell Lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated. Results Of 1,314 patients, 243 (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred in 13% and 30% of patients, respectively. Five-year overall and failure-free survivals were 33% and 18%, respectively. At presentation, prognostic models were evaluated, including the standard International Prognostic Index, which comprised the following factors: age 60 years, stages III to IV disease, lactic dehydrogenase (LDH) normal, extranodal sites (ENSs) one, and performance status (PS) 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age 60 years, PS 2, LDH normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age 60 years, PS 2, ENSs one, B symptoms, and platelet count 150 10 9 /L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P .0065). Conclusion AITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies. J Clin Oncol 31:240-246. © 2012 by American Society of Clinical Oncology
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Peripheral T-Cell Lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-Cell Lymphoma Project
Blood, 2011Co-Authors: Dennis D. Weisenburger, Elaine S Jaffe, Shigeo Nakamura, Kerry J. Savage, Nancy Lee Harris, Randy D. Gascoyne, Kenneth A. Maclennan, Thomas Rüdiger, Stefano Pileri, Bharat N. NathwaniAbstract:The International Peripheral T-Cell Lymphoma Project is a collaborative effort to better understand peripheral T-Cell Lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.
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peripheral t cell Lymphoma with progression to a clonally related epstein barr virus cytotoxic aggressive t cell Lymphoma evidence for secondary ebv infection of an established malignant t cell clone
The American Journal of Surgical Pathology, 2010Co-Authors: Rupert Langer, Thomas Rüdiger, Eva Geissinger, Christoph Von Schilling, Sonja Mandlweber, Leticia Quintanillamartinez, Falko FendAbstract:We report a case of primary Epstein Barr virus (EBV) negative peripheral T-Cell Lymphoma (PTCL) NOS in a 56-year-old female who-after an initially indolent course – simultaneously developed an aggressive, EBV+ cytotoxic large T-Cell Lymphoma, clonally related to the primary PTCL, and an EBV+, clonal
Kerry J. Savage - One of the best experts on this subject based on the ideXlab platform.
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clinicopathologic characteristics of angioimmunoblastic t cell Lymphoma analysis of the international peripheral t cell Lymphoma project
Journal of Clinical Oncology, 2013Co-Authors: Massimo Federico, Elaine S Jaffe, Nancy Lee Harris, Thomas Rüdiger, Stefano Pileri, Bharat N. Nathwani, Monica Bellei, Stefano Luminari, Bertrand Coiffier, Kerry J. SavageAbstract:Purpose The International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-Cell and natural killer (NK) ‐cell Lymphomas. Patients and Methods Angioimmunoblastic T-Cell Lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated. Results Of 1,314 patients, 243 (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred in 13% and 30% of patients, respectively. Five-year overall and failure-free survivals were 33% and 18%, respectively. At presentation, prognostic models were evaluated, including the standard International Prognostic Index, which comprised the following factors: age 60 years, stages III to IV disease, lactic dehydrogenase (LDH) normal, extranodal sites (ENSs) one, and performance status (PS) 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age 60 years, PS 2, LDH normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age 60 years, PS 2, ENSs one, B symptoms, and platelet count 150 10 9 /L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P .0065). Conclusion AITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies. J Clin Oncol 31:240-246. © 2012 by American Society of Clinical Oncology
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Peripheral T-Cell Lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-Cell Lymphoma Project
Blood, 2011Co-Authors: Dennis D. Weisenburger, Elaine S Jaffe, Shigeo Nakamura, Kerry J. Savage, Nancy Lee Harris, Randy D. Gascoyne, Kenneth A. Maclennan, Thomas Rüdiger, Stefano Pileri, Bharat N. NathwaniAbstract:The International Peripheral T-Cell Lymphoma Project is a collaborative effort to better understand peripheral T-Cell Lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.
