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Matsumoto NP, Xu ML. Angioimmunoblastic T-cell lymphoma: Current Diagnostic Insights and Advances. Hum Pathol 2025; 156:105696. [PMID: 39571692 DOI: 10.1016/j.humpath.2024.105696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 11/11/2024] [Accepted: 11/18/2024] [Indexed: 11/28/2024]
Abstract
Angioimmunoblastic T-cell lymphoma (AITL), or nodal T-follicular helper cell lymphoma, angioimmunoblastic type, is a rare and aggressive type of T-cell lymphoma characterized by a spectrum of clinical and histopathological features that can present diagnostic challenges. Derived from T-follicular helper cells, the genesis of AITL is thought to be a multistep process involving mutations in epigenetic regulatory genes such as TET2 and DNMT3A, followed by driver mutations in RHOAG17V and IDH2R172 which promote clonal expansion as well as a characteristic inflammatory milieu. This review aims to provide a comprehensive overview of AITL, including its clinical presentation, epidemiology, pathogenesis, histomorphology and treatment options. Despite advancements in the understanding of AITL biology and the development of novel treatment strategies, the prognosis for patients with AITL remains poor.
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Affiliation(s)
- Nana P Matsumoto
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, 3477 Euler Way, Pittsburgh, PA, 15213, USA.
| | - Mina L Xu
- Department of Pathology and Laboratory Medicine, Yale-New Haven Hospital, New Haven, CT, 310 Cedar Street, Ste BML 116C, New Haven, CT, 06510, USA.
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Soilleux EJ, Rodgers DT, Situ JJ, Evans SC, Konda VN, Yang HC, Pang J, Gilbey Smith I, Rajesh P, Salimi M, Ng SW, Jones J, Miller JL, Etherington R, Ashton-Key M, Ogg G. Demonstration of T-Cell Monotypia Using Anti-TCRbeta1/2 ( TRBC1/2) Immunostaining as a Rapid and Cost-Effective Alternative to PCR-Based Clonality Studies for the Diagnosis of T-Cell Lymphoma. Diagnostics (Basel) 2024; 14:2479. [PMID: 39594145 PMCID: PMC11593183 DOI: 10.3390/diagnostics14222479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/03/2024] [Accepted: 11/04/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates, and diagnosis typically relies on slow, complex, and expensive multiplexed PCR reactions, requiring significant training and experience to interpret them. We aimed to raise highly specific antibodies against the two alternatively used and very similar T-cell receptor beta constant regions, TCRbeta1 and TCRbeta2, encoded by the TRBC1 and TRBC2 gene segments, respectively. We sought to demonstrate the feasibility of detecting TCRbeta1 and TCRbeta2 immunohistochemically in routine clinical (formalin-fixed, paraffin-embedded (FFPE)) tissue sections as a novel diagnostic strategy for T-cell lymphomas. METHODS Recombinant rabbit antibodies were validated using Western blotting and FFPE immunostaining of T-cell leukemia lines. The immunostaining of FFPE tissue containing benign and lymphomatous T-cell populations was undertaken, with corroboration by BaseScopeTM high-sensitivity in situ hybridization and quantitative real-time PCR (Q-PCR). An additional Q-PCR literature review and analysis of publicly available RNAseq data was used to determine the TCRbeta2/TCRbeta1 ratio cut-off to separate benign and malignant T-cell populations. RESULTS Our TCRbeta1/TCRbeta2 antibody pair gave highly specific FFPE tissue staining. All benign samples analyzed (immunohistochemically, by BaseScopeTM, by Q-PCR, and by RNAseq data analysis) had TCRbeta1/TCRbeta2 or TRBC1/TRBC2 ranges well within the previously published flow cytometric benign range (TCRbeta2/TCRbeta1 = 0.18:1-5.7:1), while samples of T-cell lymphoma did not. One out of thirteen (7.7%) lymphoma samples showed some detectable TCRbeta1/TCRbeta2 protein co-expression, and 4 out of 13 (30.8%) T-cell lymphomas showed a TRBC1/TRBC2 transcript co-expression using BaseScopeTM. CONCLUSIONS Analyzing T-cell monotypia immunohistochemically, analogous to B-cell monotypia (kappa: lambda ratio for B-cell and plasma cell neoplasms), could make the diagnosis of T-cell lymphomas cheaper, quicker, and more accurate. Larger studies are needed to validate our antibodies for clinical use.
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Affiliation(s)
- Elizabeth J. Soilleux
- Department of Pathology, University of Cambridge, Cambridge CB2 0SP, UK; (J.J.S.); (V.N.K.); (H.-C.Y.); (J.P.); (I.G.S.); (P.R.)
- Haematopathology and Oncology Diagnostic Service (HODS), Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK
| | - Daniel T. Rodgers
- Human Research Tissue Bank, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK;
| | - Jinlong J. Situ
- Department of Pathology, University of Cambridge, Cambridge CB2 0SP, UK; (J.J.S.); (V.N.K.); (H.-C.Y.); (J.P.); (I.G.S.); (P.R.)
| | - Shelley C. Evans
- Department of Pathology, University of Cambridge, Cambridge CB2 0SP, UK; (J.J.S.); (V.N.K.); (H.-C.Y.); (J.P.); (I.G.S.); (P.R.)
| | - Venkata N. Konda
- Department of Pathology, University of Cambridge, Cambridge CB2 0SP, UK; (J.J.S.); (V.N.K.); (H.-C.Y.); (J.P.); (I.G.S.); (P.R.)
| | - Han-Chieh Yang
- Department of Pathology, University of Cambridge, Cambridge CB2 0SP, UK; (J.J.S.); (V.N.K.); (H.-C.Y.); (J.P.); (I.G.S.); (P.R.)
| | - Jianxiong Pang
- Department of Pathology, University of Cambridge, Cambridge CB2 0SP, UK; (J.J.S.); (V.N.K.); (H.-C.Y.); (J.P.); (I.G.S.); (P.R.)
| | - Isabella Gilbey Smith
- Department of Pathology, University of Cambridge, Cambridge CB2 0SP, UK; (J.J.S.); (V.N.K.); (H.-C.Y.); (J.P.); (I.G.S.); (P.R.)
| | - Pete Rajesh
- Department of Pathology, University of Cambridge, Cambridge CB2 0SP, UK; (J.J.S.); (V.N.K.); (H.-C.Y.); (J.P.); (I.G.S.); (P.R.)
| | - Maryam Salimi
- MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; (M.S.); (S.W.N.); (G.O.)
| | - Soo Weei Ng
- MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; (M.S.); (S.W.N.); (G.O.)
| | - Julia Jones
- Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; (J.J.); (J.L.M.)
| | - Jodi L. Miller
- Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; (J.J.); (J.L.M.)
| | - Rachel Etherington
- MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; (M.S.); (S.W.N.); (G.O.)
| | - Margaret Ashton-Key
- Department of Cellular Pathology, University Hospital Southampton, Southampton SO16 6YD, UK;
| | - Graham Ogg
- MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK; (M.S.); (S.W.N.); (G.O.)
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Krug A, Saidane A, Martinello C, Fusil F, Michels A, Buchholz CJ, Ricci JE, Verhoeyen E. In vivo CAR T cell therapy against angioimmunoblastic T cell lymphoma. J Exp Clin Cancer Res 2024; 43:262. [PMID: 39272178 PMCID: PMC11401350 DOI: 10.1186/s13046-024-03179-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 09/03/2024] [Indexed: 09/15/2024] Open
Abstract
BACKGROUND For angioimmunoblastic T cell lymphoma (AITL), a rare cancer, no specific treatments are available and survival outcome is poor. We previously developed a murine model for AITL that mimics closely human disease and allows to evaluate new treatments. As in human AITL, the murine CD4+ follicular helper T (Tfh) cells are drivers of the malignancy. Therefore, chimeric antigen receptor (CAR) T cell therapy might represent a new therapeutic option. METHODS To prevent fratricide among CAR T cells when delivering an CD4-specific CAR, we used a lentiviral vector (LV) encoding an anti-CD4 CAR, allowing exclusive entry into CD8 T cells. RESULTS These anti-CD4CAR CD8-targeted LVs achieved in murine AITL biopsies high CAR-expression levels in CD8 T cells. Malignant CD4 Tfh cells were eliminated from the mAITL lymphoma, while the CAR + CD8 T cells expanded upon encounter with the CD4 receptor and were shaped into functional cytotoxic cells. Finally, in vivo injection of the CAR + CD8-LVs into our preclinical AITL mouse model carrying lymphomas, significantly prolonged mice survival. Moreover, the in vivo generated functional CAR + CD8 T cells efficiently reduced neoplastic T cell numbers in the mAITL tumors. CONCLUSION This is the first description of in vivo generated CAR T cells for therapy of a T cell lymphoma. The strategy described offers a new therapeutic concept for patients suffering from CD4-driven T cell lymphomas.
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Affiliation(s)
- Adrien Krug
- Université Côte d'Azur, INSERM, C3M, 06204, Nice, France
- Equipe Labellisée Ligue Contre Le Cancer, 06204, Nice, France
| | - Aymen Saidane
- Université Côte d'Azur, INSERM, C3M, 06204, Nice, France
- Equipe Labellisée Ligue Contre Le Cancer, 06204, Nice, France
| | | | - Floriane Fusil
- CIRI - International Center for Infectiology Research, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, F-69007, Lyon, France
| | - Alexander Michels
- Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, 63225, Langen, Germany
| | - Christian J Buchholz
- Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, 63225, Langen, Germany
- Frankfurt-Cancer-Institute (FCI), Goethe-University, Frankfurt, Germany
| | - Jean-Ehrland Ricci
- Université Côte d'Azur, INSERM, C3M, 06204, Nice, France
- Equipe Labellisée Ligue Contre Le Cancer, 06204, Nice, France
| | - Els Verhoeyen
- Université Côte d'Azur, INSERM, C3M, 06204, Nice, France.
- Equipe Labellisée Ligue Contre Le Cancer, 06204, Nice, France.
- CIRI - International Center for Infectiology Research, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, F-69007, Lyon, France.
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Kleeberg A, Bauer G, Jung E, Purrucker JC. Inflammatory neuropathy with evidence of anti-GQ1b antibodies in angioimmunoblastic T cell lymphoma (AITL): a case report. J Neurol 2024; 271:2880-2885. [PMID: 38329539 PMCID: PMC11055795 DOI: 10.1007/s00415-024-12217-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 01/22/2024] [Accepted: 01/22/2024] [Indexed: 02/09/2024]
Affiliation(s)
- Antonia Kleeberg
- Department of Neurology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
| | - Gregor Bauer
- Department of Neurology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
| | - Erik Jung
- Department of Neurology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
| | - Jan C Purrucker
- Department of Neurology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany
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Wen X, Yu H, Zhang L, Li L, Wang X, Fu X, Sun Z, Zhang X, Zhu L, Wu X, Yan J, Shi C, Zhang M, Zhang M, Li X. The relationship and clinical significance of serum cytokine expression level and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma. Int Immunopharmacol 2024; 131:111777. [PMID: 38489975 DOI: 10.1016/j.intimp.2024.111777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 02/19/2024] [Accepted: 02/27/2024] [Indexed: 03/17/2024]
Abstract
Pruritus of lymphoma is commonly associated with both Hodgkin lymphoma (HL) and angioimmunoblastic T cell lymphoma (AITL) and critically affects the life quality of patient. Recent evidence suggests that the pruritogenic cytokines seem to play a significant role in the genesis of chronic. This study aims to investigate the cytokines associated with itching in lymphoma patients and provide the basis for potential therapeutic targets. Serum samples were collected from 60 lymphoma patients, including 47 with Hodgkin lymphoma (HL) and 13 with angioimmunoblastic T-cell lymphoma (AITL), serving as the observation group (lymphoma group, LP group, n = 60). Additionally, serum samples from 8 healthy donors (HD group, n = 8) were collected for comparison. Within the lymphoma group, patients were stratified into those with pruritus (LWP group, n = 30) and those without pruritus (LWOP group, n = 30) based on the presence of skin pruritus symptoms. Elevated levels of multiple cytokines were significantly observed in the LP group in comparison to the HD group (p < 0.01). Patients in LWP group exhibited higher serum levels of IL-31 (p < 0.001), IL-1β (P = 0.039), and IL-1α (P = 0.037) compared to LWOP group. Notably, serum IL-31 levels were higher in advanced AITL patients (stage IV) than in early AITL patients (stage I-Ⅲ, P < 0.05). In subgroup analysis, patients with pruritus in the AITL group exhibited higher serum levels of MIG and CTACK compared to HL group, whereas PDGF-BB levels were significantly lower (p < 0.05). Elevated serum levels of IL-31, IL-1β, and IL-1α are linked to lymphoma-associated pruritus. Differences in serum cytokine profiles between HL and AITL subgroups are also highlighted. These findings offer valuable insights for clinical intervention in managing lymphoma-related pruritus.
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Affiliation(s)
- Xin Wen
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Hui Yu
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Lei Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Ling Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Xinhua Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Xiaorui Fu
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Zhenchang Sun
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Xudong Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Linan Zhu
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Xiaolong Wu
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Jiaqin Yan
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Cunzhen Shi
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Mengjuan Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China
| | - Mingzhi Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China.
| | - Xin Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Henan 450052 Zhengzhou, China; Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan 450052, China.
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Chen J, Li XL, Huang M. Utility of 18F-FDG PET/CT for differential diagnosis between IgG4-related lymphadenopathy and angioimmunoblastic T-cell lymphoma. Clin Radiol 2024; 79:205-212. [PMID: 38218705 DOI: 10.1016/j.crad.2023.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 12/07/2023] [Accepted: 12/10/2023] [Indexed: 01/15/2024]
Abstract
AIM To explore the utility of the 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in the differential diagnosis of IgG4-related lymphadenopathy (IgG4-RLAD) and angioimmunoblastic T-cell lymphoma (AITL). MATERIALS AND METHODS Retrospective analysis of 18F-FDG PET/CT imaging findings in clinically diagnosed IgG4-RLAD and AITL cases was undertaken to record the distribution, morphological characteristics, and imaging features of the affected lymph nodes, as well as FDG uptake of the spleen and bone marrow. Standardised uptake values normalised to lean body mass were evaluated for maximum (SULmax), average (SULavg), and peak values (SULpeak). Univariate and multivariate logistic regression was used to screen for statistically significant imaging findings to discriminate IgG4-RLAD from AITL. RESULTS Twenty-two cases of IgG4-RLAD (17 men, five women, median age 49.5 years) and 22 cases of AITL (16 men, six women, median age 55 years) were finally included in the analysis. There were no AITL patients with involvement of a single lymph node region. AITL patients had more involvement of the different nodal regions except cervical and pelvic nodal regions. A practical assessment method based on a combination of SULpeak-LN/SULavg-liver, SULpeak-spleen, and the number of involved nodal regions, improved the performance for differential diagnosis between both groups with an overall classification accuracy of 90.9%. CONCLUSIONS 18F-FDG PET/CT is a useful tool for distinguishing AITL from IgG4-RLAD, and it can also help determine the optimal biopsy site for suspected cases of IgG4-RLAD or AITL, reduce the need for re-biopsy procedures, and enable physicians to develop timely treatment strategies.
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Affiliation(s)
- J Chen
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
| | - X L Li
- Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
| | - M Huang
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
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Tanaka K, Miyoshi H, Yamashita Y, Iwamoto R, Yokoya Y, Tochino Y, Arakawa F, Tamura S, Murata SI, Sonoki T, Ohshima K. Angioimmunoblastic T-Cell Lymphoma after Treatment of Classic Hodgkin Lymphoma: A Case Report. Hematol Rep 2023; 15:662-669. [PMID: 38132275 PMCID: PMC10742454 DOI: 10.3390/hematolrep15040067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/30/2023] [Accepted: 11/13/2023] [Indexed: 12/23/2023] Open
Abstract
We report a case of a 24-year-old man who developed angioimmunoblastic T-cell lymphoma (AITL) after treatment for refractory lymphocyte-rich classic Hodgkin lymphoma (LR-CHL). This patient was treated with the BV+AVD (brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine) protocol for LR-CHL but progressed before completing chemotherapy. The pathological imaging showed the typical findings of LR-CHL at the first onset and first progression. Rescue chemotherapy and high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (AHSCT) were performed for refractory LR-CHL, and complete remission was achieved. However, the recurrence was suspected 6 months after AHSCT. The pathological findings of the lymph node biopsy at this time were different from those of the previous two lymph node biopsies, demonstrating findings of AITL. The finding of the immunohistochemical staining and polymerase chain reaction results supported the diagnosis. Although it has been reported that the risk for the development of non-Hodgkin lymphoma after treatment for Hodgkin lymphoma is increased, most are B-cell lymphomas, and few cases of AITL have been reported. AITL is a type of peripheral T-cell lymphoma that generally occurs in middle-aged and elderly people and that rarely occurs in young people. Here, we were able to make an accurate diagnosis by performing re-examination even when recurrence of LR-CHL was suspected. As there are no detailed case reports of AITL developing into secondary non-Hodgkin lymphoma, here we report on an identified case.
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Affiliation(s)
- Ken Tanaka
- Department of Pathology, Kurume University School of Medicine, Kurume 8300011, Japan; (K.T.); (F.A.); (K.O.)
- Department of Hematology/Oncology, Wakayama Medical University, Wakayama 6418509, Japan; (Y.Y.); (Y.Y.); (Y.T.); (S.T.); (T.S.)
| | - Hiroaki Miyoshi
- Department of Pathology, Kurume University School of Medicine, Kurume 8300011, Japan; (K.T.); (F.A.); (K.O.)
| | - Yusuke Yamashita
- Department of Hematology/Oncology, Wakayama Medical University, Wakayama 6418509, Japan; (Y.Y.); (Y.Y.); (Y.T.); (S.T.); (T.S.)
| | - Ryuta Iwamoto
- Department of Diagnostic Pathology, Wakayama Medical University, Wakayama 6418509, Japan; (R.I.); (S.-I.M.)
| | - Yuma Yokoya
- Department of Hematology/Oncology, Wakayama Medical University, Wakayama 6418509, Japan; (Y.Y.); (Y.Y.); (Y.T.); (S.T.); (T.S.)
| | - Yuichi Tochino
- Department of Hematology/Oncology, Wakayama Medical University, Wakayama 6418509, Japan; (Y.Y.); (Y.Y.); (Y.T.); (S.T.); (T.S.)
| | - Fumiko Arakawa
- Department of Pathology, Kurume University School of Medicine, Kurume 8300011, Japan; (K.T.); (F.A.); (K.O.)
| | - Shinobu Tamura
- Department of Hematology/Oncology, Wakayama Medical University, Wakayama 6418509, Japan; (Y.Y.); (Y.Y.); (Y.T.); (S.T.); (T.S.)
| | - Shin-Ichi Murata
- Department of Diagnostic Pathology, Wakayama Medical University, Wakayama 6418509, Japan; (R.I.); (S.-I.M.)
| | - Takashi Sonoki
- Department of Hematology/Oncology, Wakayama Medical University, Wakayama 6418509, Japan; (Y.Y.); (Y.Y.); (Y.T.); (S.T.); (T.S.)
| | - Koichi Ohshima
- Department of Pathology, Kurume University School of Medicine, Kurume 8300011, Japan; (K.T.); (F.A.); (K.O.)
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8
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Gaillard JB, Chapiro E, Daudignon A, Nadal N, Penther D, Chauzeix J, Nguyen-Khac F, Veronese L, Lefebvre C. Cytogenetics in the management of mature T-cell and NK-cell neoplasms: Guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH). Curr Res Transl Med 2023; 71:103428. [PMID: 38016421 DOI: 10.1016/j.retram.2023.103428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 10/24/2023] [Accepted: 10/25/2023] [Indexed: 11/30/2023]
Abstract
Mature T-cell and natural killer (NK)-cell neoplasms (MTNKNs) are a highly heterogeneous group of lymphomas that represent 10-15 % of lymphoid neoplasms and have usually an aggressive behavior. Diagnosis can be challenging due to their overlapping clinical, histological and immunophenotypic features. Genetic data are not a routine component of the diagnostic algorithm for most MTNKNs. Indeed, unlike B-cell lymphomas, the genomic landscape of MTNKNs is not fully understood. Only few characteristic rearrangements can be easily identified with conventional cytogenetic methods and are an integral part of the diagnostic criteria, for instance the t(14;14)/inv(14) or t(X;14) abnormality harbored by 95 % of patients with T-cell prolymphocytic leukemia, or the ALK gene translocation observed in some forms of anaplastic large cell lymphoma. However, advances in molecular and cytogenetic techniques have brought new insights into MTNKN pathogenesis. Several recurrent genetic alterations have been identified, such as chromosomal losses involving tumor suppressor genes (SETD2, CDKN2A, TP53) and gains involving oncogenes (MYC), activating mutations in signaling pathways (JAK-STAT, RAS), and epigenetic dysregulation, that have improved our understanding of these pathologies. This work provides an overview of the cytogenetics knowledge in MTNKNs in the context of the new World Health Organization classification and the International Consensus Classification of hematolymphoid tumors. It describes key genetic alterations and their clinical implications. It also proposes recommendations on cytogenetic methods for MTNKN diagnosis.
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Affiliation(s)
- Jean-Baptiste Gaillard
- Unité de Génétique Chromosomique, Service de Génétique moléculaire et cytogénomique, CHU Montpellier, Montpellier, France.
| | - Elise Chapiro
- Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS_1138, Drug Resistance in Hematological Malignancies Team, F-75006 Paris, France; Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Service d'Hématologie Biologique, F-75013 Paris, France
| | - Agnès Daudignon
- Institut de Génétique Médicale - Hôpital Jeanne de Flandre - CHRU de Lille, France
| | - Nathalie Nadal
- Service de génétique chromosomique et moléculaire, CHU Dijon, Dijon, France
| | - Dominique Penther
- Laboratoire de Génétique Oncologique, Centre Henri Becquerel, Rouen, France
| | - Jasmine Chauzeix
- Service d'Hématologie biologique CHU de Limoges - CRIBL, UMR CNRS 7276/INSERM 1262, Limoges, France
| | - Florence Nguyen-Khac
- Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS_1138, Drug Resistance in Hematological Malignancies Team, F-75006 Paris, France; Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Service d'Hématologie Biologique, F-75013 Paris, France
| | - Lauren Veronese
- Service de Cytogénétique Médicale, CHU Estaing, 1 place Lucie et Raymond Aubrac, 63003 Clermont-Ferrand; EA7453 CHELTER, Université Clermont Auvergne, France
| | - Christine Lefebvre
- Unité de Génétique des Hémopathies, Service d'Hématologie Biologique, CHU Grenoble Alpes, Grenoble, France
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9
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Ondrejka SL, Amador C, Climent F, Ng SB, Soma L, Zamo A, Dirnhofer S, Quintanilla-Martinez L, Wotherspoon A, Leoncini L, de Leval L. Follicular helper T-cell lymphomas: disease spectrum, relationship with clonal hematopoiesis, and mimics. A report of the 2022 EA4HP/SH lymphoma workshop. Virchows Arch 2023; 483:349-365. [PMID: 37500795 PMCID: PMC10541838 DOI: 10.1007/s00428-023-03607-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 06/30/2023] [Accepted: 07/17/2023] [Indexed: 07/29/2023]
Abstract
Follicular helper T-cell lymphomas (TFH lymphomas) were discussed in session V of the lymphoma workshop of the European Association for Haematopathology (EA4HP)/Society for Hematopathology (SH) 2022 meeting in Florence, Italy. The session focused on the morphologic spectrum of TFH lymphoma, including its three subtypes: angioimmunoblastic-type (AITL), follicular-type, and not otherwise specified (NOS). The submitted cases encompassed classic examples of TFH lymphoma and unusual cases such as those with early or indolent presentations, associated B-cell proliferations, or Hodgkin/Reed-Sternberg-like cells. The relationship between TFH lymphoma and clonal hematopoiesis was highlighted by several cases documenting divergent evolution of myeloid neoplasm and AITL from shared clonal mutations. The distinction between TFH lymphoma and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), was stressed, and many challenging examples were presented. Various cases highlighted the difficulties of differentiating TFH lymphoma from other established types of lymphoma and reactive conditions. Cutaneous T-cell lymphoma expressing TFH markers, particularly when resulting in lymph node involvement, should be distinguished from TFH lymphomas. Additional immunophenotyping and next-generation sequencing studies were performed on various cases in this session, highlighting the importance of these technologies to our current understanding and classification of TFH lymphomas.
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Affiliation(s)
- Sarah L Ondrejka
- Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Catalina Amador
- Division of Hematopathology, Department of Pathology and Laboratory Medicine, University of Miami, Miami, FL, USA
| | - Fina Climent
- Pathology Department, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet De Llobregat, Barcelona, Spain
| | - Siok-Bian Ng
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Lorinda Soma
- Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA
| | - Alberto Zamo
- Institute of Pathology, University of Würzburg, Würzburg, Germany
| | - Stefan Dirnhofer
- Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Leticia Quintanilla-Martinez
- Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany
| | | | - Lorenzo Leoncini
- Department of Medical Biotechnology, University of Siena, Siena, Italy
| | - Laurence de Leval
- Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland.
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10
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Basnet A. Angioimmunoblastic T-cell lymphoma: an immunological masquerade. QJM 2023; 116:577-578. [PMID: 37021962 DOI: 10.1093/qjmed/hcad057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 04/03/2023] [Indexed: 04/07/2023] Open
Affiliation(s)
- A Basnet
- Rheumatology Department, ADK Hospital, Sosun Magu, Male, Kaafu atoll, 20040, Maldives
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11
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Li Y, Gao X, Kong LZ, Li J. Misdiagnosis of angioimmunoblastic T‑cell lymphoma: A case report. Oncol Lett 2023; 25:250. [PMID: 37153053 PMCID: PMC10161358 DOI: 10.3892/ol.2023.13836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 04/14/2023] [Indexed: 05/09/2023] Open
Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is a specific subtype of peripheral T-cell lymphoma that is challenging to diagnose due to the lack of specific pathological characteristics. This report describes the case of a 56-year-old man with Hodgkin lymphoma in whom the gene rearrangement results were positive for TCRβDB+Jβ1/2. Pathological and immunochemical examinations revealed a diagnosis of lymphoma that was a composite of AITL and focal classical Hodgkin lymphoma. Unfortunately, he died soon after the correct diagnosis was made. This case shows that a combination of immunohistochemistry and gene rearrangement analysis can increase the diagnostic accuracy for AITL. A review of the literature on the misdiagnosis of AITL indicates that this disease progresses rapidly with a high mortality rate. Our experience, in this case, highlights the need for early diagnosis.
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Affiliation(s)
- Yan Li
- Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
- Correspondence to: Dr Yan Li, Department of Hematology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei 050051, P.R. China, E-mail:
| | - Xiaohan Gao
- Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
| | - Ling-Zhijie Kong
- Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
- Department of Graduate School, Hebei North University, Zhangjiakou, Hebei 075000, P.R. China
| | - Jie Li
- Department of Hematology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
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12
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Marques-Piubelli ML, Amador C, Vega F. Pathologic and molecular insights in nodal T-follicular helper cell lymphomas. Front Oncol 2023; 13:1105651. [PMID: 36793612 PMCID: PMC9923156 DOI: 10.3389/fonc.2023.1105651] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 01/13/2023] [Indexed: 01/31/2023] Open
Abstract
T-follicular helper (TFH) cells are one of the T-cell subsets with a critical role in the regulation of germinal center (GC) reactions. TFH cells contribute to the positive selection of GC B-cells and promote plasma cell differentiation and antibody production. TFH cells express a unique phenotype characterized by PD-1hi, ICOShi, CD40Lhi, CD95hi, CTLAhi, CCR7lo, and CXCR5hi . Three main subtypes of nodal TFH lymphomas have been described: 1) angioimmunoblastic-type, 2) follicular-type, and 3) not otherwise specified (NOS). The diagnosis of these neoplasms can be challenging, and it is rendered based on a combination of clinical, laboratory, histopathologic, immunophenotypic, and molecular findings. The markers most frequently used to identify a TFH immunophenotype in paraffin-embedded tissue sections include PD-1, CXCL13, CXCR5, ICOS, BCL6, and CD10. These neoplasms feature a characteristic and similar, but not identical, mutational landscape with mutations in epigenetic modifiers (TET2, DNMT3A, IDH2), RHOA, and T-cell receptor signaling genes. Here, we briefly review the biology of TFH cells and present a summary of the current pathologic, molecular, and genetic features of nodal lymphomas. We want to highlight the importance of performing a consistent panel of TFH immunostains and mutational studies in TCLs to identify TFH lymphomas.
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Affiliation(s)
- Mario L Marques-Piubelli
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Catalina Amador
- Division of Hematopathology, Department of Pathology and Laboratory Medicine, University of Miami, Miami, FL, United States
| | - Francisco Vega
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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13
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Mejia Saldarriaga M, Alhomoud M, Roboz G, Allan JN, Ruan J, Ouseph MM, Simonson PD, Bustoros M, Niesvizky R. Angioimmunoblastic T-cell lymphoma presenting with severe plasmacytosis mimicking plasma cell leukemia. Am J Hematol 2023. [PMID: 36785525 DOI: 10.1002/ajh.26878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 01/30/2023] [Accepted: 02/01/2023] [Indexed: 02/15/2023]
Abstract
Peripheral blood smear (A) demonstrates increased numbers of plasma cells (representative cells indicated by arrows), (B) demonstrates polytypic nature of plasma cells.
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Affiliation(s)
| | - Mohammad Alhomoud
- Division of Oncology & Hematology, Weill Cornell Medicine, New York, New York, USA
| | - Gail Roboz
- Division of Oncology & Hematology, Weill Cornell Medicine, New York, New York, USA
| | - John N Allan
- Division of Oncology & Hematology, Weill Cornell Medicine, New York, New York, USA
| | - Jia Ruan
- Division of Oncology & Hematology, Weill Cornell Medicine, New York, New York, USA
| | - Madhu M Ouseph
- Division of Pathology & Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Paul D Simonson
- Division of Pathology & Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
| | - Mark Bustoros
- Division of Oncology & Hematology, Weill Cornell Medicine, New York, New York, USA
| | - Ruben Niesvizky
- Division of Oncology & Hematology, Weill Cornell Medicine, New York, New York, USA
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14
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Andriano TM, Tannenbaum R, Xu H, Magro CM. Linear IgA bullous dermatosis in the setting of angioimmunoblastic T-cell lymphoma. J Cutan Pathol 2023; 50:43-46. [PMID: 35942597 DOI: 10.1111/cup.14309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 08/01/2022] [Accepted: 08/03/2022] [Indexed: 01/03/2023]
Abstract
We report an 80-year-old male developing linear IgA bullous dermatosis (LAD) in the setting of angioimmunoblastic T-cell lymphoma (AITL). This phenomenon is rare, as only three cases have been described in the literature. The pathophysiologic process can be attributed to dysregulation in somatic hypermutation and the expression of chemokine receptor 5 in AITL, contributing to increased IgA. Immunoglobulin production resulting from clonal plasma cell expansion may be because of the B-cell promotional effect by neoplastic follicular helper T-cells. Beyond providing a pathophysiologic platform for AITL-associated LAD, we also briefly summarized prior cases. This report demonstrates the importance of considering LAD in the differential diagnosis for patients with a bullous eruption in the setting of AITL.
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Affiliation(s)
| | - Rachel Tannenbaum
- Donald and Barbara Zucker Northwell School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
| | - Haoming Xu
- Department of Dermatology, Weill Cornell Medicine, New York, New York, USA
| | - Cynthia M Magro
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA
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15
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Meeuwes FO, Brink M, van der Poel MWM, Kersten MJ, Wondergem M, Mutsaers PGNJ, Böhmer L, Woei-A-Jin S, Visser O, Oostvogels R, Jansen PM, Diepstra A, Snijders TJF, Plattel WJ, Huls GA, Vermaat JSP, Nijland M. Impact of rituximab on treatment outcomes of patients with angioimmunoblastic T-cell lymphoma; a population-based analysis. Eur J Cancer 2022; 176:100-109. [PMID: 36208568 DOI: 10.1016/j.ejca.2022.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 09/08/2022] [Accepted: 09/08/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND Patients with angioimmunoblastic T-cell lymphoma (AITL) are treated with cyclophosphamide, doxorubicin, vincristine and prednisone with or without etoposide (CHO(E)P). In the majority of cases, Epstein-Barr virus (EBV)-positive B-cells are present in the tumour. There is paucity of research examining the effect of rituximab when added to CHO(E)P. In this nationwide, population-based study, we analysed the impact of rituximab on overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) of patients with AITL. METHODS Patients with AITL diagnosed between 2014 and 2020 treated with ≥one cycle of CHO(E)P with or without rituximab were identified in the Netherlands Cancer Registry. Survival follow-up was up to 1st February 2022. Baseline characteristics, best response during first-line treatment and survival were collected. PFS was defined as the time from diagnosis to relapse or to all-cause-death. OS was defined as the time from diagnosis to all-cause-death. Multivariable analysis for the risk of mortality was performed using Cox regression. FINDINGS Out of 335 patients, 146 patients (44%) received R-CHO(E)P. Rituximab was more frequently used in patients with a B-cell infiltrate (71% versus 89%, p < 0·01). The proportion of patients who received autologous stem cell transplantation (ASCT) was similar between CHO(E)P and R-CHO(E)P (27% versus 30%, respectively). The ORR and 2-year PFS for patients who received CHO(E)P and R-CHO(E)P were 71% and 78% (p = 0·01), and 40% and 45% (p = 0·12), respectively. The 5-year OS was 47% and 40% (p = 0·99), respectively. In multivariable analysis, IPI-score 3-5, no B-cell infiltrate and no ASCT were independent prognostic factors for risk of mortality, whereas the use of rituximab was not. INTERPRETATION Although the addition of rituximab to CHO(E)P improved ORR for patients with AITL, the PFS and OS did not improve.
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Affiliation(s)
- Frederik O Meeuwes
- Department of Hematology, Treant Hospital, Emmen, the Netherlands; Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands
| | - Mirian Brink
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands
| | - Marjolein W M van der Poel
- Department of Internal Medicine, Division of Hematology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Marie José Kersten
- Department of Hematology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Mariëlle Wondergem
- Department of Hematology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Pim G N J Mutsaers
- Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Lara Böhmer
- Department of Hematology, Haga Hospital, The Hague, the Netherlands
| | - Sherida Woei-A-Jin
- Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
| | - Otto Visser
- Department of Hematology, Isala Hospital, Zwolle, the Netherlands
| | - Rimke Oostvogels
- Department of Hematology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Patty M Jansen
- Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
| | - Arjan Diepstra
- Department of Pathology, University Medical Center Groningen, Groningen, the Netherlands
| | - Tjeerd J F Snijders
- Department of Hematology, Medisch Spectrum Twente, Enschede, the Netherlands
| | - Wouter J Plattel
- Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands
| | - Gerwin A Huls
- Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands
| | - Joost S P Vermaat
- Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands
| | - Marcel Nijland
- Department of Hematology, University Medical Center Groningen, Groningen, the Netherlands.
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16
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Pesqué D, Marcantonio O, Vázquez I, Papaleo N, Sánchez-González B, Gallardo F, Colomo L, Pujol RM. Cutaneous Involvement of Angioimmunoblastic T-Cell Lymphoma Masquerading as B-Cell Reactive Lymphoid Hyperplasia. Am J Dermatopathol 2022; 44:e41-e45. [PMID: 34966050 DOI: 10.1097/dad.0000000000002110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
ABSTRACT A 59-year-old woman presented with a persistent eruption manifested as multiple agminated miliary facial papules. Histopathological examination showed prominent nodular dermal lymphoid infiltrates with hyperplastic follicles that were initially interpreted as B-cell reactive lymphoid hyperplasia. Several years later, an additional biopsy showed a dense perifollicular infiltrate with reactive primary and secondary follicles. Accompanying T cells corresponded to CD3/CD4/PD1/CXCL13-positive cells and scattered Epstein-Barr virus-positive B cells were identified by in situ hybridization. A monoclonal T-cell population was demonstrated by TCRγ and TCRβ Polymerase Chain Reaction amplification, as well as a minor abnormal circulating T-cell population by flow cytometry (0.62% of the white blood cells, CD4+CD3s-CD7-). A biopsy specimen from an enlarged right supraclavicular lymph node disclosed nodal involvement by angioimmunoblastic T-cell lymphoma. The observation of B-cell dermal nodular infiltrates with well-demarcated lymphoid aggregates forming primary lymphoid follicles may lead to overlook the T-cell component in some cases of angioimmunoblastic T-cell lymphoma. In such cases, a careful assessment of the apparently minor T-cell component is important to establish a correct diagnosis.
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Affiliation(s)
| | | | - Ivonne Vázquez
- Pathology, Hospital del Mar-Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
- Department of Pathology, Universitat Pompeu Fabra, Barcelona, Spain; and
| | - Natalia Papaleo
- Pathology, Hospital del Mar-Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
- Department of Pathology, Universitat Pompeu Fabra, Barcelona, Spain; and
| | - Blanca Sánchez-González
- Department of Hematology, Hospital del Mar-Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | | | - Luis Colomo
- Pathology, Hospital del Mar-Institut Mar d'Investigacions Mèdiques, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
- Department of Pathology, Universitat Pompeu Fabra, Barcelona, Spain; and
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17
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Genetic profiling and biomarkers in peripheral T-cell lymphomas: current role in the diagnostic work-up. Mod Pathol 2022; 35:306-318. [PMID: 34584212 DOI: 10.1038/s41379-021-00937-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/15/2021] [Accepted: 09/16/2021] [Indexed: 11/08/2022]
Abstract
Peripheral T-cell lymphomas are a heterogeneous, and usually aggressive, group of mature T-cell neoplasms with overlapping clinical, morphologic and immunologic features. A large subset of these neoplasms remains unclassifiable with current diagnostic methods ("not otherwise specified"). Genetic profiling and other molecular tools have emerged as widely applied and transformative technologies for discerning the biology of lymphomas and other hematopoietic neoplasms. Although the application of these technologies to peripheral T-cell lymphomas has lagged behind B-cell lymphomas and other cancers, molecular profiling has provided novel prognostic and diagnostic markers as well as an opportunity to understand the biologic mechanisms involved in the pathogenesis of these neoplasms. Some biomarkers are more prevalent in specific T-cell lymphoma subsets and are being used currently in the diagnosis and/or risk stratification of patients with peripheral T-cell lymphomas. Other biomarkers, while promising, need to be validated in larger clinical studies. In this review, we present a summary of our current understanding of the molecular profiles of the major types of peripheral T-cell lymphoma. We particularly focus on the use of biomarkers, including those that can be detected by conventional immunohistochemical studies and those that contribute to the diagnosis, classification, or risk stratification of these neoplasms.
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18
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Zhang C, Mi L, Wu M, Liu W, Ma H, Ren J, Zhao L, Wang X, Song Y, Zhu J. Angioimmunoblastic T-cell lymphoma: treatment strategies and prognostic factors from a retrospective multicenter study in China. Leuk Lymphoma 2021; 63:1152-1159. [PMID: 34957894 DOI: 10.1080/10428194.2021.2015586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is a unique sub-type of peripheral T-cell lymphoma (PTCL). We aimed to evaluate treatment programs and prognostic factors of 121 newly diagnosed patients with AITL in China from January 2001 to December 2018. The median age was 58 years with male predominance. Bone marrow involvement appeared in only 8.3% of patients, which was different from the previously published literature. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) were 29.7% and 44.0%, respectively. Univariate and multivariate analyses showed that involvement of >5 nodal areas, age and Beta-2 microglubulin were highly predictive of OS but only the involvement of fewer than five nodal areas was significant for PFS. We identified a novel prognostic model including the three factors that may be applied in clinical practice and offer an alternative to IPI and PIT.
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Affiliation(s)
- Chen Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Lan Mi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Meng Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Weiping Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hongmei Ma
- Department of Hematology, Cangzhou People's Hospital, Cangzhou, China
| | - Jianxin Ren
- Department of Hematology, Cangzhou People's Hospital, Cangzhou, China
| | - Linjun Zhao
- Department of Lymphoma, Peking University International Hospital, Beijing, China
| | - Xiaopei Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yuqin Song
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jun Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China
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19
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The Role of a Routine Bone Marrow Biopsy in Autoimmune Hemolytic Anemia for the Detection of an Underlying Lymphoproliferative Disorder. Hemasphere 2021; 6:e674. [PMID: 34938958 PMCID: PMC8687727 DOI: 10.1097/hs9.0000000000000674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/22/2021] [Indexed: 12/02/2022] Open
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20
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Gupta P, Gupta N, Bal A, Rastogi P, Prakash G, Malhotra P, Dey P, Srinivasan R, Das A. Cytomorphological characterisation of angioimmunoblastic T cell lymphoma: a case-control study. J Clin Pathol 2021; 76:320-326. [PMID: 34697030 DOI: 10.1136/jclinpath-2021-207887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 10/11/2021] [Indexed: 11/04/2022]
Abstract
AIMS Angioimmunoblastic T cell lymphoma (AITL) is often misdiagnosed in cytology. Hence, the present study was conducted to identify the distinctive cytomorphological features of AITL in lymph node fine-needle aspirates (LN-FNA). METHODS This was a 4-year retrospective case-control study. Cases included LN-FNAs from patients with histopathologically confirmed AITL. The controls included LN-FNAs from patients with histopathologically confirmed reactive lymphoid hyperplasia (RLH; n=25). Eleven cytomorphological features were assessed in all the aspirates; the strength of association was determined by OR, Cramer's V and multiple correspondence analysis (MCA). RESULTS Of a total of 22 cases of AITL reported on histopathology, 19 adequate aspirates from 14 patients (63.6%) were available for review. On univariate analysis, 5 of 11 cytomorphological variables were found to be significant for AITL; however, on MCA, 3 of these parameters, viz absence of tingible body macrophages (OR=0.014; V=0.74), presence of atypical lymphoid cells (OR=10.8; V=0.41) and singly scattered epithelioid cells (OR=19.3; V=0.31), were found to be the strongest predictors of AITL. CONCLUSIONS The absence of tingible body macrophages, presence of atypical lymphoid cells and singly scattered epithelioid cells in polymorphic LN-FNAs are significant cytomorphological predictors of AITL in comparison with RLH. Knowledge of these diagnostic predictors, supplemented by clinicoradiological correlation and appropriate ancillary studies, can help diagnose AITL on aspiration cytology.
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Affiliation(s)
- Parikshaa Gupta
- Cytology and Gynecologic Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Nalini Gupta
- Cytology and Gynecologic Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Amanjit Bal
- Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pulkit Rastogi
- Hematology Department, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Gaurav Prakash
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pankaj Malhotra
- Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pranab Dey
- Cytology and Gynecologic Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Radhika Srinivasan
- Cytology and Gynecologic Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashim Das
- Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Qiu L, Cho JH, Jelloul FZ, Vega F. SOHO State of the Art Updates and Next Questions: Pathology and Pathogenesis of Nodal Peripheral T-Cell Lymphomas. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2021; 22:287-296. [PMID: 34776400 DOI: 10.1016/j.clml.2021.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 09/30/2021] [Accepted: 10/09/2021] [Indexed: 10/20/2022]
Abstract
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous and often clinically aggressive group of neoplasms derived from mature post-thymic T-lymphocytes. These neoplasms are rare and usually diagnostically challenging. Our understanding of the pathogenesis of PTCL is increasing and this improved knowledge is leading us to better molecular characterization, more objective and accurate diagnostic criteria, more effective risk assessment, and potentially better treatments. The focus of this paper is to present a brief overview of the current pathology criteria and molecular and genetic features of nodal peripheral T-cell lymphomas focusing on distinct genetically and molecularly defined subgroups that are being recognized within each major nodal PTCL category. It is expected that the molecular stratification will improve the diagnosis and will provide novel therapeutic opportunities (biomarker-driven and targeted therapies) that might benefit and change the outcomes of patients with these neoplasms.
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Affiliation(s)
- Lianqun Qiu
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jeong Hee Cho
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Fatima Zahra Jelloul
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Francisco Vega
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; UT Health Graduate School of Biomedical Sciences, Houston, Texas.
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Kuroda K, Tambe A, Iftikhar R, Nat AS, Basnet A. A Case of Angioimmunoblastic T-cell Lymphoma That Mimics As Autoimmune Diseases and Infections. Cureus 2021; 13:e16439. [PMID: 34422471 PMCID: PMC8366574 DOI: 10.7759/cureus.16439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/17/2021] [Indexed: 11/05/2022] Open
Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive malignancy with a presentation like either autoimmune diseases, drug reactions, or infections. We hereby present a unique case of AITL. A 61-year-old Caucasian male with a past medical history of chronic obstructive pulmonary disease (COPD) presented to the emergency department with a rash over his bilateral knees, shortness of breath, and productive cough of few days. He was managed for suspected COPD exacerbation associated with community-acquired pneumonia. On the day of admission patient was having an itchy maculopapular rash, ecchymosis on the left flank, and generalized lymphadenopathy. Physical exam showed generalized lymphadenopathy. Laboratory tests revealed leukocytosis, thrombocytopenia and were positive for multiple autoantibodies. Epstein-Barr virus polymerase chain reaction and hepatitis B virus core antibody were positive. Skin biopsy revealed findings suggestive of a small vessel vasculitis. Inguinal lymph node biopsy showed AITL. The patient recovered with chemotherapy. The case illustrates that clinical presentation of AITL mimics rheumatologic disorders and infections. This complexity could arise from the follicular T helper cell, which is an important checkpoint for B cell activation and differentiation. Additionally, skin involvement is one of the important findings of AITL and a variety of lesions have been reported as skin manifestations.
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Affiliation(s)
- Kaku Kuroda
- Family Medicine, State University of New York (SUNY) Upstate Medical University, Syracuse, USA
| | - Ajay Tambe
- Hematology and Oncology, State University of New York (SUNY) Upstate Medical University, Syracuse, USA
| | - Rahila Iftikhar
- Family Medicine, State University of New York (SUNY) Upstate Medical University, Syracuse, USA
| | - Amitpal S Nat
- Internal Medicine, State University of New York (SUNY) Upstate Medical University, Syracuse, USA
| | - Alina Basnet
- Hematology and Oncology, State University of New York (SUNY) Upstate Medical University, Syracuse, USA
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23
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Pritchett JC, Yang ZZ, Kim HJ, Villasboas JC, Tang X, Jalali S, Cerhan JR, Feldman AL, Ansell SM. High-dimensional and single-cell transcriptome analysis of the tumor microenvironment in angioimmunoblastic T cell lymphoma (AITL). Leukemia 2021; 36:165-176. [PMID: 34230608 DOI: 10.1038/s41375-021-01321-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 05/20/2021] [Accepted: 06/05/2021] [Indexed: 02/08/2023]
Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive lymphoid malignancy associated with a poor clinical prognosis. The AITL tumor microenvironment (TME) is unique, featuring a minority population of malignant CD4+ T follicular helper (TFH) cells inter-mixed with a diverse infiltrate of multi-lineage immune cells. While much of the understanding of AITL biology to date has focused on characteristics of the malignant clone, less is known about the many non-malignant populations that comprise the TME. Recently, mutational consistencies have been identified between malignant cells and non-malignant B cells within the AITL TME. As a result, a significant role for non-malignant populations in AITL biology has been increasingly hypothesized. In this study, we have utilized mass cytometry and single-cell transcriptome analysis to identify several expanded populations within the AITL TME. Notably, we find that B cells within the AITL TME feature decreased expression of key markers including CD73 and CXCR5. Furthermore, we describe the expansion of distinct CD8+ T cell populations that feature an exhausted phenotype and an underlying expression profile indicative of dysfunction, impaired cytotoxicity, and upregulation of the chemokines XCL2 and XCL1.
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Affiliation(s)
| | - Zhi-Zhang Yang
- Department of Hematology, Mayo Clinic, Rochester, MN, USA
| | - Hyo Jin Kim
- Department of Hematology, Mayo Clinic, Rochester, MN, USA
| | | | - Xinyi Tang
- Department of Hematology, Mayo Clinic, Rochester, MN, USA
| | | | - James R Cerhan
- Department of Health Sciences Research and Epidemiology, Mayo Clinic, Rochester, MN, USA
| | - Andrew L Feldman
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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24
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Xie Y, Jaffe ES. How I Diagnose Angioimmunoblastic T-Cell Lymphoma. Am J Clin Pathol 2021; 156:1-14. [PMID: 34117736 DOI: 10.1093/ajcp/aqab090] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 04/22/2021] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma derived from T-follicular helper cells. For pathologists, diagnosing AITL may be challenging due to its wide clinical and histopathologic spectrum, which can mimic a variety of reactive and neoplastic processes. METHODS We summarize and discuss the clinicopathologic features of AITL, emphasizing diagnostic tools available to the practicing pathologist. Common diagnostic dilemmas are discussed. RESULTS AITL exhibits various histologic patterns and is often associated with a prominent microenvironment that can obscure the neoplastic cells. Atypical B-cell proliferations, which can take a number of forms, are common in AITL, and clonal B-cell expansion can be seen. The atypical B cells can closely resemble Hodgkin/Reed-Sternberg cells, leading to misdiagnosis as classic Hodgkin lymphoma. Molecular studies have revealed recurrent genetic alterations, which can aid in differential diagnosis, particularly in problematic cases. CONCLUSIONS Given the complex diagnostic challenges in AITL, an integrated approach, incorporating clinical, morphologic, immunophenotypic, and molecular findings, is helpful to reach an accurate diagnosis.
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Affiliation(s)
- Yi Xie
- Department of Laboratory Medicine, University of California San Francisco School of Medicine, San Francisco, CA, USA
| | - Elaine S Jaffe
- Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
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25
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Bao W, Buchanan KL, Davis LS. Not your typical morbilliform rash: Angioimmunoblastic T‐cell lymphoma. Clin Case Rep 2021. [DOI: 10.1002/ccr3.4367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Affiliation(s)
- Wendi Bao
- Medical College of Georgia at Augusta University Augusta GA USA
| | - Kendall L. Buchanan
- Department of Dermatology Medical College of Georgia at Augusta University Augusta GA USA
| | - Loretta S. Davis
- Department of Dermatology Medical College of Georgia at Augusta University Augusta GA USA
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26
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Nguyen PN, Tran NTB, Nguyen TPX, Ngo TNM, Lai DV, Deel CD, Hassell LA, Vuong HG. Clinicopathological Implications of RHOA Mutations in Angioimmunoblastic T-Cell Lymphoma: A Meta-analysis: RHOA mutations in AITL. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2021; 21:431-438. [PMID: 33849798 DOI: 10.1016/j.clml.2021.03.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/09/2021] [Accepted: 03/14/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Studies have recently shown that RHOA mutations play a crucial role in angioimmunoblastic T-cell lymphoma (AITL) pathogenesis. We aimed to pool data from these studies to provide a comparison of clinicopathological features between the RHOA mutant and RHOA wild-type groups in the AITL population. METHODS We searched PubMed and Web of Science for the keywords "RHOA AND lymphoma" and selected only studies reporting the clinical significance of RHOA mutations in AITL. We calculated the odds ratios (OR) or the mean difference with 95% CI using a random effect model. RESULTS Our pooled results showed a significant association between RHOA mutations and a T-follicular helper cell (TFH) phenotype, especially CD10 (OR, 5.16; 95% CI, 2.32-11.46), IDH2 mutations (OR, 10.70; 95% CI, 4.22-27.15), and TET2 mutations (OR, 7.03; 95% CI, 2.14-23.12). Although DNMT3A together with TET2 and IDH2 mutations are epigenetic gene alterations, we found an insignificant association between RHOA and DNMT3A mutations (OR, 1.72; 95% CI, 0.73-4.05). No significant associations of RHOA mutations with other clinicopathological features and overall survival were found. CONCLUSIONS RHOA mutations are strongly correlated with a T-follicular helper cell phenotype and epigenetic mutations such as TET2 and IDH2. Further studies with large AITL samples should be conducted to validate the relationship of TET2, DNMT3A, and RHOA co-mutations.
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Affiliation(s)
- Phuong Nhat Nguyen
- Department of Pathology, Forensic Medicine Center of Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Ngoc T B Tran
- Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, OR
| | - Truong P X Nguyen
- Department of Pathology, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | - Tam N M Ngo
- Faculty of Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Doan Van Lai
- Department of Pathology, Keck School of Medicine University of Southern California, Los Angeles, CA
| | - Chelsey D Deel
- Department of Pathology, Oklahoma University Health Sciences Center, Oklahoma City, OK
| | - Lewis A Hassell
- Department of Pathology, Oklahoma University Health Sciences Center, Oklahoma City, OK
| | - Huy Gia Vuong
- Department of Pathology, Oklahoma University Health Sciences Center, Oklahoma City, OK; Stephenson Cancer Center, Oklahoma University Health Sciences Center, Oklahoma City, OK.
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Maheswaranathan M, Lagoo AS, Diehl L, Shah A. A 79-Year-Old Female with Altered Mental Status and Anemia. Arthritis Care Res (Hoboken) 2021; 74:555-561. [PMID: 33555132 DOI: 10.1002/acr.24571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 01/05/2021] [Accepted: 02/02/2021] [Indexed: 11/12/2022]
Abstract
The authors declare that there are no disclosures or conflicts of interest regarding the publication of this manuscript. We did not receive any financial support and have no financial interests which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work.
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Affiliation(s)
| | - Anand S Lagoo
- Department of Pathology, Duke University School of Medicine, Durham, NC, USA
| | - Louis Diehl
- Division of Hematology, Duke University School of Medicine, Durham, NC, USA
| | - Ankoor Shah
- Division of Rheumatology, Duke University School of Medicine, Durham, NC, USA
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28
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Li XY, He HY, Yue SL, Pai P. Delayed diagnosis of Angioimmunoblast T-cell lymphoma presenting with type II Cryoglobulinemia and acute kidney injury: a case report and narrative review of the literature. BMC Nephrol 2020; 21:463. [PMID: 33160311 PMCID: PMC7648307 DOI: 10.1186/s12882-020-02125-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 10/26/2020] [Indexed: 11/10/2022] Open
Abstract
Background Angioimmunoblastic T cell lymphoma (AITL) is an infrequent hematological malignancy with variable and often atypical presentations. The presence of dysproteinemia, autoantibodies and systemic involvement in AITL has often led to a delay in diagnosis or even misdiagnosis in practice. We herewith present a case of AITL that primarily presented with acute kidney injury associated with type II Cryoglobulinemia, the underlying cause was only identified 8 months after the emergence of initial symptoms. Case presentation A 67-year old woman presented with 2-month history of intermittent joint pain and a 3-day history of bilateral lower limb edema and acute kidney injury. Initial laboratory investigations showed marked hypocomplementemia with positive autoantibodies of ANA, anti-cardiolipin-IgM and direct antiglobulin. The serum and urinary Immunofixation and serum cryoglobulin tests were negative, while the serum free κ to λ light chain ratio was 0.231. A renal biopsy showed a diffuse proliferative glomerulonephritis with intracapillary pseudothrombi formation. There were orderly arranged microtubular structures of 20–35 nm in diameter in the subendothelial and mesangial area on electron microscopy. Shortly afterwards, the patient developed tingling affecting her finger tips and weak hands and legs. A diagnosis of cryoglobulinemia complicated with cryoglobulinemic glomerulonephritis and polyneuropathy was made. She responded well to methylprednisolone, plasma exchange and rituximab. However, 3 months later, she presented with generalized pruritic rash, weight loss, and inguinal lymphadenopathy. A subsequent inguinal excisional lymph node biopsy at month 8 revealed AITL as the underlying disease. Conclusions AITL and its associated B cell dysregulation can give rise to autoimmunity and cryoglobulinemia which may conceal itself as the underlying disorder. In various clinical scenarios of auto-immune diseases, it is advisable that the clinicians should take into consideration the multi-faceted lymphoma.
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Affiliation(s)
- Xiang-Yang Li
- Department of Nephrology, University of Hong Kong - Shenzhen Hospital, Shenzhen, China
| | - Hai-Yan He
- Department of Nephrology, University of Hong Kong - Shenzhen Hospital, Shenzhen, China
| | - Shu-Ling Yue
- Department of Kidney Pathology, Guangzhou KingMed Center for Clinical Laboratory, Guangzhou, China
| | - Pearl Pai
- Department of Nephrology, University of Hong Kong - Shenzhen Hospital, Shenzhen, China. .,Department of Medicine, University of Hong Kong - Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
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29
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Huang C, Zhang H, Gao Y, Diao L, Liu L. Development of a Novel Clinical Prognostic Model for Patients With Angioimmunoblastic T-Cell Lymphoma. Technol Cancer Res Treat 2020; 19:1533033820964231. [PMID: 33073702 PMCID: PMC7592312 DOI: 10.1177/1533033820964231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
In this study we aimed to identify a set of prognostic factors for angioimmunoblastic T-cell lymphoma (AITL) and establish a novel prognostic model. The clinical data of 64 AITL patients enrolled to the Fourth Hospital of Hebei Medical University (from 2012 Jan to 2017 May) were retrospectively analyzed. The estimated 5-year overall survival and progression-free survival of this cohort of patients were 45.8% and 30.8%, respectively. Univariate analysis showed that age > 60 years, performance status ≥2, Ann Arbor stage III/IV, lactate dehydrogenase > 250 U/L, serum albumin (ALB) < 30 g/l, Coombs test positive, and Ki-67 rate ≥ 70% were significantly associated with poor prognosis. Multivariate analysis demonstrated that age > 60 years, ALB < 30 g/l, Ki-67 rate ≥ 70%, and Coombs test positive were independent prognosis factors for AITL. Here a new prognostic model, named as AITLI, was constructed using the top 5 significant prognostic factors for AITL prognostic prediction. The AITL patients were stratified into 3 risk groups: low, intermediate, and high risk groups. The new prognostic model AITLI showed better performance in predicting prognosis than the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) that were wisely used to predict the outcome for patients with other subtypes of lymphoma.
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Affiliation(s)
- Chen Huang
- Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
| | - Huichao Zhang
- Department of Clinic Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
| | - Yuhuan Gao
- Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
| | - Lanping Diao
- Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
| | - Lihong Liu
- Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China
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Swarup S, Kopel J, Thein KZ, Tarafdar K, Swarup K, Thirumala S, Quick DP. Sequential Complications of Hypercalcemia, Necrotizing Granulomatous Vasculitis, and Aplastic Anemia Occurring in One Patient with Angioimmunoblastic T-cell Lymphoma. Am J Med Sci 2020; 361:375-382. [PMID: 33097193 PMCID: PMC7470704 DOI: 10.1016/j.amjms.2020.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 07/05/2020] [Accepted: 09/01/2020] [Indexed: 01/04/2023]
Abstract
In this case report of a patient with angioimmunoblastic T-cell lymphoma (AITL), we describe the occurrence of three sequential complications that have been reported uncommonly in this disease subtype. Firstly, the patient developed hypercalcemia due to elevated 1,25-didydroxyvitamin D. Although hypercalcemia in AITL is not rare (1-2% incidence), this case was unusual in that the complication developed when disease appeared stable and symptomatically, he was doing well otherwise. Hypercalcemia surprisingly resolved a few months later at a time when his disease appeared to be progressing. A year later, the patient presented with digital ischemia necessitating partial amputation of a finger. Pathological exam revealed granulomatous vasculitis of small and medium arterioles with infiltrating malignant T lymphocytes. Although skin manifestations are common in AITL, necrotizing granulomatous vasculitis with accompanying tumor cells leading to severe digital ischemia appears rare. Subsequently the patient developed profound pancytopenia with bone marrow confirming severe aplastic anemia. To our knowledge only one other case of aplastic anemia has been reported in a patient with AITL. We discuss the diagnostic and management considerations involved in this patient care and review similar reported cases.
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Affiliation(s)
- Sriman Swarup
- Texas Tech University Health Sciences Center, Lubbock, Texas USA
| | - Jonathan Kopel
- Texas Tech University Health Sciences Center, Lubbock, Texas USA.
| | - Kyaw Zin Thein
- Texas Tech University Health Sciences Center, Lubbock, Texas USA
| | - Kaiser Tarafdar
- Internal Medicine and Hematology-Oncology, Covenant Health System, Lubbock, Texas USA
| | | | | | - Donald P Quick
- Texas Tech University Health Sciences Center, Lubbock, Texas USA; Internal Medicine and Hematology-Oncology, Covenant Health System, Lubbock, Texas USA
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31
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Zhu F, Li Q, Pan H, Xiao Y, Liu T, Liu X, Li J, Wu G, Zhang L. Successful Treatment of Chidamide and Cyclosporine for Refractory/Relapsed Angioimmunoblastic T Cell Lymphoma With Evans Syndrome: A Case Report With Long-Term Follow-Up. Front Oncol 2020; 10:1725. [PMID: 32984055 PMCID: PMC7481371 DOI: 10.3389/fonc.2020.01725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 08/03/2020] [Indexed: 11/13/2022] Open
Abstract
Background Refractory/relapsed angioimmunoblastic T cell lymphoma (AITL) with Evans syndrome is a very rare condition with a poor prognosis. There is no evidence-based treatment strategy for refractory/relapsed AITL with Evans syndrome. Case Presentation A 51-year-old female was admitted to our hospital with multiple enlarged bilateral cervical lymph nodes, more than 1 week-long chest distress, and night sweats in July 2014. An excision biopsy of the left cervical enlarged lymph node revealed AITL. However, the patient showed resistance to the first-line chemotherapy for AITL and was diagnosed with refractory AITL. Complete remission was achieved after the salvage treatment with the combination of chemotherapy, radiotherapy, and immunomodulatory agent lenalidomide. Unfortunately, 12 months later, the patient suffered from disease progression and was diagnosed as refractory/relapsed AITL with Evans syndrome according to the laboratory findings and imaging. With the diagnosis of refractory/relapsed AITL with Evans syndrome, the patient received the first-line treatment for Evans syndrome including prednisone and intravenous immunoglobulin. The response to the first-line treatment for Evans syndrome was poor. The combination regimen of chidamide (30 mg, po, biw) and cyclosporine were administrated considering the treatment targeting simultaneously both refractory/relapsed AITL and Evans syndrome. The efficacy evaluation was complete remission. The last follow-up of the patient was April 30th, 2020, and no evidence of disease progression was observed. The overall survival of the patient was more than 70 months. Conclusion The treatment for refractory/relapsed AITL combined with Evans syndrome remains challenging to patients and physicians. The combination of chidamide and cyclosporine may be an effective and tolerable regimen for the intractable AITL with Evans syndrome case and more observations are necessary to identify the efficacy and safety in the future.
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Affiliation(s)
- Fang Zhu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qiuhui Li
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huaxiong Pan
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yin Xiao
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Liu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xinxiu Liu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Juan Li
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Gang Wu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liling Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Galtier J, Parrens M, Milpied N. [Peripheral T cell lymphomas: diagnosis and treatment]. Rev Med Interne 2020; 41:829-837. [PMID: 32674892 DOI: 10.1016/j.revmed.2020.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 05/23/2020] [Accepted: 05/26/2020] [Indexed: 10/23/2022]
Abstract
Peripheral T cell lymphomas are rare malignancies with aggressive course, with several different subtype described in the 2016 WHO classification. Their distribution across the world is heterogenous, with marked difference between Western and Asian country. Their clinical presentation often comprise extra-nodal involvement, B symptoms and immune system disorder which can lead to wrong diagnosis orientation. Make a right diagnosis need a experienced pathologist in close collaboration with clinical datas. Peripheral T cell lymphomas are in general associated with poor prognosis when treated with anthracyclines-based regimen, and several studies and trials focused on the use of intensified regimen or novel targeted agents, whose proper indication still remain to be clarified.
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Affiliation(s)
- J Galtier
- CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, Hôpital Haut-Leveque, F-33000 Bordeaux, France.
| | - M Parrens
- CHU Bordeaux, Unité de pathologie, Hôpital Haut-Leveque, F-33000 Bordeaux, France
| | - N Milpied
- CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, Hôpital Haut-Leveque, F-33000 Bordeaux, France
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33
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Kawahigashi T, Kitagawa I, Tanaka E. Angioimmunoblastic T-cell lymphoma accompanied by pure red cell aplasia: A case report. World J Clin Oncol 2020; 11:405-411. [PMID: 32874954 PMCID: PMC7450812 DOI: 10.5306/wjco.v11.i6.405] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 05/21/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma, which is a rare subtype of lymphoma. Patients with AITL often have skin lesions, which are observed in 50% of all cases; the chief complaint of this patient was palpable purpura. AITL often complicates autoimmune or hematological disorders; however, among these, pure red cell aplasia (PRCA) is a very rare complication of AITL. We herein report a case of AITL with PRCA.
CASE SUMMARY A 77-year-old Japanese man presented to our hospital with complaints of loss of appetite for 2 mo and a 10-d history of palpable purpura. On physical examination, the patient was afebrile but had bilateral multiple palpable purpuric lesions over the lower extremities, lower abdomen, and part of the upper extremities. Moreover, lymphadenopathy of the bilateral inguinal, cervical, and supraclavicular nodes was noted. Laboratory and imaging studies and skin biopsy were conducted but were inconclusive. Based on inguinal lymph node excisional biopsy, we diagnosed the patient with AITL. Subsequently, the patient developed progressive normocytic normochromic anemia that necessitated almost daily blood transfusion. The clinical presentations and results of bone marrow assessment were consistent with those of PRCA, which is associated with AITL. Chemotherapy was initiated but was not effective. The patient refused further chemotherapy and opted to continue receiving best supportive care.
CONCLUSION PRCA is an extremely rare complication of AITL. As the pathophysiology remains unclear, further research is warranted.
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Affiliation(s)
- Teiko Kawahigashi
- Department of General Internal Medicine, Shonan Kamakura General Hospital, Kanagawa 247-8533, Japan
| | - Izumi Kitagawa
- Department of General Internal Medicine, Shonan Kamakura General Hospital, Kanagawa 247-8533, Japan
| | - Eri Tanaka
- Department of Hematology, Shonan Kamakura General Hospital, Kanagawa 247-8533, Japan
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Eladl AE, Shimada K, Suzuki Y, Takahara T, Kato S, Kohno K, Elsayed AA, Wu CC, Tokunaga T, Kinoshita T, Sakata-Yanagimoto M, Nakamura S, Satou A. EBV status has prognostic implication among young patients with angioimmunoblastic T-cell lymphoma. Cancer Med 2019; 9:678-688. [PMID: 31793218 PMCID: PMC6970042 DOI: 10.1002/cam4.2742] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/29/2019] [Accepted: 11/15/2019] [Indexed: 12/30/2022] Open
Abstract
Epstein‐Barr virus (EBV)‐positive B cells have been detected in 66%‐86% of patients with angioimmunoblastic T‐cell lymphoma (AITL). However, it remains controversial whether EBV status has an impact on the survival of patients with AITL. In this study, we aimed to reevaluate the impact of EBV on the clinicopathological characteristics of AITL. In particular, we focused on the impact of EBV in younger patients with AITL. In total, 270 cases of AITL were studied. Epstein‐Barr virus‐positive B cells were detected in 191 (71%) cases (EBER+ group). Among the patients who received anthracycline‐based therapy, the EBER status did not affect the overall survival (OS) or progression‐free survival (PFS). In the younger group of AITL (≤60 years), PFS was significantly worse in the EBER− group compared to the EBER+ group (P = .0013). Furthermore, the multivariate analysis identified EBER‐negative status, thrombocytopenia, and elevated serum IgA level as significant adverse prognostic factors for PFS (P < .001, P < .001, and P = .002). Based on these findings, we constructed new prognostic model for the younger group, based on three adverse factors. We classified the patients into two risk groups: low risk (no or 1 adverse factor) and high risk (2 or 3 adverse factors). This new model for younger patients with AITL showed that both OS and PFS were significantly related to the level of risk (P < .0001). In summary, this study showed that, among younger patients with AITL, an EBER+ status significantly improved prognosis compared to an EBER− status. Our new prognostic model should be applicable to younger patients with AITL.
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Affiliation(s)
- Ahmed E Eladl
- Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.,Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Kazuyuki Shimada
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuka Suzuki
- Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan
| | - Taishi Takahara
- Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Japan
| | - Seiichi Kato
- Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kei Kohno
- Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan
| | - Ahmed Ali Elsayed
- Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.,Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Chun-Chieh Wu
- Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.,Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Takashi Tokunaga
- Department of Hematology and Oncology Research, Nagoya Medical Center, Nagoya, Japan
| | - Tomohiro Kinoshita
- Department of hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan
| | | | - Shigeo Nakamura
- Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan
| | - Akira Satou
- Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Japan
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Colmant C, Camboni A, Dekeuleneer V, Marot L, Dachelet C, Baeck M. Linear IgA dermatosis in association with angioimmunoblastic T-cell lymphoma infiltrating the skin: A case report with literature review. J Cutan Pathol 2019; 47:251-256. [PMID: 31482600 DOI: 10.1111/cup.13576] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 08/09/2019] [Accepted: 08/14/2019] [Indexed: 11/26/2022]
Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive form of peripheral T-cell lymphoma, characterized by systemic symptoms, diffuse lymphadenopathy, hepatosplenomegaly and immunodysregulation. Half of AITL is associated with cutaneous symptoms, but only few cases with bullous eruption have been described. Association with a linear IgA dermatosis is extremely rare. Linear IgA dermatosis can be idiopathic, or linked with drug intake or neoplastic disorders. Some cases of linear IgA dermatosis presenting as toxic epidermal necrolysis (TEN) have been described, most of them being drug induced. We here present the case of a 72-year-old man recently diagnosed with AITL who developed a bullous eruption, presenting as TEN. Histopathology showed deep cutaneous involvement of the lymphoma with a sub-epidermal blistering and direct immunofluorescence revealed a heavy IgA linear deposit on the dermal-epidermal junction. A diagnosis of linear IgA dermatosis associated with cutaneous involvement of an angioimmunoblastic T-cell lymphoma was made. Chemotherapy and corticosteroids allowed cutaneous improvement but the patient died of his lymphoma shortly after.
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Affiliation(s)
- Caroline Colmant
- Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Alessandra Camboni
- Anatomopathology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Valérie Dekeuleneer
- Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Liliane Marot
- Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium.,Anatomopathology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Claire Dachelet
- Anatomopathology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Marie Baeck
- Dermatology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium
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Chernova NG, Sidorova YV, Smirnova SY, Ryzhikova NV, Nikulina EE, Kovrigina AM, Sinitsyna MN, Sudarikov AB. [Molecular diagnosis angioimmunoblastic T-cell lymphoma]. TERAPEVT ARKH 2019; 91:63-69. [PMID: 32598737 DOI: 10.26442/00403660.2019.07.000330] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 11/22/2022]
Abstract
AIM to determine molecular diagnostics routine for different tissue samples in angioimmunoblastic T-cell lymphoma. MATERIALS AND METHODS Molecular studies were performed for 84 primary AITL patients. The median age was 61 year (29-81); the male to female ratio was 48/36. T-cell and B-cell clonality was assessed by GeneScan analysis of rearranged T-cell receptor (TCRG, TCRB) and immunoglobulin heavy chain genes. For the quantitative determination of cells with RHOA G17V mutation real - time polymerase chain reaction (PCR) with allele - specific LNA modified primers was used. RESULTS In lymph nodes rearrangements of T-cell receptor genes were determined in 76 (90.5%) of 84 patients and were absent in 8 (9.5%) cases. Identification of the same clonal products of the TCRG and TCRB genes in the lymph node and in peripheral blood and/or bone marrow indicated the prevalence of the tumor process and was observed in 64.7% of patients. Clonal products in peripheral blood and/or bone marrow different from those in the lymph node indicated reactive cytotoxic lymphocyte population and were noted in 58.8% of AITL cases. Simultaneous detection of T- and B-cell clonality in the lymph node was observed in 20 (24.7%) of 81 patients. Cells with RHOA G17V mutation were detected in lymph node in 45 (54.9%) of 82 patients. The use of allele - specific PCR with LNA modified primers revealed presence of the tumor cells in peripheral blood in 100% and in bone marrow in 93.9% of patients with G17V RHOA mutation in the lymph nodes. CONCLUSION The validity of different molecular assays performed on certain tissue samples for the diagnosis of angioimmunoblastic T-cell lymphoma has been evaluated. Quantitative allele - specific PCR assay for RHOA G17V mutation based on LNA modified primers possesses sufficient sensitivity for tumor process prevalence evaluation and minimal residual disease monitoring.
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Crickx E, Poullot E, Moulis G, Goulabchand R, Fieschi C, Galicier L, Meignin V, Coppo P, Delarue R, Casasnovas O, Roos-Weil D, de Leval L, Parrens M, Michel M, Dupuis J, Le Bras F, Fataccioli V, Martin-Garcia N, Godeau B, Haïoun C, Gaulard P, Mahévas M. Clinical spectrum, evolution, and management of autoimmune cytopenias associated with angioimmunoblastic T-cell lymphoma. Eur J Haematol 2019; 103:35-42. [PMID: 30985955 DOI: 10.1111/ejh.13239] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 04/03/2019] [Accepted: 04/04/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Angioimmunoblastic T-cell lymphoma (AITL) is frequently associated with autoimmune cytopenia (AIC). Whether such patients have a particular phenotype and require particular management is unclear. METHOD Angioimmunoblastic T-cell lymphoma patients from the multicentric database of the Lymphoma Study Association presenting with AIC during disease course were included and matched to AITL patients without AIC (1/5 ratio). RESULTS At diagnosis, AIC patients (n = 28) had more spleen and bone marrow involvement (54% vs 19% and 71% vs 34%, P < 0.001), Epstein-Barr virus replication (89% vs 39%, P < 0.001), gamma globulin titers (median 23 vs 15 g/L, P = 0.002), and proliferating B cells and plasmablasts in biopsies, as compared to control patients (n = 136). The 28 AIC patients had 41 episodes of AIC, diagnosed concomitantly with AITL in 23 (82%) cases. After a median follow-up of 24 months (range 3-155), 10 patients relapsed, all associated with AITL relapse. CONCLUSION Our results provide new insight into AIC associated with AITL by highlighting the significant interplay between AITL and B-cell activation leading to subsequent autoimmunity.
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Affiliation(s)
- Etienne Crickx
- Service de médecine interne, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est, Créteil, France.,Institut Necker Enfants Malades, INSERM U1151/CNRS UMS 8253, Université Paris Descartes, Sorbonne Paris Cité, Paris Cedex, France
| | - Elsa Poullot
- Département de Pathologie, Hôpital Henri-Mondor (AP-HP), Créteil, France.,Faculté de Médecine, Université Paris-Est, Inserm U955, Créteil, France
| | - Guillaume Moulis
- Service de médecine Interne, CHU de Toulouse, Toulouse, France.,UMR 1027 Inserm-Université de Toulouse, Toulouse, France.,CIC 1436, CHU de Toulouse, Toulouse, France
| | - Radjiv Goulabchand
- Service de médecine interne, maladies multi-organiques, Hôpital Saint-Eloi, CHRU Montpellier, Montpellier, France
| | - Claire Fieschi
- Service d'immunologie clinique, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Lionel Galicier
- Service d'immunologie clinique, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Véronique Meignin
- Service d'anatomopathologie, Hôpital Saint-Louis (AP-HP), Paris, France
| | - Paul Coppo
- Service d'hématologie, Centre de référence des microangiopathies thrombotiques, Hôpital Saint-Antoine (AP-HP), Sorbonne Universités, Paris, France
| | - Richard Delarue
- Service d'hématologie, Hôpital Necker (AP-HP), Paris, France
| | - Olivier Casasnovas
- Service d'hématologie, Centre Hospitalier Universitaire de Dijon, Dijon, France
| | - Damien Roos-Weil
- Sorbonne Universités, UPMC Université Paris 06, AP-HP, GRC-11, Groupe de recherche clinique sur les hémopathies lymphoïdes (GRECHY), Hôpital Pitié-Salpétrière (APHP), Paris, France
| | - Laurence de Leval
- Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Marie Parrens
- Département de Pathologie, Hôpital Pessac, Bordeaux, France
| | - Marc Michel
- Service de médecine interne, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est, Créteil, France
| | - Jehan Dupuis
- Unité Hémopathies Lymphoïdes, Hôpital Henri-Mondor (AP-HP), Créteil, France
| | - Fabien Le Bras
- Unité Hémopathies Lymphoïdes, Hôpital Henri-Mondor (AP-HP), Créteil, France
| | - Virginie Fataccioli
- Département de Pathologie, Hôpital Henri-Mondor (AP-HP), Créteil, France.,Faculté de Médecine, Université Paris-Est, Inserm U955, Créteil, France
| | - Nadine Martin-Garcia
- Département de Pathologie, Hôpital Henri-Mondor (AP-HP), Créteil, France.,Faculté de Médecine, Université Paris-Est, Inserm U955, Créteil, France
| | - Bertrand Godeau
- Service de médecine interne, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est, Créteil, France
| | - Corinne Haïoun
- Unité Hémopathies Lymphoïdes, Hôpital Henri-Mondor (AP-HP), Créteil, France
| | - Philippe Gaulard
- Département de Pathologie, Hôpital Henri-Mondor (AP-HP), Créteil, France.,Faculté de Médecine, Université Paris-Est, Inserm U955, Créteil, France
| | - Matthieu Mahévas
- Service de médecine interne, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est, Créteil, France.,Institut Necker Enfants Malades, INSERM U1151/CNRS UMS 8253, Université Paris Descartes, Sorbonne Paris Cité, Paris Cedex, France.,Unité Inserm U955, équipe 2, Hôpital Henri-Mondor, Assistance publique-hôpitaux de Paris, Créteil, France
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38
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Bachy E, Salles G. Unravelling Subtleties of Angioimmunoblastic T-Cell Lymphoma. J Oncol Pract 2019; 15:147-148. [PMID: 30861363 DOI: 10.1200/jop.19.00089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Emmanuel Bachy
- 1 Hôpital Lyon Sud and Université Claude Bernard Lyon 1, Pierre-Bénite, France
| | - Gilles Salles
- 1 Hôpital Lyon Sud and Université Claude Bernard Lyon 1, Pierre-Bénite, France
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39
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Differentiation of angioimmunoblastic T-cell lymphoma from DRESS syndrome. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2018; 7:1684-1686.e1. [PMID: 30557716 DOI: 10.1016/j.jaip.2018.11.048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Revised: 11/29/2018] [Accepted: 11/30/2018] [Indexed: 12/17/2022]
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40
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Chasset F, Richez C, Martin T, Belot A, Korganow AS, Arnaud L. Rare diseases that mimic Systemic Lupus Erythematosus (Lupus mimickers). Joint Bone Spine 2018; 86:165-171. [PMID: 30837156 DOI: 10.1016/j.jbspin.2018.10.007] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2018] [Indexed: 12/13/2022]
Abstract
Several conditions have clinical and laboratory features that can mimic those present in Systemic Lupus Erythematosus (SLE). Some of these "SLE mimickers" are very common, such as rosacea which can be mistaken for the butterfly rash, while others such as Kikuchi disease, type-1 interferonopathies, Castleman's disease, prolidase deficiency, angioimmunoblastic T-cell lymphoma, Evans' syndrome in the context of primary immune deficiencies and the autoimmune lymphoproliferative syndrome are exceptionally uncommon. A proper diagnosis of SLE must therefore be based upon a complete medical history as well as on the adequate constellation of clinical or laboratory findings. While there is no single test that determines whether a patient has lupus or not, the search for auto-antibodies towards nuclear antigens is a key step in the diagnosis strategy, keeping in mind that ANAs are not specific for SLE. In case of persistent doubt, patients should be referred to reference centers with experience in the management of the disease.
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Affiliation(s)
- François Chasset
- Service de dermatologie et d'allergologie, hôpital Tenon, AP-HP, 75020, Paris, France
| | - Christophe Richez
- Immunoconcept, CNRS-UMR 5164, université de Bordeaux, 146, rue Léo-Saignat, 33076, Bordeaux, France; Centre hospitalier universitaire de Bordeaux, FHU ACRONIM, place Amélie-Raba-Léon, 33076, Bordeaux, France; Centre national de référence des maladies autoimmunes et systémiques rares Est Sud-Ouest (RESO)-LUPUS, 67000 Strasbourg, France
| | - Thierry Martin
- Centre national de référence des maladies autoimmunes et systémiques rares Est Sud-Ouest (RESO)-LUPUS, 67000 Strasbourg, France; Service d'immunologie clinique nouvel hôpital civil, 1, place de l'hôpital 67091 Strasbourg cedex, France
| | - Alexandre Belot
- Service de nephrologie, rhumatologie et dermatologie pédiatriques, hôpital Femme Mère-Enfant, hospices civils de Lyon, Lyon, France; Université de Lyon, 59, boulevard Pinel, 69677 Bron cedex, France; Inserm U1111, 69007 Lyon, France; Filière des maladies autoimmunes et autoinflammatoires rares (FAI2R), 69677 Lyon, France
| | - Anne-Sophie Korganow
- Centre national de référence des maladies autoimmunes et systémiques rares Est Sud-Ouest (RESO)-LUPUS, 67000 Strasbourg, France; Service d'immunologie clinique nouvel hôpital civil, 1, place de l'hôpital 67091 Strasbourg cedex, France
| | - Laurent Arnaud
- Centre national de référence des maladies autoimmunes et systémiques rares Est Sud-Ouest (RESO)-LUPUS, 67000 Strasbourg, France; Service de rhumatologie, hôpitaux universitaires de Strasbourg, 67098 Strasbourg, France; Université de Strasbourg, Inserm UMR-S 1109, 67000 Strasbourg, France.
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Mukherjee T, Dutta R, Pramanik S. Aggressive Angioimmunoblastic T Cell Lymphomas (AITL) with Soft Tissue Extranodal Mass Varied Histopathological Patterns with Peripheral Blood, Bone Marrow, and Splenic Involvement and Review of Literature. Indian J Surg Oncol 2018; 9:11-14. [PMID: 29563728 DOI: 10.1007/s13193-017-0657-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Accepted: 04/20/2017] [Indexed: 11/29/2022] Open
Abstract
Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell non-Hodgkin lymphoma with an aggressive fatal course and it has varied clinical presentation with an uncommon presentation when they present as soft tissue masses or when there is spill in the peripheral blood or there are composite lymphomas that are rare presentations. Common presentations include lymphadenopathy, fever and systemic symptoms, hemolytic anemias, skin rashes, and rheumatoid arthritis. The classical histopathology is absence of follicles in lymph nodes with presence of high endothelial venules and the tumor cells of small to medium-sized lymphocytes with pale cytoplasm mixed with reactive T cells. On immunohistochemistry, the cells are positive for CD3, CD4, CD10, BCL2, and CXCL13. In this observational study, the clinicopathologic presentation and the immunohistochemical profile of five cases who initially presented with a soft tissue mass which is an extremely rare presentation of this rare type of non-Hodgkin lymphoma that was diagnosed at our center with peripheral blood and bone marrow involvement and the clinicopathologic presentation, immunohistochemical profile, and response to treatment on follow-up are correlated with the literature review. One case had a fulminant and aggressive course and was fatal within 2 months of diagnosis. The rest of the four cases are on regular chemotherapy and follow-up. Our five cases had presented with soft tissue masses, two in the axillary regio,n two in the hand, and one in the scapular region with an extranodal presentation, and there was associated lymphadenopathy which developed subsequently with classic histomorphology and immunohistochemical findings. The age range was 46-54 years and all five cases were males. Three cases were with anemia (hemoglobin range 6.5-8.0 mg/dl) and all five cases were having peripheral blood plasmacytosis. Histopathology was classic with paracortical involvement with polymorphous population of cells with neoplastic lymphocytes of small and large sizes with numerous arborizing blood vessels which correspond to high endothelial venules. Microscopically, three architectural patterns; pattern I was seen in three cases (60%) and then pattern II and III in one case each (20% each). Immunohistochemistry revealed CD4+, CD8-, CXCL13+, CD10+, BCL6+, CD19, CD20, CD1a, Tdt, CD21, and CD23+ in follicular dendritic cells. AITL is a rare and aggressive non-Hodgkin lymphoma with varied clinical presentation with classic histomorphology with various patterns which may cause diagnostic dilemma and immunophenotypic findings, and prompt and early diagnosis is mandatory for institution of therapy.
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Affiliation(s)
- Tanushri Mukherjee
- 1Department of Oncopathology, Command Hospital, Kolkata, West Bengal 700027 India
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42
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Rai MP, Bedi PS, Marinas EB, Khan NNS. Angioimmunoblastic T-cell lymphoma: a rare subtype of peripheral T-cell lymphoma. Clin Case Rep 2018; 6:750-752. [PMID: 29636953 PMCID: PMC5889216 DOI: 10.1002/ccr3.1388] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Revised: 12/30/2017] [Accepted: 01/03/2018] [Indexed: 12/28/2022] Open
Abstract
Angioimmunoblastic T‐cell lymphoma (AITL) is a rare form of NHL and usually presents in the late stage due to the atypical laboratory findings. Immunohistochemistry of the lymph node in AITL is characterized by positive CD2, CD3, CD4, CD10, CXCL‐13, PD1 often BCL‐6 and CD20 positive. Meshworks of follicular dendritic cells are seen outside follicles with CD21 and CD23 stains. EBV can be often positive as well. Autologous transplantation should be offered in the first remission as poor outcome is reported with anthracycline‐containing regimens.
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Affiliation(s)
- Manoj Ponadka Rai
- Michigan State University/Sparrow hospital B301, 788 Service Road East Lansing Michigan 48824
| | | | | | - Nazia Naz S Khan
- Michigan State University/Sparrow hospital B301, 788 Service Road East Lansing Michigan 48824
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43
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Igawa T, Omote R, Sato H, Taniguchi K, Miyatani K, Yoshino T, Sato Y. A possible new morphological variant of mantle cell lymphoma with plasma-cell type Castleman disease-like features. Pathol Res Pract 2017; 213:1378-1383. [DOI: 10.1016/j.prp.2017.09.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 09/06/2017] [Accepted: 09/15/2017] [Indexed: 01/09/2023]
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44
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Rapid Fatal Acute Peripheral T-Cell Lymphoma Associated With IgG Plasma Cell Leukemia and IgA Hypergammaglobulinemia. Appl Immunohistochem Mol Morphol 2017; 24:e89-e93. [PMID: 27824644 DOI: 10.1097/pai.0000000000000361] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Simultaneous occurrence of T-cell and B-cell neoplasms is rare, and etiologic relationships between these 2 malignancies are poorly understood. We describe the case of a 66-year-old woman who was admitted to the hospital because of fever, hemoptysis, lymphadenopathy, and skin rash. Enlarged lymph nodes in axillary, pectoral, paratracheal, and periportal regions as well as slight hepatomegaly and splenomegaly were confirmed. A peripheral blood smear revealed rouleaux formation and numerous circulating plasma cells, with plasmacytoid lymphocytes. Immunofixation-electrophoresis detected a monoclonal band defined as immunoglobulin (IgG)-lambda light chains with broad-band polyclonal IgA. The patient died from abrupt splenic rupture before diagnostic work-up was finished. Postmortem examination revealed infiltration of atypical lymphoid cells exhibiting high proliferative activity admixed with typical and atypical plasma cells in several organs. Thus, plasma cell leukemia (IgG-lambda) as a rare and aggressive variant of plasma cell myeloma in the present case was associated with aggressive peripheral T-cell lymphoma and polyclonal (IgA) plasmacytosis.
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45
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Hill QA, Stamps R, Massey E, Grainger JD, Provan D, Hill A. Guidelines on the management of drug-induced immune and secondary autoimmune, haemolytic anaemia. Br J Haematol 2017; 177:208-220. [PMID: 28369704 DOI: 10.1111/bjh.14654] [Citation(s) in RCA: 95] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Quentin A Hill
- Department of Haematology, Leeds Teaching Hospitals, Leeds, UK
| | | | | | - John D Grainger
- Royal Manchester Children's Hospital, University of Manchester, Manchester, UK
| | - Drew Provan
- Barts and The London School of Medicine and Dentistry, London, UK
| | - Anita Hill
- Department of Haematology, Leeds Teaching Hospitals, Leeds, UK
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46
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Angioimmunoblastic T-cell lymphoma: the many-faced lymphoma. Blood 2017; 129:1095-1102. [PMID: 28115369 DOI: 10.1182/blood-2016-09-692541] [Citation(s) in RCA: 138] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 12/09/2016] [Indexed: 02/07/2023] Open
Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon subtype of mature peripheral T-cell lymphoma (PTCL). The history of AITL is much longer and deeper than the literature would suggest given the many names that have preceded it. Advanced-stage disease is common with uncharacteristic laboratory and autoimmune findings that often slow or mask the diagnosis. Significant strides in the immunohistochemical and molecular signature of AITL have brought increased ability to diagnose this uncommon type of PTCL. The 2016 World Health Organization classification of lymphoid neoplasms recently acknowledged the complexity of this diagnosis with the addition of other AITL-like subsets. AITL now resides under the umbrella of nodal T-cell lymphomas with follicular T helper phenotype. Induction strategies continue to focus on increasing complete remission rates that allow more transplant-eligible patients to proceed toward consolidative high-dose therapy and autologous stem cell rescue with improving long-term survival. There are several clinical trials in which recently approved drugs with known activity in AITL are paired with induction regimens with the hope of demonstrating long-term progression-free survival over cyclophosphamide, doxorubicin, vincristine, and prednisone. The treatment of relapsed or refractory AITL remains an unmet need. The spectrum of AITL from diagnosis to treatment is reviewed subsequently in a fashion that may one day lead to personalized treatment approaches in a many-faced disease.
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Suárez AE, Artiga M, Santonja C, Montes-Moreno S, De Pablo P, Requena L, Piris MA, Rodríguez-Pinilla SM. Angioimmunoblastic T-cell lymphoma with a clonal plasma cell proliferation that underwent immunoglobulin isotype switch in the skin, coinciding with cutaneous disease progression. J Cutan Pathol 2016; 43:1203-1210. [DOI: 10.1111/cup.12814] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Revised: 08/19/2016] [Accepted: 08/30/2016] [Indexed: 12/20/2022]
Affiliation(s)
- Ana E. Suárez
- Pathology Department; Hospital Universitario Fundación Jiménez Díaz; Madrid Spain
| | - M.J. Artiga
- Tumor Bank; Centro Nacional de Investigaciones Oncológicas; Madrid Spain
| | - Carlos. Santonja
- Pathology Department; Hospital Universitario Fundación Jiménez Díaz; Madrid Spain
| | | | - P. De Pablo
- Dermatology Department; Hospital del Tajo; Madrid Spain
| | - Luis Requena
- Dermatology Department; Hospital Universitario Fundación Jiménez Díaz; Madrid Spain
| | - Miguel A. Piris
- Pathology Department; Hospital Universitario Marqués de Valdecilla; Santander Spain
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Extranodal Marginal Zone Lymphoma-like Presentations of Angioimmunoblastic T-Cell Lymphoma: A T-Cell Lymphoma Masquerading as a B-Cell Lymphoproliferative Disorder. Am J Dermatopathol 2016; 37:604-13. [PMID: 25839892 DOI: 10.1097/dad.0000000000000266] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is the second most common type of peripheral T-cell lymphoma worldwide, and in some countries, it is the most common form. Clinically, AITL usually presents with systemic symptoms, diffuse lymphadenopathy, hepatosplenomegaly, and common laboratory abnormalities such as hypergammaglobulinemia. Rashes are seen in 50%-80% of patients. AITL derives from follicular T-helper cells (TFH), that express germinal center markers and produce hyperactivation of B-cells seen in AITL. Although the histological features of AITL in the skin could be similar to pathological findings present in lymph node biopsies, herein, we present 2 cases of AITL with histological and immunophenotypic features that were somewhat suggestive of extranodal marginal zone lymphoma. Caution is urged to exclude the possibility of a systemic T-cell lymphoma such as AITL in cutaneous and lymph node B-cell proliferations.
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Cutaneous manifestations of angioimmunoblastic T-cell lymphoma: clinical and pathological characteristics. Am J Dermatopathol 2016; 37:274-83. [PMID: 25794369 DOI: 10.1097/dad.0000000000000144] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Angioimmunoblastic T-cell lymphoma (AITL), an uncommon variant of peripheral T-cell lymphoma, affects the skin in approximately 50% of cases. Its protean clinical and histopathological cutaneous manifestations pose a challenge in diagnosis, particularly when these precede the diagnosis of AITL on a lymph node biopsy. In this retrospective study, we compared 11 cases of AITL with cutaneous manifestations (mean age 67 years; male:female ratio 1:0.8; 24 skin biopsies) with 20 control cases of inflammatory and non-AITL lymphomatous diseases (mean age 52 years; male:female ratio 1:1.5; 26 skin biopsies). Clinical, histopathological, immunohistochemical, and molecular data were documented. New insights into the clinical evolution of cutaneous involvement by AITL (C-AITL), from early macular, through papular to nodular stages, were observed. Microscopically, a parallel increment in the density of the dermal infiltrate and in the detection of lymphocyte cytological atypia was noted over time. Identification and quantification of follicular T-helper cells (Tfh), the neoplastic lineage, by immunohistochemistry helped to separate cases of C-AITL from inflammatory controls, offering promise as a useful diagnostic adjunct. The presence of T-cell clonality did not have discriminatory value between the 2 groups. Our work suggests that the early maculopapular phase of C-AITL eludes identification on pathological grounds alone and that features such as cytological atypia and high endothelial venules lack diagnostic specificity. In the context of (1) a rash that simulates a drug/viral exanthem or an acute manifestation of a connective tissue disorder, but proves recalcitrant, (2) constitutional abnormalities and/or lymphadenopathy that persist, and (3) a Tfh cell-rich perivascular dermatitis, the diagnosis of early C-AITL can be suspected, but not confirmed, without the benefit of a lymph node biopsy. The later nodular phase of C-AITL occurring in a similar constitutional background, can usually be discerned as lymphomatous, clinically and pathologically. Here a Tfh cell-rich infiltrate is a clue to the specific diagnosis, but confirmation by a nodal evaluation remains mandatory. Despite the difficulty in establishing a diagnosis of C-AITL in its early stages, and speculation that the initial eruptions might be reactive in nature, our sequential data support the concept that these are lymphomatous ab initio. To address the diagnostic challenge presented by this disease, meaningful integration of clinical and pathological data is imperative.
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de Leval L, Parrens M, Le Bras F, Jais JP, Fataccioli V, Martin A, Lamant L, Delarue R, Berger F, Arbion F, Bossard C, Copin MC, Canioni D, Charlotte F, Damaj G, Dartigues P, Fabiani B, Ledoux-Pilon A, Montagne K, Molina T, Patey M, Tas P, Peoch M, Petit B, Petrella T, Picquenot JM, Rousset T, Rousselet MC, Soubeyran I, Thiebault S, Tournilhac O, Xerri L, Gisselbrecht C, Haioun C, Delsol G, Gaulard P. Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets. Haematologica 2015; 100:e361-4. [PMID: 26045291 DOI: 10.3324/haematol.2015.126300] [Citation(s) in RCA: 95] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Affiliation(s)
- Laurence de Leval
- Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Marie Parrens
- Département de Pathologie, Hôpital Pessac, Bordeaux, France
| | - Fabien Le Bras
- Unité Hémopathies Lymphoïdes, Hôpital Henri Mondor, Assistance publique-Hôpitaux de Paris (AP-HP), F-94010 Créteil, France
| | | | | | - Antoine Martin
- Service d'Anatomie et Cytologie Pathologiques, Hôpital Avicenne, APHP, Bobigny, France
| | | | | | - Françoise Berger
- Département de Pathologie, Hôpital Lyon-Sud, Pierre-Benite, France
| | - Flavie Arbion
- Service d'Anatomie et Cytologie Pathologiques, Hôpital Bretonneau, Tours, France
| | - Céline Bossard
- Service d'Anatomie et Cytologie Pathologiques, Hôpital Hôtel Dieu, Nantes, France
| | | | | | - Frédéric Charlotte
- Département de Pathologie, Hôpital La Pitié-Salpétrière, AP-HP, Paris, France
| | | | - Peggy Dartigues
- Département de Pathologie, Institut Gustave Roussy; université Paris Sud-11, Villejuif, France
| | - Bettina Fabiani
- Département d'Anatomie Pathologique, Hôpital Saint-Antoine, AP-HP, Paris, France
| | | | - Karine Montagne
- Service de Pathologie, Hôpitaux de Brabois, Vandoeuvre, France
| | - Thierry Molina
- Département de Pathologie, Hôpital Necker, AP-HP, Paris, France
| | - Martine Patey
- Laboratoire Central d'Anatomie et de Cytologie Pathologiques, Hôpital Robert Debré, Reims, France
| | - Patrick Tas
- Service d'Anatomie et Cytologie Pathologiques, CHU Pontchaillou, Rennes, France
| | - Michel Peoch
- Service d'Anatomie et Cytologie Pathologiques, CHRU de St Etienne, France
| | - Barbara Petit
- Département de Pathologie, CHU Dupuytren, Limoges, France
| | - Tony Petrella
- Service d'Anatomie et Cytologie Pathologique, CHU Dijon, France
| | | | - Thérèse Rousset
- Laboratoire d'Anatomie et Cytologie Pathologiques, Hôpital Gui de Chauliac, Montpellier, France
| | | | | | | | - Olivier Tournilhac
- Service de Thérapie Cellulaire et d'Hématologie clinique adulte, EA3846, Inserm CIC-501, Université d'Auvergne CHU Clermont-Ferrand Hôpital Estaing, Clermont-Ferrand, France
| | - Luc Xerri
- Département de Biopathologie, Institut Paoli-Calmettes, Marseille, France
| | | | - Corinne Haioun
- Unité Hémopathies Lymphoïdes, Hôpital Henri Mondor, Assistance publique-Hôpitaux de Paris (AP-HP), F-94010 Créteil, France
| | - Georges Delsol
- Département de Pathologie, Hôpital Purpan, Toulouse, France
| | - Philippe Gaulard
- Département de Pathologie, Hôpital Henri Mondor, APHP, Créteil, France INSERM U955, Créteil, France Université Paris Est, Créteil, France
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