The Conspicuousness of High Endothelial Venules in Angioimmunoblastic T-cell Lymphoma Is Due to Increased Cross-sectional Area, Not Increased Distribution Density

2021 ◽  
Vol 69 (10) ◽  
pp. 645-657
Author(s):  
Akiya Kogami ◽  
Mana Fukushima ◽  
Hitomi Hoshino ◽  
Takuya Komeno ◽  
Tadakazu Okoshi ◽  
...  

Angioimmunoblastic T-cell lymphoma (AITL) is a T-cell lymphoma of follicular helper T-cell origin. Histologically, neoplastic T-cells proliferate to form clusters adjacent to or between arborizing high endothelial venules (HEVs). HEVs in normal lymph nodes express sulfated glycans called peripheral lymph node addressin (PNAd); however, it remains unclear whether PNAd is also expressed on HEVs in AITL. Furthermore, although it is widely accepted that HEVs are conspicuous in AITL due to their proliferation, quantitative histological support for this concept is lacking. To investigate these issues, we employed monoclonal antibodies recognizing PNAd, namely, MECA-79, HECA-452, and 297-11A, and performed quantitative immunohistochemical analysis of HEVs in 36 AITL-affected and 67 normal lymph nodes. Staining with all three antibodies confirmed that AITL HEVs express PNAd. Moreover, AITL HEVs were bound calcium-dependently by L-selectin-IgM fusion proteins, indicating that they function in the recruitment of L-selectin-expressing lymphocytes. Unexpectedly, HEV distribution density was not increased but rather decreased in AITL compared with normal lymph nodes, but HEV cross-sectional area in AITL was significantly greater than that seen in normal lymph nodes. Overall, these results indicate that the prominence of AITL HEVs is likely due to increased cross-sectional area rather than increased distribution density.

2015 ◽  
Vol 7 (2) ◽  
Author(s):  
Timothy Beer ◽  
Patrick Dorion

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma typically characterized by prominent lymphadenopathy and B-symptoms at the time of presentation, polyclonal hypergammaglobulinemia, autoimmune hemolysis and frequent but highly variable involvement of Epstein- Barr virus (EBV). Lymph node biopsy findings typically include effacement of nodal architecture, polymorphic infiltrate, atypical T-cells (usually CD4+/CD10+/PD1+) and prominent proliferations of high endothelial venules and follicular dendritic cells. However, this classic constellation of pathologic findings is often initially obscured by a prominence of EBV+ B-immunoblasts with or without associated peripherally circulating EBV DNA. Here we document the first reported case of an acute serologic EBV profile (VCA-IgM) in a patient with AITL, and we recommend that clinicians maintain a high index of suspicion for AITL in the appropriate clinical scenario, irrespective of Epstein-Barr related findings.


Blood ◽  
2012 ◽  
Vol 120 (4) ◽  
pp. 812-821 ◽  
Author(s):  
Julia I. Ellyard ◽  
Tiongsun Chia ◽  
Socorro-Maria Rodriguez-Pinilla ◽  
Jaime L. Martin ◽  
Xin Hu ◽  
...  

Abstract Angioimmunoblastic T-cell lymphoma (AITL) is the second most common peripheral T-cell lymphoma with unusual clinical and pathologic features and a poor prognosis despite intensive chemotherapy. Recent studies have suggested AITL derives from follicular helper T (TFH) cells, but the causative molecular pathways remain largely unknown. Here we show that approximately 50% of mice heterozygous for the “san” allele of Roquin develop tumors accompanied by hypergammaglobulinemia by 6 months of age. Affected lymph nodes displayed the histologic features diagnostic of AITL, except for the presence of expanded FDC networks. Accumulation of TFH cells preceded tumor development, and clonal rearrangements in the TCR-β genes were present in most tumors. Furthermore, TFH cells exhibited increased clonality compared with non-TFH cells from the same lymph nodes, even in the absence of tumors. Genetic manipulations that prevent TFH development, such as deletion of ICOS, CD28, and SAP, partially or completely abrogated tumor development, confirming a TFH-derived origin. Roquinsan/+ mice emerge as a useful model to investigate the molecular pathogenesis of AITL and for preclinical testing of therapies aimed at targeting dysregulated TFH cells or their consequences.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4545-4545
Author(s):  
Lucile Baseggio ◽  
Francoise Berger ◽  
Josiane Carret ◽  
Catherine Thieblemont ◽  
Dominique Morel ◽  
...  

Abstract Angioimmunoblastic T-cell lymphoma (AITL) is a distinct clinicopathological entity among peripheral T-cell lymphoma in the WHO classification. Whereas antigen “loss” or “deletion” of one or several pan-T cell antigens is a hepful feature of neoplastic lymphocytes in many T-cell lymphomas, no specific immunophenotypic patterns were available to recognize the tumour T-cells of AITL until recently. Indeed, Attygalle et al. reported that in this disorder neoplastic T-cells can be recognized by the aberrant expression of CD10 using immunochemistry in lymph nodes as well as in the involved extranodal sites. Lee et al. has also confirmed this specific phenotypic feature in cell suspension of lymph nodes using flow cytometry (FCM) in 3 cases of AITL. Here, we evaluated the CD10 expression by T cells in patients with AITL using four-colour FCM. The present study included lymph nodes (LN, n=10), peripheral blood (PB, n=5), bone marrow (n=1) and skin (n=1) samples from 13 patients with a diagnosis of AITL and with available cytologic histologic, immunologic and molecular data. Lymph nodes of reactive hyperplasia (n=13), B-cell lymphoma (n=23), other T-cell lymphoma (n=6) and peripheral blood from healthy donors (n=18) were used as control group. According with previous immunohistochemistry results, a fraction of T-cells expressed CD10 (using a level of at least 5% of all CD5+ cells) in 9/10 AITL lymph nodes with a mean number of 18%. Interestingly, among these 9 cases, 5 could be studied in peripheral blood also and all cases showed a fraction of T-cells expressing CD10, whatever be the lymphocytosis (median 1.1 109/l range 0.82 to 11.32 109/l). In three of these cases, tumoral T-cells presented also lack of surface CD3. In two cases of AITL diagnosed in LN, the aberrant CD10 expression by T-cells was found in bone marrow and skin, respectively. In the control group, T-cells were CD10 negative using the cut-off of 5%. In conclusion, we demonstrate that the assessment of CD10 expression by neoplastic T-cells can be achieved by multi-colour FCM in lymph nodes and involved extranodal sites. Our results are concordant with the statement of Attygalle that CD10 expression by T-cells can be used as a marker of both malignancy and AITL type. In addition, this is to our knowledge the first description of circulating CD10 neoplastic T-cells in AITL. Further study with a larger series of patients is required to confirm these data, to standardize the cut-off of positivity and to evaluate the sensibility of FCM versus immunohistochemistry. Figure Figure


2012 ◽  
Vol 74 (4) ◽  
pp. 399-404
Author(s):  
Kana KOZONO ◽  
Kazuhiko YAMAMURA ◽  
Toshihiko MASHINO ◽  
Masutaka FURUE ◽  
Hideki ASAOKU ◽  
...  

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110132
Author(s):  
Jie Sun ◽  
Sha He ◽  
Hong Cen ◽  
Da Zhou ◽  
Zhe Li ◽  
...  

Objective To explore prognostic factors and develop an accurate prognostic prediction model for angioimmunoblastic T-cell lymphoma (AITL). Methods Clinical data from Chinese patients with newly diagnosed AITL were retrospectively analysed. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier method survival curves; prognostic factors were determined using a Cox proportional hazards model. The sensitivity and specificity of the predicted survival rates were compared using area under the curve (AUC) of receiver operating characteristic (ROC) curves. Results The estimated 5-year OS and PFS of 55 eligible patients with AITL were 22% and 3%, respectively. Multivariate analysis showed that the presence of pneumonia, and serous cavity effusions at initial diagnosis were significant prognostic factors for OS. Based on AUC ROC values, our novel prognostic model was superior to IPI and PIT based models and suggested better diagnostic accuracy. Conclusions Our prognostic model based on pneumonia, and serous cavity effusions at initial diagnosis enabled a balanced classification of AITL patients into different risk groups.


2020 ◽  
Vol 9 (1) ◽  
pp. 1746553
Author(s):  
Gyu Jin Lee ◽  
Yukyung Jun ◽  
Hae Yong Yoo ◽  
Yoon Kyung Jeon ◽  
Daekee Lee ◽  
...  

2021 ◽  
Vol 9 (6) ◽  
Author(s):  
Wendi Bao ◽  
Kendall L. Buchanan ◽  
Loretta S. Davis

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