scholarly journals The microenvironment of classical Hodgkin lymphoma: heterogeneity by Epstein–Barr virus presence and location within the tumor

2016 ◽  
Vol 6 (5) ◽  
pp. e417-e417 ◽  
Author(s):  
R Wu ◽  
A Sattarzadeh ◽  
B Rutgers ◽  
A Diepstra ◽  
A van den Berg ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Classical Hodgkin Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

A fulminant case of classical Hodgkin lymphoma: A diagnostic dilemma of Epstein‐Barr virus‐positive large B‐cell neoplasms

2019 ◽  
Vol 69 (7) ◽  
pp. 407-413
Author(s):  
Shojiro Ichimata ◽  
Mikiko Kobayashi ◽  
Maki Ohya ◽  
Toshiaki Otsuki ◽  
Katsuya Yanagisawa ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Classical Hodgkin Lymphoma ◽  
Diagnostic Dilemma ◽  
Barr Virus ◽  
Epstein Barr ◽  
Large B Cell

Association ofDDX58177 C > T polymorphism with decreased risk of Epstein–Barr virus-related nodular sclerosis classical Hodgkin lymphoma

2016 ◽  
Vol 58 (2) ◽  
pp. 438-444
Author(s):  
Paloma Martin ◽  
Jimena Martínez-Velasquez ◽  
Maria Jose Coronado ◽  
Isabel Krsnik ◽  
Mariano Provencio ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Classical Hodgkin Lymphoma ◽  
Barr Virus ◽  
Nodular Sclerosis ◽  
Epstein Barr

Epstein-Barr Virus Status Correlates with Composition and Prognostic Impact of the Tumor Microenvironment in Classical Hodgkin Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 52-52
Author(s):  
Peter Kamper ◽  
Knud Bendix ◽  
Stephen Jacques Hamilton-Dutoit ◽  
Bent Honore ◽  
Francesco d'Amore
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Cell Marker ◽  
Classical Hodgkin Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

Abstract Abstract 52 Background: Classical Hodgkin lymphoma (cHL) is often characterized by a minority of neoplastic cells surrounded by a heterogeneous background of reactive non-neoplastic cells. An increased amount of certain cell subsets, such as T-regulatory lymphocytes and macrophages, in the microenvironment of cHL tumor lesions has been found to correlate with an adverse prognosis, probably as a result of enhanced immune tolerance towards tumor cells. Furthermore, it has also been suggested that the presence of Epstein-Barr virus (EBV) infection in the Hodgkin Reed-Sternberg (HRS) cells, may modulate the composition of the tumor microenvironment. Aim: In the present study, we have analyzed the possible correlation between EBV-status, a number of tumor microenvironment parameters and outcome in a large retrospective series of newly diagnosed cHL patients. Design and Methods: A tissue microarray was constructed from paraffin embedded pre-therapeutic tumor tissue biopsies obtained from 288 newly diagnosed cHL cases. The expression in the tumor microenvironment of the macrophage markers CD68 and CD163, the regulatory T-cell marker FoxP3 and the cytotoxic T-cell marker Granzyme-B (GrB) was assessed by immunohistochemistry (IHC) using a previously described semi-automated stereological counting approach (Haematologica 2011;96:269–276). The presence of EBV in HRS cells was investigated using 'in situ' hybridization for EBV-encoded RNAs 1 and 2 and LMP-1 IHC. Clinical data were obtained from clinical records. The correlation between clinic-pathological features and EBV was assessed using the rank-sum or Kruskal-Wallis test. The impact of clinico-pathological parameters on event-free (EFS) and overall survival (OS) was evaluated using the log rank test. Results: The 288 patients had a median age of 37 yrs (range: 6–86 yrs). The M:F ratio was 1.3. One third (33%) of the patients were positive for EBV in the HRS cells. EBV-positive cases exhibited higher numbers of CD68 (p=0.001), CD163 (p=0.0002), GrB (p<0.0001), and FoxP3 (0.0009)-positive cells. Excluding cases of mixed cellularity from the analysis, the significant correlation between EBV and CD163 (p=0.03), GrB (p=0.003), FoxP3 (p=0.006) remained, whereas the correlation for CD68 was slightly weakened (p=0.06). In the entire cohort (n=288), a high expression of CD68, CD 163 and GrB were found to correlate with significantly lower OS and EFS (high vs. low CD68: 5-year OS, 73% vs. 87% p=0.002, 5-year EFS, 58% vs. 70% p=0.03; high vs. low CD163: 5-year OS, 78% vs. 87%, p=0.03, 5-year EFS, 62% vs. 69%, p= 0.04) and high GrB: 5-year OS, 77% vs 88 %, p=0.004, 5-year EFS, 61% vs. 69%, p= 0.02). Interestingly, the influence of tumor microenviromental parameters on outcome was more pronounced in EBV-negative cases (n=193) than in EBV-positive ones (n=95). In the former, significantly lower OS and EFS values were associated with a high expression of CD68 (high vs. low CD68: 5-year OS, 60% vs. 92%, 5-year EFS, 43% vs. 71%, both p<0.001), high CD163 (5-year OS, 72% vs. 89%, p<0.001, 5-year EFS, 58% vs. 69%, p= 0.03) and high GrB (5-year OS, 61% vs. 90%, 5-year EFS, 43%vs. 71%, both p<0.001). Among the EBV-positive cohort, the corresponding OS and EFS values were high CD68 (5-year OS, 85% vs. 82%, p=0.69, 5-year EFS, 72%vs. 66%, p=0.43), high CD163 (5-year OS, 86% vs. 84%, p=0.34, 5-year EFS, 67%vs. 71%, p=0.48) and high GrB (5-year OS, 88% vs. 81%, p=0.34, 5-year EFS, 73%vs. 65%, p= 0.63).The number of FoxP3-cells was not found to affect the prognosis in neither EBV-negative nor EBV-positive cases. Conclusions: The present study confirms that the EBV-status in cHL is associated with distinct features of the tumor microenvironment. As a novel finding, our results suggest that the prognostic impact of intratumoral reactive non-neoplastic cell subsets is EBV-status dependent, i.e. a significantly adverse impact of an increased amount of certain bystander cell subsets on outcome was only found in EBV-negative cases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Tumor microenvironment composition in pediatric classical Hodgkin lymphoma is modulated by age and Epstein-Barr virus infection

2011 ◽  
Vol 131 (5) ◽  
pp. 1142-1152 ◽  
Author(s):  
Mário Henrique M. Barros ◽  
Gabriela Vera-Lozada ◽  
Fernando A. Soares ◽  
Gerald Niedobitek ◽  
Rocio Hassan
Keyword(s):  
Tumor Microenvironment ◽  
Virus Infection ◽  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Epstein Barr Virus Infection ◽  
Classical Hodgkin Lymphoma ◽  
Barr Virus ◽  
Epstein Barr ◽  
Barr Virus Infection

scholarly journals The characterization and frequency of diagnosis of EBV-positive variants with a lymphoid predominance in the structure of Hodgkin lymphoma

2021 ◽  
Vol 66 (4) ◽  
pp. 567-579
Author(s):  
I. A. Shupletsova ◽  
A. M. Kovrigina
Keyword(s):  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Classical Hodgkin Lymphoma ◽  
Biopsy Material ◽  
Barr Virus ◽  
Histological Variants ◽  
Epstein Barr ◽  
Old Men ◽  
Age Range

Introduction. Epstein — Barr virus (EBV) plays an important role in the pathogenesis of lymphoid tumors, in particular Hodgkin lymphoma. The frequency of expression of the EBV varies in different histological variants of classical Hodgkin lymphoma and is rarely observed in nodular lymphocyte predominant Hodgkin lymphoma.Aim — to study the pathomorphological features of the histological variants of Hodgkin lymphoma with lymphoid predominance associated with the EBV, as well as the frequency of their diagnosis in the structure of Hodgkin lymphoma.Materials and methods. The retrospective study included 794 patients with a verified diagnosis of Hodgkin lymphoma using histological and immunohistochemical methods on biopsy material for the period 2018–2019 (age range — 18–91 years old; median — 34 years old; men : women — 1.1 : 1). The presence of EBV in biopsies was assessed by immunohistochemical reaction with antibodies to EBV (clone LMP1), or by chromogenic in situ hybridization with probes for EBV-encoded small RNAs.Results. Classical Hodgkin lymphoma was diagnosed in 91 % (725/794) cases, nodular lymphocyte predominant Hodgkin lymphoma — in 9 % (69/794) cases. EBV-positive Hodgkin lymphoma accounted for 11 % (82/725) of all cases of classical Hodgkin lymphoma, (age range — 18–81 years old, median — 45 years old; men : women — 2.5 : 1). All cases of nodular lymphocyte predominant Hodgkin lymphoma were EBV-negative. Lymphocyte-rich classical Hodgkin lymphoma was found in 14 patients (14/725, 2 %), 4 patients showed intermediate morphoimmunohistochemical features with nodular lymphocyte predominant Hodgkin lymphoma, which were statistically significantly different from classical Hodgkin lymphoma by the presence of B-zones in the form of large nodules (p = 0.0157) and expression CD20 by tumor cells (p = 0.0404).Conclusion. Nodular lymphocyte predominant Hodgkin lymphoma is not characterized by a connection with EBV infection, unlike classical variant — lymphocyte-rich classical Hodgkin lymphoma. The obtained data support the concept of the existence of a transient form of Hodgkin lymphoma, which has the features of nodular lymphocyte predominant Hodgkin lymphoma and classical Hodgkin lymphoma, in the pathogenesis of which the Epstein — Barr virus likely plays a role. 

Karyotypic abnormalities associated with Epstein–Barr virus status in classical Hodgkin lymphoma

2016 ◽  
Vol 209 (9) ◽  
pp. 408-416 ◽  
Author(s):  
Nathan D. Montgomery ◽  
Wilborn B. Coward ◽  
Steven Johnson ◽  
Ji Yuan ◽  
Margaret L. Gulley ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Classical Hodgkin Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

A Novel Hodgkin Lymphoma Cell Line (KHL) Established from An Untreated Patient.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1448-1448
Author(s):  
Ta-Chih Liu ◽  
Yuan-Shiang Kao ◽  
Rachael Demuth ◽  
Nina Mathews ◽  
Carmen Espinoza ◽  
...  
Keyword(s):  
Lymph Node ◽  
Cell Line ◽  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Chromosomal Aberration ◽  
Epstein Barr Virus ◽  
Early Stage ◽  
Classical Hodgkin Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

Abstract The paucity of Hodgkin cell/Reed-Sternberg cell in classical Hodgkin Lymphoma (HL) represents a general problem for molecular and cytogenetic studies. The established HL cell lines could be used for such studies. However, only about 10 cell lines have been established and all of them were isolated from patients in late stage of illness when the tumor had recurred. Only one of these cell lines is known to be positive for Epstein- Barr virus antigen. In addition, the pattern of chromosomal aberration in these cell lines is highly complex. Therefore, it is necessary to have a cell line established from the early stage of disease, without prior treatment and with less chromosomal aberration for research. A sample of left axillary lymph node from a 27-year-old male with early stage of HL, and without prior chemotherapy, was cultured in RPMI 1640 media supplemented with fetal calf serum for routine cytogenetic study. The culture, passed weekly, now in its 60st week, 57th passes is growing autonomously without supplement of any growth factor. The original lymph node biopsy showed a classical Hodgkin lymphoma, mixed cellularity (WHO Classification) and the Hodgkin cells/Reed-Sternberg cells were positive for CD30, 4+(100%), CD20, 2+(33%) and negative for CD3, CD15, CD43, ALK-1 antigen and epithelial membrane antigen. EBV nuclear antigen 1 DNA and RNA are detected by PCR method. The cell line is positive for CD30, CD20, and Epstein-Barr virus (EBV) latent membrane protein, but negative for CD3, CD79a, and EBV early antigen. By florescent insitu hybridization the cell line is negative for p53 deletion, ALK gene rearrangement, MLL gene deletion, and t(12;21). A ploidy analysis by flow cytometry shows 80.22% diploid, and 19.78% hyperploids. The cells have doubling time of 30 to 36 hours. The initial karyotypes were: 45~46, XY, i(3)(q10), der(6)t(3;6)(p11;q22), t(6;13) (p21;q32), del(7)(q32), i(14) (q10)[cp3]/46, XY, del(3)(p10), der(6)t(3;6), der(6)t(6;13), del(7)(q32), add(10)(p13), der(13)add(13)(p11.1)t(6;13), i(14)(q10)[3]/46, XY[16]. Metaphase preparations from the cell line showed 46, XY, absence of the above mentioned chromosomal abnormalities, but 97% (1422/1466 cells) of cells were diploid; 2.5% (36/1466 cells) of cells were tetraploid/near tetraploid, and 0.5% (8/1466 cells) of cells showed endore-duplication. Chromosomal comparative genomic hybridization of the cell line showed microdeletion on chromosome 5q34 and 13q22~31 region, and gain on 12q12.1. Single nucleotide polymorphism array showed no abnormalities. This newly established cell line is unique in: it is the second cell line known to be positive for EBV antigen, it shows no complex chromosomal aberration by conventional karyotyping or molecular genotyping, and since the cell line showed mostly in diploid, and only 3% of the cells are tetraploid/near tetraploid and endoreduplication by conventional cytogenetic method, the cell line is ideal for the study of formation of hyperploid cells (i.e. Reed-Sternberg cells) from diploid cells.

scholarly journals Contribution of Epstein–Barr Virus Latent Proteins to the Pathogenesis of Classical Hodgkin Lymphoma

Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 59 ◽  
Author(s):  
Katerina Vrzalikova ◽  
Taofik Sunmonu ◽  
Gary Reynolds ◽  
Paul Murray
Keyword(s):  
Host Cell ◽  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
Host Cells ◽  
Classical Hodgkin Lymphoma ◽  
Cellular Functions ◽  
Human Virus ◽  
Barr Virus ◽  
Cell Functions ◽  
Epstein Barr

Pathogenic viruses have evolved to manipulate the host cell utilising a variety of strategies including expression of viral proteins to hijack or mimic the activity of cellular functions. DNA tumour viruses often establish latent infection in which no new virions are produced, characterized by the expression of a restricted repertoire of so-called latent viral genes. These latent genes serve to remodel cellular functions to ensure survival of the virus within host cells, often for the lifetime of the infected individual. However, under certain circumstances, virus infection may contribute to transformation of the host cell; this event is not a usual outcome of infection. Here, we review how the Epstein–Barr virus (EBV), the prototypic oncogenic human virus, modulates host cell functions, with a focus on the role of the EBV latent genes in classical Hodgkin lymphoma.

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