Epstein-Barr virus in B-cell non-Hodgkin's lymphomas: Unexpected infection patterns and different infection incidence in low- and high-grade types

1995 ◽  
Vol 175 (3) ◽  
pp. 263-271 ◽  
Author(s):  
Michael Hummel ◽  
Ioannis Anagnostopoulos ◽  
Petra Korbjuhn ◽  
Harald Stein
2019 ◽  
Vol 12 (5) ◽  
pp. e227715 ◽  
Author(s):  
Rawia Albar ◽  
Moaffaq Mahdi ◽  
Fawaz Alkeraithe ◽  
Khalid Nawaf Almufarriji

Severe combined immunodeficiency (SCID) is an extremely rare disease caused by a disruption in the forkhead box N1 (FOXN1) gene, with an incidence of <1 per 1 000 000 live births. We report a boy aged 4 months who presented with a history of fever for 3 weeks and enlarged lymph nodes. The fever was associated with dry cough and runny nose. On physical examination, we noted oral thrush, generalised lymphadenopathy, nail dystrophy and alopecia. Flow cytometry of lymph node biopsy showed high-grade B-cell lymphoma. In addition, Epstein-Barr virus (EBV) infection was documented by PCR. The diagnosis of SCID was made by genetic testing, which revealed a homozygous variant of the FOXN1 gene. The variant was confirmed with Sanger sequencing. Management of EBV infection and lymphoma was initiated; unfortunately, the patient passed away on day 45 of hospitalisation.


Author(s):  
L. V. Puzyreva ◽  
A. D. Safonov

The review is dedicated to features of clinical manifestations of infections caused by Epstein-Barr virus (EBV) in HIV-infected patients, problems of diagnostics and execution of antiviral therapy in the case of combination of these infections. Individuals at AIDS stage develop tumors, associated with EBV: non-Hodgkin’s lymphomas, including Berkitt’s lymphoma, primary B-cell lymphoma ofCNS, nasopharyngeal carcinoma. Formation of lymphoid interstitial pneumonitis and leukoplakia is known to be associated with EBV. A large list of preparations that are inhibitors of EBV replication are currently known, however, there is no clear pathogenetically justified therapy scheme for patients with this infection against the background of HIV-infection.


1992 ◽  
Vol 10 (3) ◽  
pp. 383-389 ◽  
Author(s):  
B Shiramizu ◽  
B Herndier ◽  
T Meeker ◽  
L Kaplan ◽  
M McGrath

PURPOSE A molecular analysis of non-Hodgkin's lymphomas (NHLs) from patients with AIDS was undertaken to determine the prevalence and immunophenotype of polyclonal B-cell lymphoma. MATERIALS AND METHODS DNA was extracted from 40 diagnostic biopsy specimens obtained from patients seen at University of California, San Francisco (UCSF) between 1986 and 1990. Clonality, infection with Epstein-Barr virus (EBV), and presence of a rearranged c-myc gene were determined by Southern blot analysis. Lymphoma immunophenotypes were determined by frozen-section immunohistochemical analysis. RESULTS The most prevalent genotype of lymphoma in this study was that of polyclonal, EBV-negative tumors with no evidence of c-myc rearrangement (14 of 40; 35%). Monoclonal, EBV-positive tumors with no evidence of c-myc rearrangement comprised the second most prevalent class (10 of 40; 25%), and polyclonal, EBV-positive tumors similar to those seen in transplant patients were observed in only a small subset (three of 40; 8%) of specimens analyzed. The immunophenotype of B cells in the polyclonal EBV-negative subset was equally divided into B-cell-predominant and mixed-phenotype lymphomas, with the latter category containing numerous infiltrating T cells. The B cells in each category were immunoglobulin M-positive (IgM+), CD20+, CD21-. All but one of the polyclonal NHLs had large-cell histology. CONCLUSIONS EBV-negative, AIDS-associated, polyclonal B-cell lymphoma appears to be a new class of human immunodeficiency virus (HIV)-associated disease more prevalent in the current study than any other molecular subclass. The absence of CD21, the EBV receptor, may explain in part the absence of EBV within this polyclonal B-cell population.


Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 1045-1055 ◽  
Author(s):  
F d'Amore ◽  
P Johansen ◽  
A Houmand ◽  
DD Weisenburger ◽  
LS Mortensen

A series of 520 cases of non-Hodgkin's lymphoma (NHL; 374 of B-cell, 130 of T-cell, 5 of non-B/non-T-cell, and 11 of undetermined phenotype) was analyzed for the presence of Epstein-Barr virus (EBV) using RNA in situ hybridization (RISH). The aims of the study were to assess the frequency of EBV-encoded small nuclear RNAs 1 and 2 (EBER), abundant immediate early RNAs (BHLF), and latent membrane protein-1 (LMP-1) in cases covering the entire histologic spectrum of NHL, and to analyze whether EBV status had prognostic relevance with regard to patient survival. EBER positivity was found in 25 of 374 (7%) B-NHL and 40 of 130 (31%) T-NHL (P < .00005) cases, but in only 1 of 16 cases with non- B/non-T-cell or undetermined phenotype. Among T-NHL cases, EBER positivity was confined to angioimmunoblastic, lymphadenopathy-like lymphoma (11 of 13 cases, 85%), Lennert's lymphoma (five of seven cases, 71%), and pleomorphic T-NHL (24 of 67 cases, 36%). Mycosis fungoides, lymphoblastic, and CD30-positive anaplastic large T-cell NHL cases were consistently EBV-negative. Double-labeling by RISH and immunophenotyping demonstrated the presence of EBV in neoplastic T cells, but no CD21 expression was found in the EBER-positive T-NHL cases. LMP-1 was expressed in 12 of 40 (30%) EBER-positive T-NHL and 5 of 25 (20%) EBER-positive B-NHL cases. For both T- and B-NHL, no correlation was found for EBER positivity and age, sex, clinical stage, or serum level of lactate dehydrogenase (LDH) at diagnosis. However, in T-NHL but not B-NHL, EBER positivity correlated with the presence of constitutional symptoms and a poor performance score (PS < 1; scale, 0 to 4). EBER status did not have any prognostic significance in B-NHL, but it had a negative prognostic impact in high-grade T-NHL (7-year survival of EBER-negative v EBER-positive cases: 33% v 14%; P = .01). A multivariate analysis including all B- and T-NHL of intermediate-/high- grade histology showed that EBER positivity in T-NHL was one of the three most significant factors recognized by the final prognostic model, only surpassed by PS greater than 1 and age greater than 67 years, and more powerful than B symptoms, an elevated LDH, or disseminated disease (clinical stage greater than II). We conclude that patients with EBV-positive T-NHL have a very poor clinical outcome, that EBV status should be considered as additional useful information in the classification of T-NHL, and that EBV-positive T-NHL should be treated as a separate entity in the future.


2000 ◽  
Vol 124 (10) ◽  
pp. 1520-1524 ◽  
Author(s):  
Jianguo Tao ◽  
Leonard Kahn

Abstract We report an unusual case of Epstein-Barr virus (EBV)-associated mucosal-associated lymphoid tissue (MALT) lymphoma involving the lungs, kidneys, and axillary lymph nodes in a child with congenital hypoadrenalism and panhypopituitarism. The patient presented with an aggressive clinical course and histologic evolution. Initial biopsies (1994) of the lung and kidney revealed histologic features of low-grade B-cell MALT lymphoma with lymphoepithelial lesions within the renal tubules and bronchial epithelium. Subsequent biopsies (1996, 1997, and 1999) revealed progressively greater cytologic atypia, polymorphism, and necrosis; an increased mitotic rate; and a preponderance of large cells, indicative of progression from a low-grade to a high-grade MALT lymphoma. Immunophenotyping of the lung and lymph node lesions revealed identical surface marker profiles: cells were CD19+, CD20+, immunoglobulin (Ig) G+, κ+, λ−, CD5−, CD10−, CD23−, and IgM−, and also negative for T-cell markers. Genotypic analysis demonstrated the presence of immunoglobulin heavy chain rearrangement and monoclonality of EBV in the lung lesion by Southern blot hybridization and polymerase chain reaction (PCR). The clinicopathologic features suggest that these lesions might represent an immunosupression-related continuum of low-grade to high-grade MALT lymphomas. Infection with EBV may have contributed to this tumor's aggressive clinical and histologic evolution.


2020 ◽  
Vol 13 (3) ◽  
pp. 1215-1226
Author(s):  
Samah Kohla ◽  
Feryal A. Ibrahim ◽  
Deena Mudawi ◽  
Susanna Akiki ◽  
Dina Soliman ◽  
...  

Lymphomas are presently categorized according to their origin from B or T lymphocytes. The co-expression of CD3 in B-cell lymphomas or CD20 in T-cell lymphomas has been rarely reported. Immature and less often mature lymphomas may incorporate the rearrangements of both B- and T-cell antigen receptor genes (dual genotype or bigenotype). Lymphoma cells with a sole genotype hardly concurrently express both B- and T-cell markers (biphenotypic lymphomas). We describe a 63-year-old female who was presented with obstructive jaundice and epigastric pain of 10 days. Initial CBC revealed 43x10<sup>3</sup>/μL white blood cells, 11.2 g/dL hemoglobin, and 88x10<sup>3</sup>/μL platelets. CT abdomen revealed hepatomegaly and suspected pancreatic mass with large retroperitoneal lymph nodal mass. Peripheral smear showed 56% lymphoid cells with blast morphology. The bone marrow (BM) aspirate smear was infiltrated by 83% immature-looking cells. BM biopsy showed interstitial to diffuse extensive infiltration by primitive-looking cells, positive for pan-B-cell antigens CD20, CD79, and PAX5 as well as the T-cell antigen CD4, CD5, CD3, while negative for all immaturity markers (CD34, TdT, and CD1a). In situ hybridization for Epstein-Barr virus (EBV)-encoded small RNA (EBER) was negative. Flow cytometry on BM aspirate showed an abnormal population (50%) expressing the B-cell antigens (CD19, CD20, CD79, CD22) and CD10, and showed lambda light chain restriction as well as the T-cell antigens cCD3 and CD4 with partial CD5. The analysis showed, also, another abnormal population of lambda restricted monotypic B cells (8%) with dimmer CD45 (blast gate) and showed the same immunophenotype (expressing the B-cell antigens), but negative for CD10, cCD3, CD5, and CD4. Conventional cytogenetic revealed complex karyotype. Molecular studies revealed rearrangements of the immunoglobulin heavy chain region consistent with a clonal B-cell population. TCR gene rearrangement analysis was equivocal concerning clonality but was not conclusive for clonal T-cell disease. Our final diagnosis was peripheral blood and BM involvement by EBV-negative high-grade lymphoid neoplasm (in leukemic phase with blast morphology) and an ambiguous immunophenotype with a differential diagnosis that may include the rare entity of bigenotypic lymphoma or an unusual case of high-grade B-cell lymphoma with aberrant expression of T-cell markers (biphenotypic lymphomas).


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7542-7542
Author(s):  
D. V. Faller ◽  
O. Hermine ◽  
T. Small ◽  
F. Suarez ◽  
R. O’Reilly ◽  
...  

7542 Background: Malignancies associated with latent Epstein-Barr virus (EBV) are resistant to nucleoside-type anti-viral agents because the viral enzyme target of these drugs, thymidine kinase (TK), is not expressed. Short-chain fatty acids, such as butyrate, induce EBV-TK expression in latently-infected B cells. In preclinical studies, we have shown that butyrate sensitizes EBV(+) lymphoblastoid cells, tumor lines and primary lymphoma cultures to apoptosis induced by ganciclovir. Methods: We conducted a Phase I/II trial of Arginine Butyrate in combination with ganciclovir in patients with refractory EBV(+) lymphoid malignancies to evaluate toxicity, pharmacokinetic parameters, and clinical responses. Fifteen patients with heavily-pretreated, refractory EBV(+) lymphoid malignancies, consisting of monoclonal refractory lymphoproliferative disease (PTLD), B cell non-Hodgkin’s lymphomas (NHL) (including one HIV-associated anaplastic B cell lymphoma), T cell NHL (including one cutaneous lymphoma), T/NK cell lymphomas, and Hodgkin disease were studied. Ganciclovir was administered twice daily and Arginine Butyrate was administered in an intra-patient dose-escalation. Arginine Butyrate was instituted at 500 mg/kg/day by continuous infusion, and escalated to 2000 mg/kg/day, as tolerated. Results: The MTD for Arginine Butyrate was established as 1000 mg/kg/day. Overall the combination was well-tolerated, with the most common toxicities being nausea and headache. Complications from rapid tumor lysis occurred in three patients, including acute hepatic necrosis in one patient. Reversible grade 3–4 somnolence or stupor occurred in three patients at Arginine Butyrate doses of greater than 1000 mg/kg/day. Ten of fifteen patients showed significant anti-tumor responses, with 5 CR and 5 PR. In certain patients who demonstrated a clinical CR, subsequent pathological analysis showed elimination of all tumor cells. Conclusions: The combination of Arginine Butyrate and ganciclovir was reasonably well-tolerated and appears to have significant biological activity in vitro and in vivo against refractory EBV(+) lymphoid malignancies. No significant financial relationships to disclose.


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