Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2017

Open Access 01-12-2017 | Case Report

An unusual case of Epstein-Barr virus-positive large B-cell lymphoma lacking various B-cell markers

Authors: Shin-ichi Nakatsuka, Chikao Yutani, Masako Kurashige, Masaharu Kohara, Teruaki Nagano, Takayoshi Goto, Hiroyuki Takatsuka, Hidetaka Ifuku, Eiichi Morii

Published in: Diagnostic Pathology | Issue 1/2017

Login to get access

Abstract

Backgroud

Epstein-Barr virus (EBV) is associated with B-cell lymphoma in various conditions, such as immunodeficiency and chronic inflammation. We report an unusual case of EBV-positive diffuse large B-cell lymphoma (DLBCL) lacking the expression of many B-cell markers.

Case presentation

An 83-year-old man presented with a submandibular tumor. Histology of a lymph node biopsy specimen revealed diffuse proliferation of centroblast- or immunoblast-like lymphoid cells with plasmacytic differentiation. Scattered Hodgkin/Reed-Sternberg-like cells were also visible. A routine immunohistochemistry antibody panel revealed that the tumor cells were negative for B-cell and T-cell markers (i.e., CD3, CD19, CD20, CD38, CD45RO, CD79a, CD138, and Pax-5), but were positive for CD30 and MUM-1, not defining the lineage of tumor cells. The final diagnosis of EBV-positive DLBCL was confirmed based on the expression of B-cell-specific transcription factors (Oct-2 and BOB.1), PCR-based identification of monoclonal rearrangement of the immunoglobulin genes, and the presence of EBV-encoded small RNAs in the tumor cells (identified using in situ hybridization).

Conclusion

The downregulation of broad band of B-cell markers in the present case with EBV-positive DLBCL posed a diagnostic dilemma, as the possible diagnoses included differentiation from anaplastic large cell lymphoma and CD20-negative B-cell lymphomas. Results of immunohistochemical panel including B-cell-specific transcription factors and gene rearrangement analyses critically support the correct diagnosis.
Literature
1.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2008.
2.
Geng L, Wang X. Epstein-Barr Virus-associated lymphoproliferative disorders: experimental and clinical developments. Int J Clin Exp Med. 2015;8:14656–71.PubMedPubMedCentral
3.
Oyama T, Ichimura K, Suzuki R, Suzumiya J, Ohshima K, Yatabe Y, et al. Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol. 2003;27:16–26.CrossRefPubMed
4.
Pan Y, Meng B, Zhang H, Cao W, Wang H, Bi C, et al. Low incidence of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in Tianjin, northern China. Leuk Lymphoma. 2013;54:298–303.CrossRefPubMed
5.
Kaleem Z, Hassan A, Pathan MH, White G. Flow cytometric evaluation of posttransplant B-cell lymphoproliferative disorders. Arch Pathol Lab Med. 2004;128:181–6.PubMed
6.
Masir N, Marafioti T, Jones M, Natkunam Y, Rüdiger T, Hansmann ML, et al. Loss of CD19 expression in B-cell neoplasms. Histopathology. 2006;48:239–46.CrossRefPubMed
7.
Li YJ, Li ZM, Rao HL, Xia Y, Huang HQ, Xia ZJ, et al. CD20-negative de novo diffuse large B-cell lymphoma in HIV-negative patients: a matched case–control analysis in a single institution. J Transl Med. 2012;10:84.CrossRefPubMedPubMedCentral
8.
McKelvie P, Yixing Lai F, Verma A, Bazargan A. Methotrexate-associated EBV-positive CD20-negative diffuse large B-cell lymphoma localized to skin presenting as multiple chronic lower leg ulcers. Leuk Lymphoma. 2016;57:456–60.CrossRef
9.
Teruya-Feldstein J, Chiao E, Filippa DA, Lin O, Comenzo R, Coleman M, Portlock C, Noy A. CD20-negative large-cell lymphoma with plasmablastic features: a clinically heterogenous spectrum in both HIV-positive and -negative patients. Ann Oncol. 2004;15:1673–9.CrossRefPubMed
10.
Vega F, Chang CC, Medeiros LJ, Udden MM, Cho-Vega JH, Lau CC, Finch CJ, Vilchez RA, McGregor D, Jorgensen JL. Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. Mod Pathol. 2005;18:806–15.CrossRefPubMed
11.
Natkunam Y, Warnke RA, Montgomery K, Falini B, van De Rijn M. Analysis of MUM1/IRF4 protein expression using tissue microarrays and immunohistochemistry. Mod Pathol. 2001;14:686–94.CrossRefPubMed
12.
Montes-Moreno S, Gonzalez-Medina AR, Rodriguez-Pinilla SM, Maestre L, Sanchez-Verde L, Roncador G, Mollejo M, García JF, Menarguez J, Montalbán C, Ruiz-Marcellan MC, Conde E, Piris MA. Aggressive large B-cell lymphoma with plasma cell differentiation: immunohistochemical characterization of plasmablastic lymphoma and diffuse large B-cell lymphoma with partial plasmablastic phenotype. Haematologica. 2010;95:1342–9.CrossRefPubMedPubMedCentral
13.
Niller HH, Banati F, Salamon D, Minarovits J. Epigenetic Alterations in Epstein-Barr Virus-Associated Diseases. Adv Exp Med Biol. 2016;879:39–69.CrossRefPubMed
14.
Cobaleda C, Schebesta A, Delogu A, Busslinger M. Pax5: the guardian of B cell identity and function. Nat Immunol. 2007;8:463–70.CrossRefPubMed
15.
Busslinger M, Klix N, Pfeffer P, Graninger PG, Kozmik Z. Deregulation of PAX-5 by translocation of the Eμ enhancer of the IgH locus adjacent to two alternative PAX-5 promoters in a diffuse large-cell lymphoma. Proc Natl Acad Sci U S A. 1996;93:6129–34.CrossRefPubMedPubMedCentral
16.
Morrison AM, Jäger U, Chott A, Schebesta M, Haas OA, Busslinger M. Deregulated PAX-5transcription from a translocated IgH promoter in marginal zone lymphoma. Blood. 1998;92:3865–78.PubMed
17.
Cazzaniga G, Daniotti M, Tosi S, Giudici G, Aloisi A, Pogliani E, et al. The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case. Cancer Res. 2001;61:4666–70.PubMed
18.
Cook JR, Aguilera NI, Reshmi-Skarja S, Huang X, Yu Z, Gollin SM, et al. Lack of PAX5 rearrangements in lymphoplasmacytic lymphomas: reassessing the reported association with t(9;14). Hum Pathol. 2004;35:447–54.CrossRefPubMed
19.
Hiraga J, Tomita A, Sugimoto T, Shimada K, Ito M, Nakamura S, et al. Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance. Blood. 2009;113:4885–93.CrossRefPubMed
20.
Maeshima AM, Taniguchi H, Nomoto J, Maruyama D, Kim SW, Watanabe T, et al. Histological and immunophenotypic changes in 59 cases of B-cell non-Hodgkin's lymphoma after rituximab therapy. Cancer Sci. 2009;100:54–61.CrossRefPubMed
21.
Terui Y, Mishima Y, Sugimura N, Kojima K, Sakurai T, Mishima Y, et al. Identification of CD20 C-terminal deletion mutations associated with loss of CD20 expression in non-Hodgkin's lymphoma. Clin Cancer Res. 2009;15:2523–30.CrossRefPubMed
22.
Nakamaki T, Fukuchi K, Nakashima H, Ariizumi H, Maeda T, Saito B, et al. CD20 gene deletion causes a CD20-negative relapse in diffuse large B-cell lymphoma. Eur J Haematol. 2012;89:350–5.CrossRefPubMed
23.
Czuczman MS, Olejniczak S, Gowda A, Kotowski A, Binder A, Kaur H, et al. Acquirement of rituximab resistance in lymphoma cell lines is associated with both global CD20 gene and protein down-regulation regulated at the pretranscriptional and posttranscriptional levels. Clin Cancer Res. 2008;14:1561–70.CrossRefPubMed
24.
Sugimoto T, Tomita A, Hiraga J, Shimada K, Kiyoi H, Kinoshita T, et al. Escape mechanisms from antibody therapy to lymphoma cells: downregulation of CD20 mRNA by recruitment of the HDAC complex and not by DNA methylation. Biochem Biophys Res Commun. 2009;390:48–53.CrossRefPubMed
25.
Tsai PC, Hernandez-Ilizaliturri FJ, Bangia N, Olejniczak SH, Czuczman MS. Regulation of CD20 in rituximab-resistant cell lines and B-cell non-Hodgkin lymphoma. Clin Cancer Res. 2012;18:1039–50.CrossRefPubMedPubMedCentral
26.
Johnson NA, Boyle M, Bashashati A, Leach S, Brooks-Wilson A, Sehn LH, et al. Diffuse large B-cell lymphoma: reduced CD20 expression is associated with an inferior survival. Blood. 2009;113:3773–80.CrossRefPubMedPubMedCentral
27.
Suzuki Y, Yoshida T, Wang G, Togano T, Miyamoto S, Miyazaki K, et al. Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL. Ann Hematol. 2012;91:997–1005.CrossRefPubMed
Metadata
Title
An unusual case of Epstein-Barr virus-positive large B-cell lymphoma lacking various B-cell markers
Authors
Shin-ichi Nakatsuka
Chikao Yutani
Masako Kurashige
Masaharu Kohara
Teruaki Nagano
Takayoshi Goto
Hiroyuki Takatsuka
Hidetaka Ifuku
Eiichi Morii
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2017
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-017-0606-7

Other articles of this Issue 1/2017

Diagnostic Pathology 1/2017 Go to the issue

Research

Tumor containing fragment number influences immunohistochemistry positive rate of HER2 in biopsy specimens of gastric cancer

Case Report

Primary follicular dendritic cell sarcoma of the urinary bladder: the first case report and potential diagnostic pitfalls

Case Report

Malignant gastrointestinal neuroectodermal tumor: a case report and review of the literature

Case Report

Composite neuroendocrine tumor and adenocarcinoma of the rectum

Case Report

Unusual presentation of plasmablastic lymphoma involving ovarian mature cystic teratoma: a case report

Research

Clinicopathologic significance of TRAP1 expression in colorectal cancer: a large scale study of human colorectal adenocarcinoma tissues