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

Abstract

BackgroudEpstein-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 presentationAn 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).ConclusionThe 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.

Molecular analysis of a CD19-negative diffuse large B-cell lymphoma

“…Regarding DLBCL, some cases have been described as CD19 negative using immunohistochemistry, [9][10][11] but this was not confirmed by flow cytometry, which is more sensitive. 12 To the best of our knowledge, this case is the first report of DLBCL with complete loss of CD19 expression at diagnosis, as demonstrated by flow cytometry, which is the most sensitive technique.…”

Epstein-Barr Virus–Positive CD20- and CD45-Negative Diffuse Large B-Cell Lymphoma: A Diagnostic Challenge

“…5 Nakatsuka and colleagues reported an unusual case that most resembles our patient in that the case was EBV-positive DLBCL, NOS, lacking various B-cell and T-cell markers (CD19, CD20, CD38, CD45RO, CD79a, CD138, and Pax5) but was positive for Oct-2 and BOB1. 13 Unlike our healthy patient without extranodal involvement, the patient in their case was an 83-year-old elderly male who presented with an extranodal mass of the submandibular gland, more in keeping with the usual demographics and clinical presentation in the literature.…”

De Novo Unclassifiable CD20-Negative Diffuse Large B-Cell Lymphoma: A Diagnostic and Therapeutic Challenge

“…1,2,4,6 Coinfection with HIV and EBV is common. 6,7 Very rare cases of CD20-negative DLBCLs that did not meet the clinical, immunohistochemical, or genetic criteria for PBL, PEL, ALK+ LBCLs, and HHV8+ MCD LBCLs have been reported. 4,6 Some have intermediate features between DLBCLs and Burkitt lymphoma (BL), that is, gray zone lymphomas.…”

“…However, some B-cell markers, for example, CD19, CD79a, OCT2, BOB1, and MUM1, can be positive in PBLs, other lymphomas, and myeloid malignancies. [7][8][9] PAX5 is B-cell-specific activator protein that is unreactive in plasma cells. PAX5 is a good B-cell lineage marker in CD20-negative DLBCLs.…”

“…3,4 Few of the reported cases of primary CD20negative large B-cell lymphomas did not meet the criteria of the already well-established subtypes of CD20-negative DLBCLs. 4,6,7 This might expand the spectrum of unclassifiable CD20-negative DLBCLs with aberrant immunophenotypes. This imposes further diagnostic and therapeutic dilemmas.…”