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

Abstract

CD20-negative diffuse large B-cell lymphomas (DLBCLs) constitute a rare and heterogeneous group of aggressive lymphomas. Known well-documented variants include plasmablastic lymphomas, primary effusion lymphomas, anaplastic kinase-positive large B-cell lymphomas, and large B-cell lymphomas arising in human herpesvirus 8 (HHV8)-associated multicentric Castleman disease. They impose diagnostic challenges for pathologists and therapeutic confrontations for clinicians. CD20 loss in B-cell lymphomas is a well-known phenomenon after rituximab therapy. De novo loss of CD20 has been reported in human immunodeficiency virus (HIV)-positive patients. Rare cases of primary CD20-negative DLBCLs that did not meet the criteria of the well-established subtypes of CD20-negative DLBCLs have been reported. This might expand the spectrum of unclassifiable CD20-negative DLBCLs with aberrant genetic and immunophenotypes. This imposes further diagnostic and therapeutic challenges. We report a case of a primary CD20-negative DLBCL in an HIV-infected female patient with an Epstein Barr virus (EBV) coinfection, who presented with generalized lymphadenopathy and fever. The nodal neoplastic immunoblasts were positive for LCA, PAX5, CD30, OCT2, BOB1, MUM1, CD79a, and CD19. Ki67 proliferation index was 100%. They were negative for CD20, CD3, ALK, EMA, CD138, CD38, EBV, and HHV8. Our case did not meet the criteria of the known variants of CD20-negative DLBCLs. The aim of this study is to highlight the diagnostic challenges associated with CD20-negative DLBCLs. De novo unclassifiable CD20-negative DLBCLs might raise an insight into the complex genetic mechanisms of CD20 concealment with variable immunoprofiles and resistance to conventional chemotherapies.

Primary Nodal Unclassifiable CD20 Negative Diffuse Large B-cell Lymphoma With Dual IgK and TCR Gene Rearrangement: A Diagnostic Challenge

“… 17 It is speculated that genetic mutations of this gene lead to conformational changes of the surface protein resulting in CD20 negative staining. 3 On the other hand, PAX-5 is thought to be the most specific B-cell lineage marker expressed from pro-B to the mature B-cell stage and then silenced in the plasma cells. 9 Besides being the critical B-cell lineage factor, PAX-5 also upregulates the expression of various B-cell differentiation markers.…”

“… 2 This group of lymphomas usually have aggressive clinical behaviour, extranodal disease presentation and unusual morphology. 3 In addition to the above mentioned CD20 negative lymphomas, CD20 positive lymphoma can relapse as CD20 negative lymphoma after CD20 antibody therapy. 4 , 5 However, some CD20 negative DLBCL could not be classified into known variants, and they pose diagnostic as well as therapeutic dilemma.…”

Primary central nervous system CD20-negative diffuse large B-cell lymphoma: A case report

“…The current case cannot be classi ed based on existing criteria, and as it occurred in the central nervous system, is extremely rare. Unclassi able cases of CD20-negative DLBCL have been reported in foreign literature [17][18][19] ; however, these unclassi able cases have unique clinicopathological features. The current case is the rst case of CNS and unclassi able CD20-negative DLBCL.…”

Primary central nervous system CD20-negative diffuse large B-cell lymphoma: a case report

“…The current case cannot be classified based on existing criteria, and as it occurred in the central nervous system, is extremely rare. Unclassifiable cases of CD20-negative DLBCL have been reported in foreign literature [ 17 – 19 ]; however, these unclassifiable cases have unique clinicopathological features. The current case is the first case of CNS, unclassifiable CD20-negative DLBCL.…”