High-Grade B-Cell Neoplasm with Surface Light Chain Restriction and Tdt Coexpression Evolved in aMYC-Rearranged Diffuse Large B-Cell Lymphoma: A Dilemma in Classification

Abstract

According to World Health Organization (WHO) classification (2008), B-cell neoplasms are classified into precursor B-cell or a mature B-cell phenotype and this classification was also kept in the latest WHO revision (2016). We are reporting a male patient in his fifties, with tonsillar swelling diagnosed as diffuse large B-cell lymphoma (DLBCL), germinal center. He received 6 cycles of RCHOP and showed complete metabolic response. Two months later, he presented with severe CNS symptoms. Flow cytometry on bone marrow (BM) showed infiltration by CD10-positive Kappa-restricted B-cells with loss of CD20 and CD19, and downregulation of CD79b. Moreover, the malignant population showed Tdt expression. BM Cytogenetics revealed t(8;14)(q24;q32) within a complex karyotype. Retrospectively, MYC and Tdt immunostains performed on original diagnostic tissue and came negative for Tdt and positive for MYC. It has been rarely reported that mature B-cell neoplasms present with features of immaturity; however the significance of Tdt acquisition during disease course was not addressed before. What is unique in this case is that the emerging disease has acquired an immaturity marker while retaining some features of the original mature clone. No definitive WHO category would adopt high-grade neoplasms that exhibit significant overlapping features between mature and immature phenotypes.

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

“…Loss of expression of CD19 and other B-cell markers has been described in a case of high grade lymphoid neoplasm with features intermediate between DLBCL and acute lymphoblastic leukemia (TdT-positive) with a t(8;14) translocation involving cMYC. 13 The emergence of subclones with splice mutations of CD19 has been reported in acute lymphoblastic leukemias treated with CAR-T cells targeting CD19, although the mutation referred to this report was never specified. 14 In these cases, the CD19-negative subclones present a competitive advantage under the strong selective pressure exerted by the therapeutic intervention.…”

A case of primary cutaneous B‐cell lymphoma with immature features in an old man. Diffuse large B‐cell lymphoma with immature features or B‐cell lymphoblastic lymphoma?

“…Furthermore, TdT expression has been rarely reported in some nodal composite lymphomas with a component of B‐LBL and in some cases of evolution of nodal follicular B‐cell lymphoma from B‐LBL 22‐24 . Soliman et al 25 have recently described a case of tonsillar GC‐type DLBCL with MYC rearrangment, which has acquired the expression of TdT during the clinical course. Moreover, although MYC gene rearrangement is a relatively frequent event in DLBCL, it is not specific, and it was rarely reported in B‐LBL 26 …”

High-grade B-cell lymphomas with TdT expression: a diagnostic and classification dilemma

“…Morphologic review combined with a detailed immunophenotypic workup accurately classifies B-cell neoplasms in most cases. However, expression of TdT in World Health Organization (WHO) classification defined categories of B-cell lymphoma that are typically negative for TdT can occur rarely and present a diagnostic challenge [1,2].…”