Immunophenotypically diverse immature patterns, including variable TdT expression, in aggressive B-cell lymphomas and leukemia with MYC rearrangement

Daishi Kato¹Takahiro Fujino¹Reiko Isa¹Haruya Okamoto¹Taku Tsukamoto¹Shinsuke Mizutani¹Yuji Shimura¹Tsutomu Kobayashi²Hitoji Uchiyama²Masafumi Taniwaki¹Aya Miyagawa-Hayashino^3,4Junya Kuroda^1*

• ¹Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
• ²Department of Hematology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
• ³University of Saskatchewan Department of Pathology and Laboratory Medicine, Saskatoon, Canada
• ⁴Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan

This study is a retrospective analysis of our case series and literature review of aggressive B-cell lymphomas with MYC rearrangements that show immunophenotypic immaturity, including expression of terminal deoxynucleotidyl transferase (TdT), weak or negative CD20, and the absence of surface membrane immunoglobulin (smIg) and light chains. Although classified as diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL), these cases sometimes resemble B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) immunophenotypically, creating diagnostic ambiguity. We report four cases: three diagnosed as HGBCL-MYC/BCL2 with TdT expression, and one as B-ALL with MYC rearrangement. Case 1 developed from follicular lymphoma with TdT-positive blastoid transformation. Case 2 showed widespread disease, complex cytogenetics, weak TdT positivity, and absence of light chain. Case 3 displayed scattered TdT expression and surface light chain restriction. Case 4, initially diagnosed as a mature B-cell neoplasm, was ultimately reclassified as B-ALL with MYC rearrangement and focal TdT expression. In all cases, CD20 expression was weak or negative. These overlapping immunophenotypes between mature B-cell neoplasms and lymphoblastic leukemia were also documented in previous reports of 89 patients with various MYC-rearranged mature B-cell lymphoma subtypes. Through review, we identified the patient population with tumor cells showing less than 10% positive TdT expression, weak or negative CD20, and absence