B Lymphoblastic Leukemia/Lymphoma With Burkitt-like Morphology and IGH/MYC Rearrangement

Abstract

Isolated MYC rearrangement without other recurrent genetic abnormalities is rare in B lymphoblastic leukemia/lymphoma (B-ALL/LBL), with most cases reported in pediatric patients. We report 3 adult cases with lymphoblasts showing a precursor B cell immunophenotype, and isolated MYC/IGH translocation. All 3 cases occurred in male patients with initial presentation of diffuse lymphadenopathy. Cases 1 and 2 had B-ALL with significantly increased lymphoblasts in peripheral blood and bone marrow. Case 3, a patient with human immunodeficiency virus infection, had the diagnosis of B-LBL made on a retroperitoneal lymph node biopsy and had no peripheral blood or bone marrow involvement. The leukemic and lymphoma cells in all 3 cases demonstrated Burkitt lymphoma-like morphology with deeply basophilic cytoplasm and numerous cytoplasmic vacuoles. However, all 3 had immature immunophenotypes including expression of terminal deoxynucleotidyl transferase (TdT), absence of BCL6, and dim-to-negative CD45. CD20 was largely negative in 2 of 3 cases. All 3 had confirmed MYC/IGH translocation, but lacked rearrangements of BCL2 or BCL6. EBV was negative by Epstein-Barr virus encoded small RNA in situ hybridization. Treatment protocols varied, including both high-risk ALL-type (protocol 8707) and high-grade lymphoma regimens (hyper-CVAD [cyclophosphamide, vincristine, adriamycin, and dexamethasone]), but no patient achieved continuous complete remission. These cases seem to represent a distinct biological phenomenon, in which a MYC translocation may be acquired at an immature stage of differentiation, thus manifesting features of both B-ALL/LBL and Burkitt lymphoma.

Molecular characteristics of terminal deoxynucleotidyl transferase negative precursor B‐cell phenotype Burkitt leukemia with IGH‐MYC rearrangement

“…8 Among cases with a precursor B-cell immunophenotype, [9][10][11][12] only one TdT-negative cases has been reported. 8 Among cases with a precursor B-cell immunophenotype, [9][10][11][12] only one TdT-negative cases has been reported.…”

“…5 The IGH-MYC translocation in BL has been reported to arise mainly due to aberrant somatic hypermutation of class switch recombination. 11,12 Of the four adult patients with treatment and treatment course available in the reports, treatments were the Hyper-CVAD protocol (two patients), high-risk B-ALL protocol (one patient), and R-CHOP (one patient). There are limited data regarding optimal management of patients with a precursor B cell phenotype BL with IGH-MYC rearrangement.…”

“…25 BL requires intensive treatment owing to the proliferative nature of the tumor cells. 11,12 In the pediatric literature, BL treatment was more efficient than the B-ALL treatment. In reviewing the literature, we found reports of the aggressiveness and treatment resistance of precursor B-cell phenotype BL with IGH-MYC rearrangement, especially in adult cases.…”

“…immunophenotype is a rare type of BL, reported in about 5% of pediatric BL patients. 8 Among cases with a precursor B-cell immunophenotype, [9][10][11][12] only one TdT-negative cases has been reported. 9 We report two additional cases of TdT-negative precursor B cell phenotype BL with IGH-MYC rearrangement.…”

“…In reviewing the literature, we found reports of the aggressiveness and treatment resistance of precursor B-cell phenotype BL with IGH-MYC rearrangement, especially in adult cases. 11,12 Of the four adult patients with treatment and treatment course available in the reports, treatments were the Hyper-CVAD protocol (two patients), high-risk B-ALL protocol (one patient), and R-CHOP (one patient). At the time of reporting, only one patient, who received Hyper-CVAD therapy, was alive with partial remission, and was awaiting stem cell transplantation.…”