Mutation profiling in differential diagnosis between TdT-positive high grade/large B-cell lymphoma and B-lymphoblastic leukaemia/lymphoma

TdT is occasionally expressed in large B-cell lymphoma (LBCL), and this causes difficulty in differential diagnosis from B-lymphoblastic leukaemia/lymphomas (B-ALL/LBL). We reviewed 31 cases of TdT-positive LBCL and B-ALL/LBL, and their final diagnosis included 19 diffuse large/high-grade BCL with MYC and BCL2 rearrangements (DLBCL/HGBCL- MYC / BCL2 ), 3 DLBCL-NOS, 3 HGBCL-NOS, 4 B-ALL/LBL and 2 unclassifiable cases. TdT was variably expressed in all these cases, without any clear demarcation among different groups. Loss or partial loss of CD20 expression was seen in 13/17 DLBCL/HGBCL- MYC / BCL2 , 2/3 HGBCL-NOS, 2/2 unclassified, albeit not in DLBCL-NOS. Expression of BCL6 and/or MUM1 was seen in 3/4 B-ALL/LBL and 2/2 unclassified. Next generation sequencing revealed characteristic mutations associated with follicular lymphoma and its high-grade transformation in each DLBCL/HGBCL- MYC / BCL2 , and also frequent variants in genes targeted by somatic hypermutation (SHM) in almost all DLBCL/HGBCL- MYC / BCL2 , DLBCL-NOS and HGBCL-NOS but one case. In contrast, such mutations were absent in B-ALL/LBL. There were no pathognomonic mutations in the two unclassifiable cases although one showed a moderate level of somatic mutations in its rearranged IGHV . In conclusion, mutation profiling analysis including the SHM target genes is highly valuable in differential diagnosis between TdT-positive LBCL and B-ALL/LBL.