Marianne Tan, Imogen Caldwell and Anna Ruskova

 

MPALs are defined as having blasts that express antigens of more than one lineage. WHO and ICC 2022 criteria specify thresholds for the intensity of antigen expression in the leukaemic blasts with respect to normal counterparts.^1,2 We present two cases of T/myeloid MPAL that illustrate challenges of interpreting and applying strict antigen intensity thresholds.

Case 1 was a 13yo male presenting with constitutional symptoms and a neck lump. Immunophenotyping demonstrated blasts with both T-lymphoid and myeloid lineage differentiation however intensity of cCD3 did not exceed 50% of mature T-cells. Although MPAL criteria were not met, targeted gene panel testing revealed NOTCH1 mutations, typical of T-lymphoblastic leukaemia, and a diagnosis of T/myeloid MPAL was considered most appropriate.

 

Case 2 was a 7yo male who presented with fever and pancytopenia. Blasts expressed HLA-DR, CD34, CD117, MPO, TdT and cCD3 with intensity that was borderline in respect to the MPAL criteria. RNAseq revealed a ZEB2::BCL11B fusion consistent with a diagnosis of ALAL with BCL11B rearrangement. 

These cases highlight the diagnostic challenges of MPAL and potential limitations of the current immunophenotypic criteria for lineage assignment. Both RNAseq and detection of mutations can assist classification and where available should be performed, particularly in equivocal cases.

 

References

1.     WHO Classification of Tumours Editorial Board. Haematolymphoid tumours. Lyon (France): International Agency for Research on Cancer; 2024. (WHO classification of tumour series, 5^th ed.; vol.11). https://publications.iarc.who.int/637.

2.     Weinberg OK, Arber DA, Döhner H, et al. The International Consensus Classification of acute leukemias of ambiguous lineage. Blood 2023; 141 (18): 2275–2277. doi: https://doi.org/10.1182/blood.2022019493

Statement of Originality

I confirm that this work is original, has not been previously published and is not currently under consideration for publication elsewhere. Generative AI was not in the writing process. 

Author Contributions

M.T., I.C. and A.R. conceptualised the study; M.T. collected the data and undertook literature research; M.T., I.C. and A.R. analysed and interpreted the data; M.T. wrote the original draft; I.C. and A.R. critically revised and contributed to the final version; I.C. and A.C. supervised the project.