Azurophilic granular blasts are not always part of myeloid lineage: an atypical case of BCP acute lymphoblastic leukemia

A 53-year-old woman presented with asthenia, fever, and pancytopenia. The peripheral blood smear showed 32% large blasts containing many, often clustered, azurophilic granules and multiple vacuoles (panels A-C; May-Grünwald-Giemsa, objective ×100). Surprisingly, immunophenotyping detected a CD19⁺/cyCD79a⁺/CD20⁺/CD22⁺/CD24⁺/CD10⁺/cyμ⁺/light chain⁻ B phenotype, without T or myeloid antigens (cyCD3⁻/CD3⁻/CD7⁻/CD5⁻/CD2⁻/CD117⁻/CD13⁻/CD33⁻/CD123⁻/CD15⁻/CD16⁻/CD11b⁻/CD64⁻/CD14⁻) except for weak expressions of cytoplasmic myeloperoxidase (cyMPO) and cyCD13 (panels E-H). However, MPO cytochemistry staining was negative (panel D; objective ×100). The marrow karyotype was 46,XX,t(9;22)(q34;q11)[4]/47,sl,+X[1]/48,sdl,der(22)t(9;22)(q34;q11)[2]/46,XX[8], with a BCR-ABL1 fusion by fluorescence in situ hybridization. Molecular studies detected an M-BCR-ABL1 fusion transcript and an IKZF1 deletion. Lacking definitive evidence for blast crisis of chronic myeloid leukemia, a diagnosis of Philadelphia chromosome–positive (Ph⁺) B-cell precursor acute lymphoblastic leukemia (BCP-ALL)/BCR-ABL1 was established. The patient was enrolled in the GRAAPH-2014 study and achieved a hematological remission but with significant minimal residual disease. Currently, the patient is still receiving treatment.

The misleading myeloid morphology of Ph⁺ BCP-ALL reported here has been previously described and highlights once again the importance of immunophenotyping for lineage assignation. However, the case reported here also emphasizes the importance of both MPO immunophenotyping intensity and MPO cytochemistry staining to avoid overdiagnosis of mixed-phenotype leukemia, according to the revised World Health Organization classification.