A 19-year-old man had B-lymphoblastic leukemia (B-ALL) heavily involving the bone marrow (panel A; bone marrow, 100× lens objective) and blood with no tissue-based disease. Morphological and phenotypic evaluation of the marrow demonstrated numerous B-lymphoblasts with CD34 (panel B; flow cytometry, neoplastic cells express CD34, CD19 and CD10) and terminal deoxynucleotidyltransferase expression. Karyotyping showed t(14;18) confirmed by fluorescence in situ hybridization (FISH) (panel C; BCL2-IGH fusion FISH, 100× lens objective).
MYC break-apart FISH was negative (panel D; MYC break-apart FISH, 100× lens objective). Microarray showed several copy number variations including deletion of
MYC and
IKZF1 among other genetic aberrations frequently associated with B-ALL. The disease course was significant for multiple treatment failures. Next-generation sequencing performed on a relapsed sample revealed an
NRAS mutation and an
MYC-
IGH fusion. High-grade B-cell lymphoma was entertained; however, the expression of CD34, the lack of extramedullary evolvement, and the IKZF1 deletion were more supportive of B-ALL with MYC and BCL-2 rearrangement.
The MYC rearrangement was missed by karyotyping and MYC break-apart probe and presented as a small deletion by microarray. This false-negative result is due to the small size and unbalanced MYC translocation, which flanks the MYC gene and is located outside the MYC break-apart probe coverage. Retrospectively, MYC translocation was determined to be present in the initial sample by metaphase FISH using the MYC-IGH dual fusion probe (panel E; metaphase FISH MYC-IGH fusion, 100× lens objective). This case demonstrates the importance of thorough testing for MYC translocation, especially when BCL-2 rearrangement is identified, as the prognostic implications of such alteration in B-ALL can be detrimental.
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https://orcid.org/0000-0002-0037-2707
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