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Chronic lymphocytic leukemia with a t(8;14)(q24;q32): FISHing catches a (sheepish) red herring

A 65-year-old man with a history of chronic lymphocytic leukemia (CLL), diagnosed 13 years previously, presented at the time of a routine annual follow-up with new onset increased left sided abdominal pain, fatigue, and subjective fevers. A complete blood count revealed a modest leukocytosis of 16.3 3 10 cells/L, with an absolute lymphocyte count of 13.4 3 10 cells/L. The peripheral blood smear showed a marked prominence (65% of the leukocytes) of large lymphoid cells with moderately clumped chromatin and one or more prominent nucleoli (left). Flow cytometry demonstrated that these cells were bright surface immunoglobulin kappa light chain-restricted CD5(dim)1 CD20(bright)1 CD231 CD381 B-cells. Metaphase cytogenetic studies revealed the following karyotype: 47,XY,del(7)(?q32q35),t(8;14)(q24;q32),112[7]/46,XY[13] (right, top). Together with the symptoms, the morphologic and cytogenetic findings, in particular the t(8;14), were highly suggestive of progression of the CLL into a more aggressive phase, resembling prolymphocytic leukemia (PLL). However, fluorescence in situ hybridization (FISH) using a Vysis LSI MYC Dual Color Break Apart Rearrangement Probe (Abbott Molecular, Des Plaines, IL) indicated that MYC was not disrupted in this translocation. In fact, the intact MYC probe was present on 14q32, indicating that the breakpoint was proximal to (and did not involve) the MYC gene [right, bottom: fused red and green signals on der(14)]. While it has been reported previously that certain MYC probes, particularly dual fusion probes, may not detect rare MYC rearrangements [1], this is much less common with the use of the breakapart probe used here, although it is possible that an unusual far 5’ (centromeric) breakpoint may have been missed by the MYC break apart probe. Furthermore, a cryptic insertion is unlikely because a Vysis LSI IGH/CCND1 Dual Color Dual Fusion (Abbott Molecular, Des Plaines, IL) probe set revealed that IGH was also not .