“Double Hit” Aggressive B-Cell Neoplasms with B-ALL Phenotypes: Role of FISH in the Diagnosis
Raheela F Siddiqui, Ana C Baptista, Catherine Ross, David Good, Brian Sheridan, Denis Bailey, Kenneth J Craddock. University Health Network, University of Toronto, Toronto, Canada; Hamilton Health Sciences and McMaster University, Hamilton, Canada
Background: “Double-hit” lymphomas, usually referring to aggressive B cell lymphomas with rearrangements of MYC/8q24 locus in combination with another recurrent breakpoint, mainly t(14;18)(q32;q21) involving BCL2, are often classified as "B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma" or as DLBCL using current WHO criteria. However, neoplasms with these two translocations can rarely fit the classification criteria of other entities such as follicular lymphoma or B-ALL.
Design: We describe 5 patients with aggressive B cell neoplasms having phenotypes of precursor-B lymphoblastic leukemia (B-ALL), all with MYC and IGH-BCL2 translocations.
Results: Four patients (age range 54-83, M:F 2:2) were initially diagnosed as B lymphoblastic leukemia/lymphoma based on morphology and immunophenotyping, such as strong TdT and CD10 expression, and/or lack of CD20. The fifth patient (F, age 61) had a leukemic presentation with a high WBC count, CD20 negative by flow cytometry, diagnosed as "high-grade B-cell lymphoma". Four of the patients had localized masses, and one patient had a history of follicular lymphoma. In four cases, atypical or overlapping features with DLBCL prompted cytogenetic investigations specifically for MYC and BCL2 rearrangements. MYC and IGH-BCL2 rearrangements were demonstrated in all cases, all with a complex signal patterns by FISH or in the context of a complex karyotype. Interestingly, BCL6 was found to be rearranged as well in 4 of 5 cases.
Conclusions: These cases illustrate that a subset of double hit lymphomas may be diagnosed as B-ALL due to an immature B cell immunophenotype and systemic involvement, and suggest that these neoplasms are more likely to bear a third, BCL6 rearrangement. Conventional karyotyping would be time consuming and may miss the presence of these translocations due to complex or cryptic cytogenetic abnormalities. The importance of making this diagnosis is due to its association with poor prognosis, which may warrant a more aggressive treatment regimen. We suggest that the presence of atypical features for B-ALL including presentation as a localized mass, pleomorphic nuclear morphology, expression of restricted light chain immunoglobulins and bcl-2 protein, or lack of TdT nuclear expression, in an individual of > 50 years, should prompt FISH analysis to provide an expedited “double hit” diagnosis.
Monday, March 19, 2012 8:45 AM
Platform Session: Section C, Monday Morning