CD37 and CD44 evaluation by flow cytometry: can these markers improve B cell lymphoma characterization?

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PurposeDiffuse large B cell lymphoma (DLBCL) is a heterogenous entity with many prognostic ancillary tests that are based on immunohistochemistry. These include cell-of-origin determination by the Hans criteria and “double expresser” characterization. Additionally, MYC fluorescence in situ hybridization is required to distinguish DLBCL from its morphologically similar counterpart, “double hit lymphoma” or high-grade B cell lymphoma (HGBCL), a “Burkitt-like” lymphoma with a worse prognosis than DLBCL. All such ancillary tests require judicious triage of oftentimes limited specimens. Loss of expression of CD37 has been associated with worse outcomes in DLBCL. Absence of CD44 is more commonly seen in Burkitt lymphoma than in DLBCL.MethodsVery few lymphoma studies have evaluated CD37 or CD44 expression by flow cytometric analysis, which permits a more quantitative assessment. To evaluate the utility of these two markers, we retrospectively reviewed seventy-three B cell non-Hodgkin lymphoma specimens in which expression of CD37 and CD44 was evaluated by flow cytometry. Median fluorescence intensity ratio (MFIR) was calculated by dividing the median fluorescence intensity of the lymphoma population by that of background non-B mononuclear cells.ResultsIn lymphomas with DLBCL-like morphology, loss of CD44 expression was associated with MYC rearrangement (MFIR rearranged 0.3082 vs intact 1.09, p=0.003). CD44 loss in DLBCL was also associated with germinal center B cell-like (GCB) cell-of-origin (MFIR GCB 0.4139 vs non-GCB 1.499, p=0.036) as has been seen in other studies. In DLBCL, loss of CD37 expression was not associated with cell-of-origin, double expresser status, or MYC rearrangement.ConclusionsWhile our findings require confirmation in a larger case series, decreased CD44 expression by flow cytometry in an otherwise limited biopsy with DLBCL-like features may provide the impetus for FISH testing and ultimate classification.