Abstract
Introduction/Objective
B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (double- and triple-hit lymphomas, DHL/THL) are a distinct entity due to shared biology and aggressive behavior, exhibiting poor outcomes with standard therapies. While pathologic features of DHL/THLs in primary sites have been well described, little information is available regarding the clinicopathologic features of bone marrow involvement by this entity.
Methods/Case Report
Files were searched from 2010-2020 for all DHL/THLs. Since mid-2016, all aggressive B-cell lymphomas were reflexed to DHL/THL FISH testing. Prior to that, criteria for performing FISH varied. Clinical and laboratory data were obtained through chart review. Both BM and primary diagnostic specimens were reviewed when possible.
Results (if a Case Study enter NA)
There were 46 DHL/THL cases with initial staging BM evaluations, of which 13 (28%) were positive for DHL/THL; 11 were available for review (5F:6M; 28-95 years). All patients with positive BMs were stage 3 or 4 irrespective of the BM findings. Lymphoma cytology in positive BMs was blastoid in 6, large cell in 2, and high grade, NOS in 3. The cytology in primary tissues was not significantly associated with the rate of marrow involvement. PB smears were available for 9/11 BM(+) cases; of these, 6 (66.7%) had circulating lymphoma cells in the blood, ranging from rare to greater than 40% lymphoma cells (median, 4%). Lymphoma cells with cytoplasmic vacuoles were present in 5 cases (45%). No BM infiltrates had a starry-sky appearance. Infiltration patterns included diffuse (3), diffuse and interstitial (3), and interstitial (3). One exhibited only rare, scattered lymphoma cells in the aspirate and core biopsy, and another with large cell morphology showed random focal (nodular) and focally paratrabecular infiltration. The proliferation index in the marrow infiltrates ranged from 50% to >90% (median, 65%). Flow cytometry was positive in 9 of 10 cases; the single negative study was from an outside institution
Conclusion
Our study demonstrates 28% of DHL/THLs show BM involvement at diagnosis. Notably, the peripheral blood was involved in 2/3 of cases with marrow infiltration (13% of total cases), ranging from rare circulating cells to frank leukemic involvement. Cytologically, the marrow infiltrates were predominantly blastoid or high grade NOS. Marrow infiltrates generally displayed leukemic rather than lymphomatous patterns of involvement.
Simple karyotype and bcl-6 expression predict a diagnosis of Burkitt lymphoma and better survival in IG-MYC rearranged high-grade B-cell lymphomas