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L. Wang et al.
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Figure 1. A representative case of mantle cell lymphoma with MYC rearrangement. The lymphoma cells have blastoid morphology. (A) Peripheral blood, (B) core biopsy, and express CD20 (C), cyclinD1 (D), MYC (E), BCL6 (F), and with a high Ki67 proliferation rate (G). Fluorescence in situ hybridization study showed CCND1/IGH (H) and MYC rearrangement (I).
case that was originally CD5-negative and developed MYC-R subsequently. CD10 was positive in 9 of 26 (35%) cases assessed; CD10 was acquired at the time of transfor- mation when MYC-R emerged. All CD10+ cases had blas- toid morphology. Four CD10+ MCL cases were CD5-neg- ative. BCL-2 was positive in 12 of 14 (86%) cases of MCL with MYC-R. IRF4/MUM-1 and BCL-6 were positive in 4 of 8 (50%) and 4 of 13 (31%) cases assessed, respectively. Twelve of 17 (71%) cases showed P53 expression in more than 20% of cells, including all 9 cases (100%) of trans- formed MCL and 4 of the 8 (50%) de novo MCL cases test- ed. The Ki67 proliferation index was variable, but most cases had a high proliferation rate with a median Ki67 index of 90% (range, 15-100%; only three cases had Ki67<60%). All tested cases were negative for CD23 and CD200 (Table 1).
FISH showed MYC-R and CCND1 translocation in all 27 cases. One case showed both MYC-R and MYC-EC. Since there is only one such case, it was included in the MYC-R group. Conventional cytogenetic analysis was available in 18 cases and all showed a complex karyotype, including t(11;14)(q13;q32) in 17 cases. By combined FISH and karyotype, 18q21/BCL2 and 3q27/BCL6 status were available in 19 cases and all were negative for rearrange- ment except one case with BCL6-R. Based on identifiable
karyotype data, seven cases had MYC partner gene as IG gene and three with non-IG gene.
Treatment and prognosis
Detailed therapy data were available for 24 of 27 MCL patients with MYC-R. All patients were treated with combination chemotherapy: sixteen (67%) patients received intensive induction chemotherapy, mainly rit- uximab, hyperfractionated cyclophosphamide, vin- cristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine) (R-Hyper-CVAD, n=14) or rituximab, etoposide, prednisone, vincristine, and doxorubicin (R-EPOCH, n=2). Eight (33%) patients received R-CHOP (cyclophosphamide, doxorubicin, vin- cristine, and prednisone) or R (rituximab) and bendamus- tine. Eight (33%) patients reached complete remission (CR) after induction, but six relapsed. Seven patients received a stem cell transplant (SCT), including four autologous and three allogeneic. After a median follow- up of 41.5 months, 17 of 24 (71%) patients died includ- ing 10 patients with MYC-R detected during disease pro- gression/transformation. The median OS was 19.9 months and the 3-year OS rate was 33% for all 27 patients. The median OS was worse for patients with MCL in whom MYC-R emerged during disease progres-
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haematologica | 2021; 106(5)