PF323 DOUBLE‐HIT DIFFUSE LARGE B‐CELL LYMPHOMA IN TAIWAN IS PREDOMINANTLY BCL6‐REARRANGED AND OVEREXPRESSION OF MYC AND BCL6 IS NOT A GOOD SURROGATE FOR SCREENING
Authors: Su Y.‐C. , Lee C.‐H. , Hsieh S.‐M. , Liu M.‐L. , Fang C.‐L. , Chen C.‐L. , Li W.‐H. , Yen Y. , Whang‐peng J. , Chao T.‐Y. 
Published: June 2019

Background:

Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of the non‐Hodgkin's lymphoma all over the world and it is extremely heterogeneous both clinically and pathologically. Concurrent MYC and BCL2/BCL6 translocations, the so‐called double hits (DH) has been identified as an important reverse prognostic factor in DLBCL. Chang and his colleagues have published a manuscript to describe the immunophenotypic and genetic characteristics of DLBCL in Taiwan in 2016. In their study, BCL6, rather than BCL2, rearrangement seemed predominant in DH DLBCL although only 3 patients were identified. BCL6‐rearranged DH DLBCL has been less discussed because it accounts for only 20–25% of all cases in the Western countries. Therefore the importance of BCL6 rearrangement in DH DLBCL should be explored in Taiwan.

Aims:

We would like to confirm the predominance of BCL6 rearrangement in DH DLBCL in Taiwan. In addition, we would like to figure out the phenotypes and the status of Myc and BCL6 protein expression in BCL6‐rearranged DH DLBCL.

Methods:

We retrieved 154 patients with pathological‐confirmed, newly‐diagnosed DLBCL patients from Shuang‐Ho Hospital, Wan‐Fang Hospital and Taipei Meidcal University Hospital. Fluorescence insitu hybridization (FISH) to detect MYC rearrangement was performed in all patients. BCL2 and BCL6 rearrangements were checked by FISH when positive MYC rearrangement was confirmed. Immunohistochemical (IHC) stains for Myc, BCL2, BCL6, CD10 and MUM1 were done in all patients.

Results:

Among the 154 patients, 25 of them had MYC translocation (16.2%). Of the 25 MYC‐rearranged patients, concurrent BCL2 or BCL6 translocation was detected in 12 patients. Two‐thirds of them (8 patients) had simultaneous MYC and BCL6 translocations while the other 3 were MYC‐ and BCL2‐rearranged (Figure 1). We had one patient with concurrent MYC, BCL2 and BCL6 translocations, the so‐called triple hits (TH). Taken together, 75% of DH (including TH) DLBCL patients had BCL6 rearrangement and therefore we confirmed the predominance of BCL6 rearrangement in Taiwan. Among DH (including TH) DLBCL patients with BCL6 rearrangement, only 3 out of 9 (33.3%) expressed Myc and BCL6 proteins simultaneously in the IHC stains (Table 1) and consequently, simultaneous overexpression of Myc and BCL6 proteins was not a good surrogate to screen BCL6‐rearranged DH DLBCL. Five patients (55.6%) were non‐germinal center B‐cell (non‐GCB) phenotype in BCL6‐rearranged DH (including TH) patients (Figure 2), indicating the screening of DH with BCL6 rearrangement should include the non‐GCB phenotype of DLBCL.

Summary/Conclusion:

1. The majority (75%) of DH (including TH) DLBCL in Taiwan had BCL6 rearrangement and it was quite different from data of the Western countries.

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2. The concurrent overexpression of Myc and BCL6 proteins in the IHC stains was not a good surrogate to screen BCL6‐rearranged DH DLBCL.

3. More than half (55.6%) of BCL6‐rearranged DH (including TH) DLBCL were non‐GCB phenotype, indicating the screening of DH with BCL6 rearrangement should include the non‐GCB phenotype of DLBCL in Taiwan.

4. The screening of BCL6‐rearranged DH DLBCL was mandatory in Taiwan.