Two cases of diffuse large B-cell lymphoma/high-grade B-cell lymphoma carrying t(3;8)(q27;q24)/BCL6::MYC

Hitoshi Ohno; Kayo Takeoka; Chiyuki Kishimori; Miho Nakagawa; Katsuhiro Fukutsuka; Masahiko Hayashida; Shinichi Kotani; Naoya Ukyo; Shinji Sumiyoshi

doi:10.12936/tenrikiyo.27-022

Abstract

We describe two patients with diffuse large B-cell lymphoma (DLBCL)/high-grade B-cell lymphoma (HGBL) that carried t(3;8)(q27;q24)/BCL6::MYC. In case 1, the patient was an 82-year-old man who presented with widespread bone marrow (BM) involvement and leukemic manifestation. Lymphoma cells in BM and peripheral blood were composed of not only large cells but also small cells, and those in the lymph node (LN) biopsy exhibited the germinal center B-cell (GCB) phenotype and carried t(14;18)(q32;q21), suggesting transformation of previously low-grade follicular lymphoma. In case 2, the patient was a 55-year-old man who presented with generalized lymphadenopathy and M protein in serum. Lymphoma cells exhibited the non-GCB/activated B-cell phenotype and included plasma cell-stage cells that expressed CD38 at high levels, indicating that lymphoma cells originated from mature B-cells that had exited GC to secrete immunoglobulins. G-banding revealed a subtle difference between chromosome 3 and 8 homologues in both cases, and fluorescence in situ hybridization revealed co-localization of 3′ BCL6 and 3′ MYC signals at the telomeric end of der(3) and that of 5′ MYC and 5′ BCL6 signals at the telomeric end of der(8), confirming BCL6::MYC gene fusion. The case 1 patient died soon after of disease progression, while the case 2 patient survived for 3 years and 6 months following the initial treatment. LN biopsies in both cases revealed DLBCL/HGBL histopathology with a high Ki-67 proliferation index and MYC expression in 90% of lymphoma cells; however, t(3;8)(q27;q24)/BCL6::MYC may not be regarded as “true” MYC/BCL6 double-hit.

Translated Abstract

t(3;8)(q27;q24)/BCL6::MYC転座を認めたびまん性大細胞型B細胞リンパ腫（DLBCL）・高悪性度B細胞リンパ腫（HGBL）の2症例を報告する．症例1は82歳の男性で，広範な骨髄浸潤と白血化で発症した．骨髄と末梢血中のリンパ腫細胞は大型細胞だけでなく小型細胞も含み，リンパ節生検で胚中心B細胞（GCB）の表現型を示しt(14;18)(q32;q21)を認めたことから、濾胞性リンパ腫の形質転換であることが示唆された．症例2は55歳の男性で、全身のリンパ節腫脹で発症し，血清中にM蛋白が認められた．リンパ腫細胞はnon-GCB・活性化B細胞の表現型を示し，CD38を高発現する形質細胞段階の細胞も含まれていた．従って，リンパ腫細胞は，胚中心を通過し免疫グロブリン分泌細胞に分化した段階の成熟B細胞に由来することが示された．Fluorescence in situ hybridizationでは，der(3)のテロメア末端が3′ BCL6と3′ MYCのシグナルで，der(8)のテロメア末端が5′ MYCと5′ BCL6のシグナルでラベルされたことから，BCL6::MYC融合遺伝子が形成されていることが確認された．症例1は短期間で病勢進行のため死亡したが，症例2は初期治療が奏効し3年6か月生存した．両症例の生検リンパ節はDLBCL/HGBLの病理組織像を示し，Ki-67増殖指数が高く，リンパ腫細胞の90％がMYCを発現していたが，t(3;8)(q27;q24)/BCL6::MYCは“真の”MYC/BCL6ダブルヒットには該当しない可能性がある．

INTRODUCTION

The 4^th edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues defined the category of high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements that harbors recurrent cytogenetic abnormalities involving the chromosomal loci of MYC (8q24) and either BCL2 (18q21) and/or BCL6 (3q27).¹ This category has been more commonly referred to as MYC/BCL2 or MYC/BCL6 double-hit (DH) or MYC/BCL2/BCL6 triple-hit (TH) lymphomas and patients with these diseases show a lower complete response (CR) rate and shorter overall survival (OS) than those with diffuse large B-cell lymphoma (DLBCL).¹ However, in the recently published 5^th edition of the WHO Classification of Hematolymphoid Tumours, the new entity of DLBCL/HGBL with MYC and BCL2 rearrangements was proposed, and MYC/BCL6 DH, but lacking BCL2 rearrangement, has been excluded from this entity, because MYC/BCL6 DH cases represent a diverse spectrum with variable gene expression profiles and mutational spectra; these cases are now classified either as a subtype of DLBCL, not otherwise specified (NOS) or HGBL, NOS according to their cytomorphological features.^2,3 In contrast, the International Consensus Classification of Mature Lymphoid Neoplasms retains HGBL with MYC and BCL6 rearrangements as a provisional category to allow for continued study based on the poor outcomes seen in some studies.⁴

We found cryptic t(3;8)(q27;q24) in a fraction of MYC/BCL6 DH cases recognized by fluorescence in situ hybridization (FISH) applied to interphase nuclei using break-apart probes for the two genes.⁵ It has been shown that in t(3;8)(q27;q24), MYC and BCL6 are not activated independently, but rather generation of the BCL6::MYC fusion gene leads to exclusive activation of MYC.⁶ Here, we present two additional DLBCL/HGBL patients with t(3;8)(q27;q24)/BCL6::MYC who were treated at our institution. Referring to the latest findings,⁷ we discuss whether t(3;8)(q27;q24) cases should be considered as MYC/BCL6 DH.

CASE PRESENTATION

Case 1

An 82-year-old man presented with left chest pain and exertional dyspnea. Computed tomography (CT) of the body disclosed bilateral pleural effusions with left-sided predominance as well as lymphadenopathy in the cervical, supraclavicular, and para-aortic regions. His hemoglobin level was 8.0 g/dL, white blood cell count was 1.49 × 10³/µL with 44.0% lymphocytes, 44.0% atypical lymphocytes, 3.0% monocytes, 1.0% basophils, 7.0% segmented neutrophils, and 1.0% band neutrophils, and platelet count was 35 × 10³/µL. The level of lactate dehydrogenase (LD) was 8,690 U/L, aspartate aminotransferase was 267 U/L, alkaline phosphatase was 1,916 U/L, C-reactive protein was 19.89 mg/dL, and soluble interleukin-2 receptor (sIL-2R) was 6,033 U/mL (reference range, 122 to 496 U/mL). ¹⁸F-fluorodeoxyglucose-positron emission tomography combined with CT (¹⁸F-FDG-PET/CT) revealed widespread, heterogeneous accumulation of the tracer within the bone marrow (BM) space throughout the body, and the tracer had also accumulated in the tumor arising along the left chest wall, with a maximum standardized uptake value (SUVmax) of 12.32, and systemic lymph nodes (LNs) (Figure 1A).

Figure 1.

Distinctive clinical features of two DLBCL/HGBL patients carrying t(3;8)(q27;q24)/BCL6::MYC. (A) ¹⁸F-FDG-PET/CT in case 1. Anterior view of the maximum-intensity projection (MIP) image (left) and representative fused axial images along with SUVmax of the left supraclavicular LNs and the left chest wall tumor (right) are aligned. (B) Lymphoma cells in BM of case 1. The cell population was composed of large cells with dispersed nuclear chromatin (top) and small cells with cleft nuclei (bottom, left) (Wright staining, 100× objective). (C) ¹⁸F-FDG-PET/CT in case 2. Anterior view of the MIP image (left) and representative fused axial images along with SUVmax of the left supraclavicular LNs, spleen, and para-aortic LNs (right) are aligned. (D) Serum immunofixation test (left) and test results related to M proteins (right) in case 2. Levels of IgA and IgM were within normal ranges, and there was no deviation in the κ/λ ratio.

He underwent biopsy of a left supraclavicular LN, demonstrating DLBCL/HGBL. BM was composed of 90.2% lymphoma cells; the majority of the cells were large, but cells were occasionally small with cleft nuclei (Figure 1B). His ECOG performance status (PS) was 3. The patient was treated with two cycles of R-miniCHOP (375 mg/m² rituximab, 400 mg/m² cyclophosphamide, 25 mg/m² doxorubicin, and 1 mg/body vincristine on day 1, and 40 mg/m² prednisolone on days 1–5), showing a transient response to the treatment, but he died of disease progression two months after the initial presentation.

Case 2

A 55-year-old man presented with generalized lymphadenopathy. He had been well until two months earlier, when he noticed cervical LN swelling and became aware of abdominal pain. He was prescribed prednisolone, temporarily relieving his symptoms. However, blood tests revealed elevated LD levels, raising the suspicion of malignant lymphoma. On examination, multiple surface LNs were palpable. ¹⁸F-FDG-PET/CT revealed FDG-avid LNs in the cervical, supraclavicular, axillary, mediastinal, para-aortic (SUVmax of 21.46), mesenteric, iliac, and inguinal regions (Figure 1C). The spleen was enlarged and significantly labeled by the tracer. His hemoglobin level was 14.4 g/dL, white blood cell count was 5.77 × 10³/µL, and platelet count was 186 × 10³/µL. The level of LD was 666 U/L, uric acid was 14.2 mg/dL, β2 microglobulin was 3.99 µg/mL (reference range, 0.8 to 1.9 µg/mL), and sIL-2R was 1,297 U/mL. Electrophoresis and immunoelectrophoresis tests of serum proteins detected IgGλ-type M protein, the level of which was estimated to be 1.94 g/dL (Figure 1D).

LN biopsy of the neck showed DLBCL/HGBL. BM contained 1.1% atypical lymphocytes and 2.0% plasma cells, and BM involvement was suggested by the biopsy. ECOG PS was 1. The patient was treated with 6 cycles of dose-adjusted (DA) EPOCH-R therapy, starting at level 2 (60 mg/m² etoposide, 0.4 mg/m² vincristine, and 12 mg/m² doxorubicin on days 1–4, 900 mg/m² cyclophosphamide on day 5, 60 mg/m² prednisone on days 1–5, and 375 mg/m² rituximab on day 6) and escalating to level 5 (103.7 mg/m² etoposide, 20.7 mg/m² doxorubicin, and 1,555 mg/m² cyclophosphamide), and 2 cycles of high-dose methotrexate (3.0 g/m²) therapy, achieving complete response (CR). The patient remained free from relapse for 3 years and 6 months after the initial presentation.

EXAMINATION OF TUMOR SPECIMENS

The excised LN specimen in case 1 was composed of necrotic tissue, but the surrounding adipose tissue was infiltrated with viable cells. These cells were medium to large, with disperse nuclear chromatin and nucleoli, and were CD10⁺, CD20⁺, CD5⁻, BCL2⁺, BCL6⁺, and MYC⁺ (90%) based on immunohistochemistry (Figure 2, top). The LN specimen in case 2 was infiltrated with medium to large tumor cells, admixed with tingible body macrophages, creating a starry-sky appearance (Figure 2, bottom). Many mitotic figures were observed. The cells were CD10⁻, CD20⁺, CD5⁺, BCL6⁺, MUM1⁺, and MYC⁺ (90%), with a fraction of the cells being BCL2⁻. The Ki-67 index was 90% in both cases (Figure 2).

Figure 2.

Histopathology of LN biopsies. Case 1: a, hematoxylin & eosin (H&E) staining; b, anti-CD20 immunostaining; c, anti-CD10; d, anti-BCL6; e, anti-BCL2; f, anti-MYC, and g, anti-Ki-67. Case 2: h, H&E; i, anti-CD20; j, anti-BCL6; k, anti-MUM1; l, anti-BCL2; m, anti-MYC, and n, anti-Ki67. Original magnification, 40× objective.

Multicolor flow cytometry (m-FCM) of circulating tumor cells in case 1 revealed that they could be divided into two populations: the major population consisted of small to medium-sized cells that were surface (s) IgGκ⁺, CD10⁺, CD19⁺, CD20^bright+, CD21⁻, CD22⁺, CD23^−/+, CD24⁺, CD5⁻, CD38^−/+, and HLA-DR⁺, whereas cells of the minor population were small and sIgGκ^dim+, CD20⁺, and CD38⁻ (Figure 3A). Tumor cells in LNs of case 2 were sIgGλ⁺, CD10^dim+/−, CD19⁺, CD20⁺, CD21^+/−, CD22⁺, CD24^−/+, CD5^−/dim+, and CD38^{− to bright+}. M-FCM of BM cells confirmed the presence of tumor cells that were sIgλ⁺ and CD38^−/+ as well as CD38^bright+/CD138⁺ plasma cell-stage cells that expressed Igλ in the cytoplasm (Figure 3B). The DNA index was 1.00 in both cases compared with normal diploid cells.

Figure 3.

M-FCM using fluorochrome-conjugated monoclonal antibodies. (A) PB cells in case 1. Small to medium-sized lymphoma cells (orange) were CD19⁺, CD20^bright+, CD5⁻, CD10⁺, HLA-DR⁺, CD38^−/+, CD21⁻, CD22⁺, CD23^−/+, and CD24⁺ and expressed sIgG/κ, whereas small lymphoma cells (green) were CD20⁺ and CD38⁻ and dimly expressed sIgGκ. (B) BM cells in case 2. Lymphoma cells were divided into two populations: one (orange) was CD19⁺, CD20^bright+, CD5⁺, CD10⁻, HLA-DR⁺, CD38^−/+, and expressed sIgλ, and the other (purple) was CD19⁺, CD20⁺, CD5⁺ CD10⁻, HLA-DR^dim+, and CD38^bright+ and lost sIgλ. When cells were fixed and permeabilized (Fix & Perm), the latter population was found to be CD19⁺, CD138⁺, CD38^bright+, CD20⁺, and CD81⁺ and positive for cytoplasmic (c) Igλ.

CYTOGENETIC STUDIES

G-banding in case 1 revealed t(14;18)(q32;q21) and other numerical and structural abnormalities and unknown markers; that in case 2 revealed structural abnormalities of chromosomes 11 and 15 (Figure 4). FISH of interphase nuclei generated break-apart signals of not only BCL2 but also BCL6 and MYC in case 1 (Figure 5A and D), and those of BCL6 and MYC in case 2. Thus, we compared each pair of chromosomes 3 and 8 in both cases, and found that the telomeric end of one chromosome 3 was larger than that of the other chromosome 3 and stained darker, whereas the telomeric end of one chromosome 8 was smaller than that of the other chromosome 8 and stained lighter, suggesting that the chromosome materials at the telomeric end of one chromosome 3 and those of one chromosome 8 had been reciprocally translocated, i.e., t(3;8)(q27;q24) (Figure 4). FISH of metaphase spreads using MYC and BCL6 break-apart (BA) probes demonstrated that the green-labeled centromeric 3′ BCL6 and green-labeled telomeric 3′ MYC probes were co-localized at the telomeric end of der(3), whereas the red-labeled centromeric 5′ MYC and red-labeled telomeric 5′ BCL6 probes were co-localized at the telomeric end of der(8), confirming BCL6::MYC gene fusion (Figure 5B and D). Accordingly, when BCL6 and MYC BA probes were mixed and hybridized to the cytogenetic specimens, we observed one large green and one large red signal within the interphase nuclei (Figure 5C and D).⁸ The representative karyotypes according to ISCN were:⁹ 52,t(X;5)(q28;q15),del(Y)(q11),t(3;8)(q27;q24),t(5;11)(p13;q22),+7,+12,add(13)(q34),t(14;18)(q32;q21),+4mar.ish t(3;8)(q27;q24)(3′BCL6+,3′MYC+;5′MYC+,5′BCL6+) in case 1, and 46,XY,t(3;8)(q27;q24),del(11)(p11p13),del(15)(q11q15).ish t(3;8)(q27;q24)(3′BCL6+,3′MYC+;5′MYC+,5′BCL6+) in case 2.

Figure 4.

G-banding showing t(3;8)(q27;q24) in cases 1 and 2. Left, Complete karyograms; right, partial karyograms of chromosomes 3 and 8. der(3)t(3;8)(q27;q24) and der(8)t(3;8)(q27;q24) generated by t(3;8)(q27;q24) are indicated by open arrowheads. Blue arrows in case 1 indicate t(14;18)(q32;q21). Other numerical and structural abnormalities are indicated by open and closed asterisks, respectively.

Figure 5.

FISH. (A) FISH of interphase nuclei hybridized with BCL2 (top), BCL6 (middle), and MYC (bottom) break-apart (BA) probes in case 1. Hybridization signals of representative nuclei are indicated by arrowheads of their respective colors. (B) FISH of metaphase spreads hybridized with BCL6 (top) and MYC (bottom) BA probes, confirming t(3;8)(q27;q24)/BCL6::MYC. G-banding and pictures through FITC, rhodamine, and triple band-pass filters are aligned from left to right. Hybridization signals on the relevant chromosomes are indicated by arrowheads of their respective colors. (C) FISH of interphase nuclei hybridized with both BCL6 and MYC BA probes. Large green and red signals and two yellow signals are indicated by arrowheads of their respective colors. The two nuclei at the bottom are labeled with 4 yellow signals. (D) Diagrams of BCL2, BCL6, and MYC BA probes provided by the manufacturer.

DISCUSSION

Here, we described two patients with stage IV DLBCL/HGBL showing distinctive clinical features and cell-of-origin (COO) phenotypes, according to the Hans classifier.¹⁰ Case 1 was characterized by widespread BM involvement and leukemic manifestation, and tumor cells in BM and peripheral blood (PB) were composed of not only large cells but also small cells that expressed lower levels of CD20, CD38, and sIgGκ than large cells. Tumor cells in the LN biopsy specimen exhibited the germinal center B-cell (GCB) phenotype, and cytogenetic tests disclosed t(14;18)(q32;q21). These findings indicate that case 1 represented transformation of previously low-grade follicular lymphoma. In contrast, tumor cells in case 2 exhibited the non-GCB/activated B-cell (ABC) phenotype and m-FCM isolated plasma cell-stage tumor cells that expressed CD38 at high levels. Accordingly, M proteins of the same class as those expressed on the tumor cell surface were noted in the serum. These findings indicate that tumor cells in case 2 originated from mature B-cells that had exited GC to secrete immunoglobulin. Most importantly, despite the difference in clinical features and COO phenotype, both patients carried t(3;8)(q27;q24) that led to the link between BCL6 and MYC and expression of MYC in 90% of tumor cells.

As the chromosomal materials distal to band q27 of chromosome 3 and those distal to band q24 of chromosome 8 are similar in size and banding appearance, t(3;8)(q27;q32) is not reliably recognized by G-banding alone. Nevertheless, with the aid of FISH cytogenetics, sporadic case reports or small case series of B-cell tumors carrying t(3;8)(q27;q24)/BCL6::MYC have been described in the literature.^5,8,11-17 Tables 1 to 3 summarize the clinical and pathological features of a total of 6 patients with t(3;8)(q27;q24) treated at our institution, 4 of whom were described previously.⁵ Ages ranged between 55 and 82 years, and all but one had stage IV diseases. One or more extranodal sites of involvement were observed in all. LD was elevated and the international prognostic index scores were 3 or higher in all but one. All patients showed the Burkitt lymphoma/leukemia or DLBCL/HGBL histopathology with a high Ki-67 proliferation index and MYC positivity. Of 4 patients who carried t(3;8)(q27;q24)/BCL6::MYC but lacked t(14;18)(q32;q21), 3 belonged to the GCB COO subtype and one showed a non-GCB/ABC profile (Tables 1 and 2), in accordance with MYC/BCL6 DH exhibiting both COO phenotypes.³ Two elderly patients died shortly after presentation, while 3 patients survived for 3 years and 6 months to 10 years and 11 months in response to the initial treatment (Table 3).

Table 1.Clinical features of 6 patients with t(3;8)(q27;q24)/BCL6::MYC treated at Tenri Hospital

Study	Case no.	Diagnosis	Age/sex	Stage	PS	LD (U/L)	Involved extranodal organs	IPI score	sIL-2R (U/mL)	t(14;18)
Ohno (2017)	#10	BLL	80/M	IV	3	24,195	PB, BM, pancreas, adrenal grand, gall bladder, seminal vesicle, cavernous sinus	5	6,821	No
	#13	DLBCL	69/M	IE	1	159	Ileocecum	1	551	Yes
	#14	DLBCL	74/F	IV	2	599	Small intestine, peritoneal dissemination	5	1,566	No
	#15	DLBCL	76/F	IV	1	431	Small intestine	4	1,517	No
This study	Case 1	DLBCL/HGBL	82/M	IV	3	8,690	PB, BM, ribs, pleura, chest wall	5	6,033	Yes
This study	Case 2	DLBCL/HGBL	55/M	IV	2	666	BM	3	1,297	No

BLL, Burkitt lymphoma/leukemia; DLBCL, diffuse large B-cell lymphoma; HGBL, high-grade B-cell lymphoma; PS, performance status; LD, lactate dehydrogenase; PB, peripheral blood; BM, bone marrow; IPI, international prognostic index; sIL-2R, soluble interleukin-2 receptor.

Table 2.Immunohistochemistry of 6 lymphomas that carried t(3;8)(q27;q24)/BCL6::MYC

Study	Case no.	CD20	CD10	BCL6	MUM1	BCL2	Ki-67	MYC	CD5	EBER	Hans
Ohno (2017)	#10	+	+	−	−	+	>90%	+	−	−	GCB
	#13	+	+	+	−	+	≈90%	+	−	−	GCB
	#14	+	+	+	+	+	80~90%	+	−	−	GCB
	#15	+	−	+	−	−	>90%	+	−	−	GCB
This study	Case 1	+	+	+	NT	+	90%	+ (90%)	−	NT	GCB
This study	Case 2	+	−	+	+	+ or −	90%	+ (90%)	+	NT	Non-GCB/ABC

EBER, EBV-encoded small RNA; Hans, Hans classification of DLBCL; GCB, germinal-center B-cell–like; ABC, activated B-cell–like.

NT, not tested.

Table 3.Treatment and outcome of 6 patients with t(3;8)(q27;q24)/BCL6::MYC treated at Tenri Hospital

Study	Case no.	Initial treatment	Response to initial treatment	Overall survival
Ohno (2017)	#10	MTX, PSL	PD	8 days
	#13	Surgery, R-CHOP	CR	7 years and 10 months
	#14	Surgery, R-CHOP	CR	10 years and 11 months
	#15	R-CHOP	PR	12 months
This study	Case 1	R-miniCHOP	PD	2 months
This study	Case 2	DA-EPOCH-R	CR	3 years and 6 months

MTX, methotrexate; PSL, prednisolone; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; CR, complete response; PR, partial response; PD, progressive disease. See text for R-miniCHOP and DA-EPOCH-R.

In the context of DH, it is of special interest whether t(3;8)(q27;q24) leads to simultaneous activation of both BCL6 and MYC involved in translocation. Breakages of t(3;8)(q27;q24) have been reported to occur upstream of BCL6 and downstream of MYC, and as the result of translocation, 3′ MYC links to BCL6 in a tail-to-tail orientation on der(3)t(3;8)(q27;q24) and 5′ BCL6 links to MYC in a head-to-head orientation on der(8)t(3;8) (q27;q24), respectively (Figure 6). Ryan et al. used the combination of chromatin immunoprecipitation and next-generation sequencing to map acetylated enhancer elements, revealing that the 3′ MYC linked to BCL6 on der(3)t(3;8)(q27;q24) lacks acetylation, while 5′ BCL6 is broadly acetylated, and the 5′ BCL6::MYC linkage on der(8)t(3;8)(q27;q24) leads to strong activation of MYC by the interaction between the MYC promoter and BCL6 enhancer elements.⁶ The authors suggested that t(3;8)(q27;q24) does not represent MYC/BCL6 DH, but is equivalent to a single-hit (SH) MYC-activating rearrangement, and proposed the term “pseudo-DH” for this particular translocation.

Figure 6.

Figure 6. Schematic diagram of t(3;8)(q27;q24)/BCL6::MYC.

The most important question is whether t(3;8)(q27;q24)/BCL6::MYC pseudo-DH is associated with patient survival. A study reviewing the outcomes of 19 patients with t(3;8)(q27;q24) reported that 63% of patients achieved CR and 2- and 3-year OS rates were 63 and 57%, respectively.¹⁶ However, because that study was the collection of a small number of case reports from multiple centers, no conclusions could be drawn. A targeted sequencing study revealed that BCL6 is the most frequent non-IG partner gene of MYC, accounting for 8% of MYC translocations.⁶ Thus, it is likely that the translocation has been overlooked in conventional cytogenetic analysis. In a recent study, in which t(3;8)(q27;q24) was detected by a MYC/BCL6 dual fusion probe specifically designed for the translocation, 22 DLBCL patients were found to have t(3;8)(q27;q25) pseudo-DH. Survival analyses revealed that t(3;8)(q27;q24) pseudo-DH patients had a similar prognosis to MYC SH patients, while 23 t(3;8)(q27;q24)-negative MYC/BCL6 DH patients had a significantly poorer prognosis.⁷ As suggested by the authors, MYC/BCL6 DH patients should be divided into two groups based on whether they have t(3;8)(q27;q24), and only those lacking t(3;8)(q27;q24) should be considered as “true” MYC/BCL6 DH patients. Therefore, it may be premature to totally exclude MYC/BCL6 DH from the DLBCL/HGBL category, and “true” MYC/BCL6 DH patients may need to be enrolled in clinical trials addressing high-risk diseases.⁷

ACKNOWLEDGMENTS

This study was supported by the Tenri Foundation.

ETHICAL APPROVAL

The present study was performed according to the regulations of the Institutional Review Board (Approved no.: 834).

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