BCL-6 and other genomic alterations in non-Hodgkin's lymphoma (NHL).

This study reports on the frequency and disease association pattern of a number of gene rearrangements in a large panel of lymphoid tumours (n = 94). We detected the t(11;14) translocation, involving rearrangement of the BCL-1 locus, in 60% of mantle cell lymphomas. The BCL-2 gene, located at band 18q21, was rearranged in 42% of follicle centre lymphomas (FCL) and in 15% of diffuse large B-cell (DLBC) lymphomas. In this study, 80% of the c-MYC rearrangements were detected in aggressive diffuse lymphoma subsets but, interestingly, 9% of FCL showed involvement of t(8q24) translocation. In our study, rearrangements of the BCL-6 gene at band 3q27 were found in 31% of DLBC lymphomas. Interestingly, 50% of the BCL-6 rearrangement positive lymphoma cases had coexisting gene rearrangements involving all of the aforementioned gene loci. The molecular dissection of these genes will improve our understanding of the genesis of the diverse clinicopathological subtypes.     

Follicular lymphoma without t(14;18) and with BCL-6 rearrangement: a lymphoma subtype with distinct pathological, molecular and clinical characteristics.

Translocations involving the BCL-6 gene are frequently observed in diffuse large B cell lymphoma, but have rarely been reported in follicular lymphoma (FL). We studied a distinct cohort of FLs with a 3q27/BCL-6 gene rearrangement, but lacking the t(14;18) translocation. In 13/15 cases, translocations involved the 3q27 and the 14q32 regions. All cases displayed a marked follicular growth pattern and, in some instances, a monocytoid component. Tumor cells were CD5(-) CD20(+) CD23(-) CD43(-) BCL-6(+), and in the main CD10 negative (n = 10, 71%) and BCL-2 negative (n = 11, 78%). When compared to 20 typical t(14;18)(+) FLs, the presence of large follicles (P = 0.01) and a CD10(-)/BCL-2(-) phenotype were more frequently observed (P = 0.001) in our cohort. Clonal mutations arising in the BCL-6 first intron were observed in 5/7 cases with evidence of intraclonal heterogeneity, consistent with a germinal center origin. No significant difference was found in comparison to t(14;18)(+) FL regarding age, sex, performance status, bone marrow involvement or overall survival. However, in the 3q27(+) FL group, a stage III/IV disease and a bulky mass were less frequently observed. This study indicates that 3q27(+) FL without t(14;18) translocation have peculiar clinico-pathologic features and may correspond to a rare and distinct subtype of lymphoma originating from the germinal center.     

BCL-6 mRNA expression in higher grade transformation of follicle center lymphoma: correlation with somatic mutations in the 5' regulatory region of the BCL-6 gene.

Follicle center lymphoma (FCL) is an indolent low-grade B cell non-Hodgkin's lymphoma (NHL) that frequently transforms to aggressive diffuse large B cell lymphoma (DLBCL). Histological transformation of FCL is commonly associated with accumulation of secondary genetic alterations. The BCL-6 gene is commonly implicated in the pathogenesis of DLBCL and its expression may be altered by clonal rearrangements and somatic point mutations in its 5' non-translated regulatory region. Recently, somatic mutations of the BCL-6 gene were associated with the transformation process. Here, we examined BCL-6 mRNA expression and BCL-6 mutations in paired biopsies from the same patients obtained at the time of FCL diagnosis and after transformation. BCL-6 mRNA expression markedly increased upon transformation (1.9- to 4.8-fold) in three cases, remained unchanged in one case and decreased compared to the diagnosis FCL specimens in four cases. The three specimens that demonstrated an increase in the BCL-6 mRNA expression upon transformation harbored BCL-6 gene mutations in the 5' region of the first intron that overlapped with the previously reported negative regulatory region of the gene. Accumulation of new mutations in this region was not observed in DLBCL biopsies in which the BCL-6 mRNA expression did not increase. The present study demonstrates that although BCL-6 gene mutations do accumulate during the transformation process and, depending on their location within the first intron, may deregulate BCL-6 mRNA expression, increase in BCL-6 mRNA expression is not uniformly required for transformation from FCL to DLBCL.     

A polymorphism in the BCL-6 gene is associated with follicle center lymphoma

Follicle center lymphoma (FCL) accounts for approximately 40% of all non-Hodgkin's lymphomas (NHL). The genetic-environmental interactions involved in the etiology and pathogenesis of this disease are unknown. In our previous study a single nucleotide polymorphism (SNP) (397C) in the regulatory untranslated first intron region of the BCL-6 gene was found in four of the eight FCL patients but in none of the 10 healthy controls. To further evaluate the potential association between the 397C allele of the BCL-6 gene and FCL, we performed a case-control study. Genomic DNA was isolated from 85 FCL patients, from 98 control cases without a previous history of malignancy, treated at Stanford University Medical Center for non-malignant disorders and from 90 samples from the DNA Polymorphism Discovery Resource. The 397G and the 397C polymorphic alleles were identified by a PCR-RFLP method. To evaluate the possible effect of this polymorphism on gene expression, BCL-6 mRNA levels in nine FCL tumors with the 397G-G genotype and in nine FCL tumors with the 397G-C genotype were measured by quantitative real-time RT-PCR. The 397C polymorphic allele was found in 32 FCL cases (37.6%), in 20 controls (20.4%) and in 17 (18.9%) samples from the DNA Polymorphism Discovery Resource. The prevalence of the 397G-C and 397C-C genotypes was significantly higher in FCL cases than in control group (p = 0.01). No difference in BCL-6 gene expression was observed between FCL cases with 397G-G and 397G-C genotypes. The present study demonstrates a possible association between the 397C allele of the BCL-6 proto-oncogene and FCL. The similar levels of BCL-6 mRNA expression in 397G-G and in 397G-C FCL cases suggests that any possible oncogenic effect of the polymorphic allele would not simply be related to a direct effect on BCL-6 gene expression and suggests the existence of other FCL susceptibility genes that are in linkage disequilibrium with the 397C allele of the BCL-6 gene.     

Comparison of genetic aberrations in CD10+ diffused large B-cell lymphoma and follicular lymphoma by comparative genomic hybridization and tissue-fluorescence in situ hybridization

CD10 is one of the hallmarks of germinal center B-cells where follicular lymphomas (FL) originate. It has not been clearly established, however, whether CD10(+) diffuse B-cell lymphomas (DLBCL) are genetically similar to FL. We therefore examined 19 CD10(+) DLBCL and 40 FL by means of comparative genomic hybridization (CGH) and tissue-fluorescence in situ hybridization (T-FISH). Chromosomal imbalance was more frequently detected in CD10(+) DLBCLs (19/19) than in FLs (24/40). Significant differences were found in eight frequently imbalanced regions, namely those with gains of chromosomes 7q and 12 and those with losses of chromosomes 1p, 4p, 6q, 15q, 16p and 17. Amplification of the 3q region where BCL6 is located is reported to occur frequently in DLBCL, but it was only found in one of the 19 CD10(+) DLBCL cases we examined. The involvement of t(14;18) in CD10(+)+ DLBCL (31%) and in FL (73%) was significantly different (P = 0.0064). The CGH pattern of CD10(+) DLBCL with t(14;18) was also different from that of FL with t(14;18). Taken together, our results indicate that CD10(+) DLBCL constitutes a unique subtype entity with genetic characteristics significantly different from those of FL and DLBCL.     

Protein expression of B-cell lymphoma gene 6 (BCL-6) in invasive breast cancer is associated with cyclin D1 and hypoxia-inducible factor-1alpha (HIF-1alpha)

B-cell lymphoma gene (BCL-6) upregulation contributes to immortalization of mouse embryo fibroblast and primary B cells via upregulation of cyclin D1. As cyclin D1 overexpression is a common phenomenon in different cancers, BCL-6 protein overexpression may not be restricted to lymphomas. In this study, expression of BCL-6 was investigated by immunohistochemistry on paraffin-embedded specimens from 150 breast cancer patients and 10 specimens of normal breast tissue. The results showed BCL-6 overexpression (> or =10% of cells) in 24/150 (16%) breast cancer patients, whereas in normal breast low expression (<1%) of BCL-6 was observed. In linear regression analysis BCL-6 expression was associated with cyclin D1 (r=0.197, P=0.016). Further, in chi2 analyses, BCL-6-positivity was associated with overexpression of p53 (P=0.016), and hypoxia-inducible factor-1alpha (P<0.001). Involvement of BCL-6 in breast carcinogenesis is further underscored by comparative genomic hybridization analysis that showed gains at the BCL-6 locus (3q27) in 14/86 (16%) breast cancer tissues. The cases with amplification in BCL-6 showed an increased (25%) incidence of BCL-6 protein overexpression. Thus, this study is the first to show that BCL-6 oncogene activation plays a role in cancers other than lymphomas.     

Mutation of the ATM gene is not involved in the pathogenesis of either follicle center lymphoma or its transformation to higher-grade lymphoma

Loss of function of the ataxia-telangiectasia mutated (ATM) gene, located on human chromosome 11q22-23, is the cause of ataxia-telangiectasia (A-T), which is associated with an extremely high risk for lymphoma. Abnormalities in 11q22-23, including deletions and mutations of the ATM gene, have been reported in T-cell prolymphocytic leukemias, B-CLL and in mantle cell lymphoma. In a survey of gene expression in follicle center lymphomas (FCL) and diffuse large B-cell lymphomas (DLBCL), almost all FCL expressed significant levels of ATM and the majority of DLBCL expressed low levels of ATM. This finding raised the possibility that the transformation of some FCL to DLBCL might be associated with inactivation of the ATM gene. Therefore, we analyzed biopsy specimens of 17 patients with FCL obtained at the time of diagnosis, four subsequent biopsies obtained at the time of FCL relapse and seven subsequent biopsies at the time of transformation to DLBCL. A comprehensive analysis of the ATM gene was performed by denaturing high performance liquid chromatography and sequencing. The analysis covered all of the 66 exons including the 9168 base pairs of ATM coding sequence as well as 16,676 base pairs of non-coding sequence. Twenty-eight known polymorphisms and rare sequence variants were observed, but no classic A-T mutations were detected. In 11 tumors, both tumor B-cells and normal T-cells were sorted for separate examination, and in each case, polymorphisms and rare variants were present in both tumor and normal cells. No new ATM gene mutations were associated with transformation from FCL to DLBCL. Thus, ATM gene mutations do not play a pivotal role either in the pathogenesis of FCL or in its transformation to DLBCL.     

Circulating immune markers and risks of non-Hodgkin lymphoma subtypes: A pooled analysis

Although prediagnostic circulating concentrations of the immune activation markers soluble CD27 (sCD27), sCD30 and chemokine ligand-13 (CXCL13) have been associated with non-Hodgkin lymphoma (NHL) risk, studies have been limited by sample size in associations with NHL subtypes. We pooled data from eight nested case-control studies to investigate subtype-specific relationships for these analytes. Using polytomous regression, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) relating study-specific analyte tertiles to selected subtypes vs controls (n = 3310): chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; n = 623), diffuse large B cell lymphoma (DLBCL; n = 621), follicular lymphoma (FL; n = 398), marginal zone lymphoma (MZL; n = 138), mantle cell lymphoma (MCL; n = 82) and T cell lymphoma (TCL; n = 92). We observed associations with DLBCL for elevated sCD27 [OR for third vs first tertile (OR_T3) = 2.2, 95% CI = 1.6-3.1], sCD30 (OR_T3 = 2.0, 95% CI = 1.6-2.5) and CXCL13 (OR_T3 = 2.3, 95% CI = 1.8-3.0). We also observed associations with sCD27 for CLL/SLL (OR_T3 = 3.3, 95% CI = 2.4-4.6), MZL (OR_T3 = 7.7, 95% CI = 3.0-20.1) and TCL (OR_T3 = 3.4, 95% CI = 1.5-7.7), and between sCD30 and FL (OR_T3 = 2.7, 95% CI = 2.0-3.5). In analyses stratified by time from phlebotomy to case diagnosis, the sCD27-TCL and all three DLBCL associations were equivalent across both follow-up periods (<7.5, ≥7.5 years). For other analyte-subtype comparisons, associations were stronger for the follow-up period closer to phlebotomy, particularly for indolent subtypes. In conclusion, we found robust evidence of an association between these immune markers and DLBCL, consistent with hypotheses that mechanisms related to immune activation are important in its pathogenesis. Our other findings, particularly for the rarer subtypes MZL and TCL, require further investigation.     

A novel B-cell line (U-2932) established from a patient with diffuse large B-cell lymphoma following Hodgkin lymphoma

Little is known about mechanisms leading to secondary non-Hodgkin lymphomas (NHL) in patients treated for Hodgkin lymphoma (HL). Our aim was to characterise in detail a cell line derived from a diffuse large B-cell lymphoma (DLBCL) that had developed in a patient with relapsing HL. The cell line U-2932 was established from ascites in a patient suffering from DLBCL previously treated for HL with multiple chemotherapy regimens. Characterisation was based on morphology, immunophenotype, Epstein-Barr virus (EBV)-status, IgH gene rearrangement status, tumourigenicity, p53 sequencing, and immunohistochemical expression of p53, BCL-2 and BCL-6. The karyotype was investigated using G-banding, comparative genomic hybridisation (CGH) and spectral karyotype (SKY) analysis. This cell line shows typical morphological features of a DLBCL and grows as colonies in nude mice. It expresses a B-cell phenotype with a somatically hypermutated V(H)4-39 gene and is negative for EBV. The origin of U-2932 was confirmed by demonstrating an identical V(H)4 rearrangement in ascites from the patient. A point mutation of the tumour-suppressor gene p53 was detected in amino acid position 176 and immunohistochemical over-expression of the p53 protein was also demonstrated. U-2932 carries a complex karyotype including high-level amplifications of the chromosomal bands 18q21 and 3q27 and expresses aberrant BCL-2 and BCL-6 immunohistochemically. We were unable to investigate the clonal relationship between the original HL and U-2932. In conclusion, U-2932 is a unique B cell line established from a patient suffering from HL followed by NHL. Overexpression of BCL-2, BCL-6 and p53 may play a role in the tumourigenesis and drug resistance. This cell line may become a useful tool to better understand the mechanisms responsible for development of secondary NHL in patients treated for HL.     

Analysis of Aurora-A and hMPS1 mitotic kinases in mantle cell lymphoma

Aurora-A and hMPS1 are kinases involved in spindle checkpoint and centrosome duplication regulation and whose alterations have been associated with cell transformation and chromosome instability in different tumor models. In this study, we have examined the possible alterations of these genes in 58 mantle cell lymphomas (MCLs) and 4 MCL-related cell lines. Aurora-A was also examined in 46 diffuse large B-cell lymphomas (DLBCLs). Aurora-A and hMPS1 mRNA expression levels were related to tumor proliferative activity. Interestingly, a MCL case with the highest number or chromosomal imbalances also showed an extremely high value of Aurora-A mRNA expression. No Aurora-A gene amplifications were detected in any tumor or cell line, whereas hemizygous hMPS1 gene deletions were observed in 23% of MCLs and 3 of the 4 cell lines. However, no expression alterations or gene mutations were detected in these cases. The Aurora-A proposed cancer susceptibility polymorphic variant (P31I) was observed with a similar frequency in MCL, DLBCL, chronic lymphocytic leukemia and in the 431 healthy controls. However, the 3 MCLs and 4 DLBCLs with the homozygous variant of this polymorphism had particular clinical characteristics with an unusual early-age presentation and second epithelial malignancies in MCL and extranodal origin in DLBCL. These findings indicate that Aurora-A and hMPS1 aberrations are uncommon in aggressive lymphomas but Aurora-A overexpression may contribute to numerical chromosomal alterations in occasional MCL. Although the Aurora-A P31I polymorphic variant is not directly involved in a genetic predisposition to these lymphomas, it may modulate the clinical presentation of these tumors.     

3q27-3q29相关的p63蛋白表达在弥漫性大B细胞淋巴瘤中的意义

 目的　探讨3q27-3q29相关的p63蛋白表达在弥漫性大B细胞淋巴瘤（DLBCL）中的意义。方法　应用免疫组织化学EnVision二步法检测102例DLBCL与15例反应性淋巴组织增生（RHL）中p53蛋白和3q27-3q29相关的p63蛋白的表达并进行随访。结果　p53、p63蛋白在DLBCL中的阳性率分别为62 %和56 %,在RHL中的阳性率分别为0和13 %,p53、p63蛋白在DLBCL与RHL中比较差异均有统计学意义（P＜0.05）;p53、p63蛋白的表达在Ⅰ+Ⅱ期中的阳性率分别为48.3 %和41.4 %,在Ⅲ+Ⅳ期中的阳性率分别为79.5 %和75 %,差异有统计学意义（P＜0.05）;p53、p63蛋白的表达在生发中心B细胞型（GCB型）中的阳性率分别为28 %和28 %,在非GCB型（non-GCB型）中的阳性率分别为72.7 %和64.9 %,差异均有统计学意义（P＜0.05）。p53、p63蛋白表达与患者性别、年龄、有无B症状和发病部位等无相关性（P＞0.05）。p53蛋白表达与p63蛋白表达呈正相关性（r＝0.629,P＜0.05）。p53、p63蛋白表达阴性组的5年总体生存率高于阳性组（38 %∶6 %,51 %∶4 %）,差异有统计学意义（P＜0.05）。结论　p63可能作为癌基因与p53共同参与了DLBCL的发生和发展,两者在肿瘤的发生中可能起着协同作用;联合检测p63蛋白和p53蛋白在DLBCL中的表达,可能成为判断DLBCL预后指标之一。     

Cyclin D1和bcl-2在B细胞淋巴瘤中的表达及其在鉴别诊断中的意义

 B细胞淋巴瘤根据免疫表型可分为不同亚型,且不同亚型侵袭度不同,预后也有很大差异。Cyclin D1是已被证实与肿瘤有最直接关系的细胞周期蛋白,在大多B细胞淋巴瘤[套细胞淋巴瘤（MCL）、慢性淋巴细胞白血病（CLL）、边缘区淋巴瘤（MZL）、弥漫大B细胞淋巴瘤（DLBCL）等]中均有表达。多数B细胞淋巴瘤[滤泡性淋巴瘤（FL）、DLBCL等]都能可见易位活化的bcl-2表达增强。Cyclin D1及bcl-2作为B细胞淋巴瘤重要的细胞周期蛋白及抗凋亡基因,在淋巴瘤的鉴别诊断中起重要作用,其检测及检测手段的灵敏度和特异度具有重要的临床价值。     

bcl-2与bcl-6在弥漫性大B细胞淋巴瘤中表达的研究

 目的　从蛋白水平和基因水平研究bcl-2、bcl-6在弥漫性大B细胞淋巴瘤（DLBCL）的表达。方法　应用免疫组织化学EnVision法对73例DLBCL进行CD3、CD10、CD20、bcl-2、bcl-6、MUM-1的标记。应用荧光原位杂交（FISH）技术检测其中57例t（14;18）染色体异位bcl-2基因的异常情况和54例bcl-6基因所在的3q27染色体的断裂和扩增情况。结果　肿瘤细胞表达CD10、bcl-6、MUM-1、bcl-2的阳性率分别为15.1 %、38.4 %、71.2 % 、79.2 %。57例患者中16例（28.1 %）存在t（14;18）。bcl-2蛋白表达与免疫学亚型有相关性（P＝0.035）,t（14;18）与预后有相关性（P＝0.045）,t（14;18）与bcl-2蛋白表达无相关性（P＝0.710）。54例中3q27染色体断裂11例（20.4 %）,扩增14例（25.9 %）。bcl-6阳性表达较阴性者预后好（P＝0.041）。bcl-6与3q27断裂和扩增无相关性（均P＝1.000）。结论　bcl-2、bcl-6蛋白和基因表达是各自独立的事件,它们在DLBCL中的意义不同。bcl-2蛋白是与免疫学亚型相关的预后标志物,bcl-2阳性的GCB型预后较差;t（14;18）是独立预后事件,阳性者预后较差,对靶向治疗患者应检测t（14;18）;bcl-6蛋白的表达有助于DLBCL的预后判断,可作为独立的预后因子。3q27染色体断裂可能提示预后较差。     

弥漫性大B细胞淋巴瘤C-MYC基因异常分析

  目的   探讨弥漫性大B细胞淋巴瘤(DLBCL) MYC基因异常情况及其与BCL-2、BCL-6基因异常的关系。   方法   应用组织芯片和FISH技术对194例DLBCL的MYC、BCL-2、BCL-6基因异常情况进行检测, 并用免疫组织化学法检测CD10、BCL-6、MUM-1及Ki-67等蛋白标记物, 分析其相互关系。   结果   在164例MYC基因异常为38例(23.17%), 其中基因易位9例(5.49%), 基因扩增29例(17.68%); 同时存在MYC和BCL-6基因易位有2例, 未发现MYC和BCL-2同时易位或三者同时易位的病例; 资料完整(同时获得三种基因FISH结果) 的159例病例中, MYC基因扩增28例(17.61%) 与BCL-2基因扩增38例(23.90%) 呈显著正相关(r=0.291 6, P=0.000 4);MYC基因易位病例Ki-67高表达率(5/8, 62.50%) 明显高于非MYC基因易位病例(33/149, 22.15%, P=0.027 7), 2例MYC和BCL-6同时易位的病例均为Ki-67高表达, MYC基因扩增与Ki-67高表达无显著相关性。   结论   有关MYC基因在弥漫性大B细胞淋巴瘤中的异常改变除基因重排外, 还有基因扩增等活化方式, 目前对其作用机制尚缺乏了解, 值得进行深入研究。      

Two patterns of chromosomal breakpoint locations on the immunoglobulin heavy-chain locus in B-cell lymphomas with t(3;14)(q27;q32): relevance to histology

The t(3;14)(q27;q32) is the most common translocation involving BCL6 in B-cell lymphoma. Although this translocation was predominantly associated with diffuse large B-cell lymphoma (DLBCL), recent studies have shown that it can also be found in follicular lymphomas (FL), often associated with a large cell component. To further investigate the relationship that might exist between this translocation and the phenotype of the tumors, we studied 34 lymphomas with a t(3;14)(q27;q32). Twenty cases were DLBCL, 14 FL and most cases, regardless of histology, were negative for the expression of CD10 (26/32, 81%). We identified the IGH switch region involved in the translocation for 32 cases. Our data indicate that in DLBCL most breakpoints involve the switch mu (17/19; 89%), whereas in FL most involve a switch gamma (9/13; 70%) (P=0.0016, Fisher's exact test). This correlation between the histology and the structure of the translocated allele suggests that the lymphomas with Smu and Sgamma translocations may originate from different cells, or that the substituted regulatory regions that come to deregulate BCL6 may affect the presentation of the disease.     

Comparison of the expression and prognostic significance of differentiation markers between diffuse large B-cell lymphoma of central nervous system origin and peripheral nodal origin.

PURPOSE: Whether diffuse large B-cell lymphoma (DLBCL) of primary central nervous system origin (PCNSL) is biologically different from DLBCL of peripheral nodal origin (NL) remains unclear. The purpose of this study was to compare the expression frequencies and prognostic significance of a panel of cell differentiation markers between these two disease entities. EXPERIMENTAL DESIGN: This study included HIV-unrelated patients with PCNSL (n = 51) and NL (n = 72) treated at four hospitals in Taiwan for whom archival tumor tissue was available. Immunohistochemistry for CD10, BCL-6, MUM-1, vs38c, CD138, and BCL-2 was done. CD10, BCL-6, and MUM-1 expression results were used to classify all cases into the germinal center B-cell (GCB) or the non-GCB subgroup. The prognostic significances of clinical and immunophenotypic markers were evaluated. RESULTS: Nuclear MUM-1 expression was significantly higher in PCNSL than in NL (P < 0.001; 84% versus 53%). PCNSL tumors were more frequently classified into the non-GCB subgroup than NL tumors (P = 0.020; 78% versus 62%). For patients with PCNSL, univariate analysis showed that patients with BCL-6 expression had a trend towards longer survival (P = 0.073; median survival, 25.3 versus 7.3 months), and multivariate analysis showed BCL-6 was an independent prognostic factor (P = 0.026). For patients with NL, both of univariate (P = 0.003) and multivariate analyses (P = 0.002) showed that GCB was significantly associated with favorable survival. CONCLUSION: The higher frequency of non-GCB subclassification, which was mainly contributed by nuclear MUM-1 expression in PCNSL implies that it has a more differentiated cellular origin than NL. BCL-6 expression in patients with PCNSL and GCB subgroup in patients with NL were favorable prognostic factors.     

t(8;14)(q24;q32) in two patients with CD10-negative primary thyroid diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) with the 8q24 translocation is occasionally seen in the gastrointestinal tract, but has rarely been reported in the thyroid gland. We experienced two cases of primary thyroid DLBCL having t(8;14)(q24;q32). The immunophenotype and karyotype of Case 1 (66-year-old female) and Case 2 (70-year-old female) were: CD10-, CD20+, BCL-2+/add(13)(q34), t(8;14)(q24;q32) and CD10-, CD20-, CD79a+, BCL-2-/t(8;14)(q24;q32), respectively. Although long-term complete remission could be achieved in both of our patients by conventional chemotherapy with/without radiation therapy, accumulation of further such cases is necessary to develop a standard treatment protocol and also to elucidate the pathogenesis of t(8;14)(q24;q32)-positive primary thyroid DLBCL.