1.Molecular characteristics of diffuse large B-cell lymphoma with high expression of MYC:analysis of 45 cases
Nian LIU ; Dongshen MA ; Ying GU ; Dan LUO ; Meiting FAN ; Yubo WANG ; Chenxi XIANG ; Hui LIU
Chinese Journal of Clinical and Experimental Pathology 2024;40(1):60-65
Purpose To explore the molecular features of diffuse large B-cell lymphoma(DLBCL)with high expression of MYC.Methods The clinical data of 45 cases of DLBCL were collected.Immunohistochemical EnVision method was used to classify the patients into the group with high expression of MYC and the group with low expression of MYC.All samples were subjected to DNA targeted sequencing and molecular typing was performed using the LymphGen online tool.Cellular origin was determined by using the Lymph2Cx method.The correlation be-tween MYC overexpression and clinicopathological parameters was analyzed by the x2 test and Fisher precise test.Survival curves were drawn and survival-related factors were analyzed u-sing Cox univariate and multivariate regression.ResultsCases were classified into DLBCL with high expression of MYC(n=17)and DLBCL with low expression of MYC(n=28).Com-pared to the group with low expression of MYC,the group with high expression of MYC had more PIM1,MYD88,CD79B,CD58 and PRDM1 mutations(76.5%vs 28.6%,70.6%vs 32.1%,58.8%vs28.6%,29.4%vs3.6%,29.4%vs 3.6%,P<0.05),MCD were more frequently found(58.8%vs 10.7%,P=0.001),GCB were rarely found(17.6%vs 50.0%,P=0.030).Overall survival was significantly shorter in DLBCL with high expression of MYC(P<0.05).Cox multi-factorial analysis showed that age was an independent prognostic factor for DLBCL(P<0.05).Conclusion Patients with high expression of MYC were frequently characterized as MCD and ABC,and PIM1,MYD88,CD79B,CD58 and PRDM1 muta-tions were common.Patients with high expression of MYC had a poorer prognosis.
2.Diagnosis and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement
Dan LUO ; Chenxi XIANG ; Dongshen MA ; Guangzhen LIU ; Meiting FAN ; Yubo WANG ; Jing ZHAO ; Yuqing YUAN ; Qingqing SHEN ; Xinyu LIU ; Hui LIU
Chinese Journal of Pathology 2024;53(6):563-569
Objective:To analyze the clinicopathological features and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement, aiming enhance its recognition and prevent misdiagnosis.Methods:The clinicopathological features, immunophenotype, and fluorescence in situ hybridization (FISH) results of six cases diagnosed with IRF4 rearrangement-positive B-cell lymphoma at the Affiliated Hospital of Xuzhou Medical University from 2015 to 2023 were retrospectively analyzed. Additionally, a comprehensive review of the literature was conducted.Results:Six patients with IRF4 rearrangement-positive large B-cell lymphoma were included. Patients 1 to 5 included three males and two females with a median age of 19 years ranging from 11 to 34 years. Four patients presented with head and neck lesions, while the other one had a breast nodule; all were in clinical Ann Arbor stages I to Ⅱ. Morphologically, entirely diffuse pattern was present in two cases, purely follicular pattern in one case, and diffuse and follicular patterns in other two cases. The tumor cells, predominantly centroblasts mixed with some irregular centrocytes, were of medium to large size, with a starry sky appearance observed in two cases. Immunophenotyping revealed all cases were positive for bcl-6 and MUM1, with a Ki-67 index ranging from 70% to 90%, and CD10 was positive in two cases. IRF4 rearrangement was confirmed in all cases by FISH analysis, with dual IRF4/bcl-6 rearrangements identified in two cases, leading to a diagnosis of LBCL-IRF4. Case 6, a 39-year-old female with a tonsillar mass and classified as clinical Ann Arbor stage Ⅳ, displayed predominantly diffuse large B-cell lymphoma (DLBCL) morphology with 20% high-grade follicular lymphoma characteristics. Immunohistochemistry showed negative CD10 and positive bcl-6/MUM1, with a Ki-67 index of approximately 80%. Triple rearrangements of IRF4/bcl-2/bcl-6 were identified by FISH, leading to a diagnosis of DLBCL with 20% follicular lymphoma (FL). All six patients achieved complete remission after treatment, with no progression or relapse during a follow-up period of 31-100 months.Conclusions:Large B-cell lymphoma with IRF4 rearrangement is a rare entity with pathological features that overlap with those of FL and DLBCL. While IRF4 rearrangement is necessary for diagnosing LBCL-IRF4, it is not specific and requires differentiation from other aggressive B-cell lymphomas with IRF4 rearrangement.