The Expression And Significance Of MUM1/IRF4 In Diffuse Large B-cell Lymphoma And Two Cases Of IRF4 Gene Rearrangement Positive Large B-cell Lymphoma Were Reported

Purpose:To investigate the relationship between MUM1/IRF4 expression and prognosis of diffuse large B-cell lymphoma.Combined with literature review,clinical data,histopathological characteristics,immunophenotype and fluorescence in situ hybridization are summarized for large B-cell lymphoma with IRF4 gene rearrangement positive.The results of FISH detection can provide the basis for the diagnosis and treatment of this disease.Methods:The clinical data of 85 newly diagnosed patients with diffuse large B-cell lymphoma admitted to the hematology department of XX Hospital from January 2017 to October2022 were retrospectively analyzed.The patient’s gender,age of onset,lactate dehydrogenase level(LDH),Ann Arbor staging,ECOG score,NCCN-IPI score,extranodal involvement,fever and other symptoms of group B,pathological characteristics and immune surface typing results were included.The progression-free survival time(PFS)of the patients were followed up and recorded.The pathologic sections of the patients were borrowed from the pathology department,and experienced pathologists were invited to help guide the reading of the slices.The specific quantitative score of MUM1 was performed.According to the pathological characteristics and immune typing results of the patients,17 patients with positive CD10 expression and/or BCL-6 expression and MUM1 expression were screened out for fluorescence in situ hybridization(FISH)detection.Two cases of LBCL-IRF4 were detected,and their clinical data,histopathological features and immunophenotype were analyzed.Meanwhile,the clinical features of large B-cell lymphoma with positive IRF4 gene rearrangement were analyzed combined with the review of domestic and foreign literature.Results:Among the 85 patients with diffuse large B-cell lymphoma,41 were male(48.2%),44 were female(41.8%),33 were under 60 years old(38.8%),and 52 were over 60 years old(61.2%).There were 34 patients(40%)with Ann Arbor stage I /II and 51 patients(6%)with stage III /IV.64 patients(75.3%)had NCCN-IPI score less than or equal to 3 points(low-risk group and low-medium-risk group),and 11 patients(24.7%)had NCCN-IPI score greater than 3 points(medium-risk group and high-risk group).46 patients(54.1%)had an ECOG pin score of 0-1,39 patients(45.9%)had an ecog pin score of >2,and 27patients(31.8%)had unexplained symptoms of Group B,such as fever,night sweats and weight loss.There were 24 patients(58.8%)with normal LDH level(LDH≤250U/L)and58 patients(41.2%)with higher LDH level than normal(LDH> 250U/L).Extranodal vital organ involvement was observed in 23 patients(19.7%).According to the expression types of CD10,mum1 and BCl6,29 cases were GCB(34.1%)and 56 cases were non GCB(65.9%).2.The critical value of MUM1 calculated by ROC curve was 6 points,which was statistically significant.3.To compare the relationship between MUM1 expression degree and clinical characteristics of diffuse large B-cell lymphoma patients,the proportion of stage Ⅲ/Ⅳ patients in MUM1>6 group(P<0.001),IPI>3(P=0.032),symptoms in group B(P=0.002),ECOG score >2 points were all higher than those in MUM1≤6 group.4.Survival analysis showed that patients with MUM1>6 had shorter PFS and OS than those with MUM1≤6.5.Univariate analysis showed that MUM1 expression,LDH>250U/L,symptoms in group B and Ann Arbor stage III /IV were all associated with worse PFS and OS in diffuse large B-cell lymphoma(P<0.05).COX multivariate regression analysis suggested that MUM1 and NCCN-IPI scores were independent risk factors for PFS and OS.6.Through the FISH test of 17 patients with CD10 and/or BCL-6 and MUM1 positive expression,2 patients with IRF4 rearrangement were detected,Among them,1female and 1 male,aged 58 and 13 years old,respectively.The onset sites of the two patients were in the stomach and tonsil,respectively.After four cycles of R-CHOP chemotherapy,the efficacy was evaluated as complete response.Conclusion:1.The degree of MUM1/IRF4 expression is associated with poor prognosis in patients with diffuse large b-cell lymphoma.2.The incidence of large b-cell lymphoma with positive IRF4 gene rearrangement may be underestimated.It is necessary to pay more attention to pathological examination and FISH to avoid misdiagnosis.3.Large b-cell lymphoma with IRF4 gene rearrangement has a high expression of MUM1,but has a good prognosis.It is necessary to explore whether there is a specific therapeutic model in the future.