Purpose To investigate the clinicopathological features and prognosis of adult large B-cell lymphoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 63 adult LBCL-IRF4r cases were collected.The EnVision two-step method was employed for immunohistochemical staining,and fluorescence in situ hybridization was used to detect rearrangements or deletions of the IRF4,BCL2,MYC,BCL6,and TP53 genes.The relationship be-tween clinicopathological features and prognosis was analyzed and compared with data from 132 adult non-specified dif-fuse large B-cell lymphoma(DLBCL)cases.Results Among the 63 adult LBCL-IRF4r patients,the male to female ratio was 1.1∶1,with a median age of 54.0 years(range 20-84 years),and 14 cases(22.2％)were＜40 years old,24 cases(38.1％)were between 40 and 60 years old,and 25 cases(39.7％)were＞60 years old.18 cases(28.6％)were involved in Waldeyer's ring,along with 8 cases(12.7％)in cervical lymph nodes,7 cases(11.1％)in other lymph nodes and lymphatic organs,13 cases(20.6％)in stomach,4 cases(6.4％)in intestine,and 13 cases(20.6％)in other extranodal sites.63 cases showed IRF4 rearrangements,with no BCL2 and MYC translocations(0/58),30.9％(17/55)had BCL6 translocations,and 16.3％(8/49)had TP53 deletions.59 pa-tients were followed up for a median of 28 months(range 1-65 months).48 patients(81.4％)achieved complete re-sponse,10 patients(16.9％)experienced disease progression or relapse,and 3 patients(5.1％)died.Univariate a-nalysis showed that lactate dehydrogenase level,Ann Arbor stage,international prognostic index(IPI)score,growth pattern,Hans classification,and double expression of BCL2 and C-MYC were significantly associated with progression-free survival.Age,Ann Arbor stage,and IPI score were significantly associated with overall survival.Multivariate Cox regression analysis showed that double expression of BCL2 and C-MYC was an independent prognostic factor for pro-gression-free survival.Adult LBCL-IRF4r had significantly higher complete response rate and progression-free survival than adult DLBCL.Conclusion LBCL-IRF4r occurs in adults of all age groups,commonly affecting Waldeyer's ring,cervical lymph nodes,and gastrointestinal tract,and has a favorable clinical prognosis.

Objective:To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Methods:The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed. Morphological characteristics were observed. Immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization, clonal rearrangement analysis of T-cell receptor (TCR) genes, and targeted next-generation sequencing (NGS) were performed.Results:Among the 42 patients (male/female ratio of 2.8∶1.0), the age range was 32-77 years with a median age of 59.5 (52.0-65.0) years. Grossly, the tumors were presented as ulcerative or exophytic lesions, with a maximum diameter of 2-18 cm. There were 34 cases with a single lesion and 8 cases with more than 1 lesion. The tumor cells in all 42 cases were relatively monotonous in histology and small or medium in size. They had round or oval nuclei, moderately pale or clear cytoplasm, evenly distributed nuclear chromatin, inconspicuous nucleoli, and frequent mitotic figures. In one of the cases, there were moderately large cells, vacuolated nuclei, and clear nucleoli. Lymphoepithelial lesions were observed in 36 (85.7%) of the 42 cases, tumor necrosis in 4 (9.5%) cases, scattered eosinophils and/or plasma cell infiltration in the background in 9 (21.4%) cases, and a "starry sky" phenomenon in 1 (2.4%) case. The tumor cells in all cases exhibited high expression of CD3, CD2, CD7, CD8, CD56, TIA1, Granzyme B, and Perforin, while some also expressed CD4 (5/41, 12.2%), CD5 (3/41, 7.3%), CD20 (4/41, 11.9%), CD79α (2/37, 5.4%), and CD30 (1/34, 2.9%). The Ki-67 proliferation index ranged from 40% to 90%. EBER in situ hybridization tests were negative in all cases. TCR gene clonal rearrangement was detected in 96.4% (27/28) of the tested cases. Targeted NGS revealed commonly mutated genes including SETD2, STAT5B, JAK3, TP53, and CREBBP. The primary treatment was chemotherapy, with 2 cases undergoing autologous hematopoietic stem cell transplantation. Follow-up information was obtained for 29 cases, with a follow-up period of 1-73 months. The mortality was 93.1% (27/29).Conclusions:MEITL is a rare and highly aggressive peripheral T-cell lymphoma. Its clinical manifestations are diverse, and diagnosis primarily relies on a comprehensive assessment of pathological morphology, immunohistochemical profiles, and EBV infection status, supplemented by genetic testing if necessary. At present, there is no effective treatment, and its overall prognosis is poor.

Purpose To investigate the clinical,imaging,and pathological features of Kikuchi-Fujimoto disease(KFD).Methods A retrospective analysis was conducted on 123 pathologically confirmed KFD cases.Clinical and imaging data were collected,and histopathological features were evaluated using HE staining,immunohistochemistry,in situ hybridization for EBER,and molecular analyses(TCR/Ig gene rearrangements by PCR with capillary electro-phoresis).Results Among the 123 patients,the male-to-female ratio was 1∶2,with a median age of 30 years.All patients presented with lymphadenopathy.Among 30 hospitalized patients,63.3％(19/30)had fever,and 23.3％(7/30)had concurrent autoimmune diseases.Of the 12 patients who underwent PET-CT,91.7％(11/12)were sus-pected of malignancy,prompting biopsy recommendations.Among 47 consultation cases,27.7％(13/47)were ini-tially misdiagnosed as lymphoma.Histopathological examination revealed proliferative,necrotic,and xanthomatous phases,which coexisted or occurred independently.The proliferative phase was characterized by atypical lymphocytes and histiocytes,the necrotic phase by abundant eosinophilic fibrin deposits and nuclear debris,and the xanthomatous phase by clusters of foam-like histiocytes.Immunohistochemically analyses revealed that atypical lymphocytes were neg-ative for CD20,CD4,and CD56 but positive for CD3,CD8,TIA1,Granzyme B,and Perforin.Histiocytes expressed CD68,CD163,and MPO,while CD123-positive plasmacytoid dendritic cells were predominantly located around the le-sions and blood vessels.EBER was positive in individual cells in 4 cases.TCR gene rearrangement was positive in 2 cases and suspected positive in 3 cases,while Ig rearrangement was positive and suspected positive in 1 case each.Conclusion KFD exhibits clinical,imaging,and pathological features that can mimic lymphoma,highlighting the im-portance of accurate diagnosis to avoid misdiagnosis and inappropriate treatment.

Purpose To investigate the clinicopathological features and prognosis of adult large B-cell lymphoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 63 adult LBCL-IRF4r cases were collected.The EnVision two-step method was employed for immunohistochemical staining,and fluorescence in situ hybridization was used to detect rearrangements or deletions of the IRF4,BCL2,MYC,BCL6,and TP53 genes.The relationship be-tween clinicopathological features and prognosis was analyzed and compared with data from 132 adult non-specified dif-fuse large B-cell lymphoma(DLBCL)cases.Results Among the 63 adult LBCL-IRF4r patients,the male to female ratio was 1.1∶1,with a median age of 54.0 years(range 20-84 years),and 14 cases(22.2％)were＜40 years old,24 cases(38.1％)were between 40 and 60 years old,and 25 cases(39.7％)were＞60 years old.18 cases(28.6％)were involved in Waldeyer's ring,along with 8 cases(12.7％)in cervical lymph nodes,7 cases(11.1％)in other lymph nodes and lymphatic organs,13 cases(20.6％)in stomach,4 cases(6.4％)in intestine,and 13 cases(20.6％)in other extranodal sites.63 cases showed IRF4 rearrangements,with no BCL2 and MYC translocations(0/58),30.9％(17/55)had BCL6 translocations,and 16.3％(8/49)had TP53 deletions.59 pa-tients were followed up for a median of 28 months(range 1-65 months).48 patients(81.4％)achieved complete re-sponse,10 patients(16.9％)experienced disease progression or relapse,and 3 patients(5.1％)died.Univariate a-nalysis showed that lactate dehydrogenase level,Ann Arbor stage,international prognostic index(IPI)score,growth pattern,Hans classification,and double expression of BCL2 and C-MYC were significantly associated with progression-free survival.Age,Ann Arbor stage,and IPI score were significantly associated with overall survival.Multivariate Cox regression analysis showed that double expression of BCL2 and C-MYC was an independent prognostic factor for pro-gression-free survival.Adult LBCL-IRF4r had significantly higher complete response rate and progression-free survival than adult DLBCL.Conclusion LBCL-IRF4r occurs in adults of all age groups,commonly affecting Waldeyer's ring,cervical lymph nodes,and gastrointestinal tract,and has a favorable clinical prognosis.

Purpose To investigate the clinical,imaging,and pathological features of Kikuchi-Fujimoto disease(KFD).Methods A retrospective analysis was conducted on 123 pathologically confirmed KFD cases.Clinical and imaging data were collected,and histopathological features were evaluated using HE staining,immunohistochemistry,in situ hybridization for EBER,and molecular analyses(TCR/Ig gene rearrangements by PCR with capillary electro-phoresis).Results Among the 123 patients,the male-to-female ratio was 1∶2,with a median age of 30 years.All patients presented with lymphadenopathy.Among 30 hospitalized patients,63.3％(19/30)had fever,and 23.3％(7/30)had concurrent autoimmune diseases.Of the 12 patients who underwent PET-CT,91.7％(11/12)were sus-pected of malignancy,prompting biopsy recommendations.Among 47 consultation cases,27.7％(13/47)were ini-tially misdiagnosed as lymphoma.Histopathological examination revealed proliferative,necrotic,and xanthomatous phases,which coexisted or occurred independently.The proliferative phase was characterized by atypical lymphocytes and histiocytes,the necrotic phase by abundant eosinophilic fibrin deposits and nuclear debris,and the xanthomatous phase by clusters of foam-like histiocytes.Immunohistochemically analyses revealed that atypical lymphocytes were neg-ative for CD20,CD4,and CD56 but positive for CD3,CD8,TIA1,Granzyme B,and Perforin.Histiocytes expressed CD68,CD163,and MPO,while CD123-positive plasmacytoid dendritic cells were predominantly located around the le-sions and blood vessels.EBER was positive in individual cells in 4 cases.TCR gene rearrangement was positive in 2 cases and suspected positive in 3 cases,while Ig rearrangement was positive and suspected positive in 1 case each.Conclusion KFD exhibits clinical,imaging,and pathological features that can mimic lymphoma,highlighting the im-portance of accurate diagnosis to avoid misdiagnosis and inappropriate treatment.

Objective:To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Methods:The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed. Morphological characteristics were observed. Immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization, clonal rearrangement analysis of T-cell receptor (TCR) genes, and targeted next-generation sequencing (NGS) were performed.Results:Among the 42 patients (male/female ratio of 2.8∶1.0), the age range was 32-77 years with a median age of 59.5 (52.0-65.0) years. Grossly, the tumors were presented as ulcerative or exophytic lesions, with a maximum diameter of 2-18 cm. There were 34 cases with a single lesion and 8 cases with more than 1 lesion. The tumor cells in all 42 cases were relatively monotonous in histology and small or medium in size. They had round or oval nuclei, moderately pale or clear cytoplasm, evenly distributed nuclear chromatin, inconspicuous nucleoli, and frequent mitotic figures. In one of the cases, there were moderately large cells, vacuolated nuclei, and clear nucleoli. Lymphoepithelial lesions were observed in 36 (85.7%) of the 42 cases, tumor necrosis in 4 (9.5%) cases, scattered eosinophils and/or plasma cell infiltration in the background in 9 (21.4%) cases, and a "starry sky" phenomenon in 1 (2.4%) case. The tumor cells in all cases exhibited high expression of CD3, CD2, CD7, CD8, CD56, TIA1, Granzyme B, and Perforin, while some also expressed CD4 (5/41, 12.2%), CD5 (3/41, 7.3%), CD20 (4/41, 11.9%), CD79α (2/37, 5.4%), and CD30 (1/34, 2.9%). The Ki-67 proliferation index ranged from 40% to 90%. EBER in situ hybridization tests were negative in all cases. TCR gene clonal rearrangement was detected in 96.4% (27/28) of the tested cases. Targeted NGS revealed commonly mutated genes including SETD2, STAT5B, JAK3, TP53, and CREBBP. The primary treatment was chemotherapy, with 2 cases undergoing autologous hematopoietic stem cell transplantation. Follow-up information was obtained for 29 cases, with a follow-up period of 1-73 months. The mortality was 93.1% (27/29).Conclusions:MEITL is a rare and highly aggressive peripheral T-cell lymphoma. Its clinical manifestations are diverse, and diagnosis primarily relies on a comprehensive assessment of pathological morphology, immunohistochemical profiles, and EBV infection status, supplemented by genetic testing if necessary. At present, there is no effective treatment, and its overall prognosis is poor.

Objective:To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL).Methods:Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed.Results:492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations ( P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive ( P<0.05). Conclusions:The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

Objective:To investigate the relationship between the protein expression of C-MYC, bcl-2 and bcl-6 and the clinicopathological characteristics in patients with de novo CD5-positive diffuse large B cell lymphoma (CD5 +DLBCL). Methods:Fifty seven cases of de novo CD5 +DLBCL were collected at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from February 2013 to September 2018. The hematoxylin-eosin stained slides were reviewed, and immunohistochemical (IHC) staining and FISH were used to analyze the relationship between C-MYC, bcl-2, bcl-6 expression and the clinicopathologic characteristics of patients. Results:Among these 57 cases, 27 were male and 30 were female. The age of onset was 35-99 years old. The IHC expression rates of C-MYC, bcl-2 and bcl-6 were 50.9% (29/57), 84.2% (48/57), and 75.4% (43/57) respectively; and co-expression rate of C-MYC and bcl-2 proteins was 40.4 (23/57). There was no significant correlation between protein expression and patients′ genders, clinical stage, the level of serum LDH,β2 microglobulin, IPI,B symptoms, bone marrow involvement and central nervous system recurrence ( P>0.05). Univariate analysis showed that the median OS of C-MYC negative patients was significantly longer than C-MYC positive patients ( P<0.05); and the median OS of patients without double expression was significantly longer than that of patients with positive expression ( P<0.05), and bcl-6 positive patients had longer median OS than bcl-6 negative patients ( P<0.05). There was no significant correlation between prognosis and bcl-2 protein expression ( P>0.05) . Cox multivariate analysis showed C-MYC protein expression was an independent predictor of OS in de novo CD5 +DLBCL ( P<0.05). Conclusions:Bcl-2 protein expression has no effect on the prognosis in de novo CD5 +DLBCL whereas bcl-6 expression is correlated with good prognosis. C-MYC protein expression could be used as an independent and effective index to predict the prognosis of patients with de novo CD5 +DLBCL.However, the relationship between protein expression and gene rearrangement of C-MYC, bcl-2 and bcl-6 needs to be further explored.

Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan-Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple ( ⩾ 3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P < 0.001) and OS (68.5% vs. 85.8%, P = 0.001) than those without multiple abnormal immunologic markers. Multivariate analysis revealed that the presence of multiple abnormal immunologic markers and the elevated serum levels of lactate dehydrogenase were the independent adverse prognostic factors for PFS (P = 0.008, P < 0.001) and OS (P = 0.003, P < 0.001). Meanwhile, advanced Ann Arbor stage was an independent adverse prognostic factor for PFS (P = 0.001) and age > 60 years for OS (P = 0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers ; China ; Disease Progression ; Female ; Humans ; Immunotherapy ; methods ; Lymphoma, Large B-Cell, Diffuse ; mortality ; therapy ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Young Adult

Germinal center is a site of B cell maturation and development, in which B cell activation and differentiation was regulated by inherent complexity signal and transcription factors networks. Under the normal condition, the interaction between these transcription factors maintain dynamic stability of B cell in germinal center. When cytogenetic abnormalities or viral infection appear, a variety of.abnormal expression of transcription factors induced the imbalance of B cell signal networks regulation. manifested as abnormal B cell proliferation, apoptosis, and differentiation was blocked. B cell malignancies were often associated with genetic change of B cell and abnormal expression of transcription factors.