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A 47-year-old male with an unremarkable medical history was referred for atypical endodontic pain and treatment of his left upper molars. Clinical and radiographic examinations revealed an extensive, undefined osteolytic area around these teeth. A subsequent bone biopsy diagnosed diffuse large B-cell lymphoma, a high-grade non-Hodgkin's lymphoma. The hematology team prescribed six cycles of chemotherapy, supplemented by two cycles of methotrexate. Practitioners should be alerted by atypical tooth pain to consider 3D imaging to exclude malignant pathology as early as possible. Teaching point: An atypical tooth pain should alert the practitioner and guide them towards 3D imaging to eliminate diagnostic of malignant pathology as early as possible.

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The general population in China is aging, and thus the number of older patients with diffuse large B-cell lymphoma (DLBCL) will continue to increase. Individualized treatment is required to maximize therapeutic potential while minimizing the risk of toxicity. To improve the diagnosis and treatment of DLBCL in older people in China, the Lymphocyte Disease Group of the Hematology Division of the Chinese Medical Association and Lymphoma Expert Commitee of Chinese Society of Clinical Oncology (CSCO) have organized relevant experts to formulate this consensus.

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Objective: To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) . Methods: Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model. Results: Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy (P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months (P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL (HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions: In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.

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OBJECTIVE: To determine prognostic value of bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) measured on baseline dual-phase 18F-FDG PET/CT in a series of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) treated homogeneously with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. PATIENTS AND METHODS: This prospective study enrolled 135 patients with newly diagnosed DLBCL. All patients underwent dual-phase 18F-FDG PET/CT. The following PET parameters were calculated for both tumor and bone marrow: maximum standardized uptake value (SUVmax) at both time points (SUVmax early and SUVmax delayed), SUVmax increment (SUVinc), RI, and BLR. Patients were treated with R-CHOP regimen and response at end of treatment was assessed. RESULTS: The final analysis included 98 patients with complete remission. At a median follow-up of 22 months, 57 patients showed no relapse, 74 survived, and 24 died. The 2-year relapse-free survival (RFS) values for patients with higher and lower RI-bm were 20% and 65.1%, respectively (p < 0.001), and for patients with higher and lower BLR were 30.2% and 69.6%, respectively (p < 0.001). The 2-year overall survival (OS) values for patients with higher and lower RI-bm were 60% and 76.3%, respectively (p = 0.023), and for patients with higher and lower BLR were 57.3% and 78.6%, respectively (p = 0.035). Univariate analysis revealed that RI-bm and BLR were independent significant prognostic factors for both RFS and OS (hazard ratio [HR] = 4.02, p < 0.001, and HR = 3.23, p < 0.001, respectively) and (HR = 2.83, p = 0.030 and HR = 2.38, p = 0.041, respectively). CONCLUSION: Baseline RI-bm and BLR were strong independent prognostic factors in DLBCL patients. CLINICAL RELEVANCE STATEMENT: Bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) could represent suitable and noninvasive positron emission tomography/computed tomography (PET/CT) parameters for predicting pretreatment risk in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. KEY POINTS: • Bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) are powerful prognostic variables in diffuse large B-cell lymphoma (DLBCL) patients. • High BLR and RI-bm are significantly associated with poor overall survival (OS) and relapse-free survival (RFS). • RI-bm and BLR represent suitable and noninvasive risk indicators in DLBCL patients.

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Objective:To explore the antitumor effect of ADU-S100/doxorubicin in situ vaccine on diffuse large B-cell lymphoma (DLBCL) and its mechanism.Methods:The 6-week-old female BALB/c mice were selected, and the bilateral murine subcutaneous B-cell lymphoma model was established with murine B-cell lymphoma A20 cells. The subcutaneous tumor-bearing mice were randomly divided into untreated group (without treatment), ADU-S100 in situ vaccine treatment group (intratumoral injection of interferon gene stimulating factor agonist ADU-S100), doxorubicin in situ vaccine treatment group (intratumoral injection of doxorubicin), and ADU-S100/doxorubicin in situ vaccine treatment group (intratumoral injection of ADU-S100 and doxorubicin) by using random number table method, with 5 mice in each group. The right tumors of the bilateral subcutaneous tumor-bearing mice were defined as proximal tumors, and the left tumors of the bilateral subcutaneous tumor-bearing mice were defined as distal tumors. Only the proximal tumors were treated via the intratumoral route, and the distal tumors were not treated. On day 23 after tumor inoculation, the percentages of CD11c + dendritic cells (DC), CD8 + CD11c + DC and CD80 + CD11c + DC in the spleen of mice in each group were detected by flow cytometry. The splenocytes of mice in each group were stimulated with A20 tumor cell lysate in vitro, the percentages of 5'-ethynyl-2'-deoxyuridine-positive (EdU +) cells and tumor necrosis factor-α-positive (TNF-α +) cells in CD8 + T cells in each in situ vaccine treatment group were detected by flow cytometry, and the killing effect of cytotoxic T lymphocyte (CTL) in each group was measured by using the lactate dehydrogenase (LDH) cytotoxicity assay kit. The mice treated with ADU-S100/doxorubicin in situ vaccine were intraperitoneally injected with anti-mouse CD8α (clone 53-6.7) mAb or isotype control on days 7, 12 and 17 after tumor inoculation to eliminate CD8 + cells. On day 23 after tumor inoculation, the proximal and distal tumor volumes of mice in the ADU-S100/doxorubicin in situ vaccine combined with anti-mouse CD8α (clone 53-6.7) mAb or isotype control treatment group were measured, the percentages of CD8 + T cells and CD8 + CD11c + DC in the spleen of tumor-bearing mice in these two groups were detected by flow cytometry, and the infiltration of CD8 + T cells in the tumor tissues from these two groups was detected by immunohistochemistry (IHC) staining. Results:On days 11, 14, 17, 20 and 23 after tumor inoculation, the proximal and distal tumor volumes of mice in each treated group were lower than those in the untreated group (all P < 0.05). The proportions of CD11c + DC in the spleen of the untreated group, ADU-S100 in situ vaccine treatment group, doxorubicin in situ vaccine treatment group and ADU-S100/doxorubicin in situ vaccine treatment group were (4.92±0.63)%, (7.54±0.84)%, (7.45±0.86)% and (11.63±0.85)%, respectively, and the difference was statistically significant ( F = 72.30, P < 0.001); the proportions of CD8 + CD11c + DC were (1.36±0.34)%, (4.02±0.43)%, (4.22±0.61)% and (6.11±0.73)%, respectively, and the difference was statistically significant ( F = 76.09, P < 0.001); the proportions of CD80 + CD11c + DC were (0.51±0.24)%, (1.69±0.23)%, (1.82±0.25)% and (4.09±0.39)%, respectively, and the difference was statistically significant ( F = 167.40, P < 0.001). The CTL responses and the proportion of EdU + cells and TNF-α + cells in CD8 + T cells in each in situ vaccine treatment group were higher than those in the untreated group (all P < 0.05). Furthermore, the enhanced CTL responses and the increased proportion of EdU + cells and TNF-α + cells in CD8 + T cells were observed in the ADU-S100/doxorubicin in situ vaccine treatment group as compared to the ADU-S100 in situ vaccine treatment group and doxorubicin in situ vaccine treatment group (all P < 0.05). The proportions of CD8 + T cells and CD8 + CD11c + DC in the spleen of mice treated with ADU-S100/doxorubicin in situ vaccine and anti-mouse CD8α mAb were lower than those in ADU-S100/doxorubicin in situ vaccine and isotype control group (both P < 0.05) and both proximal and distal tumor volumes of mice treated with ADU-S100/doxorubicin in situ vaccine and anti-mouse CD8α mAb were larger than those in ADU-S100/doxorubicin in situ vaccine and isotype control group (both P < 0.05). Conclusions:ADU-S100/doxorubicin in situ vaccine can induce profound regression of proximal tumors in bilateral murine subcutaneous B-cell lymphoma model and generate systemic immune responses capable of partially inhibiting distant tumor growth, and the antitumor efficacy of ADU-S100/doxorubicin in situ vaccine may require CD8 + CD11c + DC-mediated CD8 + T cell immune responses.

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Objective:To investigate the clinical efficacy and safety of ZR2 (zevalin + lenalidomide + rituximab) regimen in the treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was conducted. The clinical data of 16 elderly (>65 years old) non-germinal center B-cell-like DLBCL patients treated with ZR2 regimen at the Taixing People's Hospital from January 2021 to March 2023 were retrospectively analyzed. The efficacy, adverse reactions and prognosis of patients were observed.Results:Of the 16 patients, 11 were male and 5 were female, with the age [ M ( Q1, Q3)] of 76 years old (70 years old, 78 years old), and 10 cases were Ann Arbor stage Ⅲ-Ⅳ. Among the 16 patients, 9 achieved complete remission, 4 patients achieved partial remission. All 16 patients experienced varying degrees of reversible bone marrow suppression, grade Ⅲ-Ⅳ hematologic adverse reactions included neutropenia (7 cases) and thrombocytopenia (2 cases), and the bone marrow hematopoiesis recovered after treatment with granulocyte colony-stimulating factor and thrombopoietin. The main ≥grade Ⅱ non-hematologic adverse reactions were gastrointestinal reactions (5 cases), liver function abnormalities (3 cases) and peripheral neuropathy (2 cases), which were improved after the appropriate treatment. Two patients discontinued the treatment of this regimen due to disease progression, and 1 patient died from complications after 2 cycles of treatment. No deep vein thrombosis, cardiac toxicity or renal toxicity occurred during the treatment process. Conclusions:The ZR2 regimen is effective in the treatment of elderly DLBCL patients with tolerable adverse reactions.

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Objective:To investigate the level of serum lipoprotein a [Lp (a)] in patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:A retrospective cohort study was performed. The clinical data of 87 patients with DLBCL who were treated at Changshu No.2 People's Hospital from January 2017 to June 2022 (the newly treated DLBCL group) were retrospectively analyzed, and 78 healthy physical examination subjects were selected as the control group. The level of Lp(a) in the two groups and the level of Lp(a) in DLBCL patients achieving different therapeutic effects after treatment were compared. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum Lp(a) in predicting the therapeutic effect of DLBCL patients, and the area under the curve (AUC) was calculated to determine the optimal critical value. Based on the optimal critical value, patients with DLBCL were divided into low Lp(a) group and high Lp(a) group, and the clinicopathological characteristics of DLBCL patients with different Lp(a) levels were compared. Cox proportional hazards model was used to analyze the factors affecting the prognosis of DLBCL patients. Kaplan-Meier method was used to compare the relapse-free survival (RFS) and overall survival (OS) of DLBCL patients with different Lp(a) levels.Results:The level of Lp (a) in the newly treated DLBCL group was higher than that in the control group[ (0.24±0.09) g/L vs. (0.09±0.06) g/L], and the difference was statistically significant ( t = 3.61, P = 0.019). Among 87 patients, 54 achieved complete remission (CR), 23 achieved partial remission (PR), and 10 achieved progression of the disease (PD). The Lp (a) levels of patients achieving CR, PR, and PD were (0.09±0.09) g/L, (0.12±0.08) g/L, and (0.25±0.15) g/L, respectively. The Lp (a) levels in patients achieving CR and PR were lower than those in the newly treated DLBCL patients [(0.24±0.09) g/L], and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in the Lp (a) levels between patients achieving PD and the newly treated DLBCL patients ( P > 0.05). The ROC curve results showed that the optimal critical value of serum Lp (a) in predicting the efficacy of DLBCL patients was 0.25 g/L, AUC was 0.776 (95% CI: 0.676-0.876, P < 0.05), and its sensitivity and specificity was 66.67%, 82.76%, respectively. According to the optimal critical value of Lp (a) (0.25 g/L), patients were divided into the low Lp (a) group (≤ 0.25 g/L) (57 cases) and the high Lp (a) group (>0.25 g/L) (30 cases). The proportion of patients with lactate dehydrogenase level >227 U/L, Ann Arbor stage Ⅲ-Ⅳ, and extranodal organ involvement >1 in the high Lp (a) group was higher than that in the low Lp (a) group, and the differences were statistically significant (all P < 0.05). Cox multivariate analysis results showed that Ann Arbor stage Ⅲ-Ⅳ, international prognostic index (IPI) score 3-5, and Lp (a)>0.25 g/L were independent risk factors for OS in DLBCL patients (all P < 0.05); Ann Arbor stage Ⅲ-Ⅳ and IPI score 3-5 were independent risk factors for RFS in DLBCL patients (all P < 0.05). The median OS in the low Lp (a) group was not reached; the median OS of the high Lp (a) group was 21 months, and there was a statistically significant difference in OS between the two groups ( P = 0.001). The median RFS time was not reached in the low Lp (a) group and the high Lp (a) group; and there was no statistically significant difference in RFS between the two groups ( P = 0.102) . Conclusions:Lp(a) level of DLBCL patients is increased, and Lp(a) could be a factor influencing the prognosis of DLBCL.

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Objective:To investigate the clinicopathological features, mutation, therapeutic efficacy and the factors influencing the prognosis of patients with cardiac diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 cardiac DLBCL patients in Ruijin Hospital of Shanghai Jiao Tong University School of Medicine from January 2016 to October 2020 were retrospectively analyzed. NovaSeq sequencing platform was used to detect gene mutations in 5 patients, and bioinformatics analysis of sequencing data was conducted through public database to identify the mutation sites of pathogenic genes. Kaplan-Meier method was used to analyze the progression-free survival (PFS) and the overall survival (OS). Univariate Cox proportional risk model was used to analyze the influencing factors of prognosis.Results:Among 11 patients with cardiac DLBCL, 5 were male and 6 were female. The age [ M ( Q1, Q3)] was 61 years (45 years, 70 years). All 11 patients were non-germinal center B-cell (non-GCB) type. There were 2 primary cases and 9 secondary cases; 9 cases with Ann Arbor stage of Ⅲ-Ⅳ, 10 cases with increased lactate dehydrogenase (LDH) and 9 cases with international prognostic index (IPI) score equal to or higher than 3 scores. Among 11 patients, 9 cases received a first-line treatment based on the R-CHOP (rituximab, cyclophosphamide, epirubicin/doxorubicin hydrochloride liposomes, vincristine and prednisone) regimen, of which 8 patients achieved complete remission (CR), and 1 patient achieved stable disease (SD); 1 patient received IR2 (ibrutinib + rituximab + lenalidomide) treatment regimen and achieved SD, and 1 patient received supportive treatment only and achieved progression of the disease. The follow-up time was 39.9 months (25.6 months, 57.3 months). The 3-year PFS rate and 3-year OS rate of 11 patients was 54.5%, 77.9 %, respectively. Univariate Cox regression analysis showed that gender, B symptoms, Ann Arbor stage, LDH level, number of extranodal lesions, IPI score were not correlated with PFS and OS of patients (all P > 0.05). Among 5 cases undergoing gene detection, KMT2D mutations and PIM1 mutations were detected in 2 cases,respectively. Interestingly, KMT2D mutations were only found in secondary cardiac DLBCL patients (2/3), while PIM1 mutations were only detected in primary cardiac DLBCL patients (2/2). Conclusions:Most cardiac DLBCL patients are non-GCB type and have advanced clinical stage, while may benefit from R-CHOP treatment regimen. PIM1 and KMT2D are the commonly mutated genes in cardiac DLBCL.

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Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

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Objective:To explore the efficacy and safety of tislelizumab combined with zanubrutinib in the treatment of refractory diffuse large B-cell lymphoma (DLBCL).Methods:A prospective observational study was conducted. A total of 10 patients with refractory DLBCL admitted to Beijing Chaoyang District Third Ring Cancer Hospital, a specialist medical consortium of Cancer Hospital Chinese Academy of Medical Sciences from November 2020 to February 2023 were prospectively collected. All the 10 refractory DLBCL patients at least received first-line systemic therapy containing rituximab; and they were given tislelizumab 200 mg, intravenous infusion, on day 1 and zanubrutinib 160 mg, orally, twice a day, day 1-day 21, with 21 days as 1 cycle; 6 patients received second-line therapy and 4 patients received ≥ third-line therapy. Subsequent regimens were added with rituximab (375 mg/m 2, intravenous infusion on day 1). The primary endpoint will be reached 12 months after enrollment if there was no disease progression or other events that were scheduled to withdraw from the study. The therapeutic efficacy was summarized at the end of the follow-up in March 2023. Kaplan-Meier method was used to make survival analysis and the adverse reactions were summed up. Results:There were 6 males and 4 females, all at stage Ⅲ-Ⅳ; and age [ M ( Q1, Q3)] was 55 years (50 years, 69 years). All 10 patients completed 90 cycles of treatment with tislelizumab and zanubrutinib, with the cycle number of 8 cycles (2 cycles, 24 cycles). The follow-up time was 19 months (11 months, 28 months); 4 cases achieved complete remission, 3 cases achieved partial remission and 1 case had the stable disease. The progression-free survival was 8.5 months (1.3 months, 27.0 months); the median remission duration time and median overall survival time were not reached. Treatment-related adverse reactions included 2 cases of neutropenia, 1 case of anemia, and 1 case of elevated alanine aminotransferase and aspartate aminotransferase, all of which were grade 1-2. Conclusions:Tislelizumab combined with zanubrutinib has good clinical efficacy and safety in the treatment of refractory DLBCL.

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Objective:To evaluate the clinical efficacy of rituximab injection combined with CHOP regimen (cyclophosphamide+doxorubicin+vincristine+prednisolone) in the treatment of diffuse large B-cell lymphoma (DLBCL).Methods:One hundred and twenty patients with DLBCL who treatment in the First Affiliated Hospital of Xinjiang Medical University from June 2019 to June 2022 were selected as the study object. They were randomly divided into the study group (60 cases) and the control group (60 cases). The control group was treated with CHOP regimen, and the study group was treated with rituximab injection on the basis of CHOP regimen. The clinical efficacy, inflammatory reaction, immune function and adverse reaction were evaluated after 6 courses of treatment.Results:After treatment, the total clinical effective rate in the study group was higher than that in the control group: 88.33%(53/60) vs. 70.00%(42/60), there was statistical difference ( χ2 = 6.11, P<0.05). Before treatment, the levels of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the two groups had no significant differences ( P>0.05); after treatment, the levels of serum IL-6 and TNF-α were decreased, and the levels of serum IL-6 and TNF-α in the study group were lower than those in the control group: (223.56 ± 21.28) ng/L vs. (267.35 ± 25.36) ng/L, (9.34 ± 2.75) μg/L vs. (11.96 ± 3.83) μg/L, there were statistical differences ( P<0.05). Before treatment, the levels of serum immunoglobulin (Ig) A, IgM and IgG in the two groups had no significant differences ( P>0.05); after treatment, the levels of serum IgA, IgM and IgG were decreased, but the levels of serum IgA, IgM and IgG in the study group were higher than those in the control group: (1.83 ± 0.46) g/L vs. (1.34 ± 0.34) g/L, (1.15 ± 0.22) g/L vs. (0.83 ± 0.24) g/L, (10.67 ± 1.65) g/L vs. (8.02 ± 1.62) g/L, there were statistical differences ( P<0.05). After treatment, the incidence of thrombocytopenia, leucopenia, gastrointestinal reaction, bone marrow suppression and liver function injury in the study group were lower than those in the control group: 6.67%(4/60) vs. 20.00%(12/60), 15.00%(9/60) vs. 31.67%(19/60), 30.00%(18/60) vs. 58.33%(35/60), 5.00%(3/60) vs. 16.67%(10/60), 10.00%(6/60) vs. 25.00%(15/60), there were statistical differences ( χ2 = 4.62, 4.66, 9.77, 4.33, 4.88, P<0.05). Conclusions:The treatment effect of rituximab injection combined with CHOP regimen in DLBCL is significant, which can reduce the inflammatory reaction of the body, reduce the damage of immune function, and reduce the adverse reactions of chemotherapy.

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Objective:To analyze clinical characteristics of primary pancreatic lymphoma (PPL) patients.Methods:Clinical features of 22 patients diagnosed as PPL admitted to Peking Union Medical College Hospital from January 2002 to May 2023 were analyzed retrospectively.Results:The median age was 56.4±13.3 years. The median time from onset to diagnosis was 1.0 (1.0, 3.0) months. The main clinical manifestations were abdominal pain (15/22), weight loss (14/22) and jaundice (10/22). Elevated lactate dehydrogenase (LDH) was observed in 15/20 (75%) patients. Only 2 (2/9, 22.2%) patients had increased CA199 levels and 2 (2/9, 22.2%) patients had increased CEA levels. The maximum tumor diameter was 5.0 (3.8, 6.9) cm. Contrast-enhanced CT mostly showed low enhancement lesions. Major pancreatic duct dilatation were rare on CT scan (4/20). Fifteen patients were confirmed by pancreatic pathology, of which 8 were obtained by surgery, 4 were obtained by CT or ultrasound-guided percutaneous biopsy, and 3 were obtained by EUS-FNA. The main pathological type was diffuse large B-cell lymphoma (14/22). 19 patients received chemotherapy, and 6 patients died with a median follow-up of 5.0 (1.5, 35.5) months.Conclusions:PPL is rare and easy to be misdiagnosed. Elevated LDH levels, normal tumor markers, and non-dilatation of main pancreatic duct are important diagnostic clues. It is important to obtain pathology by EUS-FNA and other methods for definite diagnosis.

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Fundamento: Los linfomas primarios de ovario son poco frecuentes; el 1 % de estos se presenta en ovario y el 1.5 % de los tumores malignos de ovario son linfomas. Los tipos histológicos más frecuentes es el linfoma no Hodgkin difuso de células B grande y el BurKitt; el tratamiento consiste en cirugía combinada con quimioterapia. Objetivo: Reportar un caso de un linfoma no Hodgkin difuso de células B grande primario de ovario. Presentación de caso: Se presentó el caso de una paciente de 39 años de edad, con antecedentes patológicos personales de salud; la cual fue al cuerpo de guardia de ginecología por presentar dolor abdominal difuso que no se aliviaba con analgésicos. En la exploración física presentaba dolor a la palpación superficial y profunda en hipocondrio y fosa ilíaca derecha con masa tumoral palpable. Ecografía hacia proyección anexial derecha se observó una imagen de baja ecogenicidad y en la laparoscopia de urgencia se concluyó como una formación de aspecto tumoral que parecía corresponderse con ovario derecho. Se le realizó una histerectomía con doble anexectomía. El diagnóstico anatomopatológico fue un linfoma no Hodgkin primario de ovario. Conclusiones: La paciente del caso presentado tuvo una clínica oligosintomática y la confirmación de la enfermedad fue a partir de una muestra quirúrgica, lo que expresa que el diagnóstico del linfoma no Hodgkin de células B es difícil y aunque es poco frecuente siempre se debe tener en cuenta en el diagnóstico diferencial de las tumoraciones unilaterales de ovario.

Background: Primary ovarian lymphomas are uncommon, 1% of these malignancies occur in the ovary, and 1.5% of all ovarian malignancies are lymphomas. The most common histologic types are diffuse large B-cell non-Hodgkin's lymphoma and BurKitt's lymphoma; treatment consists of surgery combined with chemotherapy. Objective: To report a case of primary ovarian diffuse large B-cell non-Hodgkin lymphoma. Case presentation: A 39-year-old female case is presented, with a personal pathological history; she went to the gynecology emergency service because she presented diffuse abdominal pain that was not relieved by analgesics. Physical examination revealed superficial and deep pain on palpation in the hypochondrium and right illiac fossa with a palpable tumor mass. Right adnexal ultrasound showed an image of low echogenicity and at the emergency laparoscopy, it was diagnosed as a tumor-like formation that appeared to correspond to the right ovary. She underwent a hysterectomy with double adnexectomy. The anatomopathologic diagnosis was primary ovarian non-Hodgkin's lymphoma. Conclusions: The patient in the presented case had an oligosymptomatic clinical presentation. Confirmation of the disease was obtained from a surgical sample, which means that B-cell non-Hodgkin's lymphoma is difficult to diagnose and although it is uncommon, it should always be considered in the differential diagnosis of unilateral ovarian tumors.

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Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

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Objective: To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma (DLBCL) . Methods: Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed. Gene mutation profiles were evaluated by targeted sequencing (55 lymphoma-related genes). Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival (OS) and progression-free survival (PFS) . Results: Overall, 80 patients were included; 12 patients had primary pancreatic DLBCL (PPDLBCL), and 68 patients had secondary pancreatic DLBCL (SPDLBCL). Compared with those with PPDLBCL, patients with SPDLBCL had a higher number of affected extranodal sites (P<0.001) and had higher IPI scores (P=0.013). There was no significant difference in the OS (P=0.120) and PFS (P=0.067) between the two groups. Multivariate analysis indicated that IPI intermediate-high/high risk (P=0.025) and double expressor (DE) (P=0.017) were independent adverse prognostic factors of OS in patients with pancreatic DLBCL. IPI intermediate-high/high risk (P=0.021) was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL. Targeted sequencing of 29 patients showed that the mutation frequency of PIM1, SGK1, BTG2, FAS, MYC, and MYD88 in patients with pancreatic DLBCL were all >20%. PIM1 (P=0.006 for OS, P=0.032 for PFS) and MYD88 (P=0.001 for OS, P=0.017 for PFS) mutations were associated with poor OS and PFS in patients with SPDLBCL. Conclusion: There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL. IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL. PIM1, SGK1, BTG2, FAS, MYC, and MYD88 were common mutations in pancreatic DLBCL. PIM1 and MYD88 mutations indicated worse prognosis.

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Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

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Objective:To investigate the mutation of proviral integration site for Moloney murine leukemia virus 1 (PIM1) in diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:Paraffin-embedded tissues of 38 DLBCL patients surgically resected at Shiyan Taihe Hospital from January 2016 to March 2022 were collected. The mutation of PIM1 gene was detected by polymerase chain reaction (PCR)-Sanger sequencing. The DLBCL-related DUKE, DFCI and TCGA datasets in the cBioPortal database were screened to collect information on PIM1 gene mutation and expression and clinical prognosis. Patients were divided into PIM1 mutation-positive group and PIM1 mutation-negative group, and the differences in clinicopathological characteristics, tumor mutational burden (TMB), microsatellite instability (MSI) levels and overall survival (OS) between the two groups were compared. Kaplan-Meier method was used for survival analysis, and univariate and multivariate survival analyses were performed using Cox proportional hazards model.Results:The PIM1 mutation rates of DLBCL patients in DUKE, DFCI, TCGA datasets and Shiyan Taihe Hosipital were 14.3% (96/673), 26.3% (26/99), 19.5%(8/41) and 28.9% (11/38), respectively, in which mutation site and mutation form were more commonly found in exon 4 and missense mutations. There were statistical differences in the PIM1 mutation rate among DLBCL patients with different age (DUKE dataset) and cell of origin (COO) classification (DFCI dataset) ( χ2 values were 8.22 and 4.40, both P<0.05). Compared with PIM1 mutation-negative group, the PIM1 mutation-positive group had a higher TMB in DUKE, DFCI and TCGA datasets (all P<0.05). In DUKE and DFCI datasets, the OS of PIM1 mutation-positive group was worse than that of PIM1 mutation-negative group (both P<0.05), and multivariate Cox regression analysis showed that PIM1 gene mutation-positive was an adverse prognostic factor of OS (DUKE dataset: HR = 1.661, 95% CI 1.151-2.396, P = 0.007; DFCI dataset: HR = 2.074, 95% CI 1.031-4.172, P =0.041). Conclusions:PIM1 gene mutation may be related to the poor prognosis of DLBCL patients.

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Objective:To investigate the clinicopathologic characteristics, gene mutation profile and prognostic influencing factors of diffuse large B-cell lymphoma (DLBCL) complicated with follicular lymphoma (FL) (DLBCL/FL).Methods:The clinicopathological data of 50 DLBCL/FL patients admitted to Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine from February 2018 to November 2021 were retrospectively analyzed. Targeted sequencing was performed to assess the mutation profile of 55 lymphoma-related genes. The clinicopathological characteristics were summarized to evaluate the short-term therapeutic efficacy of all patients. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS) of patients. Cox regression risk models were used to assess the factors affecting the OS and PFS.Results:Among 50 DLBCL/FL patients, 23 cases (46%) were male, 22 cases (44%) had an international prognosis index (IPI) score ≥ 2 points, 16 cases (32%) were double-expression lymphoma (DEL) and 4 cases (8%) were double-hit lymphoma (DHL). The complete response (CR) and overall response rates were 68% (34/50) and 78% (39/50), respectively after the first-line therapy. The median follow-up time was 23.3 months (5.1-50.9 months). The 2-year OS rate was 82.1% and 2-year PFS rate was 67.1%; and the median OS and PFS were not reached. Targeted sequencing results showed that the mutation frequencies of KMT2D, MYD88, TP53, BTG2, DTX1, EZH2, CD70, CREBBP, DUSP2, HIST1H1C, HIST1H1E and PRDM1 genes in this cohort were more than 15%. Multivariate Cox regression analysis showed that male ( HR = 4.264, 95% CI 1.144-15.896, P = 0.031) and IPI score ≥ 2 points ( HR = 6.800, 95% CI 1.771-37.741, P = 0.007) were independent risk factors of PFS in newly diagnosed DLBCL/FL patients, and TP53 mutation ( HR = 4.992, 95% CI 1.027-24.258, P = 0.046) was an risk influencing factor of OS. Conclusions:The proportion of male and female DLBCL/FL patients is similar, with a small proportion of DHL. Mutations of KMT2D, MYD88 and TP53 genes are commonly found in DLBCL/FL patients. Generally, DLBCL/FL patients can have a high overall response and good prognosis. Male and IPI score ≥ 2 points are the independent risk factors of PFS, and TP53 mutation is an independent risk factor of OS in DLBCL/FL patients.

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Objective:To investigate the clinicopathological and molecular genetic characteristics and prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinicopathological data of 152 DLBCL patients receiving consultation and routine physical examination in Peking University Third Hospital and Peking University School of Basic Medicine from January 2008 to December 2015 were retrospectively analyzed. Immunohistochemistry was used to detect the expressions of CD10, bcl-6, MUM1, GCET1, FOXP1. EB virus encoded small RNA (EBV-EBER) was detected by using in situ hybridization. The aberrations of bcl-2, bcl-6 and c-myc genes were detected by using fluorescence in situ hybridization (FISH) to screen double-hit lymphoma (DHL). Kaplan-Meier method was used to make survival analysis.Results:Among 152 cases of DLBCL, the ratio of male to female was 1.49:1, the median age of onset was 59 years (7-90 years), and 79 cases (52.0%) were primary lymph nodes. The median overall survival (OS) time of all cases was 16 months (1-101 months). The 1-year, 3-year and 5-year OS rates were 70.2%, 44.7%, 30.3%, respectively. The OS of R-CHOP treatment group was better than that of CHOP treatment group and untreated group ( P = 0.001). Among all 137 patients receiving double-hit histochemistry score (DHS), there were 56 cases with 0 score, 57 cases with 1 score, 24 cases with 2 scores; and the difference in the OS of different DHS score groups ( P = 0.311). FISH detection showed that among 29 cases achieving results of c-myc gene detection, there were 2 cases of splitting gene and 3 cases of gene amplification; among 26 cases achieving results of bcl-2 gene detection, 2 cases had bcl-2 gene amplification; among 26 cases achieving results of bcl-6 gene detection, 2 cases had bcl-6 gene amplification and 3 cases had splitting gene. It was found that myc and bcl-2 genes were amplified simultaneously in 1 case, accompanied with bcl-6 gene splitting, which was called triple-hit lymphoma. In DHS 0-score group, 1 case of double gene abnormality was found, and 1 case of single gene abnormality was found in group 1-score; in group 2-score, 5 cases were single gene abnormality and 1 case was three gene abnormality, so the gene abnormality was inconsistent with the protein expression. Conclusions:The incidence of DHL in DLBCL patients in China is low. The major gene abnormalities are c-myc or bcl-2, bcl-6 single gene abnormalities.