Purpose To compare the expression and pattern of EBNA2 in infectious mononucleosis(IM),EBV-positive diffuse large B-cell lymphoma(EBV+DLBCL),and EBV+DLBCL arising in immune deficiency/dysregulation(IDD-related EBV+DLBCL),and to investigate the potential diagnostic value of EBNA2 in IM and EBV-associated diffuse large B-cell lymphoma.Methods A retrospective study was conducted on 46 cases of IM,31 cases of EBV+DLBCL,and 16 cases of IDD(post-transplantation)-related EBV+DLBCL.Clinical information,immunohistochemis-try and EBER were reviewed to further confirm the diagnoses.All samples were stained for EBNA2.The expression ra-tio and intensity of EBER and EBNA2 in the same area were assessed.Results EBER was positive in all IM,EBV+DLBCL,and IDD(post-transplantation)-related EBV+DLBCL,while the positivity rate of EBNA2 was 95.65％,6.45％,and 100％,respectively.The positive intensity of EBNA2 was weak(71.73％),strong(87.5％)and nega-tive(93.54％)in IM,IDD(post-transplantation)-related EBV+DLBCL and EBV+DLBCL respectively.The average values of EBNA2/EBER were 31％,3％,and 78％among the three groups.The positivity rate and average value of EBNA2/EBER in IM were significantly higher than those in EBV+DLBCL(P＜0.001);however,the average value of EBNA2/EBER was significantly lower than that in IDD(post-transplantation)-related EBV+DLBCL(P＜0.001).The weak positive expression of EBNA2 in IM was significantly higher than that in EBV+DLBCL(P＜0.001),where-as strong positive expression of EBNA2 in IDD(post-transplantation)-related EBV+DLBCL was higher than that in IM(P＜0.001).Conclusion EBNA2 is often positive in IM and predominantly weakly positive,which is distinct from the pattern in EBV+DLBCL and IDD(post-transplantation)-related EBV+DLBCL.EBNA2 can serve as an effective marker for distinguishing them.

Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of primary bladder lymphoma.Methods:A retrospective study was conducted on 23 cases of primary bladder lymphoma diagnosed at Beijing Friendship Hospital of Capital Medical University between February 2010 and April 2024. The clinicopathological data were collected and analyzed, and literature was reviewed.Results:Among the 23 cases, 7 were male and 16 were female, with a male-to-female ratio of 1.0∶2.5. The median age was 65 (58, 71) years, ranged 38-84 years. The main clinical manifestation was painless visible hematuria, followed by frequent urination, urgency, and lower abdominal discomfort. Only one case presented with fever, and all cases primarily presented as bladder masses or lesions. The histological types included 17 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), 4 cases of diffuse large B-cell lymphoma (DLBCL), 1 case of ALK-negative anaplastic large cell lymphoma (ALCL), and 1 case of indolent NK-cell lymphoproliferative disease (INKLPD). EMZL exhibited relatively uniform morphology. Among them, 2 cases showed marked plasmacytic differentiation, 1 case had an increased number of large cells, 6 cases had residual germinal centers, and 2 cases presented with lymphoepithelial lesions. All cases demonstrated irregular FDC networks. DLBCL cells were larger in size; 3 cases showed diffuse infiltration, while 1 case had scattered, clustered distribution in a background of small lymphocytes,and with aberrant expression of GATA3. ALCL negative ALCL showed classic anaplastic morphology with "kidney-shaped" nuclei. INKLPD cells were of medium size and irregular in shape, with some cells containing eosinophilic granules in the cytoplasm. EBER in situ hybridization was negative.Conclusions:The primary histological types of bladder lymphoma are EMZL and DLBCL, with occasional cases of T-cell lymphoma and INKLPD. Clinical manifestations lack specificity and may overlap with inflammatory conditions or epithelial tumors. Both clinicians and pathologists should be aware of these rare diseases to facilitate accurate diagnosis and treatment.

Purpose To observe the clinical and pathological characteristics of indolent NK-cell lymphoprolifera-tive disorder(iNKLPD)of the gastrointestinal tract.Methods A retrospective analysis was conducted on the clinical pathological features,endoscopic findings,and immunophenotypes of 7 cases of iNKLPD.The study included in situ hybridization detection and literature review.Results The cohort comprised two males and five females,aged 28 to 54 years,with a median age of 40 years.The clinical manifestations varied,including acid reflux(two cases),nausea(three cases),stomach flatulence(five cases),and abdominal pain(one case).Lesions were observed at single sites in five cases and multiple sites in two cases.Involvement of the stomach,small intestine,and colon showed mucosal infiltration of small lymphocytes with abundant and clear cytoplasm,fine nuclear chromatin,and rare mitoses.Scat-tered eosinophils were observed in the background.Cases involving the gallbladder and bladder exhibited structural damage.The gallbladder lesion demonstrated cell with clear cytoplasm,condensed chromatin and prominent nucleoli.All cases were positive for CD3,CD56,CD7,TIA1 and Granzyme B,but negative for CD20,CD8 and CD5.Ki67 proliferation index from 10％to 50％.EBER in situ hybridization was negative in all cases.Follow-up periods ranged from 25 to 57 months(mean:38 months).All patients survived:four were asymptomatic,one had multiple-site in-volvement,and two experienced recurrence.Conclusion iNKLPD has an indolent clinical course and can involve multiple sites in the gastrointestinal tract and other organs.Differentiating it from invasive gastrointestinal lymphomas is critical to avoid misdiagnosis.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Purpose To compare the expression and pattern of EBNA2 in infectious mononucleosis(IM),EBV-positive diffuse large B-cell lymphoma(EBV+DLBCL),and EBV+DLBCL arising in immune deficiency/dysregulation(IDD-related EBV+DLBCL),and to investigate the potential diagnostic value of EBNA2 in IM and EBV-associated diffuse large B-cell lymphoma.Methods A retrospective study was conducted on 46 cases of IM,31 cases of EBV+DLBCL,and 16 cases of IDD(post-transplantation)-related EBV+DLBCL.Clinical information,immunohistochemis-try and EBER were reviewed to further confirm the diagnoses.All samples were stained for EBNA2.The expression ra-tio and intensity of EBER and EBNA2 in the same area were assessed.Results EBER was positive in all IM,EBV+DLBCL,and IDD(post-transplantation)-related EBV+DLBCL,while the positivity rate of EBNA2 was 95.65％,6.45％,and 100％,respectively.The positive intensity of EBNA2 was weak(71.73％),strong(87.5％)and nega-tive(93.54％)in IM,IDD(post-transplantation)-related EBV+DLBCL and EBV+DLBCL respectively.The average values of EBNA2/EBER were 31％,3％,and 78％among the three groups.The positivity rate and average value of EBNA2/EBER in IM were significantly higher than those in EBV+DLBCL(P＜0.001);however,the average value of EBNA2/EBER was significantly lower than that in IDD(post-transplantation)-related EBV+DLBCL(P＜0.001).The weak positive expression of EBNA2 in IM was significantly higher than that in EBV+DLBCL(P＜0.001),where-as strong positive expression of EBNA2 in IDD(post-transplantation)-related EBV+DLBCL was higher than that in IM(P＜0.001).Conclusion EBNA2 is often positive in IM and predominantly weakly positive,which is distinct from the pattern in EBV+DLBCL and IDD(post-transplantation)-related EBV+DLBCL.EBNA2 can serve as an effective marker for distinguishing them.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Purpose To observe the clinical and pathological characteristics of indolent NK-cell lymphoprolifera-tive disorder(iNKLPD)of the gastrointestinal tract.Methods A retrospective analysis was conducted on the clinical pathological features,endoscopic findings,and immunophenotypes of 7 cases of iNKLPD.The study included in situ hybridization detection and literature review.Results The cohort comprised two males and five females,aged 28 to 54 years,with a median age of 40 years.The clinical manifestations varied,including acid reflux(two cases),nausea(three cases),stomach flatulence(five cases),and abdominal pain(one case).Lesions were observed at single sites in five cases and multiple sites in two cases.Involvement of the stomach,small intestine,and colon showed mucosal infiltration of small lymphocytes with abundant and clear cytoplasm,fine nuclear chromatin,and rare mitoses.Scat-tered eosinophils were observed in the background.Cases involving the gallbladder and bladder exhibited structural damage.The gallbladder lesion demonstrated cell with clear cytoplasm,condensed chromatin and prominent nucleoli.All cases were positive for CD3,CD56,CD7,TIA1 and Granzyme B,but negative for CD20,CD8 and CD5.Ki67 proliferation index from 10％to 50％.EBER in situ hybridization was negative in all cases.Follow-up periods ranged from 25 to 57 months(mean:38 months).All patients survived:four were asymptomatic,one had multiple-site in-volvement,and two experienced recurrence.Conclusion iNKLPD has an indolent clinical course and can involve multiple sites in the gastrointestinal tract and other organs.Differentiating it from invasive gastrointestinal lymphomas is critical to avoid misdiagnosis.

Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of primary bladder lymphoma.Methods:A retrospective study was conducted on 23 cases of primary bladder lymphoma diagnosed at Beijing Friendship Hospital of Capital Medical University between February 2010 and April 2024. The clinicopathological data were collected and analyzed, and literature was reviewed.Results:Among the 23 cases, 7 were male and 16 were female, with a male-to-female ratio of 1.0∶2.5. The median age was 65 (58, 71) years, ranged 38-84 years. The main clinical manifestation was painless visible hematuria, followed by frequent urination, urgency, and lower abdominal discomfort. Only one case presented with fever, and all cases primarily presented as bladder masses or lesions. The histological types included 17 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), 4 cases of diffuse large B-cell lymphoma (DLBCL), 1 case of ALK-negative anaplastic large cell lymphoma (ALCL), and 1 case of indolent NK-cell lymphoproliferative disease (INKLPD). EMZL exhibited relatively uniform morphology. Among them, 2 cases showed marked plasmacytic differentiation, 1 case had an increased number of large cells, 6 cases had residual germinal centers, and 2 cases presented with lymphoepithelial lesions. All cases demonstrated irregular FDC networks. DLBCL cells were larger in size; 3 cases showed diffuse infiltration, while 1 case had scattered, clustered distribution in a background of small lymphocytes,and with aberrant expression of GATA3. ALCL negative ALCL showed classic anaplastic morphology with "kidney-shaped" nuclei. INKLPD cells were of medium size and irregular in shape, with some cells containing eosinophilic granules in the cytoplasm. EBER in situ hybridization was negative.Conclusions:The primary histological types of bladder lymphoma are EMZL and DLBCL, with occasional cases of T-cell lymphoma and INKLPD. Clinical manifestations lack specificity and may overlap with inflammatory conditions or epithelial tumors. Both clinicians and pathologists should be aware of these rare diseases to facilitate accurate diagnosis and treatment.

Purpose To investigate the expression of Che-mokine(C-X-C Motif)receptor 5(CXCR5)and its clinico-pathological significance in classic Hodgkin lymphoma(CHL).Methods The expression of CXCR5 was assessed in 33 pa-tients by immunohistochemistry(IHC),and retrospectively ana-lyzed the expression and clinical significance of CXCR5 in the four subtypes of CHL.Meanwhile,10 cases of ALK-positive an-aplastic large cell lymphoma(ALCL)and 10 cases of ALK-neg-ative ALCL were collected as the control group.ResultsThere were 31 cases with CXCR5-positive in all 33 cases(93.94％),including 15/16(93.75％)in nodular sclerosis CHL,12/13(92.31％)in mixed cellularity CHL,2/2 in lymphocyte-rich CHL,and 2/2 in lymphocyte-depleted CHL.The positive ex-pressions of CXCR5 in different immunophenotypes of CHL were as follow,31/33(93.94％)in CD30 positive and PAX5 weakly positive CHL.12/14(85.71％)in CD15 negative CHL,24/26(92.31％)in CD20 negative CHL,10/11(90.91％)in EBER-negative CHL and 5/6 in LMP1-negative CHL.CXCR5 were not expressed in all 20 cases of ALCL.Conclusion The positive expression rate of CXCR5 in CHL is high.When the tumor cells are negative for CD15,LMP1 and CD20 or EBER,CXCR5 also has a high positive expression rate,which is helpful for the diagnosis of CHL.CXCR5 can be used to differentiate CHL from ALCL,especially the cases lacking typical morpholo-gy and immunohistochemistry.

Objective:To investigate the clinical and pathologic features and diagnosis of follicular lymphoma (FL) with a predominantly diffuse growth pattern (DFL) with 1p36 deletion.Methods:Eight cases of DFL with 1p36 deletion diagnosed at Department of Pathology, Beijing Friendship Hospital, Capital Medical University ( n=5) and the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital ( n=3) from January 2017 to January 2023 were included. Their clinicopathologic features and follow-up data were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed. Results:There were five males and three females, with a median age of 67 years, and inguinal lymphadenopathy was found as the main symptom. Histologically, similar morphologic features were sheared among all cases, with effaced nodal structure and characterized by proliferation of centrocytes in a diffuse pattern, with or without follicular components. The germinal center-related markers such as CD10 and/or bcl-6 were expressed in the tumor cells, and 1p36 deletion but not bcl-2 translocation was appreciable in these cases.Conclusions:DFL with 1p36 deletion is a rare subtype of FL, with some overlaps with other types of FL or indolent B-cell lymphomas in their pathologic features. An accurate diagnosis requires comprehensive considerations based on their clinical, pathologic, immunohistochemical, and molecular features.