| Objective:1.To analyze the clinicopathologic characteristics of lymphoma in Dali Bai Autonomous Prefecture in recent 10 years,and compare the differences and similarities of lymphoma epidemiological characteristics with those in other parts of China,Asia,Europe and the United States.2.To detect and follow up EBV infection in different pathological types of lymphoma and analyze the impact of EBV infection on the prognosis of lymphoma.Methods:1.The clinical data of newly diagnosed patients with lymphoma admitted to Dali Bai Autonomous Prefecture third Class A Hospital(the first affiliated Hospital of Dali University,the people’s Hospital of Dali Bai Autonomous Prefecture and the first people’s Hospital of Dali City)from January 2012 to December 2021 were collected.The patients were classified according to the fifth edition of WHO classification of hematopoietic and lymphoid tissue tumors in 2022,and the clinical information such as sex,age,location and pathological types were studied retrospectively.The clinicopathological features of lymphoma in this area in recent 10 years were analyzed.Chi-square test and Fisher exact test were used to compare and analyze the differences between other regions of China and other countries.2.EBER of lymphoma was detected by in situ hybridization to understand EBV infection.Combined with clinicopathological data and survival outcome,chi-square test and Fisher accurate test were used to analyze the difference of EBV infection among clinicopathological features.Kaplan-Meier and Log-rank test were used for survival analysis to explore the effect of EBV infection on the prognosis of lymphoma.Results:Part Ⅰ1.Pathological types of 545 cases of lymphoma: from January 2012 to December2021,545 cases of lymphoma were diagnosed for the first time(those with unclear exclusive diagnosis or incomplete clinicopathological information).Among the 545 cases of lymphoma,503 cases were non-Hodgkin’s lymphoma(NHL),accounting for92.3% of all lymphomas in the same period.42 cases were Hodgkin’s lymphoma(HL),accounting for 7.7%.Of the 503 cases of NHL,384(76.3%)were B-lineage NHL and119(23.7%)were T/NK NHL,of which 338(67.2%)were mature B-cell tumors,98(19.5%)were mature NK/T-cell tumors,and 67(13.3%)were lymphoblastomas.In B-cell NHL,the common subtypes were diffuse large B-cell lymphoma(52.6%),B-lymphoblastic leukemia/lymphoma(12.0%),follicular lymphoma(6.0%),extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue(4.7%)and chronic lymphoblastic leukemia/small lymphocyte lymphoma(4.7%).18 pr 384),mantle cell lymphoma(3.1% dint 12 pm 384).In T/NK cell NHL,the common subtypes are extranodal NK/T cell lymphoma(44.5%),T lymphoblastic leukemia/lymphoma(17.6%),anaplastic large cell lymphoma(13.4%),and angioimmunoblastic T-cell lymphoma(10.9%).Among the 42 patients with HL,there were 2 cases of nodular lymphocyte predominant Hodgkin’s lymphoma(4.8%)and 40 cases of classical Hodgkin’s lymphoma(95.2%).In classical Hodgkin’s lymphoma,the most common type is mixed cell type(40.5%),followed by nodular sclerosing type(31.0%).2.Epidemiological characteristics:(1)the incidence of lymphoma tends to increase in the past 10 years.It was relatively stable from 2012 to 2015,and showed an increasing trend from 2016 to 2019,with the most significant increase in the number of cases of NHL,with a growth rate of 36.3%.(2)ethnic composition: the Han nationality accounts for the vast majority,with a total of 265 cases(48.6%),followed by 206 cases of the Bai nationality(37.8%),and 74 cases of other ethnic minorities(13.6%).The Yi nationality(6.2%),Lisu nationality(2.6%)and Hui nationality(1.7%)ranked in the top three.(3)Age and sex composition: the age range of the whole group was 384 years old,the average age was 51.5 ±17.7 years old,the median age was 55 years old,and the peak age of onset was 40 years old to 69 years old,accounting for 65.5%.The age range of 42 patients with HL was 680 years old,the mean age was 47.018.4 years old,the median age was 51.5 years old,the age of onset was 40 to 59 years old,and the age range of 503 patients with NHL was 384 years old,the average age was 51.9 ±17.6years old,the median age was 55 years old,and the age of onset was 50 to 69 years old.There were 321 males and 224 females,with a male-to-female ratio of 1.4.There were32 males and 10 females in HL,and the male-to-female ratio was 3.2.There were 289 males and 214 females,and the male-to-female ratio was 1.4.(4)the first symptoms or signs were enlarged superficial lymph nodes in 217 cases(39.8%),followed by abdominal pain and abdominal distension in 83 cases(15.2%),fever and fatigue in 43cases(7.9%),nasal obstruction and rhinitis in 42 cases(7.7%),pharynx pain and pharyngeal foreign body sensation in 28 cases(5.1%).(5)the location of the disease:261 cases(47.9%)occurred in the first lymph nodes,mostly superficial lymph nodes,followed by cervical lymph nodes(164 cases,30.1%),inguinal lymph nodes(42 cases,7.7%),axillary lymph nodes(19 cases,3.5%).284 cases(52.1%)occurred in extranodal lymphoid tissues or organs,and the most common causes of extranodal organs were gastrointestinal tract(82 cases,15.0%),nasal cavity(37 cases,6.8%),tonsil(27 cases,5.0%)and pharynx(14 cases,2.6%).(6)Clinical stage: there were 258 patients in stageⅠ and Ⅱ,accounting for 47.3%,and 287 cases in stage Ⅲ and Ⅳ,accounting for52.7%.StageⅠA,ⅡAn and ⅣB were the most,accounting for 19.4%,18.0% and17.4%,respectively.The most common clinical stage of 42 cases of HL was stage ⅢA,followed by stage Ⅱ An and stageⅠA(list the top three),accounting for 28.6%,19.0% and 16.7%,respectively.The most common clinical stage of NHL was stage ⅠA,followed by stage ⅣB and stage ⅡA(the top three were listed),accounting for19.7%,18.0% and 17.9%,respectively.(7)hepatomegaly,splenomegaly and mass:hepatomegaly was found in 18 cases of lymphoma(3.3%),splenomegaly in 109 cases(20.0%),and large mass in 67 cases(12.3% 7.5cm).(8)Peripheral blood: the percentage of WBC increased and decreased was 18.5% and 13.8% respectively,and that of hemoglobin(HGB)was 6.2% and 32.1% respectively.The absolute value of lymphocytes(LYMP)increased and decreased in 3.7% and 10.5% of the patients respectively.The patients with elevated erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),lactate dehydrogenase(LDH)and β 2-microglobulin(β 2-MG)accounted for 51.7%,50.6%,41.4% and 16.2%,respectively.(9)virus infection: there were 32 cases of HBV infection in blood(5.9%),5 cases of HCV infection(0.9%),and6 cases of HIV infection(1.1%).All of them were found in NHL.Of the 137 patients with EBV in situ hybridization results,57(41.6%)were EBER positive,of which 7(12.3%)were found in HL patients and 50(87.7%)in NHL patients.3.Statistical analysis of clinicopathological features:(1)univariate analysis of clinical stage of 503 patients with NHL: nationality,location of onset,B symptom,hepatomegaly,splenomegaly,serum WBC,HGB,LYMP,ESR,CRP,LDH,β2-microglobulin level and HIV infection were the influencing factors of clinical stage of NHL.(2)Multivariate analysis of clinical stage in 503 patients with NHL: nationality,location of onset,B symptom,splenomegaly,serum WBC level and HGB level were the influencing factors of clinical stage of NHL.(3)there were significant differences in the distribution of nationality,sex and location of onset between HL and NHL patients(P <0.05),but there was no difference in age distribution.(4)compared with the results of the national multicenter study,there was no significant difference in the sex and location of lymphoma patients in this area(P > 0.05).(5)comparison of the distribution of HL and NHL subtypes between Dali and other regions of China and other countries:comparison of HL and NHL subtypes between Dali and other regions of China(national polycenter,Sichuan,Beijing,Shanxi,Hubei,Heilongjiang,Jiangsu).The proportion of HL in this region(7.7%)is similar to that of national polycenters(8.9%),Beijing(8.6%),Hubei(8.0%)and Heilongjiang(9.5%),lower than Sichuan(13.1%)and Shanxi(16.4%),and higher than Jiangsu(5.2%).Compared with the distribution of HL and NHL subtypes in other regions of the world(South Korea,Japan,the United Kingdom,Australia),the proportion of HL in this region(7.7%)is similar to that in Japan(6.0%)and Australia(7.8%),higher than that in Korea(3.8%)and lower than that in the United Kingdom(14.4%).(6)comparison of the distribution of NHL subtypes between Dali and other regions of China and abroad: compared with the distribution of NHL subtypes in other regions of China(Shandong,Jiangsu,Sichuan,Hubei),there are some similarities and differences in the distribution of NHL subtypes in different regions.The proportion of DLBCL in this region(40.2%)is similar to that of Jiangsu(42.6%),Sichuan(41.2%)and Hubei(41.3%),but higher than that of Shandong(36.0%).The proportion of LBL in this region(13.3%)is higher than that in Shandong,Sichuan and Hubei(about 5%),especially in Jiangsu(1.8%).The proportion of FL in this region is the same as that in Jiangsu(4.6 per cent),lower than that in Shandong,Sichuan and Hubei(6%～8 %).The proportion of MALT in this region(3.6 per cent)is similar to that in Jiangsu(3.8%)and lower than that in Shandong(5.4%),Sichuan(6.3%)and Hubei(8.0%).The proportion of CLL/SLL in this region(3.6%)is similar to that in Shandong(3.2%),Sichuan(4.6%)and Hubei(3.5%),and significantly lower than that in Jiangsu(14.4%).The proportion of ENKTCL in this region(10.5%)is higher than that in Shandong(8.8%)and Jiangsu(5.5%),but lower than that in Sichuan(17.1%)and Hubei(13.4%).The proportion of AITL in this region(2.6%)is similar to that in Jiangsu,Sichuan and Hubei(20.4%),and higher than that in Shandong(0.8%).The proportion of ALCL is similar in different regions.Compared with the distribution of NHL subtypes in other regions of the world(South Korea,India,France,the United States),DLBCL is the most common subtype in Asia,Europe and the United States.The incidence of FL in Europe and America is higher than that in China and other Asian regions.The proportion of MALT in South Korea is higher than that in China,India,Europe and the United States.The incidence of CLL/SLL in Europe and America is higher than that in Asia.The proportion of ENKTCL in China and other Asian regions(except India)is higher than that in Europe and the United States.Part Ⅱ1.EBV infection in different pathological types of lymphoma: according to the fifth edition of WHO classification of hematopoietic and lymphoid tissue tumors in2022,the clinicopathological data of newly diagnosed patients with lymphoma from January 2012 to December 2021 were screened.A total of 137 patients with lymphoma were detected by EB virus(EBV)in situ hybridization.(1)EBV infection of HL,B-NHL and T/NK-NHL: among the 137 patients with lymphoma,57 were EBER positive and 80 were EBER negative,with a positive rate of 41.6%.Among them,the EBER positive rate of HL was 50.0%,the EBER positive rate of NHL was 40.7%,and the positive rate of EBER in HL was higher than that of EBER in NHL;B-NHL(16.0%).The positive rate of EBER in T/NK-NHL was 79.2%(38 + 48),and the positive rate of EBER in T/NK-NHL was significantly higher than that in B-NHL.(2)EBV infection in different subtypes of HL,B-NHL and T/NK-NHL: in HL,the positive rates of EBER in mixed cell classical Hodgkin’s lymphoma,nodular sclerosing classical Hodgkin’s lymphoma and lymphocyte-rich classical Hodgkin’s lymphoma were 50.0%,50.0% and50.0%,respectively.The positive rate of EBER in classical Hodgkin’s lymphoma with lymphocytopenia was 100.0%,while that of tumor cells with nodular lymphocyte predominant Hodgkin’s lymphoma was EBER negative.In B-NHL,the positive rates of EBER and EBER in diffuse large B-cell lymphoma and Burkitt’s lymphoma were11.3% and 37.5%,respectively,and in 3 of the other 14 cases of B-NHL,the positive rate of EBER was 37.5%.In T-NHL,the positive rate of EBER in extranodal NK/T-cell lymphoma and angioimmunoblastic T-cell lymphoma was 100.0% and 75.0%,respectively.Of the other 11 cases of T-NHL,2 cases were positive for EBER.The positive rate of EBV infection in extranodal NK/T cell lymphoma was significantly higher than that in other T cell NHL.2.The relationship between EBV infection and clinicopathological features: of the137 cases in this study,14(10.2%)were HL and 123(89.8%)were NHL.The main results were as follows:(1)the clinical characteristics of 14 cases of HL showed that there was no significant difference in age,sex,location of onset,B symptoms,clinical stage,hepatomegaly,splenomegaly,serum WBC,HGB,LYMP and LDH levels between EBV positive and negative HL patients.(2)the clinicopathological features of NHL were analyzed.The results showed that there was significant difference in the proportion of onset site and pathological type between EBV positive and negative NHL patients.3.Prognostic analysis of EBV infection and NHL:(1)Survival analysis of NHL patients: of the 77 patients with NHL,35 died and 42 survived.The 1-year survival rate,3-year survival rate and 5-year survival rate of NHL patients were 74.0%,59.5% and33.8% respectively.(2)Survival analysis of patients with EBV infection: the average survival time of EBV positive NHL patients was 27 months,while that of EBV negative NHL patients was 56 months,the difference was statistically significant.The death risk of EBV positive patients was 2.348 times higher than that of EBV negative patients.Conclusions:1.The incidence of lymphoma in Dali area has increased in the past 10 years.,among which the number of cases of NHL has increased most significantly with a growth rate of 36.3%.2.In NHL,the most common subtype was diffuse large B-cell lymphoma,followed by extra-nodal NK/T-cell lymphoma,and in HL the most common type was mixed cell type,followed by nodular sclerosing type.3.The age range of the whole group of patients in this study was 3-84 years,with a mean age of 51.5±17.7 years and a median age of 55 years,and the age of onset was concentrated between 40 and 69 years.There were significantly more male patients than female patients in all age groups.4.The first symptoms of patients with superficial lymph node enlargement were most common,with more extra-nodal than intra-nodal onset,and more patients with stage III and IV than stage I and II.5.The epidemiological characteristics of lymphoma in Dali Bai Autonomous Prefecture are similar to those in other regions of China and other Asian countries,while there are differences compared with Western countries such as Europe and the United States.6.Different pathological types of lymphoma(HL,B-NHL,T/NK-NHL)are likely to be infected with EBV,with the highest rate of infection in T/NK cell types.7.The rate of EBER positivity was higher in HL than in NHL,and higher in T/NK-NHL than in B-NHL.8.EBV-positive NHL has a worse prognosis than EBV-negative NHL. |
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