The Clinicopathological And Genetic Features Of Ovarian Diffuse Large B-cell Lymphoma

[Background]Ovarian lymphoma whether a primary or secondary condition,is very rare.Primary ovarian lymphoma accounts for only 0.5%of all non-Hodgkin lymphomas and 1.5%of all ovarian neoplasms.Earlier studies have reported the most common subtypes of ovarian lymphoma are diffuse large B-cell lymphoma,Burkitt and follicular lympho-ma.Due to the rarity of ovarian lymphoma,its immunophenotypic and genetic featu-res are largely unknown.In Qilu hospital,there has been a total of 11 patients diagno-sed with ovarian lymphoma over the past 10 years.Out of the 11 cases,9 wre diagno-sed as diffuse large B-cell lymphoma(DLBCL).The purpose of this study was to inv-estigate the clinicopathologic and genetic characteristics of ovarian diffuse large B-cell lymphoma,to better understand ovarian lymphoma,and to find a new reference for its diagnosis and treatment.[Methods](1)Coleecting eleven cases of ovarian lymphoma in qilu hospital of shandong university from 2007 to 2018,and screening out the most 9 cases of diffuse large b-cell lymphoma.Then collect their clinical and pathological data.At the same time,9 common extranodoal diffuse large b-cell cases were used as controls,and the clinicopathological characteristics of ovarian diffuse large b-cell lymphoma a-re further compared and analyzed.(2)The histomorphological characteristics of ovarian DLBCL and common extranodoal DLBCL were observed and compared by HE staining of paraffin sections under optical microscope.(3)Immunohistochemical staining was used to detect the 10 immunhistochemical markers in ovarian DLBCL and common extranodoal DLBCL(4)Fluorescence in situ hybridization was used to detect Myc,Bcl2,and Bcl6 in ovarian DLBCL and common extranodoal DLBCL.(5)The expression of EBV ovarian DLBCL and common extranodoal DLBCL was detected by in situ hybridization.(6)After the above studies,we will further conduct genome-wide exon sequencing analysis of the relevant cases.We sent a total of 21 samples.Among them,9 cases were ovarian DLBCL(ovarian DLBCL group),9 cases were common extranodoal DLBCL(common extranodoal group),and 3 cases were reactive hyperplasiacases(control group).(7)The data were analyzed using the Statistical Package for Social Sciences(SPSS)(version 20)statistical program(SPSS,Chicago,IL).χ2 test and t-tests were used to assess the differences between groups.The results were considered statistically significant when P<0.05.[Results](1)The age of ovarian DLBCL patients ranged from 25-79(mean 52.7)years.The tumor size ranged in diameter from 0.5 to 19 cm(mean 6.8 cm).Six cases were bilateral and the remaining 3 cases were left-sided.Four cases had only ovarian involvement.Four cases had omentum involvement and one case had uterus involvement.The age of common extranodoal DLBCL patients ranged from 31-74(mean 56.3)years.The tumor size ranged in diameter from 1.8 to 16cm(mean 6.1cm).The most cases had gastrointestinal tract involvement,some had spleen,maxillary bone and retroperitoneum involement.(2)Morphologically,compared to the common extranodal DLBCL,the tumor cells of ovarian DLBCL were homogeneous and starry sky phenomenon was very common presenting a Burkitt-like appearance.(3)9 cases of ovarian DLBCL and 9 cases of common extranodoal DLBCL are positive for CD20 and CD79a,and negative for CD30.Ki67 was highly expressed in B-all 9 cases of ovarian DLBCL(>90%),while in the 9 cases of common extranodoal DLBCL,the expression of Ki67 varied from 40%to 95%,and only 4 cases were highly expressed(>90%).Among the 9 cases of ovarian DLBCL,only 3 have dual expression of myc and bcl2,while 7 have dual expression of myc and bcl2 among the common extranodoal DLBCL.In all cases of ovarianDLBCL,muml was negative,while in the common extranodoal DLBCL,2 cases were positive for muml.(4)A "double-hit"(including Myc and Bcl6)was present in one case of ovarian DLBCL.(5)All cases of ovarian DLBCL and common extranodoal DLBCL were negative for EBER.(6)Whole exome sequencingSNP and Indel:(1)In total,2094 mutation sites(1359 genes involved)were identified in≥5/9 cases of ovarian DLBCL compared with the control group.Among them,34 mutation sites(23 genes involved)were found in all of the ovarian DLBCL cases.(3)In the common extranodal DLBCL,2271 mutation sites(1442 genes involved)were identified in≥5/9 cases compared with the control group and 46 mutation sites(31 genes involved)were found among the 9 cases.(3)These mutated genes were enriched in several important signaling pathways including some lymphoma-related pathways.CNV:(1)The results indicated that 166 gene alterations were identified in≥ 5/9 cases of ovarian DLBCL,and the same number of alterations were identified in≥ 5/9 cases of common extranodal DLBCL.(2)The CNV results also indicated several important signaling pathways that are involved in ovarian DLBCL and common extranodal DLBCL,such as EBV infection and HTLV-1 infection pathways.[Conclusion](1)The main subtype of ovarian lymphoma is diffuse large B-cell lymphoma,which is similar to Burkitt lymphoma in histomorphology.The sites of ovarian diffuse large B-cell lymphoma may be ethnically different.(2)Compared with common exteranodal DLBCL,ovarian DLBCL had both common characteristic and certain differences,proving that ovarian DLBCL had its unique molecular phenotype.(3)Ovarian DLBCL and common extranodal DLBCL shared many mutated genes,but each also had its unique genetic features.