Aggressive B Cell Lymphoma In Gastrointestinal Tract:Clinicopathologic Analysis Of54Cases

Objective:To study the histological features, diagnosis, differential diagnosis and investigate the correlation between prognosis and clinicopathological parameters or immunophenotyping of the aggressive B cell lymphoma in gastrointestinal tact. And obversation was focused on the antibody against c-MYC with regard to its expression characteristic and influence in the prognosis and the value and practical significance in predicting the status of c-myc gene.Methods:54cases of aggressive B cell lymphomas in gastrointestinal tract with complete clinical and pathologic information were retrospectively collected including49cases of DLBCL,4cases of DLBCL/BL,1cases of BL. All the cases were reviewed and followed up. Then immunophenotyping for the49cases of DLBCL was detected by the antibodies CD10, Bcl-6, Mum-1and CD5using En Vision method. Meanwhile, the c-myc status was estimated in contrast with8cases of BL outside gastrointestinal tract. Other detection antibodies included CD20, CD79a, CD5, CD3, CD43, Bcl-2, CD4, CD30, Ki-67. Using chi-square test or Fisher’s exact probabilities investigated the correlation between the immune markers and clinicopathological parameters or prognosis, Kaplan-Meier explored the considerable factors of prognosis by univariate analysis, and Cox Regression studied the independent negative factors of prognosis by means of SPSS16.0analysis software.FISH were applied to examine the c-myc status in the54cases and8cases of BL outside gastrointestinal tract as control by virtue of c-myc dual-color break-apart commercial probe, and furthermore, ROC curves confirmed the accuracy to take advantage of c-MYC immunostaining. In addition, cases positive for c-MYC and strongly positive for Bcl-2immuochemistry were detected their bcl-2status.Results:(1) Clinical data54cases aggressive B cell lymphomas in gastrointestinal tract were comprised of33males and21females with average age52and median age56, including12cases of DLBCL,1case of DLBCL/BL in stomach,35cases of DLBCL,3cases of DLBCL/BL,1case of BL in intestinal tract, and2cases of DLBCL in both. Patients often presented with gastrointestinal masses emerging the symptom of abdominal discomfort or pain, sometimes coupled with constitutional symptoms such as fever, night sweating and cachexia. A share of the patients were hospitalized due to an acute abdomen as gastrointestinal perforation.(2) Follow-up data All the follow-up data of the54cases were acquired, with the duration ranging from2～150months(median follow-up time45months). Patients were mainly treated by CHOP regimen, part of which added rituximab.11(9DLBCL,1DLBCL/BL,1BL) out of54patients had died within97months, with median survival time42months, and others had been undergoing a relatively stable situation.(3) Histologic characteristics Lymphoma cells, mainly composed of centroblasts and centrocytes with or without plasmocytoid differentiation and multinucleated gaint cells, showed full-thickness infiltration of the gastrointestinal wall.17cases presented evident phagocytosis of karyorrhexis by macrophages("starry sky"). Interstitial fibrosis and vessel growth sometimes would be encountered.(4) Immunohistochemisty characteristics54cases consisted of11cases of GCB DLBCL,38cases of ABC DLBCL,4cases of DLBCL/BL(positive for CD20, CD10, Bcl-6, Bcl-2),1case of BL(positive for CD20, CD10, Bcl-6but Bcl-2). The tumor cells of7cases of DLBCL expressed CD5.19cases were positive for c-MYC including14cases of DLBCL,4cases of DLBCL/BL,1cases of BL. All the cases were negative for CD30, and also for CD4, CD3except positive for some reactive lymphoma cells. And proliferation index Ki-67was40-100%, median80%.(5) FISH detection results1case of DLBCL,2cases of DLBCL/BL,1case of BL and8BL outside gastrointestinal tract as control emerged c-myc translocation, all of which were positive for c-MYC by immunostaining, with percentage of positive cells varying from80%to100%. In addition,4c-myc-translocated cases and cases positive for Bcl-2exceeding50%positive cells were detected by FISH, in which1case presented fusion gene bcl-2/IgH. (6) Statistic analysis Chi-square test or Fisher’s exact probabilities showed cases positive for c-MYC and the index as karyorrhexis, Tcl-1, Ki-67had significant differences(P<0.05). Correlation analysis revealed there existed linear correlation between c-MYC percentage of positive cells and Ki-67labeling index. Kaplan-Meier displayed B symptoms, high LDH, high ECGO, distant metastasis, high IPI index and high clinical stage were negative factor for the patients’survival rate, and in addition, cases positive for CD5had unfavorable prognosis, all of which showed significant differences by Log-rank analysis(P<0.05). Cox regression analysis showed translocation of c-myc, distant metastasis and high LDH were independent unfavorable prognosis factors. ROC curve revealed the positive percentage for c-MYC would contribute to forecast the c-myc status, with75%as the optimal threshold.Conclusion:(1) DLBCL, DLBCL/BL, BL are a group of aggressive B cell lymphomas, and gastrointestinal tract is one of the most predilection sites. A correct diagnosis needs the comprehensive evaluation including clinical data and immunohistochemistry, and the exclusion of other round cell tumors developing in gastrointestinal tract.(2) Various clinicopathologic factors such as B symptom, LDH, performance, distant metastasis, IPI index, clinical stage, CD5and c-myc status are relevant with prognosis.(3) DLBCL and DLBCL/BL could possess translocation of c-myc. Theses types tend to be Burkitt-like or atypia Burkitt lymphoma(BL/aBL), which present with obvious karyorrhexis and "starry sky", but celluar size and morphology, lacking of uniformity, usually behave more atypia and always display significantly high proliferation index even close to100%. As independent factors influencing prognosis, detection of c-myc will contribute to assess the patientts’ curative effect and prognosis.(4) High c-MYC positive percentage of tumor cells combined with Tcl-1and CD38will contribute to predict the translocation of c-myc. That method using immunohistochemistry would provide a new and potential approach with cheap and fast characteristics as preliminary screening, however, more comfirmation is needed to popularize this method. Cases strong positive for Bcl-2were not always of translocation, but FISH detection still be recommended in practical.