Clinicopathologic study of mantle cell lymphoma with epstein-barr virus infection: A case series and literature review.

Background: Mantle cell lymphoma (MCL) with Epstein-Barr virus (EBV) infection is rarely reported. The objective of this study was to analyze the prevalence and clinicopathological features of MCL with EBV infection in the largest series thus far. Methods: After screening 138 cases of MCL, we identified eight cases of MCL with EBV infection. Results: Most of them (7/8) had non-neoplastic bystander cells with positivity for EBV and no expression of latent membrane protein 1 (LMP1) and EBV nuclear antigen 2 (EBNA2). The cases of MCL with EBER positivity did not have abnormal immune function or other lymphomas. Moreover, their histopathological morphology was indicative of classical MCL. Cases of MCL with EBER positivity exhibited statistically significant differences in lactate dehydrogenase, anemia status, and MCL international prognostic index grouping (P=0.008, P=0.02, P=0.001, and P=0.011, respectively). The differences between the two groups in age, sex ratio, clinical manifestations, and immunohistochemical phenotypes were not statistically significant. Conclusions: The incidence of MCL with EBV infection was low (5.8%). Clinicopathologically, cases of MCL with EBER positivity were similar to their EBV-negative counterparts. Our findings revealed that most cells infected by EBV in MCL are background cells rather than tumor cells. This is inconsistent with data from previous studies, indicating that tumor cells in MCL may not be prone to EBV infection.

G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage of Plasmodium berghei Infection.

Epidemiological studies provide compelling evidence that glucose-6-phosphate dehydrogenase (G6PD) deficiency individuals are relatively protected against Plasmodium parasite infection. However, the animal model studies on this subject are lacking. Plus, the underlying mechanism in vivo is poorly known. In this study, we used a G6pd-deficient mice infected with the rodent parasite Plasmodium berghei (P.berghei) to set up a malaria model in mice. We analyzed the pathological progression of experimental cerebral malaria (ECM) and acute liver injury in mice with different G6pd activity infected with P.berghei. We performed dual RNA-seq for host-parasite transcriptomics and validated the changes of proinflammatory response in the murine model. G6pd-deficient mice exhibited a survival advantage, less severe ECM and mild liver injury compared to the wild type mice. Analysis based on dual RNA-seq suggests that G6pd-deficient mice are protected from ECM and acute liver injury were related to proinflammatory responses. Th1 differentiation and dendritic cell maturation in the liver and spleen were inhibited in G6pd-deficient mice. The levels of proinflammatory cytokines were reduced, chemokines and vascular adhesion molecules in the brain were significantly down-regulated, these led to decreased cerebral microvascular obstruction in G6pd-deficient mice. We generated the result that G6pd-deficiency mediated protection against ECM and acute liver injury were driven by the regulatory proinflammatory responses. Furthermore, bioinformatics analyses showed that P.berghei might occur ribosome loss in G6pd-deficient mice. Our findings provide a novel perspective of the underlying mechanism of G6PD deficiency mediated protection against malaria in vivo.

The correlation and overlaps between PD-L1 expression and classical genomic aberrations in Chinese lung adenocarcinoma patients: a single center case series.

OBJECTIVE: To investigate the correlation and overlaps between PD-L1 expression and classical genomic aberrations in Chinese lung adenocarcinoma (LADC) patients. METHODS: We reviewed 428 consecutive, surgically resected cases of LADC from October 2015 to December 2016 from our center. PD-L1 expression was evaluated based on tumor proportion score (TPS). Correlation and co-occurrence of PD-L1 expression level with those of classical driver genes, such as EGFR, ALK, ROS-1, and KRAS and with clinical variables and disease-free survival (DFS) were analyzed. RESULTS: Seventy of the 428 cases (16.4%) showed TPS ≥ 1%, and 21 cases (4.9%) showed TPS ≥ 50%. PD-L1 positive expression was significantly associated with male gender, smoking, advanced TNM stage, and solid histologic subtype. Both TPS ≥ 1% and ≥ 50% were correlated with the absence of an EGFR mutation (P < 0.001) and the presence of ALK rearrangement ( P = 0.024). KRAS mutation was associated with TPS ≥ 50% (P = 0.035). PD-L1 positivity commonly overlapped with the alterations of classical driver oncogenes (58.5% with TPS ≥ 1% and 42.9% with TPS ≥ 50%). Approximately three-quarters of PD-L1 positive cases co-occurred with classical therapeutic-gene aberrations in cases with stage III/IV cancer or cancer progression. LADC could be divided into four subgroups based on the expression profile of current routine biomarkers for potential therapeutic strategies. CONCLUSIONS: PD-L1 expression is not only closely correlated with classic gene alterations but also commonly overlaps with the aberrations of classical driver oncogenes in Chinese LADC patients. These findings provide a useful overview of clinical strategies that rely on the profile of routinely used molecular biomarkers.