Inflammatory pseudotumor-like follicular dendritic cell sarcoma of the spleen:2 cases report and literature review / 复旦学报（医学版）

Inflammatory pseudotumor-like follicular dendritic cell sarcoma(IPT-like FDCS)is a very rare malignant tumor that is considered to be associated with Epstein-Barr virus.Two patients in this report were generally healthy,and the spleen tumor was found during physical examination.After completing the examination,laparoscopic total splenectomy was performed,and the pathological result showed IPT-like FDCS.Postoperative chemoradiotherapy was not performed in either case.The disease has no characteristic clinical manifestations,and imaging overlaps with sarcoma.Microscopic manifestation showed CD21,CD23 and EBER positive spindle tumor cells in the inflammatory background with matted arrangement.Due to the interwoven distribution of tumor cells and lymphocytes,diagnosis is difficult.In this article,we report this two cases with literature review and summarize their clinical and pathological features to improve diagnostic cognition.

Circular RNAs Involved in The Development of Nasopharyngeal Carcinoma / 生物化学与生物物理进展

Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.

Establishment of mouse models of lymphoma with dual-labeled EBV-immortalized lymphoblastoid cell lines by intravenous versus subcutaneous injection / 中国肿瘤临床

Objective:To establish a green fluorescent protein(GFP)and firefly luciferase(Luc)double-labeled Epstein-Barr virus(EBV)infec-ted B lymphoblastoid cell lines(B-LCL)and apply them to mouse models,then compare the advantages and disadvantages of models inocu-lated by intravenous(IV)or subcutaneous(SC).Methods:B lymphoblastoid cell lines double-tagged with GFP/Luc(B-LCL-GL)were con-structed through lentivirus transduction,puromycin intervention.Subcutaneous xenograft and hematogenous metastasis models were re-spectively established by subcutaneous or intravenous injection of B-LCL-GL cells at three concentrations in(NOD)/Prkdcscid/IL-2Rγnull(NPG)mice for in vivo bioluminescence imaging.Results:In the B-LCL-GL group,the ratio of the GFP-positive cell population was 92.5%,and the average luminescence intensity was as high as 4.80E+08 Photons/s,which was considerably higher than that of untreated B-LCLs.In the hematogenous metastasis models,tumor bioluminescence was initially located in the peritoneal area and then spread throughout the en-tire body between 7 and 28 days.In the subcutaneous xenograft models,strong central and weak peripheral tumor-related biolumines-cence signal was detected on day 7 in the three groups,which then spread throughout the body on day 28 in the high-dose group.Taken to-gether,there was no significant difference in tumor progression between the two routes of administration when using the same dose of B-LCL-GL cells.However,the survival analysis indicated that the IV injection group,in which all the mice ultimately died,had a shorter time frame for testing than that of the SC injection group,in which the mice survived until day 100 in the low-dose and medium-dose groups,thus allowing for long-term testing.Conclusions:GFP and Luc dual-positive B-LCLs were successfully established to generate hematogenous metastasis and subcutaneous xenograft models,which allow the monitoring of the location and size of lymphomas in vivo.It provide plat-form for the study of tumor characteristics and selecting anti-tumor drugs.

Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Association of plasma EBV-DNA copy number and cytokines with B symptoms in patients with extranodal natural killer/T-cell lymphoma, nasal type / 中华放射肿瘤学杂志

Objective:To investigate the association of plasma EBV-DNA copy number, serum cytokines and B symptoms in patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), unravel the mechanism and assess the prognostic value of clinical indicators.Methods:Clinical data of 173 newly-diagnosed ENKTL patients (116 male, 57 female; median age: 43, 4 to 71 years)were retrospectively analyzed. According to Ann Arbor stage, 126 cases were classified as stage I-II and 47 cases of stage Ⅲ-IV. The primary sites of tumors included nasal cavity (n=100), extranasal upper aerodigestive tract (extranasal UADT, n=34), and extra-upper aerodigestive tract (extra-UADT, n=39). Prior to treatment, 91 patients had B symptoms and 82 cases of without B symptoms. According to plasma EBV-DNA copy levels, all patients were divided into the negative group (n=36), low load group (<10 4 copies/ml, n=73) and high load group (≥10 4 copies/ml, n=64). Serum cytokines including IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α were detected. Correlation analysis was performed by Cochran-Armitage trend test and Spearman correlation analysis. Survival analysis was conducted using univariate and multivariate Cox regression hazard analysis and survival curves were derived from Kaplan-Meier survival analysis. Results:The incidence of B symptoms and fever showed a significant upward trend with the increasing plasma EBV-DNA copy levels. In addition, serum levels of IFN-γ, IL-6 and IL-10 cytokines were higher in patients with B symptoms than those without B symptoms (all P<0.05). Serum IFN-γ, IL-6, and IL-10 levels were also positively correlated with plasma EBV-DNA copy number. The occurrence of B symptoms was associated with high-risk clinical features including advanced stage, primary tumor invasion, regional lymph node involvement, and elevated pre-treatment LDH. Survival analysis showed that stage, B symptoms, plasma EBV-DNA, and the above serum cytokines affected the prognosis of overall survival (OS) and progression-free survival (PFS) (all P<0.05). However, multivariate analysis showed that the occurrence of B symptoms was not an independent prognostic factor of ENKTL patients. Conclusion:This exploratory study suggests that the incidence of B symptoms is associated with increasing levels of EBV-DNA copies and cytokines, and these indicators are also important factors influencing the prognosis of ENKTL patients.

Application of Flow Cytometry Combined Fluorescence in Situ Hybridization to Indentify the Lymphocyte Subtypies with Epstein-Barr Virus Infection / 中国实验血液学杂志

OBJECTIVE@#To establish the technique that take the advantages of flow cytometry combined fluorescence in situ hybridization (Flow-FISH) to identify the Epstein-Barr virus(EBV) infected lymphocyte subtypies in patients' peripheral blood sample.@*METHODS@#Peripheral Blood monocyte from 9 patients with EBV infection enrolled at Children's Hospital in Chongqing Medical University were isolated by Ficoll-paque centrifugal separation. The expressions of EBER1, EBER2 in cell were detected by qRT-PCR. The surface markers of cell were detected by Flow cytometry after staining with their antibodies. The cell was treated Fix-Permeabilization Buffer before hybridization with fluorescent labeled probe at 37 ℃ overnight. The cell status, surface markers and targeted mRNA are detected by flow cytometry and fluorescence microscope.@*RESULTS@#It was optimized that the Fix-Permeabilization Buffer and recipe with 0.2% Tween-20 were picked out as providing a good cell integrity and high resolution of surface markers. Hybridization with 20% formamide and 7% dextran sulfate at 37 ℃ overnight is the optimal hybridization condition as a good hybridization effect, a detectable cell integrity and a high resolution of cell markers under flow cytometry detection. Finally, upon the established Flow-FISH method, lymphocyte subpopulations of the EBV+ cells from cell lines and blood samples of patients were identified successfully.@*CONCLUSION@#A Flow-FISH technology is established, which can be applied in the identification of EBV infected cell subtypes. This research provides a foundmental for its application in clinical test in EBV+ related proliferative diseases.

Analysis of carcinogenic virus infection in HIV-infected patients / 上海预防医学

Objective To investigate the status of carcinogenic infection in people infected with HIV and those with negative HIV test results in VCT clinics. To analyze the epidemiological characteristics and provide scientific basis for more targeted disease prevention and control strategies. Methods The serum levels of Epstein-Barr virus （EBV）， human herpesvirus type 8 （HHV-8） and human T-lymphotropic virus type Ⅰ （HTLV-Ⅰ） antibodies were detected by ELISA method in 224 HIV-infected patients and 480 HIV-negative visitors treated in VCT clinics during the same period from 2014 to 2017， to compare the differences in the infection rates of this virus between HIV-infected and HIV-negative individuals and to systematically analyze the correlation between viral infections and high-risk sexual behavior. Results Among the 224 HIV-infected patients， 79 were positive for EBV antibody， with the infection rate of 35.27%； 151 were positive for HHV-8 antibody， with the infection rate of 67.41%； and 95 were positive for HTLV-Ⅰ， with the infection rate of 42.41%. A total of 480 HIV negative visitors were tested. 7 patients were positive for EBV antibody， with the infection rate of 1.46%. 26 patients were infected with positive HHV-8 antibody， with the infection rate of 5.41%. 9 patients had positive HTIV-Ⅰ antibody， with the infection rate of 1.86%. The infection rates of the three carcinogenic viruses in HIV-infected patients were all higher than those in HIV-negative groups， and the differences were statistically significant （ P <0.05）. Conclusion There is a high prevalence of three highly carcinogenic viruses in HIV-infected patients and serious co-infection. It is necessary to improve the education of safe sex among HIV-infected patients and people with high risk of infection in order to curb the epidemic of HIV and other infectious diseases.

Analysis of carcinogenic virus infection in HIV-infected patients / 上海预防医学

Objective To investigate the status of carcinogenic infection in people infected with HIV and those with negative HIV test results in VCT clinics. To analyze the epidemiological characteristics and provide scientific basis for more targeted disease prevention and control strategies. Methods The serum levels of Epstein-Barr virus （EBV）， human herpesvirus type 8 （HHV-8） and human T-lymphotropic virus type Ⅰ （HTLV-Ⅰ） antibodies were detected by ELISA method in 224 HIV-infected patients and 480 HIV-negative visitors treated in VCT clinics during the same period from 2014 to 2017， to compare the differences in the infection rates of this virus between HIV-infected and HIV-negative individuals and to systematically analyze the correlation between viral infections and high-risk sexual behavior. Results Among the 224 HIV-infected patients， 79 were positive for EBV antibody， with the infection rate of 35.27%； 151 were positive for HHV-8 antibody， with the infection rate of 67.41%； and 95 were positive for HTLV-Ⅰ， with the infection rate of 42.41%. A total of 480 HIV negative visitors were tested. 7 patients were positive for EBV antibody， with the infection rate of 1.46%. 26 patients were infected with positive HHV-8 antibody， with the infection rate of 5.41%. 9 patients had positive HTIV-Ⅰ antibody， with the infection rate of 1.86%. The infection rates of the three carcinogenic viruses in HIV-infected patients were all higher than those in HIV-negative groups， and the differences were statistically significant （ P <0.05）. Conclusion There is a high prevalence of three highly carcinogenic viruses in HIV-infected patients and serious co-infection. It is necessary to improve the education of safe sex among HIV-infected patients and people with high risk of infection in order to curb the epidemic of HIV and other infectious diseases.

Prevalence of Epstein-Barr virus infection in individuals with nasopharyngeal carcinoma in Malaysia: The first systematic review and meta-analysis

@#Epstein-Barr virus (EBV) was the first herpesvirus associated to human malignancies. Despite the well-known association between EBV and malignancies, the prevalence of EBV infection in Malaysians with malignancies is unknown. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to conduct a systematic review and metaanalysis of published data in this study. Studies reporting the occurrence of EBV infection in Malaysian malignancy patients were searched in electronic databases like PubMed, Scopus, ScienceDirect, and Google Scholar without year or language constraints. The study protocol was filed in PROSPERO (CRD42021273769). A total of 21 studies were included, with 1,036 EBV infection cases among 2,078 malignancy patients. The random-effects model was used to produce summary estimates. The pooled prevalence of EBV infection in Malaysians with malignancy was 36.3% (95% CI, 20.3 – 56.2). When the prevalence estimates were stratified by malignancy type, nasopharyngeal carcinoma has the highest prevalence (90.5%), followed by lymphoma (23.4%), and gastric carcinoma (10.0%). Male patients had a higher cases prevalence and most patients were above the age of 40. In Malaysia, many malignancies are increasingly linked to EBV infection. Screening for EBV infection in malignancy patients is therefore important to determine disease recurrence and metastases.

Comparison of EB virus infection between short term and long term use of mycophenolate mofetil for prophylaxis of graft versus host disease after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective:To investigate the role of short-term use of mycophenolate mofetil (MMF) in EB viral infection and acute graft-versus host disease (GVHD) in patients receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) .Method:Adult patients (≥14 years) who were diagnosed with hematological malignancies received haplo-HSCT in Peking University Institute of Hematology from May 2016 to December 2017 were retrospectively reviewed. The median age was 30 (14-60) years old. A total of 498 patients including 277 males and 221 females were enrolled. Donors' median age was 38 (8-66) years old. All patients were classified into long-term use of MMF ( n=199), which was defined as 500 mg every 12 hours from day 9 pre-transplant to 250 mg every 12 hours from day 30 after transplant then withdrawal on day 45 to 60 after transplant, and short-term use of MMF ( n=299), which was defined as 500 mg every 12 hour from day 9 pre-transplant then withdrawal till neutrophil engraftment. Kaplan-Meier model was used to analyze the cumulative incidence of EBV infection, and the Cox proportional regression model for multivariate analysis. Result:Characteristics including sex, age, disease types, mismatched HLA loci, donor-recipient relationship, donor-recipient blood type, donor age, and donor sex were comparable between two groups (all P＞0.05). According to once, the incidence of EBV viremia, defined as EBV＞10 3 copies/ml at least once, in short-term group and long-term group was 19.4% (58/299) and 27.6% (55/199) respectively ( P=0.046).Donor age and the duration of MMF prophylaxis (short-term group as reference) were associated with EBV viremia according to multivariate analysis [ HR=1.022(95% CI 1.006-1.038),1.600(95% CI 1.059-2.418); P=0.006 and 0.026, respectively]. The incidence of grade Ⅱ-Ⅳ and Ⅲ/Ⅳ acute GVHD in long-term and short-term group was 32.2% (64/199) versus 20.7% (62/299)( P=0.005) and 10.1% (20/199) versus 8.0% (24/299) ( P=0.427), respectively. Donor sex (female as reference) and duration of MMF prophylaxis (short-term group as reference) were associated with grade Ⅱ-Ⅳ acute GVHD [ HR=1.908(95% CI 1.079-3.373),1.752(95% CI 1.161-2.643); P=0.026 and 0.008, respectively].There were no statistical differences in the incidence of CMV viremia, refractory CMV viremia and hemorrhagic cystitis (all P＞0.05) between the two groups. Conclusion:Short-term use of MMF can reduce EBV viremia without increasing the development of acute GVHD in haplo-HSCT patients.

Role of EphA2 in pathogenesis of nasopharyngeal carcinoma and its potential as a therapeutic target / 中国肿瘤临床

The erythropoietin-producing hepatocellular receptor (Eph) and its ligand ephrin are the largest of the receptor tyrosine kinases (RTKs) family in humans. Since ephrin ligands and Eph receptors are membrane-bound proteins, binding and activation of Eph/ephrin intracellular signaling pathways can only occur via direct cell-cell interaction. Eph-ephrin complexes emanate bidirectional signals that affect cells expressing Eph and ephrin, respectively. Its repulsive signaling effects include retraction, which plays an important role in many physiological and pathological processes. EphA2 has been found to have a strong association with tumors and is most widely studied. EphA2 signal transduction in tumor cells may promote or inhibit tumor, depending on the tumor microenvironment. EphA2 "canonical" signaling involves ligand binding and kinase activity; thus EphA2 "noncanonical" signaling is ligand independent and lacks kinase activity. This review summarizes the pathogenesis of EphA2 in nasopharyngeal carcinoma (NPC), including ligand independent signal and EBV infection receptor, furthermore evaluates the prospect of its potential utilization as a target for cancer therapeutics. This may provide a new method for the prevention and treatment of NPC.

Research progress on posttransplant lymphoproliferative disease after lung transplantation / 器官移植

Posttransplant lymphoproliferative disease (PTLD) is a fatal complication after lung transplantation, which is intimately associated with age, immunosuppression level and Epstein-Barr virus (EBV) infection, etc. Reducing immunosuppression level, rituximab therapy and T cell immunotherapy are common treatments for PTLD. With the rapid development of lung transplantation in China, PTLD after lung transplantation has attracted widespread attention. This article reviews the risk factors, pathological types, clinical manifestations, diagnosis, treatment, prognosis and prevention of PTLD after lung transplantation, aiming to provide reference for early monitoring and management of the incidence and progression of PTLD.

Progress on biomarkers of EB virus-related posttransplant lymphoproliferative disease / 器官移植

Posttransplant lymphoproliferative disease (PTLD) is a series of heterogeneous lymphoproliferative diseases and a severe complication after solid organ transplantation in children. Over 70% of PTLD is associated with Epstein-Barr virus (EBV). EBV-related B-cell lymphoma is also the main malignant tumor after pediatric organ transplantation. EBV-related PTLD is still a challenge in pediatric solid organ transplantation, which is mainly caused by immune function damage induced by immune suppression after transplantation. However, the specific mechanism remains elusive. In recent years, biomarkers have been developed to guide the diagnosis and individualized treatment of EBV-related PTLD, which possesses excellent application prospect. In this article, research progresses on the incidence of EBV-related PTLD in solid organ transplantation and its biomarkers were reviewed, aiming to explore novel ideas for clinical diagnosis and treatment.

EBV-positive diffuse large B-cell lymphoma, NOS, in a Filipino patient: Mimickers and essential ancillary studies

@#Epstein-Barr virus positive diffuse large B-cell lymphoma (EBV+ DLBCL) is prevalent among Asians but is underreported in the Philippine setting. We report the case of an 88-year-old male who presented with difficulty swallowing. CT scan showed an ill-defined soft tissue focus with calcifications in the supraglottic to hypopharyngeal region measuring approximately 2.6 x 1.7 x 1.5 cm, and multiple lymphadenopathies in the head and neck. Biopsy of the masses at the left tonsil, left arytenoid mucosa, pyriform sinus, and aryepiglottic fold showed large lymphoid cells with several Reed-Sternberg-like cells in a background of small lymphocytes, neutrophils, few eosinophils and histiocytes. A panel of immunohistochemical stains and EBER-ish were performed to differentiate among six entities that were morphologically similar to the patient’s case, namely, classic Hodgkin lymphoma, T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL), DLBCL, NOS, anaplastic variant, B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic HL (gray zone lymphoma), and infectious mononucleosis (IM). The neoplastic cells expressed CD20, CD30, CD45, PAX5, CD10, MUM-1, BCL6, BCL2, and c-myc, while CD3, CD15 and ALK-1 were negative. The cells of interest also showed nuclear staining (30-40%) on Epstein-Barr virus encoding RNA in-situ hybridization (EBER-ish). The Ki-67 showed a proliferation index of 40-50%. Given the differences in prognosis and treatment among these diseases, judicious use of immunostains and EBER-ish is recommended for accurate diagnosis.

Mediastinitis as a complication of Epstein-Barr virus infection: a rare entity

Epstein-Barr virus (EBV) is a member of the herpes virus family that can infect humans. Common manifestations of Epstein-Barr virus infection include fever, lymphadenopathy and pharyngitis with some rare complications including mediastinitis, myocarditis, pancreatitis, acute kidney failure and neurological disorders. Clinical findings along with serological evidences are needed to diagnose the infection. Early investigation for EBV in febrile patients can expedite both diagnosis and treatment.

Genotypes of Epstein-Barr virus (EBV1/EBV2) in individuals with infectious mononucleosis in the metropolitan area of Belém, Brazil, between 2005 and 2016

Abstract Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans. Although their genomes are similar, the regions containing the EBNA genes differ. This study aimed to characterize the EBV genotypes of infectious mononucleosis (IM) cases in the metropolitan region of Belém, Brazil, from 2005 to 2016. A total of 8295 suspected cases with symptoms/signs of IM were investigated by infectious disease physicians at Evandro Chagas Institute, Health Care Service, from January 2005 to December 2016. Out of the total, 1645 (19.8%) samples had positive results for EBV by enzyme immunoassay and 251 (15.3%) were submitted to polymerase chain reaction (PCR) technique, using the EBNA3C region, in order to determine the type of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were also performed. EBV type was identified by PCR in 30.3% (76/251) of individuals; of those, 71.1% (54/76) were classified as EBV1, 17.1% (13/76) as EBV2, and 11.8% (9/76) as EBV1+EBV2. The main symptoms/signs observed with EBV1 infection were cervical lymphadenopathy (64.8%, 35/54), fever (63%, 34/54), headache (20.4%, 11/54), arthralgia (20.4%, 11/54), and exanthema (18.5%, 10/54). EBV2 infection was detected in all but two age groups, with an average age of 24 years. The most common signs/symptoms of EBV2 were fever (76.9%, 10/13), average duration of 18 days, and lymphadenopathy (69.2%, 9/13). In contrast, EBV1+EBV2 coinfections were more frequent in those aged five years or less (20.0%, 2/10). The symptoms of EBV1+EBV2 coinfection included fever (66.7%, 6/9), and cervical lymphadenopathy and headache (33.3%, 3/9) each. The mean values of hepatic enzymes according to type of EBV was significantly different (p<0.05) in those EBV1 infected over 14 years of age. Thus, this pioneering study, using molecular methods, identified the EBV genotypes in 30.3% of the samples, with circulation of EBV1, EBV2, and EBV1+EBV2 co-infection in cases of infectious mononucleosis in the northern region of Brazil.

Single Patient Classifier Assay, Microsatellite Instability, and Epstein-Barr Virus Status Predict Clinical Outcomes in Stage II/III Gastric Cancer: Results from CLASSIC Trial

PURPOSE: Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer. MATERIALS AND METHODS: Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status. RESULTS: There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101–3.205), 2.399 (1.415–4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161–0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer. CONCLUSION: SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.

Primary subcutaneous lymphomatous granuloma: a case report and review of literature / 临床与实验病理学杂志

Purpose To investigate the clinicopathological features of primary subcutaneous lymphomatoid granulomatosis (LYG). Methods A case of primary subcutaneous LYG was observed by analysis of the clinical, histological features, immunophenotype and molecular pathology with review of the related literature. Results The male patient, 78-year-old, inadvertently found a mass of right axillary for more than 10 days. The boundary of the mass was clear, it seemed to have a capsule, the cut surface was grayish yellow and grayish red, the texture was medium. A large amount of coagulative necrosis was observed in the center of the mass under microscope. The peripheral area showed a morphological change of panniculitis, accompanied by pleomorphic lymphoid infiltration, showed central and vascular destructive infiltration, pathological mitosis was occasionally observed. Immunophenotyping showed that atypical large lymphoid cells expressed CD45 RB, CD20, CD30, while CD3, CD15, CD56, TIA-1, Granzyme B, ALK, CD21, Langerin and CD1 a, S-100 and CK (AE1/AE3) were negative. The proliferation index of Ki-67 ranged from 50％ to 60％. EBER in situ hybridization showed that positive cells were> 20/HPF.Neither acid fast staining nor TB-DNA testing supported tuberculosis. Molecular pathology found clonal Ig K gene rearrangement, TCRB + TCRG gene rearrangement showed the absence of monoclonal proliferating T cell population. Conclusion The primary subcutaneous LYG is a rare tumor. which can be diagnosed by combination of morphology, immunophenotype and molecular pathology.

Extranodal NK/T-cell lymphoma mimicking Crohn’s colitis

@#Introduction: Extranodal NK/T cell lymphoma is a rare tumour, typically involving the upper aerodigestive tract. Even rarer is primary extranasal disease involving the skin, testis, soft tissue and gastrointestinal tract. Case Report: We report a case of a 46-year-old Chinese male who presented with six months history of abdominal pain, weight loss and rectal bleeding. Diagnostic colonoscopy revealed multiple aphthous ulcers within the ileo-caecal region and distal transverse colon, separated by normal mucosa, mimicking skip lesions of Crohn’s colitis. Computer topography (CT) scan of the abdomen showed multiple circumferential thickenings involving predominantly the right colon. A clinical diagnosis of colonic Crohn’s disease with possible perforation was made. An extended right hemicolectomy was performed due to uncontrolled rectal bleeding. Histopathology examination of the colon showed infiltration by malignant lymphoid cells associated with necrosis, angiocentricity and angiodestruction. Immunohistochemical studies confirmed T-cell monoclonality, presence of cytotoxic granules and Epstein-Barr virus (EBV) infection. A diagnosis of extranodal NK/T cell lymphoma of the colon was made. Discussion: These findings highlight that colonic NK/T cell lymphoma may clinically mimic other benign inflammatory lesions and should be one of the differential diagnoses in patients presenting with gastrointestinal lesions. The final diagnosis is only possible with appropriate histological and immunohistochemical studies.