Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT.

BACKGROUND: Hepatitis C virus (HCV) infection is frequently associated with B-cell non-Hodgkin's lymphomas. We investigated the prevalence of HCV infection in nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) in order to define the relationship between the viral infection and the presenting features, treatment, and outcome. METHODS: We retrospectively studied 172 patients with a histological diagnosis of marginal zone B-cell lymphoma of MALT, except for stomach, and with available HCV serology, among a series of 208 patients. RESULTS: HCV infection was documented in 60 patients (35%). Most HCV-positive patients (97%) showed a single MALT organ involvement. HCV-positive patients showed a more frequent involvement of skin (35%), salivary glands (25%), and orbit (15%). The majority of stage IV HCV-positive patients (71%) had a single MALT site with bone marrow involvement. The overall response rate was similar in HCV-positive (93%) and HCV-negative patients (87%). Overall survival (OS) and event-free survival (EFS) did not differ according to HCV infection. In multivariate analysis, advanced disease (stage III-IV) was associated with a poorer OS (P = 0.0001), irrespective of HCV serostatus. CONCLUSIONS: This study shows that nongastric marginal zone lymphomas are characterized by a high prevalence of HCV infection. Patients with involvement of a single MALT site have the highest prevalence of HCV. HCV-positive nongastric lymphomas of MALT show an indolent course similar to HCV-negative patients and seem an ideal target for exploiting the antilymphoma activity of antiviral treatments.     

Lymphomas associated with chronic hepatitis C virus infection: A prospective multicenter cohort study from the Rete Ematologica Lombarda (REL) clinical network

Chronic hepatitis C virus (HCV) infection is related with an increased risk of non‐Hodgkin lymphomas (NHL). In indolent subtypes, regression of NHL was reported after HCV eradication with antiviral therapy (AT). In 2008 in Lombardy, a region of Northern Italy, the “Rete Ematologica Lombarda” (REL, Hematology Network of Lombardy—Lymphoma Workgroup) started a prospective multicenter observational cohort study on NHL associated with HCV infection, named “Registro Lombardo dei Linfomi HCV‐positivi” (“Lombardy Registry of HCV‐associated non‐Hodgkin lymphomas”). Two hundred fifty patients with a first diagnosis of NHL associated with HCV infection were enrolled; also in our cohort, diffuse large B cell lymphoma (DLBCL) and marginal zone lymphoma (MZL) are the two most frequent HCV‐associated lymphomas. Two thirds of patients had HCV‐positivity detection before NHL; overall, NHL was diagnosed after a median time of 11 years since HCV survey. Our data on eradication of HCV infection were collected prior the recent introduction of the direct‐acting antivirals (DAAs) therapy. Sixteen patients with indolent NHL treated with interferon‐based AT as first line anti‐lymphoma therapy, because of the absence of criteria for an immediate conventional treatment for lymphoma, had an overall response rate of 90%. After a median follow‐up of 7 years, the overall survival (OS) was significantly longer in indolent NHL treated with AT as first line (P = 0.048); this confirms a favorable outcome in this subset. Liver toxicity was an important adverse event after a conventional treatment in 20% of all patients, in particular among DLBCL, in which it is more frequent the coexistence of a more advanced liver disease. Overall, HCV infection should be consider as an important co‐pathology in the treatment of lymphomas and an interdisciplinary approach should be always considered, in particular to evaluate the presence of fibrosis or necroinflammatory liver disease.     

Clinical outcome in diffuse large B-cell lymphoma with hepatitis C virus infection in the rituximab era: a single center experience

Clinical outcome of diffuse large B-cell lymphoma (DLBCL) patients with hepatitis C virus (HCV) infection in the rituximab era remains unclear. The aim of the present study was to compare the clinical outcome, treatment response and hepatotoxicity in DLBCL patients who received rituximab containing immunochemotherapy that had HCV infection and those that did not have HCV infection between January 2004 and October 2011. Of the 272 consecutive histopathologically diagnosed DLBCL patients in our department, a total of 248 were retrospectively analyzed in the present study. There were 28 DLBCL patients with HCV infection (the HCV group) and 220 DLBCL patients without HCV infection (the control group). We compared overall survival (OS), progression-free survival (PFS), treatment response and hepatotoxicity according to HCV infection. In terms of OS (P=0.525) and PFS (P=0.759), there were no significant differences between the HCV group and the control group. Objective response rates were 92.9% (26/28) in the HCV group and 95.9% (211/220) in the control group (P=0.619). In the HCV group, seven patients (25.0%) developed hepatotoxicity during immunochemotherapy. In the control group, 35 patients (15.9%) developed hepatotoxicity during chemotherapy. No patient required discontinuation of immunochemotherapy owing to hepatotoxicity in either group. In terms of hepatotoxicity, there was no significant difference between these two groups (P=0.281). In conclusion, our study results suggested that HCV infection might not influence the clinical course in DLBCL patients who receive rituximab-containing immunochemotherapy.     

Clinical characteristics and outcome for hepatitis C virus-positive diffuse large B-cell lymphoma

Several previous studies have addressed the association between hepatitis C virus (HCV) infection and non-Hodgkin lymphoma (NHL), but there are few studies on HCV-related diffuse large B-cell lymphoma (DLBL). We conducted this retrospective study to investigate the distinctive clinical characteristics and outcome for HCV-positive DLBL. We compared the clinical characteristics and outcomes of 32 HCV-positive DLBL cases from nine Korean institutions with those of 371 HCV-negative DLBL cases. A higher percentage of HCV-positive DLBL cases were associated with old age (≥60) than HCV-negative DLBL cases at diagnosis (59.4% vs. 36.1%, respectively, P = 0.009) and HCV-positive cases were less likely than HCV-negative cases to have extranodal involvement (53.1% vs. 71.1%, respectively, P = 0.044). The nodal presentation was the only independent factor favorably influencing the event free survival (EFS) in HCV-positive DLBL (HR = 0.11, 95% CI; 0.01 - 0.95, P = 0.012). In comparison to patients with HCV-negative DLBL, HCV-positive DLBL patients had a superior complete response rate (P = 0.023) and EFS (P = 0.02). In Korean patients, HCV-positive DLBL is more common with old age and has less extranodal involvement than does HCV-negative DLBL. The superior survival outcome for HCV-positive DLBL should be verified by further investigation, especially with respect to its correlation with transformed low-grade NHL.     

Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi

BackgroundTumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL).Patients and methodsWe carried out a cohort study of 704 consecutive HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control.ResultsFor entire cohort, 5-year overall survival (OS) was 78% [95% confidence interval (CI): 74%–82%] and 5-year progression-free survival (PFS) was 48% (95% CI: 44%–53%). In multivariate analysis, the use of AT during the patients’ life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%–73%). CR + PR rate was 85% with AT as second-line treatment.ConclusionAT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.     

Comparison of peripheral T-cell lymphomas and diffuse large B-cell lymphoma

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are a biologically heterogeneous subgroup of lymphomas with poor prognosis. In this study, the authors analyzed the clinical behaviors of PTCLs and diffuse large B-cell lymphoma (DLBCL). METHODS: The authors compared the characteristics and outcomes of 59 patients with PTCLs, including 33 angioimmunoblastic T-cell lymphomas and 26 unspecified peripheral T-cell lymphomas, with the characteristics and outcomes of 193 patients with DLBCLs who were treated in the era before rituximab. RESULTS: Based on the clinical characteristics, elevated lactate dehydrogenase (LDH), poor PS, advanced stage, higher International Prognostic Index score, and B symptoms were more common in patients with PTCLs, and bulky mass was more common in patients with DLBCL. The rates of complete response (CR) or an unconfirmed CR (CRu) were higher in patients with DLBCL (72%) than in patients with PTCLs (56%; P = .03). The 5-year overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) rates were 31%, 26%, and 47%, respectively, in patients with PTCLs and 59%, 55%, and 73%, respectively, in patients with DLBCL (P = .001, P < .001, and P = .003, respectively). Although multivariate analysis identified several risk factors that were significant in PTCLs, but not in DLBCLs, for the CR/CRu, OS, PFS, and DFS rates, the immunophenotype was not identified as a risk factor. CONCLUSIONS: The poor response and survival of patients who had PTCLs, compared with patients who had DLBCL, was caused by numerous initial risk factors. T-cell phenotype itself did not appear to have a significant impact on either response or survival.     

HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and open questions

There is plenty of data confirming that hepatitis C virus (HCV) infection is a predisposing factor for a B-cell non-Hodgkin’s lymphoma (B-NHL) outbreak, while relatively few reports have addressed the role of HCV in affecting B-NHL patients’ outcome. HCV infection may influence the short-term outcome of B-NHL because of the emergence of severe hepatic toxicity (HT) during immunochemotherapy. Furthermore, the long term outcome of HCV-related liver disease and patients’ quality of life will possibly be affected by Rituximab maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic stem cell transplantation. In this review, data dealing with aggressive and low-grade B-NHL were separately analyzed. The few retrospective papers reporting on aggressive B-NHL patients showed that HCV infection is a risk factor for the outbreak of severe HT during treatment. This adverse event not infrequently leads to the reduction of treatment density and intensity. Existing papers report that low-grade B-NHL patients with HCV infection may have a more widespread disease, more frequent relapses or a lower ORR compared to HCV-negative patients. Notwithstanding, there is no statistical evidence that the prognosis of HCV-positive patients is inferior to that of HCV-negative subjects. HCV-positive prospective studies and longer follow-up are necessary to ascertain if HCV-positive B-NHL patients have inferior outcomes and if there are long term sequels of immunochemotherapies on the progression of liver disease.     

Epstein‐Barr virus‐positive diffuse large B‐cell lymphoma association is not only restricted to elderly patients

Diffuse large B‐cell lymphoma (DLBCL), the most common group of malignant lymphomas, account for 30% of adult non‐Hodgkin lymphomas. The 2008 World Health Organization (WHO) classification included a new entity, Epstein‐Barr virus (EBV)+ DLBCL of the elderly, affecting patients aged 50 years or older. However, some reports of younger EBV+ DLBCL cases, without evidence of underlying immunosuppression, can be found. The role of EBV in tumor microenvironment composition in DLBCL is still not well understood. Our aim was to assess EBV presence and latency pattern as well as tumor T‐cell population in an adult DLBCL series of Argentina. The study was conducted on biopsies from 75 DLBCL patients. EBERs expression was performed by in situ hybridization, while EBV gene expression was analyzed using real‐time polymerase chain reaction. LMP1, LMP2A, EBNA2, EBNA3A, CD4, CD8 and Foxp3 expression was assessed by immunohistochemistry. Nine percent of cases showed EBV expression, with similar frequency among patients younger than 50 years and 50 years or older (13% and 8%, respectively). T‐cell subsets were not altered by EBV presence. Latency type II was the most frequently observed, together with lytic gene expression in EBV+ DLBCL, with ≥20% of EBERs+ cells. These findings suggest that EBV+ DLBCL in our series was similar to the previously described in Asia and Latin‐America, displaying latency II or III expression profile and no age‐specific characteristics. Finally, EBV+ DLBCL may be an entity that is not only restricted to patients who are older than 50 years of age, in consequence the age cutoff revision may be a current goal.     

Metal contents in the liver of patients with chronic liver disease caused by hepatitis C virus. Reference to hepatocellular carcinoma

BACKGROUND/AIMS: The aim of this study was to investigate the relationship between trace metals and the prevalence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis or hepatic cirrhosis caused by hepatitis C virus (HCV). METHODS: We measured the contents of copper, iron, and zinc in HCC tissue (n = 112), dysplastic nodules (n = 7), and liver parenchyma in patients with (n = 112) and without (n = 12; 7 with grade F3 fibrosis, 5 with grade F4 fibrosis) HCC. Metals were quantified in thin-needle biopsy specimens using the particle-induced X-ray emission method (PIXE). RESULTS: Copper level in liver parenchyma was higher in patients with HCC than in those without HCC (p < 0.01), while there was no such difference in hepatic iron. In patients with grade F4 fibrosis, copper content in the liver parenchyma was higher in the presence of HCC than in its absence (p < 0.05). Multiple regression analysis showed that the only factor significantly associated with the coexistence of HCC in HCV-positive patients with chronic liver disease was the copper level in the liver parenchyma. CONCLUSIONS: Hepatic copper overload may contribute to the development of HCC in HCV-positive patients with chronic hepatitis or cirrhosis.     

Clinical implications of hepatitis C virus infection in MALT-type lymphoma of the ocular adnexa.

BACKGROUND: A pathogenic link between hepatitis C virus (HCV) and MALT-type lymphomas has been suggested. However, studies assessing the role of HCV infection separately in different forms of MALT lymphomas are not available. PATIENTS AND METHODS: The prevalence and clinical implications of HCV seropositivity were analyzed in 55 patients with ocular adnexa lymphoma (OAL) of MALT-type. RESULTS: HCV seropositivity was detected in seven (13%) patients. At presentation, HCV infection was significantly associated with concomitant extra-orbital disease, lymph node dissemination and involvement of additional extranodal organs. HCV seropositivity was associated also with a higher relapse rate and worse progression-free survival. In fact, 16 patients experienced relapse after first-line treatment: five (71%) were HCV-seropositive and 11 (23%) were HCV-seronegative, with a median TTP of 31 and 50+ months (P = 0.01), and a 5-year progression-free survival of 43 +/- 18% and 77 +/- 7% (P = 0.005), respectively. HCV-seropositive patients experienced frequent relapses despite further lines of therapy; relapses were systemic in all cases but one; multiple subcutaneous nodules were common at relapse. CONCLUSIONS: HCV seropositivity is present in 13% of OAL of MALT-type. Concomitant HCV infection is associated with more disseminated disease and aggressive behavior in OAL, with a consequent potential negative impact in patients managed with radiotherapy alone.     

Clinical,Epidemiological and Histopathological Aspects in Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation

Background: Hepatocellular Carcinoma (HCC) is the primary liver cancer with high incidence and mortality rates.Currently one of the major etiologies for liver disease, HCC and liver transplantation is nonalcoholic fatty liver disease(NAFLD). The aim of the present study was to evaluate the epidemiological, histopathological and clinical aspects ofHCC transplant patients, with emphasis on NAFLD etiology. Methods: This study included all HCC patients submittedto liver transplantation from 2010 to 2016 of the University Reference Center. The analyzed variables were age, gender,ethnicity, causes that led to liver transplantation, alpha-fetoprotein (AFP) dosage, histological aspects, recurrence,survival and NAFLD. Results: A total of 60 patients were included in the study being 80% men with a mean age of58.3 ± 10.6 years. All patients were cirrhotic. The causes that led to the transplantation were the presence of the hepatitisC virus (HCV) (56.6% of the patients), an association of the virus with alcohol (20%), the presence of the hepatitis Bvirus (HBV) (20%), alcoholic liver disease (ALD) (50.9%) and NAFLD (25%). Of the latter, eight were diagnosedpre-transplantation and seven were NAFLD carriers without a previous diagnosis. Regarding the Edmondson-Steinerhistological classification, 58.5% of the patients were classified as grade ≤ II. Conclusions: There is predominance ofmale patients with a mean age of 58.3 years. Degree ≤ II is the most frequent to the Edmondson-Steiner histologicalclassification in the evaluated casuistic. HCV, ALD and NAFLD is the most common etiological agents found in thestudy. The (high) underestimated prevalence of NAFLD in the pre-transplanted patients is due to the fact that all patientspresented cirrhosis, masking NAFLD signals.     

Prevention of intrahepatic recurrence by adjuvant (131)iodine-labeled lipiodol after resection for hepatocellular carcinoma in HCV-related cirrhosis.

AIM: To evaluate the impact of postoperative injection into the hepatic artery of 131-iodine-labeled lipiodol on disease-free and overall survival rates in patients who underwent liver surgical resection for hepatocellular carcinoma. METHODS: Ten consecutive patients with HCV (hepatitis C virus)-related cirrhosis who underwent liver surgical resection for hepatocellular carcinoma were treated with adjuvant injection of 131-iodine-labeled lipiodol. They were matched with 20 HCV-positive cirrhotic controls who underwent liver resection alone; patients were paired in terms of age, Child-Pugh class, tumor size, microscopic vascular invasion, tumor histological pattern, presence of satellite nodules and type of surgical resection. Recurrence was defined as the development of a new hypervascularizated nodule in the liver. RESULTS: No significant differences were found between the two groups in clinical, biologic and histologic characteristics, except a lower platelet count in the control group. None of the treated patients developed an intrahepatic recurrence until the 15th month from liver resection, whereas recurrences occurred in nine of the 20 patients in the control group (p=0.01). From 18 months onwards, recurrences appeared also in the treated patients, and after 36 months of follow-up both recurrence rate and overall survival were not significantly different between the two groups. CONCLUSIONS: Intrahepatic injection of 131-iodine-labeled lipiodol improves the disease-free survival rate following liver resection of hepatocellular carcinoma in the short term up to 15 months; this advantage fades, however, away after 36 months.     

Large Cell Lymphoma: Correlation of HIV Status and Prognosis with Differentiation Profiles Assessed by Immunophenotyping

Diffuse large B cell lymphoma (DLBCL) and plasmablastic lymphoma (PBL) represent aggressive non-Hodgkin lymphomas, particularly in the setting of HIV infection. Since the introduction of highly active antiretroviral therapy (HAART), recent studies have documented improved survival outcome in patients with AIDS-related lymphomas. This study contributes a South African perspective by correlating the HIV status and prognosis of DLBCL and PBL with differentiation profiles assessed by immunophenotyping. Analysis of the morphologic, immunophenotypic and clinicopathologic features of 52 cases of DLBCL and 9 cases of de novo PBL was performed. The overall survival of patients with PBL was poorer than that of DLBCL (logrank p value 0.002). Despite HAART, the overall survival with DLBCL and HIV infection was significantly poorer than HIV negative patients with DLBCL (p value <0.001). Profound immunosuppression was evident in the HIV positive group as the mean CD4 count was 151 cells/mm³ in DLBCL and 61 cells/mm³ in PBL. HIV positive patients were significantly younger at presentation with greater likelihood of extranodal lymphoma. When Hans’ and Muris’ algorithmic stratification of DLBCL were applied, no statistical significance was demonstrated (p values 0.188 and 0.399 respectively). However, when Bcl-2 expression occurred in germinal center-type DLBCL (Hans’ defined), improved survival was conferred by the germinal center immunophenotype (p value 0.007). The study demonstrates that DLBCL and PBL have significant potential for aggressive behaviour and poor outcome in the setting of profound immunosuppression due to HIV infection. Further studies are required to assess the effect of targeted-immunotherapy (Rituximab) in combination with recent amendment of the South African national antiretroviral treatment guidelines which has created tremendous potential for improved survival in patients with AIDS-related non-Hodgkin B-cell lymphomas.     

Prospective study on the risk of hepatocellular carcinoma among hepatitis C virus-positive blood donors focusing on demographic factors, alanine aminotransferase level at donation and interaction with hepatitis B virus

The risk for hepatocellular carcinoma (HCC) among asymptomatic hepatitis C virus (HCV) carriers is not well understood. A community-based prospective study was conducted for over 8 years by record linkage to the Osaka Cancer Registry. The subjects were 1,927 individuals who were positive for anti-HCV through screening for second-generation HCV antibody (passive hemagglutination assay: >or= 2(12)) in voluntary blood donation. The risk factors for HCC and interaction between HCV and hepatitis B virus (HBV) infection were evaluated by including additional blood donors: 2,519 individuals positive for hepatitis B virus surface antigen (HBsAg) alone, 25 positive for both anti-HCV and HBsAg, 150,379 negative for both anti-HCV and HBsAg. The incidence of HCC (/10(5) person-years) among the HCV-positive individuals increased with age in both genders, ranging from 68 to 1,306 among those aged 45-74 years. In the HCV-positive individuals, the cumulative risk of developing HCC between the ages of 40 and 74 year was 21.6% among males and 8.7% among females. A stepwise increase in risk was noted as the serum alanine aminotransferase level increased or serum cholesterol level at baseline decreased in multivariate Cox proportional hazard analysis. The 9-year cumulative incidence of HCC among individuals positive for HCV alone, those positive for HBsAg alone and those positive for both was 3.0%, 2.0% and 12.0%, respectively. The age-and-sex-adjusted rate ratio was 126, 102 and 572, respectively, when those negative for both were used as a reference. The results demonstrate an increased risk for HCC among asymptomatic HCV-positive individuals in Japan. Coinfection with HBV and HCV carried a superadditive risk for HCC.     

Epidemiology of viral hepatitis infections in an area of southern Italy with high incidence rates of liver cancer

Southern Italy shows the highest rates of liver cancer for Europe, mainly related to infection with hepatitis viruses. We thus described incidence rates of liver cancer and investigated prevalence and determinants of HCV and HBV infections in 4496 individuals randomly selected from the general population of the province of Naples. 7.5% was infected with HCV and 27.6% with HBV (2.2% was HBsAg-positive). Prevalence of both infections increased with age, 23.2% of those aged 65 years or older was HCV-positive and 47.9% were HBV-positive. Intravenous drug use (odds ratio (OR)=16.4 for anti-HCV and 4.7 for anti-HBc), history of blood transfusions (OR=2.8 and 1.5, respectively) and surgery, and household contacts with infected people (OR=2.1 and 1.6, respectively) increased risks for both infections. Sexual intercourse with HCV-positive individuals conveyed a 3-fold higher risk of HCV infection. This study quantified the spread of HCV and HBV in the population of southern Italy heavily affected by liver cancer.     

Focal liver lesions in non-Hodgkin's lymphoma: investigation of their prevalence,clinical significance and the role of Hepatitis C virus infection

Imaging techniques like ultrasonography (US) or computed tomography (CT) allow full liver scanning and the accurate detection of focal lesions of the liver parenchyma. The occurrence of such lesions in concomitance with non-Hodgkin's lymphoma (NHL), both at the onset of the disease and during follow-up, is of great significance, because it affects staging, prognosis and therapeutic choices. Moreover, the occurrence of focal liver lesions in the setting of a lymphoma is generally considered to be a marker of liver involvement. Nonetheless, data on the prevalence and clinical significance of focal liver lesions occurring in these clinical conditions are limited. Therefore, we retrospectively evaluated the prevalence, nature and clinical significance of focal liver lesions diagnosed by imaging techniques (US and CT) in 414 consecutive NHL patients. The nature of the lesions was established either by US-guided biopsy or by evaluation of the response to chemotherapy for the underlying disease and confirmed by clinical and US follow-up. Subtype of NHL (aggressive or indolent) and Hepatitis C virus (HCV) status were also considered. We detected 129 focal liver lesions (76 at onset and 53 during the follow-up). Hepatic involvement by NHL was found in 69 cases (53%). We observed 7 cases of Hepatocellular Carcinoma (HCC) and 3 cases of metastasis. At onset, only 39% of the detected lesions were due to lymphoma and 58% were benign. Conversely, 74% of the liver lesions detected during the follow-up were due to NHL while 15% to a malignancy other than NHL. All HCC cases occurred in HCV-positive patients with chronic liver disease. We concluded that the focal liver lesions detected at onset in NHL patients are frequently benign and unrelated to the underlying disease. Conversely, most focal liver lesions detected during the follow-up period are malignant and the possibility of HCC occurrence in HCV-positive patients should always be considered. Therefore, these lesions should undergo a full diagnostic work-up, including US-guided biopsy.     

Type Distribution of Lymphomas in Lebanon: Five-Year Single Institution Experience

Background: Lymphomas represent the fifth most frequent cancer in Lebanon. However, little is knownconcerning epidemiologic characteristics and distribution of lymphoid neoplasms according to the 2008 WHOclassification. Materials and Methods: We conducted a retrospective study of lymphoma cases diagnosed from2008 till 2012 at Hôtel-Dieu de France University Hospital. Results: A total of 502 new cases of lymphoma werediagnosed at our institution during a five year period: 119 cases (24%) were Hodgkin lymphomas (HL) and 383cases (76%) were non-Hodgkin lymphomas (NHL). HLs were equally distributed in both sexes with a meanage at diagnosis of 30 years. Among NHL, 87% (332 cases) were B cell lymphomas, 9% (34 cases) were T celllymphomas and 4%(17 cases) were classified as precursor lymphoid neoplasms. Among B cell lymphomas,44% (147 cases) were diffuse large B cell lymphomas (DLBCL), 20% (65 cases) follicular lymphomas and 8%(27 cases) mantle cell lymphomas. DLBCL were equally distributed in both sexes with a mean age of 58 years.Follicular lymphomas were characterized by a male predominance (57%) and a mean age of 60 years. Mantlecell lymphomas showed a pronounced male predominance (85%) with a mean age of 60 years in men and 70years in women. Some 72% of patients having T cell lymphomas were men, with a mean age of 57 years in menand 45 years in women, while 65% of patients having precursor lymphoid neoplasms were women with a meanage of 22 years in women and 30 years in men. Conclusions: The lymphoma subtype distribution in Lebanon isunique when compared to other countries from around the world. In fact, Hodgkin and follicular lymphomasare more frequent than in most Far Eastern, European and American countries, while T-cell lymphomas andDLBCL are less frequent.     

Promoter hypermethylation of the bone morphogenetic protein-6 gene in malignant lymphoma.

PURPOSE: Bone morphogenetic proteins (BMP), belonging to the transforming growth factor-beta superfamily, are important regulators of cell growth, differentiation, and apoptosis. The biological effects of BMPs on malignant lymphoma, however, remain unknown. Promoter methylation of the BMP-6 gene in lymphomas was investigated. EXPERIMENTAL DESIGN: We investigated BMP-6 promoter methylation and its gene expression in various histologic types of 90 primary lymphomas and 30 lymphoma cell lines. The effect of BMP-6 promoter hypermethylation on clinical outcome was also evaluated. RESULTS: BMP-6 was epigenetically inactivated in subsets of lymphomas. The silencing occurred with high frequency in diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma in association with aberrant BMP-6 promoter methylation. The methylation was observed in 60% (21 of 35) of DLBCL cases and 100% (7 of 7) of DLBCL cell lines, and in 83% (5 of 6) of Burkitt's lymphoma cases and 86% (12 of 14) of Burkitt's lymphoma cell lines. In contrast, other histologic types of primary lymphomas studied had little or no detectable methylation (1 of 49; 2%). The presence of BMP-6 promoter hypermethylation in DLBCL statistically correlated with a decrease in disease-free survival (P = 0.014) and overall survival (P = 0.038). Multivariate analysis showed that the methylation profile was an independent prognostic factor in predicting disease-free survival (P = 0.022) and overall survival (P = 0. 046). CONCLUSION: BMP-6 promoter was hypermethylated more often in aggressive types of lymphomas, and the hypermethylation is likely to be related to the histologic type of lymphomas. BMP-6 promoter methylation may be a potential new biomarker of risk prediction in DLBCL.     

Hepatitis C infection and risk of malignant lymphoma

The association between hepatitis C virus (HCV) infection and risk of malignant lymphoma remains controversial, perhaps due to small-sized studies and low prevalence of HCV in the general population. On the basis of a large Danish-Swedish population-based case-control study, 2,819 lymphoma patients and 1,856 controls of second-generation Danish-Swedish origin were screened for HCV infection using an enzyme-linked immunosorbent assay and a confirming recombinant immunoblot assay (RIBA) test. Positive samples were tested with real-time PCR for the presence of HCV RNA. The association between HCV infection and risk of malignant lymphoma was assessed by logistic regression. When intermediate RIBA test results were interpreted as positive, anti-HCV antibody positivity was associated with a nonsignificant increased risk of non-Hodgkin lymphoma (NHL) overall (odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.9-5.3; n = 20 cases), of B-cell lymphomas combined (OR = 2.4 [1.0-5.8]; n = 20) and of lymphoplasmacytic lymphoma (OR = 5.2 [1.0-26.4]; n = 2). No patients with T-cell or Hodgkin lymphoma were HCV-positive. A more conservative definition of HCV positivity (disregarding intermediate RIBA results) resulted in an OR = 1.6 (0.3-8.5; n = 5) for NHL overall. When the definition was further restricted to require HCV RNA positivity, OR was 1.7 (0.2-16.2; n = 3) for NHL overall. Our findings from a population with a low prevalence of HCV suggest a positive association between HCV and risk of NHL, in particular of B-cell origin.