Analysis of hepatitis B virus infection in 1424 patients with different pathological types of lymphoma (2018-2022): A real-world, retrospective study.

OBJECTIVE: Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non-Hodgkin's lymphoma (NHL), especially B-cell non-Hodgkin's lymphoma (B-NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes. METHODS: The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression-free survival (PFS), and overall survival (OS) of HBV-positive and negative B-NHL subtypes were compared according to HBV infection. RESULTS: The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p < 0.05). The HBV infection rate in the B-NHL was higher than that in the T-cell non-Hodgkin's lymphoma (T-NHL) (8.14% vs. 4.95%). The HBV infection rate in the aggressive B-NHL was similar to that of the indolent B-NHL (8.30% vs. 7.88%), and the highest HBV infection rates were found in diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, but no significant differences in clinical characteristics, PFS, and OS were seen between HBV-positive and negative patients in the two subtypes. CONCLUSIONS: There was an association between HBV infection and the development of NHL and HBV infection may play a role in the pathogenesis of B-NHL, but not T-NHL.

Next-Generation Sequencing as an Auxiliary Tool in Pediatric Laryngeal Lymphoma Diagnosis.

Lymphomatous involvement of the larynx is a rare entity. We present a case of atypical laryngotracheitis as the initial manifestation of non-Hodgkin's lymphoma in a pediatric patient. The diagnosis was aided through the use of microbial cell-free DNA (mcfDNA) testing, which detected the presence of Epstein-Barr virus in the patient's plasma. This enabled the consideration of an Epstein-Barr virus-related lymphoproliferative process, leading to additional workup and the final diagnosis of lymphoma. To our knowledge, this is the first case of mcfDNA testing leading not simply to an infectious organism, but further to a new oncologic diagnosis. Plasma mcfDNA testing has the potential to inform clinical practice beyond classic infectious disease manifestations. In this article, we review both the possible future applications and the areas of further investigation that remain.

Long-Term Evolution of SARS-CoV-2 in an Immunocompromised Patient with Non-Hodgkin Lymphoma.

Recent studies have shown that persistent SARS-CoV-2 infections in immunocompromised patients can trigger the accumulation of an unusual high number of mutations with potential relevance at both biological and epidemiological levels. Here, we report a case of an immunocompromised patient (non-Hodgkin lymphoma patient under immunosuppressive therapy) with a persistent SARS-CoV-2 infection (marked by intermittent positivity) over at least 6 months. Viral genome sequencing was performed at days 1, 164, and 171 to evaluate SARS-CoV-2 evolution. Among the 15 single-nucleotide polymorphisms (SNPs) (11 leading to amino acid alterations) and 3 deletions accumulated during this long-term infection, four amino acid changes (V3G, S50L, N87S, and A222V) and two deletions (18-30del and 141-144del) occurred in the virus Spike protein. Although no convalescent plasma therapy was administered, some of the detected mutations have been independently reported in other chronically infected individuals, which supports a scenario of convergent adaptive evolution. This study shows that it is of the utmost relevance to monitor the SARS-CoV-2 evolution in immunocompromised individuals, not only to identify novel potentially adaptive mutations, but also to mitigate the risk of introducing "hyper-evolved" variants in the community. IMPORTANCE Tracking the within-patient evolution of SARS-CoV-2 is key to understanding how this pandemic virus shapes its genome toward immune evasion and survival. In the present study, by monitoring a long-term COVID-19 immunocompromised patient, we observed the concurrent emergence of mutations potentially associated with immune evasion and/or enhanced transmission, mostly targeting the SARS-CoV-2 key host-interacting protein and antigen. These findings show that the frequent oscillation in the immune status in immunocompromised individuals can trigger an accelerated virus evolution, thus consolidating this study model as an accelerated pathway to better understand SARS-CoV-2 adaptive traits and anticipate the emergence of variants of concern.

Chronic viral hepatitis, HIV infection and Non-Hodgkin lymphomas in West Africa, a case-control study.

Non-Hodgkin lymphomas (NHL) are underestimated causes of cancer in West Africa where chronic viral hepatitis and HIV are endemic. While the association with HIV infection has already been characterized, limited information is available on the association between chronic viral hepatitis and NHL in sub-Saharan Africa. A case-control study was conducted in referral hospitals of Abidjan (Cote d'Ivoire) and Dakar (Senegal). Cases of NHL were matched with controls on age, gender and participating site. The diagnosis of NHL relied on local pathological examination completed with immunohistochemistry. HIV, HBV and HCV serology tests were systematically performed. A conditional logistic regression model estimated the associations by the Odds Ratio (OR) with their 95% confidence interval (CI). A total of 117 NHL cases (Abidjan n = 97, Dakar n = 20) and their 234 matched controls were enrolled. Cases were predominantly men (68.4%) and had a median age of 50 years (IQR 37-57). While Diffuse Large B-cell lymphoma were the most reported morphological type (n = 35) among mature B-cell NHL, the proportion mature T-cell NHL (30%) was high. The prevalence figures of HBV, HCV and HIV infection were 12.8%, 7.7% and 14.5%, respectively among cases of NHL. In multivariate analysis, HBV, HCV and HIV were independently associated with NHL with OR of 2.23 (CI 1.05-4.75), 4.82 (CI 1.52-15.29) and 3.32 (CI 1.54-7.16), respectively. Chronic viral hepatitis B and C were significantly associated with NHL in West Africa. Timely preventive measures against HBV infection and access to curative anti-HCV treatment might prevent a significant number of NHL.

Use of pembrolizumab with or without pomalidomide in HIV-associated non-Hodgkin's lymphoma.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is currently the most common malignancy among people living with HIV (PLWH) in the USA. NHL in PLWH is more frequently associated with oncogenic viruses than NHL in immunocompetent individuals and is generally associated with increased PD-1 expression and T cell exhaustion. An effective immune-based second-line approach that is less immunosuppressive than chemotherapy may decrease infection risk, improve immune control of oncogenic viruses, and ultimately allow for better lymphoma control. METHODS: We conducted a retrospective study of patients with HIV-associated lymphomas treated with pembrolizumab±pomalidomide in the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute. RESULTS: We identified 10 patients with stage IV relapsed and/or primary refractory HIV-associated NHL who were treated with pembrolizumab, an immune checkpoint inihibitor, with or without pomalidomide. Five patients had primary effusion lymphoma (PEL): one had germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL); two had non-GCB DLBCL; one had aggressive B cell lymphoma, not otherwise specified; and one had plasmablastic lymphoma. Six patients received pembrolizumab alone at 200 mg intravenously every 3 weeks, three received pembrolizumab 200 mg intravenously every 4 weeks plus pomalidomide 4 mg orally every day for days 1-21 of a 28-day cycle; and one sequentially received pembrolizumab alone and then pomalidomide alone. The response rate was 50% with particular benefit in gammaherpesvirus-associated tumors. The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three patients with PEL had leptomeningeal disease: one had a complete response and the other two had long-term disease control. There were four immune-related adverse events (irAEs), all CTCAEv5 grade 2-3; three of the four patients were able to continue receiving pembrolizumab. No irAEs occurred in patients receiving the combination of pembrolizumab and pomalidomide. CONCLUSIONS: Treatment of HIV-associated NHL with pembrolizumab with or without pomalidomide elicited responses in several subtypes of HIV-associated NHL. This approach is worth further study in PLWH and NHL.

Clearance of Hepatitis C Virus (HCV) Is Associated With Improved Outcomes in HCV-Associated Lymphoma.

BACKGROUND: Improved hepatitis C virus (HCV) clearance due to directly acting antiviral agents has led to remarkably improved outcomes of indolent HCV-associated non-Hodgkin lymphoma (NHL). The impact of directly acting antivirals on the outcomes of aggressive NHL is still under investigation. Characteristics of HCV-associated NHL in black patients are not well characterized. We report outcomes of HCV-associated NHL compared to their HCV-negative counterparts in a predominantly black population. PATIENTS AND METHODS: Patients with lymphoma between January 2007 and December 2017 were retrospectively studied. Depending on presence or absence of HCV RNA, patients were grouped into HCV positive (HCV+) and HCV negative (HCV-) cohorts. Depending on virologic clearance (VC), HCV+ were classified into HCV+ with VC and HCV+ without VC. Overall response rate (ORR), complete response, overall survival (OS), and progression-free survival (PFS) of HCV+ patients with and without VC were compared to HCV- patients. RESULTS: Of 397 patients with lymphoma, 40 had HCV. Black comprised 90% of HCV+ patients. Diffuse large B-cell lymphoma was most frequent (47%) in the HCV+ group. HCV+ patients without VC had significantly worse OS and PFS compared to HCV- patients. There were no differences in ORR, complete response, PFS, and OS of HCV+ patients with VC and HCV- patients. These results were consistent in subgroups of diffuse large B-cell lymphoma and aggressive lymphoma. CONCLUSION: HCV clearance is positively associated with lymphoma outcomes in black patients. Patients who clear HCV have noninferior outcomes to HCV- patients, while those who fail to clear HCV have significantly worse outcomes.

Biomarkers in HCV-related mixed cryoglobulinemia patients withnon-Hodgkin lymphoma.

OBJECTIVE: Chronic Hepatitis C virus (HCV) infection can cause severe extrahepatic manifestations, such as mixed cryoglobulins (MC), up to the development of B cell nonHodgkin's lymphoma (B-NHL). Mechanisms transforming of HCV infection into lymphoproliferative and/or autoimmune disorders are still poorly understood. In course of HCV infection, the sustained virus-driven antigenic stimulation may probably induce a B-cell clonal expansion. Measurements of serum free light chains (FLCs) levels, considered as a direct marker of B cell activity, are analyzed with increasing interest in clinical practice, for diagnosis, monitoring and follow-up of plasma cell dyscrasia. Syndecan-1 (CD138) is a transmembrane heparan sulfate proteoglycan expressed and actively shed by most myeloma cells. Membrane CD138 represents the major receptor protein for HCV attachment to the hepatocyte surface and high levels of circulating sCD138 levels are detected in patients at early stage of B-cell chronic lymphocytic leukemia. This study is aimed to evaluate sCD138 and FLC levels as diagnostic biomarkers of HCV-related MC with B-NHL. PATIENTS AND METHODS: We enrolled 35 HCV-MC-NHL patients, characterized for the specific type of cryoglobulins, and 25 healthy blood donors (HBD) as negative control. Serum sCD138 levels were determined using ELISA kits specific for human sCD138. Serum FLCs were assessed by means of the turbidimetric assay. RESULTS: We found that serum levels of sCD138, as well as FLCs, were significantly higher in patients than in HBD (p<0.001). CONCLUSIONS: In agreement with the definition of HCV-driven lymphoproliferative disorders as the consequence of a multifactorial and multistep pathogenetic process, we suggest that sCD138 and FLCs could be considered putative independent markers of worsening progression of the disease.

Frequent traces of EBV infection in Hodgkin and non-Hodgkin lymphomas classified as EBV-negative by routine methods: expanding the landscape of EBV-related lymphomas.

The Epstein-Barr virus (EBV) is linked to various B-cell lymphomas, including Burkitt lymphoma (BL), classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) at frequencies ranging, by routine techniques, from 5 to 10% of cases in DLBCL to >95% in endemic BL. Using higher-sensitivity methods, we recently detected EBV traces in a few EBV-negative BL cases, possibly suggesting a "hit-and-run" mechanism. Here, we used routine and higher-sensitivity methods (qPCR and ddPCR for conserved EBV genomic regions and miRNAs on microdissected tumor cells; EBNA1 mRNA In situ detection by RNAscope) to assess EBV infection in a larger lymphoma cohort [19 BL, 34 DLBCL, 44 cHL, 50 follicular lymphomas (FL), 10 T-lymphoblastic lymphomas (T-LL), 20 hairy cell leukemias (HCL), 10 mantle cell lymphomas (MCL)], as well as in several lymphoma cell lines (9 cHL and 6 BL). qPCR, ddPCR, and RNAscope consistently documented the presence of multiple EBV nucleic acids in rare tumor cells of several cases EBV-negative by conventional methods that all belonged to lymphoma entities clearly related to EBV (BL, 6/9 cases; cHL, 16/32 cases; DLBCL, 11/30 cases), in contrast to fewer cases (3/47 cases) of FL (where the role of EBV is more elusive) and no cases (0/40) of control lymphomas unrelated to EBV (HCL, T-LL, MCL). Similarly, we revealed traces of EBV infection in 4/5 BL and 6/7 HL cell lines otherwise conventionally classified as EBV negative. Interestingly, additional EBV-positive cases (1 DLBCL, 2 cHL) relapsed as EBV-negative by routine methods while showing EBNA1 expression in rare tumor cells by RNAscope. The relapse specimens were clonally identical to their onset biopsies, indicating that the lymphoma clone can largely loose the EBV genome over time but traces of EBV infection are still detectable by high-sensitivity methods. We suggest EBV may contribute to lymphoma pathogenesis more widely than currently acknowledged.

Impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH and outcomes with vorinostat (AMC-075 trial).

EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle. Up to 1 prior cycle of systemic chemotherapy was allowed. The primary end point was complete response (CR). In 86 evaluable patients with diffuse large B-cell lymphoma (DLBCL; n = 61), plasmablastic lymphoma (n = 15), primary effusion lymphoma (n = 7), unclassifiable B-cell NHL (n = 2), and Burkitt lymphoma (n = 1), CR rates were 74% vs 68% for EPOCH vs EPOCH-vorinostat (P = .72). Patients with a CD4+ count <200 cells/mm3 had a lower CR rate. EPOCH-vorinostat did not eliminate HIV reservoirs, resulted in more frequent grade 4 neutropenia and thrombocytopenia, and did not affect survival. Overall, patients with Myc+ DLBCL had a significantly lower EFS. A low diagnosis-to-treatment interval (DTI) was also associated with inferior outcomes, whereas preprotocol therapy had no negative impact. In summary, EPOCH had broad efficacy against highly aggressive HIV-NHLs, whereas vorinostat had no benefit; patients with Myc-driven DLBCL, low CD4, and low DTI had less favorable outcomes. Permitting preprotocol therapy facilitated accruals without compromising outcomes. This trial was registered at www.clinicaltrials.gov as #NCT0119384.

Characterization of hepatitis B virus infection and viral DNA integration in non-Hodgkin lymphoma.

Hepatitis B virus (HBV) infection has been reported to be associated with non-Hodgkin lymphoma (NHL). However, the evidence is limited to the seroepidemiological study. There is a lack of evidence showing the HBV infection and integration in NHL cells. Here, we reported that in the Shanghai area, the positive rates of serum HBsAg (OR: 3.11; 95% CI: 2.20-4.41) and HBeAg (OR: 3.99; 95% CI: 1.73-9.91) were significantly higher in patients with NHL. HBsAg, HBcAg and HBV DNA were detected in 34.4%, 45.2% and 47.0% of the NHL tissues, respectively. Furthermore, by using a high-throughput viral integration detection approach (HIVID), integrated HBV DNA was identified from 50% (6/12) HBV-related NHL tissues. There were a total of 313 HBV integration sites isolated from the NHL tissues, among which four protein-coding genes (FAT2, SETX, ITGA10 and CD63) were interrupted by HBV DNA in their exons. Seven HBV preferential target genes (ANKS1B, HDAC4, EGFLAM, MAN1C1, XKR6, ZBTB38 and CCDC91) showed significantly altered expression levels in NHL, suggesting a potential role of these genes in NHL development. Taken together, HBV integration is a common phenomenon in NHL. This finding opens up a new direction of research into the mechanistic link between HBV infection and NHL.

Primary non-Hodgkin lymphoma of the tongue base: the clinicopathology of seven cases and evaluation of HPV and EBV status.

OBJECTIVES: Non-Hodgkin's lymphoma (NHL) primarily derived from the base of the tongue, is rare. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are important aetiological risk factors for tumours of the head and neck. This study describes the clinicopathological features of NHL in the tongue base and the status of HPV and EBV in these cases. METHODS: Seven cases were identified from the Pathological Registry Database at Peking Union Medical College Hospital (PUMCH). The study utilized immunochemistry, in situ hybridization (ISH), and gene rearrangement to confirm the disease and and performed a clinical follow up for each case. RESULTS: All 7 lymphomas were localized at the base of the tongue. Six of the cases exhibited tongue base masses with smooth surface membranes. One case presented as multiple deep ulcers. The most common histologic subtype was diffuse large B-cell lymphoma (DLBCL), which occurred in five cases. The other two cases were mantle cell lymphoma (MCL) and peripheral T cell lymphoma, not otherwise specified (PTCL, NOS). One of the DLBCL cases was positive for HPV DNA and diffusely expressed P16 protein. During the follow up period, the MCL patient and an elderly DLBCL patient died. The remaining five patients were alive through the end of follow up. CONCLUSIONS: Most lymphomas of the tongue base manifest as an endogenous mass without membranous change. The most common subtype of NHLs of the tongue base is DLBCL, and the occurrence at this site may have a good prognosis. With proper therapy, even late stage tongue base lymphomas can be suppressed and remain in remission.

Germinotropic lymphoproliferative disorder: a systematic review.

Germinotropic lymphoproliferative disorder is a rare and rather enigmatic novel entity with distinctive clinicopathological features, one of which is the typical co-infection by Human herpesvirus 8 and Epstein-Barr virus. Human herpesvirus 8 is a lymphotropic virus detected in Kaposi sarcoma, multicentric Castleman disease, primary effusion lymphoma, Human herpesvirus 8-positive diffuse large B cell lymphoma not otherwise specified, and germinotropic lymphoproliferative disorder. Co-infection by Human herpesvirus 8 and Epstein-Barr virus is identified only in two lymphoproliferative diseases: germinotropic lymphoproliferative disorder and primary effusion lymphoma, which are otherwise diseases with totally different clinical presentations and outcomes. Unlike primary effusion lymphoma mostly occurring in immunocompromised individuals and following an aggressive course, germinotropic lymphoproliferative disorder usually presents with single or multiple lymphadenopathy affecting mainly immunocompetent individuals and mostly follows an indolent course. Based on the PRISMA guidelines, we carried out a systematic search on PubMed/MEDLINE, Web of Science, Scopus, EMBASE, and Cochrane Library using the search terms "germinotropic" and "lymphoproliferative disorder." Current scientific literature reports just 19 cases of germinotropic lymphoproliferative disorder. The purpose of our systematic review is to improve our understanding of the disease, focusing on epidemiology, clinical presentation, pathological features, treatment, and outcome. In addition, we discuss the differential diagnosis with the other Human herpesvirus 8-related lymphoproliferative diseases as currently recognized in the World Health Organization classification, adding a focus on lymphoproliferative disorders showing overlapping features.

HIV-Associated "Double-Hit" Lymphoma of the Tonsil: A First Reported Case.

Double-hit lymphoma (DHL) is a unique subtype of non-Hodgkin lymphoma characterized by atleast two rearrangements involving MYC, BLC2, and/or BCL6. These lymphomas are uncommon and aggressive, responding poorly to typical chemotherapy regimens. Lymphomas rarely arise from the oral cavity or tonsils, and those presenting as a neck mass are predominantly diffuse large B-cell lymphoma. To date, primary DHL of the tonsils has yet to be described in the literature. Here, we report a case of a 44 year-old male patient with well-controlled human immunodeficiency virus (HIV) who presented with a sore throat. He subsequently developed acute respiratory compromise due to a rapidly enlarging tonsillar mass. Pathologic and genetic analysis confirmed the presence of BCL6 and MYC rearrangements suggestive of DHL of the tonsils. In a young patient with HIV and a neck mass, it is essential that lymphoma remains on the list of differential diagnoses as prompt diagnosis and treatment may prevent complications from its rapid expansion.

Molecular detection of Epstein-Barr virus in different types of lymphoma.

Epstein-Barr virus (EBV) is a member of the γ herpesvirus subfamily. It is widely spread, potentially oncogenic and has been studied in different human cancers such as gastric carcinoma, nasopharyngeal carcinoma and both Hodgkin's and non-Hodgkin's lymphomas. EBV replicates in the oral epithelium, and resting B lymphocytes trafficking through the pharynx develop a latent infection in which only EBV genes related to the B cell growth program are expressed: LMP1, -2a/b, BARTs, EBERs and EBNAs. EBNA1 binds a specific DNA sequence in the viral genome responsible for episome replication, segregation and persistence of the viral genome, and is involved in p53 degradation and oncogenesis. It is also involved in p53 degradation and oncogenesis. Since EBV infection is associated with the progression of malignancy in lymphoma, we used EBNA1-based PCR to determine the frequency of EBV infection in lymphoma specimens from patients with different types of lymphomas. Biopsies from lymphoma patients obtained from National Cancer Institute, Misurata and Tripoli Medical Centre (Libya) showed the presence of EBV in 31 of 40 cases (77%). EBV infection rates did not differ significantly between Hodgkin's lymphoma, and non-Hodgkin's lymphoma. The rates did not vary significantly between the sexes or age groups.

Hepatitis virus B and C infections are associated with an increased risk of non-Hodgkin lymphoma: A nested case-control study using a national sample cohort.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are suspected of being associated with non-Hodgkin lymphoma (NHL); however, persuasive data are lacking. Hence, a nested large-population case-control study was performed to investigate such associations in Koreans. METHODS: Data were collected from 929 patients with NHL and 3716 healthy subjects, who were matched 1:4 for age, sex, income, and region of residence, from the Korean Health Insurance Review and Assessment Service-National Sample Cohort. The diagnoses of NHL and HBV/HCV infection were based on the International Classification of Diseases (version 10) codes. Conditional logistic regression models were used to assess odds ratios (ORs) for NHL with respect to HBV or HCV with adjustment for the Charlson comorbidity index. RESULTS: HBV and HCV rates were higher in the NHL group (3.3% and 1.3%, respectively) than in the control group (0.9% and 0.3%, respectively; P < .001 for each). The adjusted OR of hepatitis infection in patients with NHL were 3.25 (95% confidence interval [CI] = 1.99-5.31) for HBV and 3.36 (95% CI = 1.51-7.46) for HCV (P < .001 for each). Subgroups categorized by age (<55 vs ≥55 years) or sex showed significantly higher adjusted ORs of HBV for NHL. Moreover, patients with NHL ≥ 55 years of age or those who were female showed significantly higher adjusted ORs of HCV; those <55 years or who were male also tended to have higher ORs of HCV. CONCLUSION: Infection with either HBV or HCV is associated with NHL in Koreans.

Identification of Noncanonical Transcripts Produced by Systematic Nucleotide Exchanges in HIV-Associated Centroblastic Lymphoma.

Noncanonical transcriptions include transcriptions that systematically exchange nucleotides, also called bijective transformations or swinger transformations. Swinger transformation A↔T+C↔G recovers identities of 8 among 9 unknown RNAs differentially expressed in centroblastic lymphoma, a human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma. The identified RNAs align with human genes with known anti-HIV1 or oncogenic activities. Function disruption through swinger-transformed transcription potentially enables avoiding antiviral responses and contributes to cancer induction.

Epstein-Barr virus-associated B-cell lymphoproliferative disorders and lymphomas: a review.

In this review, we focus on B-cell lymphoproliferative disorders (LPDs) and lymphomas associated with Epstein-Barr virus (EBV). In some of these diseases-such as EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified-virus detection is required for the diagnosis, while in others its detection is not necessary for diagnosis. EBV infection has three main latency patterns (types III, II, and I). Different latency patterns are found in different LPD types and are related to the host immune system status. For each of the LPDs/lymphomas, we discuss the clinical presentation, epidemiology, pathology, immunophenotype, and genetic or molecular basis. We provide data for a better understanding of the relationships among the discussed diseases and other information that can be useful in differential diagnosis. Not included in this review are classic Hodgkin lymphoma and some specific variants of DLBCL, as these entities are discussed in separate reviews in this issue.

Oncologic Implications of Chronic Hepatitis C Virus Infection.

Chronic hepatitis C virus (HCV) infection increases the risk for several types of cancer, including hepatocellular carcinoma (HCC) and B-cell non-Hodgkin lymphoma, as primary and second primary malignancies. HCV-infected patients with cancer, particularly those undergoing anticancer therapy, are at risk for development of enhanced HCV replication, which can lead to hepatitis flare and progression of liver fibrosis or cirrhosis. Risk factors for HCV infection include injection drug use, blood transfusion, or solid organ transplantation before 1992, receipt of clotting factor concentrates before 1987, long-term hemodialysis, chronic liver disease, HIV positivity, and occupational exposure. Widely available direct-acting antivirals are highly effective against HCV and well tolerated. Identification of HCV-infected individuals is the essential first step in treatment and eradication of the infection. One-time screening is recommended for persons born from 1945 to 1965; screening is also recommended for persons with risk factors. Recently, a public health recommendation has been drafted to screen all adults age 18 to 79 years. Two oncology organizations recommend screening all patients with hematologic malignancies and hematopoietic cell transplant recipients, and a recently published multicenter prospective study supports universal HCV screening for all patients with cancer. HCV screening entails testing for anti-HCV antibodies in serum and, when results are positive, HCV RNA quantitation to confirm infection. Direct-acting antiviral therapy eradicates HCV in almost all cases. Virologic cure of HCV prevents chronic hepatitis and progression to liver fibrosis or cirrhosis. HCV eradication also decreases the risk of developing HCV-associated primary and second primary malignancies, and it may allow HCV-infected patients access to important cancer clinical trials. Patients with HCV-related cirrhosis require lifelong surveillance for HCC, even after viral eradication.