Molecular characterization of diffuse large B-cell lymphomas associated with hepatitis C virus infection.

Hepatitis C virus (HCV)-associated diffuse large B-cell lymphoma (DLBCL) displays peculiar clinicopathological characteristics, but its molecular landscape is not fully elucidated. In this study, we investigated the clinicopathological and molecular features of 54 patients with HCV-associated DLBCL. The median age was 71 years. An underlying marginal zone lymphoma component was detected in 14.8% of cases. FISH analysis showed rearrangements involving BCL6 in 50.9% of cases, MYC in 11.3% and BCL2 in 3.7%. Lymph2Cx-based assay was successful in 38 cases, recognizing 16 cases (42.1%) as ABC and 16 cases as GCB subtypes, while six resulted unclassified. ABC cases exhibited a higher lymphoma-related mortality (LRM). Next-generation sequencing analysis showed mutations in 158/184 evaluated genes. The most frequently mutated genes were KMT2D (42.6%), SETD1B (33.3%), RERE (29.4%), FAS and PIM1 (27.8%) and TBL1XR1 (25.9%). A mutation in the NOTCH pathway was detected in 25.9% of cases and was associated with worst LRM. Cluster analysis by LymphGen classified 29/54 cases within definite groups, including BN2 in 14 (48.2%), ST2 in seven (24.2%) and MCD and EZB in four each (13.8%). Overall, these results indicate a preferential marginal zone origin for a consistent subgroup of HCV-associated DLBCL cases and suggest potential implications for molecularly targeted therapies.

Future perspectives of radiation therapy for Hodgkin Lymphoma: Risk-adapted, response-adapted, and safer than before.

Classical Hodgkin lymphoma is a lymphoproliferative disease with a good prognosis mainly seen in young people. Nevertheless secondary malignancy, cardiac disease and infertility may affect the long survivors with significant impact on quality of life, morbidity and overall survival. In the last decades several treatment strategies were evaluated to reduce the toxicity of first line treatment such as avoiding radiotherapy or its reduction in terms of dosage and extension. Many trials including interim Positron Emission Tomography evaluation fail to compare efficacy between combined modality treatment versus chemotherapy alone in particular in early stage disease. In this review we analyze which subset of patients could take advantage from proton therapy in terms of toxicity and cost effectiveness.

Retrospective Investigation of Human Papillomavirus Cervical Infection and Lymphoma Incidence: A Clinical and Pathological Evaluation.

OBJECTIVE: Human papillomavirus (HPV) persistence is considered the main risk factor for neoplastic progression, and evidence suggests that regulatory T cells play an important role in the failure of viral elimination. Regulatory T cells may be involved in maintaining a microenvironment favourable for viral persistence and neoplasticity, through a deregulation of the local immune response. The association between altered immune function and the development of chronic infections, cancer (solid and haematological), and autoimmune diseases is documented in the literature. The purpose of this retrospective analysis was to evaluate the possible correlation between HPV cervical infection and lymphoma incidence in women attending colposcopy due to an abnormal Pap smear during a period of 15 years. DESIGN: This is a cross-sectional study. PARTICIPANTS: We investigated retrospectively the incidence of haematological diseases in women aged 21-84 with an abnormal Pap smear who referred to our centre between 2004 and 2019. SETTING: This study was conducted at the university hospital. METHODS: In our analysis, we included women with diagnoses of HL and NHL after the detection of abnormal Pap smears and HPV infections. We excluded patients with a diagnosis of lymphoma preceding the date of the abnormal Pap smear and HPV test. RESULTS: We divided the patients into two groups in order to analyse the standard incidence ratio (SIR): HL patients (19/7,064, 0.26%) and NHL patients (22/7,064, 0.31%). In our sample, we reported a significant risk of developing lymphoma compared to the general population, both for HL and NHL disease, at age <45 years. Regarding HL, the SIR of disease in women <45 years was 4.886 (95% CI 2.775-9.6029) and in women between 45 and 59 years was 2.612 (95% CI 0.96-7.108804). On the other hand, for NHL in women <45 years, we reported an SIR of about 3.007 (95%, CI 1.273-7.101575), in women aged 45-59 years, the SIR was 4.291 (95% CI 2.444-7.534399), and in women aged 60-74 years, the SIR was 3.283 (95% CI 1.054-10.22303). LIMITATIONS: This retrospective analysis was conducted in a single centre in Northern Italy and did not consider all interregional differences existing in the country in terms of HPV genotypes, ethnicity, and population characteristics. Regarding the analysis of SIR for HL and NHL, we did not divide the disease into subtypes because of the small sample of cases. Finally, we considered in our analysis only women with an abnormal Pap smear and not the general population. CONCLUSIONS: Women with chronic and persistent HPV infections may have a higher relative risk of developing lymphoma. This possible association may be caused by the deregulation of the immune system response against HPV and the failure of viral clearance, especially in younger women.

Role of Rituximab Addition to First-line Chemotherapy Regimens in Nodular Lymphocyte-predominant Hodgkin Lymphoma: A Study by Fondazione Italiana Linfomi.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare entity whose neoplastic cells retain a B-cell phenotype with expression of CD20. Radiotherapy is recommended for favorable stage IA disease while for other stages guidelines suggest therapeutic strategies similar to those used for classic HL. The role of rituximab, although quite widespread, is not completely elucidated. We retrospectively analyzed baseline characteristics of 308 consecutive patients with NLPHL diagnosed in 19 Italian centers from 2000 to 2018. With a median follow-up of 8.4 years (interquartile range: 4.5-12.4) for treated patients, median overall survival (OS) was not reached and estimated 5-year OS was 97.8% and 5-year progression-free survival (PFS) was 84.5%. Five-year cumulative incidence of histological transformation was 1.4%, 95% confidence interval (CI), 0.5%-3.8%. After adjusting for lymphocyte count, splenic involvement, bulky disease and B symptoms (fever, drenching night sweats, unintentional loss >10% of body weight within the preceding 6 months), patients with stage II or more showed superior PFS with immunochemotherapy in comparison to chemotherapy alone (hazard ratio = 0.4, 95% CI, 0.2-0.8; P = 0.015). Our data suggest an advantage of the use of rituximab combined with chemotherapy ± radiotherapy in the treatment of stage II-III-IV NLPHL.