Feldman, Andrew L

SummaryWe evaluated the association of Human Pegivirus (HPgV) viraemia with risk of developing lymphoma, overall and by major subtypes. Because this virus has also been associated with better prognosis in the setting of co‐infection with human immunodeficiency virus, we further assessed the association of HPgV with prognosis. We used risk factor data and banked plasma samples from 2094 lymphoma cases newly diagnosed between 2002 and 2009 and 1572 frequency‐matched controls. Plasma samples were tested for HPgV RNA by reverse transcription polymerase chain reaction (RT‐PCR), and those with RNA concentrations <5000 genome equivalents/ml were confirmed using nested RT‐PCR methods. To assess the role of HPgV in lymphoma prognosis, we used 2948 cases from a cohort study of newly diagnosed lymphoma patients (included all cases from the case‐control study). There was a positive association of HPgV viraemia with risk of lymphoma overall (Odds ratio = 2·14; 95% confidence interval [CI] 1·63–2·80; P < 0·0001), and for all major subtypes except Hodgkin lymphoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma, and this was not confounded by other lymphoma risk factors. In contrast, there was no association of HPgV viraemia with event‐free survival (Hazard ratio [HR] = 1·00; 95% CI 0·85–1·18) or overall survival (HR = 0·97; 95% CI 0·79–1·20) for lymphoma overall, or any of the subtypes. These data support the hypothesis for a role of HPgV in the aetiology of multiple lymphoma subtypes.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma derived from germinal center B lymphocytes that typically presents with localized lymph node involvement and can mimic a variety of both reactive and other neoplastic conditions. Extranodal involvement is uncommon in NLPHL and typically occurs in the context of previously documented or synchronous nodal disease. Involvement of the gastrointestinal tract is exceedingly rare. Here, we present the first case to our knowledge of NLPHL involving the ileum that was discovered incidentally on routine screening colonoscopy in an asymptomatic patient. An awareness of the spectrum of clinical presentations, careful morphologic evaluation, and a comprehensive panel of immunohistochemical stains are essential for correct diagnosis of NLPHL presenting in unusual anatomic sites.

AbstractHigher ratios of the pre‐treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre‐treatment serum cytokines are associated with inferior outcomes. The relationship between pre‐treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B‐cell, follicular, mantle cell, T‐cell, and Hodgkin lymphoma. Different pre‐treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n = 390) lower ALC/AMC ratios modestly correlated with higher IL‐2R (r = −0.36), IL‐12 (r = −0.17), IP‐10 (r = −0.23), and MIG (r = −0.32) concentrations (p < 0.001). Elevated IL‐2R was independently associated with suppressed ALC (OR 2.69, 95% CI 1.77–4.07,p < 0.001), elevated AMC (OR 2.05, 95% CI 1.34–3.14,p < 0.001), and suppressed ALC/AMC ratios (OR 3.51, 95% CI 2.31–5.34,p < 0.001). Both elevated IL‐2R (HR 2.27, 95% CI 1.48–3.49,p < 0.001) and suppressed ALC/AMC ratios (HR 1.53, 95% CI 1.03–2.28,p = 0.037) were independently associated with inferior overall survival. These data support the notion that elevated serum cytokines are immunosuppressive and provide further rationale to target the tumor microenvironment for therapeutic benefit.