👤 Paolo Giorgio Arcidiacono

The diagnosis of lymphoplasmacytic lymphoma (LPL) in the bone marrow (BM) is challenged by aberrant phenotypes and by overlapping histological features with marginal zone lymphoma (MZL). To address these issues, we (i) assessed LPL immunophenotype on a large series of BM samples, (ii) drew possible correlations between LPL phenotype and clinical/molecular data and (iii) investigated the role of new phenotypical markers in the differential diagnosis between LPL and MZL. The study retrospectively considered 81 clinically annotated LPL diagnosed at Padua University Hospital (Padua, Italy) during a 5-year period. BM findings were correlated with clinical laboratory findings and with MYD88 and CXCR4 mutational status. The obtained results were compared with a series of 77 MZL in the BM, including 46 splenic MZL (SMZL), 14 nodal MZL (NMZL) and 17 extra-nodal MZL (EMZL). The LPL cohort included 52 males and 29 females (median age at diagnosis = 71 years). Aberrant CD10 and CD5 positivity was documented in 3 of 81 (3.7%) and 13 of 81 (16.1%) cases, respectively. CD23 positivity occurred in 56 of 81 (69.1%) cases, being usually partial/focal. CD23 expression did not correlate with any specific clinical-pathological parameter. Comparison with SMZL, NMZL and EMZL highlighted less frequent splenomegaly, higher serum paraprotein, higher CD23 expression and fewer follicular dendritic cell networks in LPL. A combined clinical-pathological score supported the differential diagnosis between LPL and MZL of any type. The highest diagnostic yield was obtained for the differential diagnosis between LPL and SMZL. Partial positivity for CD23 is a common feature of LPL in the BM. Together with other clinical and histological parameters, CD23 expression supports the differential diagnosis between LPL and MZL. Show less

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P = 2.46 × 10-9), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P = 1.53 × 10-6). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting reanalysis of genome-wide association studies (GWASs) in light of functional data. Show less

A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases Show less