Sinonasal B-cell lymphomas:A nationwide cohort study, with an emphasis on the prognosis and the recurrence pattern of primary diffuse large B-cell lymphoma

Lymphomas of the nasal cavity and paranasal sinuses (NPS) are rare. Knowledge on sinonasal B‐cell lymphoma (SNBCL) primarily comes from case series or single‐center studies on small cohorts. We sought to determine the subtype distribution, clinical characteristics, disease behavior, and prognosis on a nationwide scale, with an emphasis on prognostic factors for the most common sinonasal lymphoma, primary sinonasal diffuse large B‐cell lymphoma (PSDLBCL). We collated all data from medical records and national databases on patients registered with SNBCL from 1980 through 2018 in the national pathology registry and collected all tissue samples for validation of diagnosis. We included 205 patients and found 10 different subtypes of lymphoma. Diffuse large B‐cell lymphoma (DLBCL) was the predominant subtype (80%). The incidence of SNBCL was 0.14/100,000 person‐years. The five‐year progression‐free survival (PFS) and overall survival rates for PSDLBCL were 50% and 56%, respectively. For PSDLBCL, Rituximab showed a statistically significant effect (Hazard Ratio 0.22, p < 0.001), whereas consolidative radiotherapy combined with immunochemotherapy was of limited value (PFS, p = 0.93). When treatment failure occurred, DLBCL showed a distinct pattern of recurrence/dissemination to the NPS, skin, breast, central nervous system (CNS), and/or testis. Collectively, DLBCL comprised a clear majority of SNBCLs, although nine other subtypes were represented. Data showed that immunochemotherapy increased survival for PSDLBCL and that the addition of radiotherapy did not benefit patients. Furthermore, treatment failure for sinonasal DLBCL showed a possible common pathogenesis with primary extranodal lymphomas of specific locations (e.g., CNS, skin, breast, and testis)

miR-18b overexpression identifies mantle cell lymphoma patients with poor outcome and improves the MIPI-B prognosticator

Recent studies show that mantle cell lymphoma (MCL) express aberrant miRNA profiles, however, the clinical effect of miRNA expression has not previously been examined and validated in prospective, large, homogenously treated cohorts. We analyzed diagnostic MCL samples from the Nordic MCL2 and MCL3 clinical trials, in which all patients had received Rituximab-high-dose cytarabin alternating with Rituximab-maxiCHOP, followed by BEAM and autologous stem cell support. We performed genome-wide miRNA microarray profiling of 74 diagnostic MCL samples from the MCL2 trial (screening cohort). Differentially expressed miRNAs were re-analyzed by qRT-PCR. Prognostic miRNAs were validated by qRT-PCR in diagnostic MCL samples from 94 patients of the independent MCL3 trial (validation cohort). Three miRNAs (miR-18b, miR-92a, miR-378d) were significantly differentially expressed in patients who died from MCL in both the screening- and the validation cohort. MiR-18b was superior to miR-92a and miR-378d in predicting high risk. Thus, we generated a new MIPI-B-miR prognosticator, combining expression-levels of miR-18b with MIPI-B data. This prognosticator improved identification of high risk patients compared to MIPI-B with regard to cause-specific survival (P=0.015), overall survival (P=0.006) and progression-free survival (P<0.001). Transfection of two MCL cell lines with miR-18b decreased their proliferation rate without inducing apoptosis, suggesting miR-18b may render MCL cells resistant to chemotherapy by decelerating cell proliferation. Thus, we conclude that overexpression of miR-18b identifies patients with poor prognosis in two large prospective MCL cohorts and adds prognostic information to MIPI-B. MiR-18b may reduce the proliferation rate of MCL cells as a mechanism of chemoresistance