2026-08-05 | A 13-Year Review of Non-Diffuse Large B Cell Lymphomas of the Central Nervous System at a Tertiary Hospital: A Case Series Study.
Non-diffuse large B-cell lymphomas (non-DLBCL) of the central nervous system (CNS) are rare and diagnostically challenging. This study aims to characterize the clinical, radiological, and pathological features of non-DLBCL CNS lymphomas diagnosed at a tertiary care center over 13 years, highlighting diagnostic pitfalls. A retrospective review was conducted of non-DLBCL CNS lymphoma cases diagnosed at Sunnybrook Health Sciences Centre, Toronto, from 2010 to 2022. Clinical, demographic, and radiological data were extracted from medical records. Imaging was reviewed by a neuroradiologist, and histopathological slides and molecular data were re-evaluated by a pathology team. Additional tests were performed to update classifications per the 5th edition of the WHO Classification of Haematolymphoid Tumors. Seventeen cases were identified (11 males, 6 females; age 38-76), compared to 72 DLBCL cases during the same period. Nine cases were extra-axial and eight intra-axial. Eight were primary and nine secondary CNS lymphomas. B-cell lymphomas (n = 13) included extra-nodal marginal zone lymphoma (n = 6), follicular lymphoma, mantle cell lymphoma, CLL, intravascular large B-cell lymphoma (n = 2), EBV+ LBCL, and polymorphic PTLD. T-cell lymphomas (n = 4) included PTCL, NOS (n = 2), ALK-negative ALCL, and secondary mycosis fungoides. Imaging revealed four major patterns, and symptoms were largely due to mass effect. This case series emphasizes the considerable heterogeneity of non-DLBCL CNS lymphomas and the diagnostic challenges they present. It highlights key features that can aid recognition and improve diagnostic accuracy for these rare CNS entities. Trial Registration: SUN-5771.
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2026-08-02 | NLRC5-Deficient Macrophages Promote a Tumor-Permissive Phenotype via AXL- and MERTK-Mediated Efferocytosis.
The innate immune protein NLRC5 plays a key role in cancer immune surveillance. Reduced NLRC5 expression is associated with a poor prognosis for many types of cancers. Previously, we showed that mice with a myeloid-specific deletion of Nlrc5 (Nlrc5mø-KO) develop gastric lymphoid lesions to Helicobacter infection resembling early-stage marginal zone lymphoma. We hypothesized that NLRC5 deficiency may promote a tumor-permissive microenvironment mediated by tumor-associated macrophages (TAMs). Consistent with this hypothesis, splenic macrophages from Helicobacter-infected Nlrc5mø-KO mice had upregulated expression of genes encoding the TAM receptor tyrosine kinases, Axl and Mertk. The levels of AXL and MERTK gene expression and MERTK phosphorylation were increased in NLRC5-/- THP-1 macrophages when compared with WT cells. In response to Helicobacter stimulation, Nlrc5-/- macrophages had significantly elevated anti-inflammatory responses (IL-10, TGF-β, Socs1, Socs3) compared with WT cells. Importantly, Nlrc5-/-macrophages showed enhanced efferocytosis and reduced antigen presentation to CD8+ T cells. Pretreatment of macrophages with AXL and MERTK inhibitors (R428, UNC2025) resulted in reduced efferocytosis and phosphorylation of downstream signaling molecules, STAT3 and ERK1/2. We propose that defective NLRC5 signaling in macrophages leads to tumor-permissive responses, thereby promoting the development of gastric lymphoid neogenesis to Helicobacter infection.
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2026-07-17 | Extranodal Marginal Zone Lymphoma of the Breast in a Patient with Chronic Hepatitis C Infection: A Case Report
Primary breast lymphomas account for less than 1% of all non-Hodgkin lymphomas and 0.04–0.5% of all malignant breast neoplasms. We report a case of breast extranodal marginal zone lymphoma (EMZL) in a 60-year-old woman with chronic hepatitis C virus (HCV) infection. After comprehensive evaluation excluded other known etiologies, chronic HCV infection emerged as the most plausible contributing factor. Epidemiologic and biological evidence supports an association between HCV and B-cell non-Hodgkin lymphomas, particularly marginal zone lymphomas. Our case adds to the limited literature suggesting that HCV should be considered as a potential etiological factor in breast EMZL. We discuss the emerging role of direct-acting antiviral (DAA) therapy in HCV-associated indolent lymphomas and its implications for management.
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2026-06-29 | CEACAM1 expression by immunohistochemistry in B-cell lymphomas and plasma cell myeloma.
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with limited curative treatment options. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) has recently been implicated in B-cell receptor signaling in MCL. We evaluated CEACAM1 expression by immunohistochemistry across MCL and other mature B-cell neoplasms, including small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM). We retrospectively analyzed 164 lymphoma cases, 35 MM cases, and 2 plasmacytomas. CEACAM1 expression was assessed on tissue microarrays by immunohistochemistry and scored using a prespecified dichotomous cutoff. In DLBCL, CEACAM1 status was correlated with cell-of-origin classification and targeted mutational data. CEACAM1 was expressed in 27 of 30 MCL cases (90%), higher than in the other lymphoma subtypes combined (35%; P < .0001). Expression was also seen in SLL (20/30, 67%), MM (23/35, 66%), MZL (8/22, 36%), and DLBCL (19/82, 23%). In DLBCL, expression was more frequent in germinal center B-cell subtype than activated B-cell subtype cases (30% vs 13%; P = .023). Within sequenced DLBCL cases, CEACAM1 expression was associated with BCL2 and TNFRSF14 mutations. In MM, CEACAM1 expression was not significantly associated with recurrent cytogenetic abnormalities, although a nonsignificant trend toward higher expression in t(11;14) cases (75% vs 53%, Fisher exact P = .28). CEACAM1 is frequently expressed in MCL and in subsets of other mature B-cell neoplasms and MM. These findings support further investigation of CEACAM1 as a biologically relevant marker and potential therapeutic target in selected lymphoid malignancies.
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2026-06-02 | Obinutuzumab plus bendamustine as first-line therapy for indolent B-cell lymphomas: a prospective multicenter open-label study.
This study evaluated the efficacy and safety of obinutuzumab plus bendamustine (GB) as first-line treatment for indolent B-cell lymphomas. In this prospective, multicenter, single-arm trial (NCT06415708), adults with newly diagnosed indolent B-cell lymphomas-including follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), hairy cell leukemia variant (HCL-v), and unclassified B-cell lymphoproliferative disorder (BCLPD-U)-received six induction cycles of GB followed by 2 years of obinutuzumab maintenance in responders (⩾ partial response). The primary endpoint was overall response rate (ORR), whereas secondary endpoints included complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Among 220 enrolled patients (149 with FL and 71 with non-FL), 210 completed ⩾ 3 treatment cycles. At a median follow-up of 13.1 months, ORRs in the different patient subgroups were 96.6% (FL), 100% (MZL, HCL-v), 92.9% (WM), and 88.9% (BCLPD-U). The median DOR was 16.7 months in the FL group and was not reached in the non-FL group. PFS and OS were not reached in any subgroup. The FL and non-FL groups had comparable ORRs (P = 0.435); however, the FL group showed a higher CRR (92.4% vs. 78.5%; P = 0.004) and shorter PFS (P = 0.020). Treatment-emergent adverse events occurred in 42 patients and were more frequent in the non-FL group than in the FL group (26.8% vs. 15.4%; P = 0.046), particularly infections (18.3% vs. 6.0%; P = 0.005). Overall, the GB regimen demonstrated high response rates and manageable safety in Chinese patients with indolent B-cell lymphoma.
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