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Open research questions in Lymphoma Diagnosis and Treatment

681 gap statements mined from Lymphoma Diagnosis and Treatment papers in our 7.9M-paper local library, which holds 3,509 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The authors highlight the need for intensified EBV surveillance protocols in this population. The paper discusses the challenge of extending JAK inhibitor use into younger children and first-line settings.

    Epstein-Barr virus reactivation and post-transplant lymphoproliferative disease risk deserve a place in the JAK inhibitor toxicity profile. Comment on: “Janus kinase inhibitors as an evolving treatment for lymphomas and immune-mediated complications” · 2026 · DOI

  • The wide confidence interval for the hazard ratio of bone marrow involvement warrants cautious interpretation.

    Association of TNF-α, TGF-β1, IFN-γ, IL-6, and IL-10 Gene Polymorphisms with Hodgkin Lymphoma: Susceptibility and Clinical Outcomes · 2026 · DOI

  • The pathogenesis of SI-DLBCL remains unclear. There is a lack of research on secondary intestinal diffuse large B-cell lymphoma compared to primary intestinal diffuse large B-cell lymphoma.

    Clinical characteristics and prognosis analysis of secondary intestinal diffuse large B-cell lymphoma: a multi-center retrospective study over a decade · 2026 · DOI

  • The role of B cell intrinsic factors and autoimmune processes in lymphomagenesis is not well understood. The mechanisms of BCR autoreactivity in lymphoma development and survival are unclear. Prior studies have not investigated the clonal variations and dominating sequences in RA-DLBCL patients.

    Diffuse large B cell lymphoma in rheumatoid arthritis express polyreactive and autoreactive BCRs binding protein modifications · 2026 · DOI

  • The limitation of the study to CHOP-14-based regimens, which may not be generalizable to other contemporary DLBCL regimens. The need to interpret the findings cautiously due to the post hoc nature of the analysis and the possibility of type I error.

    Beta-blocker use and survival in diffuse large B-cell lymphoma: a post hoc analysis of the RICOVER-60 trial · 2026 · DOI

  • There is a lack of understanding of the health-related quality of life and symptom burden in patients with diffuse large B-cell lymphoma before treatment with tafasitamab and lenalidomide. The study aims to address this gap by characterizing HRQoL and symptom burden in the PRO-MIND cohort.

    Health-Related Quality of Life and Symptom Burden in Patients with Diffuse Large B-Cell Lymphoma Before Treatment with Tafasitamab and Lenalidomide: An Ad Hoc Analysis of Italian Real-World Data from the PRO-MIND Study · 2025 · DOI

  • Emerging applications in immunotherapy, including checkpoint inhibitors and CAR-T cell therapy, highlight the evolving role of PET in response prediction and treatment monitoring, although paediatric-specific data remain limited.

    PET/CT In paediatric lymphoma: Current role and advances · 2026 · DOI

  • The thymus provides a specialized niche for lymphocyte differentiation, yet the developmental trajectories of its rare B-cell population and their relationship to thymic B-cell lymphomagenesis remain poorly understood.

    Developmental origins of thymic B-cell lymphomas · 2026 · DOI

  • Whether adult LBCL cases with IRF4 rearrangement ( IRF4 ‐R) should be classified as LBCL‐ IRF4 ‐R remains unclear.

    Biological heterogeneity in adult IRF4 ‐rearranged large B‐cell lymphoma: Stratification by age and anatomical site · 2026 · DOI

  • AEs and efficacy of NAVD as frontline therapy in cHL patients have not been reported outside of a clinical trial.

    Nivolumab in combination with AVD as frontline treatment for patients with classic Hodgkin lymphoma: A real‐world analysis from 20 US centers · 2026 · DOI

  • No targeted therapies are available for HSTCL, and preclinical models to test new treatment options have not been established.

    Preclinical models of hepatosplenic γδ T‐cell lymphoma with an activating STAT5B mutation display sensitivity to JAK inhibitor upadacitinib · 2026 · DOI

  • High-grade B-cell lymphomas (HGBLs) with concurrent rearrangements of MYC and BCL6 represent a biologically and clinically heterogeneous subset of aggressive B‑cell neoplasms, the optimal classification and risk stratification of which remain incompletely defined.

    The rearrangement partner and the presence of MYC mutations determine the outcome of patients with MYC and BCL6 rearrangements · 2026 · DOI

  • Recent studies suggest that lymphomas harboring t(3;8)(q27;q24) can have more favorable outcomes than conventional double‑hit lymphomas, but the molecular basis for this prognostic discrepancy—particularly in comparison with other MYC/BCL6‑rearranged tumors involving immunoglobulin (IG) partners—remains unclear.

    The rearrangement partner and the presence of MYC mutations determine the outcome of patients with MYC and BCL6 rearrangements · 2026 · DOI

  • Epigenetic reprogramming is increasingly recognized as a key driver of clonal evolution and therapeutic resistance in diffuse large B-cell lymphoma (DLBCL), yet how epigenetic mutations shape the tumor microenvironment (TME) remains unclear.

    CREBBP mutation promotes tumor growth and CD8+ T-cell dysfunction in DLBCL via NOTCH-STAT1-LGALS9 signaling · 2026 · DOI

  • The AYA population warrants special attention given their unique characteristics that may affect treatment strategies and patterns of care.

    Shifting the Balance of Therapeutic Radiation in Adolescent and Young Adult Hodgkin Lymphoma · 2025 · DOI

  • Immunochemotherapy has historically been the mainstay of treatment, but recent data indicate that addition of novel agents, especially covalent Bruton tyrosine kinase inhibitors (cBTKi), may substantially improve outcome in younger and older patients, although a curative approach remains to be shown.

    EHA–EU MCL network guidelines for diagnosis and treatment of mantle cell lymphoma · 2025 · DOI

  • Primary adrenal extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is exceptionally rare, and it remains unclear whether this subtype of ENKTL exhibits distinct clinicopathological features.

    Primary adrenal CD56-negative extranodal NK/T-cell lymphoma: Case report and literature review · 2025 · DOI

  • The advent of combined chemotherapy and radiation has improved survival, but long-term trends and prognostic factors remain underexplored.

    Trends in Survival and Factors Associated with Survival in Primary Thyroid Lymphoma: A SEER-Based Analysis (1975–2021) · 2025 · DOI

  • There is limited information about the clinical behavior and no standardized treatment guidelines for primary thyroid lymphoma (PTL).

    Survival Outcomes and Treatment Strategies in Primary Thyroid Lymphoma: A Population-Based Study of 401 Cases from the Tokyo Cancer Registry · 2025 · DOI

  • Prognostic factors and treatment outcomes remain poorly defined despite diagnostic and therapeutic advancements.

    Survival Outcomes and Treatment Strategies in Primary Thyroid Lymphoma: A Population-Based Study of 401 Cases from the Tokyo Cancer Registry · 2025 · DOI

  • No standardized methods exist for the publication of phase 1 trial results, with significant variation in details included in publications.

    Toxicity outcomes in phase 1 lymphoma trials abstracts are under‐reported, with high use of minimizing language · 2026 · DOI

  • The wide CI for HR warrants cautious interpretation, - No inferential comparisons were performed on continuous variables in their original scale, - Multiple comparisons were addressed using the Benjamini-Hochberg false discovery rate (FDR)…

    Association of TNF-α, TGF-β1, IFN-γ, IL-6, and IL-10 Gene Polymorphisms with Hodgkin Lymphoma: Susceptibility and Clinical Outcomes · 2026 · DOI

  • The difficulty of inhibiting BCL6 due to its lack of conventional binding pockets - The potential for resistance to emerge under therapeutic pressure - The need to understand the determinants of sensitivity and resistance to BCL6-directed…

    BCL6 in B-cell lymphomas: old target, new tricks? · 2026 · DOI

  • Investigation of the mechanism by which BBs improve NK cell function, - Study of the association between BB use and survival outcomes in other cancer types, - Evaluation of the effectiveness of BBs in combination with other…

    Beta-blocker use and survival in diffuse large B-cell lymphoma: a post hoc analysis of the RICOVER-60 trial · 2026 · DOI

  • Systematic HRQoL assessment at the time of the treatment decision in patients with transplant-ineligible R/R DLBCL. Further research on the combined influence of advanced age, comorbidities, disease status, and prior therapy on HRQoL impairments.

    Health-Related Quality of Life and Symptom Burden in Patients with Diffuse Large B-Cell Lymphoma Before Treatment with Tafasitamab and Lenalidomide: An Ad Hoc Analysis of Italian Real-World Data from the PRO-MIND Study · 2025 · DOI

Most-cited papers in Lymphoma Diagnosis and Treatment

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Open questions raised by papers listed on this page include: (1) There is a lack of research on secondary intestinal diffuse large B-cell lymphoma compared to primary intestinal diffuse large B-cell lymphoma (“Clinical characteristics and prognosis analysis of secondary intestinal diffuse…”, 2026); (2) The role of B cell intrinsic factors and autoimmune processes in lymphomagenesis is not well understood (“Diffuse large B cell lymphoma in rheumatoid arthritis express polyreactive and…”, 2026); (3) Emerging applications in immunotherapy, including checkpoint inhibitors and CAR-T cell therapy, highlight the evolving role of PET in response prediction and treatment monitoring, although paediatric-specific data remain limited (“PET/CT In paediatric lymphoma: Current role and advances”, 2026); (4) The thymus provides a specialized niche for lymphocyte differentiation, yet the developmental trajectories of its rare B-cell population and their relationship to thymic B-cell lymphomagenesis remain poorly understood (“Developmental origins of thymic B-cell lymphomas”, 2026); (5) Whether adult LBCL cases with IRF4 rearrangement ( IRF4 ‐R) should be classified as LBCL‐ IRF4 ‐R remains unclear (“Biological heterogeneity in adult IRF4 ‐rearranged large B‐cell lymphoma:…”, 2026). 681 gap statements have been mined from Lymphoma Diagnosis and Treatment papers in our 7.9M-paper local library, which holds 3,509 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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