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Open research questions in Lymphoma Diagnosis and Treatment

216 unresolved questions extracted from the limitations and future-work sections of 656 Lymphoma Diagnosis and Treatment papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The technical challenge is the difficulty in diagnosing AOSD due to the overlap of clinical manifestations with other diseases like lymphoma. The domain challenge is the need for a better understanding of the role of ferritin in AOSD. The paper also identifies the challenge of distinguishing AOSD from lymphoma using imaging studies such as 18F-FDG PET/CT.

    Case Report: Breaking the diagnostic dilemma of “lymphoma-like” presentation: a case of adult-onset Still's disease characterized by generalized lymphadenopathy and extremely elevated ferritin · 2026 · DOI

  • The gap in the literature is the lack of understanding of AOSD with a rare presentation of generalized lymphadenopathy and extremely elevated ferritin. The paper identifies the need for a diagnostic approach that can distinguish AOSD from lymphoma. The gap also includes the need for a better understanding of the role of ferritin in AOSD.

    Case Report: Breaking the diagnostic dilemma of “lymphoma-like” presentation: a case of adult-onset Still's disease characterized by generalized lymphadenopathy and extremely elevated ferritin · 2026 · DOI

  • Limited pathology capacity in sub-Saharan Africa, - exclusion of participants who had previously received chemotherapy or immunotherapy, - limited validated immunohistochemistry panel

    Liquid biopsy for the diagnosis of EBV-positive Burkitt’s lymphoma in endemic areas · 2026 · DOI

  • Further evidence is needed to support clinical implementation of liquid biopsy in low-resource settings, - evaluation of liquid biopsy in other cancer types

    Liquid biopsy for the diagnosis of EBV-positive Burkitt’s lymphoma in endemic areas · 2026 · DOI

  • The diagnosis of ALK + DLBCL remains challenging because of its rarity and overlapping pathological features with other aggressive lymphoid malignancies. The patient ultimately developed aggressive post-transplant relapse. Limited treatment duration of brigatinib rechallenge.

    Sequential targeted therapy for anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: a case report · 2026 · DOI

  • There is limited evidence to guide optimal treatment for ALK+DLBCL. The clinical utility and optimal sequencing of ALK inhibitors in ALK+DLBCL remain unclear. More effective combination or consolidation strategies are needed for this rare and highly aggressive lymphoma subtype.

    Sequential targeted therapy for anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: a case report · 2026 · DOI

  • Investigation of ΔSUVmax thresholds in larger cohorts, - Comparison of DS and IPS in different patient populations, - Evaluation of LMR as a prognostic factor

    The Comparative Prognostic Value of the Interim PET Deauville Score and ΔSUVmax in Classical Hodgkin Lymphoma: A Real-World Study of Imaging and Inflammatory Markers · 2026 · DOI

  • Published ΔSUVmax thresholds are not reproducible. The higher HL-specific cutoffs do not discriminate PFS, and only a lower threshold retains prognostic value. There is a need for a simple and effective risk stratification model in classical Hodgkin lymphoma.

    The Comparative Prognostic Value of the Interim PET Deauville Score and ΔSUVmax in Classical Hodgkin Lymphoma: A Real-World Study of Imaging and Inflammatory Markers · 2026 · DOI

  • Future studies in larger clinical cohorts and functional models are warranted to validate these results and assess the potential of integrating SH3BP5 expression profiling into precision medicine strategies for DLBCL.

    SH3BP5-driven metabolic-immune crosstalk in DLBCL: a prognostic biomarker and therapeutic target for reshaping immunosuppressive microenvironment · 2025 · DOI

  • Tumor microenvironment (TME) components, particularly absolute monocyte count (AMC), tumor-associated macrophages (TAMs), and tumor-infiltrating lymphocytes (TILs) have been implicated in prognosis, although findings remain inconsistent.

    Prognostic Role of Monocytes, Macrophages, and Lymphocytes in Diffuse Large B-Cell Lymphoma Patients Receiving R-CHOP: A Two-Year Survival Analysis · 2025 · DOI

  • Material and Methods: Given the lack of standard staging PET scans until 2011, only 31 out of 103 PMBCL patients in our retrospective study had both pre-treatment and end-of-treatment (EoT) scans.

    Evaluating Outcome Prediction via Baseline, End-of-Treatment, and Delta Radiomics on PET-CT Images of Primary Mediastinal Large B-Cell Lymphoma · 2024 · DOI

  • However, the responses, clinical outcomes, and toxicities of these regimens currently remain poorly understood, mainly because these individuals are not usually included in controlled clinical trials.

    Predictors of Survival, Treatment Modalities, and Clinical Outcomes of Diffuse Large B-Cell Lymphoma in Patients Older Than 70 Years Still an Unmet Medical Need in 2024 Based on Real-World Evidence · 2024 · DOI

  • Currently, data on derangements of immunological proteins, such as cytokines and acute phase reactants, and their impact on outcomes in HIV-associated DLBCL (HIV-DLBCL) is lacking.

    Derangements of immunological proteins in HIV-associated diffuse large B-cell lymphoma: the frequency and prognostic impact · 2024 · DOI

  • The risk of relapse or progression in HL patients is not negligible despite optimal 5-year relative survival. There is a need for improved risk stratification and treatment planning for HL patients.

    The predictive and prognostic role of baseline 2-[18F]FDG PET/CT volumetric and dissemination features in classical Hodgkin lymphoma · 2026 · DOI

  • Future prospective, multicenter trials are necessary to validate MTV and Dmax thresholds and determine if treatment de-escalation or escalation based on baseline values can improve long-term patient outcomes while balancing efficacy, safety…

    The predictive and prognostic role of baseline 2-[18F]FDG PET/CT volumetric and dissemination features in classical Hodgkin lymphoma · 2026 · DOI

  • The emergence of new [18F]FDG-avid foci during therapy poses a recurrent diagnostic dilemma. Current response criteria offer limited guidance for interpreting newly emergent foci. The study had to differentiate lymphoma-related from benign lesions using quantitative metabolic parameters.

    Differentiating lymphoma progression from benign lesions: features of incident [18F]FDG-avid foci on interim and end-of-treatment PET/CT · 2026 · DOI

  • Further studies are needed to validate the optimal cutoff values of SUVmax and TBR for discriminating lymphoma from benign lesions. Studies with larger sample sizes and longer follow-up durations are needed to confirm the study's findings. Research on other quantitative metabolic parameters may provide additional discriminatory metrics for differentiating lymphoma-related from benign lesions.

    Differentiating lymphoma progression from benign lesions: features of incident [18F]FDG-avid foci on interim and end-of-treatment PET/CT · 2026 · DOI

  • There are no gold standard diagnostic criteria for differentiating orbital inflammatory syndrome from orbital lymphoid lesions. Prior works typically examined one or two modalities in isolation.

    Estimating morphological, diffusion, and susceptibility perfusion criteria in discrimination between the perplexing orbital lymphocytic mimickers: lymphoma versus inflammatory pseudotumor · 2026 · DOI

  • This study’s limitations include its retrospective design, relatively small cohort, and the use of T2*-DSC sus- ceptibility perfusion instead of quantitative DCE-MRI. Qualitative assessment of perfusion without full phar- macokinetic modeling which is different from previous studies using more quantitative or semiquantitative tech- niques (mostly DCE-MRI) in head and neck regions. A very important limitation is the use of subjective method, and reason for this was illustrated and explained in meth- odology. Lastly, the proposed ADC cutoffs are clinically problematic: Sensitivity of 60%, resulting in a high false negative rate, must be listed as a limitation and can be justified by very small study cohort for relatively rare dis- eases. Another issue that may or may not be listed as a limitation—as being beyond definitive aim of study—is lack of sharp distinction of subtypes of orbital inflam- matory disease (IOIs/PT versus IgG4 disease) still some morphological notes have been discussed in view of the literature, with recommendations made of further stud- ies made in dedication to differentiate these inflamma- tory subtypes using DWI and perfusion techniques. Still, these limitations are confronted by usage of rapid echo- planar DSC perfusion which is time-saving compared to time-consuming DCE, with susceptibility effects not hampering results, and readable color maps can be gen- erated with quantitative perfusions and blood volume metrics. These artifacts were overcome by adjustment of imaging parameters of contrast and spatial resolution on good dedicated machines.

    Estimating morphological, diffusion, and susceptibility perfusion criteria in discrimination between the perplexing orbital lymphocytic mimickers: lymphoma versus inflammatory pseudotumor · 2026 · DOI

  • Heterogeneity of follicular lymphoma, limited understanding of lactate transport-related proteins in this context, need for novel therapeutic strategies

    Study on the expression of lactate transport-related proteins in follicular lymphoma and their relationship with clinicopathologic features · 2026 · DOI

  • There is a need for effective treatments for PTCL patients who have failed prior therapies. Allogeneic hematopoietic cell transplantation may be a viable option for these patients, but its efficacy and safety are not well established.

    Allogeneic hematopoietic cell transplantation in mature T- or NK-lymphomas: a phase II clinical trial · 2026 · DOI

  • Diagnostic challenges in the emergency setting due to rare presentation. The need for a cautious approach to surgical intervention. The importance of considering lymphoma in the differential diagnosis of retroperitoneal masses with acute systemic manifestations.

    Non-Hodgkin’s lymphoma presenting as a retroperitoneal mass in the emergency department: a case report · 2026 · DOI

  • Non-Hodgkin's lymphoma presenting primarily as a retroperitoneal mass with acute symptoms is rare and often misdiagnosed. The clinical incidence of the retroperitoneal space is as low as 0.1 to 0.2%, with diverse pathological components.

    Non-Hodgkin’s lymphoma presenting as a retroperitoneal mass in the emergency department: a case report · 2026 · DOI

  • The impact of T-stage discrepancy on oncologic outcomes in patients treated with OPHL is unclear. There is a need to investigate the relationship between T-stage discordance and oncologic outcomes in patients with LSCC.

    Clinical–pathological T-stage discrepancy in OPHL: impact on oncologic outcomes · 2026 · DOI

  • The study has a limited sample size. The study is a retrospective analysis and may be subject to biases. The study acknowledges model instability in the multivariate Cox analysis.

    Therapeutic Outcomes in Aggressive B‑Cell Lymphomas: A Propensity‑Matched Comparison of Grade 3B Follicular Lymphoma and Transformed DLBCL from a Real‑World Chinese Cohort · 2026 · DOI

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216 open questions have been extracted from the limitations and future-work passages of 656 Lymphoma Diagnosis and Treatment papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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