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Open research questions in Lymphoma Diagnosis and Treatment

54 unresolved questions extracted from the limitations and future-work sections of 494 Lymphoma Diagnosis and Treatment papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Nevertheless, their presence underscores the genetic complexity and intratumoral heterogeneity of this case; their potential biological relevance warrants further investigation. At present, there is insufficient evidence to support a direct causal role of these low-frequency alterations in driving the CD30-negative phenotype, and they are more likely to represent incidental passenger events. While the significance of these subclonal mutations remains uncertain, PRDM1 deletions have previously been reported to occur more frequently in ALK-negative large cell lymphoma.

    Does CD30 loss preclude the diagnosis of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma? Insights from a rare case · 2026 · DOI

  • Background: Although elevated body mass index (BMI) is a recognized risk factor for non-Hodgkin lymphoma (NHL), the global burden and geographic heterogeneity of high-BMI-associated NHL remain inadequately characterized.

    Trends and projections of high body mass index-associated non-hodgkin lymphoma burden (1990–2040): A global burden of disease 2021 analysis · 2026 · DOI

  • Multiple patient-reported fatigue measures are used in lymphoma research, including FACIT-Fatigue and PROMIS Fatigue instruments, but direct comparisons of their responsiveness and ability to detect individual-level change in this population are lacking.

    Measuring group‑ and individual‑level change of FACIT- fatigue, NFLymSI-18 and PROMIS fatigue measures (4a, 7a and 13a) in lymphoma · 2026 · DOI

  • Abstract Diffuse large B-cell lymphomas (DLBCLs) with a dark zone (DZ)-like transcriptional profile correlate with poor outcomes to rituximab-based chemoimmunotherapy, but the mechanisms underlying this resistance remain unclear.

    Abstract LT02: Aggressive B-cell lymphomas retain ATR-dependent determinants of T-cell exclusion from the Germinal Center Dark Zone · 2026 · DOI

  • All patients living with HIV who present with persistent l y m p h a d e n o p a t h y, r a p i d l y e n l a rg i n g m a s s e s, constitutional symptoms, or extranodal lesions should undergo early evaluation for lymphoma. Management of HIV-associated lymphoma should involve a multidisciplinary approach including haematologists, oncologists, infectious disease physicians, neurologists, cardiologists, pathologists, and supportive care teams. This is particularly important in patients with multiple comorbidities such as hypertension, diabetes mellitus, and cerebrovascular disease. Healthcare institutions in resource-limited settings should strengthen access to diagnostic facilities including immunohistochemistry, molecular studies, neuroimaging, viral load testing, and CD4 monitoring to improve diagnostic accuracy and prognostication. More multicentre studies are needed in Sub-Saharan Africa to evaluate the clinical characteristics, treatment outcomes, prognostic factors, and survival patterns of HIV-associated lymphomas in resource-constrained environments. West J Med & Biomed Sci | Vol. 1 No. 1-2 | 2026 For Reprint Contact: [email protected] Okoli R O, Osunde I, Omenka L associated Burkitt lymphoma. Lancet Haematol. 2020;7(8):e594-e600. 11. Huguet M, Navarro JT, Moltó J, Ribera JM, Tapia G. Diffuse Large B-Cell Lymphoma in the HIV Setting. Cancers (Basel). 2023;15(12):3191. doi:10.3390/cancers15123191 12. Xiong Y, Liu W, Chen X, Mo P, Xiong Y, Deng L et al. Survival of HIV associated diffuse large B-cell lymphoma and Burkitt lymphoma in China. Sci Rep;2024;14(1):30397. https://doi.org/10.1038/s41598-024- 80749-9 13. Noy A. Optimizing treatment of HIVassociated lymphoma. Blood. 2019;134(17):1385-1394. https://doi.org/10.1182/blood-2018-01- 791400 14. Magangane PS, Mohamed Z, Naidoo R. Diffuse large B-cell lymphoma in a high human immunodeficiency virus (HIV) prevalence, low-resource setting. S. Afr. j. oncol. 2020;4(0), a104. https://doi.org/10.4102/sajo.v4i0.104 Pg 21 REFERENCES 1. Berhan A, Bayleyegn B, Getaneh Z. HIV/AIDS Associated Lymphoma: Review. Blood Lymphat Cancer. 2022;12:31-45. doi:10.2147/BLCTT.S361320 2. Wang C, Liu J and Liu Y. Progress in the Treatment of HIV-Associated Lymphoma When Combined With the Antiretroviral Therapies. Front. Oncol.2011;11:798008. doi: 10.3389/fonc.2021.798008 3. Wu D, Chen C, Zhang M, Li Z, Wang S, Shi J, et al. The clinical features and prognosis of 100 AIDS-related lymphoma cases. Sci Rep. 2019;9:5381. https://doi.org/10.1038/s41598- 019-41869-9 4. Czepiel J, Kluba-Wojewoda U, Biesiada G, Mach T, Garlicki A. The case of a diffuse large B-cell lymphoma (DLBCL) in a course of HIV. HIV AIDS Rev. 2010;9(1):22-25. doi.org/10.1016/S1730-1270(10)60095-1 5. Straista M, Caccuri F, Arnaut N, Caruso A, Slevin M. Pathological Mechanisms Involved in HIV-Associated Lymphomagenesis: Novel Targeted Therapeutic Approaches. Cells. 2025;14(10):705. doi:10.3390/cells14100705 6. Hübel K, Bower M, Aurer I, Bastos-Oreiro M, Besson C, Brunnberg U et al. Human immunodeficiency virus-associated lymphomas: EHA–ESMO Clinical Practice Guideline for diagnosis, treatment and followup. Annals of Oncology, 2024; 35, 840-859 7. Khwaja J, Burns JE, Ahmed N, Cwynarski K. HIV-associated lymphoma—advances in clinical management. Ann Lymphoma 2021;5:26. doi: 10.21037/aol-21-16 8. Liu Y, Li J, Liu Y.

    HIV Associated Diffuse Large B-Cell Lymphoma: A Case Study And Literature Review · 2026 · DOI

  • Our case adds to this limited literature by documenting a cecal diffuse large B-cell lymphoma with an exceptionally high proliferation index (antigen Ki-67, 90%) presenting with fecal peritonitis.

    Colonic Diffuse Large B-Cell Lymphoma Presenting as Fecal Peritonitis: A Case Report · 2026 · DOI

  • 2%, as pathological components of retro- peritoneal occupancy are diverse, including primary retroperito- neal benign and malignant tumors, metastatic tumors, and inflammatory changes (1, 2); therefore, non-Hodgkin’s lymphoma with retroperitoneal occupancy is rare and rarely reported in the literature (8).

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

  • The diagnostic performance of baseline positron emission tomography/computed tomography (PET/CT) for identifying BMI remains unclear, and its consistency with bone marrow biopsy (BMB) results varies greatly across studies.

    Diagnostic Performance of Baseline FDG‐PET/CT for Detecting Bone Marrow Involvement in Classic Follicular Lymphoma · 2026 · DOI

  • The ETS transcription factors ETS1 and FLI1 are recurrently gained and functionally relevant in DLBCL, yet their pathogenic role remains to be fully elucidated.

    The RNA helicase DDX21 cooperates with ETS1 and FLI1 in cell cycle, immune evasion, and snoRNA processing in activated B-cell-like diffuse large B-cell lymphoma cells · 2026 · DOI

  • Pola-R-CHP treatment represents a superior and standard frontline treatment for DLBCL due to the superior PFS over R-CHOP according to the phase III POLARIX study, although the OS benefit has not been confirmed yet [4].

    Comparison of dose-adjusted EPOCH-R and R-CHOP in diffuse large B-cell lymphoma with high Ki67 expression: Results from a prospective observational study · 2026 · DOI

  • Another two-centre study further explored the feasibility of interpretable machine learning models for predicting BMI in lymphoma; however, its region-of-interest (ROI) cover- age was mainly limited to the pelvic region and it did not focus on FL, an indolent lymphoma subtype with relatively distinctive biological behaviour [20].

    An interpretable PET/CT-based radiomic-clinical model for predicting bone marrow involvement in follicular lymphoma: comparison of pelvic and spine-pelvis VOI frameworks · 2026 · DOI

  • This report has several limitations. First, long-term follow-up and treatment response data were not available at the time of manuscript preparation. As a result, the clinical course after referral for systemic therapy could not be assessed. Second, this is a single case, and the findings should not be generalized to all hypermetabolic mesenteric root tumors. Third, although PET/CT showed a dominant mesenteric root mass, mild FDG uptake in other lymph node stations means that the case should be described cautiously as DLBCL presenting as a dominant mesenteric root mass rather than definitively as primary mesenteric DLBCL unless complete staging supports that designation.

    Diffuse Large B-cell Lymphoma Presenting as a Hypermetabolic Mesenteric Root Mass Without Preoperative Imaging Suspicion of Lymphoma: A Case Report · 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

  • Correlating PET parameters with circulating tumor DNA or other molecular biomarkers may yield insights into the biological underpinnings of true progression versus benign mimicry.

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

  • Long study period (2007-2023) resulted in heterogeneity due to evolution of PET/CT technology, reconstruction protocols, and first-line treatment standards including introduction…

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

  • The CADTH pan-Canadian Oncology Drug Review Expert Review Committee (pERC) recommends that polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R- CHP) not be reimbursed for the treatment of adult patients with previously untreated large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high-grade B-cell lymphoma, Epstein-Barr virus (EBV)–positive DLBCL NOS, and T-cell/histiocyte-rich LBCL.

    Polatuzumab Vedotin (Polivy) · 2024 · DOI

  • Canadian Journal of Health Technologies Summary CADTH Reimbursement Recommendation What Is the CADTH Reimbursement Recommendation for Polivy? CADTH recommends that Polivy in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) not be reimbursed by public drug plans for the treatment of adult patients with previously untreated large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high-grade B-cell lymphoma, Epstein-Barr virus–positive DLBCL NOS, and T-cell/ histiocyte-rich LBCL. Why Did CADTH Make This Recommendation? • Evidence from a clinical trial showed that 6.6% more patients with newly diagnosed moderate- to high-risk LBCL were alive without their disease progressing 2 years after treatment with Polivy in combination with R-CHP compared to those treated with traditional chemoimmunotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]). However, there is uncertainty whether this difference observed in the clinical trial translates to a meaningful difference in the real world. The evidence from the trial did not show that Polivy combined with R-CHP prolonged survival compared to R-CHOP. It is also unknown if Polivy in combination with R-CHP would reduce disease symptoms or improve functioning compared to R-CHOP because there were no differences between the 2 groups. • Patients identified a need for treatments that prolong disease remission, prolong survival, control disease symptoms, normalize blood counts, and improve quality of life. Based on the evidence submitted, it is not clear that Polivy in combination with R-CHP would provide a meaningful benefit in prolonging remission or meet the other important needs in LBCL.

    Polatuzumab Vedotin (Polivy) · 2024 · DOI

  • However, the impact of DuoHexaBody-CD37 on direct cytotoxic signaling has not yet been studied.

    DuoHexaBody-CD37 induces direct cytotoxic signaling in diffuse large B-cell lymphoma · 2026 · DOI

  • However, the clinical relevance of CD79B expression and the frequency of loss or decrease after PV-containing therapy remain unclear.

    Association between CD79B expression and polatuzumab vedotin efficacy, and therapy-induced changes in CD79B expression in diffuse large B-cell lymphoma · 2026 · DOI

  • These real‐world data suggest upfront ASCT prolongs PFS in patients with advanced‐stage NKTCL in CR1, yet its impact on OS remains unclear.

    Upfront Autologous Stem Cell Transplantation in First Complete Remission for Advanced‐Stage Extra‐Nodal <scp>NK</scp> /T‐Cell Lymphoma: A Multicenter Retrospective Study · 2026 · DOI

  • Follicular lymphoma of the prostate is often asymptomatic and underrecognized, especially when PSA is not markedly elevated.

    Concomitant recurrent follicular lymphoma and prostate adenocarcinoma detected during routine urologic follow-up: a rare case report · 2026 · DOI

  • Whether these differentially expressed genes represent pri- mary driver events, downstream consequences of subtype-specific biology, or reflections of tumour microenvironment interactions remains to be determined.

    Transcriptomic and differential gene analysis investigating the differences in biological behaviour between subtypes of feline alimentary lymphoma · 2026 · DOI

  • Limited statistical power may have prevented detection of significant differences between groups regarding the association between residual disease activity and subsequent true progression, warranting exploration in larger cohorts.

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

  • Lack of universal standardization of MTV and TLG measurement and establishment of shared methodology across…

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

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54 open questions have been extracted from the limitations and future-work passages of 494 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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