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Related Topics

  • T-cell/histiocyte-rich Large B-cell Lymphoma
  • T-cell/histiocyte-rich Large B-cell Lymphoma
  • Follicular Lymphoma Patients
  • Follicular Lymphoma Patients
  • Follicular Lymphoma Grade
  • Follicular Lymphoma Grade
  • Indolent Lymphoma
  • Indolent Lymphoma
  • Aggressive Lymphoma
  • Aggressive Lymphoma
  • Follicular Lymphoma
  • Follicular Lymphoma

Articles published on Nodular Lymphocyte Predominant Hodgkin Lymphoma

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  • Research Article
  • 10.1111/bjh.70294
T-cell/histiocyte-rich large B-cell lymphoma in the era of novel immunotherapy: A focused review.
  • Dec 23, 2025
  • British journal of haematology
  • Joleen P Choy + 1 more

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is an uncommon aggressive large B-cell lymphoma variant which can develop synchronously or following a diagnosis of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). There is morphological, immunophenotypic and molecular overlap between THRLBCL and NLPHL suggesting that these two entities may lie on the same spectrum. Due to the rarity of THRLBCL, accurate diagnosis can be challenging and there is a paucity of data on which to base treatment decisions. The management has largely followed diffuse large B-cell lymphoma (DLBCL) with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone established as the standard of care in the first line, with outcomes comparable to international prognostic index matched DLBCL. In the relapsed/refractory (R/R) setting, there is no standard of care. There is a move towards inclusion of THRLBCL patients in clinical trials evaluating novel agents, although historically they were commonly excluded. Due to the small numbers included in clinical trials, it has been difficult to discern the effect of novel agents in this cohort. Thus, we are reliant on larger real-world datasets to inform our understanding. This review will examine the data available in the first line and R/R setting with a focus on immunotherapeutic approaches.

  • Research Article
  • 10.1007/s12308-025-00666-2
IgG4 plasma cells in hematopathology: beyond IgG4-related disease.
  • Nov 20, 2025
  • Journal of hematopathology
  • Vaclav Stejskal + 3 more

IgG4 plasma cells are well-known in the context of IgG4-related disease (IgG4-RD). Meanwhile, their role in other disorders remains enigmatic. In hematopathology practice, the presence of these cells can be non-specific in reactive lymphadenopathy, requiring clinicopathological correlation to exclude IgG4-RD. A high density of IgG4 plasma cells may help distinguish progressive transformation of germinal centers from early nodular lymphocyte-predominant Hodgkin lymphoma. IgG4 plasma cells are also present in a subset of classic Hodgkin lymphomas, particularly the nodular sclerosis subtype. Despite their morphological similarities, Rosai-Dorfman disease and IgG4-RD appear to be distinct entities. Idiopathic multicentric Castleman disease and IgG4-RD can be histologically indistinguishable, which necessitates clinical and laboratory differentiation. Marginal zone lymphoma and, rarely, myeloma can express IgG4, with some cases of marginal zone lymphoma having concurrent IgG4-RD. This review provides a comprehensive analysis of IgG4 plasma cells in hematopathology and discusses their diagnostic significance and associated challenges.

  • Research Article
  • 10.1182/blood-2025-1842
Outcomes of allogeneic hematopoietic stem cell transplantation in nodular lymphocyte-predominant Hodgkin lymphoma: A registry-based study from the EBMT-LWP
  • Nov 3, 2025
  • Blood
  • Maria Carmen Martinez Munoz + 24 more

Outcomes of allogeneic hematopoietic stem cell transplantation in nodular lymphocyte-predominant Hodgkin lymphoma: A registry-based study from the EBMT-LWP

  • Research Article
  • 10.1182/blood-2025-2733
Academic cancer programs deliver improved long-term survival in nodular lymphocyte predominant Hodgkin lymphoma: Insights from 7,000+ United States patients
  • Nov 3, 2025
  • Blood
  • Nikki Verma + 8 more

Academic cancer programs deliver improved long-term survival in nodular lymphocyte predominant Hodgkin lymphoma: Insights from 7,000+ United States patients

  • Research Article
  • 10.1182/blood-2025-5404
Early-stage nodular lymphocyte predominant Hodgkin lymphoma: Disease characteristics, treatment pattern, and long-term outcomes from a tertiary care cancer institute in India
  • Nov 3, 2025
  • Blood
  • Bhausaheb Bagal + 20 more

Early-stage nodular lymphocyte predominant Hodgkin lymphoma: Disease characteristics, treatment pattern, and long-term outcomes from a tertiary care cancer institute in India

  • Research Article
  • 10.1182/blood-2025-7052
Gene expression profiling of pediatric mature B-cell non-Hodgkin lymphomas/lymphoproliferative disorders through whole transcriptome analysis
  • Nov 3, 2025
  • Blood
  • Yen-Chun Liu + 5 more

Gene expression profiling of pediatric mature B-cell non-Hodgkin lymphomas/lymphoproliferative disorders through whole transcriptome analysis

  • Research Article
  • 10.1038/s41467-025-63339-9
Distinct cell state ecosystems for nodular lymphocyte-predominant Hodgkin lymphoma
  • Sep 26, 2025
  • Nature Communications
  • Ajay Subramanian + 33 more

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and few studies have comprehensively investigated the immune microenvironment and rare lymphocyte-predominant (LP) cells. Here we develop a NLPHL specific lymphocyte-predominant ecotype (LPE) model to identify 34 distinct cell states across 14 cell types that co-occur within 3 LPEs for 171 cases. LPE1 and LPE2 were characterized by immunosuppressive microenvironments with high expression of B2M on LP cells, CD8 T-cell exhaustion, immune checkpoint genes expressed by follicular T-cells, and an improved freedom from progression compared to LPE3 in training (n = 109, with 65% LPE1/2) and validation cohorts (n = 62, with 61% LPE1/2). We validate the co-occurrence and co-localization of cell states using spatial transcriptomics. Protein expression of HLA-I and HLA-II on LP cells and SSTR2 on dendritic cells was predictive of LPE1 (C-statistic=0.69), LPE2 (C-statistic=0.79), and LPE3 (C-statistic=0.60). This study establishes a clinically relevant biologic categorization for NLPHL.

  • Research Article
  • 10.1371/journal.pone.0331439
Behavioral investigation of reactive and neoplastic lymphocytes in human lymph nodes in 4D
  • Sep 4, 2025
  • PLOS One
  • Diana Elisa Theil + 6 more

This study deals with a 4D investigation of lymphocytes in human tissue under reactive and neoplastic conditions. The immune system’s response to pathogens highly depends on cell interaction and movement, which makes it essential to analyze these dynamics. To achieve this, we observed cells and their movement in 4D. Human lymphoid tissue was examined, including 8 cases with 23 movies of hyperplastic tissue from the pharyngeal tonsil and 12 cases with 35 movies of lymphadenitis. Additionally, there were 4 cases involving 16 movies of marginal zone lymphoma (MZL), 3 cases with 19 movies of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), 3 cases with 6 movies of follicular lymphoma grade 1/2 (FL), and 2 cases with 10 movies of diffuse large B-cell lymphoma (DLBCL). We tracked the movement, analyzed the activity of B cells and PD1-positive T cells under reactive conditions, and compared the results to different types of lymphomas. In this study, CD20-positive B cells were examined in the context of CD35 staining. CD35 stains follicular dendritic cells (FDC), an indication for a germinal center, so we primarily analyzed B cells in the germinal center areas and partially in the immediate periphery. We categorized cells by defining track types (Low motion cells, Moving and turning in place, Long distance movement) to describe their movement pattern and action types (Passive cells, Interactive cells, Active cells) to describe their behavior and interactions. In neoplastic tissue, slower cellular dynamics and fewer interactions were observed compared to reactive tissue. This indicates differences in cellular behavior between reactive and neoplastic tissues, with a more dynamic cellular environment observed in reactive tissue.

  • Research Article
  • 10.1177/10935266251368431
Primary Splenic Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL): First Reported Case in a Young Child.
  • Aug 27, 2025
  • Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
  • Josselyn Sofia Vergara + 2 more

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of B-cell lymphoma. NLPHL is usually indolent, involves lymph nodes and shows a favorable prognosis with high overall survival. In a minority of cases, patients may present and/or progress to advanced disease with involvement of the spleen, liver, and/or bone marrow. While splenic involvement by NLPHL is usually presumed evidence of advanced disease with poor prognosis, here we report to our knowledge, the first case of primary splenic NLPHL occurring in a child who showed no overt nodal disease and is currently free of disease 3 years post-splenectomy without additional treatment.

  • Research Article
  • 10.3389/fonc.2025.1586441
Observations on seasonal occurrence in lymphomas with proven or presumed infectious etiology.
  • Jul 8, 2025
  • Frontiers in oncology
  • Ioannis Anagnostopoulos + 6 more

There are relatively few studies on seasonal occurrence of lymphomas, most dealing with Hodgkin lymphoma (HL). Most studies were based on small datasets leading to partly conflicting patterns and results with only two using the large Surveillance, Epidemiology and End Results database. By doing this, the study on HL showed a peak incidence in March and the lowest in September, while the study on a broadly defined B-cell lymphoma group identified a peak in March and April. Among the hypotheses regarding seasonal occurrence of lymphomas, a potential infectious etiology has been proposed, at least for some patient subgroups. For the present study, we used the files from one of Germany's lymphoma reference centers and addressed not only seasonal occurrence but also whether lymphoma entities with proven or suspected infectious etiology were associated with a particular seasonal clustering. We also investigated whether the COVID-19 pandemic (period 2020-21) influenced any observed seasonal patterns. Our study population comprised 8,038 cases with primary diagnosis of classic HL (CHL) including 2,434 cases with Epstein-Barr virus (EBV) infection of the neoplastic cells, 1,402 cases of nodular lymphocyte predominant HL, 487 cases with cutaneous marginal zone lymphoma (MZL), 247 cases with pulmonary MZL, 451 cases with hairy cell leukemia (HCL) and 4,577 cases with diffuse large B cell lymphoma (DLBCL). Our data show that among HL only CHL exhibited seasonal fluctuation with a peak in the first quarter and a trough in the third quarter of the year. Similar seasonal patterns were observed in the nodular sclerosing CHL subtype and the younger patient age group (0-39 years). No seasonal fluctuation was identified in lymphomas with proven (EBV-positive CHL) or presumed infectious etiology (cutaneous and pulmonary MZL, HCL). COVID-19 pandemic did not significantly influence the seasonal occurrence patterns observed in CHL.

  • Research Article
  • 10.1002/ajh.27762
Association Between Moraxella catarrhalis and Nodular Lymphocyte-Predominant Hodgkin Lymphoma.
  • Jul 4, 2025
  • American journal of hematology
  • Izidore S Lossos + 7 more

Nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) may be an antigen-driven malignancy. Recent studies demonstrated that in NLPHL patients, lymphoma B-cell receptor can bind proteins derived from Moraxella catarrhalis (MC) and Rothia mucilaginosa (RM). We examined whether MC and RM can be detected in NLPHL lymph nodes. The presence of MC DNA and RNA was tested by polymerase chain reaction (PCR) and RNAScope insitu hybridization (ISH), respectively. The presence of RM DNA was tested by PCR. We demonstrated the presence of MC DNA in 29 of 49 (59.2%) NLPHL patient tumor samples and RNA in 14 of 39 biopsies (35.9%), with good concordance between the assays, considering lower RNA stability in older biopsies and lower sensitivity of ISH compared to PCR. In comparison, 36 lymph nodes with follicular hyperplasia and a specimen with tubular adenoma were negative for MC by PCR, and only 6 of 37 non-NLPHL lymphoma tissues (16.2%) were positive for detection of MC by PCR, demonstrating a statistically higher detection rate of MC in patients with NLPHL (p = 0.00006). MC was detected in NLPHL samples at diagnosis and relapses, and there was no statistical difference in the detection rate for MC between IgD positive and negative samples. In contrast, RM was detected by PCR in 9 of 49 (18.4%) NLPHL patient tumor samples, always concomitantly with MC without statistical difference in comparison to other lymphomas. The high prevalence of MC in NLPHL tumor tissues provides direct evidence for its association with NLPHL.

  • Research Article
  • 10.1016/j.pathol.2025.05.013
T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is extensively expressed in the microenvironment of nodular lymphocyte-predominant Hodgkin lymphoma and T-cell-/histiocyte-rich large B-cell lymphoma.
  • Jul 1, 2025
  • Pathology
  • Georgia Karpathiou + 3 more

T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is extensively expressed in the microenvironment of nodular lymphocyte-predominant Hodgkin lymphoma and T-cell-/histiocyte-rich large B-cell lymphoma.

  • Research Article
  • Cite Count Icon 1
  • 10.2147/cmar.s529589
The Role of Artificial Intelligence and Radiomics in the Management of Lymphomas by PET/CT: The Clairvoyance in Clinic.
  • Jul 1, 2025
  • Cancer management and research
  • Chong Ling Duan + 8 more

Lymphomas are a hematopoietic malignancies that encompass over 90 subtypes. Traditionally, they have been categorized into two main groups, non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Based on morphology and immunohistochemistry, HL can be classified into nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and classical HL (cHL). NHL represents the most common form of lymphoma, including more than 50 subtypes, such as mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), and the most common, diffuse large B-cell lymphoma (DLBCL). Medical imaging plays a pivotal role in lymphoma management, with positron emission tomography/computed tomography (PET/CT) serving as an indispensable tool. 2-Deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) PET/CT is extensively utilized in lymphoma management, having demonstrated its value in providing crucial data for precise disease burden quantification, treatment response evaluation, and prognostic assessment. Radiomics is an innovative approach that entails the computer-aided extraction of quantitative, searchable data from medical images and its association with biological and clinical outcomes. The rapid advancement of radiomics research has opened new avenues for cancer diagnosis and therapy. Our findings indicate that artificial intelligence based PET/CT radiomics has demonstrated significant potential in lymphoma diagnosis, subtyping, staging, treatment selection, and survival prognosis assessment, offering clinicians powerful decision-support tools. However, challenges remain, such as the lack of standardized image quality in machine learning applications.

  • Research Article
  • 10.31083/rcm24981
Cardiovascular Disease Mortality Risk among Long-term Survivors of Different Hodgkin Lymphoma Types.
  • Jun 30, 2025
  • Reviews in cardiovascular medicine
  • Zhenxing Lu + 9 more

The temporal trend and disparities in cardiovascular disease (CVD) mortality risk among long-term survivors of different Hodgkin lymphoma (HL) types are unclear. Therefore, we aimed to examine the temporal trend and disparities in CVD mortality risk among survivors of various HL subtypes. This multicenter cohort included 20,423 patients with HL diagnosed between 1975 and 2018, with an average follow-up time of 18.5 years. Proportional mortality ratio, cumulative cause-specific mortality accounting for competing risks, standardized mortality ratio, and absolute excess risk were calculated. Patients with nodular lymphocyte-predominant HL (NLPHL) and classical HL exhibited higher CVD-related deaths than HL-related deaths after approximately 12 and 120 months of follow-up, respectively. From the initial diagnosis to >500 months of follow-up, the cumulative CVD mortality increased continuously without a plateau and exceeded that of HL at different times in most patients with various HL types. However, CVD mortality risk exceeded that of HL earlier in NLPHL than in other types. Black or male patients with nodular sclerosing classical HL exhibited a higher CVD mortality risk, while a contrary trend was noted among those with lymphocyte-rich classical HL or lymphocyte-depleted classical HL. Over the past decades, CVD mortality risk has decreased slowly or remained unchanged. Patients with HL exhibited higher risks of CVD mortality than the general population. CVD mortality risk exceeded that of HL over time among many survivors. This temporal trend was significantly different among various HL subtypes. Thus, more effective strategies are required to reduce the risk of CVD mortality, depending on subtypes.

  • Research Article
  • 10.1093/bjd/ljaf085.426
BI17 Generalized morphoea associated with anaplastic lymphoma and Hodgkin lymphoma: a report of two cases
  • Jun 27, 2025
  • British Journal of Dermatology
  • Saerrah Murryam + 3 more

Abstract Managing generalized morphoea in the context of lymphoma poses significant challenges due to the complexities of balancing immunosuppressive therapy with the need to treat malignancy. These issues are further compounded by the increased risk of transformation or recurrence in patients with autoimmune conditions who require immunosuppression treatment. Here, we present two cases that highlight these challenges. The first case involves a 59-year-old woman with a history of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), previously treated with six cycles of rituximab, cyclophosphamide, vincristine sulfate and prednisolone chemotherapy. After achieving remission, she remained under active surveillance. Her medical history also included acromegaly secondary to a pituitary microadenoma, treated with transsphenoidal adenectomy, and Sjögren syndrome. Seven years following treatment for lymphoma, she presented with progressive skin hardening involving the arms, submammary region, thighs and lower legs. Examination revealed widespread indurated plaques, significant movement restriction, and active erythematous areas, which severely impacted her activities of daily living. Initial management included methotrexate, pulsed methylprednisolone, hydroxychloroquine and ultraviolet (UV)A1 phototherapy. However, a year later, she developed recurrent NLPHL, with high-grade transformation to T-cell-rich B-cell lymphoma. She was treated with six cycles of cyclophosphamide, doxorubicin, prednisone, rituximab and vincristine chemotherapy and remains in remission. Her morphoea has since recurred, requiring hydroxychloroquine and further UVA1 therapy, with a good clinical response. The second case involved a 54-year-old woman with a background of long-standing psoriasis and Sjögren syndrome, who presented with generalized morphoea characterized by extensive skin thickening, induration and joint mobility restriction. Treatment was initiated with hydroxychloroquine and methotrexate. However, within 4 months, she developed cervical lymphadenopathy, and a biopsy confirmed stage IVB anaplastic large cell lymphoma. Immunosuppressive medications for morphoea were discontinued, and she had a poor response to the initial chemotherapy regimen of brentuximab, cyclophosphamide, doxorubicin and prednisolone. She is due to begin an alternative chemotherapy regimen, with plans for autologous stem cell transplantation. These cases highlight the intricate interplay between generalized morphoea and lymphoma, emphasizing the need for a tailored approach to therapy. The heightened risk of lymphoma in autoimmune conditions necessitates careful balancing of immunosuppression and oncological treatment, with a close multidisciplinary approach to optimize patient outcomes.

  • Research Article
  • 10.1200/jco.2025.43.16_suppl.7003
A phase 1 study of KITE-363 anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy in patients (pts) with relapsed/refractory (R/R) B-cell lymphoma (BCL).
  • Jun 1, 2025
  • Journal of Clinical Oncology
  • Saurabh Dahiya + 17 more

7003 Background: Approximately 30% of pts with R/R LBCL who relapse after CAR T-cell therapy experience CD19 antigen escape (Spiegel et al. Blood. 2021).KITE-363 is a bicistronic, autologous CAR T-cell therapy that can potentially prevent CD19 escape through upfront dual targeting of CD19 and CD20. Here we report safety and preliminary efficacy from an open-label, multicenter Phase 1 study of KITE-363 in R/R BCL. Methods: Eligible adults had LBCL, indolent NHL, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), or mediastinal gray zone lymphoma R/R after ≥2 lines of therapy (LoT). Pts with LBCL may have had primary refractory disease after ≥1 LoT. Study included dose escalation (1A) and expansion (1B; LBCL only) cohorts. After lymphodepleting chemotherapy, pts received KITE-363 at dose levels (DLs) 1, 2, or 3 (0.5×10 6 , 1×10 6 , or 2×10 6 CAR T cells/kg, respectively). Primary endpoints were incidence of dose-limiting toxicities (DLTs; Phase 1A) and investigator-assessed objective response rate (ORR per Lugano; Phase 1B). Results: As of 10/14/2024, 41 pts enrolled and 37 received KITE-363 (see table). For pts with LBCL (n = 34), 50% were primary refractory and 44% had IPI 3-4. No DLTs occurred. Grade ≥3 adverse events (AEs) occurred in 76% of treated pts and serious AEs in 49%. Grade 3 cytokine release syndrome (CRS; per Lee et al. 2014) occurred in 1 pt (3%; NLPHL; DL 3); Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 pts (8%; 1 DL 2; 2 DL 3); no Grade ≥4 CRS/ICANS occurred. Median onset of ICANS was 6 d with median duration of 5 d, and median onset of CRS was 4 d with median duration of 5 d. Six pts died (5 to progression; 1 to myelodysplastic syndrome concurrent with LBCL relapse, unrelated to KITE-363). At 7.3 months median follow-up, ORR in CAR-naive pts at DL 3 was 87%; complete response (CR) rate was 78%. Among those, all 7 pts with LBCL who were CAR-naive after ≥2 LoT had a CR. Those in DL 3 who were primary refractory (n = 15) had an 80% ORR (CR rate, 67%). Median duration of response was not reached. In all pts at DL 3 (n = 26), median CAR T-cell expansion peak, area under the curve (AUC), and time to peak were 121.5 cells/µL, 711.1 cells/µL×d, and 10 d, respectively. For CAR-naive pts in DL 3, median peak and AUC were 132.2 cells/µL and 819.2 cells/µL×d; medians in those with prior CAR T-cell therapy (n = 3) were 5.7 cells/µL and 85.7 cells/µL×d, respectively. Conclusions: No DLTs occurred in Phase 1A. Safety profile of KITE-363 was tolerable, with no Grade ≥3 CRS in pts with LBCL and 2 cases of Grade 3 ICANS at the highest DL. KITE-363 demonstrated high responses in pts with highly refractory BCL, including those with primary refractory disease. Clinical trial information: NCT04989803 . Baseline characteristics. Treated Pts (N=37) a Median age, y (range) 62 (25-83) ECOG 1 59 Stage III/IV 73 ≥3 prior LoT 41 Prior CAR T-cell exposure 19 a Percent unless otherwise specified.

  • Research Article
  • 10.1111/ejh.14443
Efficacy and Safety of Bendamustine‐Rituximab for Nodular Lymphocyte Predominant Hodgkin Lymphoma
  • Jun 1, 2025
  • European Journal of Haematology
  • Alexander Robin + 6 more

ABSTRACTIntroductionBendamustine‐rituximab (BR) has demonstrated efficacy and tolerability in the treatment of various indolent B‐cell lymphomas, but there is limited data regarding its outcomes in nodular lymphocyte predominant B‐cell (Hodgkin) lymphoma (NLPBL).MethodsThis retrospective, population‐based study included consecutive patients ≥ 18 years old who received BR for NLPBL in Alberta, Canada.ResultsThe study population comprised 23 patients with a median age of 39 years (range 18–74) who received BR for treatment‐naive (n = 17) or relapsed/refractory (n = 6) NLPBL. Advanced stage disease was present in 18 (78%), splenic involvement in 9 (39%), and bone marrow involvement in 8 (35%) patients. The response rate to BR was 100%, with a complete response in 78% and a partial response in 22%. After a median follow‐up of 4.3 years (range 0.8–9.0), the 4‐year progression‐free survival and overall survival rates were 83% (95% CI: 55%–94%) and 87% (95% CI: 58%–97%) for all patients and 84% (95% CI: 50%–96%) and 91% (95% CI: 51%–99%) for recipients of first‐line BR, respectively. The safety profile was in keeping with the known toxicities of BR, with the most common adverse events consisting of neutropenia, rash, and infusion reactions.ConclusionThese findings suggest that BR is a promising treatment option for NLPBL, with a favorable efficacy and safety profile.

  • Open Access Icon
  • Research Article
  • 10.1038/s41375-025-02641-3
Refining histopathological growth pattern-based risk group discrimination in nodular lymphocyte-predominant Hodgkin lymphoma: an analysis from the German Hodgkin Study Group
  • May 13, 2025
  • Leukemia
  • Dennis A Eichenauer + 10 more

Histopathological growth patterns (GP) in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have previously been divided into GP AB (typical) vs CDEF (variant). However, it is unclear whether this division is optimal. We thus investigated alternative GP grouping approaches (GP ABC vs DEF; GP ABCF vs DE). Overall, 583 NLPHL patients who had first-line treatment within GHSG trials were included in the analysis. Median age was 39 years; 74% of patients were male; 76% presented with early-stage and 24% with advanced-stage disease. The 5-year and 10-year progression-free survival (PFS) estimates for all patients were 85.9% and 76.6%; overall survival (OS) estimates were 95.8% and 94.5%. Significant PFS and OS differences were detected for the comparison GP ABCF vs DE with worse outcomes for the GP DE group (HR: 1.7; 95%-CI: 1.1–2.7; HR: 2.5; 95%-CI: 1.1–5.7). No PFS and OS differences were observed for the comparisons GP AB vs CDEF and GP ABC vs DEF. Median time to death was shorter and death more often due to NLPHL in the GP DE (13 months; 66.7%) than in the GP ABCF (31 months; 5.6%) group. Hence, the division of GP into GP ABCF vs DE allows an optimized GP-based risk group discrimination in NLPHL.

  • Research Article
  • 10.1158/1538-7445.am2025-5270
Abstract 5270: Novel dual-stain IHC assay enables discovery with enhanced clarity
  • Apr 21, 2025
  • Cancer Research
  • Scott Anderson + 3 more

Abstract Background: Immunohistochemistry (IHC) analysis has become a powerful and integral component in the diagnostic workup of tumors. It has been essential in biomarker discovery, with a growing demand for high-output methods that maximize data from limited tissue samples. Chromoplex II, an advanced technique that enables the simultaneous detection of dual stains on a single slide, permits the selection of primary antibodies to be stained in either color, aiding tissue differentiation while minimizing the interference often seen with endogenous pigments or slide debris. The duplex approach also reduces slide usage compared to single-stains and individual slides. Methods: Using the BOND-III Automated IHC and in-situ hybridization (ISH) stainer from Leica Biosystems, Chromoplex II was evaluated in three dual-marker applications. At least five cases with known tumors of distinct tumor histology/classification were utilized to examine differences between the distinct cellular histology (i.e., adenocarcinoma and squamous carcinoma) as well as classical Hodgkin lymphoma (cHL) versus nodular lymphocyte predominant Hodgkin lymphoma (NLP). Another commonly encountered scenario is the difficulty in separating lung adenocarcinoma and bystander macrophages, so these tissues were tested as well. Stained slides were scanned using the Aperio GT 450 scanner from Leica Biosystems and evaluated by a clinical pathologist for specificity and comparability to single staining. The marker combinations and tissues tested were the following: CD20/CD30: Lymph node CK5/Napsin A: Lung CD163/PD-L1: Lung Results: In all three marker combinations, the Chromoplex II kit produced distinct red and green stains, providing a clear visualization of target markers. Importantly, it minimized background interference, significantly enhancing clarity in challenging tissue sections. The slides exhibited comparable signal and reproducibility compared to single marker staining, and many examples were noted in which the dual stain provided vital context about the nature of the relationship between the two markers studied. Conclusions: Chromoplex II represents a promising tool for high-throughput biomarker studies in research, offering benefits in both clarity of staining and operational efficiency by reducing slide volume. Furthermore, additional studies and/or combinations are necessary to explore expanded marker combinations for broader cancer biomarker research applications. Citation Format: Scott Anderson, Stephen Pyper, Jack Heath, Julio Poveda. Novel dual-stain IHC assay enables discovery with enhanced clarity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5270.

  • Research Article
  • 10.1158/1538-7445.am2025-2525
Abstract 2525: Translating clinically validated antibodies into a multiplexed immunofluorescent panel for the spatial profiling of lymphoid malignancies
  • Apr 21, 2025
  • Cancer Research
  • Tania Pannellini + 8 more

Abstract Lymphoid malignancies present significant diagnostic challenges due to overlapping immunophenotypic features between tumor cells and reactive background cells, complicating the distinction between indolent lymphomas and benign lymph node hyperplasia [Nicolae A, Hemato, 2024, DOI:10.3390/hemato5030026]. Moreover, some Hodgkin lymphoma (HL) subtypes, such as lymphocyte-rich (LRHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and certain variants of diffuse large B-cell lymphoma (DLBCL), exhibit similar phenotypic profiles despite having different therapeutic implications [PMID: 35741318]. This study aims to leverage sequential immunofluorescence (seqIF™, PMID: 37813886) for the spatial profiling of lymphoma to improve differential diagnosis and to uncover spatial patterns unique to each lymphoma subtype, providing insights into potential predictors of immunotherapy response. Here, we optimized a seqIF™ panel of 21 markers, using antibodies approved for clinical immunohistochemistry (IHC), to phenotype mature B-cell lymphomas on the COMET™ platform. This panel was applied to tissue microarrays prepared from representative cases of DLBCL, HL, indolent lymphomas, and benign lymph node hyperplasia. Each marker of the optimized panel was visually validated by certified pathologists, comparing seqIF™ results against corresponding IHC images. Computation of spatial matrix successfully identified tumor cells and reactive cells using thresholding of fluorescence intensity and cell diameter, particularly in HL and DLBCL cases that exhibited similar immunophenotypes at first glance. This enabled us to map classified cells events back to the tissue sections, allowing direct spatial correlation with stained images for a comprehensive analysis of cell distribution. Ongoing work aims at refining our lymphoma spatial profiles through the integration of spatial transcriptomics readout on the same sample cohort. Together these results highlight the potential of multiplex immunofluorescence (mIF) for the diagnostic phenotyping of lymphoma, transferring clinically validated antibodies into a mIF panel. The ability to assess both phenotypic and spatial characteristics of tumor and reactive cells will enhance our understanding of lymphoma biology and provide new insights into predictive markers for immunotherapy responses. Citation Format: Tania Pannellini, Fabio Iannelli, Valentina Tabanelli, Carmen De Simone, Roberto Chiarle, Samuel Aubert, Pedro Machado Almeida, Maria Giuseppina Procopio, Saska Brajkovic. Translating clinically validated antibodies into a multiplexed immunofluorescent panel for the spatial profiling of lymphoid malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2525.

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