Nodal Lymphoma Research Articles

Refining Diagnostic Subtypes of Peripheral T-cell Lymphoma Using a Multiparameter Approach

Peripheral T-cell lymphoma (PTCL) is a heterogeneous category, and many cases are unclassifiable and designated as PTCL-not otherwise specified (PTCL-NOS). Gene expression profiling (GEP) has delineated two prognostic subtypes within PTCL-NOS, PTCL-TBX21, and PTCL-GATA3, characterized by distinctive transcriptomes and a different prognosis. To further evaluate the pathologic features of these subgroups, 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities underwent detailed pathologic, immunophenotypic (including TFH biomarkers) and GEP analyses, separating them into PTCL-NOS (n=63) and PTCL-TFH (a.k.a. nodal PTCL-TFH, NOS, and TFH lymphoma, NOS) (n=38). PTCL-NOS cases were further categorized into PTCL-GATA3 (n=22; 34%) and PTCL-TBX21 (n=41; 66%), and a significant association (p < 0.02) with overall survival (OS) was reaffirmed. Histopathological assessment showed PTCL-GATA3 cases were characterized by monotonous medium-sized or large transformed cells with a minimal tumor microenvironment (TME) compared to PTCL-TBX21 cases, which consisted of pleomorphic cells in a polymorphous TME (p < 0.05). GEP analysis validated these TME distinctions. Immunophenotypic analysis showed that PTCL-GATA3 cases were predominantly CD4+CD8- and associated with significantly higher LEF1, MYC, and CD30 expression (p < 0.05). PTCL-TBX21 displayed a more diverse biomarker profile with two subgroups: one expressing cytotoxic antigens and enriched in CD8+CD4- or CD8-CD4- phenotype, and another lacking cytotoxic markers but showing a CD4+CD8- phenotype with increased ICOS expression, but devoid of other TFH markers. The PTCL-TFH cases correlated with an angioimmunoblastic T-cell lymphoma (AITL) gene signature, had more EBER-positive cells than the PTCL-GATA3 and PTCL-TBX21 cases, and a subset had some morphologic features of AITL (p < 0.01). This study highlights the unique morphologic and phenotypic variations within the newly-identified PTCL subtypes and should enable more precise diagnosis and tailored therapeutic strategies in the future.

Risk of second primary cancers in nodal non-Hodgkin lymphoma patients by primary lymph node location: a retrospective cohort population-based study

Background: Non-Hodgkin lymphoma (NHL) is a diverse group of blood cancers with increasing incidence and survival rates due to advancements in treatment and early detection. However, NHL survivors are at significant risk of developing second primary cancers, which can adversely impact their long-term survival. Methods: This retrospective population-based cohort study utilized data from the Surveillance, Epidemiology, and End Results database, covering 17 geographic areas in the United States from 2000 to 2021. The authors included patients diagnosed with nodal NHL as a first primary cancer and excluded those diagnosed at autopsy or via death certificate only. Standardized Incidence Ratios, Absolute Excess Risks, and Person-Years at Risk were calculated to evaluate the risk of developing SPCs according to the primary lymph node site and stratified by latency periods following the initial NHL diagnosis. Results: The cohort included 54 012 NHL patients. The authors’ results showed that for most SPCs, the risk of development was different for different primary NHL lymph node locations. The highest risks were observed for thyroid cancer, acute myeloid leukemia, and Hodgkin lymphoma. Notably, the risk for thyroid cancer was highest in the first year post-diagnosis, while hematological malignancies such as acute myeloid leukemia and Hodgkin lymphoma showed elevated risks in the intermediate and late latency periods. Conclusion: NHL survivors are at an increased risk of developing SPCs, influenced by the primary lymph node site and latency period. These findings highlight the need for tailored surveillance strategies and preventive measures to mitigate the long-term risks of SPCs in NHL survivors. Further research is necessary to elucidate the underlying mechanisms and to develop targeted interventions for this high-risk population.

Comparison of CHOP-19 and CHOP-25 for treatment of peripheral nodal B-cell lymphoma in dogs: A European multicenter retrospective cohort study.

Peripheral nodal B-cell lymphomas (PNBCL) represent the most common presentation of lymphomas in dogs. Multiagent CHOP (C = cyclophosphamide, H = hydroxydaunorubicin [Doxorubicin], O = Oncovin, P = prednisolone)-based chemotherapy protocols have been widely accepted as gold standard 1st-line treatment. CHOP-25 and CHOP-19 are most commonly prescribed but have never been directly compared. Our primary aim was to compare outcomes of dogs diagnosed with PNBCL, treated using a 1st-line CHOP-19 or CHOP-25 protocol. A secondary objective was to determine the impact of protocol-related variables on outcomes. Five hundred two dogs from 16 European oncology referral centers. One hundred fifty-five dogs were treated with CHOP-19 and 347 dogs with CHOP-25. Retrospective, multicentric cohort study of dogs diagnosed with PNBCL between 2014 and 2021. The 6-month, 1-year, and median progression-free survival (PFS) were 56.5% (95% confidence interval [CI], 49.2-65.0), 14.1% (95% CI, 9.4-21.0), and 196 days (95% CI, 176-233) with CHOP-19; and 56.4% (95% CI, 51.4-61.9), 17% (95% CI, 13.4-21.6), and 209 days (95% CI, 187-224) with CHOP-25. The 1-year, 2-year and median overall survival (OS) were 36.9% (95% CI, 29.7-46.0), 13.5% (95% CI, 8.6-21.1), and 302 days (95% CI, 249-338) with CHOP-19; and 42.8% (95% CI, 37.7-48.7), 15.4% (95% CI, 11.7-20.4), and 321 days (95% CI, 293-357) with CHOP-25. No significant difference in PFS and OS was found between the 2 protocols. Our study confirmed similar outcomes for dogs with PNBCL treated with 1st-line CHOP-19 or CHOP-25. Both protocols therefore could be used as a standard of care in future trials.

Proteomic Profiling of Lymph Nodes Differentiates Classic Hodgkin Lymphoma With and Without Skeletal Involvement.

Classic Hodgkin lymphoma (CHL) is a highly curable disease, even in advanced stages. Controversy remains over whether bone involvement negatively affects overall and progression-free survival in patients treated with intensive chemotherapy regimens. Whether cases that present with bone lesions harbor specific tumor microenvironmental features is unknown. We investigated protein expression in diagnostic lymph node biopsies from CHL patients with and without skeletal involvement at diagnosis to identify potential markers of skeletal disease. Protein expression patterns in diagnostic formalin-fixed paraffin-embedded lymphoma lymph node samples from CHL patients were analyzed by nano-liquid chromatography-tandem mass spectrometry. Patients were grouped according to skeletal involvement, which was defined as the presence of one or more FDG-avid lesions on a diagnostic FDG-PET/CT scan. Protein profiles identified patients with skeletal disease at diagnosis and showed disrupted cellular pathways, including immune system processes, cell adhesion, and cell growth/survival. Immunohistochemical evaluation also demonstrated differential expressions of angiotensin-converting enzyme (ACE), intercellular adhesion molecule 3 (ICAM3), integrin alpha-X (ITGAX), and calreticulin (CALR). In conclusion, proteomics identified altered protein expression profiles in lymph nodes among CHL cases presenting with disease disseminated to the skeletal system, which implies altered disease pathogenesis for these patients.

Pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma: additional evidence to support they are a single disease with variation in the histologic spectrum.

Pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) are two rare indolent B-cell lymphomas with overlapping features. Recently, cases showing hybridizing features of PTFL and PNMZL have been reported. Herein, we retrospectively analyzed the clinicopathologic features of 59 patients, including 39 with PTFL, 5 with PNMZL, and 15 with mixed-type tumors (MTT). And next-generation sequencing analysis was performed on 3 PTFL, 2 PNMZL, and 2 MTT cases. In addition, previously published mutational data of 96 PTFLs, 25 PNMZLs, and 46 MTTs were also analyzed. There were 52 male and 7 female patients, with a median age of 17years. Most patients (96.6%) had lymph node involvement in the head and neck region and were diagnosed with stage I disease. Among the 50 patients (85%) with telephone follow-up, 44 (88%) adopted a watch-and-wait strategy after surgical resection of the lesions. Only one PTFL patient experienced a relapse 6months after diagnosis. Microscopically, not only the MTT cases showed a composite form of enlarged follicles and interfollicular lymphocytic proliferation producing a progressively transformed germinal center (PTGC) pattern, but also focal follicles with a PTGC-like pattern were observed in PTFL cases. Genetically, the most frequently mutated genes were TNFRSF14 (in 3 PTFLs and 2 MTTs), MAP2K1 (in 2 PTFLs, 1 PNMZL and 1 MTT), and IRF8 (in 2 MTTs and 1 PNMZL). Based on the similar or overlapping clinical, pathologic, and genetic features, PTFL and PNMZL are likely to represent two different histologic patterns of the same disease.

Histomorphologic spectrum of nodal marginal zone lymphoma as defined by its methylome.

Primary nodal marginal B-cell lymphoma (NMZL) is rare and histologically very variable. Its large-cell presentation is difficult to distinguish from nodal diffuse large B-cell lymphoma (nDLBCL) due to the absence of specific markers for nodal marginal zone lymphomas in general. Using a comprehensive cohort of NMZLs and a control cohort of nDLBCLs, we conducted a methylome analysis on subgroups of both. The methylomes were strikingly different between the cohorts but unexpectedly homogeneous within the NMZL cohort. This allowed us to describe the morphologic spectrum of NMZL in all its value ranges. The considerable overlap in growth pattern and cytology of NMZL with nDLBCL was explored morphometrically, leading to an operational tool for separating both by a simple measurement of cell size and nuclear size. This was integrated in a hierarchical approach, including a scoring system for the parameter growth pattern, follicular colonization, follicular dendritic network, IgD expression, and Ki-67 rate, and led to a proposal for a classifier that we present here. This methylome-based study extends the morphological spectrum of NMZL towards large cell morphology and offers a conventional way to distinguish it from nDLBCL.

7824 Orbital Lymphoma masquerading as Thyroid Eye Disease

Abstract Disclosure: S. Ganawa: None. S. Joseph: None. C. Anshuman: None. D. Luciane L: None. A. Sajid: None. C. Anne: None. S. Dhage: None. Thyroid eye disease (TED) is the most common extrathyroidal manifestation in Graves’ disease (GD). In this case report, we present a case of a 64 years old lady, who was initially diagnosed with thyroid eye disease about 9 years ago. However, she was clinically and biochemically euthyroid. She was offered an orbital decompression surgery by local ophthalmology team. Patient wasn’t keen on the surgery at this stage.Recently she experienced increased swelling of her eyes, with conjunctival redness, oedema, and diplopia bilaterally, more evident on the left side. She was initiated on intravenous methylprednisolone (IVMP) weekly, by local ophthalmology team and was referred to our specialist thyroid eye clinic for further management.On presentation to us, her clinical activity score (CAS) was 5/7, but she was euthyroid clinically and biochemically. She was continued on weekly IVMP and oral mycophenolate mofetil (MMF) was added on as per the latest EUGOGO guidelines published in 2021. Her treatment was reviewed after the anti thyroperoxidase (TPO) and anti-Thyroid Stimulating Hormone receptor (TSH) antibodies were reported as negative and her eyes worsened despite the treatment with IVMP and MMF.Her repeat MR orbit at this stage showed possible orbital lymphoma. Her immunosuppressive medications were discontinued at this stage. After further discussions at regional thyroid eye MDT and radiology MDT, an orbital biopsy was arranged for, which confirmed Extra nodal Marginal Zone lymphoma, with no high-grade component. She has been referred to the oncology unit for further assessment and management.This case highlights the importance of considering alternative differential diagnosis in certain patients with atypical features or those who are non-responders to the first line immunosuppressive therapies for thyroid eye disease. Details of this case and relevant literature will be reviewed in this report. Presentation: 6/3/2024

Coexpression of MYC and BCL2 oncoproteins in primary nodal versus primary extranodal diffuse large B-cell lymphoma

Objectives: Diffuse large B-cell lymphoma (DLBCL) is a morphologically and molecularly diversified disease with aggressive biological behavior. The double expression of MYC/BCL2 proteins portends a poorer prognosis. This study aims to evaluate the frequency, describe the clinicopathological features of the double-expressor phenotype of DLBCL in primary nodal (PN) versus primary extranodal (PEN) sites, and investigate their associations. Materials and Methods: A total of 48 patients with the double-expressor phenotype of lymphoma (DEPL) in a tertiary care hospital were included over three years. Clinicopathological parameters and associations were investigated based on the primary site. Statistical Analysis: Data were documented and analyzed using appropriate statistical tests. Results: The incidence of DEPL in our study was 28.7%. The median age of all DEPL patients was 56 years, with a predominance of men (69%). DEPL cases were further subcategorized as PN-DEPL (n = 33) and PEN-DEPL (n=15). Males were affected almost equally in both groups. More PN-DEPL patients exhibited B symptoms (82%), elevated lactate dehydrogenase (LDH) levels (73%), III/IV stage disease (71%), and maximum revised international prognostic index (R-IPI) score (64%) compared to PEN-DEPL patients. On the other hand, bone marrow (BM) involvement (87%), activated B-cell-type phenotype (80%), pathologic stage I/II (67%), and Ki67 index &gt;90% (93%) were more common in PEN-DEPL patients. Conclusions: Significant differences were observed between PN-DEPL and PEN-DEPL in terms of B symptoms, LDH levels, stage at presentation, BM involvement, pathological subtype, Ki67 index, and R-IPI score. This study provides an estimate of the burden of this aggressive entity and encourages further prognostic studies and therapeutic trials.

Histologic, Phenotypic, and Molecular Characterization of Feline Hodgkin-Like Lymphoma With Classical Reed-Sternberg Cells.

Hodgkin-like lymphoma (HLL) is a rare neoplasm in cats that shares characteristics with the human disease. The hallmark of HLL is the presence of Reed-Sternberg (RS) cells expressing CD30 and CD20. This study aimed to elucidate the clinicopathologic features, immunophenotype and clonality patterns of feline HLL. A comprehensive retrospective review of clinicopathologic and molecular data of nodal lymphomas over a 6-year period was conducted in MyLav laboratory. Twenty-four cases were identified. All cats presented with submandibular or retropharyngeal lymphadenopathy. Histopathologic examination revealed a multifocal to diffuse proliferation of medium-to-large lymphoid cells with low mitotic activity, interspersed RS cells, and a heterogeneous inflammatory infiltrate comprising T-cells, plasma cells and neutrophils. In addition, extensive necrosis was a consistent finding. Immunohistochemistry showed a variable membranous CD20 and nuclear PAX5 expression in neoplastic cells, while RS cells displayed only mild to moderate CD20 positivity and were negative to PAX5. In 21/24 cases (87.5%), RS cells were diffusely CD30-positive. PARR analysis demonstrated clonal B-cell expansion in 60% of cases, with the remaining 40% exhibiting polyclonality. For the 10 cats with available follow-up, the prognosis was generally favourable, with only two cats succumbing to progressive disease. In conclusion, diagnosing feline HLL is challenging. The expression of CD30 and CD20 by RS cells should be considered a hallmark of the disease, but only after excluding differential diagnoses such as anaplastic B-cell lymphoma and granulomatous lymphadenopathy.

A case of BIA-ALCL in which postoperative chest wall recurrence was highly suspected: the third reported case of BIA-ALCL in Japan

BackgroundBreast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare malignancy. Many cases of BIA-ALCL are identified based on the presence of late-onset effusion and/or masses. Importantly, the United States Food and Drug Administration noted that in all cases diagnosed in patients with textured implants, the patients either had a history of mixed implantation of smooth and textured devices or no clinical history was supplied for review. In Japan, the first case of BIA-ALCL was reported in 2019, and we encountered the third case in Japan in December 2021. There have been a total of five cases of BIA-ALCL previously reported at Japanese academic conferences (Japan Oncoplastic Breast Surgery Society. http://jopbs.umin.jp/medical/index.html), of which only the first case has been published. Unlike the first case, this patient had clinical features that were highly suggestive of the postoperative chest wall recurrence of breast cancer, with a mass and rash on the skin.Case presentationThe patient was a 45-year-old woman who had undergone breast reconstruction after breast cancer surgery of the right breast 8 years previously. The patient presented with a mass and skin rash inside the inframammary area, and we suspected a damaged silicone breast implant (SBI) or chest wall recurrence. We examined the mass by a core needle biopsy and made a pathological diagnosis of BIA-ALCL. Imaging findings suggested internal thoracic lymph node swelling and lymphoma infiltration beyond the capsule but no metastatic lesions (cStage III). After en bloc resection of the SBI and lymphoma, adjuvant systemic therapy was performed.ConclusionWe encountered the third case of BIA-ALCL in Japan. This was a case with clinically advanced stage of disease; however, the BIA-ALCL was found to be in remission.

Simultaneous occurrence of papillary thyroid carcinoma, medullary thyroid carcinoma, and lymphoma: A case report.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, the coexistence of PTC and medullary thyroid carcinoma (MTC) is uncommon. While the simultaneous occurrence of both cancers with small lymphocytic lymphoma (SLL) in lymph nodes with PTC metastasis is very rare. This study presents a unique case of concurrent PTC, MTC, and SLL, highlighting the exceptional rarity of these coexisting tumors. A 75-year-old female with a thyroid tumor underwent total thyroidectomy, bilateral central neck lymph node dissection, and right radical neck lymph node dissection. Histopathological examination revealed a low-grade medullary thyroid carcinoma (MTC) in the left lobe and classical papillary thyroid carcinoma (PTC) in the right lobe, with PTC metastasis in the cervical lymph nodes and concurrent SLL in the affected lymph nodes. Coexistence of PTC, MTC and SLL in the same patient is rare, there are currently no standardized treatment guidelines due to the limited literature. However, it is essential to consider not only the treatment for each type of tumor but also the potential risks or conflicts associated with the treatments. In the case reported in this paper, the papillary carcinoma invaded the capsule of the right lobe of the thyroid and metastasized to the cervical lymph nodes, warranting radioactive iodine therapy. However, considering the potential negative impact of radioactive iodine on the pre-existing lymphoma, the radioactive iodine therapy was postponed. Meanwhile, constant monitoring of calcitonin and thyroid globulin should be performed to monitor tumor recurrence as was performed in the present case. Since MTC, PTC, and SLL may coexist, patients with PTC deserve careful surveillance for the other disease entities. This case underscores the need for heightened awareness among clinicians, radiologists, and pathologists regarding the possibility of concurrent thyroid tumors and abnormal lymph nodes, guiding comprehensive pre-operative evaluations and postoperative monitoring strategies. This study aims to provide a warning for routine pathological diagnosis and contribute data for related research.

Post-Chemotherapy Canine Lymphomatous Lymph Node Observations on B-Mode and Strain Elastographic Ultrasound.

Canine multicentric lymphoma (CML) is a prevalent hematopoietic neoplasm that initially responds well to treatment but often relapses due to chemotherapy resistance. Evaluation of treatment response is essential for effective management. Ultrasound (US) can differentiate between benign and lymphomatous lymph nodes (LLNs). However, its utility in monitoring LLNs post chemotherapy is limited. This study aimed to compare US parameters of LLNs during the first 3 weeks post treatment and evaluate their diagnostic performance compared with the conventional method for assessing treatment response. This study included 95 LLNs from 15 dogs with CML and 60 normal lymph nodes (NLNs) from 15 healthy dogs. US, including B-mode and elastography, was performed pre-treatment and weekly for 3 weeks post treatment, and compared with the results of NLNs. LLNs were categorized into partial response and stable disease groups using the conventional method. US scores were established by combining B-mode and elastography parameters. The results showed significantly higher values of LLNs in the short-to-long axis ratio, elastographic scales, and blue-to-green color histogram compared with NLNs. Additionally, LLNs at pre-treatment had significantly higher values than LLNs post treatment. US scores significantly differed among the healthy, partial response, and stable disease groups. In conclusion, B-mode US, elastography, and US scores demonstrated changes during chemotherapy consistent with the conventional method and can be used in conjunction with the conventional method to evaluate the treatment response of CML.

Assessment of Ki-67 Proliferative Index in Cytological Samples of Nodal B-Cell Lymphomas.

The Ki-67 proliferative index (PI) is part of the diagnosis of nodal B-cell lymphoma (nBCL), but its determination in cytological samples is not standardized. We aimed to establish an approach for the accurate determination of the Ki-67 PI in cytological slides to differentiate between indolent and aggressive nBCLs. Patients diagnosed with nBCL by fine-needle aspiration biopsy and subsequent excision biopsy were included. Cell suspensions were prepared from biopsy samples for CD3/Ki-67 double immunocytochemical staining and flow-cytometric verification of lymphoma B-cell counts. The Ki-67 PI was assessed by manual counting and eyeballing in cytology and eyeballing in histology. The cut-off values for the differentiation between aggressive and indolent lymphomas were determined for each method. A strong correlation between manual and flow-cytometric counting of lymphoma B cells was confirmed (interclass correlation coefficient (IC coef.) = 0.78). The correlation of the Ki-67 PI determined in cytological and histological slides was also strong (IC coef. > 0.80). Histologically, 55 cases were classified as indolent and 31 as aggressive nBCLs. KI-67 PI cut-off values of 28.5%, 27.5%, and 35.5% were established for manual counting and eyeballing in cytology and eyeballing in histology, respectively, with high sensitivity and specificity. The Ki-67 PI, assessed by manual counting and eyeballing in cytological samples, accurately differentiates between indolent and aggressive nBCLs.

Clinicopathological differences in MYC and BCL2 protein expression between primary extranodal and nodal diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) exhibits clinical, genetic, and immunohistochemical heterogeneity. However, the differences between primary extranodal or nodal DLBCL and double-expressor lymphoma (DEL), which is characterized by high MYC and BCL2 expression, remain unclear. This study aimed to elucidate the clinicopathological features, response to therapy, and clinical outcomes of primary extranodal (n=61) and nodal (n=128) DLBCL. Patients with primary nodal DLBCL had higher BCL2 expression than those with extranodal DLBCL (p=0.048), with high MYC expression and DEL as poor prognostic factors. Conversely, in patients with primary extranodal DLBCL, high BCL2 expression, low BCL6 expression, non-germinal center B-cell-like type, and DEL indicated poor prognosis. DEL was significantly associated with progression free survival and overall survival in patients with primary extranodal DLBCL (p=0.014 and p=0.021, respectively) but not in patients with primary nodal DLBCL (p=0.37 and p=0.084, respectively). Our findings highlight primary extranodal DEL as a strong adverse prognostic factor in DLBCL.

Deep phenotyping of nodal T-cell lymphomas reveals immune alterations and therapeutic targets.

Whereas immunotherapies have revolutionized the treatment of different solid and hematological cancers, their efficacy in nodal peripheral T-cell lymphomas (PTCLs) is limited, due to a lack of understanding of the immune response they trigger. To fully characterize the immune tumor microenvironment (TME) of PTCLs, we performed spectral flow cytometry analyses on 11 angioimmunoblastic T-cell lymphomas (AITL), 7 PTCL, not otherwise specified (PTCL, NOS) lymph node samples, and 10 non-tumoral control samples. The PTCL TME contained a larger proportion of regulatory T cells and exhausted CD8+ T cells, with enriched expression of druggable immune checkpoints. Interestingly, CD39 expression was up-regulated at the surface of most immune cells, and a multi-immunofluorescence analyses on a retrospective cohort of 43 AITL patients demonstrated a significant association between high CD39 expression by T cells and poor patient prognosis. Together, our study unravels the complex TME of nodal PTCLs, identifies targetable immune checkpoints, and highlights CD39 as a novel prognostic factor.

Immunophenotypic classification regarding prognosis in peripheral T cell lymphoma, NOS, and nodal T follicular helper T cell lymphoma, angioimmunoblastic-type.

This study aimed to determine the clinicopathological predictive factors of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), and nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFH, AI-type). In this single-centered, retrospective study, medical records of 59 patients who were diagnosed with PTCL, NOS, or nTFH, AI-type from March 2007 to September 2022 were reviewed. The clinicopathological variables, including immunohistochemistry(IHC) subgroups, distinguishing TBX21 from the GATA3 subgroups were analyzed. Overall, 28 patients (75.7%) in the TBX21 group were PTCL, NOS. There were 9 (24.3%) patients in the GATA3 group. In univariable analyses, lymphoma subtype, age, and performance status were associated with progression-free survival (PFS), and overall survival (OS). In multivariable analyses, lymphoma subtype, and performance status were related to PFS and OS (P = 0.012, P < 0.001, P = 0.006, and P < 0.001, respectively). The GATA3 subgroup tended to have a worse prognosis in univariable analyses; however, it became more insignificant in multivariable when lymphoma subtype and performance status were adjusted (P = 0.065, P = 0.180, P = 0.972, and P = 0.265, respectively). The double-positive group showed variable prognoses of better PFS and worse OS. PD-1 and PD-L1 were associated with the EBV in situ hybridization (P = 0.027, and P = 0.005), and PD-1 was associated with CD30 expression (P = 0.043). This study demonstrated the potential of IHC classification to predict prognosis for PTCL, NOS, as well as nTFH AI-type, although further validation is necessary. Treatments targeting CD30, PD-1, and PD-L1 appear promising for lymphoma treatment.

Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study

Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator's choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL. Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator's choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375). 86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown). Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial. Bristol-Myers Squibb. For the French translation of the abstract see Supplementary Materials section.

Analysis of early response to chemotherapy for non-Hodgkin’s lymphoma by quantitative contrast-enhanced ultrasound: A prospective case-control crossectional study

ObjectiveTo investigate the value of quantitative contrast-enhanced ultrasonography (CEUS) in assessing and predicting early therapy response of non-Hodgkin’s lymphoma (NHL). MethodsFifty-six cases of NHL were studied using CEUS before and after three cycles of R-CHOP / CHOP. Quantitative parameters such as arrival time (ATM), time to peak (TTP), △T = TTP-ATM, area under the gamma curve (Area), curve gradient (Grad), wash-out time (WT), base intensity (BI), peak intensity (PI) and ΔI = PI-BI were compared between the lymphoma and normal lymph nodes before and at mid-treatment, respectively. Changes in quantitative CEUS parameters were also compared between complete response (CR) and incomplete response(non-CR) groups. Besides, the correlation analysis was performed between pretreatment PI and changes in quantitative parameters. ResultsAfter three cycles of R-CHOP/CHOP, S/L (P < 0.001), PI (P = 0.002), ΔI (P < 0.001), Grad (P < 0.001), and Area (P < 0.001) of NHL were significantly decreased. The CR group and non-CR group only differed in ATM before treatment. In contrast, there was no statistical difference in any of the parameters between the two groups at mid-treatment. Finally, a significant correlation was observed between pre-treatment PI and PI△% (r = 0.736, P < 0.001). ConclusionsCEUS is promising for the assessment of response of NHL to R-CHOP/CHOP. Intra-lesion perfusion changes take precedence over morphological changes suggesting treatment efficacy. Pre-treatment ATM values may help to suggest efficacy outcomes and pre-treatment PI values may be a valid predictor of lymphoma perfusion response.

Iodine density of lymphoma, metastatic SCCA, and normal cervical lymph nodes: Based on DLSCT

Objective To compare iodine density (ID) and contrast-enhanced attenuation value (CEAV) from dual-layer spectral computed tomography (DLSCT) scans of lymphomatous, metastatic squamous cell carcinoma (SCCA), and normal cervical lymph nodes. Methods Data including ID and CEAV were retrospectively collected from patients who underwent DLSCT of the neck between January 2020 and August 2023. Results from each group (lymphomatous, metastatic SCCA, and normal) were compared and analyzed using one-way ANOVA and receiver operating characteristic curve. Results 129 cervical lymph nodes were collected from patients who met the inclusion criteria (50, 41, and 38 nodes from the lymphomatous, metastatic SCCA, and normal group, respectively). The mean ID of lymphomatous, metastatic SCCA, and normal nodes was 1.01±0.27, 1.36±0.28, and 1.45±0.29 mg/mL, respectively. Comparing lymphomatous nodes with metastatic SCCA nodes, the lymphomatous nodes had significantly lower values of ID (p&lt;0.002) and CEAV (p&lt;0.001). Similarly, when comparing lymphomatous nodes with normal nodes, the lymphomatous nodes had significantly lower values of ID (p&lt;0.001) and CEAV (p&lt;0.001). The optimal ID cut-off value for distinguishing between lymphomatous and metastatic SCCA nodes was 1.175 mg/ml (specificity of 84.2%, sensitivity 77.8%, AUC 0.788, P = 0.003). The optimal CEAV cut-off value was 77.5 HU (specificity 88.9%, sensitivity 78.9%, AUC 0.851, P&lt;0.001). Conclusions The ID and CEAV measurements from DLSCT were significantly different between lymphomatous, metastatic SCCA, and normal lymph nodes. These findings indicate that DLSCT can be used to distinguish between these conditions in the diagnosis of cervical lymph nodes.

Exploratory screening for micro-RNA biomarkers in canine multicentric lymphoma.

Lymphoma is one of the most frequent hematopoietic tumors in dogs and shares similar features with human counterparts. MicroRNAs (miRNA, small non-coding RNAs) are pivotal in gene regulation fine tuning and cancer hallmarks are influenced by their aberrant expression. Consequently, miRNA biomarkers may assist predicting therapeutic response and clinical outcome by providing less-invasive novel diagnostics tools. The aim of this study was to detect dysregulated miRNAs in lymphomatous lymph node tissues in comparison to lymph node material or PBMCs from healthy control dogs. Potential significant differences in miRNA expression profiles between four lymphoma entities were evaluated. A customized PCR array was utilized to profile 89 canine target miRNAs. Quantification was performed using qPCR, relative expression was determined by the delta-delta Ct method, and p-values were calculated with student's t-test. In the 14 diffuse large B-cell lymphoma (DLBCL) patients, 28 and 24 different miRNAs were significantly dysregulated compared to lymph node material or PBMCs. Sixteen miRNAs occurred in both control groups, with 12 miRNAs being down- and four miRNAs being upregulated. The six peripheral T-cell lymphoma (PTCL) samples showed 24 and 25 dysregulated miRNAs when compared to the healthy controls. A combined analysis of DLBCL and PTCL samples revealed seven shared and 19 differently expressed miRNAs. Potential biomarkers in T- and B-cell lymphoma could be the miRNA-17/92 cluster and miRNA-181-family together with miRNA-34a and miRNA-150. Diagnostic utility of potential biomarkers must be validated in larger, prospective cohorts of canine lymphoma cases and in higher numbers of physiological patient material.