Subtype Of Lymphoma Research Articles

Exploring the complexity, treatment challenges, and outcomes in pediatric nodular lymphocyte predominant Hodgkin lymphoma: a perspective from a low–middle-income country

BackgroundIn children, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Given the lack of data on the best chemotherapy regimen, there is a knowledge gap in best management.MethodsThis retrospective study included all pediatric patients with NLPHL diagnosed and treated at the Children’s Cancer Hospital, Egypt (2007–2018). We analyzed the clinical characteristics, and treatment outcome according to disease stage (early and advanced), treatment strategy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] and explored the prognostic factors for progression-free survival.ResultsThe median age at diagnosis was 12 years; 40 (68%) patients had early-stage disease, and 19 (32%) had advanced-stage disease. The median follow-up was 70 months; the 5-year EFS and OS were 75% and 97%, respectively. The 5-year EFS was 78% for early-stage disease and 60% for advanced-stage disease; the 5-year OS was 100% for early-stage disease and 88% for advanced-stage disease. The patients who underwent R-CHOP had a better 3-year EFS (100%) compared with those who underwent ABVD (65%) regimen (P = 0.01). Seventeen (25%) patients relapsed: 9/40 (22%) had early-stage disease, and 8/19 (42%) had advanced-stage disease. Splenic involvement, mediastinal disease, extranodal disease, and slow early response were independent predictors of relapse risk.ConclusionPediatric patients with early-stage NLPHL have an excellent prognosis, with a 5-year OS of 100%. However, those with advanced stages had a high relapse rate. R-CHOP was associated with a better response and relapse-free rate than ABVD.

Primary Mediastinal Large B-cell Lymphoma – A Case Report

AbstractPrimary mediastinal large B-cell lymphoma (PMBL) is an uncommon and aggressive subtype of non-Hodgkin large B-cell lymphoma that affects patients in the third and fourth decades of life. The objective of the present report is to describe the case of a male patient admitted to the emergency room with symptoms of dyspnea associated with signs of superior vena cava syndrome. The imaging exams revealed two masses in the mediastinum; the definitive diagnosis, established through an anatomopathological examination and immunohistochemistry, was of PMBL, and the patient was referred for chemotherapy.

MRD Detection in B-Cell Non-Hodgkin Lymphomas Using Ig Gene Rearrangements and Chromosomal Translocations as Targets for Real-Time Quantitative PCR and ddPCR.

Minimal residual disease (MRD) diagnostics is of high clinical relevance in patients with indolent B-cell non-Hodgkin lymphomas (B-NHL), B-cell chronic lymphocytic leukemia (CLL), and multiple myeloma and serves as a surrogate parameter to evaluate treatment effectiveness and long-term prognosis. Real-time quantitative PCR (RQ-PCR) targeting circulating lymphoma cells is still the gold standard for MRD detection in indolent B-NHL and currently the most sensitive and the most broadly applied method in follicular lymphoma (FL) and mantle cell lymphoma (MCL). Alternatively, droplet digital PCR (ddPCR) can be used for MRD monitoring in multiple myeloma, mantle cell lymphoma, CLL, and FL with comparable sensitivity, accuracy, and reproducibility.The most broadly applicable MRD target in B-NHL is the junctional regions of the rearranged immunoglobulin heavy (IGH) and light chain genes. Complete and incomplete IGH and additionally IG kappa light chain rearrangements can be used as targets for MRD. Next-generation sequencing (NGS) of IG-rearrangements (IG-NGS) as new sequencing-based technology can overcome the limitation of PCR-based approaches and has a potential for higher sensitivity. Chromosomal translocations like the t(14;18)(q32;q21) translocation associated with IGH::BCL2 fusion in FL and t(11;14)(q13;q32) translocation in MCL leading to the IGH::CCND1 fusion can be used as MRD target in selected lymphoma subtypes. In patients with CLL, both flow-cytometry and RQ-PCR are equally suited for MRD assessment as long as a sensitivity of 10-4 is achieved.MRD diagnostics targeting the IG loci is complex and requires extensive knowledge and experience because the junctional regions of each clonal rearranged gene have to be identified before the patient-specific PCR assays can be designed for MRD monitoring. In addition, the presence and load of somatic hypermutation within the rearranged IGH gene occurring during B-cell development of germinal center and post-germinal center B-cell lymphomas may hamper appropriate primer binding leading to false-negative results. The translocations mentioned above have the advantage that consensus forward primers and probes, both placed in the breakpoint regions of chromosome 18 in FL and chromosome 11 in MCL, can be used in combination with a reverse primer placed in the IGH joining region of chromosome 14. PCR-based methods using allele-specific primers can reach a high sensitivity of up to 10-5. This chapter provides all relevant background information and technical aspects for the complete laboratory process from detection of the clonal IG gene rearrangements and the chromosomal translocations at diagnosis to the actual MRD measurements in clinical follow-up samples of B-NHL. However, it should be noted that MRD diagnostics for clinical treatment protocols has to be accompanied by regular international quality control rounds to ensure the reproducibility and reliability of the MRD results. This is available by the EuroMRD network ( https://euromrd.org ), a subgroup of ESHLO ( https://eslho.org ).

Uncommon presentation of diffuse large B-cell lymphoma: oral and pulmonary involvements in a young patient: a case report

BackgroundDiffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphomas that remains a major diagnostic challenge due to the variety of its clinical presentations. This case highlights the importance of early biopsy of oral lesions without tendency to heal to attain the diagnosis more quickly. To the best of our knowledge, this study is the first to focus on both oral and pulmonary involvements in a patient with diffuse large B-cell lymphoma.Case presentationThe presented case describes an Iranian 18-year-old girl with chronic cough and dyspnea referred for evaluation of the upper jaw due to bone exposure, bone loss, and soft tissue ulceration. Her medical history revealed mediastinal mass, cavitary lesion, and mediastinal lymphadenopathy. However, cytologic and immunohistochemical analysis did not show any evidence of malignancy. In this case a lymphoproliferative disease was suspected but ultimately the oral biopsy diagnosed diffuse large B-cell lymphoma and chemotherapy could be started.ConclusionsSystemic conditions should be considered as a possible cause of oral lesions and a biopsy should also be performed immediately if there is any doubt concerning the nature of the lesion. Moreover, some conditions necessitate multiple biopsies to attain an accurate diagnosis.

A Diagnostic Challenge in the Biopsy of a Mammographic Abnormality

Abstract Introduction/Objective Primary breast marginal zone lymphoma (MZL) is an uncommon subtype of extranodal lymphoma, and its diagnosis presents challenges, particularly in distinguishing it from lymphoplasmacytic lymphoma (LPL). MYD88 L265P mutation has been identified in a subset of marginal zone lymphomas, comprising 6-9% of cases. This genetic alteration further complicates the differentiation between MZL and LPL in breast tumors. We present a case highlighting the diagnostic complexities associated with primary breast MZL. Methods/Case Report A 71-year-old female patient underwent mammographic screening, which revealed a suspicious lesion in her left breast. Subsequent PET scan showed a hypermetabolic area consistent with a primary breast lesion. Biopsy histology exhibited a diffuse atypical lymphoid infiltration with varying proportions of neoplastic lymphocytes. Immunohistochemical analysis revealed positivity for CD20, PAX5, BCL2, CD138, MUM1, and negativity for CD3, CD5, Cyclin D1, CD10, CD23, CD34, BCL6, TDT, CD30, GATA3, and CK AE1/3. Additionally, there was lambda light chain restriction, and the Ki67 proliferation rate index was approximately 50%. Fish analysis indicated abnormal BCL6 gene rearrangement. Molecular genetic testing confirmed the presence of MYD88 mutation with c.794T>C p.L265P. Notably, bone marrow biopsy showed no abnormalities, with normal hematopoiesis. Serum electrophoresis and immunofixation detected an IgM monoclonal protein with lambda light chain specificity. Results (if a Case Study enter NA) NA Conclusion The diagnosis of primary breast MZL was favored over LPL due to the absence of common LPL- associated symptoms such as bone marrow involvement. However, the distinction between these entities remains challenging, underscoring the importance of comprehensive diagnostic approaches integrating histopathology, immunohistochemistry, and molecular genetics. Further research is warranted to enhance diagnostic certainty in such cases, particularly as the management of MZL and LPL becomes increasingly specific with the advent of novel therapeutic agents and ongoing clinical trials.

A Rare Case of Diffuse Large B Cell Lymphoma Co-occurring with Small Lymphocytic Leukemia: De Novo Process or Richter’s Syndrome?

Abstract Introduction/Objective Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of lymphoma and can arise either de novo or through transformation from indolent lymphomas, such as Chronic Lymphocytic Leukemia (CLL), known as Richter syndrome (RS). DLBCL derived from RS tends to exhibit more aggressive behavior compared to de novo DLBCL. Methods/Case Report We present a case of a 57-year-old female with no significant medical history, who initially presented with antibiotic and prednisone-resistant sinusitis, progressing to bilateral neck pain and eye congestion. Computed tomography (CT) imaging revealed a 3 cm mass in the right nasal cavity extending to the right maxillary sinus and medial right orbit. Histopathological examination showed diffuse sheets of intermediate to large cells with irregular nuclear contours, dispersed chromatin, variably conspicuous nucleoli, and moderate cytoplasm. Additionally, scattered foci of monotonous, atypical lymphoid cells with lower grade morphology, including small size and condensed chromatin, were also present. Immunohistochemical analysis revealed differential staining patterns between the two cell populations. The larger atypical cells expressed CD20, PAX5, CD10, BCL-6, MUM1, BCL-2, MYC, CD19 (dim), and exhibited a high Ki-67 proliferation index (>80%). In contrast, the smaller atypical cells were positive for CD5, CD19, CD20, PAX5, BCL-2, and CD23 (subset), with a lower Ki-67 proliferation index (<5%). Flow cytometry analysis of tissue samples revealed two distinct clones: Surface Kappa-restricted CD19 dim B cells (38.9%) with CD5- CD10 dim CD20+ and surface Lambda-restricted CD19+ B cells (58.7%) with CD5+ CD10- CD20+. FISH analysis revealed no gene rearrangements. The final diagnosis was Diffuse large B-cell lymphoma, germinal center B- cell phenotype, with aggressive features and focal involvement by small lymphocytic lymphoma/chronic lymphocytic leukemia. Results (if a Case Study enter NA) NA Conclusion The relationship between the large B-cell lymphoma and SLL/CLL remains uncertain; however, given the different immunophenotype and light chain expression observed by flow cytometry, they are likely to represent separate processes.

Breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma is a subtype of non-Hodgkin's lymphoma that can occur around the surface of textured breast implants or in patients who have previously had textured breast implants. The condition should be suspected in cases of late-onset breast asymmetry and seroma formation around a breast implant. If the implant and surrounding connective tissue capsule is removed, the prognosis is usually very good. The purpose of this clinical review article is to provide a brief overview of the diagnosis and treatment of breast implant-associated anaplastic large cell lymphoma.

Genetic alterations of class I HLA in cutaneous T-cell lymphoma

Abnormalities involving class I HLA are frequent in many lymphoma subtypes but have not yet been extensively studied in cutaneous T-cell lymphomas (CTCL). We characterized the occurrence of class I HLA abnormalities in 65 patients with advanced mycosis fungoides (MF) or Sézary syndrome (SS). Targeted DNA sequencing including coverage of HLA loci revealed at least one HLA abnormality in 26/65 patients (40%). Twelve unique somatic HLA mutations were identified across nine patients, and loss of heterozygosity or biallelic loss of HLA was found to affect 24 patients. Although specific HLA alleles were commonly disrupted, these events did not associate with decreased total class I HLA expression. Genetic events preferentially disrupted HLA alleles capable of presentation of greater numbers of putative neoantigens. HLA abnormalities co-occurred with other genetic immune evasion events and were associated with worse progression-free survival. Single-cell analyses demonstrated HLA abnormalities were frequently subclonal. Through analysis of serial samples, we observed disrupting class I HLA events change dynamically over the disease course. The dynamics of HLA disruption are highlighted in a patient receiving pembrolizumab, where resistance to pembrolizumab was associated with elimination of an HLA mutation. Overall, our findings show that genomic class I HLA abnormalities are common in advanced CTCL and may be an important consideration in understanding the effects of immunotherapy in CTCL.

Prevalence and Prognostication of CD5+ Mature T-Cell Lymphomas

Background: T-cell lymphomas (TCLs) are a group of heterogenous cancers with poor rates and duration of response. There remains a great challenge in risk stratification of these cancers. Cluster of differentiation (CD) 5 has shown prognostic implication in many subtypes of B-cell lymphoma; however, its role in TCLs is not known. Methods: We performed a single-institution retrospective analysis of newly diagnosed patients with TCL. CD5 positivity was determined based on positive results via immunohistochemistry and/or flow cytometry. We used univariate and multivariable analysis of biological factors to assess their association with survival outcomes. Results: A total of 194 patients with TCL spanning 14 subtypes were identified. CD5 positivity was noted in 63% of patients, with the highest proportion of CD5 expression in TFH TCL (93.9%), PTCL-NOS (82.9%), and ATLL (77.8%) (p = 0.00004). Older age at diagnosis (p = 0.001), stage III or IV disease (p = 0.05), and bone marrow involvement (p = 0.003) were also associated with CD5 expression. Complete response rates were numerically lower in patients with CD5+ TCL across all subtypes. OS/PFS was not statistically associated with CD5 status in the overall cohort; however there was significantly decreased OS in CD5+ TFH TCL (p = 0.04) and CD5+ ATLL (p = 0.04) patients. Conclusions: This study represents the first to examine CD5 expression as a prognostic biomarker for outcomes in TCL. The frequent expression of CD5 in the most common nodal TCL in the Western world underpins its potential as an attractive target for cellular therapies. Confirmation of these findings in a larger cohort and investigation of potential pathophysiological mechanisms explaining our observations are planned.

Lymphomas of the submandibular gland: a nationwide cohort study.

This study explores the epidemiology, incidence, and survival outcomes associated with lymphomas of the submandibular gland (SMG) and examines the influence of autoimmune diseases on these parameters. This retrospective nationwide cohort study analysed data from patients diagnosed with SMG lymphomas in Denmark between 2000 and 2020. Information was extracted from medical records, the National Pathology Register, and the Danish Lymphoma Database. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models, focusing on lymphoma subtypes and autoimmune diseases. The cohort consisted of 101 patients with a lymphoma diagnosis and involvement of the SMG. Large B-cell lymphoma (LBCL) was diagnosed in 33 cases (32.7%), follicular lymphoma (FL) in 29 cases (28.7%), extranodal marginal zone lymphoma (EMZL) in 27 cases (26.7%), and 12 cases (11.9%) with other subtypes. EMZL had a significantly longer overall survival (OS) compared to other subtypes, with a median OS of 12.4 years (95% CI 11.2-12.4) vs. 8.4 years (95% CI 6.0-12.2). EMZL and FL showed favourable 5-year OS rates of 95% and 89%, respectively. LBCL had a 5-year OS rate of 65%. Age over 60 significantly negatively impacted OS. Traditional poor prognostic indicators did not significantly affect OS. A notable association between EMZL and autoimmune diseases was observed, particularly with Sjögren's syndrome, indicated by an increased relative risk of 2.67 (CI 95% 0.45-16.01). Lymphomas of the SMG are rare and have ambiguous clinical presentations. This study provides novel epidemiological, clinical, and prognostic information.

Non-cryopreserved autologous peripheral blood stem cell transplantation for multiple myeloma and lymphoma in countries with limited resources: practice considerations from the Worldwide Network for Blood and Marrow Transplantation.

Autologous peripheral blood stem cell (PBSC) transplantation is a standard treatment of multiple myeloma (MM), Hodgkin lymphoma and various subtypes of non-Hodgkin lymphoma. Cryopreservation of hematopoietic stem cells is standard practice that allows time for delivery of conditioning regimen prior to cell infusion. The aim of this Worldwide Network for Blood & Marrow Transplantation (WBMT) work was to assess existing evidence on non-cryopreserved autologous transplants through a systematic review/meta-analysis, to study feasibility and safety of this approach. We searched PubMed, Web of Science and SCOPUS for studies that utilized non-cryopreserved autologous PBSC transplantation. Identified literature was reviewed for information on mobilization, apheresis, preservation and viability, conditioning regimen, engraftment, response, and survival. Results highlight collective experience from 19 transplant centers (1686 patients), that performed autologous transplants using non-cryopreserved PBSCs. The mean of infused CD34+ was 5.6 × 106/kg. Stem cell viability at transplantation was >90% in MM and >75% in lymphomas, after a storage time of 24-144 h at +4 °C. Mean time-to-neutrophil engraftment was 12 days and 15.3 days for platelets. Pooled proportion estimates of day 100 transplant-related mortality and graft failure were 1% and 0%, respectively. Non-cryopreservation of apheresed autologous PBSCs appears feasible and safe.

Therapeutic advances for the management of adult T cell leukemia: Where do we stand?

Adult T cell leukemia (ATL) is an aggressive blood malignancy secondary to chronic infection with the human T cell leukemia virus type I (HTLV-1) retrovirus. ATL encompasses four subtypes (acute, lymphoma, chronic, and smoldering), which exhibit different clinical characteristics and respond differently to various treatment strategies. Yet, all four subtypes are characterized by a dismal long-term prognosis and a low survival rate. While antiretroviral therapy improves overall survival outcomes in smoldering and chronic subtypes, survival remains poor in lymphoma subtypes despite their good response to intensive chemotherapy. Nonetheless, acute ATL remains the most aggressive form associated with profound immunosuppression, chemo-resistance and dismal prognosis. Targeted therapies such as monoclonal antibodies, epigenetic therapies, and arsenic/IFN, emerged as promising therapeutic approaches in ATL. Allogeneic hematopoietic cell transplantation is the only potentially curative modality, alas applicable to only a small percentage of patients. The recent findings demonstrating the expression of the viral oncoprotein Tax in primary ATL cells from patients with acute or chronic ATL, albeit at low levels, and their dependence on continuous Tax expression for their survival, position ATL as a virus-addicted leukemia and validates the rationale of anti-viral treatment strategies. This review provides a comprehensive overview on conventional, anti-viral and targeted therapies of ATL, with emphasis on Tax-targeted therapied in the pre-clinical and clinical settings.

Efficacy of thiotepa-conditioned autologous stem-cell transplantation as consolidation therapy for primary leptomeningeal malignant lymphoma: a case report and review of literature.

Primary leptomeningeal malignant lymphoma (PLML) is a rare subtype of primary central nervous system lymphoma (PCNSL). Treatment is often based on PCNSL, but currently there is no established treatment strategy due to its rarity. We report a case of a 46-year-old male diagnosed with PLML through cerebrospinal fluid cytology and flow cytometry, presenting with multiple cranial nerve palsies and L5 radiculopathy. The patient achieved complete remission (CR) with R-MPV (rituximab, methotrexate, procarbazine, and vincristine) combined with intrathecal chemotherapy (methotrexate, cytarabine, and prednisolone). This was followed by autologous stem-cell transplantation (ASCT) using a thiotepa-based conditioning regimen, resulting in sustained CR. A literature review on the use of ASCT for PLML revealed three reported cases, including ours, all achieving CR with ASCT and minimal adverse events. These findings suggest that ASCT can be a promising consolidation therapy for PLML. Further studies are needed to establish standardized treatment protocols for this rare condition.

Exploring Differentially Expressed Genes and Immune Modulation in Diffuse Large B-Cell Lymphoma through RNA Sequencing Analysis.

Diffuse large B-cell lymphoma (DLBCL) is globally recognized as the most prevalent and aggressive subtype of non-Hodgkin lymphoma. While conventional treatments are effective initially, the disease can become resistant or relapse over time. This study aimed to examine the differentially expressed genes at the transcriptome level and molecular pathways in DLBCL patients. This investigation utilized RNA sequencing analysis to compare differentially expressed gene samples from five diffuse large B-cell lymphoma patients with two healthy volunteers. These participants were admitted to UKM Medical Center, Kuala Lumpur between 2019 and 2020. The differentially expressed genes were identified using the DESeq2 R package (version 1.10.1) using a negative binomial distribution model. The obtained P values were corrected with the Benjamin and Hochberg method and identified using a False Discovery Rate threshold of <0.05, with log2 fold change (FC) of ≥2 or ≤-2. Results showed 73 differentially expressed genes between the two groups, among which 70 genes were downregulated, and three genes were upregulated. The differentially expressed genes analyzed with the Reactome pathway were significantly associated with the downregulation of antimicrobial humoral response (P<0.001), neutrophil degranulation (P<0.001), chemokine receptors bind chemokines (P=0.028), defensins (P=0.028) and metabolism of angiotensinogen (P=0.040). These findings suggest that the identified pathways may contribute to cancer progression and weaken the immune response in diffuse large B-cell lymphoma patients. This study offers fresh insights into previously undiscovered downstream targets and pathways modulated by diffuse large B-cell lymphoma.

Cancer Incidence among Marines and Navy Personnel and Civilian Workers Exposed to Industrial Solvents in Drinking Water at US Marine Corps Base Camp Lejeune: A Cohort Study.

Drinking water at US Marine Corps Base Camp Lejeune, North Carolina, was contaminated with trichloroethylene and other industrial solvents from 1953 to 1985. A cohort cancer incidence study was conducted of Marines/Navy personnel who began service and were stationed at Camp Lejeune () or Camp Pendleton, California () between 1975 and 1985 and civilian workers employed at Camp Lejeune () or Camp Pendleton () between October 1972 and December 1985. Camp Pendleton's drinking water was not contaminated with industrial solvents. Individual-level information on primary invasive cancers and in situ bladder cancer diagnosed between 1996 and 2017 was obtained from 54 US cancer registries. Proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) comparing cancer incidence between the Camp Lejeune and Camp Pendleton cohorts, adjusted for sex, race, education, and rank (or blue-collar work), with age as the time variable. Precision of aHRs was evaluated using the 95% confidence interval (CI) ratio (CIR). Cancers among Camp Lejeune Marines/Navy personnel and civilian workers totaled 12,083 and 1,563, respectively. Cancers among Camp Pendleton Marines/Navy personnel and civilian workers totaled 12,144 and 1,416, respectively. Compared with Camp Pendleton, Camp Lejeune Marines/Navy personnel had aHRs with CIRs for all myeloid cancers (; 95% CI: 1.03, 1.49), acute myeloid leukemia (; 95% CI: 1.03, 1.85), myelodysplastic and myeloproliferative syndromes (; 95% CI: 1.07, 2.62), polycythemia vera (; 95% CI: 0.94, 2.11), and cancers of the esophagus (; 95% CI: 1.03, 1.56), larynx (; 95% CI: 0.98, 1.50), soft tissue (; 95% CI: 0.92, 1.59), and thyroid (; 95% CI: 1.03, 1.45). Lymphoma subtypes mantle cell and marginal zone B-cell and lung cancer subtypes adenocarcinoma and non-small cell lung cancer also had aHRs with CIRs . Compared with Camp Pendleton, Camp Lejeune civilian workers had aHRs with CIRs for all myeloid cancers (; 95% CI: 0.83, 2.36), squamous cell lung cancer (; 95% CI: 1.10, 2.41), and female breast (; 95% CI: 0.97, 1.52) and ductal cancer (; 95% CI: 1.02, 1.71). Increased risks of several cancers were observed among Marines/Navy personnel and civilian workers exposed to contaminated drinking water at Camp Lejeune compared with Camp Pendleton. https://doi.org/10.1289/EHP14966.

Mantle cell lymphoma with skin involvement: Case report of a rare manifestation in a patient with initial diagnosis of chronic lymphocytic leukemia

Mantle cell lymphoma is a rare subtype of B-cell non-Hodgkin's lymphoma, which mainly affects males. It has a variable clinical presentation, with a course ranging from indolent cases that do not require treatment for years to very aggressive cases. Skin involvement is a rare event. Although most patients have disease in stage III or IV at diagnosis, they generally present with good functional status. In immunohistochemistry, CD5 is commonly expressed, a feature it shares with chronic lymphocytic leukemia. Cyclin D1 and SOX11 expression are present in almost all cases. Treatment depends on multiple factors such as age, frailty, comorbidities, disease stage, symptoms and morphological characteristics. We present the case of a male patient initially diagnosed with chronic lymphocytic leukemia who was started on treatment with ibrutinib. A biopsy of the right earlobe was subsequently performed, which documented secondary skin involvement due to a classic histological variant of mantle cell lymphoma. The patient was treated with chemotherapy between March and July 2022, with positron emission tomography at the end of the proposed cycles with complete metabolic response, so maintenance treatment with rituximab was performed and subsequently consolidated with an autologous bone marrow transplant. To date, the patient is in remission of the disease.

CORRELATION OF T-CELL LYMPHOMA SUBTYPES WITH ANEMIA AT DR MOHAMMAD HOESIN HOSPITAL PALEMBANG 2018-2022

Lymphoma is divided into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Among NHL T-cell lymphoma is a rare malignancy of T cells, accounts for 12% of all NHL cases, it is further classified into 53 subtypes by WHO. T-cell lymphoma generally have worse prognosis than those B cells. In 2020 there were 16.125 new cases in Indonesia with 9.024 deaths for all ages and genders. Anemia occurs in some cases of lymphoma, which will make the prognosis of lymphoma worse. This study aims to determine the relationship between T-cell lymphoma subtype and anemia. This observational analytic study utilized a cross-sectional design conducted at the Department of Anatomic Pathology Faculty of Medicine Sriwiaya University/Dr. Mohammad Hoesin Palembang Hospital (RSMH) and the central laboratory of RSMH. The samples from this study were all patients who were diagnosed histopathologically and immunohistochemically as T cell lymphoma at RSMH Palembang from 2018 to 2022. Among 38 samples, T-cell lymphoma predominated in the age group &lt;55 years (73,7%), male gender (73,7%), extranodal location (73,7%), and ENKTCL, nasal subtype (55,3%). Anemia occurred in 60,5% cases and most often it is mild anemia (60,9%). There was no significant correlation between T-cell lymphoma subtype and anemia status (*p = 0.178) and T-cell lymphoma subtype and anemia degree (*p = 0.342). It can be concluded that there is no significant correlation between the T-cell lymphoma subtype and anemia.

HBx induces chemoresistance in diffuse large B cell lymphoma by inhibiting intrinsic apoptosis via the NF-κB/XIAP pathway

Diffuse large B-cell lymphoma (DLBCL) is the predominant subtype of malignant lymphoma in adults with high heterogeneity. Hepatitis B virus (HBV) has been shown to infect B lymphocytes and has been associated with a higher risk of developing DLBCL, most clearly in countries where HBV is endemic. Accumulating evidence suggests the standard chemotherapy regimens for DLBCL patients with HBV infection exhibit limited efficacy and unfavorable outcomes. The HBx antigen, encoded by the X gene in the four open reading frames of HBV, maybe a key molecule promoting the heightened malignant biological characteristics of DLBCL, but whether it affects the chemotherapy response and the mechanism in DLBCL remains unclear. Through the implementation of in vitro and vivo experiments, our study demonstrates that HBx antigen triggers excessive activation of the NF-κB pathway, resulting in increased expression of X-linked inhibitor of apoptosis protein (XIAP). This upregulation inhibits caspase 3-mediated intrinsic apoptosis and enhances resistance to first-line chemotherapeutic agents like epirubicin and vincristine in DLBCL. These findings offer insights into the development of innovative combination therapies for DLBCL patients with HBV infection.

Lymphoma cell-driven IL-16 is expressed in activated B-cell-like diffuse large Bcell lymphomas and regulates the pro-tumor microenvironment.

The activated B-cell-like subtype of diffuse large B-cell lymphoma (ABC-DLBCL) displays a worse outcome than the germinal center B-cell-like subtype (GCB-DLBCL). Currently, targeting tumor microenvironment (TME) is the promising approach to cure DLBCL with profound molecular heterogeneity, however, the factors affecting the tumor-promoting TME of ABCDLBCL are elusive. Here, cytokine interleukin-16 (IL-16) is expressed in tumor cells of ABCDLBCL and secreted by the cleavage of active caspase-3. The serum IL-16 levels are not only a sensitive marker of treatment response but also positively correlated with unfavorable prognosis in DLBCL patients. While IL-16 shows few direct promotional effects on tumor cell growth in vitro, its bioactive form significantly promotes tumor progression in vivo. Mechanically, IL-16 increases the infiltration of macrophages by the chemotaxis of CD4+ monocytes in the TME enhancing angiogenesis, and the expression of cytokine IL-6 and IL-10, as well as decreasing T cell infiltration to accelerate tumor progression. This study demonstrates that IL-16 exerts a novel role in coordinating the bidirectional interactions between tumor progression and the TME. IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα, reverses the tumorpromoting effects of IL-16,which provides new insight into treatment strategy in ABC-DLBCL.

Decreased PU.1 expression in mature B cells induces lymphomagenesis.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for 30% of non-Hodgkin lymphomas. Although comprehensive analysis of genetic abnormalities has led to the classification of lymphomas, the exact mechanism of lymphomagenesis remains elusive. The Ets family transcription factor, PU.1, encoded by Spi1, is essential for the development of myeloid and lymphoid cells. Our previous research illustrated the tumor suppressor function of PU.1 in classical Hodgkin lymphoma and myeloma cells. In the current study, we found that patients with DLBCL exhibited notably reduced PU.1 expression in their lymphoma cells, particularly in the non-germinal center B-cell-like (GCB) subtype. This observation suggests that downregulation of PU.1 may be implicated in DLBCL tumor growth. To further assess PU.1's role in mature B cells invivo, we generated conditional Spi1 knockout mice using Cγ1-Cre mice. Remarkably, 13 of the 23 knockout mice (56%) showed splenomegaly, lymphadenopathy, or masses, with some having histologically confirmed B-cell lymphomas. In contrast, no wild-type mice developed B-cell lymphoma. In addition, RNA-seq analysis of lymphoma cells from Cγ1-Cre Spi1F/F mice showed high frequency of each monoclonal CDR3 sequence, indicating that these lymphoma cells were monoclonal tumor cells. When these B lymphoma cells were transplanted into immunodeficient recipient mice, all mice died within 3 weeks. Lentiviral-transduced Spi1 rescued 60% of the recipient mice, suggesting that PU.1 has a tumor suppressor function invivo. Collectively, PU.1 is a tumor suppressor in mature B cells, and decreased PU.1 results in mature B-cell lymphoma development.