Ann Arbor Stage Research Articles

Ibrutinib and rituximab versus immunochemotherapy in patients with previously untreated mantle cell lymphoma (ENRICH): a randomised, open-label, phase 2/3 superiority trial

BackgroundFollicular lymphoma (FL) represents the most common subtype of indolent non‐Hodgkin's lymphoma. Extranodal involvement (ENI) indicates a poor clinical outcome in patients who received rituximab-based immunochemotherapy. Recent studies indicate that genetic alterations and tumor microenvironment dysregulation drive extranodal dissemination and lymphoma progression. However, the molecular mechanisms underlying ENI in FL remain to be fully elucidated.MethodsAiming to investigate the influence of oncogenic mutations and tumor microenvironment alterations on ENI in FL, the clinical features of 501 patients with newly diagnosed FL receiving rituximab-based therapy were analyzed, with DNA and RNA sequencing performed on 403 and 175 patients, respectively.ResultsMultiple ENI was observed in 120 (24%) patients and was significantly related to advanced Ann Arbor stage, decreased hemoglobin, elevated lactate dehydrogenase, elevated beta-2 microglobulin, lymph nodes ≥ 5 sites, lymph nodes > 6 cm, and high risk of progression of disease within 2 years (POD24). Increased KMT2D, CREBBP, CARD11, and STAT6 mutations, as well as downregulation of immune-associated pathways and alterations in lipid metabolism, were associated with multiple ENI. In the rituximab plus chemotherapy (R-chemo) cohort (n = 344), involvement of bone marrow, lung, liver, bones, and kidney/adrenal glands were unfavorable predictors of progression-free survival (PFS), with involvement of liver and kidney/adrenal glands as unfavorable predictors of overall survival (OS). However, in the rituximab plus lenalidomide immunotherapy (R2) cohort (n = 157), no ENI site showed a significant difference in PFS and OS.ConclusionsNegative prognostic impact of multiple ENI upon R-chemo therapy could be overcome by R2 therapy in FL. Better understanding of the biological behavior of multiple ENI could provide a potential clinical rationale for future mechanism-based therapy of FL.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13073-025-01557-y.

Non-Hodgkin lymphoma (NHL), a heterogeneous malignancy accounting for ~90% of lymphomas, often requires chemotherapy as the primary treatment for patients unsuitable for stem cell transplantation. This study aimed to analyze the therapeutic effects of gemcitabine combined with oxaliplatin on NHL and examine the prognostic factors affecting patients with NHL. A total of 106 patients with NHL were retrospectively selected and divided into a control group (CG; n=50 received oxaliplatin treatment) and an observation group (OG; n=56 received oxaliplatin combined with gemcitabine treatment) based on the differences in treatment measures. Clinical data, therapeutic efficacy, adverse reactions, improvement in B symptoms, post-treatment levels of lactate dehydrogenase (LDH) and TGF-β1 and post-treatment Karnofsky Performance Status (KPS) scores were collected from patients in both groups. Prognostic factors for NHL were analyzed based on the results of a 2-year follow-up. In the OG, the complete remission rate (CRR) was 73.21% and the disease control rate (DCR) was 91.07%, whereas in the CG, the CRR was 52.00% and the DCR was 80.00%, demonstrating a significant intergroup difference (P<0.05). The OG had an overall survival (OS) of 13.6 months and a progression-free survival (PFS) of 8.9 months, and the CG had an OS of 11.3 months and a PFS of 6.1 months. After chemotherapy, the serum LDH and TGF-β1 levels in the OG were significantly lower compared with those in the CG, and the KPS scores were higher compared with those in the CG (all P<0.05). Multivariate logistic regression analysis indicated that the Ann Arbor stage and the International Prognostic Index score for lymphoma were independent prognostic risk factors for patients with NHL (both P<0.05). The combination therapy of gemcitabine and oxaliplatin was demonstrated to be safe for patients with NHL. This combination treatment demonstrated notable overall efficacy and improved functional improvement compared with oxaliplatin monotherapy.

BackgroundPolo-like kinase 4 (PLK4) has been shown to be a tumor-promoting factor with multiple impacts on cancer growth, invasiveness, and treatment sensitivity. The current study aimed to investigate the expression of PLK4 in diffuse large B-cell lymphoma (DLBCL) versus control tissues and its relationship with disease features and prognosis in DLBCL patients undergoing R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) treatment.MethodsNinety-seven DLBCL patients who received R-CHOP treatment were retrospectively included, and the lesion tissue was retrieved and subjected to quantitative polymerase chain reaction (qPCR) for PLK expression determination. Another 30 control tissues (reactive lymphoid tissue) were also subjected to qPCR.ResultsPLK4 expression was greater in DLBCL tissue than in reactive lymphoid tissue (nearly 3-fold change, P < 0.001). PLK4 in DLBCL was correlated with increased Ann Arbor stage (P = 0.038), lactate dehydrogenase abnormality (P = 0.031), international prognostic index (IPI) score (P = 0.002) and IPI risk stratification (P = 0.001). After cutoff by quartiles, PLK4 ≥ 50% quantile (P = 0.040) and PLK4 ≥ 75% quantile (P = 0.021) were correlated with shorter progression-free survival (PFS), but PLK4 ≥ 25% quantile was not (P = 0.236); PLK4 ≥ 25% quantile (P = 0.349), PLK4 ≥ 50% quantile (P = 0.126), and PLK4 ≥ 75% quantile (P = 0.090) were not correlated with overall survival (OS). Moreover, threshold by best cutoff value (3.755), PLK4 > 3.755 was correlated with both worse PFS (P = 0.002) and OS (P = 0.036). After adjustment via multivariate Cox regression, PLK4 > 3.755 was independently correlated with PFS (hazard ratio = 3.900, P = 0.023).ConclusionsHigh PLK4 expression can reflect severe disease conditions and predict poor PFS in DLBCL patients undergoing R-CHOP treatment. This study sheds a light on the potency of PLK4 as a prognostic biomarker for DLBCL management. However, more large-sample-sized and multiple regional studies are needed for verification in the future.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12957-025-04017-4.

Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive form of non-Hodgkin lymphoma. B symptoms, including fever, night sweats and weight loss, are often overlooked but carry prognostic significance. The primary site of DLBCL also plays a crucial role in diagnosis and treatment decisions, and our study aims to explore the relationship among primary sites of DLBCL, the presence of B symptoms and patients' survival. 15,267 patients' data were analyzed in our study to investigate the potential relevance among B symptoms, primary sites and patients' survival. We assessed the influence of primary site and B symptoms on survival with the use of Survival package and Kaplan-Meier survival analysis. Age, race and Ann-Arbor stage were significantly associated with the presence of B symptoms. The incidence rate of B symptoms varied across primary sites, bone marrow had the highest probability (43.75%), while the genital system had the lowest rate (13.58%). B symptoms were siginificant prognostic indicators among nodal DLBCL patients especially those involved lymph nodes of multiple regions, as well as patients with lymphoma originating from bone marrow, glands and respiration. Survival analysis revealed that bone marrow, genital organs, lymph nodes of multiple regions and head and neck are linked to poorer survival outcomes, which happen to be either the highest or lowest B symptom incidence sites. These findings highlight the prognostic importance of both primary tumor site and B symptom status in DLBCL patients.

Study DesignRetrospective Cohort Study.ObjectivesIn this study, we aimed to evaluate the risk factors associated with cancer-specific survival (CSS) of patients with spinal and pelvic diffuse large B-cell lymphoma (SP-DLBCL) and construct a competing risk-based model for predicting 3- and 5-year CSS.MethodsData on patients diagnosed between 2010 and 2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The total dataset was randomly divided into the training and testing datasets at a ratio of 7:3. Factors associated with CSS were identified by competing risk regression for the construction of a nomogram on the training dataset. Further, the testing dataset was used to validate the performance of the nomogram.ResultsCompeting risk regression revealed that age, Ann Arbor Stage, and chemotherapy were independent prognostic factors for CSS. The nomogram exhibited satisfactory agreement on calibration plots for the training and testing datasets. The nomogram performed well on the training and testing datasets, exhibiting a good clinical net benefit. Thus, a nomogram-based web calculator was constructed for clinical application.ConclusionIn this study, we evaluated the risk factors of CSS in patients with SP-DLBCL using competing risk regression analysis. The established nomogram and web-based tool performed well and could be used widely in clinical practice.

Non-inferior outcome of abbreviated R-CHOP in patients with stage I primary testicular lymphoma.

This study aimed to evaluate diffuse large B-cell lymphoma (DLBCL) patients who have refractory/relapsed disease and characterize the heterogeneity of DLBCL using patient-level radiomics analysis based on 18F-FDG PET/CT. A total of 132 patients diagnosed with DLBCL who underwent 18F-FDG PET/CT before receiving treatment were selected for the final study. Patient-level volumes of interests (VOI) were extracted from PET/CT images, and 328 radiomics features were extracted subsequently. 8 radiomics features were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to calculate the radiomics score (rad-score). Additionally, a total of 64 potential ML classifiers were generated based on 8 distinct supervised learning algorithms. The combined model that integrates rad-scores, clinical features and standard PET parameters demonstrates excellent performance; Specifically, ML models based on Naive Bayes have the greatest predicted values (AUC = 0.73). The patient-level radiomics features were subjected to unsupervised non-negative matrix factorization (NMF) clustering analysis to identify 3 radiomics subtypes. Cluster 1 exhibited a substantially higher prevalence of refractory/relapsed DLBCL compared to Clusters 2 and 3 (P < 0.05). Moreover, Cluster 1 showed a significantly higher frequency of advanced Ann Arbor stage, high international prognostic index, and bulk disease (all P < 0.05). In conclusion, Radiomics scores and radiomics subtypes derived from patient-level data offer significant predictive value and phenotypic information for patients with refractory/relapsed DLBCL.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-08223-8.

Background: Classical Hodgkin lymphoma (cHL) demonstrates high survival rates with the ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine); however, the use of bleomycin is associated with a significant risk of pulmonary toxicity. The Risk-Adapted Treatment of HL (RATHL) trial demonstrated that omitting bleomycin in patients with favorable interim Positron Emission Tomography (PET-CT) results did not adversely affect survival outcomes. In this study, we present real-world data from advanced-stage HL patients treated according to the RATHL protocol. Methods: This multicenter, retrospective study included newly diagnosed cHL patients with Ann Arbor stage IIB–IV disease or stage IIA disease with bulky disease or with involvement of three or more sites, enrolled from 29 centers across Türkiye. The analysis focused on patients whose initial treatment was de-escalated from ABVD to AVD (bleomycin was omitted). Data were collected on demographic and clinical prognostic characteristics, interim PET-CT findings (evaluated using the Deauville score), progression-free survival (PFS) and overall survival (OS). Survival outcomes were assessed using Kaplan–Meier analysis. Results: A total of 379 patients were included, with a median age of 34 years (range: 18–78). Following interim PET-CT assessments (After 2 cycles of ABVD), Deauville scores were 1 in 39.8% of patients, 2 in 39.1%, and 3 in 21.1%. Based on these results, bleomycin was omitted immediately after interim PET-CT in 73.9% of patients, after one additional ABVD cycle in 12.1%, and after two additional cycles in 14%. The median follow-up duration was 28 months (range: 6–96). The 3-year PFS and OS rates were 86.0% and 96.1%, respectively. Patients with Deauville scores of 1–2 had a 3-year PFS rate of 87.6%, compared to 79.8% in those with a score of 3 (p = 0.087). Increased age, poor Eastern Cooperative Oncology Group Scale (ECOG) performance status, bulky disease, and higher International Prognostic Scores (IPS) were significantly associated with inferior OS (p < 0.05). There were no significant differences in OS among patients who received 2, 3, or 4 cycles of ABVD. However, among patients treated with 2 cycles of ABVD, both extranodal involvement (p = 0.039) and higher IPS (p = 0.002) were significantly associated with decreased PFS. Conclusions: Our findings demonstrate that PET-guided de-escalation of bleomycin after two cycles of ABVD is feasible, effective, and safe in real-world multicenter practice in Türkiye. The survival outcomes are comparable to those reported in the RATHL study, reinforcing the role of interim PET-CT in guiding individualized therapy. However, patients with high IPS or extranodal involvement may require more tailored management strategies.

BackgroundAngioimmunoblastic T-cell lymphoma (AITL), representing the second most prevalent subtype of peripheral T-cell lymphoma, currently lacks standardized frontline therapeutic strategies.MethodsIn this study, we evaluated the survival outcomes and prognostic factors in 154 patients with AITL treated with one of four regimens: CHOP (cyclophosphamide, vincristine, epirubicin, prednisone), CHOPE (CHOP + etoposide), CPET (chidamide, prednisone, etoposide, thalidomide), or GDPT (gemcitabine, cisplatin, dexamethasone, thalidomide). Among them, 144 patients had complete survival follow-up data. Survival differences across groups were analyzed using the log-rank test, while variations in clinical parameters were assessed via chi-square tests and one-way ANOVA. Univariate and multivariate Cox regression analyses were conducted to identify factors associated with progression-free survival (PFS) and overall survival (OS).ResultsThe 5-year OS and PFS rates for the entire cohort were 36.6% (95% CI: 0.275–0.488) and 32.2% (95% CI: 0.233–0.451), respectively. Patients who were younger (<60 or <70 years), had Ann Arbor stage I/II disease, or exhibited lower Eastern Cooperative Oncology Group (ECOG) performance status scores demonstrated significantly improved OS and PFS following treatment. Notably, among patients with ECOG <2, those treated with the CPET regimen achieved longer PFS and OS compared to those receiving CHOP or CHOPE. In contrast, for patients with ECOG ≥2, no significant survival differences were observed across treatment regimens. Both univariate and multivariate analyses identified ECOG performance status as an independent prognostic factor for survival outcomes.ConclusionFor patients with a low ECOG performance status, the CPET regimen may offer promising survival outcomes.

ObjectivesLangerhans cell histiocytosis (LCH) is a rare clonal proliferative disorder characterized by the infiltration of pathological Langerhans cells into multiple organs, exhibiting significant clinical heterogeneity. Although standard chemotherapy regimens have markedly improved patient survival rates, several challenges remain, such as low response rates, high recurrence rates, and long-term sequelae in certain patients. This study aimed to integrate multimodal 18F-FDG PET/CT metabolic parameters, genetic markers, and clinical characteristics to evaluate and predict treatment efficacy and prognosis in patients with LCH.MethodsA retrospective analysis was conducted on clinical data and 18F-FDG PET/CT imaging findings from 26 patients diagnosed with LCH via biopsy pathology between May 2016 and December 2024 at the Department of Nuclear Medicine, Jiangxi Provincial People’s Hospital. Four metabolic parameters—SUVmax, TLR, MTV, and TLG—as well as genetic markers and clinical features (e.g., gender, age, type, stage) were evaluated. All patients were followed up for at least 1 year or until disease progression or relapse occurred. Univariate and multivariate analyses were performed to assess progression-free survival.ResultsPatients with disease progression or recurrence exhibited significantly higher SUVmax, TLR, MTV, and TLG values compared to those who responded to treatment. ROC curve analysis identified optimal cutoff values for predicting disease remission as follows: SUVmax = 7.5, TLR = 5.2, MTV = 25.0, and TLG = 150. The remission rates in the high-value groups for SUVmax, MTV, and TLG were significantly lower than those in the corresponding low-value groups, with the most pronounced differences observed in the MTV and TLG groups (p < 0.01). TLG demonstrated the highest AUC value (0.91), indicating its strong predictive power. Clinicians should be vigilant about recurrence risk when MTV ≥ 25.0 or TLG ≥ 150.0. In univariate analysis, classification as multisystem LCH with risk-organ involvement (MS-LCH RO+), Ann Arbor stage III, BRAF V600E positivity, MTV > 25.0, and TLG > 150.0 were significant risk factors for worse progression-free survival (PFS) (all p < 0.05). Furthermore, patients in the high SUVmax, high MTV, and high TLG groups exhibited significantly shorter PFS. Multivariate Cox regression analysis identified the metabolic parameters MTV and TLG as independent predictors of PFS. The BRAF V600E mutation rate was significantly higher in patients with MS-LCH and those in the high SUVmax and high TLG groups.ConclusionBaseline metabolic parameters derived from 18F-FDG PET/CT represent promising imaging biomarkers for predicting therapeutic response and prognosis in LCH. When integrated with established clinical stratification systems, these metabolic indices facilitate a more comprehensive multidimensional prognostic evaluation framework.

The incidence and role of EBV and HIV in head and neck lymphomas: an institutional study.

This study investigates the differential expression of ENO2 in serum extracellular vesicles (EVs) of patients with diffuse large B cell lymphoma (DLBCL) and its correlation with clinicopathological characteristics and prognosis. Serum samples before receiving treatment, clinicopathological characteristics, and follow-up information were collected from 78 patients with DLBCL, and 40 patients with reactive hyperplasia of lymph nodes (RH) were selected as the control group. ENO2 expression in serum EVs was detected by RT-qPCR and Western blot. The diagnostic value of ENO2 in serum EVs for DLBCL was analyzed by ROC curve. The correlation between ENO2 expression and clinicopathological data was analyzed by chi square test. The 5-year overall survival (OS) was analyzed by Kaplan-Meier method. The COX proportional hazards model was employed for analyzing prognostic risk factors of DLBCL. ENO2 is highly expressed in serum EVs of DLBCL patients. ENO2 in serum EVs has moderate diagnostic efficacy for DLBCL, with a sensitivity, specificity, and AUC of 0.808, 0.725, and 0.789, respectively. ENO2 expression is closely related to ECOG score, LDH level, Ann Arbor stage, IPI, and Bcl-2. DLBCL patients with age (> 60years), ECOG (2-4), LDH level (High), Ann Arbor stage (III + IV), IPI score (3-5), Ki-67 (≥ 70%), Bcl-2 (positive), and ENO2 protein (high expression) have lower 5-year OS. ENO2 protein (high expression), ECOG (2-4), Ann Arbor stage (III + IV), and Ki-67 (≥ 70%) are independent prognostic risk factor for DLBCL. ENO2 is correlated with the clinicopathological characteristics of DLBCL and is an independent prognostic risk factor.

BackgroundPrimary pulmonary diffuse large B-cell lymphoma (PP-DLBCL) is a rare and aggressive extranodal lymphoma, with no consensus on optimal treatment strategies. For unresectable cases, current evidence is insufficient to determine whether the addition of radiotherapy (RT) to chemotherapy (CT) provides a survival benefit. To address this gap, we used data from the Surveillance, Epidemiology, and End Results (SEER) database to compare survival outcomes between combined modality therapy (CMT) and CT alone in patients with unresectable PP-DLBCL.MethodsData on patients with unresectable PP-DLBCL were extracted from the SEER database of the National Cancer Institute, using SEER*Stat software (v8.4.3). Propensity score matching (PSM) was applied to adjusted confounding factors. Overall survival (OS) and cancer-specific survival (CSS) were estimated using Kaplan-Meier methods, and differences between groups were assessed using the log-rank test. Hazard ratios (HRs) were calculated using Cox proportional hazards models.ResultsA total of 880 patients with unresectable PP-DLBCL diagnosed between 2000 and 2021 met the inclusion criteria and the median follow-up were 87 months. The estimated 5-year OS rate was 65.4% [95% confidence interval (CI): 60.1–70.7%]. Of these patients, 719 received CT alone and 161 received CMT. Significant differences in primary tumor site and laterality were observed between the two groups (P<0.001). The analysis revealed a significant association between CMT and improved OS (HR, 0.77; 95% CI: 0.59–0.99), and this association remained consistent in the sensitivity analysis using PSM. Additionally, univariate and multivariate Cox regressions indicated that sex, age and Ann Arbor stage were independent prognosis factors of OS.ConclusionsOur findings suggest that CMT may improve survival in patients with unresectable PP-DLBCL. Moreover, the prognostic factors identified in this study may help in identifying high-risk patients. Our findings provide new evidence to support the clinical management of this rare patient population.

To investigate the predictive value of circulating free DNA (cfDNA) combined with interleukin 10 (IL-10) in predicting central nervous system infiltration (CNSI) in diffuse large B-cell lymphoma (DLBCL). The clinical data of 63 patients with DLBCL in our hospital from May 2021 to April 2023 were retrospectively analyzed. The 63 patients were divided into CNSI group (15 cases) and non-CNSI group (48 cases) base on whether CNSI occurred. The age, sex, Ann Arbor stage, ECOG score, IPI risk, CNS-IPI risk, number of extranodal sites involved, bone marrow involvement, hypertrophic disease, B symptoms, source cells, glucose quantification, Pandy test, cerebrospinal fluid (CSF) chlorine, CSF nucleated cell count, CSF protein, peripheral blood cfDNA, and IL-10 status were compared between the two groups. The correlation between cfDNA, IL-10 in peripheral blood and CSF protein was analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of peripheral blood cfDNA and IL-10 on secondary CNSI in DLBCL patients. The last follow-up was on November 30, 2023. Kaplan-Meier method was used to calculate the time of secondary CNSI in the non-CNSI group. The IPI risk, CNS-IPI risk, number of extranodal sites involved, and CSF protein in the CNSI group were significantly higher than those in the non-CNSI group (all P <0.05). The levels of cfDNA and IL-10 in peripheral blood of CNSI group were significantly higher than those of non-CNSI group (both P <0.01). cfDNA and IL-10 in peripheral blood were both positively correlated with CSF protein (r =0.402 4, 0.315 1). ROC curve analysis showed that peripheral blood cfDNA and IL-10 had certain predictive value for CNSI, and the area under the curve (AUC) was 0.829 and 0.742, respectively. The AUC of the combined detection was 0.910, with a sensitivity of 80.00% and a specificity of 93.70%. The diagnostic efficacy was significantly higher than that of the two prediction values alone. The median follow-up time was 20 (6-31) months. Non-CNSI patients were grouped based on peripheral blood cfDNA combined with IL-10 positive or negative pairs. The time of secondary CNSI in positive group was significantly shorter than that in negative group (P <0.05). cfDNA and IL-10 in peripheral blood of DLBCL patients with CNSI are significantly increased, and the combined detection of cfDNA and IL-10 has good predictive value for CNSI.

To investigate the significance of serum β2-microglobulin (β2-MG) for survival and relapse of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Clinical data of 92 patients with DLBCL admitted from December 2003 to July 2015 were retrospectively analyzed. The optimal cutoff value of β2-MG levels for predicting prognosis of the DLBCL patients was determined using receiver operating characteristic (ROC) curve. KaplanMeier analysis was used to estimate progression-free survival (PFS) and overall survival (OS). Cox logistic regression analysis was used to explore potential prognostic factors associated with survival. Binary logistic regression analysis was used to analyze the relationship between various factors and relapse. The most discriminative cutoff value for β2-MG level was determined to be 2.25 mg/L by the ROC curve. Subgroup analysis showed that patients in the elevated β2-MG (＞2.25 mg/L) group had significantly worse PFS(P =0.006) and a trend toward worse OS compared with those in the low β2-MG (≤2.25 mg/L) group(P =0.053). Univariate analysis showed that elevated β2-MG, age>60 years, Ann Arbor stage III-IV, as well as IPI score ≥3 were associated with worse PFS. Binary logistic regression analysis showed that age＞60 years and β2-MG＞2.25 mg/L were potential influencing factors for relapse of DLBCL patients. Serum β 2-MG might be an important predictor for the survival and relapse of DLBCL patients in the rituximab era.

Primary vulvar lymphoma is an exceptionally rare malignancy, comprising less than 1% of all vulvar cancers and an even smaller fraction of extranodal non-Hodgkin lymphomas. Among these, high-grade T-cell lymphoma is exceedingly uncommon, with limited cases reported in the literature. Immunocompromised states, particularly HIV infection, are known to predispose individuals to aggressive and atypical lymphoid malignancies. This case report presents a rare instance of T-cell lymphoma of the vulva in a premenopausal woman, with the diagnosis confirmed through histopathological analysis of vulvar tissue. To the best of our knowledge, this is the first reported case of its kind in Tanzania. Case History: We report the rare case of a 46-year-old, P1L1, premenopausal woman living with HIV who presented with a rapidly enlarging, painful right vulvar mass with ulceration and foul discharge for 7 months. Pelvic examination revealed a large firm, friable mass with an ulcerated, erythematous surface involving the right labia majora, posterior fourchette, and perineum. She was also noted to have ipsilateral inguinal lymphadenopathy. A pelvic Magnetic Resonance Imaging (MRI) with and without IV contrast confirmed the presence of an ulcerated mass arising in the right labium measuring 6 × 2 cm. Prominent and enhancing bilateral inguinal-femoral lymph nodes were identified, the largest noted in the right inguinal region, measuring 4 × 2 cm. The radiological findings were suggestive of a right labial ulcerative malignant mass with inguinal-femoral lymphadenopathy. Staging investigations revealed localized disease without systemic involvement (Ann Arbor Stage II-E). Histopathological evaluation confirmed high-grade peripheral T-cell lymphoma, with immunohistochemistry (IHC) analysis results indicating that the tumor cells were positive for CD38, CD43, CD56, CD57, CD2, and CD3 but negative for CD4, CD5, CD20, BCL2, and PAX5. The findings favored the diagnosis of a high-grade T-cell lymphoma of the vulva, most likely extranodal NK/T-cell lymphoma. The patient was managed with combination chemotherapy Cyclophosphamide, Doxorubicin, Etoposide, Vincristine, and Prednisolone (CHOEP) protocol alongside continued antiretroviral therapy. She showed a favorable initial response with significant tumor regression and remains under close follow-up.

Background and ObjectivesDespite the discovery of cuproptosis as a new type of cell death, less is known about the role cuproptosis-related genes (CRGs) may play in B-cell Non-Hodgkin Lymphoma (NHL). There remained a lack of knowledge regarding the clinical and biological roles of CRG signatures and the therapeutic value of the potent copper ionophore (elesclomol) in B-cell NHL. In this study, the purpose is to investigate the prognostic value of CRGs and their relationship to the tumor immune microenvironment, as well as the mechanism of cuproptosis in B-cell NHL.MethodsB-cell NHL patients’ clinical and gene expression data were retrieved from Gene Expression Omnibus (GEO). Our prognostic model was developed using least absolute shrinkage and selection operator (LASSO) regression analysis and univariate Cox analysis. Prediction accuracy of the model was estimated by receiver operating characteristic (ROC) curves. Functional pathway enrichments and immune features were also analyzed. Vitro experiments were conducted to investigate the combination therapy of elesclomol and doxorubicin, and to explore the application value in B-cell NHL.ResultsSeven CRGs were strongly associated with patient survival and 4 genes were identified to construct the prognostic model. ROC curves indicated great predictive sensitivity and specificity of the model in all cohorts. Patients were divided into low-and high-risk groups by median risk score in each cohort and the survival of the low-risk group was significantly superior than that of the high-risk group. Correlations with clinical features showed that higher Risk-Score was significantly associated with advanced Ann Arbor stages, which were further confirmed in two validation cohorts. We also observed a close relationship between functional pathways and immune features with risk scores. Moreover, we combined elesclomol and doxorubicin in our in vitro experiments and found synergetic antitumor effects of the two agents, and the underlying mechanism is the overgeneration of intracellular Reactive Oxygen Species (ROS).ConclusionsWe demonstrated the important value of CRG signatures in prognosis of B-cell NHL patients, and that may be a potential antitumor target for B-cell NHL.

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma and often carries a poor prognosis. Current prognostic systems such as the International Prognostic Index (IPI) and National Comprehensive Cancer Network (NCCN)-IPI do not incorporate patients’ nutritional, immune, or inflammatory status, which may affect outcomes.MethodsWe retrospectively analyzed 423 newly diagnosed DLBCL patients and collected 12 clinical indicators reflecting nutritional, immune, and inflammatory status. Patients were randomly divided into training and validation sets in a 7:3 ratio. A LASSO-Cox regression model was applied to identify variables for constructing the Nutritional and Immune-Inflammatory Scoring System (NII). The independent prognostic value of NII was evaluated using univariable and multivariable Cox regression analyses. Its added prognostic value was further assessed in combination with the IPI and NCCN-IPI.ResultsWe developed the NII, including Nutritional Risk Screening 2002 (NRS2002), Geriatric Nutritional Risk Index (GNRI), systemic immune-inflammation index (SII), lactic dehydrogenase to albumin ratio (LAR), β2-microglobulin (β2-MG), and CD8+ T cells. A high NII (≥ 6) effectively identifies high-risk DLBCL patients and serves as an independent prognostic factor beyond other clinical characteristic, IPI, and NCCN-IPI. DLBCL patients with a high NII (≥ 6) exhibit significantly adverse clinical features, including older age, lower frequency of the non-GCB subtype, advanced Ann Arbor stage (III/IV), poor performance status (ECOG PS ≥ 2), involvement of ≥ 2 extranodal sites, presence of B symptoms, elevated lactate dehydrogenase (LDH) levels, and classification into higher-risk groups according to IPI and NCCN-IPI. Combining NII with IPI or NCCN-IPI significantly improves the assessment of patient prognosis compared to using IPI or NCCN-IPI alone.ConclusionThe NII score, integrating readily available nutritional, immune, and inflammatory markers, enhances prognostic accuracy in DLBCL and complements conventional scoring systems. This simple tool may aid in early identification of high-risk patients and guide personalized treatment.

Response gene to complement 32 (RGC32), a complement activation-inducible factor broadly expressed in normal human tissues, has been implicated in tumorigenesis through its dysregulated expression in various malignancies and its involvement in critical oncogenic processes. Despite its established roles in cancer biology, RGC32 remains uncharacterized in diffuse large B-cell lymphoma (DLBCL). This study provides the first comprehensive investigation of RGC32 expression patterns and functional contributions to DLBCL pathogenesis, elucidating its potential as a novel therapeutic target or prognostic biomarker in this disease. Immunohistochemical (IHC) staining of RGC32 was performed on specimens from 32 Reactive hyperplasia lymphoid (RHL) patients and 80 DLBCL patients. To evaluate the role of RGC32 in DLBCL, lentivirus vectors either encoding shRGC32 or shControl were transfected into DLBCL cell lines. RNA-sequencing (RNA-seq) analysis was performed between shRGC32 and shControl stably transfected OCI-LY1 cells and functional enrichment analyses used gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG). In order to explored its functions in vivo, xenograft models were established by subcutaneously injecting shRGC32 and shControl transfected DLBCL cells into SCID beige mice. Immunohistochemical analysis revealed RGC32 overexpression in DLBCL tissues contrast with RHL, and was associated advanced Ann Arbor stage (p = 0.043), B symptoms (p = 0.020), and poor progression-free survival (p = 0.015) and overall survival (p = 0.035). Functional studies demonstrated that RGC32 knockdown via shRNA significantly suppressed DLBCL cell proliferation in vitro and in vivo, with xenograft models showing reduced tumor growth and Ki-67 expression. RNA-seq analysis linked RGC32 depletion to downregulation of cell proliferation and impaired DNA damage repair (DDR) mechanisms. Western blot showed RGC32 knockdown could suppress ATM/ATR/CHK1 pathway and increase the tumor mutational burden (TMB). Furthermore, after inhibition of RGC32, infiltration of CD8+ T cells was increased in DLBCL tumor microenvironment (TME). This study highlights that RGC32 is a novel molecule in DLBCL progression and might be a potential therapeutic target for DLBCL therapy.