The role of surgery in the management of intestinal diffuse large B-cell lymphoma (DLBCL) remains controversial. The study aimed to investigate the efficacy of surgery and explore the prognostic factors for patients with intestinal DLBCL. A total of 118 patients diagnosed with intestinal DLBCL who received systemic therapy from 2011 to 2020 were retrospectively enrolled. Patients were divided into the conservative treatment group and the surgical treatment group based on whether they underwent surgical intervention prior to systemic therapy. Propensity score matching (PSM) analysis was utilized to control the confounding factors. Survival and Cox regression analyses were performed to evaluate the long-term outcome and prognostic risk factors. Patients in the surgical treatment group had significantly higher progression-free survival (PFS) rates than patients who received conservative treatment (3-year PFS: 84.6% vs. 35.9%, p<0.001; 5-year PFS: 53.8% vs. 28.2%, p=0.021). The overall survival (OS) rates of the surgery group were also significantly higher than those of the conservative treatment group (3-year OS: 87.2% vs. 43.6%, p<0.001; 5-year OS: 56.4% vs. 30.8%, p=0.022). Surgical treatment was associated with a higher complete response rate and a lower disease progression/relapse rate (complete response rate: 87.2% vs. 53.8%, p=0.001; progression/relapse rate: 10.3% vs. 28.2%, p=0.044). Multivariate Cox regression analysis indicated that serum lactate dehydrogenase level and surgical intervention were independent prognostic factors for both PFS and OS, whereas bone marrow involvement was an independent prognostic factor for PFS. Combined surgical treatment manifested a better survival outcome than conservative treatment for patients with intestinal DLBCL. Serum lactate dehydrogenase level, bone marrow involvement, and surgical intervention are independent prognostic factors for survival.

Pulmonary sarcoidosis with suspected bone marrow involvement presenting as severe thrombocytopenia: a case report.

Wilms tumor (WT) has an excellent outcome. Studies suggest that patients with WT and bone metastases (WT-BM) have a poor prognosis. This analysis describes the characteristics and outcome of patients with WT-BM, registered by the International Society of Paediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) and UK-IMPORT STUDY. We retrospectively assessed clinical characteristics and outcome of patients with WT-BM at diagnosis treated according to SIOP-RTSG 93-01, SIOP 2001/UK-IMPORT study protocols. Among 7399 patients diagnosed with WT between 1993 and 2019, 47 were identified with WT-BM (12 males/35 females), accounting for 3.3% of stage IV-WT. The median age at diagnosis was 63 months (24-292 months). Four patients (9%) had only BM involvement and 43 patients (91%) had multisite metastases. Local stage was I-II in 15 (32%) patients, stage III in 26 (55%) patients, and unknown in 6 (13%) patients. Preoperative chemotherapy consisted of three drugs in 95% of cases with available data (38/40). Histological subtyping identified low-risk (LR, n = 4), intermediate-risk (IR, n = 29), high-risk (HR, n = 7) tumors, unknown/others in seven patients. The majority had postoperative treatment according to protocol. Among 35 patients with data, 33 (94%) received any kind of radiotherapy. EFS and OS were 67% and 74% at 2 years, decreasing to 64% and 62% at five years. EFS at 2 years was 14% in the HR group and 84% in the IR group. WT-BM is a rare condition. Awareness of its existence and multimodality treatment are warranted.

Clonal mature plasmacytoid dendritic cell proliferations (MPDCP) are a recently recognized entity in the WHO fifth edition, but their pathologic spectrum remains poorly characterized. Cases with extensive MPDCP in the bone marrow (BM) are rare and can exhibit overlapping features with blastic plasmacytoid dendritic cell neoplasm (BPDCN). We compared clinicopathologic and genomic features of 11 patients with myeloid neoplasm-associated MPDCP to 5 patients with secondary BPDCN arising from clonally-related myeloid neoplasms. MPDCP exhibited variable degrees of BM involvement (5% to 50%) and architectural patterns, were uniformly positive for CD123, CD4, TCF4, and IRF8, variably positive for TCL1 (7/11), CD5 (7/11), and CD7 (2/11), and negative for SOX4, CD56, and TdT. MPDCP skin involvement was rare (1/11), with no CNS involvement. MPDCP heralded myeloid disease progression in a subset of patients, with increased blasts or progression to AML (4/11). In contrast, secondary BPDCN was uniformly positive for SOX4 and TCL1, with frequent CD56 (4/5) and subset/weak TdT (3/4). All BPDCN patients had characteristic skin lesions, and a subset with CNS involvement (2/5). The underlying myeloid neoplasms associated with MPDCP or BPDCN were enriched in TET2 , SRSF2 , ASXL1 , RUNX1 , and RAS pathway mutations. While karyotypic abnormalities were uncommon in MPDCP, all BPDCN showed chromosomal structural abnormalities and copy number variants, including deletions of 3p, 9p, and 12p. Our findings expand the histopathologic, immunophenotypic, and genetic characterization of MPDCP, and highlight pathologic features that distinguish it from BPDCN. Utilization of SOX4 immunohistochemistry, combined with careful clinical and molecular correlation, can aid in resolving these diagnostic challenges.

Excess adiposity has been associated with Hodgkin lymphoma (HL) development, but its implications remain unclear. Bone marrow (BM), a frequent extranodal involvement site, contains both red and fatty yellow marrow. We investigated whether obesity influences HL outcomes and characterized the BM and cytokine profiles. In this retrospective study, HL patients were analyzed to assess the association between obesity with relapse and mortality. Yellow and red marrow composition were evaluated using CT imaging and correlated with HL outcomes. A nested study analyzed cytokines in the interstitial marrow fluid (IMF) and in circulation of HL patients, in comparison to a control group of healthy blood donors. Further, invitro functional analyses were performed. Overweight/obesity in HL patients was associated with lower rates of BM involvement, disease relapse, and mortality. Moreover, dense yellow marrow was related to increased risk of death. HL subjects had elevated levels of adiponectin in IMF compared to marrow donors, whereas higher insulin, interleukin 8, and osteoprotegerin levels in IMF were associated with shorter time to relapse. At the molecular level in BM, HL patients had overexpression of LEPR and IGFBP3 in adipocytes, while stromal cells overexpressed IGF-axis receptors. Inin vitro studies, human recombinant IGF-1 significantly induced the L428 HL cell line proliferation, which when combined with IGFBP-3 modified apoptosis. The current findings suggest that obesity is associated with a lower incidence of BM involvement and mortality in patients with HL. The obesity together with HL mechanistically influences systemic and local BM cytokine production, thereby impacting HL fate.

Blastoïd mantle cell lymphoma, TdT-positive: Toward a more juvenile profile?

Extramedullary (or extraosseous) plasmacytoma (EMP) is a localized plasma cell neoplasm lacking apparent bone marrow involvement and other features of multiple myeloma (MM). The prognosis is usually favorable and progression to MM is infrequent. The genetic landscape of EMP remains largely unknown. Importantly, EMP must be distinguished from extramedullary disease of MM (EMD), which typically exhibits aggressive behavior. We performed a comprehensive molecular analysis of EMP (n=24) in comparison to EMD (n=24) using fluorescence in situ hybridization (FISH), copy number (CN) profiling, and targeted nextgeneration sequencing. Overall, EMP shared several genetic features with MM, but exhibited markedly lower complexity than EMD. EMP revealed a mean of 4.3 CN changes vs. 19.3 in EMD (p.

Matrix metalloproteinase 9 (MMP9) is a zinc-dependent endopeptidase involved in extracellular matrix (ECM) remodeling and inflammatory signaling. Although MMP9 has been implicated in tumor progression and immune modulation in solid tumors, its clinical relevance and microenvironmental associations in diffuse large B-cell lymphoma (DLBCL) remain incompletely defined. Publicly available transcriptomic and clinical datasets of DLBCL were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GSE56315). Differential expression and enrichment analyses were performed to characterize biological pathways associated with MMP9 expression. Immune and stromal features were estimated using CIBERSORT, TIMER, and ESTIMATE algorithms. Associations with tumor stemness indices and somatic mutational profiles were explored. In addition, peripheral blood leukocyte profiles were analyzed from an independent cohort of DLBCL patients collected at our institution to assess systemic immune alterations associated with disease status. MMP9 protein expression was further evaluated using immunohistochemical data from the Human Protein Atlas. MMP9 expression was significantly elevated in DLBCL tissues compared with normal lymphoid controls. Higher MMP9 expression was associated with inferior overall survival and increased immune and stromal scores. MMP9 expression correlated with enhanced monocyte and myeloid cell infiltration and enrichment of ECM-related and cytokine-associated signaling pathways, including PI3K-Akt signaling. Analysis of peripheral blood samples revealed altered leukocyte distributions in DLBCL patients, characterized by increased neutrophil and monocyte proportions and reduced lymphocyte fractions, particularly in cases with bone marrow involvement. In addition, MMP9-high tumors exhibited distinct mutational patterns involving genes such as KMT2D and MYD88, along with reduced tumor stemness indices. Immunohistochemical analysis confirmed increased MMP9 protein expression in DLBCL tissues. Elevated MMP9 expression is associated with adverse prognosis and immune-stromal alterations in DLBCL. Integrated transcriptomic, genomic, and clinically derived peripheral blood analyses suggest that MMP9 expression reflects ECM-associated immune remodeling at both local and systemic levels, supporting its potential value as a biomarker linked to the tumor immune microenvironment in lymphoma.

Dengue virus infection is a major global health problem with clinical outcomes ranging from mild febrile illness to severe disease. Although a reduction in platelet counts is a common feature of dengue, the mechanisms underlying the presence of viral antigens in circulating platelets remain incompletely understood. In this study, we investigated whether infection of megakaryocytic precursors contributes to the generation of platelets carrying dengue virus proteins. Using the human megakaryocytic precursor cell lines K562 and MEG-01 cell lines as in vitro models, we show that reference strains and clinical isolates of dengue virus infect megakaryocytic precursors and modulate their differentiation, as evidenced by increased expression of the differentiation marker CD41 and the production of platelet-like particles. Flow cytometry analysis demonstrated that PLPs released from infected precursors contained precursor-derived PLP-associated dengue virus envelope protein. Correlation analyses revealed significant associations between the extent of precursor infection and both differentiation markers and PLP-associated E protein levels at early time points. Consistent with these findings, dengue virus E protein was detected in platelets from dengue patients, while no statistically significant differences were observed between clinical severity groups, a trend toward higher proportions of E+ platelets were observed in patients with dengue with warning signs or severe dengue. Spearman correlation analyses further supported an association between in vitro precursor infection and the generation of E-positive PLPs. In contrast, platelets from healthy donors incubated ex vivo with dengue virus did not acquire E protein, indicating that direct uptake or infection of circulating platelets is inefficient. Together, these results support a model in which infection of megakaryocytic precursors contributes to the generation of platelets carrying dengue virus antigens, suggesting that platelet-associated E protein may reflect bone marrow involvement during dengue infection.

BackgroundThe aggregate index of systemic inflammation (AISI, calculated as neutrophil count × monocyte count × platelet count/lymphocyte count) reflects systemic inflammatory status; however, its prognostic role in diffuse large B-cell lymphoma (DLBCL) remains underexplored. This study aimed to investigate the prognostic value of AISI in DLBCL.MethodsA total of 1332 DLBCL patients (median age 62 years; 52.3% male) were included in this study. Patients were stratified based on AISI quartiles, and a cut-off value was determined using restricted cubic splines (RCS) analysis. The associations between AISI and Overall survival (OS) were assessed using Kaplan-Meier analysis and Cox proportional hazards models.ResultsHigher AISI levels were associated with adverse clinical features, including advanced Ann Arbor stage, poor performance status, and higher-risk categories of both the IPI and the NCCN-IPI. RCS analysis revealed a nonlinear relationship between AISI and OS, with an inflection point at 261.33. Kaplan-Meier analysis demonstrated that patients with AISI > 261.33 had significantly worse OS compared to those with AISI ≤ 261.33 (P = 0.003). Similarly, patients in the Q4 group had poorer OS than those in the lowest two quartiles (Q1-Q2) (P = 0.008). In fully adjusted Cox proportional hazards models (adjusted for age, sex, Ann Arbor stage, LDH, ECOG performance status, BMI, albumin, B symptoms, bone marrow involvement, central nervous system involvement, and liver/spleen involvement), high AISI level (> 261.33) were associated with increased mortality risk (HR = 1.28, 95% CI: 1.04–1.57, P = 0.018). Subgroup analyses indicated that the prognostic impact of AISI was particularly evident among patients classified as low risk by conventional prognostic systems.ConclusionElevated AISI was associated with inferior OS in DLBCL patients and may potentially serve as a prognostic biomarker.

FDG-PET Medullary Total Tumor Volume Highlights High-Risk Newly Diagnosed Multiple Myeloma Patients in CASSIOPEIA Trial.

Bone marrow involvement in breast cancer: a retrospective cohort study.

Neuroblastoma is the most common extracranial solid malignancy of childhood and typically arises from neural crest cells of the sympathetic nervous system, most frequently in the adrenal medulla or paravertebral sympathetic chain. Thoracic or thoracoabdominal localization is less common and may present with nonspecific respiratory symptoms that mimic infectious diseases. We report the case of a three-year-old boy presenting with prolonged fever, persistent cough, and progressive weight loss. Initial chest radiography and pleural fluid analysis suggested pulmonary tuberculosis, and antituberculous therapy was initiated.However, the absence of clinical improvement prompted further evaluation. Contrast-enhanced thoracoabdominal computed tomography revealed a large prevertebral mass extending into the posterior mediastinum. Ultrasound-guided biopsy followed by histopathological and immunohistochemical examination confirmed the diagnosis of neuroblastoma. Staging investigations demonstrated bone and bone marrow involvement consistent with high-risk disease. The patient was treated according to the NBL-MA- 2010 protocol with significant clinical improvement and is currently scheduled for consolidation with autologous stem cell transplantation. This case highlights an important diagnostic pitfall in tuberculosis- endemic regions and emphasizes the importance of early cross-sectional imaging and tissue diagnosis in children presenting with persistent thoracic pathology.Categories: Oncology, Pediatrics

Analyze the predictive value of body mass index (BMI), prognostic nutritional index (PNI), C-reactive protein (CRP), and CD3+CD8+T for the prognosis of lymphoma patients undergoing autologous hematopoietic stem cell transplantation. We retrospectively included 160 patients with malignant lymphoma who underwent first-line or salvage chemotherapy and successfully underwent autologous hematopoietic stem cell transplantation in our hospital between May 2010 and January 2019. The clinical data of the patients before transplantation (baseline period) were collected and analyzed. The cutoff values were obtained based on the ROC curve. The clinical characteristics of patients were compared, including age, gender, physical condition (ECOG PS) score, Ann Arbor staging, International Prognostic Index (IPI) score, extranodal involvement, bone marrow involvement, and B symptoms. Followed up for 5years, Kaplan-Meier method and Cox proportional hazards regression model were used to analyze the effects of various indicators and clinical characteristics on overall survival (OS) and progression-free survival (PFS). According to the ROC curve cutoff value, 160 patients were divided into low BMI group (83 cases) and high BMI group (77 cases), low PNI group (78 cases) and high PNI group (82 cases), low CRP group (90 cases) and high CRP group (70 cases), low CD3+CD8+T group (86 cases) and high CD3+CD8+T group (74 cases). There were significant differences in ECOG PS score, Ann Arbor staging, IPI score, and B symptoms among patients with different BMI levels (P < 0.05). There were differences in ECOG PS score, Ann Arbor staging, and IPI score among patients with different PNI levels (P < 0.05). Patients with different CRP levels also have differences in ECOG PS score, Ann Arbor staging, IPI score, spinal cord involvement, and B symptoms (P < 0.05). A total of 160 lymphoma patients were followed up for 5years, with a survival rate of 65.00% (104/160). Kaplan-Meier analysis showed that low BMI, low PNI, high CRP, and high CD3+CD8+T were all associated with poorer overall survival and progression-free survival (P < 0.05). Multivariate Cox regression analysis showed that low PNI and high CRP were independent risk factors for both OS and PFS. In addition, Ann Arbor staging (stages III-IV) was an independent risk factor for OS and PFS, but high CD3+CD8+T was an independent risk factor for PFS. Low levels of PNI and CRP before transplantation are independent risk factors affecting overall survival and progression-free survival in lymphoma patients undergoing autologous hematopoietic stem cell transplantation. In addition, high levels of CD3+CD8+T cells are an independent risk factor for progression-free survival. These indicators provide new and valuable reference for clinical doctors to more accurately evaluate patient prognosis.

Blastoid and pleomorphic mantle cell lymphoma (B/P-MCL) represents a high-risk subtype of hematological malignancy with an unfavorable prognosis. We conducted a retrospective analysis of 76 patients with classic MCL and 81 patients with B/P-MCL between January 2010 and May 2024 to investigate clinical characteristics, outcomes, and prognostic factors. Ki-67 ≥ 30%, high MCL International Prognostic Index (MIPI) scores, and frequent CD5 negativity were more prevalent in B/P-MCL than in classic MCL. In B/P-MCL, TP53 mutations (46.2%) were most common, followed by ATM (42.3%), CCND1 (23.1%), NOTCH1 (23.1%), KMT2D (23.1%), SMARCA4 (15.4%), and BIRC3 (15.4%). Multivariate analysis revealed that Ki−67% ≥90% and bone marrow involvement were independent prognostic factors for overall survival (OS); Ki−67% ≥90% and splenic involvement were independent prognostic factors for progression-free survival (PFS). The blastoid and pleomorphic variants of MCL display distinct morphological characteristics and exhibit certain clinical differences; however, no statistically significant differences in PFS or OS have been demonstrated between these two subtypes. B/P-MCL is characterized by highly aggressive features and a dismal clinical course. Even with the adoption of intensified treatment protocols, the long-term prognosis for these patients remains unsatisfactory. Strengthened efforts to explore novel therapeutic strategies are crucial and may ultimately translate into improved clinical outcomes for this patient population.

This study investigated the risk factors associated with infusion-related reactions (IRRs) in B-cell lymphoma patients receiving obinutuzumab. A retrospective analysis of Peking Union Medical College Hospital patients (January 2021–December 2024) was conducted to examine factors between patients experiencing IRRs (n = 44) and those without (n = 56). Parameters included gender, age, histological subtype, treatment status, Ann Arbor staging, extranodal/bone marrow involvement, bulky disease, splenomegaly status, serum lactate dehydrogenase (LDH), beta-2 microglobulin (β2MG) concentrations, and lymphocyte count. 100 patients (48 men, 52 women) with a mean age of 55.7 years (range: 44–67) received obinutuzumab. Univariate analyses showed higher prevalence of bone marrow involvement and splenomegaly in the IRR group. Median LDH (235 vs. 195) and β2MG (4 vs. 3) levels pre-treatment were significantly elevated in the IRR group (P < 0.05). Multivariate analysis identified splenomegaly and pre-treatment LDH levels as IRR risk factors. This research assists in predicting IRRs to improve patient outcomes.

Extranodal natural killer/T-cell lymphoma (ENKTL) is a rare and aggressive malignancy with poor outcomes in advanced stages. Current prognostic indices fail to fully account for the heterogeneity of stage Ⅲ–Ⅳ ENKTL. We aimed to develop a nomogram integrating inflammatory and clinical parameters to improve prognostic prediction. We retrospectively analyzed 291 patients with stage III/IV ENKTL across eight hospitals for model development and 145 patients for validation. Optimal cut-off values for absolute lymphocyte count (ALC), absolute monocyte count (AMC), and lymphocyte-to-monocyte ratio (LMR) were determined. Cox regression yielded independent prognostic indicators, which were incorporated into a nomogram. The model was validated with the concordance index (C-index), receiver operating characteristic curves, area under the curve (AUC) and calibration analysis. Five factors for overall survival (OS) were identified: age > 60 years (HR: 1.749), AMC > 0.4 × 10⁹/L (HR: 1.423), LMR ≤ 1.47 (HR: 1.460), visceral organ involvement (HR: 1.979), and bone marrow involvement (HR: 1.559). These were integrated into a nomogram with a C-index of 0.644 (95% CI: 0.601–0.687). The nomogram showed better discriminatory ability compared to both the prognostic index of natural killer lymphoma (PINK) (AUC: 0.721 vs. 0.595, P = 0.0085) and nomogramrevised risk index (NRI) (AUC: 0.721 vs. 0.585, P = 0.0034). Patients were stratified into high- and low-risk groups based on median nomogram score, with the low-risk group showing significantly better OS ( High-risk vs. low-risk group, P < 0.0001) and progression-free survival (PFS) (High-risk vs. low-risk group, P < 0.0001). In the validation cohort, the C-index was 0.634 and the 3-year AUC for OS was 0.705. Both OS and PFS were significantly inferior in the high-risk group (OS: P = 0.0015; PFS: P = 0.02). We developed an inflammation-based prognostic nomogram for advanced-stage ENKTL with moderate predictive accuracy potentially aiding clinicians in individualized risk stratification. Prospective multicenter studies are warranted to further optimize and validate its clinical applicability.

Bone marrow involvement in sarcoidosis is rare and poorly understood. This case highlights the hematologic complexity of sarcoidosis, including its association with aplastic anemia and T-cell large granular lymphocytic leukemia (T-LGLL). We report a 70-year-old male with longstanding sarcoidosis who developed multiple hematologic complications, including bone marrow granulomatous infiltration, aplastic anemia, and T-LGLL.

162 patients with relapsed secondary central nervous system lymphoma (R-SCNSL) (median age, 65years; male, 59.9%) including central nervous system (CNS)-only (n=120) and concomitant CNS/systemic relapse (n=42) were retrospectively analyzed. Overall, 21.9% of patients were classified as high risk according to the CNS International Prognostic Index (CNS-IPI). Several biological and clinical features were significantly associated with leptomeningeal involvement, including double- or triple-hit (DHL/THL) status, MYC rearrangement, negative BCL6 expression by IHC, bone marrow involvement, and concomitant R-SCNSL. Multivariable analysis showed that leptomeningeal involvement independently predicted inferior OS and was associated with a 98% increase in the hazard of death compared with parenchymal relapse (HR=1.98, 95% CI: 1.20-3.26, p=0.008). Based on anatomical localization, R-SCNSL was classified into four subtypes: parenchymal-only involvement (parenchymal-CNS [P-CNS], 68/42%) and parenchymal involvement plus systemic relapse (parenchymal-concomitant [P-concomitant], 17/10.5%); and leptomeningeal with or without parenchymal involvement (leptomeningeal-CNS [LM-CNS], 52/32.1%) and leptomeningeal with systemic relapse (leptomeningeal-concomitant [LM-concomitant], 25/15.4%). This anatomical classification significantly impacted OS and PFS (p<0.001). Two-year OS and PFS were 58.2% and 29.1% for P-CNS, 32.4% and 17.7% for P-concomitant, 22% and 13.9% for LM-CNS, and 7.1% and 0% for LM-concomitant, respectively. ASCT showed a trend toward improved survival among patients with a response (CR/PR) in a 4-month landmark analysis. These findings support the clinical application of the anatomical classification in the management of R-SCNSL.

Bone marrow involvement in B-cell non-Hodgkin lymphoma is an adverse prognostic factor; therefore, its detection is necessary at the time of diagnosis and during follow-up. This study evaluates the concordance between flow cytometry (FC) and bone marrow biopsy (BMB) in detecting bone marrow involvement in B-cell non-Hodgkin lymphomas as well as their prognostic relevance in a Chilean cohort. A total of 202 samples from 172 patients with diffuse large B-cell (DLBCL), follicular (FL), marginal-zone (MZL), and mantle cell (MCL) lymphoma were retrospectively analyzed; all patients underwent simultaneous BMB and FC. Bone marrow involvement was identified in 29% of samples via BMB and in 40% via FC, with an overall concordance of 89% (kappa: 0.75), which was lower in mantle cell lymphoma. Eleven percent of cases showed BMB-FC+ discordance, generally associated with low tumor burden. In survival analyses, the BMB+/FC+ group exhibited shorter overall and progression-free survival, and concordant involvement was associated with a higher risk of mortality and progression, particularly among patients with an intermediate or high IPI. Involvement detected exclusively by FC did not have a significant prognostic impact. These findings support the role of FC as a complementary or alternative diagnostic tool in settings with limited resources, improving sensitivity for detecting bone marrow involvement without compromising clinical relevance.