<b>Objective:b>To compare the clinical characteristics of nasal NK/T-cell lymphoma（NKTL） and diffuse large B-cell lymphoma（DLBCL） to improve the diagnosis and differential diagnosis of nasal lymphomas. <b>Methods:b>A retrospective analysis of cases of nasal NKTL and DLBCL was conducted. The clinical symptoms, signs, and imaging features of both groups were compared and statistically analyzed. Results: The DLBCL group showed more symptoms like exophthalmos/diplopia and epiphora compared to the NKTL group （both P=0.040）. NKTL cases were more likely to be misdiagnosed as sinusitis（P=0.007）. In NKTL cases, nasal mucosal swelling（P<0.01）, destruction of nasal structures（P=0.002）, and external nasal structural abnormalities（P=0.003） were more prevalent. In imaging, the DLBCL group more commonly demonstrated worm-eaten destruction of sinus bones （P=0.004）, sinus masses （P=0.018）, and invasion of adjacent structures including the pterygopalatine fossa, infratemporal fossa （P<0.01）, orbit （P=0.039）, and skull base （P=0.011）. NKTL involved the turbinates（P=0.001）, nasal cavity and septum（P=0.016）, nasopharynx（P<0.01）, and "skip" infiltration of external nasal tissues（P=0.042） more frequently. No statistically significant differences were found in other clinical features between the two groups. <b>Conclusion:b>For patients with nasal obstruction and discharge, it is essential to inquire about systemic B symptoms, such as fever, and eye symptoms, such as periorbital swelling, diplopia, and lacrimation. Lymphoma should be suspected if local examination reveals diffuse nasal swelling, destruction of turbinates or septum, and external nasal structural abnormalities. Worm-eaten bone destruction and "cast-like" changes of the turbinates, septum, and nasal cavity, as well as "skip" infiltration of the external nose, are more common in NKTL. Sinus masses with invasion of the pterygopalatine fossa, infratemporal fossa, skull base, and orbit are more typical of DLBCL.
Humans ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/diagnosis* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Nasal Cavity/pathology* ; Male ; Diagnosis, Differential ; Female ; Middle Aged ; Nose Neoplasms/diagnosis* ; Adult ; Aged

Nodal marginal zone B-cell lymphoma(NMZL),the least common subtype of marginal zone lymphoma,represents a low-grade malignancy arising from the marginal zone of lymph node follicles,composed of small B-cells with an inert non-Hodgkin lymphoma nature.It accounts for 1.5% to 1.8% of all non-Hodgkin lymphomas and 10% of all marginal zone lymphomas.The low incidence and lack of typical clinical and pathological features pose a challenge to the diagnosis and clinical management of NMZL.In this article,we reported the diagnosis and treatment of a case of NMZL located in the parapharyngeal space of the left neck and reviewed the relevant literature from both domestic and international sources.We summarized the clinical manifestations,histopathological features,immunohistochemical characteristics,imaging features,diagnosis and treatment modalities,and prognosis of NMZL.
Humans ; Lymphoma, B-Cell, Marginal Zone/pathology* ; Lymph Nodes/pathology* ; Neck/pathology* ; Male

OBJECTIVE: To explore the expression and clinical significance of XPO1 in newly diagnosed adult diffuse large B-cell lymphoma (DLBCL), and further investigate its functional mechanism. METHODS: Immunohistochemical testing was conducted for XPO1 expression in 93 cases of DLBCL and 30 cases of reactive lymphoid hyperplasia. A risk model was construed to find survival related genes in DLBCL patients. Cell proliferation, apoptosis, and cell cycle assays were performed to explore the effect of XPO1 inhibitor (KPT-8602) and XPO1 knockdown. Differential expression gene (DEG) was examined based on the transcriptomes. RESULTS The expression of XPO1 in DLBCL patients was higher than that of the controls. Compared with XPO1 low-expression group, XPO1 high-expression group had a worse prognosis. The constructed risk model indicated that XPO1 and 14 genes in nucleocytoplasmic transport pathway (NTP) might be potential prediction marker of adverse outcome in DLBCL. Moreover, KPT-8602 as well as the XPO1 knockdown could inhibit cell proliferation, promote apoptosis, and induce cell cycle arrest in two DLBCL cell lines, Farage and SU-DHL-4. Based on the gene expression profiling in the datasets of DLBCL, patients were classified into XPO1 high and XPO1 low expression groups, and the MYBL1 was identified as the down-stream effector of XPO1. Inhibiting the function of XPO1 or reducing its expression can significantly decrease the expression of MYBL1 Conclusion: XPO1 is highly expressed in DLBCL, which is associated with poor prognosis. The oncogenic roles of the new XPO1/MYBL1 signaling are identified in DLBCL and XPO1 inhibitor may be a potential option for newly-diagnosed DLBCL patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Exportin 1 Protein ; Karyopherins/metabolism* ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cell Proliferation ; Apoptosis ; Prognosis ; Cell Line, Tumor ; Clinical Relevance

OBJECTIVE: To investigate the effect of TBL1XR1 mutation on cell biological characteristics of diffuse large B-cell lymphoma (DLBCL). METHODS: The TBL1XR1 overexpression vector was constructed and DNA sequencing was performed to determine the mutation status. The effect of TBL1XR1 mutation on apoptosis of DLBCL cell line was detected by flow cytometry and TUNEL fluorescence assay; CCK-8 assay was used to detect the effect of TBL1XR1 mutation on cell proliferation; Transwell assay was used to detect the effect of TBL1XR1 mutation on cell migration and invasion; Western blot was used to detect the effect of TBL1XR1 mutation on the expression level of epithelial-mesenchymal transition (EMT) related proteins. RESULTS: The TBL1XR1 overexpression plasmid was successfully constructed. The in vitro experimental results showed that TBL1XR1 mutation had no significant effect on apoptosis of DLBCL cells. Compared with the control group, TBL1XR1 mutation enhanced cell proliferation, migration and invasion of DLBCL cells. TBL1XR1 gene mutation significantly increased the expression of N-cadherin protein, while the expression of E-cadherin protein decreased. CONCLUSION TBL1XR1 mutation plays a role in promoting tumor cell proliferation, migration and invasion in DLBCL. TBL1XR1 could be considered as a potential target for DLBCL therapy in future research.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Proliferation ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics* ; Apoptosis ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Cell Movement ; Repressor Proteins/genetics* ; Nuclear Proteins/genetics* ; Cadherins/metabolism*

OBJECTIVE: To investigate the biological behavior, differentiation ability, and differential gene expression of lymph node mesenchymal stem cells (MSCs) in patients with diffuse large B-cell lymphoma (DLBCL) and reactive lymphoid hyperplasia (RLH), providing a theoretical basis for clinical chemotherapy resistance. METHODS: Lymph node MSCs from patients with DLBCL and RLH were separated, passaged and cultured. The cell morphology and growth status were observed. Flow cytometry was performed to detect the immune phenotype of MSCs. The in vitro directed differentiation ability of the two types of MSCs was observed. High-throughput sequencing was used to analyze the differential gene expression and enrichment of two groups of MSCs. RESULTS: The lymph node MSCs of patients with DLBCL and RLH had similar cell morphology and growth characteristics, and both groups of MSCs expressed CD90, CD105, and CD73 on the cell surface. Compared with lymph node MSCs derived from patients with RLH, lymph node MSCs derived from DLBCL patients showed stronger osteogenic and adipogenic differentiation abilities. High-throughput sequencing results displayed that lymph node MSCs derived from DLBCL patients significantly upregulated some genes such as TOP2A, LFNG, GRIA3, SEC14L2, SPON2, AURKA, LRRC15, FOXD1, HOXC9, CDC20 and remarkably downregulated some genes such as TBC1D8, LDLR, PCDHAC2, POLH, PKP2, ANKRD37, DMKN, HSD11B1, ARHGAP20, PTGS1,etc. CONCLUSION Lymph node MSCs in DLBCL patients exhibit unique biological behavior and gene expression profiles, which may be closely related to clinical chemotherapy resistance.
Humans ; Mesenchymal Stem Cells/cytology* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Differentiation ; Lymph Nodes/pathology* ; Pseudolymphoma/pathology*

OBJECTIVE: To investigate the inhibitory effect of Celastrus orbiculatus extracts (COE) on the proliferation of lymphoma cells and the immune regulation ability on inflammation and thrombophilia in vivo. METHODS: The 38B9 lymphoma cells were treated with COE (160 µ g/mL) and CTX (25 µ mol/L). The apoptosis rate and cell cycle of each group were detected by flow cytometry. The secretion of inflammatory factors, including interleukin (IL)-6, IL-10, and tumor necrosis factor α (TNF-α), in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). In vivo, BALB/c mice were subcutaneously injected with 38B9 lymphoma cells to establish lymphoma model. COE (3 mg·kg^-1·d^-1) and CTX (40 mg·kg^-1·d^-1) were administered to the model mice, respectively. The expression of plasma inflammatory factors (IL-6, IL-10 and TNF-α) and thrombus indexes, including D-dimer (D-D), von Willebrand factor (vWF) and tissue factor (TF), were detected by ELISA before tumor bearing (1 d), after tumor formation (14 d) and after intervention (21 d). PicoGreen dsDNA was used to detect the level of serum neutrophil extracellular traps (NETs). Flow cytometry was used to detect the expression of platelet activation marker calcium-dependent lectin-like receptor 2 (CLEC-2). The tumor growth and survival of mice were recorded. RESULTS: The 38B9 lymphoma cells were apoptotic after the intervention of COE and CTX. The ratio of G₂-M phase cells decreased in COE intervented cells compared with the control cells (P<0.05), and S phase cells decreased in CTX intervented cells (P<0.05). Also, the secretion level of IL-6 was significantly reduced after COE or CTX intervention (P<0.05), and IL-10 was significantly increased (P<0.05). Furthermore, the tumor mass was reduced, and the median survival time was longer in COE and CTX intervented tumor-bearing mice than in non-intervented mice. The significantly lower levels of TNF-α, IL-6, NETs, TF, DD and CLEC-2, as well as higher IL-10 were observed in COE and CTX treatment mice in comparision with the control mice (P<0.05). CONCLUSION COE has a mild and stable anti-tumor effect, which can reduce the secretion of inflammatory factors by lymphoma cells and regulate thrombophilic state caused by tumor inflammatory microenvironment.
Animals ; Plant Extracts/pharmacology* ; Mice, Inbred BALB C ; Thrombosis/drug therapy* ; Celastrus/chemistry* ; Cell Line, Tumor ; Lymphoma, B-Cell/pathology* ; Apoptosis/drug effects* ; Inflammation/pathology* ; Cell Proliferation/drug effects* ; Mice ; Cell Cycle/drug effects* ; Male ; Cytokines/metabolism* ; Inflammation Mediators/metabolism*

OBJECTIVE: To explore the effect of microRNA-424-5p (miR-424-5p) on the drug resistance of diffuse large B-cell lymphoma (DLBCL) cells by regulating the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway. METHODS: Human DLBCL cell line CRL2631 cells were induced to construct CRL2631-CHOP resistant cell line. RT-qPCR and Western blot were used to detect the expression levels of MiR-424-5p, PD-L1 mRNA and protein, and multidrug resistance gene-1 (MDR-1) protein in CRL2631 cells and CRL2631-CHOP cells, respectively. The target genes of MiR-424-5p was verified by dual luciferase reporter assay. The miRNA simulation/interference technology and thiazole blue (MTT) method were used to detect the resistance of CRL2631 cells and CRL2631-CHOP cells to CHOP. RESULTS: Compared with CRL2631 cells, the drug resistance of CRL2631-CHOP cells to CHOP and the levels of MDR-1 protein (P<0.05), PD-L1 mRNA and protein in the cells were significantly increased (both P<0.001), while the relative level of MiR-424-5p was significantly reduced (P<0.001). The result of the dual luciferase reporter assay showed that PD-L1 was the direct downstream target gene of MiR-424-5p (P<0.001). After transfection of MiR-424-5p inhibitor, the resistance of CRL2631 cells to CHOP drugs increased, and the expression level of MDR-1 protein (P<0.01), PD-L1 mRNA and protein also increased significantly (both P<0.01). After transfection of MiR-424-5p mimics, the resistance of CRL2631-CHOP cells to CHOP drugs decreased, and the expression level of MDR-1 protein (P<0.001), PD-L1 mRNA and protein also decreased significantly (both P<0.001). Overexpression of PD-L1 could reverse the inhibitory effect of upregulating MiR-424-5p on PD-L1 (P<0.001). CONCLUSION Down-regulation of MiR-424-5p enhances the drug resistance of DLBCL cells by regulating the PD-1/PD-L1 signaling pathway.
Humans ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Drug Resistance ; Luciferases ; Lymphoma, Large B-Cell, Diffuse/pathology* ; MicroRNAs/metabolism* ; Programmed Cell Death 1 Receptor ; RNA, Messenger ; Signal Transduction

OBJECTIVE: To study the clinical, imaging, and pathological features of pulmonary lymphoma. METHODS: Patients with pulmonary lymphoma diagnosed by lung biopsy in Zhongda Hospital Affiliated to Southeast University from November 2013 to December 2020 were collected and divided into secondary pulmonary lymphoma (SPL) group and primary pulmonary lymphoma (PPL) group according to the primary site of lymphoma. The clinical characteristics, stages, imaging features, diagnostic methods and pathological types of the two groups were analyzed. RESULTS: A total of 22 patients were included, 10 cases were PPL and 12 cases were SPL. The main symptoms of the two groups were cough, dyspnea and chest pain. The proportion of stage III/IV patients and international prognostic index (IPI) in SPL group were significantly higher than those in PPL group (P<0.05). Chest high-resolution computed tomography (HRCT) mainly showed masses, nodules and consolidation in both groups. The proportions of single mass and air bronchial sign in PPL group were significantly higher than those in SPL group, while the proportions of multiple nodules, mediastinal/hilar lymphadenopathy and pleural effusion were significantly lower (P<0.05). The max standardized uptake value (SUV_max), peak standardized uptake value (SUV_peak), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) in PPL group were lower than those in SPL group, but the differences were not statistically significant (P>0.05). In PPL group, 8 cases were diagnosed by transbronchial lung biopsy (TBLB) and 2 cases by percutaneous lung puncture. In SPL group, 4 cases were diagnosed by TBLB, 7 cases by percutaneous lung puncture, and 1 case by surgery. 95.5% patients were diagnosed by non-surgical methods. The main pathological type of PPL was mucosa-associated lymphoid tissue (MALT) lymphoma, while that of SPL was diffuse large B-cell lymphoma (P<0.05). CONCLUSION The clinical symptoms of pulmonary lymphoma are nonspecific, but the chest HRCT has characteristic manifestations, which can also help to distinguish between SPL and PPL. ¹⁸F-FDG PET/CT is also a potential method to distinguish between SPL and PPL. TBLB and percutaneous lung puncture biopsy are reliable methods for the diagnosis of lung lymphoma. The main pathological type of PPL is MALT lymphoma, while that of SPL is diffuse large B-cell lymphoma.
Humans ; Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; Lung Neoplasms/pathology* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Lymphoma, B-Cell, Marginal Zone/diagnosis* ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the clinicopathological characteristics and factors influencing the prognosis of non-Hodgkin lymphoma (NHL) in oral and maxillofacial regions. METHODS: Clinicopathological data of 369 patients with oral and maxillofacial NHL initially diagnosed in Peking University Hospital of Stomatology from 2008 to 2020 were collected and analyzed retrospectively. RESULTS: There were 180 males and 189 females. The median age of the patients was 56 years (3 months to 92 years), and the median duration was three months. Clinically, 283 cases manifested as mass, 38 cases as ulcerative necrotizing lesions, and 48 cases as diffuse soft tissue swelling. The lesions of 90 cases located in face and neck (75 cases neck, 20.3%), 99 cases were of major salivary glands (79 cases parotid glands, 20.9%), 103 cases of oral cavity, 50 cases of maxillofacial bones, 20 cases of Waldeyer's ring, and 7 cases of infratemporal fossa. In the study, 247 of the 369 patients had cervical lymphadenopathy, only 40 cases had B symptoms, and 23 cases had the bulky disease. Of the 369 NHLs, 299 (81%) were B-cell NHL, and 70(19%) were T-cell NHL. Diffuse large B-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, follicular lymphoma, and extranodal natural killer (NK)/T-cell lymphoma nasal type were the most common pathological subtypes. According to Ann Arbor staging, 87, 138, 106, and 38 cases were classified as staged Ⅰ, Ⅱ, Ⅲ, Ⅳ, respectively. The me-dian follow-up time was 48 months, 164 patients died during the follow-up period. The overall survival rates for one year, two years, and five years were 90.1%, 82.4%, and 59.9%, respectively, and the median survival was (86.00±7.98) months. Multivariate analysis showed that age (P < 0.001), Ann Arbor staging (P < 0.001), elevated lactate dehydrogenase (P=0.014), and pathological subtype (P=0.049) were the independent factors influencing the overall survival rate of NHL patients. CONCLUSION Oral and maxillofacial NHL has unique clinical characteristics and distribution patterns of pathological subtypes. Fewer patients had systemic symptoms. Neck and parotid glands were the most common sites invaded by NHL. Advanced age, Ann Arbor stage Ⅲ-Ⅳ, B symptoms, and T-cell NHL may predict a poor prognosis in oral and maxillofacial NHL patients.
Male ; Female ; Humans ; Middle Aged ; Retrospective Studies ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Lymphoma, B-Cell, Marginal Zone/pathology* ; Neck/pathology* ; Neoplasm Staging

BACKGROUND: Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL. METHODS: The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens. RESULTS: We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo . CONCLUSION Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.
Humans ; Animals ; Mice ; Rituximab/therapeutic use* ; Hippo Signaling Pathway ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Prognosis ; Semaphorins/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics*