Objective:To explore the application of genetic abnormalities in the diagnosis of angioimmunoblastic T-cell lymphoma(AITL)and the reliable pathological prognostic factors.Methods:This study included 53 AITL cases,whic...Objective:To explore the application of genetic abnormalities in the diagnosis of angioimmunoblastic T-cell lymphoma(AITL)and the reliable pathological prognostic factors.Methods:This study included 53 AITL cases,which were reviewed for morphological patterns,immunophenotypes,presence of Hodgkin and Reed-Sternberg(HRS)-like cells,and co-occurrence of B cell proliferation.The Epstein-Barr virus(EBV)-positive cells in tissues were counted,and cases were classified into“EBV encoded RNA(EBER)high-density”group if>50/HPF.Targeted exome sequencing was performed.Results:Mutation data can assist AITL diagnosis:1)with considerable HRS-like cells(20 cases):RHOA mutated in 14 cases(IDH2 co-mutated in 3 cases,4 cases with rare RHOA mutation),TET2 was mutated in 5 cases(1 case comutated with DNMT3A),and DNMT3A mutated in 1 case;2)accompanied with B cell lymphoma(7 cases):RHOA mutated in 4 cases(1 case had IDH2 mutation),TET2 mutated in 2 cases and DNMT3A mutated in 1 case;3)mimic peripheral T cell lymphoma,not otherwise specified(5 cases):RHOA mutated in 2 cases(IDH2 co-mutated in 1 case),TET2 mutated in 3 cases,and DNMT3A mutated in 1 case;4)pattern 1(1 case),RHOA and TET2 co-mutated.Besides RHOAG17V(30/35),rare variant included RHOAK18N,RHOAR68H,RHOAC83Y,RHOAD120G and RHOAG17del,IDH2R172 co-mutated with IDH2M397V in one case.There were recurrent mutations of FAT3,PCLO and PIEZO1 and genes of epigenetic remodeling,T-cell activation,APC and PI3K/AKT pathway.EBER high-density independently indicated adverse overall survival and progression-free survival(P=0.046 and P=0.008,KaplanMeier/log-rank).Conclusions:Over half AITL cases might be confused in diagnosis for certain conditions without mutation data.Targeted exome sequencing with a comprehensive panel is crucial to detect both hot-spot and rare mutation variants for RHOA and IDH2 and other recurrent mutated genes in addition to TET2 and DNMT3A.EBER highdensity independently indicated adverse survival.展开更多
目的:对3个血液学中心的成人早期前体T细胞白血病/淋巴瘤(ETP-ALL/LBL)患者进行回顾性分析,总结其临床特点、治疗及预后影响因素。方法:收集2006年1月至2019年1月来自北京大学第三医院、解放军第一医学中心和中国医学科学院血液学研究所...目的:对3个血液学中心的成人早期前体T细胞白血病/淋巴瘤(ETP-ALL/LBL)患者进行回顾性分析,总结其临床特点、治疗及预后影响因素。方法:收集2006年1月至2019年1月来自北京大学第三医院、解放军第一医学中心和中国医学科学院血液学研究所3个血液研究中心共113例T淋巴母细胞白血病/淋巴瘤(T-ALL/LBL)患者的临床数据资料,对其中ETP-ALL/LBL及非ETP-ALL/LBL患者的临床特征及预后进行分析比较。结果:113例T-ALL/LBL患者中,13例诊断为ETP-ALL/LBL(11.5%),其中男性患者11例(84.6%),中位年龄28(18-53)岁。与非ETP-ALL/LBL患者相比,ETP-ALL/LBL患者在年龄、性别、纵隔大包块发生率、临床分期、IPI评分、白细胞水平、乳酸脱氢酶水平方面差异无统计学意义。在13例ETP-ALL/LBL患者中,9例(69.2%)获得完全缓解,ETP-ALL/LBL患者较非ETP-ALL/LBL患者化疗诱导缓解率无统计学差异。在单纯化疗未进行异基因造血干细胞移植的患者中,ETP-ALL/LBL组较非ETP-ALL/LBL组显示出更差的5年生存率(0 vs 7.1%,P=0.008),而在进行异基因造血干细胞移植的患者中,两组5年生存率无统计学差异(37.5%vs 40.2%,P>0.05)。多因素Cox回归分析提示,诱导治疗达到完全缓解、异基因造血干细胞移植以及乳酸脱氢酶水平为影响T-ALL/LBL的独立预后因素。结论:ETP-ALL/LBL较其他类型T-ALL/LBL患者诱导化疗反应率无显著差异,诱导缓解后续贯异基因造血干细胞移植巩固治疗对于提高ETP-ALL/LBL患者远期生存率具有重要意义。展开更多
AIM:To investigate the clinical features,diagnosis,treatment and prognosis of intestinal T-cell lymphomas(ITCL)by retrospective analysis.METHODS:Sixty-eight patients who were diagnosed with ITCL in case reports in the...AIM:To investigate the clinical features,diagnosis,treatment and prognosis of intestinal T-cell lymphomas(ITCL)by retrospective analysis.METHODS:Sixty-eight patients who were diagnosed with ITCL in case reports in the Chinese literature were compiled and reviewed.Age,gender,CD56 expression,surgical management,multifocal nature,perforation and cyclophosphamide chemotherapy were analyzed as the prognostic factors.The Kaplan-Meier method was adopted for the univariate analysis and the cumulative survival curve analysis.RESULTS:The male-to-female ratio was 1.52 to 1.The median age was 41.7 years.Twenty-seven patients had symptoms of abdominal pain or diarrhea.Thirty-six of60 patients with temperature records had high fevers at the onset of the illness.Twenty-six of 34 patients who underwent fiberoptic colonoscopy were misdiagnosed with Crohn’s disease,intestinal tuberculosis or cancer.Sixty-one patients underwent surgery.Twelve of 61 surgical patients required a second operation for anastomotic leakage or secondary perforation.The sites of lesion involvement were the jejunum(8.82%),ileum(29.41%),ileum and colon(4.41%),colon(55.88%)and appendix(1.47%).The median cumulative survival rate was 3 mo(3.00±0.48).CONCLUSION:Efforts should be made to correctly diagnose ITCL and select the proper operative approach that may reduce serious complications and create opportunities for further treatment.展开更多
Background:Mature T-cell and natural killer(NK)-cell lymphomas compose a heterogeneous group of non-Hodgkin lymphomas,and extranodal NK/T-cell lymphoma,nasal type(ENKTL) is an aggressive subtype with sporadic CD30 exp...Background:Mature T-cell and natural killer(NK)-cell lymphomas compose a heterogeneous group of non-Hodgkin lymphomas,and extranodal NK/T-cell lymphoma,nasal type(ENKTL) is an aggressive subtype with sporadic CD30 expression.However,the significance of CD30 expression in ENKTL is controversial.We aimed to classify a large cohort of patients with mature T-cell and NK-cell lymphomas according to the 2016 World Health Organization(WHO) classification guidelines and to study the association between CD30 expression and prognosis of patients with ENKTL.Methods:We selected consecutive patients with mature T-cell and NK-cell lymphomas who attended our institution between September 1,2009 and August 31,2013.We classified the lymphomas according to the 2016 revision of the WHO classification of lymphoid neoplasms,analyzed the associations between CD30 expression and clinicopathologic features of ENKTL patients,and evaluated the prognostic implications of CD30 expression.Results:We identified 622 consecutive patients with mature T-cell and NK-cell lymphomas,including 317(51.0%)patients with ENKTL.In addition,CD30 expression was detected in 43(47.3%) of a subset of 91 patients with ENKTL.No clinicopathologic features were associated with CD30 expression,and CD30 positivity showed no prognostic significance in patients with ENKTL.Conclusions:ENKTL is the most common type of mature T-cell and NK-cell lymphoma diagnosed at our institution.CD30 is frequently expressed in ENKTL and represents a therapeutic target;however,it may not be a prognostic marker.展开更多
Natural killer/T-cell lymphoma(NKTCL)is a highly invasive subtype of non-Hodgkin lymphoma,typically positive for cytoplasmic CD3,CD56,cytotoxic markers,including granzyme B and TIA1,and Epstein-Barr virus(EBV).The cur...Natural killer/T-cell lymphoma(NKTCL)is a highly invasive subtype of non-Hodgkin lymphoma,typically positive for cytoplasmic CD3,CD56,cytotoxic markers,including granzyme B and TIA1,and Epstein-Barr virus(EBV).The current treatment methods for NKTCL are associated with several drawbacks.For example,chemotherapy can lead to drug resistance,while treatment with radiotherapy alone is inadequate and results in frequent relapses.Moreover,hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts.In recent years,immunotherapy has shown good clinical results and has become a hot spot in cancer research.Clinical activity of targeted antibodies,such as daratumumab(anti-CD38 antibody)and brentuximab vedotin(anti-CD30 antibody),have been reported in NKTCL.Additionally,dacetuzumab and Campath-1 H have demonstrated promising results.Further encouraging data have been obtained using checkpoint inhibitors.The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL.Furthermore,anti-CCR4 monoclonal antibodies(m Abs)exert cytotoxic actions on both CCR4+tumor cells and regulatory T cells.Depletion of these cells and the long half-life of anti-CCR4 m Abs result in enhanced induction of antitumor effector T cells.The role of IL10 in NKTCL has also been investigated.It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies.Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission.Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease.The present review outlines the known immunotherapy targets for the treatment of NKTCL.展开更多
结外鼻型NK/T细胞淋巴瘤(extranodal nasal type NK/T-cell lymphoma,ENKTL)是一种以破坏面部中份结构为主的NK/T细胞来源的非霍奇金淋巴瘤,临床少见。以口腔黏膜溃疡为首发症状的病例罕见且易与其他疾病相混淆,在诊断上极其困难。本文...结外鼻型NK/T细胞淋巴瘤(extranodal nasal type NK/T-cell lymphoma,ENKTL)是一种以破坏面部中份结构为主的NK/T细胞来源的非霍奇金淋巴瘤,临床少见。以口腔黏膜溃疡为首发症状的病例罕见且易与其他疾病相混淆,在诊断上极其困难。本文报道1例以颊黏膜及牙龈溃疡为首发表现的ENKTL的多学科诊疗,并分析该疾病的临床病理学特征、诊断、鉴别诊断和治疗,以期为临床诊治相关病例提供参考。展开更多
Primary pancreatic lymphoma(PPL)is an extremely rare form of extranodal malignant lymphoma.The most common histological subtype of PPL is diffuse large B cell lymphoma(DLBCL).In rare cases,PPL can also present as foll...Primary pancreatic lymphoma(PPL)is an extremely rare form of extranodal malignant lymphoma.The most common histological subtype of PPL is diffuse large B cell lymphoma(DLBCL).In rare cases,PPL can also present as follicular lymphoma,small lymphocytic lymphoma,and T cell lymphoma either of non-Hodgkin’s lymphoma or of Hodgkin’s lymphoma.T-cell/histiocyterich large B-cell lymphoma(T/HRBCL)is an uncommon morphologic variant of DLBCL with aggressive clinical course,it is predominantly a nodal disease,but extranodal sites such as bone marrow,liver,and spleen can be involved.Pancreatic involvement of T/HRBCL was not presented before.Herein,we report a 48-year-old male who was hospitalized with complaints of jaundice,dark brown urine,pale stools,and nausea.The radiological evaluation revealed a pancreatic head mass and,following operative biopsy,the tumor was diagnosed as T/HRBCL.The patient achieved remission after six cycles of CHOP chemotherapy.Therefore,T/HRBCL can be treated similarly to the stage-matched DLBCL and both of them get equivalent outcomes after chemotherapy.展开更多
BACKGROUND Monomorphic epitheliotropic intestinal T cell lymphoma(MEITL)is a rare extranodal T-cell lymphoma that has uniformly aggressive features with a poor prognosis.No standardized treatment protocols have been e...BACKGROUND Monomorphic epitheliotropic intestinal T cell lymphoma(MEITL)is a rare extranodal T-cell lymphoma that has uniformly aggressive features with a poor prognosis.No standardized treatment protocols have been established.Previous experience has demonstrated favorable outcomes with combination chemotherapy followed by autologous hematopoietic stem cell transplant.However,many patients are unable to tolerate the toxicities.Chidamide is a new histone deacetylase inhibitor that has shown preferential efficacy in mature T-cell lymphoma.CASE SUMMARY We herein present two cases of MEITL who were both intermediate risk according to enteropathy-associated T cell lymphoma prognostic index.Case one was a 61-year-old man.He complained of upper abdominal pain and intermittent black stool for 2 mo.Imaging examination revealed that the intestinal wall was thickened.He received a partial excision of the small intestine.A chidamidebased combination regimen was given postoperatively.Eleven months later,he presented with recurrence in the bilateral lungs.He passed away 15 mo after his diagnosis.Case two was a 35-year-old woman who complained of abdominal distention for 1 mo.Positron emission tomography/computed tomography demonstrated wall thickening of the small intestine and upper sigmoid colon.Colon perforation and septic shock occurred on the fourth day of her admission.She was treated by sigmoid colostomy.Chidamide-based combination therapy was then provided.She was recurrence-free for 6 mo until lesions were found in the bilateral brain and lived for 17 mo since her diagnosis.Compared to historical data,chidamide seems to improve the prognosis of MEITL slightly.CONCLUSION MEITL is a type of aggressive lymphoma.Chidamide is a new promising approach for the treatment of MEITL.展开更多
Subcutaneous panniculitis-like T cell lymphoma(SPTCL) is a very rare variant of non-Hodgkin's lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response....Subcutaneous panniculitis-like T cell lymphoma(SPTCL) is a very rare variant of non-Hodgkin's lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response. Here, we describe our use of fluorine-18 fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT) for staging and monitoring of treatment response in 3 cases of SPTCL. Primary staging by PET/CT showed that all 3 patients had multiple foci in the subcutaneous fat tissue, with SUVmax from 10.5 to 14.6. Involvement of intra-abdominal fat with high SUVmax was identified in 2 of the patients. Use of the triple drug regimen of gemcitabine, cisplatin and methylprednisolone(commonly known as "GEM-P") as first-line therapy or second-line therapy facilitated complete metabolic response for all 3 cases. FDG PET/CT provides valuable information for staging and monitoring of treatment response and can reveal occult involvement of the intraabdominal visceral fat. High FDG uptake on pre-treatment PET can identify patients with aggressive disease and help in selection of first-line therapy.展开更多
Objective:Angioimmunoblastic T cell lymphoma(AITL)is an aggressive form of non-Hodgkin lymphoma derived from mature T cells.However,the underlying pathogenesis of AITL remains unresolved.We aimed to explore the role o...Objective:Angioimmunoblastic T cell lymphoma(AITL)is an aggressive form of non-Hodgkin lymphoma derived from mature T cells.However,the underlying pathogenesis of AITL remains unresolved.We aimed to explore the role of FOXO1-mediated signaling in the tumorigenesis and progression of AITL.Methods:FOXO1 expression was assessed using immunohistochemistry on a total of 46 AITL tissue samples.Retroviruses encoding FOXO1 shRNA were used to knockdown FOXO1 expression in CD4^+T cells.Flow cytometric assays analyzed the proliferation and survival of FOXO1 knockdown CD4^+T cells.Furthermore,we performed adoptive T-cell transfer experiments to identify whether inactivation of FOXO1 induced neoplastic follicular-helper T(Tfh)cell polarization and function.Results:Patients with low FOXO1 protein levels were prone to have an advanced tumor stage(P=0.049),higher ECOG ps(P=0.024),the presence of bone marrow invasion(P=0.000),and higher IPI(P=0.035).Additionally,the survival rates of patients in the FOXO1 high-expression group were significantly better than those in the FOXO1 low-expression group(χ^2=5.346,P=0.021).We also observed that inactivation of FOXO1 increased CD4^+T cell proliferation and altered the survival and cell-cycle progression of CD4^+T cells.Finally,we confirmed that inactivation of FOXO1 induces Tfh cell programing and function.Conclusions:Inactivation of FOXO1 in AITL plays a key role in the tumorigenesis and progression of AITL.We propose that FOXO1 expression could be a useful prognostic marker in AITL patients to predict poor survival,and to design appropriate therapeutic strategies.展开更多
基金supported by“Hygiene and Health Development Scientific Research Fostering Plan of Haidian District Beijing”(No.HP2021-31-50302).
文摘Objective:To explore the application of genetic abnormalities in the diagnosis of angioimmunoblastic T-cell lymphoma(AITL)and the reliable pathological prognostic factors.Methods:This study included 53 AITL cases,which were reviewed for morphological patterns,immunophenotypes,presence of Hodgkin and Reed-Sternberg(HRS)-like cells,and co-occurrence of B cell proliferation.The Epstein-Barr virus(EBV)-positive cells in tissues were counted,and cases were classified into“EBV encoded RNA(EBER)high-density”group if>50/HPF.Targeted exome sequencing was performed.Results:Mutation data can assist AITL diagnosis:1)with considerable HRS-like cells(20 cases):RHOA mutated in 14 cases(IDH2 co-mutated in 3 cases,4 cases with rare RHOA mutation),TET2 was mutated in 5 cases(1 case comutated with DNMT3A),and DNMT3A mutated in 1 case;2)accompanied with B cell lymphoma(7 cases):RHOA mutated in 4 cases(1 case had IDH2 mutation),TET2 mutated in 2 cases and DNMT3A mutated in 1 case;3)mimic peripheral T cell lymphoma,not otherwise specified(5 cases):RHOA mutated in 2 cases(IDH2 co-mutated in 1 case),TET2 mutated in 3 cases,and DNMT3A mutated in 1 case;4)pattern 1(1 case),RHOA and TET2 co-mutated.Besides RHOAG17V(30/35),rare variant included RHOAK18N,RHOAR68H,RHOAC83Y,RHOAD120G and RHOAG17del,IDH2R172 co-mutated with IDH2M397V in one case.There were recurrent mutations of FAT3,PCLO and PIEZO1 and genes of epigenetic remodeling,T-cell activation,APC and PI3K/AKT pathway.EBER high-density independently indicated adverse overall survival and progression-free survival(P=0.046 and P=0.008,KaplanMeier/log-rank).Conclusions:Over half AITL cases might be confused in diagnosis for certain conditions without mutation data.Targeted exome sequencing with a comprehensive panel is crucial to detect both hot-spot and rare mutation variants for RHOA and IDH2 and other recurrent mutated genes in addition to TET2 and DNMT3A.EBER highdensity independently indicated adverse survival.
文摘目的:对3个血液学中心的成人早期前体T细胞白血病/淋巴瘤(ETP-ALL/LBL)患者进行回顾性分析,总结其临床特点、治疗及预后影响因素。方法:收集2006年1月至2019年1月来自北京大学第三医院、解放军第一医学中心和中国医学科学院血液学研究所3个血液研究中心共113例T淋巴母细胞白血病/淋巴瘤(T-ALL/LBL)患者的临床数据资料,对其中ETP-ALL/LBL及非ETP-ALL/LBL患者的临床特征及预后进行分析比较。结果:113例T-ALL/LBL患者中,13例诊断为ETP-ALL/LBL(11.5%),其中男性患者11例(84.6%),中位年龄28(18-53)岁。与非ETP-ALL/LBL患者相比,ETP-ALL/LBL患者在年龄、性别、纵隔大包块发生率、临床分期、IPI评分、白细胞水平、乳酸脱氢酶水平方面差异无统计学意义。在13例ETP-ALL/LBL患者中,9例(69.2%)获得完全缓解,ETP-ALL/LBL患者较非ETP-ALL/LBL患者化疗诱导缓解率无统计学差异。在单纯化疗未进行异基因造血干细胞移植的患者中,ETP-ALL/LBL组较非ETP-ALL/LBL组显示出更差的5年生存率(0 vs 7.1%,P=0.008),而在进行异基因造血干细胞移植的患者中,两组5年生存率无统计学差异(37.5%vs 40.2%,P>0.05)。多因素Cox回归分析提示,诱导治疗达到完全缓解、异基因造血干细胞移植以及乳酸脱氢酶水平为影响T-ALL/LBL的独立预后因素。结论:ETP-ALL/LBL较其他类型T-ALL/LBL患者诱导化疗反应率无显著差异,诱导缓解后续贯异基因造血干细胞移植巩固治疗对于提高ETP-ALL/LBL患者远期生存率具有重要意义。
文摘AIM:To investigate the clinical features,diagnosis,treatment and prognosis of intestinal T-cell lymphomas(ITCL)by retrospective analysis.METHODS:Sixty-eight patients who were diagnosed with ITCL in case reports in the Chinese literature were compiled and reviewed.Age,gender,CD56 expression,surgical management,multifocal nature,perforation and cyclophosphamide chemotherapy were analyzed as the prognostic factors.The Kaplan-Meier method was adopted for the univariate analysis and the cumulative survival curve analysis.RESULTS:The male-to-female ratio was 1.52 to 1.The median age was 41.7 years.Twenty-seven patients had symptoms of abdominal pain or diarrhea.Thirty-six of60 patients with temperature records had high fevers at the onset of the illness.Twenty-six of 34 patients who underwent fiberoptic colonoscopy were misdiagnosed with Crohn’s disease,intestinal tuberculosis or cancer.Sixty-one patients underwent surgery.Twelve of 61 surgical patients required a second operation for anastomotic leakage or secondary perforation.The sites of lesion involvement were the jejunum(8.82%),ileum(29.41%),ileum and colon(4.41%),colon(55.88%)and appendix(1.47%).The median cumulative survival rate was 3 mo(3.00±0.48).CONCLUSION:Efforts should be made to correctly diagnose ITCL and select the proper operative approach that may reduce serious complications and create opportunities for further treatment.
基金supported by the Medical Scientific Research Foundation of Guangdong Province,China(No.2014246)Sister Institution Network Fund of the University of Texas MD Anderson Cancer Center(to Huilan Rao)
文摘Background:Mature T-cell and natural killer(NK)-cell lymphomas compose a heterogeneous group of non-Hodgkin lymphomas,and extranodal NK/T-cell lymphoma,nasal type(ENKTL) is an aggressive subtype with sporadic CD30 expression.However,the significance of CD30 expression in ENKTL is controversial.We aimed to classify a large cohort of patients with mature T-cell and NK-cell lymphomas according to the 2016 World Health Organization(WHO) classification guidelines and to study the association between CD30 expression and prognosis of patients with ENKTL.Methods:We selected consecutive patients with mature T-cell and NK-cell lymphomas who attended our institution between September 1,2009 and August 31,2013.We classified the lymphomas according to the 2016 revision of the WHO classification of lymphoid neoplasms,analyzed the associations between CD30 expression and clinicopathologic features of ENKTL patients,and evaluated the prognostic implications of CD30 expression.Results:We identified 622 consecutive patients with mature T-cell and NK-cell lymphomas,including 317(51.0%)patients with ENKTL.In addition,CD30 expression was detected in 43(47.3%) of a subset of 91 patients with ENKTL.No clinicopathologic features were associated with CD30 expression,and CD30 positivity showed no prognostic significance in patients with ENKTL.Conclusions:ENKTL is the most common type of mature T-cell and NK-cell lymphoma diagnosed at our institution.CD30 is frequently expressed in ENKTL and represents a therapeutic target;however,it may not be a prognostic marker.
文摘Natural killer/T-cell lymphoma(NKTCL)is a highly invasive subtype of non-Hodgkin lymphoma,typically positive for cytoplasmic CD3,CD56,cytotoxic markers,including granzyme B and TIA1,and Epstein-Barr virus(EBV).The current treatment methods for NKTCL are associated with several drawbacks.For example,chemotherapy can lead to drug resistance,while treatment with radiotherapy alone is inadequate and results in frequent relapses.Moreover,hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts.In recent years,immunotherapy has shown good clinical results and has become a hot spot in cancer research.Clinical activity of targeted antibodies,such as daratumumab(anti-CD38 antibody)and brentuximab vedotin(anti-CD30 antibody),have been reported in NKTCL.Additionally,dacetuzumab and Campath-1 H have demonstrated promising results.Further encouraging data have been obtained using checkpoint inhibitors.The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL.Furthermore,anti-CCR4 monoclonal antibodies(m Abs)exert cytotoxic actions on both CCR4+tumor cells and regulatory T cells.Depletion of these cells and the long half-life of anti-CCR4 m Abs result in enhanced induction of antitumor effector T cells.The role of IL10 in NKTCL has also been investigated.It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies.Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission.Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease.The present review outlines the known immunotherapy targets for the treatment of NKTCL.
文摘结外鼻型NK/T细胞淋巴瘤(extranodal nasal type NK/T-cell lymphoma,ENKTL)是一种以破坏面部中份结构为主的NK/T细胞来源的非霍奇金淋巴瘤,临床少见。以口腔黏膜溃疡为首发症状的病例罕见且易与其他疾病相混淆,在诊断上极其困难。本文报道1例以颊黏膜及牙龈溃疡为首发表现的ENKTL的多学科诊疗,并分析该疾病的临床病理学特征、诊断、鉴别诊断和治疗,以期为临床诊治相关病例提供参考。
文摘Primary pancreatic lymphoma(PPL)is an extremely rare form of extranodal malignant lymphoma.The most common histological subtype of PPL is diffuse large B cell lymphoma(DLBCL).In rare cases,PPL can also present as follicular lymphoma,small lymphocytic lymphoma,and T cell lymphoma either of non-Hodgkin’s lymphoma or of Hodgkin’s lymphoma.T-cell/histiocyterich large B-cell lymphoma(T/HRBCL)is an uncommon morphologic variant of DLBCL with aggressive clinical course,it is predominantly a nodal disease,but extranodal sites such as bone marrow,liver,and spleen can be involved.Pancreatic involvement of T/HRBCL was not presented before.Herein,we report a 48-year-old male who was hospitalized with complaints of jaundice,dark brown urine,pale stools,and nausea.The radiological evaluation revealed a pancreatic head mass and,following operative biopsy,the tumor was diagnosed as T/HRBCL.The patient achieved remission after six cycles of CHOP chemotherapy.Therefore,T/HRBCL can be treated similarly to the stage-matched DLBCL and both of them get equivalent outcomes after chemotherapy.
文摘BACKGROUND Monomorphic epitheliotropic intestinal T cell lymphoma(MEITL)is a rare extranodal T-cell lymphoma that has uniformly aggressive features with a poor prognosis.No standardized treatment protocols have been established.Previous experience has demonstrated favorable outcomes with combination chemotherapy followed by autologous hematopoietic stem cell transplant.However,many patients are unable to tolerate the toxicities.Chidamide is a new histone deacetylase inhibitor that has shown preferential efficacy in mature T-cell lymphoma.CASE SUMMARY We herein present two cases of MEITL who were both intermediate risk according to enteropathy-associated T cell lymphoma prognostic index.Case one was a 61-year-old man.He complained of upper abdominal pain and intermittent black stool for 2 mo.Imaging examination revealed that the intestinal wall was thickened.He received a partial excision of the small intestine.A chidamidebased combination regimen was given postoperatively.Eleven months later,he presented with recurrence in the bilateral lungs.He passed away 15 mo after his diagnosis.Case two was a 35-year-old woman who complained of abdominal distention for 1 mo.Positron emission tomography/computed tomography demonstrated wall thickening of the small intestine and upper sigmoid colon.Colon perforation and septic shock occurred on the fourth day of her admission.She was treated by sigmoid colostomy.Chidamide-based combination therapy was then provided.She was recurrence-free for 6 mo until lesions were found in the bilateral brain and lived for 17 mo since her diagnosis.Compared to historical data,chidamide seems to improve the prognosis of MEITL slightly.CONCLUSION MEITL is a type of aggressive lymphoma.Chidamide is a new promising approach for the treatment of MEITL.
文摘Subcutaneous panniculitis-like T cell lymphoma(SPTCL) is a very rare variant of non-Hodgkin's lymphoma. Currently, there is no standard imaging method for staging of SPTCL nor for assessment of treatment response. Here, we describe our use of fluorine-18 fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT) for staging and monitoring of treatment response in 3 cases of SPTCL. Primary staging by PET/CT showed that all 3 patients had multiple foci in the subcutaneous fat tissue, with SUVmax from 10.5 to 14.6. Involvement of intra-abdominal fat with high SUVmax was identified in 2 of the patients. Use of the triple drug regimen of gemcitabine, cisplatin and methylprednisolone(commonly known as "GEM-P") as first-line therapy or second-line therapy facilitated complete metabolic response for all 3 cases. FDG PET/CT provides valuable information for staging and monitoring of treatment response and can reveal occult involvement of the intraabdominal visceral fat. High FDG uptake on pre-treatment PET can identify patients with aggressive disease and help in selection of first-line therapy.
基金supported by Natural Science Foundation of Fujian Province (Grant No. 2015J01314)
文摘Objective:Angioimmunoblastic T cell lymphoma(AITL)is an aggressive form of non-Hodgkin lymphoma derived from mature T cells.However,the underlying pathogenesis of AITL remains unresolved.We aimed to explore the role of FOXO1-mediated signaling in the tumorigenesis and progression of AITL.Methods:FOXO1 expression was assessed using immunohistochemistry on a total of 46 AITL tissue samples.Retroviruses encoding FOXO1 shRNA were used to knockdown FOXO1 expression in CD4^+T cells.Flow cytometric assays analyzed the proliferation and survival of FOXO1 knockdown CD4^+T cells.Furthermore,we performed adoptive T-cell transfer experiments to identify whether inactivation of FOXO1 induced neoplastic follicular-helper T(Tfh)cell polarization and function.Results:Patients with low FOXO1 protein levels were prone to have an advanced tumor stage(P=0.049),higher ECOG ps(P=0.024),the presence of bone marrow invasion(P=0.000),and higher IPI(P=0.035).Additionally,the survival rates of patients in the FOXO1 high-expression group were significantly better than those in the FOXO1 low-expression group(χ^2=5.346,P=0.021).We also observed that inactivation of FOXO1 increased CD4^+T cell proliferation and altered the survival and cell-cycle progression of CD4^+T cells.Finally,we confirmed that inactivation of FOXO1 induces Tfh cell programing and function.Conclusions:Inactivation of FOXO1 in AITL plays a key role in the tumorigenesis and progression of AITL.We propose that FOXO1 expression could be a useful prognostic marker in AITL patients to predict poor survival,and to design appropriate therapeutic strategies.
