Updating targets for natural killer/T-cell lymphoma immunotherapy

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.

CD30 expression in extranodal natural killer/T-cell lymphoma,nasal type among 622 cases of mature T-cell and natural killer-cell lymphoma at a single institution in South China

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.

Intestinal T-cell lymphomas:A retrospective analysis of 68 cases in China

AIM: To investigate the clinical features, diagnosis, treatment and prognosis of intestinal T-cell lymphomas (ITCL) by retrospective analysis.

Chidamide based combination regimen for treatment of monomorphic epitheliotropic intestinal T cell lymphoma following radical operation:Two case reports

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.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography evaluation of subcutaneous panniculitis-like T cell lymphoma and 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.

Inactivation of FOXO1 induces T follicular cell polarization and involves angioimmunoblastic T cell lymphoma

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.

Synchronous adenocarcinoma and extranodal natural killer/T-cell lymphoma of the colon:A case report and literature review

Extranodal natural killer/T-cell lymphoma(ENKTL) is a distinct subtype of non-Hodgkin's lymphoma and is rare in the colon.Synchronous adenocarcinoma and ENKTL of the colon has not been reported in the literature.In the present study,we report a 63-year-old male who suffered from intermittent bloody stools for 2 mo.He did not have fever,body weight loss or night sweat.Endoscopic and imaging studies revealed a 4.5-cm ulcerative mass in the ascending colon and a 3.0-cm polypoid,easy bleeding mass in the sigmoid colon,respectively.Thought to have double carcinoma of the colon,he received simultaneous right hemicolectomy and sigmoidectomy.The pathological diagnosis was a synchronous ENKTL(ascending colon) and adenocarcinoma(sigmoid colon).The literature on synchronous adenocarcinoma and malignant lymphoma of the colon was also reviewed.

Primary site and regional lymph nodeinvolvement are independent prognosticfactors for early？stage extranodal nasal？typenatural killer/T cell lymphoma

Background:Nasal-type extranodal natural killer/T-cell lymphoma(ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract.However,it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement.The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL.Methods:To develop a nomogram,we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011.The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index(C-index) and calibration curve.Results:The 5-year overall survival(OS) and progression-free survival(PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL(OS:68.2%vs.46.0%,P = 0.030;PFS:53.4%vs.26.6%,P = 0.010).The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage HE ENKTCL(OS:66.3%vs.59.2%,P = 0.003;PFS:51.4%vs.40.3%,P = 0.009).Multivariate analysis showed that age >60 years,ECOG performance status score >2,elevated lactate dehydrogenase(LDH) level,extranasal primary site,and regional lymph node involvement were significantly associated with lower 5-year OS rate;age >60 years,elevated LDH level,extra-nasal primary site,and regional lymph node involvement were significantly associated with lower 5-year PFS rate.The nomogram included the primary site and regional lymph node involvement based on multivariate analysis.The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates,and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634,respectively.Conclusions:The primary site and regional lymph node involvement are independent prognostic factors for earlystage ENKTCL treated with chemotherapy followed by definitive radiotherapy.

miRNA-155 Modulates the Malignant Biological Characteristics of NK/T-Cell Lymphoma Cells by Targeting FOXO3a Gene

This study investigated the effects of miRNA-155 on malignant biological characteristics of NK/T-cell lymphoma cell lines and the possible mechanism. The expression of miRNA-155 was detected in lymphoma cell lines from different sources （SNK-6, YTS, Jurkat and DOHH2） by real-time PCR. Lentiviral vectors （pLL3.7） that could overexpress or downexpress miRNA-155 were constructed. Recombinant lentiviral particles were prepared and purified, and their titers determined. The expression of miRNA-155 in the infected SNK-6 cells and the cell proliferation were detected by PCR and CCK-8, respectively. Flow cytometry was used to determine the apoptosis of infected SNK-6 cells. The target of miRNA155 was predicted from Targetscan website. The effect of miRNA155 on FOXO3a expression was examined by Western blotting. The results showed that among the human NK/T-cell lymphoma cell lines SNK-6, YTS, Jurkat and DOHH2, the expression of miRNA-155 was highest in SNK-6. The infection efficiency of the recombinant lentivirns in SNK-6 was more than 70% at multiplicity of infection （MOI） of 100. The expression of miRNA-155 was significantly increased in SNK-6 cells infected by lentivirus vectors with high expression of miRNA-155 （4 times higher than the control group）, and profoundly decreased in those infected with lentivirnses with low expression of miRNA-155. The proliferation of letivirns-infected SNK-6 cells was decreased as the expression of miRNA-155 reduced. The apoptosis rate was increased with the reduction in the expression of miRNA-155. FOXO3a was found to be a possible target of miRNA155, as suggested by Targetscan website. Western blotting showed that the expression of FOXO3a was significantly elevated in SNK-6 cells with miRNA-155 inhibition. It was concluded that reduction in miRNA-155 expression can inhibit the proliferation of SNK-6 lymphoma cells and promote their apoptosis, which may be associated with regulation of FOXO3a gene.

Association between genetic variations in tumor necrosis factor receptor genes and survival of patients with T-cell lymphoma

The prognosis of T-cell lymphoma (TCL) has been shown to be associated with the clinical characteristics of patients. However, there is little knowledge of whether genetic variations also affect the prognosis of TCL. This study investigated the associations between single nucleotide polymorphisms(SNPs) in tumor necrosis factor receptor superfamily(TNFRSF) genes and the survival of patients with TCL. A total of 38 tag SNPs in 18 TNFRSF genes were genotyped using Sequenom platform in 150 patients with TCL. Kaplan-Meier survival estimates were plotted and significance was assessed using log-rank tests. Cox proportional hazard models were used to analyze each of these 38 SNPs with adjustment for covariates that might influence patient survival, including sex and international prognostic Index score. Hazard ratios (HRs) and their 95% confidence intervals(CIs) were calculated. Among the 38 SNPs tested, 3 were significantly associated with the survival of patients with TCL. These SNPs were located at LTβR (rs3759333C>T) and TNFRSF17(rs2017662C>T and rs2071336C>T). The 5-year survival rates were significantly different among patients carrying different genotypes and the HRs for death between the different genotypes ranged from 0.45 to 2.46. These findings suggest that the SNPs in TNFRSF genes might be important determinants for the survival of TCL patients.

The prognostic potential of pretreatment C-reactive protein to albumin ratio in stage IE/IIE extranodal natural killer/T-cell lymphoma

Objective The aim of this study was to determine the prognostic significance of the C-reactive protein-toalbumin ratio (CRP/Alb) for stage IE/IIE upper aerodigestive tract extranodal NK/T cell lymphoma patients. Methods One hundred and fourteen patients diagnosed with extranodal NK/T cell lymphoma at Sichuan Cancer Hospital from September 2011 to November 2016 were retrospectively reviewed. An optimal cutoff value of CRP/Alb for overall survival rate as an endpoint was obtained using the receiver operating curve (ROC). Results The optimal cutoff value of CRP/Alb was 0.15. For the low CRP/Alb group, the 3-year progression-free survival (PFS) was 78.6% and the 3-year overall survival (OS) was 80.7%. The 3-year PFS and OS values for the high CRP/Alb group were 41.6% and 45.2%, respectively. Differences for PFS (P < 0.001) and OS (P < 0.001) between the two groups were statistically significant. Univariate analysis showed that ECOG, IPI, CRP, GPS, and CRP/Alb were significantly associated with PFS. Similarly, all five were also significantly associated with OS. Multivariate analysis further confirmed that ECOG and CRP/ Alb were independent prognostic factors for both PFS and OS. Moreover, the cutoff value of CRP/Alb showed superior prognostic ability in discriminating between patients with different outcomes in low-risk group based on GPS, IPI, and KPI scores. Conclusion CRP/Alb is a promising prognostic marker for early-stage extranodal NK/T cell lymphoma.

Intestinal NK/T cell lymphoma: A case report

BACKGROUND The incidence of intestinal NK/T cell lymphoma(NKTCL)is extremely low,and the clinical symptoms are atypical,which makes it difficult to distinguish this disorder from Crohn's disease(CD),T lymphocyte proliferative disease,and other immune disorders.The misdiagnosis rate is high,and the patient's prognosis is poor.CASE SUMMARY In this case,the patient had repeated high fever,colonoscopy revealed multiple ulcers,and the initial diagnosis was CD.The patient’s condition did not improve after treatment with hormones and infliximab,and she eventually died.Positron emission tomographic-computed tomographic and B-ultrasound were performed in our hospital and showed that multiple lymph nodes were enlarged.Immunohistochemi-stry showed that CD3 and Epstein-Barr virus encoded RNA expression was positive.Colonoscopy,tissue biopsy,and histopathology showed intestinal focal mucosal infiltration of heterotypic lymphocytes with an abnormal immune phenotype.On the basis of the patient’s medical history,auxiliary examination,and pathological findings,digestive physicians and pathologists gave the diagnosis of NKTCL.CONCLUSION Clinicians need to improve their comprehensive knowledge of NKTCL,and combination of clinical symptoms,histological characteristics,as well as colonoscopy biopsies should be considered to improve the diagnosis and thereby reduce misdiagnosis.

T-cell/histiocyte-rich large B-cell lymphoma in a child:A case report and review of literature

T-cell/histiocyte-rich large B-cell lymphoma is uncommon in children population. There were few cases reported in the literature with wide range clinical presentations including advanced stage, and more involvement of liver, spleen and bone marrow. Head and neck lymphadenopathy tends to present in younger children. We report a case of 10-year-old boy who initially presented intermittent fever, headaches and neck lymphadenopathy. Subsequently, he developed diffuse lymphadenopathy and hepatosplenomegaly. T-cell/histiocyte-rich large B-cell lymphoma was diagnosed on a cervical lymph node biopsy. Cervical lymphadenopathy in this age group is most commonly reactive or nonmalignant processes. Lymphoma is much less frequent; mainly are non-Hodgkin lymphomas. However, a subset of large B-cell lymphoma called T-cell/histiocyte-rich B-cell lymphoma is rare in children.

Muscular involvement of extranodal natural killer/T cell lymphoma misdiagnosed as polymyositis: A case report and review of literature

BACKGROUND Natural killer(NK)/T cell lymphoma is a rare and highly aggressive malignant tumor,and is a special form of non-Hodgkin's lymphoma.Although extranodal involvement is frequently found in tissues such as the skin,testicular and gastrointestinal tract etc,its presence in skeletal muscle has scarcely been reported in the literature.CASE SUMMARY We report a case of extranodal NK/T cell lymphoma with muscle swelling as the first clinical manifestation.A 42-year-old man,who initially presented with localized swelling in the double lower extremities,demonstrated gradual facial and eyelid swelling,and his imaging results showed multiple sites of muscle damage throughout the body.The final pathological results suggested NK/T cell lymphoma,and immunohistochemistry showed CD20(-),CD3(+),CD30(+),CD56(-),EBER(+),Ki67(60%),TIA-1(+)and CD68(±)staining.The muscle swelling significantly improved after treatment with chemotherapy regimens.CONCLUSION This disease is difficult to diagnose and highly invasive,and should be included in the differential diagnosis of unexplained muscle swelling.

Establishment of a Human Malignant T Lymphoma Cell Line Carrying a Retrovirus-like Particles with RT Activity

We have established an IL-2 independent malignant lymphoma line (CM-1) from peripheral T lymphocytes donated by a femalc patient with nervous systcm disease, the binlogical characteristics of CM-1 cells was studied in this paper. Another T lymphocytes,such as peripheral T lymphocytes donated by a maIe patient with multiple sclerosis, could be transformed into a malignant lymphoma line by using filtered supernatant of the CM-1 cultured medium, thus the CM-2 cell line u'as estabIished. The CM-1 and CM-2 cells were transplanted by subcutaneous inoculation into nude mice, and could cause the occurrenceof typical maIignant lymphoma. The observation of eIectron micrographs suggested the existence of virions in the CM-1 and CM-2 cells, and these virions were similar toretrovirus in the ultra-structure characteristics. lt was found that this virus possesses reverse transcriptase activity. ResuIts obtained from serological assay, molecular hybridization and PCR excluded the existence of other human viruses, which were commonly usedin our laboratory. The unknown virus possesses strong transformation activity, and probably is a new retro virus. Meanwhile, the work on the clone and sequence analysis ofthis virus are being carried out.

A case of mucosa-associated lymphoid tissue lymphoma of the gastrointestinal tract showing extensive plasma cell differentiation with prominent Russell bodies

A 73-year-old Japanese woman was hospitalized for detailed examination of nausea, diarrhea and loss of appetite. Atypical erosion in the ileum was found on endoscopy. Biopsy of this erosion showed proliferation of cells containing numerous Russell bodies. Differential diagnoses considered were Russell body enteritis, crystal-storing histiocytosis, Mott cell tumor, immunoproliferative small intestinal disease(IPSID) and mucosaassociated lymphoid tissue(MALT) lymphoma. The cells containing prominent Russell bodies showed diffuse positivity for CD79 a and CD138, but negative results for CD20, CD3, UCHL-1, CD38 and CD68. Russell bodies were diffusely positive for lambda light chain, but negative for kappa light chain, and immunoglobulin(Ig)G, Ig A and Ig M. Based on these findings, Russell body enteritis, crystal-storing histiocytosis and IPSID were ruled out. As the tumor formed no mass lesions and was restricted to the gastrointestinal tract, MALT lymphoma with extensive plasma cell differentiation was finally diagnosed. The patient showed an unexpectedly aggressive clinical course. The number of atypical lymphocytes in peripheral blood gradually increased and T-prolymphocytic leukemia(T-PLL) emerged. The patient died of T-PLL 7 mo after admission. Autopsy was not permitted.

A case of rapid growing colonic NK/T cell lymphoma complicated by Crohn's disease

A 37-year-old man developed abdominal pain and bloody diarrhea 11 months before admission. The colonoscopy revealed multifocal ulcers in the colon. Histology showed active chronic inflammation. Although anti-tuberculosis medication was effective, his symptoms repeated 2 months later. The subsequent colonoscopy revealed more extensive irregular ulcers than before, and he was clinically suspected with intestinal malignant lymphoma. He underwent subtotal colectomy and was histologically suggested Crohn＇s disease, then 5-aminosalicylic and a combination of prednisone and azathioprine were administered in succession postoperatively, but they achieved minimal relief of symptoms for a period of 7 months. The third colonoscopy showed a large irregular ulcer in the ileocolon stomas, and primary colonic NK/T cell lymphoma was diagnosed through histological and immunophenotypic studies. Malignant lymphoma should be taken into consideration when clinically diagnosed Crohn＇s disease was refractory to medication or when its clinical course became aggressive.

Clonal immunoglobulin heavy chain and T-cell receptor γ gene rearrangements in primary gastric lymphoma

AIM:To study the diagnostic value of immunoglobulin heavy chain(IgH)and T-cell receptorγ (TCR-γ)gene monoclonal rearrangements in primary gastric lymphoma(PGL).METHODS:A total of 48 patients with suspected PGL at our hospital were prospectively enrolled in this study from January 2009 to December 2011.The patients were divided into three groups(a PGL group,a gastric linitis plastica group,and a benign gastric ulcer group)based on the pathological results(gastric mucosal specimens obtained by endoscopy or surgery)and follow-up.Endoscopic ultrasonography(EUS)and EUSguided biopsy were performed in all the patients.The tissue specimens were used for histopathological examination and for IgH and TCR-γ gene rearrangement polymerase chain reaction analyses.RESULTS:EUS and EUS-guided biopsy were successfully performed in all 48 patients.In the PGL group(n=21),monoclonal IgH gene rearrangements were detected in 14(66.7%)patients.A positive result for each set of primers was found in 12(57.1%),8(38.1%),and 4(19.0%)cases using FR1/JH,FR2/JH,and FR3/JH primers,respectively.Overall,12(75%)patients with mucosal-associated lymphoid tissue lymphoma(n=16)and 2(40%)patients with diffuse large B-cell lymphoma(n=5)were positive for monoclonal IgH gene rearrangements.No patients in the gastric linitis plastica group(n=17)and only one(10%)patient in the benign gastric ulcer group(n=10)were positive for a monoclonal IgH gene rearrangement.No TCRgene monoclonal rearrangements were detected.The sensitivity of monoclonal IgH gene rearrangements was 66.7%for a PGL diagnosis,and the specificity was96.4%.In the PGL group,8(100%)patients with stage IIE PGL(n=8)and 6(46.1%)patients with stage IE PGL(n=13)were positive for monoclonal IgH gene rearrangements.CONCLUSION:IgH gene rearrangements may be associated with PGL staging and may be useful for the diagnosis of PGL and for differentiating between PGL and gastric linitis plastica.

Gastrosplenic fistula occurring in lymphoma patients: Systematic review with a new case of extranodal NK/T-cell lymphoma

AIM To provide the overall spectrum of gastrosplenic fistula(GSF) occurring in lymphomas through a systematic review including a patient at our hospital.METHODS A comprehensive literature search was performed in the MEDLINE database to identify studies of GSF occurring in lymphomas. A computerized search of our institutional database was also performed. In all cases, we analyzed the clinicopathologic/radiologic features, treatment and outcome of GSF occurring in lymphomas. RESULTS A literature search identified 25 relevant studies with 26 patients. Our institutional data search added 1 patient. Systematic review of the total 27 cases revealed that GSF occurred mainly in diffuse, large B-cell lymphoma(n = 23), but also in diffuse, histiocytic lymphoma(n = 1), Hodgkin's lymphoma(n = 2), and NK/T-cell lymphoma(n = 1, our patient). The common clinical presentations are constitutional symptoms(n = 20) and abdominal pain(n = 17), although acute gastrointestinal bleeding(n = 6) and infection symptoms due to splenic abscess(n = 3) are also noted. In all patients, computed tomography scanning was very helpful for diagnosing GSF and for evaluating the lymphoma extent. GSF could occur either post-chemotherapy(n = 10) or spontaneously(n = 17). Surgical resection has been the most common treatment. Once patients have recovered from the acute illness status after undergoing surgery, their long-term outcome has been favorable. CONCLUSION This systematic review provides an overview of GSF occurring in lymphomas, and will be helpful in making physicians aware of this rare disease entity.

Clinical Impact of t(14;18) in Diffuse Large B-cell Lymphoma

Objective： Recent studies have suggested that t（14;18） is present in a significant proportion of diffuse large B-cell lymphomas （DLBCLs）. However, the prognostic significance of this translocation and its relationship with BCL-2 protein expression remains controversial. Our study aimed to investigate the predictive power of t（14;18） and BCL-2 protein expression in the prognosis of DLBCLs. Methods： Biopsy specimens from 106 DLBCLs were analyzed using interphase fluorescence in situ hybridization （FISH）. Immunophenotypic analysis of CD20, CD3, CD10, BCL-6, MUM1 and BCL-2 was performed by immunohistochemistry. SPSS 13.0 software was used for statistical analysis. Results： The t（14;18） was identified in 27 of 106 cases （25.5%）. The percentages of tumor cells expressing CD10, BCL-6, MUM1 and BCL-2 were 21.7%, 26.4%, 56.6% and 73.6%, respectively. The presence of this translocation was significantly correlated with the expression of CD10 and immunophenotypic subtype （p0.001）. No association was observed between BCL-2 protein expression and the presence of t（14;18）. Multivariate analysis confirmed that both t（14;18） and BCL-2 expression were significantly associated with survival. Moreover, patients with t（14;18） had worse prognosis, compared with those with BCL-2 expression （for overall survival： hazard ratio, 4.235; 95%CI, 2.153-8.329, p0.001 vs. hazard ration, 2.743; 95%CI, 1.262-5.962, p=0.011）. Conclusions： The t（14;18） is a useful prognostic tool for the evaluation of DLBCL immunophenotype and prognosis. The prognosis of GCB （germinal centre-like B cell） DLBCL patients should be made with the consideration of the presence of this translocation, and the detection of t（14;18） should be included as a routine diagnostic test in these cases.