RPRD1B/CREPT facilitates the progression of diffuse large B-cell lymphoma by inhibiting apoptosis through the NF-κB signaling pathway

Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic target.Methods:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival analysis.In vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and apoptosis.Results:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor prognosis.In vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling pathway.Conclusions:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular proliferation.Targeting RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies.

Monomorphic epitheliotropic intestinal T-cell lymphoma with bone marrow involved: A case report

BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We present a 52-year-old female patient who was diagnosed with MEITL.Further disease progression was observed after multiline chemotherapy.Eventually,the patient died of a severe infection.CONCLUSION MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior,a high risk of severe life-threatening complications,and a poor prognosis.

Diffuse large B-cell lymphoma successfully treated with amplified natural killer therapy alone: A case report

BACKGROUND The prognosis of patients with advanced diffuse large B-cell lymphoma(DLBCL)is poor,with a 5-year survival rate of approximately 50%.The mainstay of treatment is multidrug combination chemotherapy,which has been associated with serious side effects.Amplified natural killer(ANK)cell therapy amplifies and activates natural killer(NK)cells to attack only malignant tumors.As ANK cells attack programmed death ligand 1(PD-L1)-positive tumor cells,ANK therapy is considered effective against adult T-cell lymphoma and malignant lymphoma.CASE SUMMARY Herein,we report a case of an older patient with advanced DLBCL who was successfully treated with ANK immunotherapy.A 91-year-old female visited our hospital with sudden swelling of the right axillary lymph node in April 2022.The patient was diagnosed with stage II disease,given the absence of splenic involvement or contralateral lymphadenopathy.ANK therapy was administered.Six rounds of lymphocyte sampling were performed on July 28,2022.To reduce the occurrence of side effects,the six samples were diluted by half to obtain 12 samples.Cultured NK cells were administered twice weekly.The treatment efficacy was evaluated by performing computed tomography and serological tests every 1 or 2 mo.The treatment suppressed lesion growth,and the antitumor effect persisted for several months.The patient experienced mild side effects.PD-L1 immunostaining was positive,indicating that the treatment was highly effective.CONCLUSION ANK therapy can be used as a first-line treatment for malignant lymphoma;the PD-L1 positivity rate can predict treatment efficacy.

Coexistence of diffuse large B-cell lymphoma,acute myeloid leukemia,and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient:A case report

BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.

SENP3 Promotes Mantle Cell Lymphoma Development through Regulating Wnt10a Expression

Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of various tumors.However,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains unclear.This study was aimed to elucidate the effect of SENP3 in MCL.Methods The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or immunohistochemistry.MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs.Cell proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow cytometry.mRNA sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo.Results SENP3 was upregulated in MCL patient samples and cells.Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis.Meanwhile,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown.Furthermore,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model.Conclusion SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.

Diagnostic and management challenges in primary cutaneous anaplastic large cell lymphoma with necrosis,inflammation,and surgical intervention:A case report

BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)poses significant diagnostic difficulties due to its similarity in the appearance of skin lesions with chronic inflammatory disorders and other dermatological conditions.This study aims to investigate these challenges by conducting a comprehensive analysis of a case presenting with PC-ALCL,emphasizing the necessity of accurate differentiation for appropriate management.CASE SUMMARY An 89-year-old female patient with diabetes and hypertension presented with arm and abdominal ulcerated mass lesions.Diagnostic procedures included skin biopsies,histopathological assessments,and immunohistochemistry,complemented by advanced imaging techniques to confirm the diagnosis.The patient’s lesions were determined as PC-ALCL,characterized by necrosis,chronic inflammation,and a distinct immunophenotypic profile,including CD30,CD3,CD4,and EBER,CD56,MUM-1,Ki 67-positive in>80%of tumor cells,CD10,but negative for anaplastic lymphoma kinase,CD5,CD20,PAX-5,Bcl-2,Bcl-6,CD8,and CD15.Recurrence was not reported at the 6-month follow-up.CONCLUSION Accurate PC-ALCL differentiation from similar conditions is crucial for effective management and requires a multidisciplinary approach.

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

Dihydroartemisinin enhances cell apoptosis in diffuse large B cell lymphoma by inhibiting the STAT3 activity

Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess the antitumor effect of DHA on diffuse large B cell lymphoma cells and to determine the potential underlying mechanisms of DHA-induced cell apoptosis.Methods:Here,the Cell Counting Kit 8 assay was conducted to study cell proliferation.We performed Annexin V-FITC/propidium iodide staining,real-time polymerase chain reaction,and western blot analysis to analyze cell apoptosis and potential molecular mechanisms.Results:The results showed that DHA substantially suppressed cell proliferation and induced cell apoptosis in vitro in a time-and concentration-dependent fashion.Moreover,STAT3 activity could be inhibited after stimulation with DHA.Conclusion:These results imply that the underlying anti-tumoral effect of DHA may increase apoptosis in diffuse large B cell lymphoma cells via the STAT3 signaling pathway.In addition,DHA might be an effective drug for diffuse large B cell lymphoma therapy.

Genetic abnormalities assist in pathological diagnosis and EBVpositive cell density impact survival in Chinese angioimmunoblastic T-cell lymphoma patients

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.

Pathological complete response to neoadjuvant alectinib in unresectable anaplastic lymphoma kinase positive non-small cell lung cancer:A case report

BACKGROUND The development of anaplastic lymphoma kinase(ALK)-tyrosine kinase inhibitors(TKIs)has remarkably improved the prognosis of patients with ALK-positive advanced non-small cell lung cancer(NSCLC).Alectinib,the second-generation ALK-TKI,has been approved as first-line treatment for advanced or metastatic NSCLC patients with ALK rearrangement.Neoadjuvant therapy can achieve tumor downstaging and eradicate occult lesions in patients with potentially resectable disease.Whether neoadjuvant alectinib can be a conversion therapy in ALK-positive advanced NSCLC patients remains unclear.CASE SUMMARY A 41-year-old man was pathologically diagnosed with locally advanced ALKpositive stage IIIB NSCLC.Alectinib was prescribed to induce tumor downstaging and facilitate the subsequent surgical resection.The tumor was successfully downstaged and pathological complete response was achieved.Left upper lobectomy with mediastinal lymphadenectomy was performed after tumor downstaging.The patient has continued to receive alectinib as adjuvant therapy during postoperative follow-up with a recurrence-free survival of 29 mo as of writing this report.CONCLUSION This case sheds light on the feasibility and safety of alectinib as a neoadjuvant treatment for stage IIIB NSCLC patients with ALK rearrangement.Its efficacy needs to be validated in prospective clinical trials.

Hemophagocytic lymphohistiocytosis after autologous stem cell transplantation in angioimmunoblastic T-cell lymphoma:A case report

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.

Effect of T-regulatory cells and interleukin-35, interleukin-10, and transforming growth factor-beta on diffuse large B-cell lymphoma

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is an aggressive non-Hodgkin lymphoma that affects B lymphocytes.It can develop in the lymph nodes and can be localized or generalized.Despite DLBCL being considered potentially curable,little research has been conducted on the relationship between the body's immune response and DLBCL.AIM To study the expression and significance of T-regulatory cells(Tregs)interleukin(IL)-35,IL-10,and transforming growth factor-beta(TGF-β)in DLBCL.METHODS Data from 82 patients with DLBCL who were initially admitted to The First Affiliated Hospital of Ningbo University(Zhejiang Province,China)between January 2017 and June 2022 and treated with standard first-line regimens were reviewed.Three patients were lost to follow-up;thus,79 patients were included in the statistical analysis and then divided into three groups according to the evaluation of clinical efficacy:Incipient(new-onset and treatment-naïve),effectively treated,and relapsed-refractory.Thirty healthy individuals were included in the control group.The expression of peripheral blood T lymphocytes and their associated factors IL-35,IL-10,and TGF-βin the four groups were observed.RESULTS In contrast to the successfully treated and normal control groups,both the incipient and relapse-refractory groups exhibited greater proportions of CD4-positive(+)Tregs(P<0.05),whereas the proportion of CD8+Tregs did not differ substantially between the groups.Serum levels of IL-35 and IL-10 in the incipient and relapsed-refractory groups were higher than those in the effectively treated and normal control groups(P<0.05).There was no statistically significant distinction in the expression level of TGF-βbetween the groups(P>0.05).The correlation between IL-35 and IL-10 concentrations was significantly positive,with a correlation coefficient of 0.531(P<0.05).The correlation between IL-35 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.375(P<0.05).The correlation between IL-10 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.185(P<0.05).The expression concentrations of IL-35,IL-10 and TGF-βwere apparently and positively correlated(P<0.05).CONCLUSION Tregs IL-35,and IL-10 may be closely associated with the occurrence and development of DLBCL and the detection of related indices may be helpful in the analysis of disease prognosis.

Primary bone anaplastic lymphoma kinase positive anaplastic largecell lymphoma: A case report and review of the literature

BACKGROUND Primary bone lymphoma(PBL)is an uncommon extranodal disease that represents approximately 1%-3%of lymphomas.Anaplastic lymphoma kinase(ALK)positive anaplastic large-cell lymphoma(ALCL)is an extremely rare type of PBL.The aim of this report is describe the symptoms,diagnosis,and treatment of primary bone ALK-positive ALCL.CASE SUMMARY A 66-year-old man presented to our hospital with neck and shoulder pain and intermittent fever that lasted for 1 mo.After extensive evaluation,positron emission tomography-computed tomography(CT)examination showed multiple osteolytic bone lesions without other sites lesions.CT-guided biopsy of the T10 vertebral body was performed,and the pathology results showed that neoplastic cells were positive for ALK-1,CD30,and CD3.A diagnosis of primary bone ALK positive ALCL was ultimately made.The patient was in partial response after four cycle soft cyclophosphamide,doxorubicin,vincristine,and prednisone chemotherapy,and we planned to repeat the biopsy and radiological examination after completion of the fifth cycle of therapy.CONCLUSION Primary bone ALK positive ALCL is a rare disease and physicians should keep in mind that ALCL can present with isolated osseous involvement without nodal involvement,and lymphoma should be considered in the differential diagnosis of primary bone lesions.

Diffuse large B cell lymphoma originating from the maxillary sinus with skin metastases:A case report and review of literature

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common type of malignant lymphoma(ML),accounting for 30%-40%of cases of non-Hodgkin’s lymphoma(NHL)in adults.Primary paranasal sinus lymphoma is a rare presentation of extranodal NHL that accounts for only 0.17%of all lymphomas.ML from the maxillary sinus(MS)is a particularly rare presentation,and is thus often difficult to diagnose.We have reported the first known case of DLBCL originating from the MS with rapidly occurrent multiple skin metastasis.CASE SUMMARY An 81-year-old Japanese man visited our hospital due to continuous pain for 12 d in the left maxillary nerve area.His medical history included splenectomy due to a traffic injury,an old right cerebral infarction from when he was 74-years-old,hypertension,and type 2 diabetes mellitus.A plain head computed tomography(CT)scan revealed a 3 cm×3.1 cm×3 cm sized left MS.On day 25,left diplopia and ptosis occurred,and a follow-up CT on day 31 revealed the growth of the left MS mass.Based on an MS biopsy on day 50,we established a definitive diagnosis of DLBCL,non-germinal center B-cell-like originating from the left MS.The patient was admitted on day 62 due to rapid deterioration of his condition,and a plain CT scan revealed the further growth of the left MS mass,as well as multiple systemic metastasis,including of the skin.A skin biopsy on day 70 was found to be the same as that of the left MS mass.We notified the patient and his family of the disease,and they opted for palliative care,considering on his condition and age.The patient died on day 80.CONCLUSION This case suggests the need for careful,detailed examination,and for careful follow-up,when encountering patients presenting with a mass.

Disseminated soft tissue diffuse large B-cell lymphoma involving multiple abdominal wall muscles:A case report

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common subtype of non�Hodgkin lymphoma,and patients with DLBCL typically present rapidly growing masses.Lymphoma involving muscle is rare and accounts for only 5%;furthermore,multiple muscles and soft tissue involvement of DLBCL is unusual.Due to unusual clinical manifestation,accurate diagnosis could be delayed.CASE SUMMARY A 61-year-old man complained of swelling,pain and erythematous changes in the lower abdomen.Initially,soft tissue infection was suspected,however,skin lesion did not respond to antibiotics.18Fluoro-2-deoxy-D-glucose(18F-FDG)positron emission tomography-computed tomography demonstrated FDG uptake not only in the skin and subcutaneous tissue of the abdomen but also in the abdominal wall muscles,peritoneum,perineum,penis and testis.DLBCL was confirmed by biopsy of the abdominal wall muscle and subcutaneous tissue.After intensive treatment including chemotherapy with rituximab,cyclophosphamide,doxorubicin,vincristine and prednisolone,central nervous system prophylaxis(intrathecal injection of methotrexate,cytarabine and hydrocortisone)and orchiectomy,he underwent peripheral blood stem cell mobilization for an autologous hematopoietic stem cell transplantation.Despite intensive treatment,the disease progressed rapidly and the patient showed poor outcome(overall survival,9 mo;disease free survival,3 mo).CONCLUSION The first clinical manifestation of soft tissue DLBCL involving multiple muscles was similar to the infection of the soft tissue.

Role of non-Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma,trailing behind diffuse large B-cell lymphoma and follicular lymphoma.Gastric mucosa-associated lymphoid tissue lymphoma(GML)is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori(H.pylori)-induced chronic gastritis.On the other hand,a specific subset of individuals diagnosed with GML does not exhibit H.pylori infection.In contrast to its H.pylori-positive counterpart,it was previously believed that H.pylori-negative GML was less likely to respond to antimicrobial therapy.Despite this,surprisingly,increasing evidence supports that a considerable proportion of patients with H.pylori-negative GML show complete histopathological remission after bacterial eradication therapy.Nonetheless,the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended.In recent years,there has been growing interest in investigating the role of non-H.pylori gastric helicobacters(NHPHs)in the pathogenesis of H.pylori-negative GML.However,additional research is required to establish the causal relationship between NHPHs and GML.In this minireview,we examined the current understanding and proposed prospects on the involvement of NHPHs in H.pylori-negative GML,as well as their potential response to bacterial eradication therapy.

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

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.

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.METHODS:A group of 24 HCV related B-NHL patients(11 indolent,13 DLBCL) in whom the biological and clinical characteristics were described and confronted.Patients with DLBCL were managed with the standard of care of treatment.Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed.The outcomes of the different approaches were compared.RESULTS:Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype.Five of the 9 patients with indolent HCV-relatedB-NHL treated with only antiviral therapy,achieved a complete response of their onco-haematological disease(55%).Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response(54%).CONCLUSION:HCV genotypes and duration of HCV infection differed between B-NHL subtypes.Indolent lymphomas can be managed with antiviral treatment,while DLBCL is not affected by the HCV infection.

HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and open questions

There is plenty of data confirming that hepatitis C virus (HCV) infection is a predisposing factor for a B-cell non-Hodgkin's lymphoma (B-NHL) outbreak, while relatively few reports have addressed the role of HCV in affecting B-NHL patients' outcome. HCV infection may influence the short-term outcome of B-NHL because of the emergence of severe hepatic toxicity (HT) during immunochemotherapy. Furthermore, the long term outcome of HCV-related liver disease and patients' quality of life will possibly be affected by Rituximab maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic stem cell transplantation. In this review, data dealing with aggressive and low-grade B-NHL were separately analyzed. The few retrospective papers reporting on aggressive B-NHL patients showed that HCV infection is a risk factor for the outbreak of severe HT during treatment. This adverse event not infrequently leads to the reduction of treatment density and intensity. Existing papers report that low-grade B-NHL patients with HCV infection may have a more widespread disease, more frequent relapses or a lower ORR compared to HCV-negative patients. Notwithstanding, there is no statistical evidence that the prognosis of HCV-positive patients is inferior to that of HCV-negative subjects. HCV-positive prospective studies and longer follow-up are necessary to ascertain if HCV-positive B-NHL patients have inferior outcomes and if there are long term sequels of immunochemotherapies on the progression of liver disease.

Diffuse large B-cell lymphoma arising from follicular lymphoma with warthin’s tumor of the parotid gland-immunophenotypic and genetic features: A case report

BACKGROUND Warthin’s tumor(WT)is composed of several cysts that are lined with tall,bilayered oncocytic columnar cells and lymphoid stroma.Within WT,the two components rarely transform into carcinoma or lymphoma,and when it does,carcinoma is the most common type.Approximately 28 cases of lymphoma with WT have been reported,most of which were non-Hodgkin lymphomas,and only a few cases were Hodgkin lymphomas.In the present report,we studied a case of diffuse large B cell lymphoma(DLBCL)arising from follicular lymphoma(FL)with WT in the parotid gland and its immunophenotypic and genetic features.CASE SUMMARY A 67-year-old man presented with a slowly enlarging right cheek mass for 12 years,and the mass began to change in size over a 2-mo time period.Over time,the patient felt mild local pain and right cheek discomfort.His medical history included a hepatitis B virus infection for 20 years and 30 years of smoking.Gross examination of the excised specimen showed a gray-red and gray-white appearance and a soft texture lobulated external surface neoplasm that measured 9 cm×8 cm×7 cm and was well circumscribed by relative normal parotid gland tissue.In cross section,the cut surfaces of the neoplasm were multicystic and had a homogeneous scaly appearance.A small fluid was discovered in the cyst.Bilateral oxyphilic,cuboidal or polygonal epithelium cells and lymphoid intraparenchymal components were observed.Many medium-to large-sized lymphoid cells were observed diffusely in part of the neoplasm,and a few secondary lymphoid follicles were observed at the center or edge of the neoplasm.Immunohistochemical staining showed that the columnar oncocytic cells were positive for AE1/AE3;neoplastic cells located in coarctate follicular were positive for CD20,Pax-5,bcl-2 and bcl-6;and the adjacent diffusely medium-to large-sized lymphoid cells were positive for Pax-5,bcl-6,CD20,MUM-1,bcl-2 and CD79a.The bcl-6(3q27)break-apart rearrangement was observed,and an Epstein Barr virus test was negative in the tumor cells.The patient survived 6 months after being diagnosed without any treatment.CONCLUSION WT-associated lymphoma is a very rare neoplasm in the parotid gland.Most cases are B cell non-Hodgkin lymphomas and involve middle-age and older males.This case highlights the extremely rare association of DLBCL arising from FL with WT and the importance of deliberate evaluation of the WT intraparenchymal stroma.Molecular detection techniques have potential advantages in the diagnosis of lymphoma with WT.