Bendamustine and rituximab as frontline therapy in extranodal marginal zone lymphoma:a single-institution experience

Extranodal marginal zone lymphoma(EMZL)encompasses 70%of cases of marginal zone lymphoma.Frontline bendamustine and rituximab(BR)were derived from trials involving other indolent non-Hodgkin’s lymphomas.Only one trial has evaluated frontline BR prospectively in EMZL.This retrospective study reports outcomes among EMZL patients receiving frontline BR.Twenty-five patients were included with a median age of 69 years(40–81).Five(20.0%)patients had stage Ⅰ/Ⅱ disease,and 20(80.0%)had stage Ⅲ/Ⅳ disease.The median number of cycles was 6.0(3.0–6.0).Maintenance rituximab was administered to 10(41.7%)individuals.Overall response rate(ORR)was 100.0%(60.0%complete response,40.0%partial response).Medians of overall survival and progression-free survival were not reached.The estimated 2-year progression-free survival was 85.2%and overall survival was 100.0%.Four(16.6%)patients had infections related to treatment;3(12.0%)transformed to diffuse large B-cell lymphoma;5(20.8%)had a relapse or progression of EMZL;and 3(12.0%)died unrelated to BR.BR is an efficacious and well-tolerated front-line regimen for EMZL with response data consistent with existing literature.

Marginal zone lymphoma with severe rashes: A case report

BACKGROUND Marginal zone lymphoma(MZL)is an indolent subtype of non-Hodgkin lymphoma(NHL),which is rare clinically with severe rashes as the initial symptom.CASE SUMMARY This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge.First-line treatment with rituximab combined with zanubrutinib had poor effects.However,after switching to obinutuzumab combined with zanubrutinib,the case was alleviated,and the rashes disappeared.CONCLUSION For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody(mAb)combination therapy,switching to a type II anti-CD20 mAb combination regimen may be considered.This approach may provide a new perspective in the treatment of MZL.

Non-Hodgkin's lymphoma involving chronic difficult-to-heal wounds:A case report

BACKGROUND Non-Hodgkin's lymphoma(NHL)is a malignant tumor that originates from the lymphoid tissues and can potentially affect numerous organs within the body.Among these,the skin stands out as one of the primary sites affected by NHL,often presenting with multiple extra-nodal manifestations.In this report,we present an unusual case of NHL involving chronic wounds in the lower extremities that were difficult to heal.The scars were successfully treated using radiotherapy in combination with extended excision debridement and peroneal artery perforator flap grafting,resulting in satisfactory outcomes.CASE SUMMARY A 19-year-old male patient presented with ulceration of the skin on the left calf near the ankle accompanied by purulent discharge.Subsequent pathologic biopsy confirmed a diagnosis of NHL(extranodal NK/T-cell lymphoma,nasal type).Initial treatment comprised local radiotherapy and wound care;however,the wound exhibited prolonged non-healing.Consequently,the patient underwent a series of interventions including radiotherapy,wound enlargement excision debridement,and peroneal artery perforator flap grafting.Ultimately,successful healing was achieved with favorable postoperative outcomes characterized by good texture of the flap without any signs of rupture or infection.CONCLUSION The combination of radiotherapy,wound enlargement excision debridement,and peroneal artery perforator flap grafting may present a favorable treatment modality for chronic non-healing lower leg wounds resulting from NHL.

Outcomes of patients treated with SVILE vs.P-GemOx for extranodal natural killer/T-cell lymphoma,nasal type:a prospective,randomized controlled study

Objective:To compare the efficacy and safety of the novel SVILE regimen with the P-GemOx regimen in patients with newly diagnosed extranodal natural killer/T-cell lymphoma,nasal type(ND-ENKTL).Methods:From April 2015 to July 2018,103 patients with ND-ENKTL were randomly assigned to SVILE(experimental group)or P-GemOx(control group)chemotherapy followed by radiotherapy and consolidation chemotherapy.The primary endpoint was the overall response rate after 3 cycles of chemotherapy,and secondary study endpoints were complete response(CR),progression-free survival(PFS),and overall survival(OS).Safety was also evaluated.Results:There were no significant differences in baseline characteristics in the experimentalvs.control groups.In experimental and control groups,respectively,the overall response rates were 91.7%vs.97.0%for stageI/II and 75.0%vs.72.2%for stage III/IV.The CR rates were 83.4%vs.97.0%for stage I/II and 68.8%vs.61.1%for stage III/IV.None of those differences were significant.There was no significant difference in PFS and OS between groups and between patients in stage I/II and stage III/IV.The 3-year PFS and OS in stage I/II were 88.3%vs.93.3%and 88.8%vs.97.0%,respectively.The 3-year PFS and OS in stage III/IV were 46.2%vs.65.7%and 68.8%vs.72.2%,respectively.The common adverse events were hematological toxicity,hepatotoxicity,and coagulation abnormalities,which were found to be reversible with supportive therapy.Conclusions:The novel SVILE regimen has comparable effects to those of P-GemOx in patients with ND-ENKTL and is well tolerated.SVILE is a therapeutic option for ND-ENKTL.

Primary mucosal-associated lymphoid tissue extranodal marginal zone lymphoma of the bladder from an imaging perspective: A case report

BACKGROUND Mucosal-associated lymphoid tissue extranodal marginal zone(MALT)lymphoma is a low-grade tumor that rarely occurs in the urinary bladder.There is currently no consensus on the common imaging findings or most appropriate treatment in MALT lymphoma in the urinary bladder due to the limited number of reports.CASE SUMMARY A 48-year-old woman was admitted to the hospital with a 1-year history of macroscopic hematuria.Imaging showed a large homogeneous mass with an unclear boundary and an irregular morphology in the bladder.The mass had an abundant blood supply.For further diagnosis,transurethral cystoscopic biopsy and bone marrow biopsy was performed,and the patient was finally diagnosed with primary MALT lymphoma of the bladder.R-CHOP chemotherapy was carried out.After three cycles of chemotherapy,the mass disappeared and the bladder wall thickness was only 4 mm,which indicated excellent therapeutic response to the chemotherapy.To date,the patient remains asymptomatic and she visits our hospital regularly for the completion of the remaining chemotherapy cycles.CONCLUSION Primary MALT lymphoma of the bladder is rare,and there are certain characteristics in the ultrasonographic findings.Imaging findings play an important role in evaluating the therapeutic efficacy and are critical during long-term follow-up after therapy.

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.

Primary intestinal extranodal natural killer/T-cell lymphoma, nasal type: A case report

BACKGROUND Primary intestinal extranodal natural killer/T-cell lymphoma,nasal type(PIENKTCL)is a rare non-Hodgkin’s lymphoma(NHL)subtype,and its prognosis is extremely poor.Clinical characteristics of the disease are not obvious and easily misdiagnosed.In this case report,we describe a patient with PI-ENKTCL who presented with intermittent hematochezia.The advantages of positron emission tomography/computed tomography(PET-CT)as a useful diagnostic tool and the role of surgery as an important therapy are highlighted.CASE SUMMARY A 45-year-old man,hospitalized due to intermittent hematochezia,underwent gastroscopy,colonoscopy,biopsy and CT,but no cause was found.Hence,we carried out a multidisciplinary team(MDT)discussion on the causes and treatment of this patient,and it was decided to perform PET-CT imaging with a MDT discussion of the results.PET-CT demonstrated a diagnosis of lymphoma and it was decided to surgically resect the lesion,and a R0 resection was successfully performed.Postoperative pathology showed negative resection margins,and examination of the lesion confirmed the diagnosis of PI-ENKTCL.After surgery,the patient underwent a follow-up period of 6 mo and received 6 cycles of gemcitabine,oxaliplatin and L-asparaginase.No recurrence or metastasis occurred.CONCLUSION PI-ENKTCL is rare,and MDT discussion is required during diagnosis.PET-CT can be performed for imaging diagnosis.Treatment is based on surgical resection,and the best treatment regimen is determined according to postoperative pathological results to improve prognosis and to extend survival in patients.

Combination of atezolizumab and chidamide to maintain long-term remission in refractory metastatic extranodal natural killer/T-cell lymphoma:A case report

BACKGROUND The prognosis of refractory extranodal natural killer/T-cell lymphoma(ENKTL)is poor.Recent data have indicated that immune checkpoint blockade with a programmed cell death protein-1(PD-1)antibody in combination with administration of histone deacetylase inhibitors represents a potentially effective treatment strategy.Compared with PD-1 antibodies,programmed death-ligand 1 antibodies have fewer side effects.Here,we present a rare case of a patient with refractory metastatic ENKTL who achieved sustained remission of approximately 10 mo with minor adverse effects after combination therapy with atezolizumab,chidamide,and radiotherapy.CASE SUMMARY A 56-year-old woman underwent resection of a tumour in her left nasal cavity and was diagnosed with ENKTL(nasal type).Medical examination revealed tumours observed in the bilateral nasal mucosa,the subcutaneous soft tissue of the inner side of the left eye,the soft tissue of the nasopharynx,the bilateral tonsils,and the left preauricular,right hilar,bilateral neck lymph nodes and bone marrow.However,tomography/computed tomography showed increased metabolism of the bilateral nasal mucosa and subcutaneous soft tissue of the inner side of the left eye and newly increased metabolism of the left cervical lymph node after chemotherapy.Therefore,combination therapy with chidamide,atezolizumab,and radiotherapy was performed.Fortunately,the patient achieved a complete response following 10 mo of combination therapy.CONCLUSION The outcome in this case suggests that the combination of atezolizumab,chidamide,and radiotherapy is a promising regimen for treating refractory metastatic ENKTL following chemotherapy treatment failure.

Primary lymphomas of the genitourinary tract:A population-based study

Objective:We performed a population-based analysis focusing on primary extranodal lymphoma of either testis,kidney,bladder or prostate(PGUL).Methods:We identified all cases of localized testis,renal,bladder and prostate primary lymphomas(PL)versus primary testis,kidney,bladder and prostate cancers within the Surveillance,Epidemiology,and End Results database(1998e2015).Estimated annual proportion change methodology(EAPC),multivariable logistic regression models,cumulative incidence plots and multivariable competing risks regression models were used.Results:The rates of testis-PL,renal-PL,bladder-PL and prostate-PL were 3.04%,0.22%,0.18%and 0.01%,respectively.Patients with PGUL were older and more frequently Caucasian.Annual rates significantly decreased for renal-PL(EAPC:5.6%;pZ0.004)and prostate-PL(EAPC:3.6%;pZ0.03).In multivariable logistic regression models,older ager independently predicted testis-PL(odds ratio[OR]:16.4;p<0.001)and renal-PL(OR:3.5;p<0.001),while female gender independently predicted bladder-PL(OR:5.5;p<0.001).In surgically treated patients,cumulative incidence plots showed significantly higher 10-year cancer-specific mortality(CSM)rates for testis-PL,renal-PL and prostate-PL versus their primary genitourinary tumors.In multivariable competing risks regression models,only testis-PL(hazard ratio[HR]:16.7;p<0.001)and renal-PL(HR:2.52;p<0.001)independently predicted higher CSM rates.Conclusion:PGUL rates are extremely low and on the decrease in kidney and prostate but stable in testis and bladder.Relative to primary genitourinary tumors,PGUL are associated with worse CSM for testis-PL and renal-PL but not for bladder-PL and prostate-PL,even after adjustment for other-cause mortality.

The Role of Surgery in Primary Thyroid Lymphoma: Experience in the Last 10 Years of a Specialized Unit

Primary Thyroid Lymphoma (PTL) is an uncommon disease, although its incidence is of 5%. Ultrasound and Fine Needle Aspiration Cytology (FNAC) usually do not provide the diagnosis. Surgery is one of the treatment options because it enables histological diagnosis and can also relieve compression symptoms in patients with rapid growth cervical mass. We present 7 cases of PTL diagnosed in the last 10 years in our unit. Five were female (71.4%) and 2 were male (28.6%). The mean age was 64.2 (range: 40 - 81);4 patients (57.1%) had associated Hashimoto’s Thyroiditis (HT). One patient (14.2%) had concomitant Graves disease. 5 cases presented with compressive symptoms and cervical mass. Ultrasound was not diagnostic in any case. FNAC was diagnostic only in one patient (14.3%). Five patients underwent total thyroidectomy (71.4%). All the cases were diagnosed with lymphoma postoperatively. Two interventions consisted of left hemithyroidectomies (28.6%). No complications appeared. 5 patients (71.4%) were classified as Mucosa-Associated Lymphoid Tissue (MALT) lymphoma. We also observed 1 Follicular grade I lymphoma and 1 Burkitt case. When the extension study was done, 1 patient was at stage IIIE (14%), 2 at IIE (28.5%) and 4 at IE (57.14%). Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) and Iphosphamide, ethoposide and high dose Cytarabine (IVAC) were the treatment scheme when chemotherapy was used (in three cases). Two cases were treated only with total thyroidectomy, and 2 with total thyroidectomy and rituximab, and the latter was MALT. Complete Remission (CR) was achieved in all patients in the first year. All are still alive and in CR. In our experience, PTL diagnose can be challenging before surgery. Although surgery is not the gold standard for treatment, when it is done, it should be curative in MALT lymphomas confined to the thyroid.

Primary gastric non-Hodgkin lymphomas:Recent advances regarding disease pathogenesis and treatment

Primary gastric lymphomas(PGLs)are distinct lymphoproliferative neoplasms described as heterogeneous entities clinically and molecularly.Their main histological types are diffuse large B-cell lymphoma(DLBCL)or mucosaassociated lymphoma tissue.PGL has been one of the main fields of clinical research of our group in recent years.Although gastric DLBCLs are frequent,sufficient data to guide optimal care are scarce.Until today,a multidisciplinary approach has been applied,including chemotherapy,surgery,radiotherapy or a combination of these treatments.In this minireview article,we provide an overview of the clinical manifestations,diagnosis and staging of these diseases,along with their molecular pathogenesis and the most important related clinical published series.We then discuss the scientific gaps,perils and pitfalls that exist regarding the aforementioned studies,in parallel with the unmet need for future research and comment on the proper methodology for such retrospective studies.Aiming to fill this gap,we retrospectively evaluated the trends in clinical presentation,management and outcome among 165 patients with DLBCL PGL who were seen in our institutions in 1980-2014.The study cohort was divided into two subgroups,comparing the main 2 therapeutic options[cyclophosphamide doxorubicin vincristine prednisone(CHOP)vs rituximab-CHOP(R-CHOP)].A better outcome with immunochemotherapy(R-CHOP)was observed.In the next 2 mo,we will present the update of our study with the same basic conclusion.

Management of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene

AIM To identify the clinical features of gastric mucosaassociated lymphoid tissue(MALT) lymphoma with extra copies of MALT1.METHODS This is a multi-centered,retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11;18) translocation. Patients were subdivided into patients without t(11;18) translocation or extra copies of MALT1(Group A,n = 88),patients with t(11;18) translocation(Group B,n = 27),and patients with extra copies of MALT1(Group C,n = 31). The clinical background,treatment,and outcomes of each group were investigated.RESULTS Groups A and C showed slight female predominance,whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A(69.3%),22 in Group B(81.5%),and 21 in Group C(67.7%). Helicobacter pylori(H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B,14 patients underwent radiotherapy alone,which resulted in lymphoma disappearance. Although the difference was not statistically significant,event-free survival in Group C tended to be inferior to that in Group A(P = 0.10).CONCLUSION Patients with t(11;18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication,similar to patients without t(11;18) translocation or extra copies of MALT1.

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.

Correlation between the clinicopathological features and prognosis in patients with extranodal natural killer/T cell lymphoma

Objective: To investigate the correlation between the clinicopathological features and prognosis in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTCL). Methods: One hundred and four patients diagnosed with ENKTCL at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China from November 1991 to September 2011 were included in the study. The clini-copathological features and their correlations with disease prognosis were evaluated in these patients. Results: The number of effective follow-up cases was 56 (53.8％) by the end of last follow-up in October 2015. Univariate survival analysisshowedthatgranzymeB,perforin,andBcl-2expressionwassignificantlyassociatedwithapoorprognosisinENKTCL(P= 0.033, 0.004, and 0.034, respectively), whereas platelet-derived growth factor receptor-alpha (PDGFRA) expression was significantly associated withabetterprognosis(P= 0.034).Ki-67overexpression(≥50％)wassignificantlyassociatedwithapoorprognosis(P= 0.017).Different treatment approaches were also associated with prognosis (P = 0.014); specifically, the efficacies of combination treatments including chemotherapy and radiotherapy, and autologous hematopoietic stem cell transplantation were significantly better than those involving radiotherapy and chemotherapy alone. Patient gender, age, tumor location, staging, the presence of B symptoms, pretreatment lactate dehydrogenase levels, and β2-microglobulin levels were not associated with the prognosis of ENKTCL (P > 0.05). However, multivariate analyses showed that the treatment approach and all the immune markers were not independent prognostic factors for ENKTCL. Conclusion: Granzyme B, perforin, and Bcl-2 expression and Ki-67 overexpression (≥50％) might be adverse prognostic factors for ENKTCL, whereas PDGFRA-positivity suggested a better disease prognosis. In addition, different treatment approaches might be closely related to patient prognosis.

Classification, diagnosis, and management of conjunctival lymphoma

Lymphoma is a malignant lymphoproliferative tumor that can involve the conjunctiva.Approximately 5–15%of all extranodal lymphomas are found in the ocular adnexal region,with approximately 25%of those involving the conjunctiva.Ninety-eight percent of conjunctival lymphomas arise from B-lymphocytes.The most common subtype of conjunctival lymphoma is extranodal marginal zone lymphoma(80%),followed by follicular lymphoma(8%),diffuse large B-cell lymphoma(3%)and mantle cell lymphoma(3%).Natural killer and T cells(NK/T)are rare causes of lymphoma.While most conjunctival lymphomas are localized to the ocular adnexa at the time of presentation,systemic examination and management are of key importance in the long-term care of the patient.This review outlines the classification,etiology,presentation,diagnosis,and management of conjunctival lymphoma.The novel use of high resolution optical coherence tomography,both as a diagnostic tool and as a means for ongoing evaluation during treatment,is illustrated.Treatment options discussed include external beam radiation,chemotherapy,immunotherapy,antibiotic therapy,and combination regimens.Future investigation of the etiology and pathogenesis of conjunctival lymphoma is expected to reveal opportunities for innovative and individualized therapeutic agents.Collaboration between multiple disciplines is key in the advancement of the field.

Progress in the treatment of NK-cell lymphoma/leukemia

Natural killer(NK)/T cell lymphoma includes two major subtypes of disease,specifically extranodal NK/T cell lymphoma,nasal type(ENKL)and aggressive NK cell leukemia(ANKL).Both are strongly associated with Epstein Barr virus and are prevalent in East Asia and Latin America.Except for that of limited-stage ENKL,the prognosis of both diseases was poor in the previous decade.The advent of non-anthracycline-based chemoradiotherapy has contributed to an improvement in ENKL prognosis,but there is still room for further treatment progress.Recently,the high efficacy of PD-1 antibody was reported in relapsed or refractory ENKL patients.This was later supported by the finding that PD-L1/PD-L2 genetic alterations are frequently observed in ENKL and ANKL patients.Due to the rarity of the disease,a standard treatment for ANKL remains to be established.Currently,allogeneic stem cell transplantation is the only curative treatment,and this is even applicable to chemo-resistant ANKL patients.In this review,we focus on recent treatment approaches for NK/T cell lymphomas including novel agents.