A retrospective analysis of mature T-and NK-cell lymphomas

Mature T-and natural killer(NK)-cell lymphomas are heterogeneous groups of malignant lymphoid neoplasms arising from T and NK cells. The incidence of mature T-and NK-cell lymphomas is 2.1 per 100,000 people, according to a US report~1.

Comparison of clinical features of patients with or without severe gastrointestinal complications in aggressive gastrointestinal lymphomas

BACKGROUND Aggressive primary gastrointestinal non-Hodgkin lymphoma(PGINHL)is an uncommon and heterogeneous group of lymphoid malignancies,that differs from indolent lymphoma and has a high incidence of severe gastrointestinal complications(GICs).AIM To investigate and compare the clinicopathological characteristics,treatments and outcomes in the GICs and No-GICs group with aggressive PGINHL.METHODS This retrospective analysis was performed on aggressive PGINHL patients between January 2013 and December 2021 at our hospital.The independent influence factors of GICs were obtained by univariate and multivariate Logistic regression analysis,the selected variables significantly related to GICs were selected as the final predictors to construct nomogram.Kaplan-Meier curves further analyzed the survival of patients in GICs and No-GICs groups.Survival analysis of GICs group was performed using Cox regression.RESULTS We focused on 124 aggressive PGINHL cases,which had a relatively high incidence 48.4%(60/124 cases)of GICs,the most common histological type in GICs group was diffuse large B-cell lymphoma(DLBCL)(n=49,81.7%).In the GICs group,small intestine was the most common anatomic site of lesion(43.3%),followed by large intestine(31.7%),and then stomach and esophagus(25.0%).Multivariate Logistic regression analysis showed that the independent risk factors for GICs were the small intestine[odd ratio(OR)=3.33;95%confidence interval(CI):1.47-9.41;P=0.009),aggressive B-cell(OR=0.09;95%CI:0.01-0.83;P=0.033),maximum tumor diameter(OR=1.25;95%CI:1.07-1.47;P=0.005),invaded deep serous layer(OR=3.38;95%CI:1.24-9.19;P=0.017).We developed a nomogram to predict risk of GICs in aggressive PGINHL patients based on independent risk factors.The value of area under curve calculated by receiver operating characteristic curve was 0.815,and calibration curve and decision curve analysis further indicated that the prediction effect was superior.The majority of patients with GICs were given combination therapy(chemotherapy combined with surgery or radiation).Event-free survival and overall survival in GICs group were no worse than those in the No-GICs group.CONCLUSION The complication rate of GICs in patients with aggressive PGINHL was relatively high,particularly in PGI-DLBCL.The independent risk factors for GICs were the small intestine,PGI-TNKL,bulky tumor,and depth of invasion.A combination treatment,involving surgery,improved survival in the GICs group.

Nodal peripheral T-cell lymphomas in the new classification systems

Peripheral T-cell lymphomas(PTCLs)encompass a biologically diverse group of non-Hodgkin lymphomas derived from mature T-lymphocytes.Most PTCLs present as nodal diseases and include several subtypes characterized by distinct clinical and pathologic features,and will be the focus of this editorial.The PTCL group presenting as rare distinctive extranodal diseases will not be discussed.While T-cell neoplasms,like B-cell lymphomas,recapitulate stages of normal differentiation,the biology is notably intricate and exhibits remarkable plasticity.

Gene targeted and immune therapies for nodal and gastrointestinal follicular lymphomas

Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increase.Genetic abnormalities related to t(14;18)translocation,BCL2 overexpression,NF-κB pathway-related factors,histone acetylases,and histone methyltransferases cause FL and enhance its proliferation.Meanwhile,microRNAs are commonly used in diagnosing FL and predicting patient prognosis.Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted,resulting in a marked improvement in therapeutic outcomes for FL.Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options,FL treatment has become more complex,requiring combinatorial therapeutic regimens.However,optimal treatment combinations have not yet been achieved,highlighting the importance of a complete understanding regarding the pathogenesis of gastrointestinal FL.Accordingly,this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations.Moreover,the results of clinical trials are summarized,with a particular focus on treating nodal and gastrointestinal FLs.

Endoscopic features of gastro-intestinal lymphomas: From diagnosis to follow-up

Many progresses have been done in the management of gastrointestinal(GI) lymphomas during last decades, especially after the discovery of Helicobacter pylori-dependent lymphoma development. The stepwise implementation of new endoscopic techniques, by means of echoendoscopy or double-balloon enteroscopy, enabled us to more precisely describe the endoscopic features of GI lymphomas with substantial contribution in patient management and in tailoring the treatment strategy with organ preserving approaches. In this review, we describe the recent progresses in GI lymphoma management from disease diagnosis to follow-up with a specific focus on the endoscopic presentation according to the involved site and the lymphoma subtype. Additionally, new or emerging endoscopic technologies that have an impact on the management of gastrointestinal lymphomas are reported. We here discuss the two most common subtypes of GI lymphomas: the mucosaassociated lymphoid tissue and the diffuse large B cell lymphoma. A general outline on the state-of-the-art of the disease and on the role of endoscopy in both diagnosis and follow-up will be performed.

Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment

The relationships between lymphomas and their microenvironment appear to follow 3 major patterns:(1)an independent pattern;(2)a dependent pattern on deregulated interactions;and(3)a dependent pattern on regulated coexistence.Typical examples of the third pattern are hepatitis C virus(HCV)-associated marginal zone lymphomas(MZLs)and mucosa-associated lymphoid tissue lymphomas.In these lymphomas,a regulated coexistence of the malignant cells and the microenvironmental factors usually occurs.At least initially,however,tumor development and cell growth largely depend on external signals from the microenvironment,such as viral antigens,cytokines,and cell-cell interactions.The association between HCV infection and B-cell lymphomas is not completely defined,although this association has been demonstrated by epidemiological studies.MZL and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV infection.Many mechanisms have been proposed for explaining HCV-induced lymphomagenesis;antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell lymphomas.Recently,antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent lymphomas.Importantly,clinically responses were linked to the eradication of the HCV-RNA,providing a strong argument in favor of a causative link between HCV and lymphoproliferation.

The expression of cyclooxygenase-2 （COX-2） and p16 in non-Hodgkin＇s lymphomas and its clinical significance

Objective： To investigate the expression of cyclooxygenase-2 （COX-2） and p16 proteins in non-Hodgkin＇s lymphomas （NHL） and their relationship with the genesis and progress of it. Methods： The expression of COX-2 and p16 protein were studied in the lymph nodes tissue from 60 NHL patients and 10 control patients with non-malignant diseases by flow cytometry. Results： Positive rate of COX-2 protein expression in NHL tissues （63.3%, 38/60） was higher than that in normal lymphaden tissues （0, 0/10）. The difference was significant between the two groups （P 〈 0.01）. Expression of COX-2 protein was related with the clinical stage of NHL. In stage Ⅰ ＋ Ⅱ patients, it was significantly lower （35.0% ± 54.6%） than that in stage Ⅲ ＋ Ⅳ patients （84.6% ±87.5%） （P 〈 0.01）. In different sex, age, tumor malignant degree, IPI grade, extranodal involvement and B symptoms groups, the differences of COX-2 expression were not statistically significant （P 〉 0.05）. Positive rate of p16 protein expression （41.7%, 25/60） in NHL＇ was statistically lower than that in normal lymphomas （100%, 10/10） （P 〈 0.01）. Expression of p16 protein was related to malignant degree of NHL. The positive rates of p16 protein in low malignant degree tissues （64.7%, 11/17） was higher than that in high malignant degree tissues （14.3%, 2/14） （P 〈 0.05）. Positive rates of p16 protein of NHL tissues in different sex, age, IPI grade, extranodal involvement, clinical stages and B symptoms were not statistically significant （P 〉 0.05）. The p16 protein expression in COX-2 positive patients was 47.4% （18/38）, and in negative patients it was 31.8% （7/22）. There was no statistically difference between them （P 〉 0.05）. Correlation analysis revealed there was no correlation between expression of COX-2 and p16 protein. Conclusion： Both COX-2 and p16 protein may all have relationship with the genesis and progress of NHL. The expression of COX-2 protein in NHL may be a poor prognostic indicator. COX-2 and p16 protein probably have different mechanisms in the genesis and progress of NHL. Their relationship is firstly put forward in this article and needed further studying.

Gastrointestinal B-cell lymphomas:From understanding B-cell physiology to classification and molecular pathology

The gut is the most common extranodal site where lymphomas arise. Although all histological lymphoma types may develop in the gut, small and large B-cell lymphomas predominate. The sometimes unexpected finding of a lymphoid lesion in an endoscopic biopsy of the gut may challenge both the clinician (who is not always familiar with lymphoma pathogenesis) and the pathologist (who will often be hampered in his/her diagnostic skill by the limited amount of available tissue). Moreover, the past 2 decades have spawned an avalanche of new data that encompasses both the function of the reactive B-cell as well as the pathogenic pathways that lead to its neoplastic counterpart, the B-cell lymphoma. Therefore, this review aims to offer clinicians an overview of B-cell lymphomas in the gut, and their pertinent molecular features that have led to new insights regarding lymphomagenesis. It addresses the question as how to incorporate all presently available information on normal and neoplastic B-cell differentiation, and how this knowledge can be applied in daily clinical practice (e.g., diagnostic tools, prognostic biomarkers or therapeutic targets) to optimalise the managment of this heterogeneous group of neoplasms.

Area under the curve of methotrexate and creatinine clearance are outcome - determining factors in primary CNS lymphomas

Although high-dose methotrexate(HD-MTX)is the most effective drug against primary CNS lymphomas(PCNSL),outcome-de-termining variables related to its administration schedule have not been defined.The impact on toxicity and outcome of the area under thecurve(AUC(MTX)),dose intensity(DI(MTX))and infusion rate(IR(MTX))of MTX and plsamatic creatinine clearance(CL(crea))was investigated in a retrospective series of 45 PCNSL patients treated with three different HD-MTX-basedcombinations.Anticon-vulsants were administered in 31 pts(69%).Age>60 years,anticonvulsant therapy,slow IR(MTX)(

Point mutation of 5' noncoding region of BCL-6gene in primary gastric lymphomas

AIM: To investigate the mutations of the 5' noncoding region of BCL-6 gene in Chinese patients with primary gastric lymphomas. METHODS: PCR and direct DNA sequencing were used to identify BCL-6 gene mutations in the 5' noncoding region in 29 cases of gastric diffuse large B-cell lymphoma (DLBCL) and 18 cases of gastric mucosa-associated lymphoid tissue (MALT) lymphoma as well as 10 cases of reactive hyperplasia of lymph node (LRH). RESULTS: Six of 29 gastric DLBCLs (20.7%), 4 of 18 gastric MALT lymphomas (22.2%) and 1 of 10 LRHs(10%) were found to have mutations. All mutations were single-base substitutions and the frequency of single-base changes was 0.20×1O^(-2)-1.02×1O^(-2)per bp. CONCLUSION: Point mutations in the 5' noncoding region of BCL-6 gene are found in Chinese patients with primary gastric DLBCLs and MALT lymphomas, suggesting that they may, in some extent, participate in the pathogenesis of primary gastric DLBCLs and MALT lymphomas.

NUCLEOLAR ORGANIZER REGIONS IN CUTANEOUS T CELL LYMPHOMAS

The present work studied the application of AgNOR count to differential diagnosis between cutaneous T cell lymphoma (CTCL) and cutaneous pseudolymphoma (CPL). Paraffin sections from 50 mycosis fungoides (22 MFI-Premycotic stage, 24 MF Ⅰ infiltrative stage and 4 MF Ⅲ - tumor stage), 2 nonepidermotropic cutaneous T cell lymphoma (NECTCL) and 9 CPL were investigated. In each case, 200 cells randomly selected were examined using a × 100 oil immersion lens. The mean number, standard deviation and standard error of the mean of AgNOR counts were as follows: MFⅠ 1.17±0.09, SEM = 0.01; MⅡ 1.17±0.01, SEM = 0.01; MF Ⅲ. 3.55±0.87, SEM = 0.43; NECTCL 4.5±0.28, SEM -0.199; CPL 1.17±0.1, SEM ± 0.03. The results revealed a highly significant difference between CTCL (MFⅢ+NECTCL) and CPL (t = 4.75, P<0.001), tumor stage (MF Ⅲ) and pretumor stage (MFI, MF Ⅱ) of mycosis fungoides (t = 4.75, P<0.001). Thus. AgNOR count is valuable in differential diagnosis.

Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas

T-cell lymphomas(TCLs)represent a group of lymphoid neoplasms characterized by an aggressive clinical course,even after an anthracycline-containing regimen.Novel agents for patients with relapsed/refractory TCL are urgently needed.Lenalidomide is an oral drug with immunomodulatory,antiangiogenic and direct antineoplastic effects.These peculiar mechanisms of action make TCL an attractive target for lenalidomide.We have identified five clinical trials in which lenalidomide monotherapy was investigated to treat TCL,including cutaneous TCL(CTCL)and adult T-cell lymphoma/leukemia(ATLL).In the ATLL-002 study,the overall response rate(ORR)was 42%and median progression-free survival(PFS)and overall survival were 3.8 mo and 20.3 mo,respectively.In a phase II trial for CTCL,ORR was 28%and median PFS and overall survival were 8 mo and 43 mo,respectively.For nodal peripheral TCL,ORR was between 10%and 43%in three clinical trials,with a median PFS of about 4 mo,even if some patients had a durable response.Overall toxicity is manageable and grade 3-4 events are mainly hematological and reversible.Combination strategies did not improve PFS.In conclusion,lenalidomide could represent a suitable treatment option for relapsed/refractory TCL,especially for neoplasms with a T-follicular helper origin,such as angioimmunoblastic TCL.

IMMUNOPHENOTYPING OF CUTANEOUS GERMINAL CENTER CELL-DERIVED LYMPHOMAS

Monoclonal antibodies were used to label cutaneous germinal center cell-derived lymphomas <CGCCL) obtained from 10 patients. According to the Kiel classification, they were classified into 2 types. Eight patients had centroblastic/centrocytic <CB/CC) lymphomas while 2 patients and centrocytic (CC) lymphomas. After monoclonal antibody labelling, the results were consistent with those of the clinical and morphologic analyses. Of the 10 cases, 9 were B1 positive, 6 were K positive, and 4 were λ positive. In 8 cases labeled with immunoglobulin, 6 were IgGFab positive, 2 were IgM positive and 8 were IgA negative. Five cases (CB/CC 3, CC 2) were both Bl, K and IgG positive (γ K). Four cases CB/CC were both Bl and A positive. Only one case (CB/CC) was both K and IgM positive (μ K). Two cases (CB CC) were both A and IgG positive (γ λ). The results indicate that Bl, K and A are the most important markers to phenotype cutaneous B-cell lymphomas. Our findings also show a higher percentage of y K types in CGCCL as compared with Western countries.

DETECTION OF BCL-2 GENE MAJOR BREAKPOINT REGION REARRANGEMENT IN HUMAN B-CELL LYMPHOMAS

Objective To investigate the frequency of t(14; 18) in different subtypes of B-cell lymphomas and the ability or the polymerase chain reaction(PCR) to detect this rearrangement in frozen samples. Methods 1o7 cases of B-cell lymphomas were studied uslng DNA extracted from rresh-frozen tissues. The DNA samples were amplified by PCR for bcl-2 MBR/JH. The products of bcl-2/JH rearrangement were hybridized with an internal olignucleotide probe or bcl-2 MBR. Results The rearranged bcl-2MBR/JH gene was detected in 13 of the 25(52. o% ) follicular center lymphomas, according to REAL classification: 8 of 11 (72. 7%) grade 1, 2 of 5(40. 0%) grade I, and 3 of 90 (33. 3%) grade, 17 of 82(2o. 8%) cases or difruse large B-cell lymphomas were found to have detectable bel-2 MBR/J. rearrangement- Conclusion The rrequency or bcl-2 MBR/JH rearrangement in diffuse large B-cell lymphomas is significantly lower than those in follicular center lympkomas(X2= 9. 28, P <o. oo5), suggesting that bcl2/JH rearrangements occur mainly in follicular center lymphomas. in addition, the result of reconstruction experiments suggest that amplification or bcl-2 MBR/JH rearrangements by PCR is both sensitive and specific for detection of t (14; 18 ) translocation.

Natural killer reprogramming in cutaneous T-cell lymphomas: Facts and hypotheses

To better understand the pathogenesis of Sézary cells, distinguish them from reactive skin-infltrating T-cells and improve disease treatment, efforts have been made to identify molecular targets deregulated by the malignant process. From immunophenotypic analysis and subtractive differential expression experiments to pan-genomic studies, many approaches have been used to identify markers of the disease. During the last decade several natural killer （NK） cell markers have been found aberrantly expressed at the surface of Sézary cells. In particular, KIR3DL2/CD158k, expressed by less than 2% of healthy individuals CD4＋ T-cells, is an excellent marker to identify and follow the tumor burden in the blood of Sézary syndrome patients. It may also represent a valuable target for specifc im-munotherapy. Other products of the NK cluster on chromosome 19q13 have been detected on Sézary cells, raising the hypothesis of an NK reprogramming process associated with the malignant transformation that may induce survival functions.

Contribution of Immunohistochemistry in the Diagnosis of Lymphomas

Objective: Making the interest of using immunohistochemistry clear in addition to histological test in the diagnosis of lymphomas. Methods: This is a retrospective study from January 2011 to June 2013 involving 18 cases of lymphomas collected in the teaching hospitals of Treichville and Yopougon. Results: 1) 38.88% diagnosis of LMNH B large-cell in histology against 38.88% LDGCB with IHC. 2) 11.11% diagnosis of LMNH small cell in histology against 11.11% with IHC. 3) 5.55% diagnosis of T lymphoma in histology against 27.77% diagnosis of T lymphoma with IHC. 4) 5.55% diagnosis of follicular lymphoma in histology against 11.11% diagnosis of LF with IHC. 5) 11.11% diagnosis of Burkitt lymphoma in histology against 5.55% diagnosis of LB with IHC. 6) 5.55% diagnosis of medullary hypoplasia in histology against 5.55% diagnosis of Hodgkin’s disease. Our results confirm the contribution of immunohistochemistry in the diagnosis of lymphomas in addition to histological test. This is striking, especially as there is 27.77% of T lymphoma with immunohistochemistry against only 5.55% with histology.

Non Hodgkin Lymphomas (NHL) in the Pediatric Oncology Unit of the Gabriel TouréTeaching Hospital, Bamako Mali

Background :Non-Hodgkin lymphomas are the first childhood cancer in sub-Saharan Africa. Objective: The purpose of this study was to assess non-Hodgkin lymphomas cases in our setting. Methodology: A retrospective and descriptive study carried out in the pediatric oncology unit of the Gabriel Touré Teaching Hospital Bamako over 10 years from 1st January 2005 to 31th December 2015. Results: We exploited 274 (21.6%) cases of Non-Hodgkin Lymphoma out of 1295 cancer cases registered, the age group 6 - 10 years was the most represented (46.4%);the male sex was predominant with a sex-ratio of 1.8;digestive signs were the most common signs of discovery (44.2%) followed by maxillary swelling (42.7%);the majority of patients (52.9%) consulted between 1 and 3 months after the onset of signs;the malnutrition rate was 39.8%, of which 24.1% were severe cases and 15.7% were moderate rate. Abdominal localization was the most common (43.1%) followed by maxillofacial localization (33.9%). Almost all were Burkitt type cytology (92.7%), the majority (73.4%) were in Murphy stage III. Almost all (96%) had received chemotherapy and the modified LMB 01 protocol was widely used (62.4%). The majority of patients (85%) were chemosensitive at day 7 or after the third cyclophosphamide injection but at the end of induction only 31% were in complete remission. Gastrointestinal toxicity was the most common (37.13%) followed by hematologic toxicity 35.09 %;9.12 % of patients were lost of follow-up and 22.26% died. Tumor progression was the most common cause of death (60.66%) followed by infection (21.31%). Conclusion: In light of these findings, the late diagnosis and the poor management of NHL, as well as the limited ability to primarily treat metabolic complications, explain the high case-fatality rate, hence the important role of early diagnosis and treatment multidisciplinary.

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.

Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue lymphomas

Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent extranodal marginal zone B-cell lymphoma, originating in acquired MALT that is induced in mucosal barriers as part of a normal adaptive immune response to a chronic immunoinflammatory stimulus, most notably chronic infection by Helicobacter pylori (H. pylori). This antigenic stimulation initially leads to lymphoid hyperplasia; the acquisition of additional genetic aberrations culminates in the activation of intracellular survival pathways, with disease progression due to proliferation and resistance to apoptosis, and the emergence of a malignant clone. There are descriptions of MALT lymphomas affecting practically every organ and system, with a marked geographic variability partially attributable to the epidemiology of the underlying risk factors; nevertheless, the digestive system (and predominantly the stomach) is the most frequently involved location, reflecting the gastrointestinal tract’s unique characteristics of contact with foreign antigens, high mucosal permeability, large extension and intrinsic lymphoid system. While early-stage gastric MALT lymphoma can frequently regress after the therapeutic reversal of the chronic immune stimulus through antibiotic eradication of H. pylori infection, the presence of immortalizing genetic abnormalities, of advanced disease or of eradication-refractoriness requires a more aggressive approach which is, presently, not consensual. The fact that MALT lymphomas are rare neoplasms, with a worldwide incidence of 1-1.5 cases per 105 population, per year, limits the ease of accrual of representative series of patients for robust clinical trials that could sustain informed evidence-based therapeutic decisions to optimize the quality of patient care.

Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review

Since Isaacson and Wright first reported on the extranodal marginal zone B-cell lymphoma of the stomach in 1983,following studies have clarified many aspects of this disease.We now know that the stomach is the most affected organ by this disease,and approximately90% of gastric mucosa-associated lymphoid tissue(MALT) lymphomas are related to Helicobacter pylori(H.pylori) infection.This implies that approximately 10% of gastric MALT lymphomas occur independent of H.pylori infection.The pathogenesis of these H.pylori-negative gastric MALT lymphomas remains unclear.To date,there have been several speculations.One possibility is that genetic alterations result in nuclear factor-kappa B(NF-κB) activation.Among these alterations,t(11;18)(q21;q21) is more frequently observed in H.pylori-negative gastric MALT lymphomas,and such translocation results in the synthesis of fusion protein API2-MALT1,which causes canonical and noncanonical NF-κB activation.Another possibility is infection with bacteria other than H.pylori.This could explain why H.pylori eradication therapy can cure some proportions of H.pylori-negative gastric MALT lymphoma patients,although the bacteria responsible for MALT lymphomagenesis are yet to be defined.Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment.A certain proportion of H.pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence,H.pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H.pylori infection status.