Case Of Marginal Zone Lymphoma Research Articles

Transformation risk and associated survival outcome of marginal zone lymphoma: A nationwide study.

Histological transformation into an aggressive B-cell lymphoma indicates a poor survival outcome for patients with indolent marginal zone lymphoma (MZL), which has been less studied. Large-scale data with long-term follow-up to investigate MZL transformation is limited. Here, by reporting a US-Nationwide cohort of 30,619 MZL patients diagnosed between 2000 and 2019, we found that transformation occurred in 2.08% (N = 624) of MZL cases, with the transformation incidence of 3.1 per 1,000 person-years. Advanced Ann Arbor stage, nodal MZL (NMZL) and splenic MZL (SMZL) were associated with an elevated risk of transformation. Certain subtype-specific characteristics, such as non-gastric extra-nodal MZL (vs. gastric, HR, 1.51, 95%CI 1.13-2.04; p = 0.006), and receiving splenectomy for SMZL (HR, 2.04, 95%CI 1.28-3.26; p = 0.003), also indicated a higher risk of transformation. Besides, transformation independently increased the overall mortality risk (HR, 1.38, 95%CI 1.24-1.53, p < 0.001), especially the higher lymphoma-caused mortality risk (HR, 3.21, 95%CI 2.81-3.67, p < 0.001). Transformation was also associated with a higher percentage of lymphoma-caused deaths. The post-transformation prognostic analyses demonstrated that female gender and age ≥ 65 years independently affected patients' mortalities. These findings, based on the largest cohort to date, contribute to a better understanding of transformed MZL, and provide valuable reference points for guidelines and patient counseling.

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.

The clinical significance of increased large cells in marginal zone lymphoma

Marginal zone lymphoma (MZL) is a primary, indolent small B-cell lymphoma. Subtypes include nodal, splenic, and those of extranodal mucosa-associated lymphoid tissue (MALT). These are slow growing and generally exhibit low rates of transformation to diffuse large B-cell lymphoma (DLBCL). At initial diagnosis, there can be an increase in large cells (LCs) that does not meet criteria for DLBCL. Prior studies have noted this finding, but the clinical significance of these LCs has not been well established. A total of 161 cases of MZL from 1994 to 2021 were evaluated, including all subtypes. There were 33 cases with increased LCs (>10 LCs per high-power field [hpf]), with the majority containing >15 LCs/hpf (28/33) and 128 cases without increased LCs. Cases with increased LCswere significantly more likely to have a Ki-67 proliferation index of ≥30% (P<.0001). Overall survival was not significantly different between the groups but progression-free survival was significantly worse in the LC group (P<.0001). MZL with increased LCs was also associated with a higher stage at diagnosis (P=.0035), was more likely to transform to DLBCL (P=.0016), and had a greater frequency of relapse (P<.0001). Subgroup analysis showed that both nodal and MALT LC groups had a worse progression-free survival and a higher rate of relapse than their standard nodal and MALT lymphoma counterparts, but only within the MALT subgroup did the LC cases present at a higher stage and have a higher rate of transformation to DLBCL than the standard cases. Although larger studies are needed for validation, these results suggest that the presence of LCs in MZL may serve as a useful prognostic indicator and potentially help guide clinical decision-making.

Extranodal Marginal Zone Lymphoma of Thyroid – An Unusual Tumor at Unusual Location

Primary thyroid lymphoma accounts for 5% of all the malignancies of the thyroid gland. The thyroid is very rare and unusual site for lymphoma, only few cases have been described in the literature. It is associated with chronic inflammatory lesions such as chronic lymphocytic thyroiditis. We report a rare case of Marginal Zone lymphoma in a 44 year old male patient presented with complaint of swelling in the right side of neck since 3 months. The definitive diagnosis was confirmed by histopathological examination and immunohistochemistry.

Clinical Features and Outcomes of the Patients with B-Cell Chronic Lymphoproliferative Disease in the New Drug Era

To analyze the clinical characteristics of the patients with B-cell chronic lymphoproliferative disease（B-CLPD） in the new drug era and the effect of new drug treatment on efficacy and survival. The clinical and laboratory data of 200 cases B-CLPD patients diagnosed between April 2015 and August 2021 were analyzed retrospectively. The clinical efficacy and survival of the patients under different treatments including Bruton tyrosine kinase（BTK） inhibitors， rituximab， and chemotherapy alone were analyzed. The prognostic factors affecting the survival of patients were analyzed by univarite analysis and multivariate analysis. There were 119 male（59.5％） and 81 female（40.5%） in 200 cases B-CLPD patients， the sex ratio(male/female) was 1.5∶1 with median age of 61（30- 91） years old. The distribution of subtypes were as fallows: 51 cases (25.5%) of chronic lymphocytic leukemia/small lymphocytic lymphoma（CLL/SLL）， 64（32.0%） cases of follicular lymphoma（FL）， 40（20.0%） cases mantle cell lymphoma（MCL）， 30（15.0%） cases of marginal zone lymphoma（MZL）， 10（5%） cases of lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia（LPL/WM）， 5（2.5%） cases of B cell chronic lymphoproliferative disorders unclassified（B-CLPD-U） . The main clinical manifestation of 102 patients was lymph node enlargement, 32 cases were complicated with B symptoms. Among CLL/SLL patients， there were 12（23.5%） cases in Binet A and 39（76.5%） cases in Binet B/C. There were 29 patients（20.9%） in Ann Arbor or Lugano stage I-II and 110 cases（79.1%） in stage III-IV of other subtypes. The complete remission（CR） rate was 43.1%（25/58）， 40.2%（39/97）， 7.1%（1/14）， and overaIl response rate（ORR） was 87.9%（51/58）， 62.9%（61/97）， 28.6%（4/14） in the groups of BTK inhibitors， rituximab-based therapy， and chemotherapy alone. The 3-year OS rate and PFS rate in all patients was 79.2% and 72.4% respectively. The 3-year OS rate of patient with MZL, CLL/SLL, FL,WM was 94.7%, 87.7%, 86.8% and 83.3% respectively, while the 3-year OS rate of MCL was only 40.6%, which was significantly lower than other subtypes. The median OS of patients treated with BTK inhibitors and rituximab-based therapy was 20.5 and 18.5 months respectively， and the 3-year OS rate was 97.4% and 90.7%. However， the median PFS of patients receiving chemotherapy alone was 4 months， and the 1-year OS rate was 52.7%， which was statistically significant compared with the other two groups（P<0.05）. Univarite analysis showed that anemia， elevated lactate dehydrogenase， elevated β2-microglobulin， and splenomegaly were the poor prognostic factors for OS（P<0.05）， elevated lactate dehydrogenase was also poor prognostic factors for PFS（P<0.05）. Multifactor analysis showed that anemia and elevated lactate dehydrogenase were the independent poor prognostic factors for survival（P<0.05）. The clinical features of B-CLPD was various， anemia and elevated lactate dehydrogenase are the prognostic factors for poor survival. BTK inhibitors and new immunotherapy can improve the survival and prognosis of patients in the new drug era.

Estimating the Burden of Illness of Relapsed Follicular Lymphoma and Marginal Zone Lymphoma in Ontario, Canada.

Many patients with advanced follicular lymphoma (FL) and marginal zone lymphoma (MZL) relapse after first-line chemotherapy. To examine healthcare resource utilization (HCRU) and cost, treatment patterns, progression, and survival of patients with FL and MZL who relapse after first-line treatment, in Ontario, Canada. A retrospective, administrative data study identified patients with relapsed FL and MZL (1 January 2005-31 December 2018). Patients were followed for up to three years post relapse to assess HCRU, healthcare costs, time to next treatment (TTNT), and overall survival (OS), stratified by first- and second-line treatment. The study identified 285 FL and 68 MZL cases who relapsed after first-line treatment. Average duration of first-line treatment was 12.4 and 13.4 months for FL and MZL patients, respectively. Drug (35.9%) and cancer clinic costs (28.1%) were major contributors to higher costs in year 1. Three-year OS was 83.9% after FL and 74.2% after MZL relapse. No statistically significant differences were observed in TTNT and OS between patients with FL who received R-CHOP/R-CVP/BR in the first line only versus both the first- and second- line. A total of 31% of FL and 34% of MZL patients progressed to third-line treatment within three years of initial relapse. Relapsing and remitting nature of FL and MZL in a subset of patients results in substantial burden to patients and the healthcare system.

A RARE CASE OF PRIMARY PLEURAL LOW GRADE MARGINAL ZONE NONHODGKIN'S LYMPHOMA: A CASE REPORT

A primary pleural based marginal zone low grade NHL is very rare. Primary pleural Lymphomas account for less than 0.5% off all Non-Hodgkin Lymphomas and DLBCL is the most common subtype of primary pleural lymphomas. Here, we report a rare case of marginal zone lymphoma of low grade with Mib index of 15-20% presenting as a pleural based mass in a middle age individual. A 52 years old male presented with right sided pleural effusion with pleural thickening of soft tissue density. Thoracoscopy showed pleural based mass lesion and pleural biopsy revealed low grade marginal zone NHL which is very rare with very few cases documented till date. Diagnosis was based on Bcl-2 and CD20 marker positivity on IHC. Treatment of such Low-grade Marginal zone lymphoma is with Bendamustine and Rituximab.

Immunohistochemical analysis of arachidonate 5-lipoxygenase expression in B-cell lymphomas: Implication for B cell differentiation and its analogy with lymphomagenesis.

Arachidonate 5-lipoxygenase (ALOX5) is a cardinal enzyme in the synthesis of leukotrienes, which are powerful immune-regulating lipid mediators. We previously reported that ALOX5 is preferentially expressed in B lymphocytes in the mantle zone of human lymphoid tissue. In the context of physiological relevance, the loss of the Alox5 gene in mice significantly impairs the development of follicular B helper T cells and antibody production. However, ALOX5 expression in B-cell lymphomas has not been investigated in detail. In this study, we examined ALOX5 expression in representative B-cell lymphomas and non-neoplastic lymphoid tissues by immunohistochemistry with a commercially available anti-ALOX5 antibody that can be used on formalin-fixed paraffin-embedded specimens. Interestingly, 22/22 cases of mantle cell lymphoma, 7/7 cases of chronic lymphocytic leukemia/small cell lymphoma, and 20/20 cases of follicular lymphoma expressed ALOX5. A small proportion of extranodal marginal zone lymphoma/mucosa-associated lymphoid tissue lymphoma or nodal marginal zone lymphoma cases were positive for ALOX5 (2/13 or 1/3, respectively). In contrast, no cases with diffuse large B-cell lymphoma, regardless of germinal center B cell (GCB) or non-GCB type, expressed ALOX5 (0/25 cases). These findings suggest that ALOX5 may be a novel marker for identifying the cell of origin of B-cell lymphoma. Further investigation is required to clarify the biological significance of ALOX5 expression in lymphoma cells.

EXPRESSION PATTERNS OF CD90, CD117, CD123, AND CD147 IN MATURE B CELL NEOPLASMS

Summary. Aim: to analyze the expression patterns of CD90, CD117, CD123, and CD147 on cells of the mature B-cell neoplasms, in particular marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) and the expression of CD147 on chronic lymphocytic leukemia (CLL) cells. Object and methods: the expression patterns of the surface antigens on the transformed B cells were analyzed in the peripheral blood samples of the MZL, MCL, and CLL patients (34 patients in total) by the flow cytometry using the monoclonal antibodies. Results: at least one of the antigens – CD90, CD117, or CD123 was expressed in 20.0–33.3% of MCL cases and 27.2–54.5% of MZL cases at the level ≥ 1% of the cells in the subpopulation of CD45-positive lymphoid cells. One MCL case demonstrated the high content of CD117-positive cells (31.0%) accompanied by CD90 expression on 3.8% of cells. The high content of the CD147-positive cells was found not only in MZL and MCL but also in CLL. Conclusion: a small fraction of cells of lymphoid neoplasms expresses several antigens of the leukemic stem cells and cells of the myeloid lineage. The ubiquitous pattern of CD147 expression on cells of these neoplasms has been demonstrated. The diagnostic and prognostic significance of the expression of the studied antigens remains unknown necessitating further clinical studies of the clinical features of these diseases taking into account the expression of the atypical markers.

Impact of Circulating Lymphoma at Diagnosis on Outcomes in Patients with Marginal Zone Lymphoma

Introduction Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma that includes 3 subtypes: extranodal marginal zone lymphoma (EMZL) of the mucosa-associated lymphatic tissue (MALT), splenic MZL (SMZL), and nodal MZL (NMZL). Although flow cytometry can detect circulating lymphoma cells in many cases of MZL, outside of case reports and small case series, the relevance of this circulating lymphoma (CL) in patients with MZL at diagnosis is largely unknown. Hence, we sought to evaluate the impact of CL at diagnosis on outcomes in patients with MZL. Methods This multicenter, retrospective cohort study of MZL patients treated at 3 US medical centers included patients who were ≥18 years old, diagnosed with MZL from 2010-2020, and had peripheral blood flow cytometry performed at diagnosis. Patients who never received therapy for MZL were excluded. Patients were classified according to positive or negative flow cytometry results as CL+ and CL-, respectively. The primary endpoint was progression-free survival (PFS) defined as the time from the start of first-line therapy until lymphoma relapse/progression or death from any cause, censoring at the last clinical assessment. Secondary endpoints were overall survival (OS, from the start of first-line therapy until death or last follow-up) and time from diagnosis to systemic therapy in CL+ and CL- groups. Results Among 294 eligible patients with newly diagnosed MZL, 75 (25%) had detectable CL at diagnosis. The CL+ group had a higher median age (66 vs 63 years), advanced-stage disease (100% vs 53%), bone marrow involvement (91% vs 35%), elevated LDH (49% vs 22%), lower albumin (24% vs 13%), and less often received R-chemotherapy (39% vs 41%) compared to the CL- group. SMZL constituted the predominant subtype (52%, n=39) in the CL+ group with NMZL and EMZL constituting 24% each (n=18). The median PFS was not significantly different between the CL+ (6.2 years, 95%CI=3.6-NR) and CL- (5.9 years, 95%CI=4.3-8.4), p=0.73 (Figure 1) groups. Similar results were noted across the MZL subtypes with no significant difference in median PFS in EMZL (p=0.51), NMZL (p=0.51), or SMZL (p=0.38) according to the CL status. The median PFS was not significantly different between CL+ and CL- groups among patients treated with rituximab monotherapy (median PFS 4.1 vs 3.2 years, respectively, p=0.69) or immunochemotherapy (median PFS NR vs 8.7 years, respectively, p=0.84, Figure 2). After adjusting for factors associated with PFS in multivariate cox regression (age, B symptoms, albumin level, LDH>ULN, and type of first-line treatment regimen), there was no difference in PFS between CL+ and CL- groups (HR=0.73, 95%CI=0.45-1.20, p=0.22). We did not observe a significant difference in OS between the CL+ and CL- groups with a 5-year rate of OS being 89% vs 82% in the CL+ and CL- groups (p=0.31). Furthermore, the time from diagnosis to systemic therapy initiation did not significantly differ between the CL+ and CL- groups with % of patients who started treatment at 1, 3, and 5 years from diagnosis being 83% vs 92%, 95% vs 96%, and 97% vs 99%, respectively (p=0.42). Conclusions This is the first study to compare the outcomes of patients with CL+ and CL- groups in newly diagnosed MZL. In this largest study to date evaluating the prognostic relevance of CL in patients with MZL, we found that CL at diagnosis was not associated with shorter PFS, OS, or time from diagnosis to first-line therapy. Further studies should evaluate whether the presence of CL is associated with specific molecular or other clinically relevant markers that were not available in our patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Case of Primary Dural Lymphoma Treated with Bendamustine and Rituxan

Background Primary CNS lymphoma (PCNSL) is an aggressive form of extranodal non-Hodgkin lymphoma that arises in the brain parenchyma, eyes, meninges, or spinal cord in the absence of systemic disease. Primary dural lymphoma (PDL) arises from the dura mater of the brain. It differs biologically from other CNS lymphomas. It is usually a low-grade B-cell marginal zone lymphoma (MZL), whereas other types of PCNSL are usually high-grade large B-cell lymphoma. This specific pathological subtype has important therapeutic and prognostic implications, making PDL a distinct subtype of PCNSL. Herein, we report a case of PDL in an African American patient who was treated with bendamustine and rituximab. Case Presentation A 38-year-old African American female patient presented with chronic intermittent headaches. MRI of the brain showed a dural-based homogeneously enhancing extra-axial mass along the left hemisphere with extension to the anterior interhemispheric falx and anterior right frontal lobe measuring up to 11 cm. This was found to have a significant mass effect and 1-2 cm left-to-right midline shift on the underlying brain parenchyma with vasogenic edema. The patient underwent an emergent craniotomy and debulking of the mass. The tumor was contained within the anterior and parietal dural matter. The malignant cells stained diffusely positive for CD19, CD20, and CD22 but negative for CD5, CD10, Cyclin D1, and CD56. Ki67 was 10-20%, consistent with extranodal marginal zone lymphoma. Given the location and pathology, the patient was diagnosed with PDL. She was started on treatment with bendamustine and rituximab. She completed six cycles, and post-therapy MRI brain showed complete remission. She continues to do well two years after finishing treatment. Discussion The Dura mater is devoid of lymphoid tissue; however, it is hypothesized that chronic inflammation of the dura due to chronic infection or autoimmune disorder may attract polyclonal lymphocytes from which monoclonal lymphoma could arise. PDL has not been definitively associated with any infectious or autoimmune disease, but patients with hepatitis C, scleroderma, Graves' disease, and Sjogren disease have been reported. Developmentally, the dura originates from the mesoderm. In contrast, the CNS originates from the ectoderm, which leads to the presence of the dura outside the blood-brain barrier and is easily exposed to systemic therapies. So, HDMTX regimens are excessive for PDL, where MZL is the most common pathology. Because of this and the known efficacy of bendamustine-rituximab in extranodal MZL, we decided to treat our patient with this regimen. Tsutsumi et al. reported 2 cases of dural MZL that were treated successfully with bendamustine-rituximab. However, those two cases also had evidence of systemic disease, not only dural disease like our patient. Because of its indolent pathology, surgery and/or radiation have also been used as treatment modalities, although complete resection of dural lymphomas can be technically difficult Conclusion Our case adds to the sparse literature about primary dural lymphoma. It emphasizes the importance of recognizing it as a separate entity from parenchymal PCNSL, an aggressive disease with a poor prognosis. Surgery, radiation, and/or chemoimmunotherapy used for other extranodal MZL are appropriate treatments for PDL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinching the Diagnosis: A Case of Marginal Zone Lymphoma Diagnosed on Kidney Biopsy

Clinching the Diagnosis: A Case of Marginal Zone Lymphoma Diagnosed on Kidney Biopsy

Challenges in the diagnosis of marginal zone lymphoma with symptoms of small intestinal disease: a case report and scoping review of the literature.

Marginal zone lymphoma can be accompanied by symptoms of small intestinal disease including abdominal pain and malabsorption. However, the best diagnostic approach for suspected marginal zone lymphoma is unknown and intestinal biopsies are frequently negative. We describe the case of a patient with symptoms of small bowel involvement where marginal zone lymphoma could only be detected upon peripheral lymph node resection. To assess the clinical variability of intestinal marginal zone lymphoma as a rare clinical entity, a scoping review with systematic literature research was performed. A 57-year-old man presented with a 10-year history of postprandial abdominal pain, systemic inflammation and recent weight loss. Endoscopies and a surgical small bowel specimen revealed non-specific findings. Flow cytometry from the bone marrow was highly suspicious for marginal zone lymphoma. A 2-18F-fluorodeoxyglucose-positron emission tomography/computed tomography (2-18F-FDG-PET/CT) showed hypermetabolic lymph nodes on both sides of the diaphragm. Cervical lymph node dissection finally confirmed marginal zone lymphoma. Immunochemotherapy yielded lasting oncological remission and resolved symptoms. We searched PubMed, Embase and Ovid MEDLINE® for additional case reports limited to the last 25 years. Five primary search terms combined using "AND" were used freely and as controlled vocabulary. Additional studies were identified by reviewing the reference lists of included articles. Our review revealed 52 cases of marginal zone lymphoma with small intestinal manifestation. Patients presented with abdominal pain, bowel obstruction, weight loss or gastrointestinal bleeding. Diagnosis was mainly established by surgery (73%). The most frequent endoscopic findings were mucosal erosions and ulcerations. A 2-18F-FDG-PET/CT was positive in 9/15 patients. Treatment included rituximab, chemotherapy, surgery and/or radiation resulting in clinical remission in 82% of cases. Diagnostic workup for suspected small intestinal marginal zone lymphoma is challenging, necessitating a multidisciplinary approach. Endoscopy, imaging including 2-18F-FDG-PET/CT and small bowel resection or dissection of hypermetabolic lymph nodes can be useful. If marginal zone lymphoma is suspected vigorous diagnostic efforts are justified since remission can be achieved in most patients. Our review highlights the variable clinical presentation of this underdiagnosed disease and adds systematic data to the literature.

Aberrant expression of CD54 detected by flow cytometry is a characteristic of B-lymphoma cells in bone marrow specimens

BackgroundFlow cytometry (FC) is a popular method to detect bone marrow (BM) involvement in patients with B-cell non-Hodgkin lymphoma (B-NHL). The majority of screen panels of FC still rely on finding monoclonal B-cells, e.g., B-cells with immunoglobin (Ig) light-chain restriction, which has many limitations. Therefore, exploring new markers is warranted.MethodsA total of 52 cases of B-NHL with BM involvement were collected. The median age was 60 years. Out of these 52 cases, 34 were male, and 18 were female. A 10-color FC panel was used to detect the expression of CD54 on lymphoma cells. The expression of CD54 was calculated as the mean fluorescence index ratio (MFIR) and was described as the mean ± standard error of the mean (SEM).ResultsUp to 18/52 (34.62%) of BM specimens abnormally expressed an increased level of CD54, including 1/10 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 9/13 cases of mantle cell lymphoma (MCL), 2/14 cases of follicular lymphoma (FL), 5/9 cases of marginal zone lymphoma (MZL), and 1/3 cases of high-grade B-NHL (HG B-NHL). The expression level of CD54 was significantly increased in MCL cases (53.41 ± 11.04) compared with CLL/SLL cases (11.66 ± 2.79) and FL cases (13.49 ± 2.81). The lowest percentage of CD54-positive B-cells attained 0.13%. In 5/9 cases of MZL and 1/3 cases of HG B-NHL, increased expression of CD54 was the only abnormal immunophenotype detected besides Ig light-chain restriction. No aberrant CD54 expression was identified by FC in lymphoplasmacytic lymphoma (LPL) (0/2) and Burkitt lymphoma (BL) (0/1) cases. Aberrant expression of CD54 was not related to plasma cell differentiation.ConclusionLymphoma cells, especially in MCL and MZL cases, frequently show increased expression of CD54. Such aberrant expression is not related to plasma cell differentiation. We highly recommend adding CD54 to the FC screening panel to detect BM involvement in patients with B-NHL.

THE EFFECT OF COMORBIDITY AND BODY MASS INDEX ON SURVIVAL IN PATIENTS WITH MARGINAL ZONE LYMPHOMA

Marginal zone lymphoma is a biologically and clinically heterogeneous group of indolent lymphoproliferative diseases, constituting 5-15% of all NHLs (Non-Hodgkin Lymphoma) 1 . By the World Health Organization; subgroups as extranodal marginal zone lymphoma (ENMZL, MALT lymphoma, Maltoma), nodal marginal zone lymphoma (NMZL), splenic marginal zone lymphoma (SMZL) constitute 70%, 20%, 10% of MZL (Marginal Zone Lymphoma) cases, respectively. A total of 50 patients with a diagnosis of MZL who applied to our hospital between 2013 and 2021 were included in this retrospective study. All analyzes were performed on SPSS v21. The Kolmogorov-Smirnov test was used for normality control. Data are given as mean ± standard deviation for continuous variables and frequency for categorical variables. Survival times were calculated using the Kaplan Meier method. Cox regression analysis (enter method) was performed to identify important prognostic factors. p&lt;0.05 values were accepted as statistically significant results. The mean age of 50 people in the study group was 62.88 ± 11.50 years and ranged from 34 to 84 years. 50% of the participants were male and 50% were female . The mean follow-up period of the patients was 51.80 ± 27.47 months. It was observed that none of the parameters measured in the study, such as age, gender, body mass index, diabetes, heart disease, thyroid diseases, non-hematological malignancies, chemotherapy, and radiotherapy intake, had an effect on survival. Age at diagnosis should be considered in risk assessment of patients with marginal zone lymphoma. It is thought that the fact that the patients are predominantly in the advanced stage MZL group, and the relatively short follow-up period compared to the indolen lymphoma group, has an effect on the absence of a determining effect of comorbid diseases on mortality. Prognostic markers determined by multicenter and detailed studies are needed to provide a better prediction.

Comprehensive Genomic Profiling (CGP) Informs Molecular Diagnosis, Prognosis, and Therapeutic Decision-Making for Patients with Angioimmunoblastic T-Cell Lymphoma (AITL)

Background: AITL, under the 2016 WHO umbrella classification of nodal peripheral T cell lymphomas (PTCL) with a T follicular helper (TFH) phenotype, accounts for ~20% of all PTCL cases. Genomic analysis has revealed recurrent somatic mutations, such as RhoA G17V, that are hallmarks of AITL. Overlapping genomics have been observed in other PTCL subgroups, such as PTCL not otherwise specified (PTCL-NOS). We and others have reported frequent co-occurrence of RhoA G17V with mutations in the epigenetic regulators TET2 and IDH2R172 in AITL (Morley Blood 2015). Since treatment for the disease remains unsatisfactory, efforts are underway to assess the clinical utility of genomic information to guide therapy. The current study aimed to comprehensively assess the genomic landscape of AITL further, including identification of diagnostically and therapeutically relevant alterations.Methods: We explored the FoundationCORE™ database (Foundation Medicine Inc, Cambridge, MA) for cases assigned as AITL or harboring RhoA G17V positivity irrespective of disease ontology. This led to the inclusion of 42 cases: confirmed AITL (concordant diagnoses by internal and external pathologists, 29), suspected AITL (discordant diagnoses, 9), lymph node lymphoma NOS (PTCL, 1), or other neoplasm [pleomorphic myxofibrosarcoma (MFS), 1; marginal zone lymphoma (MZL), 1; cutaneous T-cell lymphoma (CTCL), 1]. Median cohort age was 65.5 years, 65 years for the AITL-specific subset; range for both, 34-88y. Pathology reports indicated Epstein-Barr virus positivity in 16/38 of AITL cases and prior autologous stem cell transplant in 4/38. DNA and RNA were extracted from formalin-fixed paraffin embedded samples or peripheral blood, and CGP performed using the CLIA-certified, NYS-approved, CAP-accredited FoundationOne® Heme assay (He Blood 2016).Results: RhoAG17V was seen in 57% (24/42) of cases in the cohort, including 53% (20/38) of AITL samples and in 1 case each of MFS, MZL, CTCL, and PTCL. Confirmed AITL harbored RhoAG17V in 52% (15/29), and suspected AITL in 56% (5/9), of samples. TET2 mutations (m TET2) were found in 89% of AITLs (26/29, confirmed; 8/9, suspected), and in 1/1 PTCL; as reported previously, m TET2 was not identified in the MFS, MZL, or CTCL. IDH2 mutations (m IDH2), all occurring at R172, were seen in 16% (6/38) of AITL cases, with all 6 co-occurring with RhoAG17V plus m TET2 . DNMT3A mutations (m DNMT3A) were seen in 32% (12/38) of AITLs (9/29, confirmed; 3/9, suspected) and in the single PTCL. RhoAG17V co-occurred with m TET2 (but notm DNMT3A orm IDH2) in 26% (10/38), m TET2 plus m DNMT3A in 7.9% (3/38), and m TET2, mDNMT3A, plus m IDH2 in 7.9% (3/38) of cases; all RhoAG17V cases(20/20) co-occurred with m TET2 . TP53 mutation was seen in 21% (8/38) of AITL cases. Other recurrent somatic mutations included BRCA1 or BRCA2 in 7.9% (3/38), CTNNB1 in 7.9% (3/38), and KRAS, ATM or STAT3 in 2.6% (1/38), of AITL samples. Assessment of tumor mutational burden (TMB), a biomarker for checkpoint inhibitor efficacy in solid tumors, revealed low TMB (<6 mutations/Mb) in 8/10 AITL cases and intermediate TMB (TMB-Intermediate, 6-19 mutations/Mb) in 2/10.Conclusion: This study utilized CGP to explore alterations of diagnostic and therapeutic potential in AITL. Confirming prior studies, in a significant proportion of AITL cases RhoAG17V co-occurred with m TET2 and m IDH2 ; all AITL cases positive for RhoAG17V had concurrent m TET2. We also found RhoAG17V, but not m TET2 or m IDH2, in solitary cases of MZL, MCL, and CTCL.Taken together, co-occurrence of RhoAG17V and m TET2 may provide greater specificity for AITL diagnosis than RhoAG17V alone. We also detected putative actionable targets in AITL. While predictors of response to hypomethylating agents (e.g. m TET2, m IDH2) were seen in most cases, a subset were found to have mutations in BRCA1/2 (3 pts), KRAS (1 pt), CTNNB1 (3 pts), or STAT3 (1 pt). These findings suggest alternative therapeutic opportunities in AITL (e.g. inhibitors of PARP, MEK, mTOR, and STAT3). We further report that mutational burden in AITL is generally low; however, a subset of cases (2/10) were TMB-Intermediate. Although the predictive power of TMB in lymphoma is unclear, in some solid tumors TMB-Intermediate status predicts response to immune checkpoint inhibition. In total, our findings highlight the utility of CGP to identify alterations that may influence the clinical management of AITL. DisclosuresMorley:Foundation Medicine: Employment, Other: Stock. He:Foundation Medicine, Inc: Employment, Other: Stock. Bailey:Foundation Medicine: Employment, Other: stock. Nahas:Foundation Medicine inc: Employment, Other: stockholder. Heilmann:Foundation Medicine, Inc: Employment, Other: Stockholder. Chudnovsky:Foundation Medicine, Inc: Employment, Other: Stockholder. Fabrizio:Foundation Medicine, Inc: Employment, Other: Stockholder. Ali:Foundation Medicine, Inc: Employment, Other: Stock. Lipson:Foundation Medicine: Employment, Other: stock. Stephens:Foundation Medicine Inc.: Employment, Equity Ownership. Ross:Foundation Medicine Inc: Employment, Other: stockholder. Miller:Foundation Medicine: Employment, Other: Stock. Severson:Foundation Medicine: Employment, Other: Stock. Vergilio:Foundation Medicine: Employment, Other: Stock. Erlich:Foundation Medicine: Employment, Other: stock. Mughal:Foundation Medicine, Inc: Employment, Other: Stock.

Epidemiology of Marginal Zone Lymphoma.

In 2016 there were an estimated 7,460 newly diagnosed patients with marginal zone lymphoma (MZL) in the US, which comprised 7% of all mature non-Hodgkin lymphomas (NHL). Based on data from the US SEER-18 program from 2001-2017, the age-standardized incidence rate for MZL was 19.6 per 1,000,000 person-years; 9% of MZL cases were splenic MZL (SMZL), 30% nodal MZL (NMZL), and 61% extranodal MZL (EMZL) of mucusa-associated lymphoid tissue (MALT). Incidence rates were slightly higher in men for SMZL and NMZL, but similar for EMZL, and increased steeply with age for all MZL subtypes. The incidence (age-standardized per 1,000,000) of MZL was highest among non-Hispanic whites (20.7), followed by Hispanics of all races (17.6), non-Hispanic blacks (15.4), and Asian/Pacific islanders (15.0). The incidence of MZL increased +1.0% per year in the US from 2001-2017, with increases reported in other countries during this timeframe. The 5-year relative survival rate for MZL in the US was 89.8% and was similar across racial/ethnic groups and by sex; survival rates have been increasing in the US and other countries. Established risk factors for MZL (or MZL subtypes) include family history of NHL, genetic loci in the HLA region, Helicobacter pylori infection (gastric MALT lymphoma), and several autoimmune diseases (Sjögren syndrome, systemic lupus erythematosus and Hashimoto thyroiditis), with strong (but not definitive) evidence for Chlamydia psittaci (ocular adnexal MALT lymphoma), Borrelia burgdorferi (cutaneous MZL), hepatitis C virus, human immunodeficiency virus, and solid organ transplantation. Promising risk factors that require additional study include other infections, other autoimmune conditions, trichloroethylene exposure, certain occupations, hair dye, cigarette smoking, sun exposure (protective), and alcohol use (protective). MZL is a model of an antigen-driven malignancy, where epidemiologic risk factors, tissue-specific factors, and host immune response (including the impact of chronic inflammation and immunosuppression) drive lymphomagenesis with implications for prevention.

Metachronous Marginal Zone Lymphoma Followed by a Peripheral T-Cell Lymphoma in the Same Patient. Report of Two Cases and Review of the Literatures

Marginal Zone Lymphomas (MZL) and Peripheral T Cell Lymphomas (PTCL) are uncommon neoplasms and patients affected by both lymphomas in a lifetime have been rarely reported. Here we present two patients with an initial diagnosis of a MZL who further developed a PTCL. We also present the review of the literature of six other cases of MZL. Half of the cases reported are synchronous and the other half metachronous. Most MZLs reported are MALT subtype. There is no predominant subtype amongst PTCLs. Chronic exposure to proinflammatory cytokines, genetic predisposition or exposure to carcinogenic agents could be possible causes underlying this rare phenomenon.

Clinical and biological features of B-cell neoplasms with CDK6 translocations: an association with a subgroup of splenic marginal zone lymphomas displaying frequent CD5 expression, prolymphocytic cells, and TP53 abnormalities.

A translocation involving the cyclin-dependent kinase 6 (CDK6) gene [t(CDK6)] is a rare but recurrent abnormality in B-cell neoplasms. To further characterise this aberration, we studied 57 cases; the largest series reported to date. Fluorescence in situ hybridisation analysis confirmed the involvement of CDK6 in all cases, including t(2;7)(p11;q21) immunoglobulin kappa locus (IGK)/CDK6 (n=51), t(7;14)(q21;q32) CDK6/immunoglobulin heavy locus (IGH) (n=2) and the previously undescribed t(7;14)(q21;q11) CDK6/T-cell receptor alpha locus (TRA)/T-cell receptor delta locus (TRD) (n=4). In total, 10 patients were diagnosed with chronic lymphocytic leukaemia, monoclonal B-cell lymphocytosis or small lymphocytic lymphoma, and 47 had small B-cell lymphoma (SmBL) including 36 cases of marginal zone lymphoma (MZL; 34 splenic MZLs, one nodal MZL and one bronchus-associated lymphoid tissue lymphoma). In all, 18 of the 26 cytologically reviewed cases of MZL (69%) had an atypical aspect with prolymphocytic cells. Among the 47 patients with MZL/SmBL, CD5 expression was found in 26 (55%) and the tumour protein p53 (TP53) deletion in 22 (47%). The TP53 gene was mutated in 10/30 (33%); the 7q deletion was detected in only one case, and no Notch receptor 2 (NOTCH2) mutations were found. Immunoglobulin heavy-chain variable-region (IGHV) locus sequencing revealed that none harboured an IGHV1-02*04 gene. Overall survival was 82% at 10years and not influenced by TP53 aberration. Our present findings suggest that most t(CDK6)+ neoplasms correspond to a particular subgroup of indolent marginal zone B-cell lymphomas with distinctive features.

Expression of germinal center cell markers by extranodal marginal zone lymphomas of MALT type within colonized follicles, a diagnostic pitfall with follicular lymphoma

We reviewed 341 consecutive cases of marginal zone lymphoma (MZL) (47) or follicular lymphoma (FL) (294) of which 7 were difficult to distinguish due to perceived coexpression of BCL6 and BCL2 by tumor cells in follicular foci. This stimulated us to develop dual BCL6/BCL2 immunohistochemistry, allowing us to assess coexpression among individual cells. Dual staining confirmed coexpression in 6 of 7 cases, all extranodal MZL (ENMZL) based on overall features and representing 13% of MZL in this series. These findings confirm that MZL cells have plasticity regarding protein expression within the germinal center (GC) microenvironment, an important diagnostic pitfall. Intriguingly, in all MZL expressing BCL6, non-neoplastic GC B cells within colonized follicles showed diminished or absent CD10 expression but preserved BCL6 and high ki67. This finding suggests plasticity of CD10 expression in non-neoplastic GC B cells in the context of colonization by MZL, possibly related to NF-kB dysregulation.