Non-Hodgkin lymphoma involving the parotid gland: CT and MR imaging findings.
ABSTRACT: OBJECTIVES: As an uncommon neoplasm, parotid non-Hodgkin lymphoma (NHL) comprises mucosa-associated lymphoid tissue (MALT) and non-MALT lymphomas. Both types of lymphoma vary in prognosis and treatment. The aim of this study was to explore CT and MRI characteristics of these two types of lymphoma. METHODS: 61 cases of parotid NHL, 34 MALT and 27 non-MALT lymphomas with histopathological confirmation were examined with routine CT and MR scans prior to treatment, and retrospectively reviewed. RESULTS: On CT and MRI, 34 MALT lymphomas presented with 11 solid and 23 solid-cystic forms, whereas 27 non-MALT lymphomas presented with 25 solid and 2 solid-cystic forms (p < 0.01). CONCLUSIONS: Parotid MALT lymphoma is characterized mainly by the solid-cystic form, whereas non-MALT lymphoma is characterized mainly by the solid form. The differences on CT and MRI can offer helpful information for differentiation of both types of parotid NHL.
Project description:Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis.
Project description:BACKGROUND:Cell-mediated immunity is often suppressed in patients with hematological malignancies. Recently, we found that low T cell receptor (TCR)-CD3 signaling was related to abnormal expression of the negative regulator of nuclear factor kappa B (NF-?B) A20 in acute myeloid leukemia. To investigate the characteristics of T cell immunodeficiency in lymphomas, we analyzed the expression features of A20 and its upstream regulating factor mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) and genes downstream of NF-?B in patients with different lymphoma subtypes, including T cell non-Hodgkin lymphoma (T-NHL), B cell non-Hodgkin lymphoma (B-NHL) and NK/T cell lymphoma (NK/T-CL). METHODS:Real-time PCR was used to determine the expression level of the MALT1, MALT-V1 (variant 1), A20 and NF-?B genes in peripheral blood mononuclear cells (PBMCs) from 24 cases with T-NHL, 19 cases with B-NHL and 16 cases with NK/T-CL, and 31 healthy individuals (HI) served as control. RESULTS:Significantly lower A20 and NF-?B expression was found in patients with all three lymphoma subtypes compared with the healthy controls. Moreover, the MALT1 expression level was downregulated in all three lymphoma subtypes. A significant positive correlation between the expression level of MALT1 and A20, MALT1-V1 and A20, MALT1-V1 and NF-?B, and A20 and NF-?B was found. CONCLUSIONS:An abnormal MALT1-A20-NF-?B expression pattern was found in patients with lymphoma, which may result a lack of A20 and dysfunctional MALT1 and may be related to lower T cell activation, which is a common feature in Chinese patients with lymphoma. This finding may at least partially explain the molecular mechanism of T cell immunodeficiency in lymphomas.
Project description:To identify key target genes and activated signaling pathways associated with the pathogenesis of Sjögren's syndrome (SS) by conducting a systems analysis of parotid glands manifesting primary SS or primary SS/mucosa-associated lymphoid tissue (MALT) lymphoma phenotypes.A systems biology approach was used to analyze parotid gland tissue samples obtained from patients with primary SS, patients with primary SS/MALT lymphoma, and subjects without primary SS (non-primary SS controls). The tissue samples were assessed concurrently by gene-expression microarray profiling and proteomics analysis, followed by weighted gene-coexpression network analysis.Gene-coexpression modules related to primary SS and primary SS/MALT lymphoma were significantly enriched with genes known to be involved in the immune/defense response, apoptosis, cell signaling, gene regulation, and oxidative stress. Detailed functional pathway analyses indicated that primary SS-associated modules were enriched with genes involved in proteasome degradation, apoptosis, signal peptides of the class I major histocompatibility complex (MHC), complement activation, cell growth and death, and integrin-mediated cell adhesion, while primary SS/MALT lymphoma-associated modules were enriched with genes involved in translation, ribosome biogenesis and assembly, proteasome degradation, class I MHC signal peptides, the G13 signaling pathway, complement activation, and integrin-mediated cell adhesion. Combined analyses of gene expression and proteomics data implicated 6 highly connected "hub" genes for distinguishing primary SS from non-primary SS, and 8 hub genes for distinguishing primary SS/MALT lymphoma from primary SS.Systems biology analyses of the parotid glands from patients with primary SS and those with primary SS/MALT lymphoma revealed pathways and molecular targets associated with disease pathogenesis. The identified gene modules/pathways provide further insights into the molecular mechanisms of primary SS and primary SS/MALT lymphoma. The identified disease-hub genes represent promising targets for therapeutic intervention, diagnosis, and prognosis.
Project description:Primary Sjogren's syndrome (pSS) confers increased risk for non-Hodgkin lymphoma (NHL) development. Two common polymorphisms, the c. 677C?>?T and c. 1298A?>?C, of the methylene-tetrahydrofolate reductase (MTHFR) gene, an enzyme essential in DNA synthesis and methylation, have been associated with susceptibility to NHL. Herein, we tested the hypothesis that MTHFR variants contribute to pSS-related lymphomagenesis. 356 pSS patients, of whom 75 had MALT and 19 non-MALT NHL and 600 healthy controls were genotyped for the detection of MTHFR polymorphisms. DNA methylation levels were assessed by pyrosequencing of the LINE-1 retroelement promoter in DNA from 55 salivary gland tissues from pSS patients. DNA double-strand breaks were determined in peripheral blood mononuclear cells from 13 pSS patients, using comet assay. ?nalysis according to lymphoma subtype revealed increased frequency of c. 677C?>?T TT genotype and T allele, as well as reduced prevalence of the c. 1298A?>?C C allele in the pSS non-MALT group compared to controls and patients without NHL. MTHFR c. 677C?>?T TT genotype was associated with reduced DNA methylation levels, while MTHFR c. 1298A?>?C AC genotype with reduced DNA double-strand breaks levels. MTHFR variants may be involved in SS non-MALT NHL development, through contribution to defective DNA methylation and genomic instability.
Project description:microRNAs (miRNAs) are small non-coding RNAs that can function as endogenous silencers of target genes and play critical roles in human malignancies. To investigate the molecular pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the miRNA expression profile was analyzed. miRNA microarray analysis with tissue specimens from gastric MALT lymphomas and surrounding non-tumor mucosae revealed that a hematopoietic-specific miRNA miR-142 and an oncogenic miRNA miR-155 were overexpressed in MALT lymphoma lesions. The expression levels of miR-142-5p and miR-155 were significantly increased in MALT lymphomas which do not respond to Helicobacter pylori (H. pylori) eradication. The expression levels of miR-142-5p and miR-155 were associated with the clinical courses of gastric MALT lymphoma cases. Overexpression of miR-142-5p and miR-155 was also observed in Helicobacter heilmannii-infected C57BL/6 mice, an animal model of gastric MALT lymphoma. In addition, miR-142-5p and miR-155 suppress the proapoptotic gene TP53INP1 as their target. The results of this study indicate that overexpression of miR-142-5p and miR-155 plays a critical role in the pathogenesis of gastric MALT lymphoma. These miRNAs might have potential application as therapeutic targets and novel biomarkers for gastric MALT lymphoma.
Project description:Primary intestinal non-Hodgkin lymphoma (NHL) is a heterogeneous disease with regard to anatomic and histologic distribution. Thus, analyses focusing on primary intestinal NHL with large number of patients are warranted.We retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes.B-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ? 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival.The survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might be related to histologic distribution, the proportion of tumor stage, and need for surgical resection.
Project description:Treatment modalities for resistant/relapsing gastric mucosa associated lymphoid tissue (MALT) non-Hodgkin's lymphoma (NHL) are not yet well standardized. In the past, most patients were treated surgically with a gastrectomy, while, more recently, radiotherapy and systemic approaches (chemotherapy and immunotherapy) have been used with improving results.Here, we report the case of a patient affected by MALT NHL resistant to antibiotics, chemotherapy and immunotherapy, who achieved a durable complete remission after radio-immunotherapy treatment with Zevalin ((90)Y ibritumomab-tiuxetan), administered in a single-standard dose. This observation must be confirmed on a larger series but suggests that radio-immunotherapy may be a valid approach in treating relapsing MALT NHL patients, or those resistant to conventional therapies, so avoiding more aggressive and toxic approaches.
Project description:AIMS:To evaluate the chromosomal translocation t(11;18)(q21;q21) in gastrointestinal lymphomas. METHODS:A possible API2-MLT fusion transcript specific to t(11;18)(q21;q21) was examined by means of reverse transcription-polymerase chain reaction (RT-PCR) in tumours from 47 cases of primary gastrointestinal lymphoma (28 low grade mucosa associated lymphoid tissue (MALT) lymphomas, four low grade MALT lymphomas with a high grade component, nine secondary diffuse large B cell lymphomas, four primary diffuse large B cell lymphomas, and two T cell lymphomas). RESULTS:API2-MLT fusion was seen in four of 28 cases of low grade MALT lymphoma, but it was not seen in other types of lymphoma. Among the low grade MALT lymphomas, the fusion transcript was seen more frequently in colonic tumours than in gastric tumours (two of three compared with two of 24) and in tumours with submucosal invasion than in those confined to the mucosa (four of 13 compared with 0 of 15). Helicobacter pylori negative tumours tended to show a higher positive rate than H pylori positive tumours (three of six compared with one of 21). None of the gastric tumours that responded to H pylori eradication expressed the API2-MLT fusion transcript. CONCLUSIONS:t(11;18)(q21;q21) seems to be one of the genetic alterations related to the development of gastrointestinal low grade MALT lymphoma. Such translocations may be predominantly associated with the development of intestinal MALT lymphoma.
Project description:The epidemiology of lymphomas has changed since the use of antiretroviral therapy. The incidence of Non-Hodgkin Lymphomas (NHL) has significantly decreased in high income countries but not in low and middle-income countries where AIDS-related events remain high. This observational study describes the characteristics, infectious complications and main outcomes of patients diagnosed with HIV and lymphoma at the Instituto Nacional de Cancerología.All adults >18 years diagnosed with HIV and lymphoma from January 2010 to December 2017 were included. Information on HIV and lymphoma was collected, as well as the occurrence of co-infections at diagnosis and during therapy. Multiple regression was done with NHL patients to evaluate independent variables associated to death.One hundred fifty three patients were included: 127 patients with NHL (83%) and 26 (17%) with Hodgkin lymphoma (HL). Of the NHL, 49 (38%) were diffuse large B cell Lymphomas (DLBCL), 35 (27%) plasmablastic, 28 (23%) Burkitt, 10 (8%) primary DLBCL of Central Nervous system, 3 (2%) T-cell lymphomas, and 2 (2%) pleural effusion lymphoma. Most patients were diagnosed in an advanced stage: 70% of NHL had a high International Prognostic Index (IPI); 68% of patients had <200?cells/mm. Almost 25% of NHL patients had an opportunistic infection at lymphoma diagnosis. During chemotherapy, 60% of all patients presented with at least 1 serious non-opportunistic infectious complication, and 50% presented 2 or more infectious complications, mostly bacterial infections. Thirty six percent of NHL and 23% of HL died. After adjusting for confounders, the variables associated with death were IPI and lymphoma type.HIV positive patients with lymphoma in our institution are diagnosed with an advanced stage and a high burden of infections complications. Death remains high and the variables strongly associated with death are those related to lymphoma prognosis such as lymphoma type and IPI.
Project description:Human aggressive B-cell non-Hodgkin lymphomas (NHL) encompass the continuum between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL), and display considerable clinical and biologic heterogeneity, most notably related to therapy response. We previously showed that lymphomas arising in the E?-Myc transgenic mouse are heterogeneous, mirroring genomic differences between Burkitt lymphoma and DLBCL. Given clinical heterogeneity in NHL and the need to develop strategies to match therapeutics with discrete forms of disease, we investigated the extent to which genomic variation in the E?-Myc model predicts response to therapy. We used genomic analyses to classify E?-Myc lymphomas, link E?-Myc lymphomas with NHL subtypes, and identify lymphomas with predicted resistance to conventional and NF-?B-targeted therapies. Experimental evaluation of these predictions links genomic profiles with distinct outcomes to conventional and targeted therapies in the E?-Myc model, and establishes a framework to test novel targeted therapies or combination therapies in specific genomically defined lymphoma subgroups. In turn, this will rationally inform the design of new treatment options for aggressive human NHL.