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Zone B-cell Lymphoma (zone + b-cell_lymphoma)
Kinds of Zone B-cell Lymphoma Selected AbstractsPlatelet satellitism and lympho-agglutination as presenting finding in marginal zone B-cell lymphomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009Véronique Latger-Cannard No abstract is available for this article. [source] Molecular-cytogenetic comparison of mucosa-associated marginal zone B-cell lymphoma and large B-cell lymphoma arising in the gastro-intestinal tractGENES, CHROMOSOMES AND CANCER, Issue 4 2001Thomas F.E. Barth Extranodal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type may represent a model of lymphoma progression, because a small cell component frequently occurs in the large cell variants. We studied 52 extranodal B-cell lymphomas: 18 extranodal marginal zone B-cell lymphomas of MALT type (MZBL,MT), 7 MZBL,MT of the gastro-intestinal tract with a diffuse large B-cell component (giMZBLplusLBCL), and 27 diffuse large B-cell lymphomas of the gastro-intestinal tract without small cell component (giLBCL). Analytical techniques were comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The translocation t(11;18) was found as the sole aberration in two MZBL,MT only. In contrast to this, t(11;18)-negative MZBL,MT were characterized by frequent gains on chromosome 3 and DNA amplifications on 2p13,p15. Furthermore, we found a clonal lymphoma progression from the small to the large cell component with accumulation of gains and losses of chromosomal material in the large cell component in giMZBLplusLBCL. Aberrations overlapping with MZBL,MT and giMZBLplusLBCL included losses on chromosome 13, amplifications of the REL proto-oncogene, or gains on chromosome 12. In addition, the large cell component revealed gains on 8q24, including amplifications of the MYC proto-oncogene, and losses on 2q. The giLBCL had frequent gains on chromosomes 12 and 9, as well as on 11q, and losses on 6q. We conclude that, based on the distinctive and partly overlapping patterns of genetic aberrations, MALT lymphomas can be divided into different genetic subgroups. © 2001 Wiley-Liss, Inc. [source] Cutaneous marginal zone B-cell lymphoma in the setting of fluoxetine therapy: a hypothesis regarding pathogenesis based on in vitro suppression of T-cell-proliferative responseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2006Thomas S. Breza Jr Introduction:, Drugs may be an important cause of atypical lymphocytic infiltration. Oftentimes, these infiltrates are in the context of pseudolymphomata. We report a patient who developed lymphocytoma cutis temporally associated with initiation of fluoxetine therapy that later went on to develop cutaneous marginal zone B-cell lymphoma. The response of peripheral blood lymphocytes to fluoxetine and other drugs was examined in an attempt to ascertain the potential role for drugs in the propagation of these infiltrates. Materials and Methods:, Routine light microscopic analysis and phenotypic studies were performed on tissue obtained from a skin biopsy. Lymphocyte mitogenic studies were carried out using increasing concentrations of fluoxetine, bupropion, and two anticonvulsants. Results:, An initial biopsy was consistent with lymphocytoma cutis. The patient stopped fluoxetine associated with lesional regression. The lesions recurred despite being off fluoxetine; a repeat biopsy was compatible with marginal zone lymphoma. Lymphocyte proliferation assays revealed a suppressive effect on T-lymphocyte proliferation at physiologic concentrations. Other tested drugs did not have a similar suppressive effect. Conclusion:, Fluoxetine may be associated with pseudolymphomata and marginal zone lymphoma. The inhibitory effects on T-lymphocyte function and more specifically T-suppressor function may lead to excessive antigen-driven B-cell proliferation. [source] Marginal zone B-cell lymphoma of minor salivary gland representing tumor-forming amyloidosis of the oral cavity.JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2006A case report We report here a case of mucosa-associated lymphoid tissue (MALT)-type lymphoma arising from the minor salivary gland of the oral cavity exhibiting tumor-forming amyloidosis. The patient was a 64-year-old Japanese woman who presented with 4-year history of a left soft palate mass. Despite multiple and multifocal recurrences including the lip, soft palate, tongue, oral base and vocal code and soft palate, the tumor remained localized in the upper aerodigestive tract, and the patient did not develop multiple myeloma during the course of disease. Histologically, the majority of the lesion was occupied by amyloid deposition. Only the periphery of the lesion contained numerous plasmacytoid cells, along with occasional centrocyte-like cells. In addition, lymphoepithelial lesion and follicular colonization were noted. The present case indicates that primary minor salivary gland MALT-type lymphoma appears to be the cause of tumor-forming amyloidosis of the upper aerodigestive tract including the larynx. [source] Thymic epithelial cells expressed unusual follicular dendritic cell markers: Thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuePATHOLOGY INTERNATIONAL, Issue 6 2008Atsuko Masunaga Described herein is a case of thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Using immunohistochemical double staining it was found that most of the thymic lymphoid follicles in this case possessed cytokeratin-positive and follicular dendritic cell (FDC) marker-positive cells. Moreover, using immunoelectron microscopy it was confirmed that some of the double-positive cells were thymic epithelial cells. The candidate of cytokeratin subtype expressed on the double-positive cells was cytokeratin 1 (CK1), which was expressed only by the epithelium of Hassall's corpuscles in thymuses from age-matched patients with myasthenia gravis. The present case indicates a possibility that some thymic epithelial cells become FDC, although it was uncertain whether they were derived from the epithelia of Hassall's corpuscles or whether they were at the same differentiation stage as Hassall's corpuscles. [source] Rearrangement of immunoglobulin heavy and light chains and VH family in thyroid and salivary gland lymphomasPATHOLOGY INTERNATIONAL, Issue 12 2002Kei Kato It is often difficult to differentiate extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) from non-neoplastic inflammatory conditions. Demonstration of clonal lymphoid proliferation by molecular procedures is important for accurate diagnosis. We examined the clonal population of B-cell lymphomas in nine cases of thyroid and two cases of salivary gland B-cell lymphoma using semi-nested polymerase chain reaction (PCR)-based assay for IgH gene arrangement and reverse transcription (RT)-PCR single-strand conformation polymorphism (SSCP) for the detection of IgL gene rearrangement. Clonality was evident in nine out of 11 cases of B-cell lymphomas examined by PCR, and in six of eight cases by RT-PCR SSCP. In addition, analysis of VH families was performed in eight cases. Although VH3 family was frequently used, each case demonstrated the VH4, VH5 or VH6 family. It is possible that the normal counterpart of thyroid or salivary gland lymphoma might be different from peripheral blood B lymphocytes, which usually use VH3 family. Our results indicate that although no clonality was noted in one case by both PCR and SSCP, these molecular methods are useful as supplementary diagnostic tests for both thyroid and salivary gland lymphomas. [source] Relapsed or refractory nongastric marginal zone B-cell lymphoma: Multicenter retrospective analysis of 92 cases,AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009Sung Yong Oh Over its long survival duration, marginal zone B-cell lymphoma (MZL) routinely involves frequent relapses. In this study, we conducted a retrospective analysis to identify the clinical features and outcomes of relapsed or refractory MZL. From 1995 to 2008, a total of 92 patients with relapsed MZL were retrospectively analyzed. The median age of our subjects was 53.5 years (range: 23,82 years). The most common primary sites of involvement were the orbit and ocular adnexa (28.3%) followed by the lymph node and lymphatic organs (23.9%), and multiple mucosa-associated lymphoid tissue (MALT) sites (13.0%). The median time to relapse from initial diagnosis was 25.5 months. Of the 53 patients with Stage I or II at diagnosis, 42 patients (79.2%) evidenced locoregional recurrence. Among these locoregional relapsed patients, 27 patients achieved CR (54.1%) or PR (18.9%). In addition to the 39 patients initially in advanced Stage III or IV, a total of 50 patients were in advanced stage at relapse. Among those patients with advanced stage at relapse, 44 patients were treated. The overall response rate was 54.5% (24 patients), with 18 CRs and 6 PRs. The median time to progression (TTP) was 34.1 months (95% CI: 11.3,56.9 months) and the estimated 5-year overall survival (OS) was 84.3%. The majority of them was controlled well with salvage treatment, and could achieve prolonged survival. However, patients' refractory to initial therapy and advanced relapse evidenced shorter TTP and OS. Thus, we need to consider more aggressive treatment in cases of refractory MZL or advanced relapsed MZL. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Marginal zone B-cell lymphoma of the sinonasal tract in an eleven-year-old girlPEDIATRIC BLOOD & CANCER, Issue 6 2003Jean-Louis Dargent MD No abstract is available for this article. [source] Nodal marginal zone B-ceil lymphoma resembling plasmacytoma arising from a plasma cell variant of localized Castleman's diseaseAPMIS, Issue 7-8 2002a case report Nodal marginal zone B-cell lymphoma (NMZBL) occasionally represents prominent plasma cell differentiation. Recently, primary lymph node plasmacytoma has been suggested to represent an extremely plasmacytic differentiation of NMZBL. We here report a case of NMZBL showing histological features resembling plasmacytoma arising from a plasma cell variant of localized Castleman's disease (PCLCD). The patient was a 69-year-old Japanese female with a 20-year history of a right inguinal mass. Histologically, a prominent proliferation of plasma cells occupied the interfollicular area of the central portion of the lymph node, whereas centrocyte-like (CCL) cells were the main cellular component in the peripheral portion of the lymph node. Although most of the plasma cells were mature ,Marshalko-type', occasional atypical forms with enlarged nuclei were also present. The majority of the lymphoid follicles had atrophic or regressive germinal centers. A few lymphoid follicles were colonized by CCL cells. Immunohistochemistry study revealed that both plasma cells and some CCL cells had a monotypic intracytoplasmic lambda light chain. When monoclonal plasma cell infiltration is observed in PCLCD, the light chains are mostly restricted to the lambda chain. This case suggests that some plasma cell-containing tumors arising from PCLCD may represent a variant of NMZBL. [source] Combination therapy with rituximab and intravenous or oral fludarabine in the first-line, systemic treatment of patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type,,CANCER, Issue 22 2009Antonio Salar MD Abstract BACKGROUND: Currently, there are no consensus guidelines regarding the best therapeutic option for patients with extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue (MALT) type. METHODS: Patients with systemically untreated or de novo extranodal MALT lymphoma received rituximab 375 mg/m2 intravenously on Day 1 and fludarabine 25 mg/m2 intravenously on Days 1 through 5 (Days 1-3 in patients aged >70 years) every 4 weeks, for 4 to 6 cycles. After the first cycle, oral fludarabine could be given orally at 40 mg/m2 on the same schedule. After 3 cycles, a workup was done. Patients who achieved a complete remission (CR) received an additional cycle, and patients who achieved a partial remission (PR) received a total of 6 cycles. RESULTS: Twenty-two patients were studied, including 12 patients with gastric lymphoma and 10 patients with extragastric MALT lymphoma. Six patients (27%) had stage IV disease. In total, 101 cycles were administered (median, 4 cycles per patients). After the third cycle, 13 patients (62%) achieved a CR, and 8 patients (38%) achieved a PR. Primary extragastric disease was an adverse factor to achieve CR after 3 cycles of chemotherapy (hazard ratio, 23.3; 95% confidence interval, 2.0-273.3). At the end of treatment, the overall response rate was 100%, and 90% of patients achieved a CR. The progression-free survival rate at 2 years in patients with gastric and extragastric MALT lymphoma was 100% and 89%, respectively. Toxicities were mild and mainly were hematologic. CONCLUSIONS: Combination therapy with rituximab and fludarabine is a very active treatment with favorable safety profile as first-line systemic treatment for patients with extranodal MALT lymphoma. Cancer 2009. © 2009 American Cancer Society. [source] Radiotherapy for extranodal, marginal zone, B-cell lymphoma of mucosa-associated lymphoid tissue originating in the ocular adnexaCANCER, Issue 4 2003A multiinstitutional, retrospective review of 50 patients Abstract BACKGROUND Due to the small number of patients and differences in the pathologic classification in most radiotherapy series, information regarding the adequacy of tumor control in patients with ocular-adnexal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is limited. METHODS A multiinstitutional, retrospective study was performed on 50 patients with Stage IE ocular-adnexal MALT lymphoma who were treated with radiotherapy between 1989 and 1999. The impact of patient characteristics and other variables on tumor control was analyzed. RESULTS Responses to radiotherapy include a complete response (CR) in 26 patients, a partial response (PR) in 20 patients, and no change in 4 patients. Forty-nine of 50 patients obtained tumor control in the ocular adnexa at 24 months. Overall, 6 patients exhibited disease recurrence at 4,97 months. Three patients developed recurrence in the ocular adnexa. Two patients had isolated extranodal failure involving the oral floor and the submandibular gland, and one patient experienced failure in the neck lymph node. The initial tumor response had a marginal impact on the development of recurrence. None of the 26 patients who achieved a CR experienced ocular-adnexal recurrence. All three patients who experienced local treatment failure belonged to the initial PR group. In total, five of six patients who developed recurrent disease had obtained a PR after initial radiotherapy. Age, gender, tumor location, and dose of radiotherapy did not influence the development of recurrence. There was only one death due to lymphoma. The 5-year overall survival rate was 91% with a median follow-up of 46 months. CONCLUSIONS Radiotherapy offers excellent local control with a prolonged clinical course for patients with MALT lymphoma in the ocular adnexa. The initial response to radiotherapy marginally influenced the probability of recurrence. Cancer 2003;98:865,71. © 2003 American Cancer Society. DOI 10.1002/cncr.11539 [source] Clinical implications of nodal marginal zone B-cell lymphoma among Japanese: study of 65 casesCANCER SCIENCE, Issue 1 2007Masaru Kojima To clarify the clinical presentation and outcome of nodal marginal zone B-cell lymphoma (NMZBL), 65 Japanese patients with this disease were studied and compared with the published literature from western countries. The clinical findings of our 65 cases were similar to those of their cases in some aspects: (1) 58% of the patients were >60 years old (median age, 64 years); (2) there was a slight female predominance; (3) 90% of the patients exhibited asymptomatic lymphadenopathy in the head and neck area; (4) only a minority of patients had B symptoms (6%) and poor performance status (8%); and (5) only 5% of patients were positive for M-protein. However, the 65 patients in this series exhibited relatively longer 5-year overall survival (85%) and failure-free survival (60%) than the NMZBL series published in western literature, suggesting that NMZBL should be classified as indolent lymphoma. Moreover, based on the histological findings, we further classified four histological subtypes as follows: (1) splenic type (n = 7); (2) floral type (n = 9); (3) mucosa-associated lymphoid tissue (MALT) type (n = 29); and (4) diffuse large B-cell lymphoma (DLBCL) + MALT type (n = 20). DLBCL + MALT type exhibited significantly poorer 5-year overall survival than the splenic variant. The recognition of DLBCL + MALT type appears important. No API2,MALT1 fusion transcript was detected in any of the 14 cases examined. (Cancer Sci 2007; 98: 44,49) [source] Microsatellite Instability and k- ras, p53 Mutations in Thyroid LymphomaCANCER SCIENCE, Issue 3 2000Tetsuya Takakuwa Patho-epidemiological studies showed that thyroid lymphoma (TL) arises in inflammatory lesions of chronic lymphocytic thyroiditis (CLTH). Replication error (RER) is found in inflammatory lesions and associated cancer, suggesting that chronic inflammation could be a risk factor for neoplastic development through causing RER. To clarify whether RER is involved in the pathogenesis of TL, we examined the microsatellite instability (MSI) in 9 cases with CLTH and 19 with TL, including 10 diffuse large B-cell lymphoma (DLBL), 4 follicle center cell lymphoma, 3 marginal zone B-cell lymphoma of extranodal (MALT) type, and 2 lymphoplasmacytic type. Sixteen distinct microsatellite repeats were analyzed. Mutations of p53 and k- ras genes were also examined. When alterations at 2 or more microsatellite loci were judged as positive, only 5 DLBL cases exhibited MSI. The frequency of MSI in DLBL was significantly higher than that in other types of TL and CLTH (P < 0.05). Four of 19 cases (21.1%) showed point mutation of the k- ras gene. The k- ras mutations occurred in the cases with DLBL with RER, and four of five cases with RER had a k- ras mutation, indicating a close association between RER and k- ras mutation. p53 mutations were not found in the CLTH. Two of 19 TL cases showed mutations of p53 gene. There was no significant association between RER and p53 mutation. These findings indicate that genomic instability contributes to the progression of TL from low grade to high grade, but not to the development of low grade lymphoma in CLTH lesions. [source] Molecular-cytogenetic comparison of mucosa-associated marginal zone B-cell lymphoma and large B-cell lymphoma arising in the gastro-intestinal tractGENES, CHROMOSOMES AND CANCER, Issue 4 2001Thomas F.E. Barth Extranodal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type may represent a model of lymphoma progression, because a small cell component frequently occurs in the large cell variants. We studied 52 extranodal B-cell lymphomas: 18 extranodal marginal zone B-cell lymphomas of MALT type (MZBL,MT), 7 MZBL,MT of the gastro-intestinal tract with a diffuse large B-cell component (giMZBLplusLBCL), and 27 diffuse large B-cell lymphomas of the gastro-intestinal tract without small cell component (giLBCL). Analytical techniques were comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The translocation t(11;18) was found as the sole aberration in two MZBL,MT only. In contrast to this, t(11;18)-negative MZBL,MT were characterized by frequent gains on chromosome 3 and DNA amplifications on 2p13,p15. Furthermore, we found a clonal lymphoma progression from the small to the large cell component with accumulation of gains and losses of chromosomal material in the large cell component in giMZBLplusLBCL. Aberrations overlapping with MZBL,MT and giMZBLplusLBCL included losses on chromosome 13, amplifications of the REL proto-oncogene, or gains on chromosome 12. In addition, the large cell component revealed gains on 8q24, including amplifications of the MYC proto-oncogene, and losses on 2q. The giLBCL had frequent gains on chromosomes 12 and 9, as well as on 11q, and losses on 6q. We conclude that, based on the distinctive and partly overlapping patterns of genetic aberrations, MALT lymphomas can be divided into different genetic subgroups. © 2001 Wiley-Liss, Inc. [source] 18F-FDG uptake and its clinical relevance in primary gastric lymphomaHEMATOLOGICAL ONCOLOGY, Issue 2 2010Jun Ho Yi Abstract We studied the clinical relevance of 18F-fluorodeoxyglucose (18F-FDG) uptake in patients with primary gastric lymphoma underwent positron emission tomography (PET)/ computed tomography (CT) scan. Forty-two patients with primary gastric lymphoma were analysed: 32 diffuse large B-cell lymphomas (DLBCL) and 10 extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas). The PET/CT scans were compared with clinical and pathologic features, and the results of CT and endoscopy. Nine patients were up-staged based on the results of their PET/CT scan compared to CT (seven DLBCLs, two MALT lymphomas) while six patients were down-staged by the PET/CT scan. The standard uptake value (SUV) was used as an indicator of a lesion with a high metabolic rate. The high SUVmax group, defined as an SUVmax , median value, was significantly associated with an advanced Lugano stage (p,<,0.001). Three patients with DLBCL, who showed an initially high SUVmax, died of disease progression. Among 24 patients for whom follow-up PET/CT scan with endoscopy was performed, 11 patients with ulcerative or mucosal lesions showed residual 18F-FDG uptake. All of these gastric lesions were grossly and pathologically benign lesions without evidence of lymphoma cells. In conclusion, PET/CT scan can be used in staging patients with primary gastric lymphoma; however, the residual 18F-FDG uptake observed during follow-up should be interpreted cautiously and should be combined with endoscopy and multiple biopsies of the stomach. Copyright © 2009 John Wiley & Sons, Ltd. [source] p53 expression, K- ras gene mutation and microsatellite instability in gastric B-cell lymphomasJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2003TORU HIYAMA Abstract Background and Aims:, Genetic mechanisms involved in the development of gastric B-cell lymphomas remain unclear. The aim of the present study was to clarify the roles of mutations of the p53 and K- ras genes, and microsatellite instability (MSI) in the development of gastric B-cell lymphomas. Methods:, We investigated p53 immunoreactivity, mutations of the K- ras gene, and MSI in 27 gastric marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type (MZBCL) and 24 diffuse large B-cell lymphomas (DLBCL). p53 immunoreactivity was examined using a monoclonal antibody, DO-7. Mutation of the K- ras gene was detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. MSI was examined at five microsatellite loci with a microsatellite assay. Cases were classified as having high-frequency MSI (MSI-H) (, 2 loci showing instability), low-frequency MSI (MSI-L) (only one locus showing instability), or as microsatellite stable. Results:, p53 immunoreactivity was detected in 1 of 16 (6%) MZBCL and 8 of 19 (42%) DLBCL. Frequency of p53 immunoreactivity in DLBCL was significantly higher than that in MZBCL (P = 0.018). MSI-H was detected only in 1 of 20 (5%) DLBCL. None of the cases examined showed mutation of the K- ras gene. Conclusions:, These data suggest that mutations of the p53 gene may play an important role in the development of gastric DLBCL, and that mutations of the K- ras gene and MSI may be involved in little part of the development of gastric B-cell lymphomas. [source] Bcl-2, Bcl-6 and CD10 expression in cutaneous B-cell lymphoma: further support for a follicle centre cell origin and differential diagnostic significanceBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2003J.J. Hoefnagel Summary Background Primary cutaneous follicle centre cell lymphomas (PCFCCLs) are the most common type of cutaneous B-cell lymphoma. There is ongoing discussion on the origin of the neoplastic B cells in these PCFCCLs, and consequently on their relation to the groups of primary cutaneous marginal zone B-cell lymphomas (PCMZLs) and nodal follicular lymphomas. Objectives To define better the neoplastic B cells in PCFCCLs, and to find out if differences in the expression of the antiapoptopic protein Bcl-2, and Bcl-6 and CD10, molecules which are normally expressed by the neoplastic B cells in nodal follicular lymphomas, might have diagnostic or prognostic significance in cutaneous B-cell lymphoproliferative disorders. Methods Pretreatment biopsies of well-defined groups of PCFCCL (n = 24), PCMZL (n = 14), primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg; n = 19), secondary cutaneous follicular lymphoma (n = 3) and cutaneous pseudo-B-cell lymphoma (n = 6) were investigated by immunohistochemistry for expression of Bcl-2, Bcl-6 and CD10. Results The PCFCCLs consistently expressed Bcl-6, whereas CD10 and Bcl-2 were expressed in only one and two of 24 cases, respectively. In contrast, PCMZLs were always negative for Bcl-6 and CD10, but were Bcl-2 positive, whereas skin and lymph node localizations of secondary cutaneous follicular lymphomas consistently expressed all of Bcl-2, Bcl-6 and CD10. Reactive follicle centre cells in pseudo-B-cell lymphomas expressed Bcl-6 (six of six cases) and CD10 (five of six cases), but not Bcl-2. PCLBCL-leg was Bcl-6 positive and CD10 negative in all cases, irrespective of clinical outcome, and strongly expressed Bcl-2 protein in all but two cases. Conclusions The results of the present study provide further support for the follicle centre cell origin of both PCFCCL and PCLBCL-leg, and indicate that staining for Bcl-2, Bcl-6 and CD10 can serve as an important adjunct in the differential diagnosis of cutaneous B-cell lymphoproliferative disorders. [source] 4368: Hypermethylation of tumour suppressor genes in ocular adnexal lymphomaACTA OPHTHALMOLOGICA, Issue 2010H MA Purpose Promoter hypermethylation occurs in various tumours, including ocular adnexal lymphomas (OAL), and is a mechanism by which tumour suppressor genes can be inactivated during tumourigenesis. This study aimed to investigate the levels of hypermethylation and specific genes that are hypermethylated in different subtypes of OAL using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and pryrosequencing. Methods DNA was extracted from formalin-fixed, paraffin-embedded tissues from 33 extra-marginal zone B-cell lymphomas (EMZL) and 37 non-EMZL. Using two MS-MLPA assays (MRC-Holland) the methylation status and copy number of 36 genes was detected. MS-MLPA results were validated using pyrosequencing. Results MLPA and pyrosequencing results were comparable with 75-100% concordancy. Ten common genes were hypermethylated in the EMZL and non-EMZL, diffuse large B-cell lymphomas (DLBCL) and mantle cell lymphomas (CDH13, DAPK1, ESR1, GATA5, IGSF4, PAX6, RAR,, THBS1, TIMP3, and WT1). In non-EMZLs, a greater number of genes showed hypermethylation when diagnosed in the orbit and patients had a poorer prognosis. Deletion of the 9p21 region was seen in 7/13 DLBCLs including the p14ARF, p15 and p16 genes. Conclusion Hypermethylation is a feature of OALs suggesting a role for epigenetic deregulation in OAL development. In non-EMZLs greater epigenetic deregulation may be indicative of poorer patient prognosis. We hypothesise that EMZL, DLBCL and mantle cell lymphomas share a similar epigenetic aetiology and that genes in the 9p21 region may be important to DLBCL development. Correlation of hypermethylation and copy number data with clinical presentation and follow-up could reveal biomarkers of diagnostic and prognostic value in OALs. [source] | |||||||||||||||||||||||||