Gastric Diffuse Large B-cell Research Articles

LINTERET DE LILEO-COLOSCOPIE DANS LE BILAN DEXTENSION DU LYMPHOME GASTRIQUE

Gastric lymphomas are rare tumorsand accounts for only 3%. There are two groups of lymphomas: mucosa-associated lymphoid tissue (MALT) gastric lymphoma or diffuse large B-cell lymphoma. The management of this tumordepends on the histological grade and extension workup. It includes a clinical examination, radiological and endoscopic work-up including a total ileo-coloscopy in order to look for a synchronous intestinal localization.We report in this article the experience of our department concerning the interest of ileo-coloscopy in the assessment of gastric lymphoma extension. We included 87 patients followed for gastric lymphoma, 34 of whom underwent ileo-coloscopy preceded by thoracoabdomino-pelvic CT scan. Colonoscopy revealed an ulcerative colonic process in only 02 patients, whose CT scan also revealed a colonic thickening and the anatomopathological study was in favour of a colonic lymphoma.In the light of these results, is it not necessary to reconsider the interest of an invasive procedure in the work-up of gastric lymphoma with a normal abdominal scan?

Possibility of PET/CT in Patients’ with Extranodal Diffffuse Large B-Cell Lymphoma of Stomach at Difffferent Treatment Stages

Introduction: Gastric extranodal diffuse large B-cell lymphoma (DLBCL) is one of the most common types of lymphoma. The management of patients with DLBCL of s tomach includes immunochemotherapy, radiotherapy and surgery, but there is no standard approach. Endoscopy as a part of diagnostic workup is obligatory, but using positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) is not obligatory at different stages of observation and treatment.Purpose: To evaluate the diagnostic precision of PET/CT with 18F-FDG in both assesement and treatment stages for patients with extranodal DLBCL of stomach. Materials and methods. In this study we describe early and late therapeutic outcomes of 23 patients with primary extranodal DLBCL of stomach, treated in our center between 2010 and 2018, who received R-CHOP immunochemotherapy regimen. There were PET/CT and fibrogastroduodenoscopy (EGD) provided for all patients on every stage of assessment.Results: The diagnostic accuracy of PET/CT before the treatment was 87 %, after immunochemotherapy — 91,3 %, after radiotherapy — 100 %.Conclusions: This study shows up the role of including PET/CT scan as an observation method for patients with extranodal DLBCL of stomach on each stage of treatment and response assessment, especially for long-term prognosis evaluation.

Synchronous gastric cancer and primary lymphoma of right adrenal gland: a case report

This report presents an extremely rare case of synchronous gastric cancer and primary adrenal diffuse large B-cell lymphoma (DLBCL). An 82-year-old man underwent computed tomography, which revealed a heterogeneous appearing and hypodense adrenal mass and a gastric mass with no enlarged lymph nodes in the neck, mediastinum, abdomen, and inguinal region. Upper gastrointestinal endoscopy revealed a protruding gastric tumor. The specimens obtained from endoscopic biopsy were histologically confirmed to be adenocarcinoma. The hormonal findings eliminated functional adrenal tumor. The patient underwent distal gastrectomy with regional lymph node resection for gastric cancer and incisional biopsy of the adrenal mass. Based on the pathological findings, diagnoses of mixed mucinous and tubular adenocarcinomas of the stomach and adrenal DLBCL were confirmed. Postoperation, the patient received rituximab combined with low-dose doxorubicin, cyclophosphamide, vincristine, and prednisone (R-miniCHOP). Six courses of R-miniCHOP were planned, but were completed in only one course at the patient’s request. The patient died 2 months after surgery.

Efficacy of surgery and rituximab in primary gastric diffuse large B-cell lymphoma

目的探讨手术联合化疗与单纯化疗对原发胃弥漫大B细胞淋巴瘤（PGDLBCL）患者生存的影响，并分析化疗过程中联合应用利妥昔单抗（R）对其预后的影响。方法回顾性分析83例PGDLBCL患者的临床资料，并分析外科手术及利妥昔单抗对患者生存的影响。结果83例患者中男43例，女40例，中位年龄52 (20~76）岁，中位随访时间为36 (4~59）个月。手术联合化疗组（40例）和单纯化疗组（43例）患者的5年总生存（OS）率分别为68.4%、85.9%（P=0.117），疾病无进展生存（PFS）率分别为66.7%、82.6%（P=0.258），差异均无统计学意义。手术联合化疗患者中R-CHOP方案组（23例）和CHOP方案组（17例）患者的5年OS率分别为73.6%、64.2%（P=0.113），PFS率分别为71.2%、62.5%（P= 0.147）；单纯化疗患者中R-CHOP方案组（24例）和CHOP方案组（19例）患者的5年OS率分别为85.7%、83.5%（P=0.152），PFS率分别为83.4%、81.8%（P=0.307）。单纯化疗组和手术联合化疗组Lugano分期早期（Ⅰ~Ⅱ1期）患者的5年OS率分别为86.4%、78.7%，差异无统计学意义（P=0.283）；晚期（Ⅱ2~Ⅳ期）患者分别为74.6%、58.5%，差异有统计学意义（P=0.040）。多因素分析显示IPI评分是影响预后的独立因素（RR=0.370，95% CI 0.089~3.537，P=0.015）。结论单纯化疗或手术联合化疗对PGDLBCL患者长期生存的影响差异无统计学意义，但由于手术可能造成患者生存质量的下降，因此对于无手术指征者更倾向于推荐单纯化疗。本研究中利妥昔单抗的联合应用未能使大部分这类患者的生存显著获益，但这需要进一步多中心、大样本的研究来证实。

An Uncommon Cause of Abdominal Pain, Vomiting, Weight Loss, Melena - Gastric and Intestinal Diffuse Large B-cell Lymphoma (DLBCL)

An Uncommon Cause of Abdominal Pain, Vomiting, Weight Loss, Melena - Gastric and Intestinal Diffuse Large B-cell Lymphoma (DLBCL)

Abstract 258: Molecular features and functional consequence of CD44 activation by a novel recurrent IGH translocation t(11;14) (p13;q32) in mature B-cell lymphoid neoplasm

Abstract Dysregulation of an oncogene by translocation to Ig locus is a common event in the pathogenesis of most non-Hodgkin's lymphoma. Using inverse-PCR, CD44 on 11p13 was identified as a novel translocation partner of IgH in 9 of 114 cases of gastric, non-gastric extranodal, follicular and nodal diffuse large B-cell lymphomas (DLBCLs) analyzed. IgHSμ/CD44 translocation juxtaposes the enhancer of IgHSμ to the 5’ regulatory region of CD44 in a tail-to-head orientation, leading to the removal of exon 1 of CD44. Sequencing analysis showed microhomology sequences at the junction breakpoints of all the IGHSμ/CD44 translocations, suggesting that these translocations were the results of illegitimate switch recombination facilitated by homologous sequences present on both chromosomes. By interphase-FISH using home-grown CD44 dual-color break-apart probes (consisting of BACs RP4-607I7 and RP4-683L5), breakage at the CD44 locus in each of the nine IGHSμ/CD44 translocation-positive cases was confirmed. By 5’ RACE analysis, fusion Iμ-CD44ΔEx1 hybrid transcripts (with a splicing of the Iμ exon upstream of Sμ to exon 2 of CD44), were identified in all the nine lymphomas with IGHSμ/CD44 translocations. Notably, these translocations were detected exclusively in GCB-type DLBCLs. However, CD44 mRNA was minimally or not expressed in CD10+ microdissected reactive GCB cells. The IGHSμ/CD44 translocation substitute Sμ for the CD44 promoter and remove exon 1 of CD44, resulting in over-expression of the Iμ-CD44 hybrid transcript which encodes for a new CD44 variant lacking leader peptide sequence but retaining a unique C-terminus (CD44ΔEx1). The Iμ-CD44ΔEx1 ORF would encode for the CD44ΔEx1 protein starting from the ATG at nucleotide 254 with strong Kozak sequence. The new CD44ΔEx1 variant showed some similarity to CD44v5, but it lacked the leader peptide. The IGHSμ/CD44 translocation was detected in patients with advanced-stage disease (stages III and IV). When overexpressed in vitro in the CD44-negative GCB-DLBCL cell line BJAB, the CD44ΔEx1-GFP was localized to the cytoplasm and nucleus, while CD44s-GFP (standard form) was localized to the plasma membrane. The ectopic expression of CD44ΔEx1 in BJAB cells enhanced the cell proliferation rate and its clonogenic ability. These findings indicate a possible pathogenic role of the recurrent translocation in several malignant B-cell lymphomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 258.

Long-term follow-up of gastric lymphoma after stomach conserving treatment

The therapeutic strategy in gastric lymphoma has completely changed over the last two decades. This change is mainly characterised by the abandonment of surgery in favour of conservative therapies and the introduction of Helicobacter pylori eradication therapy. It became evident that conservative treatment with radiation and/or chemotherapy is at least as effective as surgical resection and additionally offers the advantage of stomach preservation and better quality of life. The therapeutic goal is undoubtedly complete remission of the lymphoma as a necessary basis for cure of the disease. Both radiotherapy and chemotherapy have a high curative potential in gastric MALT lymphoma and diffuse large B-cell lymphoma (DLBCL), respectively. An open question is the additional benefit of radiation following Rituximab-CHOP chemotherapy in DLBCL. In patients with gastric MALT lymphoma of stage I H. pylori eradication offers complete remission rates of up to 80% with excellent long-term prognosis and a real chance of cure. Patients with MALT lymphoma of stage II and those with DLBCL of stage I may also respond to eradication therapy in the individual case. It also emerged recently that there is no need for any oncological therapy in patients revealing minimal histological residuals after successful H. pylori eradication. A watch-and-wait strategy is the adequate management of this condition. In summary, therapy of gastric lymphoma is nowadays individualised with lymphoma type, stage, and H. pylori status as the determinants of the choice of treatment. Efficacy and quality of life are strong arguments for a definite conservative approach encompassing H. pylori eradication, radiation and chemotherapy.

Early stage gastric diffuse large B-cell lymphomas: results of a randomised trial comparing chemotherapy alone versus chemotherapy + involved field radiotherapy

Here, we present the results of a randomised clinical trial carried out between 1998 and 2004, evaluating the possible role of radiotherapy (RT) as consolidation treatment after induction chemotherapy (CT) in diffuse large B-cell (DLBC) gastric lymphoma. Fifty-four patients were enrolled and all received anthracycline containing regimens as induction CT. Patients were evaluated after four to six cycles and those in complete remission (CR) were randomised to receive gastric involved field (IF) RT or two addition cycles of the same CT. Forty-five patients (83%) were randomised after the induction CT. Clinical results of patients allocated to the RT arm showed a significant reduction in incidence of local relapse versus patients who received CT alone. However, overall survival was not different between the two arms. Our results confirm that CT could be considered as first line therapy for newly diagnosed gastric DLBC lymphoma; IF RT delivered in those patients achieving CR after induction CT is able to prevent local relapse.

Differences in germinal centre and non-germinal center phenotype in gastric and intestinal diffuse large B-cell lymphomas

The gastrointestinal tract is the most common extranodal site of lymphoma, and the most common gastrointestinal lymphoma is diffuse large B-cell type (DLBCL). DLBCL can be separated into germinal centre (GCP) and non-germinal centre phenotypes (non-GCP) using CD10, BCL-6 and MUM1 immunohistochemistry, but primary gastrointestinal DLBCL has not been extensively studied. We investigated 48 cases of primary gastrointestinal DLBCL (33% involving the small intestine, 50% the stomach, 13% the large intestine and 4% the ileocecal junction) and found that most (88%) DLBCL in the intestines were of GCP, while only 58% of gastric DLBCL were of GCP. This difference in GCP and non-GCP in gastric vs. intestinal DLBCL may be due to variations in lymphomagenesis reflecting acquired vs. native mucosa-associated lymphoid tissue. There was no significant difference in either overall survival or disease-free survival between the germinal centre and non-germinal centre groups. The distribution of Helicobacter pylori in different gastric DLBCL phenotypes raises interesting questions about the pathogenesis of H. pylori-associated lymphomas.

C-myc gene mutation in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma.

The c-myc gene is involved in important cellular processes, including cell proliferation, differentiation, and apoptosis. We analyzed mutation of the c-myc gene in 51 patients with gastric lymphoma [27 patients with low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, 11 with high-grade MALT lymphoma, and 13 with diffuse large B-cell lymphoma (DLL)], by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. We also evaluated the relationship between mutation of the c-myc gene and regression of low-grade MALT lymphoma after Helicobacter pylori (H. pylori) eradication. Mutation in exon 2 of the c-myc gene was present in 2 of 20 (10%) patients with low-grade MALT lymphoma, in 1 of 7 (14%) patients with high-grade MALT lymphoma, and none of 10 patients with DLL. The 3 patients who had mutations of the gene, showed different patterns of mobility shift, suggesting different mutations. In addition, 15 patients with low-grade MALT lymphoma received anti-H. pylori therapy. All the patients achieved eradication. Nine of the 15 (60%) patients with low-grade MALT lymphoma showed complete regression (CR), 3 (20%) showed partial regression (PR), and 3 (20%) showed no change (NC). One of the 9 (11%) CR patients had a mutation of the c-myc gene. None of the 3 PR and 3 NC patients had mutation of the gene. There was no significant difference between the frequencies among the c-myc gene mutation in CR, in PR and in NC patients. These data suggest that mutation of the c-myc gene may not be commonly associated with development of gastric MALT lymphoma and DLL, and may not be associated with regression of low-grade MALT lymphoma after H. pylori eradication.