胃粘膜相关淋巴组织淋巴瘤临床与内镜表现特征

目的 探讨胃粘膜相关淋巴组织（MALT）淋巴瘤临床和内镜表现特征及其内在联系。方法 总结1985年－1999年我院经手术及病理证实的32例胃MALT淋巴瘤患者临床和内镜资料。结果 32例患者平均就诊时间为15.6月,平均年龄51.3岁,30－39岁及60－69岁为发病高峰,男女比例1.9:1。患者症状不具有特异性,腹痛是其最常见表现。病变累及胃窦12例,胃体8例,多部位者12例。内镜下表现为弥漫型10例,溃疡型16例,结节型6例。各型症状、体 征无显著差异。弥漫型病灶在累及浆膜层前已发生淋巴结转移。内镜确诊率62.5%。32例均为B细胞淋巴瘤,其中27例伴幽门螺杆菌（Hp）感染(84.4%)。结论 胃MALT淋巴瘤发病年龄呈双峰现象,男性居多,起病隐袭,症状、体征不具有特异性。内镜下病变范围广、病灶多发是其特点,各型临床表现无显著差异,但弥漫型容易发生周围淋巴结转移。内镜下多块取检、深取检以及及时做免疫组化检查可提高内镜诊断准确率。Hp感染可能与胃MALT淋巴瘤的发生有关。     

Chronic lymphocytic leukaemia profiled for prognosis using a fluorescence in situ hybridisation panel

A panel of fluorescence in situ hybridisation (FISH) probes was used on 894 cases to target chromosome 11q, 13q, 17p deletions (del), trisomy 12 (+12) in all and 6q deletion in 59. Chronic lymphocytic leukaemia (CLL) immunophenotype (CD5 and CD19 with CD23) was found in 509 cases (average age 67.7 years, 319 males and 190 females). Among the 509 CLL cases 349 (68.6%) had FISH (4-probe panel) abnormalities: 160 del 13q [45.8% (122-del 13q, 18-biallelic del 13q, 20-monoallelic/biallelic del 13q)], 71 tri 12 (20.3%), 17 del ATM (5%), 12 del p53 (3.4%) and 89 > or = 2 FISH abnormalities (25.5%). Of 151/509 cases karyotyped, 108 were normal and 43 (43/151 = 28.5%) abnormal. Del 6q was found in 1/59 (1.6%) FISH cases and in 6/151 (4%) karyotypes. In 14 CD23 negative cases IGH/BCL1 FISH detected t(11;14) and was confirmed to be mantle cell lymphoma. Multiple probes/panels that included IGH probe were ordered for 57 CLL cases, 11 had an IGH rearrangement with an unidentified partner. This study favours the inclusion of del 6q and IGH probes in the CLL panel. The FISH panel could also serve to monitor 13q deletion for secondary changes with adverse prognosis. Understanding prognosis in specific types of 13q deletion would enhance outcome prediction.     

Immunoglobulin light chain gene translocations in non-Hodgkin's lymphoma as assessed by fluorescence in situ hybridisation

In non-Hodgkin's lymphoma (NHL), the majority of translocations involve the immunoglobulin heavy chain gene ( IGH ) locus, while a few involve the immunoglobulin light chain gene ( IGL ) locus, consisting of the kappa light chain gene ( IGκ ) and the lambda light chain gene ( IGλ ). Although many reports have dealt with the translocation and/or amplification of IGH in NHL, only a few have identified IGL translocations. To identify cytogenetic abnormalities and the partner chromosomes of IGL translocations in NHL, we performed dual-colour fluorescence in situ hybridisation (DC-FISH) and spectral karyotyping (SKY) in seven NHL cell lines and 40 patients with NHL. We detected IGL translocations in two cell lines and nine patients: four patients with diffuse large B-cell lymphoma, three with follicular lymphoma, one with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue and one with mantle cell lymphoma. Five distinct partners of IGλ translocation were identified by SKY analysis: 3q27 in three patients, and 1p13, 6p25, 17p11.2 and 17q21 in one patient each. Three cases featured double translocations of IGH and IGL. These findings warrant the identification of novel genes 1p13, 6p25, 17p11.2 and 17q21.     

Metachronous gastric MALT lymphoma and early gastric cancer: a case report.

Metachronous association between gastric lymphoma and early gastric cancer is a rare event. Recent studies have suggested that a relationship exists between gastric mucosa-associated lymphoid tissue (MALT) lymphoma and gastric carcinoma although the mechanism is unknown. Herein, we report a 53-year-old man who visited to our hospital due to melena. Esophagogastroduodenoscopy (EGD) revealed a MALT lymphoma on the greater curvature of lower body. The patient received anti-Helicobacter pylori eradication therapy, followed by 6 cycles of chemotherapy and radiation therapy, and achieved complete remission 12 months after the therapy. Three years later, he revisited our hospital with epigastric pain. EGD revealed an early gastric cancer on the anterior wall of proximal antrum, nearly opposite to the previous lymphoma site, and a partial gastrectomy was performed. To the best of our knowledge, this is the first case report of metachronous MALT lymphoma and subsequent gastric carcinoma in Korea.     

Molecular diagnosis of t(11;14) in mantle cell lymphoma using two-colour interphase fluorescence in situ hybridization

t(11;14) is observed in up to 70% of mantle cell lymphoma (MCL) cases and is therefore an important diagnostic element. In routine practice, detection of t(11;14) by conventional cytogenetic techniques is hindered by the low yield and quality of tumour metaphases. Molecular techniques (Southern blot, PCR) are unable to detect a large number of 11q13 breakpoints due to scattering over distances up to 1 Mb. Using 23 MCL patients with karyotypically determined t(11;14) and eight negative controls, we have devised a two-colour interphase FISH assay for detection of the 14q+ chromosome. We chose an 11q13 probe telomeric to the major 11q13 translocation cluster sites and an IGH probe centromeric of the 14q32 breakpoints. This method detected the translocation in all 23 t(11;14) positive patients, with an overall average of 60% nuclei showing colocalized signals. Widespread application of this technique will constitute an important diagnostic aid in clinical management of MCL patients. Since FISH is a convenient method for retrospective analysis of large numbers of patient specimens, this method should contribute to an accurate estimation of t(11;14) frequency in MCL and other chronic B-cell malignancies and consequently to their better nosological characterization.     

An interphase fluorescence in situ hybridisation assay for the detection of 3q26.2/EVI1 rearrangements in myeloid malignancies

Chromosome rearrangements involving band 3q26.2 are associated with myeloid malignancies, aberrant expression of the human ecotropic virus integration site-1 (EVI1) gene, an unfavourable prognosis and an aggressive clinical course. The 3q26.2 rearrangements are characteristically heterogeneous and typically difficult to detect in poor quality metaphases. To develop a dual-colour fluorescence in situ hybridisation (FISH) assay for the detection of 3q26.2/EVI1 aberrations, a series of 10 BAC clones corresponding to the EVI1 gene region were systematically evaluated and narrowed down to two probe sets; one probe set encompassed the EVI1 gene extending centromeric, while the second probe set covered the EVI1 gene and extends telomeric. Both probe sets were evaluated on 35 patient samples with cytogenetically defined 3q26.2 rearrangements collected at various treatment time points, the inv(3)(q21q26.2) Kasumi-4 cell line, and 10 known negative samples. The two-probe set strategy identified all samples, despite the vast breakpoint heterogeneity observed. In samples from acute myeloid leukaemia and myelodysplastic syndrome cases, the majority of inversion breakpoints were 3' to EVI1 whereas 3q26.2 translocation breakpoints frequently mapped 5' to EVI1. However, two 3q26.2 translocation samples had breakpoints 3' to EVI1. Most inv(3q) chronic myeloid leukaemia samples showed breakpoints within the EVI1 gene. This study demonstrated that, despite the extensive breakpoint heterogeneity observed with 3q26.2 aberrations, this FISH strategy is effective for the detection of 3q26.2 abnormalities in myeloid malignancies.     

Molecular biology of gastric MALT lymphoma: application in clinical management

The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma depends critically on Helicobacter pylori infection. The bacterial infection stimulates the lymphoma B-cells through both direct (auto-antigen) and indirect (H. pylori specific intra-tumour T-cells) immunological stimulation. It also promotes the acquisition of genetic abnormality through activated neutrophils, which release oxygen reactive species. Malignant clones bearing t(11;18)(q21;q21) form lymphomas that are H. pylori growth independent. Those without t(11;18)(q21;q21) but with other genetic abnormality such as trisomy 3 depend critically on H. pylori mediated immune response at early stages and are therefore responsive to H. pylori eradication. However, at late stages when additional genetic defects such as t(1;14)(p22;q32) accumulate, the tumour may escape its growth dependence on H. pylori mediated immune response. Detection of these chromosomal translocations has significant implication in clinical management of patients with gastric MALT lymphoma.     

Prevalence of Helicobacter pylori infection in gastric MALT lymphoma: a systematic review]

OBJECTIVE: To perform a systematic review of studies evaluating H. pylori prevalence in patients with MALT lymphoma, and to analyze predictive factors of response. METHODS: A literature search in Pubmed was performed of papers studying H. pylori prevalence in patients with MALT lymphoma. RESULTS: 38 studies were identified including 1,844 patients. The average prevalence of H. pylori infection was 79%. In patients diagnosed with H. pylori infection using 2 or more methods prevalence was 85%, whereas it was 77% when only one diagnostic method was used (p < 0.0001). H. pylori prevalence in patients diagnosed by histology was 75%, whereas it was 85% when serology was used (p < 0.0001). H. pylori prevalence in high-grade lymphomas was 60%, and 79% in low-grade lymphomas (p < 0.0001). H. pylori infection was detected in 74% of lymphomas confined to the submucosa, but only in 44% of those reaching deeper beyond the submucosa (p < 0.0001). CONCLUSIONS: H. pylori prevalence in patients with MALT lymphoma is variable, and seems to depend, at least partly, on the number and type of diagnostic methods used, histologic grade, and deep tumor invasion. If appropriate diagnostic methods are used, and if only low-grade lymphomas are considered, H. pylori prevalence is high, nearly 90%, which reinforces the role of these bacteria in gastric MALT lymphoma.     

Unusual treatment of a gastric marginal zone B-cell lymphoma of MALT type

Patients with gastric marginal zone-B-cell lymphoma of MALT-type of stage I are usually treated by eradication therapy as Helicobacter pylori infection is evident in the majority (> 90%) of them. In case of a negative Helicobacter pylori status, if the lymphoma does not reveal regression after successful eradication of the bacterium, or in stage II, radiation is nowadays the treatment of choice. Gastrectomy is only reserved for special conditions such as endoscopically not treatable bleeding or patient's explicit request. All treatment modalities follow a curative intention. We here report on a patient with a Helicobacter pylori negative MALT lymphoma of stage I presenting as a localized polypoid lesion in the gastric fundus. Radiotherapy was indicated. However, the patient refused this standard therapy as well as surgical resection as a possible alternative. When signs of lymphoma progression became evident we performed an endoscopy-assisted laparoscopic resection of the fundus which resulted in a continuing lymphoma-free condition. Thus, local treatment modalities such as endoscopic mucosal resection or laparoscopic resection may represent a therapeutic option in case of a localized lymphoma finding in the individual patient who is not suitable for or who refuse standard therapeutic approaches.     

Treatment of gastric MALT lymphoma with a focus on Helicobacter pylori eradication

International Journal of Hematology - Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent disease with a prolonged clinical course that most often involves the stomach. Clinically, for...     

Decreased frequency of HLA-B35 in patients with gastric MALT lymphoma

Persistent infection with Helicobacter pylori has been shown to be strongly associated with the development of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the prevalence of H. pylori infection exceeds the incidence of MALT lymphoma by far. This discrepancy might at least partially be explained on a genomic basis of the host. To evaluate the association between HLA type and MALT lymphoma, we investigated 46 patients with MALT lymphoma recruited in a prospective multicenter study from October 1998 to March 2001. Over 13,000 voluntary stem cell donors from over 40 German blood banks represented the control group. Exploratory statistical analysis using Fishers exact test showed significantly decreased frequency of HLA-B35 in the MALT lymphoma group compared to the control group. Our data suggest a negative association between HLA-B35 and MALT lymphoma; however, larger studies are necessary to confirm a protective role of this HLA antigen.