胃黏膜相关淋巴组织淋巴瘤的临床和内镜下表现

背量：原发性胃B细胞淋巴瘤发生于黏膜相关淋巴组织(MALT)，与幽门螺杆菌(H．pylori)感染密切相关。内镜检查是早期诊断胃MALT淋巴瘤的重要方法。目的：探讨胃MALT淋巴瘤的临床和内镜下表现。方法：分析总结经术后病理检查证实为胃MALT淋巴瘤的20例患者的临床、内镜和病理资料。20例患者中，男10例，女10例，男女比例为1：1，平均发病年龄为55．6岁(21～78岁)。结果：20例患者的临床表现均无特异性，上腹疼痛最为常见，其次是饥饿痛、腹胀、恶心、呕吐、黑便等。内镜下表现：病变发生于胃窦部5例，胃体部5例，胃角部1例，贲门部1例，多部位8例：形态表现多样，其中溃疡型10例，弥漫浸润型3例，结节型5例，结节溃疡型2例；内镜活检确诊率较低，仅为5％。20例患者中有12例检测了H.pylori，阳性率为83．3％(10／12)。手术标本免疫组化染色结果均为B细胞恶性淋巴瘤。结论：胃MALT淋巴瘤的临床表现无特异性，内镜下表现多样，病变范围较大。H．pylori感染率高可能与胃MALT淋巴瘤的发病有关。     

胃黏膜相关淋巴组织淋巴瘤39例临床分析

背景:胃黏膜相关淋巴组织(MALT)淋巴瘤是一种相对少见的胃恶性肿瘤,具有特殊的病因学、组织病理学和临床生物学行为特点。目的:提高对胃MALT淋巴瘤诊治的认识。方法:回顾性分析39例胃MALT淋巴瘤患者的临床、内镜、组织病理学表现以及治疗方案和随访结果。结果:本组胃MALT淋巴瘤患者临床表现缺乏特异性,多有上腹痛;内镜下可见病变主要位于胃窦和胃体部,以溃疡型最为多见:18例患者的免疫组化标记结果显示多数为LCA~+ CD20~+ CD79α~+ CD3~- CD43~- CD45RO~-,16例为B细胞来源,2例为T细胞来源。经根除幽门螺杆菌(H.pylori)、手术、化疗以及手术联合化疗等方案治疗,随访发现多数患者预后良好。结论:内镜检查可早期发现胃MALT淋巴瘤,可通过活检标本组织病理学检查和免疫组化标记确诊。根除H.pylori、手术、化疗等治疗方案可获得较好的临床疗效。     

胃黏膜相关淋巴组织淋巴瘤BCL10核表达与其对幽门螺杆菌根除治疗无反应相关

背景：经幽门螺杆菌（H．pylori）根除治疗，约75％的早期胃黏膜相关淋巴组织（MALT）淋巴瘤患者可获得完全缓解。肿瘤细胞有BCL10核表达和t（11；18）（q21；q21）可能提示胃MALT淋巴瘤对根除治疗无反应。目的：探讨单纯H．pylori根除治疗对国人早期胃MALT淋巴瘤的疗效，以及肿瘤细胞BCL10核表达和t（11；18）（q21；q21）对治疗方案选择的提示作用。方法：收集19例早期胃MALT淋巴瘤患者，以免疫组化方法检测BCL10核表达，以间期荧光原位杂交方法检测t（11：18）（q21；q21）。所有患者均首选H．pylori根除治疗，并行内镜活检病理随访。结果：本组19例早期胃MALT淋巴瘤患者中10例（52．6％）经单纯H．pylori根除治疗获得完全缓解。10例完全缓解者中2例（20，0％）肿瘤细胞BCL10核表达阳性，9例对根除治疗无反应者中7例（77．8％）阳性，阳性率显著高于完全缓解者（P〈0．05）。14例患者行t（11；18）（q21；q21）检测，8例完全缓解者均未检出该易位，6例对根除治疗无反应者中3例（50．0％）检出该易位．两组检出率差异无统计学意义（P〉0．05）。结论：单纯H．pylori根除治疗可使本组52．6％的早期胃MALT淋巴瘤患者获得完全缓解。胃MALT淋巴瘤肿瘤细胞BCL10核表达与其对根除治疗无反应相关。     

原发性胃黏膜相关淋巴组织淋巴瘤29例临床分析

目的：分析胃黏膜相关淋巴组织（MALT）淋巴瘤临床、胃镜、病理特征,提高早期检出率。方法：回顾性分析经胃镜活检及手术后病理证实胃MALT淋巴瘤29例患者的临床资料。结果：29例患者临床表现多样,以上腹痛多见,幽门螺杆菌（HP）感染率高达93%,胃镜下病灶好发于胃窦、胃体,但胃镜下活检阳性率较低,仅占48%。结论：胃MALT淋巴瘤临床表现无特异性,胃镜下表现多样,提高临床和胃镜医师对本病的认识以及提高胃镜下活检阳性率活检标本加做免疫组织化学染色是早期诊断胃MALT淋巴瘤的关键。     

Collision Tumors of Gastric Adenocarcinoma and Mucosa-associated Lymphoid Tissue Lymphoma

A 65-year-old woman with a history of treatment for splenic marginal zone B-cell lymphoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma underwent esophagogastroduodenoscopy. A reddish elevated lesion was found in the fundus of the stomach. On image-enhanced endoscopy, several findings, such as glandular structures of varying sizes suggesting well-differentiated adenocarcinoma, pruned blood vessels, and dilated blood vessels in deeper mucosa suggesting MALT lymphoma, were observed. The final pathological diagnosis after surgical resection was collision tumors of well-differentiated adenocarcinoma and MALT lymphoma. The features of both tumors could be observed simultaneously with image-enhanced endoscopy.     

组织学结合分子生物学参数诊断早期胃黏膜相关淋巴组织淋巴瘤

背景：胃黏膜相关淋巴组织（MALT）是幽门螺杆菌（H．pylori）感染的特殊征象，临床上较为常见．而胃MALT淋巴瘤则极为少见，两者在形态学上难以鉴别。目的：建立胃活检组织胃MALT淋巴瘤的阶梯式诊断流程，为H.pylori根除治疗提供依据。方法：收集31例胃淋巴样增生（GLH）病例，行组织学、蛋白质、DNA和染色体水平的阶梯式检查。GLH组织学分级参照Isaacson标准，以免疫组化方法检测L26、UCHL-1、免疫球蛋白轻链κ、λ和Ki-67，半巢式聚合酶链反应（PCR）检测免疫球蛋白重链（IgH）基因重排，逆转录（RT）-PCR检测AP12-MALT1融合。29例H.pylori感染者接受根除治疗，比较治疗前后的内镜和组织学表现。结果：23例GLH病例组织学分级为Ⅱ或Ⅲ级。仅2例为胃MALT淋巴瘤（组织学Ⅴ级）。1例胃MALT淋巴瘤表达λ轻链限制，10例GLH（包括2例胃MALT淋巴瘤）检测到单克隆IgH基因重排，2例胃MALT淋巴瘤检测到API2-MALT1融合。随着GLH组织学分级的递增．Ki-67标记率和单克隆IgH基因重排榆出率显著增高（P〈0．05）。根除H．pylori后随访1．5～37个月，18例内镜和组织学完全缓解。4例部分缓解。7例无变化。结论：组织学结合Ki-67、IgH基因重排和API2-MALT1融合检测的阶梯式诊断流程有助于诊断早期胃MALT淋巴瘤，亦有助于药物治疗后的随访。     

CD4 + Th1-cells Predominate in Low-grade B-Cell Lymphoma of Gastric Mucosa-associated Lymphoid Tissue (MALT type)

Background: Little is known about the function of T cells in the inflammatory infiltrate in Helicobacter pylori -associated gastritis and B-cell lymphoma of mucosa-associated lymphoid tissue (MALT type). Previous studies have proposed a dominant Th1-type response in low-grade MALT lymphoma consistent with the Th1 response observed in H. pylori -associated gastritis. Methods: We performed a novel flow cytometric approach in which CD3 panning for enrichment and activation of small numbers of T cells and intracellular cytokine analysis were combined to selectively characterize the cytokine profile of T cells (IFN- &#110 for Th1) derived from the gastric mucosa of 23 patients with low-grade MALT lymphoma stage IEI 1 (lymphoma infiltration of mucosa/submucosa sparing the muscularis). Endosonography was performed in each case to control the depth of lymphoma infiltration. For comparison, 19 patients with H. pylori -positive gastritis were also analysed. Results: There was a CD4/CD8 ratio of 4 in patients with MALT lymphoma and of 2 in chronic gastritis. The proportion of IFN- &#110 producing cells within the CD4- positive T-cell population in MALT lymphoma was 22%; in chronic gastritis it was 13% while no such difference could be encountered in CD8-positive T cells. Conclusions: The data point towards a dominant intratumoral IFN- &#110 dominated T-cell response associated with early low-grade MALT lymphoma. A polarized IFN- &#110 dominated Th1-type response may either contribute to the inability of the immune system to eradicate H. pylori infection, thereby promoting the activation status of the lymphocytic infiltrate in low-grade MALT lymphoma, or may mirror a concomitant tumor-specific T-cell response accompanying early stages of tumor progression.     

Relationship Between Gastric Localization of Hepatitis C Virus and Mucosa-associated Lymphoid Tissue in Helicobacter pylori Infection

Background: Hepatitis C virus (HCV) has been localized in several extra-hepatic sites. Recent evidence suggests that the stomach can harbour HCV. We therefore evaluated the prevalence of gastric localization of HCV and its possible relationship with the chronic inflammatory response to Helicobacter pylori infection. Methods: Sixty patients with HCV infection (group A) and 60 subjects without HCV infection (control group), who underwent upper endoscopy for dyspeptic symptoms, were consecutively enrolled. Biopsy specimens of gastric mucosa obtained from each patient were assessed for H. pylori and chronic inflammatory infiltrates (classified as mild, moderate or marked). Furthermore, polymerase chain reaction (PCR) analyses were performed on the gastric biopsies to detect HCV and immunoglobulin heavy-chain (IgH) gene rearrangements of mucosal B cells. Results: In group A, 24 of 36 patients with H. pylori infection and 6 of 24 without H. pylori hosted HCV in their stomach ( P = 0.0017). In these subjects, the presence of both HCV in the gastric mucosa and H. pylori was significantly associated with marked or moderate inflammatory infiltrates. Oligoclonal IgH gene rearrangements were detected in three group A patients who harboured both H. pylori and HCV in their stomach. In the control group, PCR analyses failed to find HCV in the gastric mucosa, and polyclonal patterns were detected in all individuals. Conclusions: HCV is frequently localized in the stomach and is associated with the chronic lymphocytic inflammatory response to H. pylori. H. pylori and HCV, when both present, may favour the selection of clonal B cells.     

Synchronous Adenocarcinoma and Mucosa-associated Lymphoid Tissue Lymphoma of the Colon

Mucosa-associated lymphoid tissue (MALT) tumors are a distinct subtype of non-Hodgkin’s lymphoma. Synchronous appearance of adenocarcinoma and colonic MALT lymphoma in the same patient is quite rare. In the present report, we describe a 68-year-old female who presented with a history of bleeding per rectum. She had no history of fever, loss of weight or drenching night sweats. Rectal examination revealed no abnormality. Colonoscopy showed a large ulceroproliferative mass arising from the hepatic flexure, biopsy of which came out to be adenocarcinoma of colon. A right hemicolectomy was performed and microscopic study revealed the tumor type to be synchronous adenocarcinoma with lymphoma. The final diagnosis of this patient turned out to be a synchronous manifestation of both colonic adenocarcinoma and colonic MALT lymphoma. Although the patient remains asymptomatic two years after surgery, the case highlights the therapeutic dilemma that prevails in the definitive management in such scenarios.     

Regression of Advanced Gastric MALT Lymphoma after the Eradication of Helicobacter pylori

A 66-year-old female presented with a 1-month history of dyspepsia. An initial upper gastrointestinal endoscopy with biopsy revealed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. A rapid urease test was positive for Helicobacter pylori. Endoscopic ultrasound (EUS) and computed tomography (CT) revealed a 30×15-mm lymph node (LN) in the subcarinal area. Histopathologic and phenotypic analyses of the biopsy specimens obtained by EUS-guided fine-needle aspiration revealed a MALT lymphoma, and the patient was diagnosed with a stage 4E gastric MALT lymphoma. One year after H. pylori eradication, the lesion had disappeared, as demonstrated by endoscopy with biopsy, CT, fusion whole-body positron emission tomography, and EUS. Here, we describe a patient with gastric MALT lymphoma that metastasized to the mediastinal LN and regressed following H. pylori eradication.     

Treatment Outcome for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma according to Helicobacter pylori Infection Status: A Single-Center Experience

Background/Aims

Helicobacter pylori eradication therapy has been used as a first-line treatment for H. pylori-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the management strategy for H. pylori-negative MALT lymphoma remains controversial. Therefore, the aim of this study was to examine the success rate of each treatment option for H. pylori-positive and H. pylori-negative gastric MALT lymphomas.

Methods

In total, 57 patients with gastric MALT lymphoma diagnosed between December 2000 and June 2012 were enrolled in the study. The treatment responses were compared between H. pylori-positive and H. pylori-negative gastric MALT lymphomas.

Results

Of the 57 patients, 43 (75%) had H. pylori infection. Forty-eight patients received H. pylori eradication as a first-line treatment, and complete remission was achieved in 31 of the 39 patients (80%) with H. pylori-positive MALT lymphoma and in five (56%) of the nine patients with H. pylori-negative MALT lymphoma; no significant difference was observed between the groups (p=0.135). The other treatment modalities, including radiation therapy, chemotherapy, and surgery, were effective irrespective of H. pylori infection status, with no significant difference in the treatment response between H. pylori-positive and H. pylori-negative MALT lymphomas.

Conclusions

H. pylori eradication therapy may be considered as a first-line treatment regardless of H. pylori infection status.     

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.     

幽门螺杆菌与胃粘膜相关淋巴组织淋巴瘤关系探讨

目的：通过检测胃粘膜相关淋巴组织（MALT）淋巴瘤中的幽门螺杆菌（HP），探讨HP与胃粘膜相关淋巴组织淋巴瘤的关系。方法：收集26例胃MALT淋巴瘤，20例淋巴性胃炎与30例轻度浅表性胃炎的胃粘膜组织病理石蜡切片行0．25％甲苯胺蓝染色，显微镜检查HP，结果：胃MALT淋巴瘤组，淋巴细胞性胃炎组及轻度浅表性胃炎组的HP感染率分别为88．48％，65．00％，43．33％，经统计学分析，差异有显著性（P＜0．05），结论：HP感染与胃MALT淋巴瘤的发生有密切的关系，建议在对胃MALT淋巴瘤行化疗的同时行根除HP治疗。     

Primary Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma with the High Expression of IgG4

This is the first report describing primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma with the high expression of IgG4. The histological findings were compatible with the diagnostic criteria for MALT lymphoma and IgG4-related respiratory disease (IgG4-RRD). An unfixed sample for Southern blotting was not obtained since computed tomography findings showed multiple lung cysts, which is rare in patients with MALT lymphoma. However, polymerase chain reaction using paraffin sections showed the clonality of the immunoglobulin heavy chain variable region gene rearrangement, confirming a diagnosis of MALT lymphoma. This is an instructive case in which primary pulmonary MALT lymphoma was histologically compatible with IgG4-RRD.     

Regression of Gastroduodenal Mucosa-Associated Lymphoid Tissue Lymphoma after Eradication of Helicobacter pylori: A Case Report

Increasing evidence suggests that eradication therapy of Helicobacter pylori (H. pylori) may be an effective treatment for gastric lymphoma of mucosa-associated lymphoid tissue (MALToma), but it remains unclear whether a similar therapeutic effect may be obtained for MALToma at other sites. We describe here a case of regression of gastroduodenal MALToma after eradication therapy for H. pylori. A 39-year-old man underwent gastroscopy at a routine check-up, which demonstrated protruding lesions like a raised erosion in the antrum and multiple whitish granular lesions in the fornix. Simultaneously, multiple coarse nodular lesions were also found in the duodenal bulb. Forceps biopsy specimens obtained from both the stomach and bulb showed infiltration of small- to medium-sized lymphocytes with cleaved nuclei, centrocyte-like cells, together with atypical large lymphoid cells into the glandular lesion, and the rearrangement of immunoglobulin was positive, thereby allowing diagnosis of low grade MALToma with large cell transformation. H. pylori was positive in the stomach, while the presence of H, pylori was not detected microscopically in the bulb, although ectopic gastric mucosa was identified in the bulb. Regression of multiple coarse or granular lesions in both the stomach and bulb were observed three months after eradication of H. pylori. Thereafter the disappearance of MALToma was verified histologically a further six months later. There was no recurrence of MALToma detected over a two-year follow-up period. These findings suggest that eradication of H. pylori could be a treatment of first choice for MALToma occurring in the gastrointestinal tract outside the stomach.     

Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT lymphoma) in Ulcerative Colitis

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) occurring in inflammatory bowel diseases, including ulcerative colitis (UC) and Crohn''s disease, has been reported, although it is extremely rare. An 18-year-old man with a two-years history of UC underwent colon endoscopy, and was found to have active total UC ranging from anus to cecum. Six biopsies were obtained. The microscopic examinations showed severe infiltrations of atypical small lymphocytes. They showed hyperchromatic nuclei and increased nucleocytoplasmic ratio and scattered immunoblastic cells. Centrocyte-like atypical lymphocytes, monocytoid cells, and plasma cells were seen in some places. Vague germinal centers were present, and apparent lymphoepithelial lesions were seen. No crypt abscesses were seen, and there were few neutrophils. No apparent other findings of UC were seen. Immunohistochemically, the atypical lymphocytes were positive for vimentin, CD45, CD20, CD79α, CD138, κ-chain, λ-chain, and p53 and Ki-67 antigen (labeling index = 63%). They were also positive for CD45RO, CD3, and CD15, but these positive cells were very scant compared with CD20 and CD79α. They were negative for CD10, CD30, CD56, cytokeratin (CK) AE1/3, CK CAM5.2, CK34BE12, CK5, CK6, CK7, CK8, CK14, CK18, CK19, CK20, EMA, chromogranin, synaptophysin, NSE, S100 protein, CEA, CA19-9, p63, and HMB45. Without clinical information, the appearances are those of MALT lymphoma. However, with clinical information, making the diagnosis of MALT lymphoma was hesitated. It is only mentioned herein that atypical lymphocytic infiltrations indistinguishable from MALT lymphoma occurred in an 18-year-old male patient with a two-year history of UC.     

Specificity of Polymerase Chain Reaction Monoclonality for Diagnosis of Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma (Direct Comparison to Southern Blot Gene Rearrangement)

The specificity of polymerase chain reactionmonoclonality in the diagnosis of gastric lymphoma wasprospectively evaluated. Gastric mucosal tissue fromnormal gastric mucosa (N = 13), benign gastric ulcers (N = 3), chronic Helicobacter pylori gastritis(N = 3), gastric mucosa-associated lymphoid tissue (N =16), and gastric lymphoma (N = 15) was obtained.Polymerase chain reaction amplification of theheavy-chain framework 2A gene was performed. Thesensitivity and specificity of heavy-chain clonality, inthe detection of gastric lymphoma, were 73.3% and 45.7%,respectively. Determination of monoclonality bypolymerase chain reaction methodology is not an acceptabletechnique for confirming the diagnosis of gastriclymphoma as it is too sensitive, detecting minutepopulations of clonal lymphocytes that occur in benign diseases as well as larger populations ofclonal lymphocytes associated with malignant gastriclymphoproliferative diseases. Southern blot generearrangement testing should be utilized to determineclonality in the evaluation of gastric lymphocyticinfiltrates.     

Diagnosis of a Gastric Mucosa-associated Lymphoid Tissue Lymphoma by Endoscopic Ultrasonography-guided Biopsies in a Patient with a Parotid Gland Localization

We report the case of a 32-year-old man with a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland associated with Sjögren syndrome. He underwent an upper endoscopy as part of the screening of a gastric localization which showed a diffuse non-specific gastritis. However, endoscopic ultrasonography (EUS) evidenced a focal wall thickening of the vertical portion of the smaller curvature. EUS-guided biopsies of this area disclosed a MALT lymphoma, whereas biopsies under endoscopy concluded to mild chronic gastritis. The search for Helicobacter pylori infection remained negative. Four months after treatment with anti-CD20 antibodies, EUS showed a diminution of the abnormal thickening of the second layer. Regression was confirmed histologically on new EUS-guided biopsies. MALT lymphoma is usually considered a localized disease; however, dissemination is probably more frequent than initially believed. Our case reflects the importance of a systematic screening for a gastric localization in patients with MALT lymphoma of the salivary glands. In this situation, association to autoimmune disease such as Sjögren syndrome is more likely to explain the gastric location than infection with H. pylori. Endoscopic ultrasonography has a major impact for the staging of gastric MALT lymphoma, but may also help diagnose focal infiltration by the disease.