Diagnosis Of Gastric Mucosa-associated Lymphoid Tissue Lymphoma Research Articles

Gastric Mucosa-associated Lymphoid Tissue Lymphoma Mimicking Signet Ring Cell Carcinoma

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common type of extranodal non-Hodgkin lymphoma. Endoscopic findings are nonspecific and variable; therefore, differentiation of this malignancy from early gastric cancer is challenging during endoscopy. Although an endoscopic biopsy is the gold standard for diagnosis, a biopsy may not conclusively establish the diagnosis in all cases. Diagnostic confirmation requires interpretation of the biopsy specimen findings by an experienced histopathologist, and an additional immunoglobulin heavy chain (IgH) rearrangement test may aid with accurate diagnosis. We present a case of gastric MALT lymphoma that histopathologically mimicked signet ring cell carcinoma (SRCC) on evaluation of repeat endoscopic biopsies. Following endoscopic submucosal dissection (ESD), we confirmed the final diagnosis of gastric MALT lymphoma based on histopathological findings of prominent lymphoid infiltrates accompanied by lymphoepithelial lesions and results of the monoclonal IgH rearrangement test. Notably, a few carcinoma-like signet ring cells (SRCs) in the specimen were attributed to a reactive change. Clinicians should be mindful of possible SRCs in gastric MALT lymphoma specimens to avoid misdiagnosis of SRCC in patients with gastric MALT lymphoma. Confirmatory ESD may be useful for accurate diagnosis and appropriate management of such lesions.

Endoscopic features aiding the diagnosis of gastric mucosa-associated lymphoid tissue lymphoma.

The incidence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is increasing worldwide, but the diagnosis is difficult. Most patients are asymptomatic or complain of nonspecific gastrointestinal symptoms. As the endoscopic features of gastric MALT lymphoma are variable and nonspecific, the possibility of this condition may be overlooked during esophagogastroduodenoscopy, and it remain undiagnosed. Therefore, this condition needs to be considered when an abnormal mucosa is observed during this procedure. Biopsy performed during endoscopy is the primary diagnostic test, but false negative results are possible; large numbers of samples should be collected from both normal and abnormal mucosae. Endoscopic ultrasonography is useful to assess the depth of invasion and to predict the treatment response. After treatment, follow-up tests are required every 3 months until complete remission is achieved, and annually thereafter. Early diagnosis of gastric MALT lymphoma is difficult, and its diagnosis and follow-up require wide experience and competent endoscopic technique.

Outcomes After Reduced-Dose Intensity Modulated Radiation Therapy for Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

In patients with gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, the standard radiation therapy (RT) dose is ≥30Gy. We report the outcome of patients treated with reduced dose 24Gy compared with those treated with ≥30Gy. We reviewed results from 32 patients who received a diagnosis of gastric MALT lymphoma between 2007 and 2017 who were treated with involved site RT using intensity modulated radiation therapy (IMRT). Response to therapy was based on post-RT endoscopic biopsy. Freedom from local treatment failure (FFLTF), freedom from treatment failure (FFTF), and overall survival (OS) outcomes were determined. The median age of patients at diagnosis was 58years. Therapy for MALT was given prior to RT in 14 patients with residual biopsy proven disease documented in all cases (anti-microbial, n=11; rituximab, n=2; rituximab, cyclophosphamide, doxorubicin, vincristine, n=1). One patient received RT (36Gy) and concurrent rituximab. The median RT dose was 30Gy; it was 30 to 36Gy in 66% of patients (n=21) and 24Gy in 34% of patients (n=11). Post-RT biopsy documented a complete response in all patients. Failures occurred in the stomach and duodenum, respectively, at 3.6 and 4.5years, after 30Gy. At a median follow-up of 55.2months (73.8 for ≥30Gy compared with 28.7 for 24Gy; P<.001), the 2-year FFLTF, FFTF, and OS were 100%, 100%, and 97%, respectively. No association was found between the lower (24-Gy) dose and FFLTF (P=.819), FFTF (P=.819), or OS (P=.469). Contemporary RT with involved site targeting using IMRT is associated with high complete response rates for patients with gastric MALT lymphoma, even using reduced doses of 24Gy. Additional follow-up and increased patient numbers are required to confirm equivalent disease control.

Diagnosis and Treatment of Gastric Mucosa-associated Lymphoid Tissue Lymphoma

The stomach is the most common primary site of an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type, which is characterized by an indolent clinical course. A diagnosis of gastric MALT lymphoma requires an endoscopic biopsy that should be confirmed by an experienced pathologist. Gastric MALT lymphoma shows a variable endoscopic appearance, including erosion, erythema, discoloration, atrophy, ulcer, and subepithelial lesion. The distribution is often multifocal. Therefore, clinical suspicion and multiple biopsies are essential for an accurate diagnosis. Gastric MALT lymphoma is almost invariably associated with a Helicobacter pylori (H. pylori) infection. H. pylori eradication therapy is the mainstay of treatment, which must be delivered to all patients regardless of the H. pylori infection status or stage. For patients who have failed to achieve remission following eradication therapy, radiotherapy or chemotherapy can be considered. Radiotherapy is an effective treatment modality for a localized stage and shows excellent outcomes. In the presence of disseminated or advanced disease, chemotherapy and/or immunotherapy with the anti-CD20 monoclonal antibody, rituximab, can be applied. Treatment should be individualized according to the stage and symptoms, as well as the patients' preference. Given that the clinical course of gastric MALT lymphoma is usually indolent, watchful waiting may be an adequate strategy in selected cases where scheduled follow-up is guaranteed.

Pre-malignant signs of gastric MALT lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common type of extra-nodal non-Hodgkin lymphoma, which mostly involves the stomach. The clinical suspicion and diagnosis are often challenging because of the lack of specific symptoms and conventional endoscopic findings. Three magnifying endoscopic signs of the gastric mucosa have been described as highly specific to the diagnosis of MALT lymphoma, such as (i) tree-like appearance of the microvessels; (ii) non-structural area; and (iii) ballooning crypt pattern. We report the case of a middle-aged woman in which these signs appeared chronologically over a period of 2 years, showing the association of the sequence of the endoscopic findings and the final histological diagnosis of gastric MALT lymphoma.

The role of miRNAs and epigenetic mechanisms in primary gastric mucosa-associated lymphoid tissue lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare low-grade B-cell non-Hodgkin lymphoma associated with Helicobacter pylori infection and the subsequent chronic inflammation. Significant progress in understanding the pathogenesis of the disease has already been made. However, the exact molecular pathways of lymphomagenesis remain unclear. Furthermore, difficulties regarding accurate diagnosis of gastric MALT lymphoma and its discrimination from gastritis or other lymphoma subtypes arise. Recent studies evaluate the role of miRNAs and epigenetic alterations on MALT lymphoma pathogenesis and prognosis. This review critically summarizes the most important data on the role of miRNAs and epigenetics in MALT lymphomas pathogenesis, prognosis and treatment.

Disseminated Gastric MALT Lymphoma with Monoclonal Gammopathy, t(11;18)(q21;q21), and Subsequent Development of T-Large Granular Lymphocytic Leukemia: A Case Report and Review of the Literature.

Background. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is a well-characterized entity that may share clinical and morphological findings with other low-grade non-Hodgkin's lymphomas. Dissemination of MALT-type lymphoma to bone marrow and peripheral blood simultaneously with the presence of T-large granular cell leukemia (T-LGL) has rarely been reported. Case Presentation. This is the case of a 42-year-old male who presented with a gastric MALT-type lymphoma, disseminated to the bone marrow and the peripheral blood with high serum IgM levels and t(11;18)(q21;q21). The morphological, immunophenotypical and, immunohistochemical studies of the successive bone marrow and peripheral blood samples had revealed the coexistence of two distinct lymphoma cell populations: a B-cell, marginal zone type population expressing CD19, CD20, CD22, CD79b, IgM, and kappa light chain, and a T-large granular cell population, developed after treatment with rituximab expressing CD3, CD8, CD5, CD7, and CD45. Conclusion. Based on the analysis of this unusual case we performed an extensive review of the literature to elucidate the relationship between T-LGL and B-cell lymphomas and to emphasize the importance of paraprotein analysis at diagnosis of gastric MALT lymphoma.

Gastrointestinal: Gastric mucosa‐associated lymphoid tissue (MALT) lymphoma observed by magnifying endoscopy with narrow band imaging

Mucosa-associated lymphoid tissue (MALT) lymphoma derived from the B-lymphocytes, rarely occurs in the gastrointestinal (GI) tract. The commonest site of occurrence is the stomach. Narrow band imaging (NBI) with magnifying endoscopy can identify MALT lymphoma and there have been several reports and case series on this. We presently report a 79-year-old man who underwent GI endoscopy as part of a health checkup. Conventional endoscopy showed a depressed reddish lesion in the posterior wall of the mid-gastric body (Figure 1A). Chromoendoscopy with indigo carmine identified this to be a depressed lesion. (Figure 1B) Magnifying endoscopy with NBI showed a cleare demarcation line of this depressed lesion (Figure 1C, arrows), and revealed an loss of the normal epithelium and abnormal micro-vessels that did not have the typical tree-branching calibre changes around white round lesions (Figure 1D). Endoscopic biopsy specimens taken from the lesion showed a diffuse proliferation of abnormal lymphoid cells within the mucosa (low-power histology—not shown). High-power histology showed a diffuse proliferation of small centrocyte-like cells and lymphoepithelial lesions. Immunohistochemical analysis was positive for CD20 but negative for CD3. He was diagnosed as having gastric MALT lymphoma. The positron-emission tomography/computed tomography showed only gastric uptake and no other extra-nodal disease. Based on the histopathological findings, a diagnosis of gastric MALT lymphoma (high-grade) was made, and combination-chemotherapy with pirarubicin hydrochloride, cyclophosphamide, vincristine sulfate and rituximab was started.

Primary diffuse large B cell lymphoma of the breast eight years after the diagnosis of gastric MALT lymphoma: report of first case

Primary breast lymphoma (PBL) is an uncommon type of extranodal non-Hodgkin's lymphoma (NHL), accounting for approximately 1% of all extranodal NHL. Diffuse large B cell lymphoma (DLBCL) is the most frequent histology. Both primary mucosa-associated lymphoid tissue (MALT) lymphoma of the breast and its relapse have been documented previously. We report on a 63-year-old woman with primary DLBCL of the breast which was diagnosed 8years after gastric MALT lymphoma. Following chemotherapy, complete response was obtained. We suggest that for women presenting with a breast mass who received cytotoxic treatment for the other lymphoma, PBL should be considered in the differential diagnosis of the breast mass together with primary breast carcinoma.

Gastric mucosa-associated lymphoid tissue lymphoma complicated with hemophagocytic syndrome in an elderly woman

Dear Editor, Hemophagocytic syndrome (HPS) has been described in association with a variety of lymphomas, most commonly Tor NK-cell-type tumors [1]. More rarely, HPS occurs in association with aggressive B-cell tumors, including diffuse large B-cell lymphoma and intravascular large B-cell lymphoma [2, 3]. Although these lymphoma-associated forms of HPS generally show a poor prognosis [1], appropriate therapy for the underlying lymphoma can lead to the resolution of this condition [2]. Here, we report an elderly patient with mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach, who developed HPS during the course of the disease. An 80-year-old woman, who had been treated for cognitive disorder in a psychiatric clinic, presented with upper abdominal discomfort. Endoscopy of the upper gastrointestinal tract revealed multiple mucosal lesions from the lower body to the antrum of the stomach, including superficial erosions/ulcers and “gastritis-like” erythema (Fig. 1a). A biopsy demonstrated mucosal infiltrates of small lymphoid cells showing a monocytoid appearance associated with lymphoepithelial lesions, being compatible with gastric MALT lymphoma (Fig. 1b). Tests for Helicobacter pylori were positive. Triple therapy comprising lansoprazole, amoxicillin, and clarithromycin was initiated; however, the patient soon discontinued treatment due to the development of an allergic skin rash. As the patient’s symptoms persisted, she was finally admitted to our hospital 4 months after the initial presentation. On examination, she was febrile and icteric, and the abdomen showed hepatosplenomegaly. There was no superficial lymphadenopathy. The blood counts were: hemoglobin, 11.5 g/dl; white blood cell count, 2,500/μl with 86% neutrophils; and platelet count, 117×10/μl. The blood chemistry values included: total bilirubin, 9.2 mg/dl; asparate aminotransferase, 1,446 IU/l; alanine aminotransferase, 387 IU/l; alkaline phosphatase, 1,439 IU/l; lactate dehydrogenase, 1,851 IU/l; and γ-glutamyl transpeptidase, 143 IU/l. The level of triglyceride was 294 mg/dl, fibrinogen—83 mg/dl, fibrinogen/fibrin degradation product—15.5 μg/ml, ferritin—2,929 ng/ml, and soluble interleukin-2 receptor was as high as 17,388 U/ml. A computed tomographic scan and ultrasonography of the abdomen revealed hepatosplenomegaly and wall thickening of the gall bladder (Fig. 1c); the latter finding suggested portal cellular infiltration [4]. Bone marrow specimens obtained from the iliac crest revealed hypocellular marrow with increased numbers of macrophages ingesting blood cells (Fig. 1d); no lymphoma cells were apparent on microscopic examination or flow cytometric analysis. A diagnosis of gastric MALT lymphoma complicated with HPS was made. The patient was treated with chemotherapy consisting of vincristine, cyclophosphamide, prednisolone, and doxorubicin, in combination with rituximab. HPS responded well to the treatment; H. Ohno (*) Department of Hematology, Takeda General Hospital, 28-1, Mori-minami-cho, Ishida, Fushimi-ku, Kyoto 601-1495, Japan e-mail: hitoshi-ono@fm2.seikyou.ne.jp

Clinicopathological analysis of gastric mucosa-associated lymphoid tissue lymphoma

Objective To analyze the clinicopathological characteristics, immunophenotypes and immu-noglobulin heavy chain gene rearrangement of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Methods The clinical data of 35 patients with gastric MALT lymphoma who had been admitted to Southwest Hospital from January 1984 to June 2003 were retrospectively analyzed. The specimens of the gastric MALT lymphoma were obtained and their pathomorphological classifications were studied. The immunophenotypes and immunoglobulin heavy chain gene rearrangement were detected by immunohistochemistry and polymerase chain reaction, respectively. All the data were analyzed by chi-square test and Mann-Whitney U test. Results The main manifestations of patients with gastric MALT lymphoma were epigastric discomfort and abdominalgia. The percentage of patients with age≥40 accounted for 74% (26/35). The gastric MALT lyrnphoma has low differentia-tion in 32 patients, and high differentiation in 3 patients. There were 31 patients in Ⅰ E stage, 2 in Ⅱ E1 stage and 2 in Ⅳ stage. Pathological examination showed that gastric MALT lymphoma was composed of centrocyte-like cells and mononuclear-like B cells or lymphoplasma cells. Twenty-nine specimens were with lymphoepithelial lesions (83%), 2 with follicular colonization (6%), and 11 with plasma cells segregated beneath the surface epithelium (33%). All the 35 specimens were B cell immunotype. Restrictive expression of κ and λ light chains of the immunoglobulin was found in 19 cases, and Bcl-2 positive expression was found in 16 cases. High expres-sion of proliferating cell nuclear antigen was found in gastric MALT lymphoma with transformed blasts, which indicated that gastric MALT lymphoma with transformed blasts was more active in proliferation than those of low grade. A monoclonal pattern of immunoglobulin heavy chain gene rearrangement was detected in 33 patients (94%). Conclusions Digestive symptoms are the main manifestations of patients with gastric MALT lymphoma. The incidence of gastric MALT lymphoma increases with age. The final diagnosis of gastric MALT lymphoma depends on the pathological, immunohistochemical examination and laboratory test. Key words: Lymphoma; Mucosa-associated lymphoid tissue; Pathology; Immune phenotype

Gastric MALT Lymphoma Presenting as Waldenström's Macroglobulinemia Without Bone Marrow Involvement

We report a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with macroglobulinemia in a 59-year-old man who presented with melena. A computed tomography scan of the abdomen showed irregular thickening of the wall of the stomach, and endoscopic examination disclosed enlarged and inflammatory folds of the fundus. Histopathologic examination of gastric samples showed mucosal infiltration by small lymphocytes, which were positive for CD20 and negative for CD10 and CD23, confirming the diagnosis of gastric MALT lymphoma. Serum electrophoresis detected a monoclonal peak and immunoelectrophoresis revealed an immunoglobulin M κ component. Bone marrow aspirate and biopsy results were normal. The patient received chemotherapy. After treatment, he was in complete remission, and the serum monoclonal component had disappeared. Our observation is uncommon because of important macroglobulinemia occurring in gastric MALT lymphoma without bone marrow involvement.

Clinical study of 31 patients with primary gastric mucosa‐associated lymphoid tissue lymphoma

The purpose of the present paper was to investigate the clinical, endoscopic and histological features of 31 patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to enable correct, early stage diagnosis. A retrospective study was undertaken of 31 patients with gastric MALT lymphoma. The cases were examined immunohistologically with anti-CD(20CY) and CD(45RO) antibodies for further diagnosis. Helicobacter pylori infection was also detected with modified Giemsa staining. Patients with MALT lymphoma were aged between 22 and 73 years (mean, 45.0 years), and the male:female ratio was 11:20. The patients presented with non-specific symptoms, but chronic epigastric pain was the common symptom in a large proportion of the cases. The gastric smaller curvature was involved in 83.9% of cases (26/31) and in 13/31 cases (41.9%) it was confined the antrum. Under endoscopy, large and deep ulcers were similar to cancers in the majority of patients. Only 29.0% of patients were diagnosed by endoscopy on first examination. CD(20CY) were expressed in all cases and CD(45RO) expressed in only one case among 10 cases of indefinite diagnosis. Helicobacter pylori infection was found in 87.1% of patients. These findings suggest that primary gastric MALT lymphoma has unique clinical, endoscopic and histological features. The diagnosis for primary gastric MALT lymphoma was delayed not only due to the non-specific symptoms but also due to lack of attention to its features. Endoscopy and submucosal multiple biopsy were the principal diagnostic tools in patients with gastric MALT lymphoma. CD(20CY) and CD(45RO) immunological staining are recommended, especially for patients with indefinite diagnosis of gastric MALT lymphoma.

Clinicopathological features of gastric B-cell lymphoma: a series of 317 cases.

The stomach is a common site of extranodal malignant lymphoma. Here we examined the clinicopathological features of 317 gastric B-cell lymphomas and characterized the differences among low-grade mucosa-associated lymphoid tissue (MALT) lymphomas (LG), high-grade MALT lymphomas (HG), follicular lymphomas (FL) and diffuse large B-cell lymphomas (DL). Cases included 126 DL, 71 HG, 98 LG, 10 FL, three Burkitt's lymphoma and nine of undefined type. The age range of patients was as follows: LG, 14-96 years (mean, 61.1); HG, 20-87 years (mean, 63.9); DL, 16-88 years (mean, 62.8); and FL, 54-76 years (mean, 65.5). There were no differences in age with respect to tumor type. There were more women patients with LG (female:male, 55:43), while males predominated among DL patients (54:72). The sexes were represented almost equally in HG cases (34:37). Histological findings, especially in DL tumors, correlated significantly to the gross appearance of mass formation. Dutcher bodies were encountered mainly in HG or LG cases. Our results showed no differences in age, sex or site of disease between LG, HG and DL tumors. However, the grade of malignancy correlated strongly to gross appearance. Dutcher bodies were important for the diagnosis of gastric MALT lymphoma.

Helicobacter pylori associated gastric B cell MALT lymphoma: predictive factors for regression

See article on page 297 Experimental data have extended the knowledge of the mere association of gastric mucosa associated lymphoid tissue (MALT) lymphoma and infection with Helicobacter pylori. The acquisition...

Helicobacter Pylori除菌にて著明な改善を認めた胃MALTリンパ腫の1例

Recently, it has been reported that Helicobacter pylori (H. pylori) infection refered to the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, because MALT lymphoma was improved by eradication of H. pylori. This patient was a 56-years-old man. Barium meal examination showed a small depressed lesion in the middle body of the stomach. Endoscopic examination revealed a scattered irregular depressed lesion in the same location. Histological study of the biopsy specimen revealed proliferation of atypical lymphoid cells and lympho-epithelial lesions in the gastric mucosa, and the diagnosis of gastric MALT lymphoma was suggested. H. pylori was detected by both culture and histological findings. So, we tried antibiotic therapy for H. pylori by 30mg of lansoprazole, 1500mg of amoxicillin, and 400mg of clarithromycin for 2 weeks. Six months after the therapy, eradication of H. pylori was ascertained and the MALT lymphoma lesion had disappeared endoscopically and histologically. It is suggested that H. pylori infection play a role in the pathgenesis of gastric MALT lymphoma, and that eradication of H. pylori is the first choice treatment for gastric MALT lymphoma.