Clonality analyses in gastric MALT (mucosa-associated lymphoid tissue)

B-cell clonality, assessed by PCR for amplification of the VDJ region of the immunoglobulin heavy chain gene (IgH), is used to support the diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). It has also been described in simple gastritis cases, without any histological hint for lymphoma, especially in the presence of lymphoid follicles. We analyzed a randomly selected series of 130 gastric biopsies with histologically described lymphoid follicle formation and investigated these for the prevalence of B-cell clonality using different PCR-based methods to discuss its usefulness in the differential diagnosis of GML. A seminested PCR for the IgH gene was performed and evaluated by agarose gel electrophoresis, GeneScan technique, and melting-curve analysis. The majority of cases revealed histologically chronic active Helicobacter pylori gastritis. Monoclonality was detected in 7.5% (10 of 130) and 7% (9 of 130) of samples using GeneScan technique and melting-curve analysis, respectively. In eight of eight samples investigated, monoclonality was not demonstrated in deeper sections of the same biopsy using GeneScan technique, favoring the diagnosis of a reactive process rather than overt lymphoma. Electrophoresis proved more difficult to interpret and revealed clonal cases in 14% (18 of 130). We conclude that GeneScan technique and melting curve analysis are the methods of choice for clonality analysis in gastric biopsies. Analyses of different deep sections with advanced PCR technology might be the method of choice for future analyses. In our opinion, the question of whether detected monoclonality can be interpreted as malignant lymphoma is still open.     

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of thymus

This report describes a low-grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT) involving the thymus of a 63-year-old woman with features suggestive of a connective tissue disease. Sections of the thymic lesion and of a lung biopsy performed at the same operation were examined histologically and by immunohistochemistry using the monoclonal antibodies CD45, CD20, CD79a, CD3, CD45RO, and AE1/AE3. Polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement was also performed. The dense infiltrate of small lymphoid cells intimately admixed with ramifying epithelial elements, some of which had undergone cystic change, closely resembled a thymoma. The lymphoid infiltrate comprised centrocyte-like cells, small lymphocytes, plasma cells, and blasts. Most of the lymphoid cells were immunoreactive with the B-cell markers CD20 and CD79a, and PCR showed clonal immunoglobulin heavy chain gene rearrangement. The lung biopsy showed dense infiltration by small lymphoid cells, morphologically suggestive of lymphoid interstitial pneumonia. However, PCR showed a weak band in the amplification for immunoglobulin heavy chain gene rearrangement, identical to that within the thymus and suggesting either recirculation of cells to accumulated MALT or subhistological lymphoma. MALT lymphoma may rarely involve the thymus, and pathologists should be aware of this to avoid misdiagnosis as a thymoma. Immunohistochemical and/or molecular studies are of value in this regard. MALT lymphomas of the thymus, common with those arising in other organs, may develop in the setting of a connective tissue disease.     

Simultaneous papillary carcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid; a case report

Primary lymphoma of the thyroid is an uncommon malignancy, whereas papillary thyroid carcinoma is the most common thyroid malignancy. Both have an association with Hashimoto's thyroiditis. We discuss a case of an 83 year old male who presented with a large neck swelling, which subsequently proved to be a primary thyroid lymphoma (extra-nodal marginal zone) with concurrent papillary thyroid carcinoma. These tumours manifested on a background of Hashimoto's thyroiditis. To date there have only been 13 other cases of joint papillary thyroid carcinoma and thyroid lymphoma within the literature. Our case report adds to this by discussing diagnosis, histopathological features and pitfalls in early detection.     

Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): a multifocal disease

Gastrectomy specimens from five patients following gastroscopic biopsies which showed low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) were examined by serially sectioning and paraffin wax embedding using a 'swiss roll' technique. This procedure allowed the construction of a map of the specimen on which the distribution of the lymphoma could be plotted. In each case confluent lymphoma was identified. In addition small foci of lymphoma consisting of 1-4 lymphoid follicles surrounded by neoplastic centrocyte-like cells were seen. The positions of these 'micro-lymphomas' were plotted on the gastrectomy maps, showing multiple foci distributed throughout the gastric mucosa. The identification of these microscopic lesions may explain the development of local relapse, often after a long disease-free interval, in patients with gastric MALT lymphoma treated by partial gastrectomy where excision appears to have been complete. Patients treated in this way should, therefore, be followed-up indefinitely, with regular endoscopy and gastric biopsy, in order to identify early local disease relapse.     

涎腺粘膜相关淋巴瘤临床与病理研究

目的 探讨涎腺粘膜相关淋巴瘤的病理诊断特征及发病机制,方法 分析临床资料,利用ＨＥ染色,白细胞共同抗原,ＣＤ２０,ＣＤ４５ＲＯ,上皮膜抗原的ＳＰ法免疫组化及电镜观察了２７例涎粘膜相关淋巴瘤,结果 男性２４例,女性３例,平均年龄５３．４５岁,其中腮腺１２例,颌下腺１５例,涎腺粘膜相关淋巴瘤是由弥漫性中心细胞（ＣＣＬ）细胞组成,并有“淋巴上皮病变”。ＣＣＬ细胞呈ＣＤ２０阳性,ＣＤ４５ＲＯ阴性,电镜下瘤     

Primary mucosa-associated lymphoid tissue (MALT) lymphoma arising from the male urethra. A case report and review of the literature

Primary non-Hodgkin's lymphomas rarely arise from the lower urinary tract, the urethra being the most uncommon site of origin. Herein, we report the immunohistochemical findings of a case of primary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising from the male urethra. To clarify the clinicopathological findings of primary urethral lymphoma, we reviewed 14 previously reported cases. A 56-year-old man presented with gross hematuria. Cystourethroscopy demonstrated a nodular bulge of the urethral wall. Histologically, a transurethral biopsy specimen showed a dense lymphoplasmacytoid infiltrate in the urethral mucosa. The tumor cells were composed of centrocyte-like cells, plasma cells and plasmacytoid cells. A few plasma cells contained intracytoplasmic pseudoinclusions (Dutcher bodies). Immunohistochemical study revealed monotypic intracytoplasmic kappa-light chain in the plasma cells and plasmacytoid cells. The patient received a total of 50 Gy extrabeam irradiation. Follow-up 21 months later did not disclose any sign of local or other recurrences.     

A case of primary mucosa-associated lymphoid tissue lymphoma of the vagina

We report the first case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the vagina, the diagnosis of which is supported by genetic and immunophenotypic studies. A 65-year-old, para 2 woman presented to our hospital in July 1997 with a history of prolonged vaginal discharge. Although cytologic examination suggested possible malignancy, a biopsy of the vaginal wall was diagnosed as chronic inflammation. In June 2000, she underwent gynecologic examination because of anuria. Excisional biopsy revealed subepithelial infiltration of atypical lymphoid cells that stained for CD20, CD79a, and BCL-2; stained weakly for IgM; and did not stain for CD3, CD5, CD7, CD10, CD56, CD23, and IgD, suggesting marginal zone B-cell lineage. Monoclonality was detected by Southern blot analysis, and this patient was finally diagnosed as having primary MALT lymphoma of the vagina. She received 3 cycles of chemotherapy (THP-COP) and concurrent radiation to the whole pelvis. The patient is alive and well 40 months after treatment. Because the vagina is one of the mucosa-associated tissues, MALT lymphoma, though rare, must be included in the differential diagnosis of the vaginal neoplasms.     

Primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma with polypoid appearance. Polypoid gastric MALT lymphoma: A clinicopathologic study of eight cases

In the current study, we report eight cases with primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma endoscopically characterized by polypoid lesions in order to highlight their clinicopathologic significance. Four patients were male, their ages ranging from 40 to 78 years old. The resected specimens revealed a histology of low-grade MALT lymphoma characterized by dense lymphocytic infiltration predominantly in the submucosa and a relatively monotonous proliferation of centrocyte-like cells with reactive follicles and infrequent lymphoepithelial lesions. The tumor cells were of CD5-, CD10-, CD20+, BCL2+ and cycline D1- phenotype, and showed a monoclonal rearrangement of immunoglobulin heavy chain genes in the five of six cases examined. Interestingly, Helicobacter pylori (H. pylori) was detected in three (37.5%) of the eight patients, which was significantly lower than previous reports. Two of the H. pylori-positive cases initially underwent H. pylori eradication, but showed no change in their lymphomas after the cure of H. pylori infection. The clinicopathologic findings of the present cases appeared to closely resemble those of colorectal MALT lymphoma with a polypoid appearance and few association of H. pylori infection in their pathogenesis. These gastric polypoid cases may merit separate consideration because of the therapeutic problems they pose.     

Gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma in an animal model of 'Helicobacter heilmannii' infection

While Helicobacter pylori is accepted as the dominant human gastric bacterial pathogen, a small percentage of human infections have been associated with another organism, commonly referred to as 'Helicobacter heilmannii', which is more prevalent in a range of animal species. This latter bacterium has been seen in association with the full spectrum of human gastric diseases including gastritis, peptic ulceration, and gastric carcinomas, including gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. This study describes an analysis of the pathogenic potential of a number of 'H heilmannii' isolates in an animal model of gastric MALT lymphoma. BALB/c mice were infected with ten different 'H heilmannii' isolates originating from both human and animal hosts. The animals were examined at various time points for up to 28 months after infection. The infected animals initially developed a chronic inflammatory response within 6 months. This histological response increased in severity with the length of infection, with the development of overt lymphoma in some animals 18 months after infection. MALT lymphomas were detected in up to 25% of the infected animals. The prevalence of lymphoma was dependent on the length of infection and the origin of the infecting isolates. A range of other histological features accompanied the lymphocytic infiltration, including invaginations of the gastric epithelium and associated hyperplastic tissue, mucus metaplasia, and a small number of diffuse large B-cell lymphomas. The ability to manipulate experientially the presence of the bacterium in the animal model will allow further studies examining the role of antigen drive in the development of Helicobacter-associated MALT lymphoma.     

CD5-positive mucosa-associated lymphoid tissue (MALT) lymphoma: a clinicopathologic study of 14 cases

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a B-cell neoplasm that is typically CD5 negative. We describe the clinicopathologic, immunophenotypic, and cytogenetic features of 14 cases of CD5+ MALT lymphoma. There were 9 men and 5 women (median age, 68 years; range, 34-87 years). MALT lymphoma was initially diagnosed in salivary glands (n = 4), nasopharynx (n = 2), and 1 case each in conjunctiva, thyroid, stomach, colon, skin, lung, kidney, and retroperitoneum. Two patients had localized disease; 9 had disseminated disease with generalized lymphadenopathy (n = 8), multifocal lymphoma (n = 6), or bone marrow involvement (n = 5). No staging information was available for the remaining patients. None presented with B symptoms, splenomegaly, cytopenias, lymphocytosis, monoclonal gammopathy, or elevated serum lactate dehyrogenase. Serum β2-microglobulin was elevated in 6. Morphologically, the neoplasms had features typical of MALT lymphoma being composed of small- to medium-sized cells with round to slightly irregular nuclear contours and moderate amount of cytoplasm. Lymphoepithelial lesions were noted in 4 cases. CD5 was positive in all cases by immunohistochemistry (n = 12) and/or flow cytometry (n = 11). All cases assessed were negative for cyclin D1 (13/13) and CD10 (11/11). Conventional cytogenetics in 7 cases showed trisomy 3 in 3 and diploid in 4. With a median follow-up of 71 months (range, 2-131 months), overall survival at 5 years was 100%, although 5 patients required chemotherapy. Our results show that CD5 expression is rare in MALT lymphoma, and is often associated with nongastric disease and an increased tendency to present with disseminated disease. Overall survival is excellent with appropriate therapy.     

Immunoglobulin specificity of low grade B cell gastrointestinal lymphoma of mucosa-associated lymphoid tissue (MALT) type.

The specificity of the tumor cell immunoglobulin in three cases of low grade B cell gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma has been studied. Using anti-idiotypic antibodies to detect the reactivity of tumor immunoglobulin in tissue sections from the patients and other individuals, we observed specificity for normal tissue components in all three cases studied. Reactivity in one case was with follicular dendritic cells, in the second case with a novel antigen on mucosal post capillary venules, and, in the third case, a broad pattern of reactivity was observed. This study suggests that autoimmunity may play a role in the pathogenesis of gastric lymphoma.     

The bcl-2 gene in primary B cell lymphoma of mucosa-associated lymphoid tissue (MALT).

The bcl-2 gene rearrangement representing t(14:18) chromosomal translocation is the most frequent karyotypic abnormality in non-Hodgkin's lymphomas of follicle center-cell lineage. By using three bcl-2 DNA probes, 21 cases of non-Hodgkin's B cell lymphoma arising from gastrointestinal mucosa and eight cases of follicular lymphomas were examined. No rearrangement of the gene could be detected in the group of gastrointestinal lymphomas, although it was identified in 75% of the follicular lymphomas. The findings suggest that these two groups of lymphomas are not a family at genetic level and support the earlier suggestion that B cell lymphomas arising from gastrointestinal mucosa-associated lymphoid tissue are not of follicle center-cell lineage.     

Antigen-dependent progression of mucosa-associated lymphoid tissue (MALT)-type lymphoma in the stomach. Effects of antimicrobial therapy on gastric MALT lymphoma in mice.

In humans, low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach regress when Helicobacter pylori infection is cured by antimicrobial therapy. Using an animal model of human gastric MALT lymphoma, we observed the effects of Helicobacter felis eradication and the relationship between infection and disease progression. Antimicrobial therapy was given to one-half of the BALB/c mice infected with H. felis for 20 months. Groups of antibiotic-treated and untreated mice were killed 2, 3, and 4 months after antimicrobial therapy (ie, 22, 23, and 24 months after infection). The numbers of mice with MALT decreased after H. felis eradication with no lymphoid follicles seen 4 months after treatment. MALT lymphoma was present in a total of 23% (11/48) of antibiotic-treated infected mice compared with 75% (27/36) in untreated infected mice. These lymphomas were further graded into low-, intermediate-, and high-grade lymphoma. In the untreated mice, lymphoma development was more advanced with 36% low-grade (13/36), 39% intermediate-grade (14/36), and 6% high-grade (large B-cell) lymphoma (2/36) whereas in the treated mice the incidence was 21% (10/48), 6% (3/48), and 0% (0/48), respectively. These observations suggest that antigenic stimulation by H. felis sustained growth and progression of low-grade MALT lymphoma and that primary high-grade gastric lymphomas can evolve from the transformation of these tumors. Eradication of the organism caused low-grade tumors to regress, with inhibition or slowing down of lymphoma development toward high-grade lymphoma. The H. felis mouse model of gastric MALT lymphoma presents an opportunity to address the issues arising from antimicrobial treatment of these tumors in humans.     

Sj?gren's syndrome with MALT (mucosa-associated lymphoid tissue) lymphoma in a 13-year-old girl: a case report]

We report A case of Sj?gren's syndrome complicated with MALT (mucosa-associated lymphoid tissue lymphoma) in childhood. Additionally, Helicobacter pylori infection into the gastric mucosa was highly suspected in this case. A 13-year-old girl suffering from multiple joint pain had received treatment as Juvenile Rheumatic Arthritis with no clinical improvement until introduction to our hospital. On admission to our hospital, high levels of serum anti-SSA and anti-SSB (80.2 and 16.1 holds, respectively) were detected. Minor salivary gland biopsy showed a typical histological finding for Sj?gren's syndrome as infiltrating lymphocytes around the excretory ducts. Computed tomography and 67Gallium scintigraphy showed a gastric tumor, and it was diagnosed as primary gastric B-cell MALT lymphoma by the histopathological findings. Additionally, Helicobacter pylori infection into the gastric mucosa was highly suspected. Recently it is emphasized that infection of Helicobacter pylori is related with gastric MALT lymphoma. There has been no reports of children who have Sj?gren's syndrome associated with malignant lymphoma. Taken together, Helicobacter pylori infection superimposed with Sj?gren's syndrome might accelerate clinical course in our particular case.     

The lymphoepithelial lesion of gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): an ultrastructural study

Lymphoepithelial lesions are a characteristic feature of primary, gastric low-grade lymphomas of mucosa-associated lymphoid tissue (MALT). The lymphoepithelial lesions in 12 such lymphomas have been examined by electronmicroscopy and immunohistochemistry. The lymphocytes present in these lesions are neoplastic centrocyte-like (CCL) B-cells and are morphologically and immunophenotypically similar to those of the surrounding lymphoma. Once the CCL cells penetrate the gastric glands, there is marked structural distortion and disruption of the epithelial cells which leads to their ultimate death. The close association of the neoplastic CCL cells and epithelial cells suggests the presence of a factor, an antigen or other receptor, on the plasma membrane of the latter through which these effects are mediated.     

Spontaneous regression of primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) colliding with invasive ductal carcinoma of the breast: a case report

Malignant lymphomas of the breast, whether they are primary or secondary, are rare diseases, constituting only around 0.1 to 0.15% of the primary neoplasm of the breast. Although the most prevalent histological subtype is diffuse large B-cell lymphoma, primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) also occurs in the breast as in other extranodal sites, comprising about 15% of malignant lymphomas of the breast. In many cases, primary MALT lymphoma of the breast is low grade lymphoma, localized in the breast with indolent behavior and good prognosis. Here we report a case of spontaneous regression of primary MALT lymphoma of the breast. The lymphoma collided with invasive ductal carcinoma in the breast. Both tumors were identified in the Vacora biopsy specimen before the operation. However, the lymphoma disappeared, while the carcinoma remained, in the resected mass. To our knowledge, this is the first case report of spontaneous regression of MALT lymphoma of the breast colliding with breast cancer.     

Proliferation and differentiation of tumour cells from B-cell lymphoma of mucosa-associated lymphoid tissue in vitro

Several characteristics of lymphomas of mucosa-associated lymphoid tissue (MALT type) suggest that they are antigen-dependent and that their growth parodies a normal immune response. We have previously shown that three cases of low-grade B-cell MALT-type lymphoma recognize autoantigens. In this study, we investigated the response of three low-grade and one high-grade case of MALT-type lymphoma to anti-idiotypic antibody as a model of antigen binding either alone or as a co-stimulus with B-cell mitogens. We also studied the response of tumour cells to interleukin-6 (IL-6), which induces differentiation to immunoglobulin-producing cells in many systems. Of the four cases studied, one low-grade case showed markedly enhanced proliferation in response to anti-idiotype alone. This could not be increased by the addition of mitogens. In the remaining two low-grade cases, mitogen responsiveness was observed which was affected by anti-idiotype either by an enhancement or by a reduction in the proliferative response. The high-grade case failed to respond to the stimuli studied. No response to IL-6 was observed. This study supports the suggestion that antigen may affect the pathogenesis of low-grade tumours of MALT type.