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PubMed1975

Small lymphocytes in peripheral lymphoid tissues of nude mice. Life-span and distribution.

The distribution of small lymphocytes according to life-span in the peripheral lymphoid tissues of the mouse mutant "nude" has been studied by means of auto-radiography and scintillation counting to evaluate the localization of B lymphocytes with varying life-span. The vast majority of the lymphocytes in this congenitally athymic mouse are relatively long-lived, although few cells live for 6 weeks or more. Differences in labelling percentages of blood, spleen and lymph node lymphocytes indicated a production of lymphocytes with a short residence time in the spleen. A similar production was not seen in the lymph nodes. While the lymphocytes in the spleen were evenly distributed according to life-span, the paracortical lymphocytes in lymph nodes were found to have a generally shorter life-span than those of the cortex, in opposition to findings in normal mice. The cortical cells which were by far the most numerous in the lymph nodes seemed to be more sessile than para-cortical lymphocytes. The life-span of these latter cells are comparable to those of thoracic duct lymphocytes, and the scarcity of cells in the paracortex reflects the small number of recirculating lymphocytes in nude mice.

Animals↗

PubMed2002

Cellular proliferation of mucosa-associated lymphoid tissue with otitis media: a preliminary study.

Histopathologic and immunohistochemical analyses were used to investigate the cellular proliferation of mucosa-associated lymphoid tissue (MALT) in human temporal bones with and without evidence of otitis media (OM). Anti-proliferating cell nuclear antigen (PCNA) antibody (clone PC10) was applied after the antigen retrieval procedure. Positive PCNA expression was observed in temporal bones that had been stored for 10 to 31 years in 80% ethanol. In specimens with purulent OM, the MALT had faint germinal centers (GCs). Positive PCNA expression in the MALT was moderate and scattered. In specimens with mucous OM, the MALT had complete GCs. Positive PCNA expression in the MALT was moderate to strong, and the distribution of PCNA-positive cells was associated predominantly in the GCs, the mucosal epithelial layer, and/or the subepithelial layer. In specimens with serous OM, the MALT also had complete GCs. However, the PCNA expression was weak and scattered, and appeared to be similar to that of the MALT in the temporal bones without OM. These results indicate that the cellular proliferation of MALT in the temporal bone might reflect the activity that produces secretory IgA against invasion of foreign antigens. However, further studies are needed to elucidate whether the PCNA expression within MALT in the eustachian tube and middle ear is associated with a mucosal immune response to inflammation as in OM.

Autopsy↗

PubMed1990

Immunoglobulin gene rearrangement in the peripheral blood and bone marrow of patients with lymphomas of the mucosa-associated lymphoid tissues.

The theory of 'homing' mechanism has been proposed to explain the association of malignant lymphoma involving multiple sites of mucosa-associated lymphoid tissue (MALT). DNA rearrangement in the peripheral blood and bone marrow specimens of 20 patients with MALT lymphoma were studied utilizing JH and C beta gene probes, aiming to detect circulating lymphoma cells and unrecognized bone marrow involvement. Our search for malignant cells in the peripheral blood was unrewarding and the 'homing' theory remained unproven. However, the study of DNA rearrangement showed to be useful in determining the malignant nature of abnormal lymphoid aggregates found in the bone marrow of these patients.

Adult↗

PubMedDate not supplied

Multiparameter analysis for discreet differential diagnosis of mucosa-associated lymphoid tissue lymphoma in the intestine.

BACKGROUND: The diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma in the intestine is occasionally difficult from histological examination on small biopsy specimens obtained by endoscopy. This study focused on unusual cases of reactive lymphoproliferative disorders in the intestine in order to make a differential diagnosis of MALT lymphoma. MATERIALS AND METHODS: Five patients were examined with regards to clinical symptoms, endoscopic findings and multiparameter analysis (the morphological examination using routine hematoxylin and eosin staining by light microscopy, immunophenotyping by flow cytometry (FCM), immunohistochemistry and genotyping of extracted DNA). RESULTS: All cases showed an aggregation of lymphocytes and one case showed similar features to lymphoepithelial lesions. Analyses of FCM and genetic rearrangements denied the monoclonality in all cases. Consequently, we considered that all cases should be diagnosed as reactive lymphoid hyperplasia and inflammatory change. CONCLUSION: Multiparameter analysis is useful in making an exact diagnosis of MALT lymphoma and therefore contributes to prevent unnecessary overtreatment.

Adolescent↗

PubMed2003

Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy.

Gut-associated lymphoid tissue (GALT) harbors the majority of T lymphocytes in the body and is an important target for human immunodeficiency virus type 1 (HIV-1). We analyzed longitudinal jejunal biopsy samples from HIV-1-infected patients, during both primary and chronic stages of HIV-1 infection, prior to and following the initiation of highly active antiretroviral therapy (HAART) to determine the onset of CD4(+) T-cell depletion and the effect of HAART on the restoration of CD4(+) T cells in GALT. Severe depletion of intestinal CD4(+) T cells occurred during primary HIV-1 infection. Our results showed that the restoration of intestinal CD4(+) T cells following HAART in chronically HIV-1-infected patients was substantially delayed and incomplete. In contrast, initiation of HAART during early stages of infection resulted in near-complete restoration of intestinal CD4(+) T cells, despite the delay in comparison to peripheral blood CD4(+) T-cell recovery. DNA microarray analysis of gene expression profiles and flow-cytometric analysis of lymphocyte homing and cell proliferation markers demonstrated that cell trafficking to GALT and not local proliferation contributed to CD4(+) T-cell restoration. Evaluation of jejunal biopsy samples from long-term HIV-1-infected nonprogressors showed maintenance of normal CD4(+) T-cell levels in both GALT and peripheral blood. Our results demonstrate that near-complete restoration of mucosal immune system can be achieved by initiating HAART early in HIV-1 infection. Monitoring of the restoration and/or maintenance of CD4(+) T cells in GALT provides a more accurate assessment of the efficacy of antiviral host immune responses as well as HAART.

Adult↗

PubMed1996

Ultrastructural investigation of M-cells and lymphoepithelial contacts in naso-pharyngeal associated lymphoid tissue (NALT).

The nasopharyngeal and palatine tonsil, two lymphoepithelial structures situated at the entrance of respiratory and gastrointestinal tracts, show striking similarity with lymphoid tissue of bronchus and gut (BALT, GALT). The information obtained by previous investigations in our laboratory on M-cells in the lymphoepithelium of the Peyer's patches (PP) served as a guidance in our search for M-cells in adenoids and tonsils.

Adenoids↗

PubMed1992

Effect of gut-associated lymphoid tissue on cellular proliferation in proximal and distal colon of the rat.

In previous studies, chemically induced colonic carcinomas were found to originate preferentially from crypts adjacent to lymphoid tissue. Proliferative parameters and mucosecretion were analyzed in proximal and distal rat colon in relation to the proximity of lymphoid patches. Animals received an intraperitoneal pulse of bromodeoxyuridine 1-hr before death. In both proximal and distal colon, crypts located at the immediate proximity of the lymphoid formations contained fewer mucous cells (P less than 0.001), but a higher percentage of proliferative epithelial cells (P less than 0.001) than the crypts far from lymphoid formations. The labeling index was higher in crypts adjacent to lymphoid patches compared to crypts distant from lymphoid patches only in the lower third of the crypts. The association of an increased proliferative activity and a decrease in differentiated mucosecreting cells in colonic crypts adjacent to lymphoid patches could be related to the particular sensitivity of these crypts cells to the effects of mutagens and carcinogens.

Animals↗

PubMed2000

Immunohistochemical study of lymphoid tissues in adjuvant arthritis (AA) by image analysis; relationship with synovial lesions.

The aim of this study was to examine leucocyte populations in lymphoid organs during AA and to ascertain the relationship with lesions in synovial joints. Popliteal lymph nodes, spleen and knee synovial membranes were removed from both healthy and AA rats at intervals of 3-4 days over a 3-week period. Cryostat sections were stained with MoAbs directed against lymphocyte and macrophage subpopulations, and studied by image analysis. Throughout the arthritic period, high numbers of ED1+ and ED3+ macrophages were seen in both lymphoid compartments and intercellular adhesion molecule-1 (ICAM-1) expression also increased in some zones of lymph nodes and spleen. The percentages of CD4+ and CD8+ cells rose in the splenic zones studied but fell in the lymph node cortex. Very few natural killer (NK) cells were found in lymphoid tissues, but the number rose after AA induction. In synovia from AA rats, ED2+ macrophages proliferated but alpha/beta T cell infiltration was only occasionally observed, accompanied by ED1+ cells and ICAM-1 expression. In conclusion, synovitis developing after AA induction seems to be caused directly by macrophages and indirectly by lymphocytes placed both in popliteal lymph nodes and spleen.

Animals↗

PubMed1987

Localization of interleukin-1 in normal or reactive lymphoid tissues and skin: abundance of IL-1 in interdigitating reticulum cells.

The distribution of interleukin 1 producing cells was determined in the human lymphoid tissues and skin using immunohistochemical staining and a rabbit anti-interleukin-1 antibody. Interleukin-1 was detected mainly in the interdigitating reticulum cells localized in the T cell zone. Approximately, 10-30% of the histiocytes were also positively stained by anti-interleukin-1. The results suggests that interdigitating reticulum cells may play an important role in the initiation and amplification of T-cell immunity.

Animals↗

PubMed2004

Nasal associated lymphoid tissue & M cells, a window to persistent streptococcal infections.

BACKGROUND & OBJECTIVES: Intranasal infection of mice has been used as a model of streptococcal pharyngitis, as nasal associated lymphoid tissue (NALT) in this animal is structurally and functionally analogous to human tonsils. The present study was carried out to determine whether group A streptococci preferentially colonized or invaded NALT. METHODS: Lux(+) strain Sp3 was created and exponential phase bacteria were introduced intranasally into BALB/C female mice, total photon emission from selected areas was quantified, sections of NALT tissues were used for immunofluorescent staining and M cell staining. RESULTS: Intranasal infection of mice with bioluminescent group A streptococci or unlabeled streptococci demonstrated that NALT was a primary target of this pathogen. Streptococci readily gained access to the blood stream from this site of infection. Immunofluorescence microscopy studies showed that M cells, dispersed along the mucosal epithelium adjacent to NALT, were preferentially infected and likely to provide the window through which streptococci reached the underlying tissue. INTERPRETATION & CONCLUSION: The present study suggests that this upper respiratory Gram positive pathogen uses a mechanism similar to that of enteric pathogens in the intestine to gain access to underlying tissue, lymphatics and blood.

Animals↗

PubMed2001

Multiple organ mucosa-associated lymphoid tissue lymphomas often involve the intestine.

BACKGROUND: Low grade mucosa-associated lymphoid tissue (MALT) lymphomas usually are confined to single extranodal organs. Although some case reports have been published, clinicopathologic characteristics of multiorgan MALT lymphomas remain unclear. METHODS: The authors evaluated 7 MALT lymphoma cases involving multiorgans in the past 7 years. In this period, they experienced 304 cases of MALT lymphomas. They analyzed the clinicopathologic features of these cases, including examination of clonal comparison among the lesions. RESULTS: The patients, 4 females and 3 males, were aged 55-68 years old (average, 60.1 years). Four cases showed multiple organ involvement at the initial diagnosis or after a short period. In the other three cases, primary foci were the stomach, thyroid gland, and ocular adnexa; after a rather long period (3 years or more), distant metastases were found. Although intestinal primary lymphomas are rather rare, six of the seven cases showed large intestinal involvement. Lymph node involvement was proven in only three cases. The patients were rather resistant to the various therapeutic approaches. Although six patients are alive, five are with disease. DNA analyses revealed that in five of the cases evaluated, identical clones were detected among the different affected organs. CONCLUSIONS: Multiorgan MALT lymphomas are rather rare. Most cases probably derived from a single clone, and lymphoma cells may selectively move among MALTs via a homing system with preferential involvement of the colon. Because multiorgan MALT lymphomas rarely achieve complete remission by treatment with combination chemotherapy or irradiation, MALT lymphomatous lesions should be checked carefully, especially in the large intestine.

Aged↗

PubMed2003

Tumor-infiltrating T cells with similar antigen binding sites in different mucosa-associated lymphoid tissue type B cell lymphomas.

B cell lymphomas of mucosa-associated lymphoid tissue (MALT)-type arise on the background of chronic inflammation due to either autoimmunity or infection at various sites of the organism. Characteristically the tumor-infiltrating T cells found in large numbers in MALT-type lymphomas are predominantly of CD4(+) phenotype and may have impact on tumor pathogenesis. To assess whether the chromosomal translocation t(11;18)(q21; q21) that is specific for at least a subset of MALT-type lymphomas may have an impact on tumor environment, we investigated the antigen binding sites of tumor-infiltrating T cells from one t(11;18)-positive tumor of the thyroid and one t(11;18)-negative tumor of the stomach. MHC Allelotyping was performed and revealed common alleles in HLA-DR and HLA-DQ loci. Cloning and sequencing of the complementary determining region 3 in V(beta2) chains of T cell receptors demonstrated the use of identical J(beta)segments in both patients, suggestive for recognition of the same antigen. We therefore suggest that tumor-infiltrating CD4(+) T cells are tightly integrated in MALT-type lymphoma immunoarchitecture irrespective of genetic background and localization of the tumors.

Amino Acid Sequence↗

PubMed2001

Somatostatin-receptor scintigraphy for staging and follow-up of patients with extraintestinal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT)-type.

The majority of lymphomas of the mucosa-associated lymphoid tissue (MALT)-type arise in the stomach, but extragastric locations are also frequently encountered. Due to previous results indicating that somatostatin receptor (SSTR)-expression distinguishes between gastric and extragastric MALT-type lymphoma, we have initiated a study to evaluate the role of SSTR-scintigraphy for staging and follow-up of patients with extragastric manifestations of MALT-type lymphoma. A total of 30 consecutive patients, including 24 with primary extragastric MALT-type lymphoma, 5 patients with dissemination to extragastric sites (including colon, lung, parotid, ocular adnexa and breast) following an initial gastric MALT-lymphoma and one patient with spread to stomach, lung and lymph nodes following parotid lymphoma were prospectively studied. All patients had histologically verified MALT-type lymphoma: 2 patients had lymphoma presenting in the lung, 9 in the ocular adnexa, 7 had lymphomas in the parotid, 2 patients had disease located in the breast, 3 patients had lymph-node relapse following MALT-type lymphoma of the parotid, the lacrimal gland and the thyroid, and 1 had primary MALT-lymphoma of the liver. All patients underwent SSTR-scintigraphy using (111)In-DTPA-D-Phe(1)-Octreotide ((111)In-OCT) before initiation of therapy, while 13 also had a second scan after treatment. The results of gamma camera imaging were compared to conventional staging. No positive scans could be obtained in patients with dissemination following gastric lymphoma, while all patients with primary extragastric lymphoma had positive scans at the site of histologically documented involvement before initiation of therapy. In addition, also the patient with secondary spread to stomach, lung and lymph nodes was positive in all documented lymphoma sites. In one patient, focal tracer uptake in projection to the maxillary sinus was documented, which was bioptically verified as inflammation. In the scans performed after therapy, focal tracer accumulation in the left orbit indicated persistence of disease following irradiation in one patient with otherwise negative work-up, which was verified by MRI and biopsy 6 months later. In another patient, a positive scan indicated disease relapse in the lacrimal gland 9 months before clinical verification by means of ultrasound. In one patient, a focus not present in the pretherapeutic scan was found in the ethmoidal sinus, corresponding to a hyperplastic polyp. Both SST-scan as well as CT indicated disease persistence in one case, while negative scans corresponding to complete remission as judged by conventional staging were obtained following therapy in the remaining patients, and absence of relapse has been confirmed for a median follow-up of 2 years. These results indicate that (111)In-OCT is an excellent tool for staging and non-invasive therapy-monitoring in extragastric MALT-type lymphomas. These data further confirm our initial finding that gastric MALT-type lymphomas do not express relevant amounts of respective SSTR, and that SSTR-scanning is able to distinguish between gastric vs extragastric origin of MALT-type lymphoma irrespective of the site of presentation.

Adult↗

PubMed2005

Gastric mucosa-associated lymphoid tissue lymphoma and Helicobacter pylori: scratch and win.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is generally associated with Helicobacter pylori infection and, in the great majority of patients, regresses after eradication. H. pylori-negative MALT lymphoma occurs in a small minority of cases in which treatment is based on surgery or chemoradiotherapy. In the search for H. pylori based on histology and the C13 urea breath test, this report describes a case with a series of false-negative results, thus confirming the possibility of a lower detectability of H. pylori in patients with MALT gastric lymphoma and supporting the use of additional tests in evaluating such pathology, including polymerase chain reaction. Additionally, treatment with CD20 monoclonal antibody (rituximab) is suggested as an alternative to surgery or treatment with chemotherapy or radiotherapy in patients with truly H. pylori-negative gastric MALT lymphoma.

Adult↗

PubMed1998

Th1/Th2 cytokine profiles in the nasopharyngeal lymphoid tissues of children with recurrent otitis media.

The cytokine profile in adenoidal lymphoid tissue was studied in 22 patients. Lymphocytes from adenoid tissues and peripheral blood were submitted for cytokine assays using an enzyme-linked immunosorbent assay kit for interferon-gamma, interleukin (IL)-2, IL-4, IL-5, IL-6, and IL-10. Adenoidal lymphocytes appear to produce significantly less Th1 cytokines (IL-2, interferon gamma) compared to the patient's peripheral blood lymphocytes, whereas IL-4 and IL-5 (Th2 cytokines) appear to be synthesized to the same extent as, if not slightly more than, in the homologous peripheral blood lymphocytes. Because the relationship between Th1 and Th2 cytokines is extremely important in modulating the immune response, it is advisable to determine the role of the cytokine profiles of T-lymphocytes in the nasopharynx and its relationship to the development of inflammation of the eustachian tube and middle ear.

Adenoids↗

PubMed1998

Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with radiation alone.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach (MLS) has recently been defined as a distinct clinicopathologic entity, often associated with Helicobacter pylori infection. Many regard antibiotic therapy as the primary treatment of MLS, but in the absence of H pylori infection, or when salvage of antibiotic failures is required, gastrectomy and/or chemotherapy have frequently been used. This study evaluates the efficacy of low-dose radiotherapy alone as an alternative to surgery. PATIENTS AND METHODS: Seventeen patients with stage I to II(2) low-grade MLS without evidence of H pylori infection or with persistent lymphoma after antibiotic therapy of associated H pylori infection were included in this series. Median age was 69 years (range, 39 to 84). Median total radiation dose was 30 Gy (range, 28.5 to 43.5 Gy) delivered in 1.5-Gy fractions within 4 weeks to the stomach and adjacent lymph nodes. Following treatment, all patients underwent endoscopic evaluation and biopsy at a median of 4 months, at 6-month intervals to 2 years, and annually thereafter. RESULTS: All obtained a biopsy-confirmed complete response. At a median follow-up time of 27 months (range, 11 to 68) from completion of radiotherapy, event-free survival was 100%. Treatment was well tolerated, with no significant acute side effects. All remained asymptomatic at last follow-up. CONCLUSION: These results suggest that effective treatment of MLS with low-dose radiation therapy alone is feasible and safe, and allows stomach preservation. Longer follow-up evaluation is required to determine the long-term efficacy of this treatment approach and its side effects. Further studies should clarify the indications for radiotherapy in H pylori-negative or antibiotic-resistant cases of MLS.

Adult↗

PubMed2001

Prospective study of Helicobacter pylori eradication therapy in stage I(E) high-grade mucosa-associated lymphoid tissue lymphoma of the stomach.

PURPOSE: High-grade mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach are generally believed to be Helicobacter pylori-independent, autonomously growing tumors. However, anecdotal cases of regression of high-grade lymphomas after the cure of H pylori infection had been described. The present prospective study was conducted to evaluate the effect of anti-H pylori therapy in stage I(E) high-grade gastric MALT lymphomas. PATIENTS AND METHODS: Sixteen patients with H pylori infection and stage I(E) gastric high-grade MALT lymphoma consented to a brief antibiotic therapy as first-line treatment from June 1995 through April 2000. Then, patients underwent intensive endoscopic follow-up examinations (+/- endoscopic ultrasonography) with biopsy to evaluate tumor response. Patients with significant improvement of gross lesions that accompanied regression of large cells were followed up without additional treatment. Patients without significant improvement were immediately referred to systemic chemotherapy. RESULTS: Eradication of H pylori was achieved in 15 patients and was accompanied by rapid gross tumor regression and disappearance of large cells in 10. All 10 of these patients with early response had subsequent complete histologic remission of lymphoma. The complete remission rate was 62.5% (95% confidence interval, 35.8% to 89.1%). The response rate was not affected by the tumor grading (proportion of large blast cells within the tumor) but was adversely affected by the depth of tumor invasion. At a median follow-up of 43.5 months (range, 21.1 to 67.4 months), all 10 of these patients remained lymphoma-free. The median duration of complete response was 31.2 months (range, 14.4 to 49.1 months). CONCLUSION: These results suggest that high-grade transformation is not necessarily associated with the loss of H pylori dependence in early-stage MALT lymphomas of the stomach.

Adult↗

PubMedDate not supplied

[Mucosa-associated lymphoid tissue lymphoma of the lacrymal gland--a case report].

Mucosa-associated lymphoid tissue (MALT) lymphoma has drawn attention in the last twenty years due to its pathological and clinical characteristics. It is a question of B-cell neoplasm with extranodal origin, and with invariable prolonged localisation, indicating indolent malignancy. It is believed that this type of lymphoproliferative neoplasm is triggered by chronic antigenic stimulation. This is supported by the observation that this type of extranodal lymphoma is frequently found in regions affected by chronic inflammation, such as mucosa of the stomach, the respiratory tract, as well as of the salivary and the thyroid glands. It is not common in the breasts, liver, kidneys, and gallbladder. Primary orbital lymphomas account for 5-14% of all extranodal lymphomas. The most commonly involved orbital tissue structures are: conjunctiva, the eyelids, and retrobulbar tissue, while the development of the disease in the lachrymal gland is extremely rare. No wonder that the literature on the presentation, treatment modalities, and recommendations for the monitoring of MALT lymphoma of the lachrymal gland is so scarce. Given the aforementioned facts, the case report of a patient with primary localisation of MALT lymphoma of the lachrymal gland was considered intriguing; initially, the patient was successfully treated by surgical intervention followed by radiation therapy (TD 30 Gy).

Adult↗