Peter G. Isaacson

Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori

Certain features of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (MALT) suggest the tumour is antigen-responsive. Given the close association between gastric MALT lymphoma and Helicobacter pylori, these organisms might be evoking the immunological response, and eradication of H pylori might inhibit the tumour. 6 patients in whom biopsies showed histological and molecular-genetic evidence of low-grade gastric B-cell MALT lymphoma with H pylori infection were treated with antibiotics. In all cases H pylori was eradicated and in 5, repeated biopsies showed no evidence of lymphoma. These results suggest that eradication of H pylori causes regression of low-grade B-cell gastric MALT lymphoma, and that anti-H-pylori treatment should be given for this lymphoma.

Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma

Although lymphoid tissue is absent in normal gastric mucosa, primary lymphomas arise in the stomach and most of these recapitulate the features of mucosa-associated lymphoid tissue (MALT). Gastric lymphoid tissue is known to be acquired in response to local infection by Helicobacter pylori, and we have confirmed this in 450 patients with H pylori-associated gastritis of whom 125 showed mucosal lymphoid follicles. In 8 patients, B lymphocytes infiltrated epithelium, which is a feature characteristic of MALT. We also examined 110 cases of gastric MALT lymphoma and found H pylori infection in 101 of these (92%). We conclude that gastric MALT is acquired in H pylori infection and that this provides the necessary background in which MALT lymphoma might develop.

Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma.

As illustrated in the two cases described in this paper close morphologic and immunohistochemical similarities exist between Mediterranean lymphoma (MTL) and primary gastrointestinal lymphoma of follicle center cell (FCC) origin as it occurs in Western countries. Similarities between the two conditions include a dense noninvasive monotypic lamina propria plasma cell infiltrate, present in all cases of MTL and in some cases of Western gastrointestinal FCC lymphoma, and an invasive infiltrate of FCCs morphologically distinct from the plasma cells. A distinctive lesion produced by individual gland invasion characterizes both types of lymphoma. A clonal relationship between the lamina propria plasma cells and the invasive FCCs, long suspected but never proved in MTL, can be demonstrated in Western cases. Many of the histologic and clinical features common to these lymphomas can be explained in the context of the normal maturation sequences of gut associated lymphoid tissue. It is suggested that MTL and Western cases of primary FCC gastrointestinal lymphoma share a common histogenesis from mucosa associated lymphoid tissue.

Malignant lymphoma of mucosa‐associated lymphoid tissue

Lymphomas of the gastrointestinal tract, salivary glands, lung and thyroid are grouped together as tumours arising in mucosa‐associated lymphoid tissue. The great majority of them are of B‐cell origin but distinctive T‐cell lymphomas are also recognized in the gastrointestinal tract. These lymphomas tend to remain localized for prolonged periods but, whereas the B‐cell group respond favourably to local therapy, the T‐cell group are associated with severe morbidity and their overall prognosis is extremely poor. Accepted histological classifications of non‐Hodgkins lymphomas are difficult to apply to these tumours. In this paper their morphological features are reviewed; recent findings based on immunohistochemistry and DNA analysis are presented; and the biological behaviour of these tumours is discussed insofar as they offer insight into mucosal immunological mechanisms.

The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori.

An association has been shown between colonisation of gastric mucosa by Helicobacter pylori, acquisition of mucosa-associated lymphoid tissue (MALT), and occurrence of primary B-cell gastric MALT lymphoma. We investigated the immunological response of cells from 3 low-grade primary B-cell gastric MALT lymphomas to H pylori type NCTC 11637 and 12 isolates of H pylori from patients without lymphomas. After co-culture of tumour cells with bacteria, cells were examined for phenotypic evidence of activation and proliferation, and supernatant assayed to detect tumour-derived immunoglobulin and interleukin-2 (IL-2). Neoplastic B cells and non-neoplastic T cells proliferated, and IL-2-receptor expression by most cells in the cultures was increased with stimulating strains of H pylori. There were also increases in tumour immunoglobulin and IL-2 release when activation and proliferation were seen in response to stimulating bacteria. Removal of T cells from the tumour cell suspension reduced proliferation and IL-2-receptor expression. In comparison, no responses were seen in cells from high-grade gastric MALT lymphomas or low-grade B-cell MALT lymphomas of other sites. The response of low-grade B-cell gastric MALT lymphomas to stimulating strains of H pylori is dependent on H-pylori-specific T cells and their products, rather than the bacteria themselves.

Extranodal malignant lymphoma arising from mucosa‐associated lymphoid tissue

Four cases of extranodal malignant lymphoma, one each arising in the stomach, salivary gland, lung, and thyroid, are described. These cases have many clinical, histopathologic, and immunohistochemical features in common, and it is proposed that this is because they share a common pattern of histogenesis from mucosa‐associated lymphoid tissue (MALT). Clinical features of MALT‐derived lymphomas include a tendency to remain localized for prolonged periods, and, thus, to be responsive to locally directed therapy. Histologically, this group of tumors is characterized by a noninvasive lymphoplasmacytic infiltrate within which foci of follicle center cells (FCC) can be seen invading epithelial structures, forming lymphoepithelial lesions. Immunohistochemistry reveals monotypic cytoplasmic immunoglobulin (CIg) in the plasma cells serving to highlight the CIg‐negative lymphoepithelial lesions. The clinical and histopathologic features of these lymphomas can be understood in the context of the behavioral characteristics and morphology of MALT.

Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types

MALT B cell lymphomas with t(1;14)(p22;q32) showed a recurrent breakpoint upstream of the promoter of a novel gene, Bcl10. Bcl10 is a cellular homolog of the equine herpesvirus-2 E10 gene: both contain an amino-terminal caspase recruitment domain (CARD) homologous to that found in several apoptotic molecules. Bcl10 and E10 activated NF-kappaB but caused apoptosis of 293 cells. Bcl10 expressed in a MALT lymphoma exhibited a frameshift mutation resulting in truncation distal to the CARD. Truncated Bcl10 activated NF-kappaB but did not induce apoptosis. Wild-type Bcl10 suppressed transformation, whereas mutant forms had lost this activity and displayed gain-of-function transforming activity. Similar mutations were detected in other tumor types, indicating that Bcl10 may be commonly involved in the pathogenesis of human malignancy.

Tumours of histiocytes and accessory dendritic cells: An immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases

Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases

MALT lymphoma: from morphology to molecules

Hints that the growth of some lymphomas is stimulated by bacterial antigens and can be controlled by treatment with antibiotics first emerged in the 1970s. Subsequently, a specific type of B-cell lymphoma — mucosa-associated lymphoid tissue (MALT) lymphoma — was identified that is associated with bacterial infection and auto-antigen stimulation. This article chronicles the clinical, immunological and molecular developments in our knowledge of MALT lymphoma and the factors that contribute to its pathogenesis.

Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy

20-30% of gastric mucosa-associated lymphoid tissue (MALT) lymphoma associated with Helicobacter pylori do not regress after antibiotic therapy. Regression can be assessed only by extended follow-up. To assess whether t(11;18, q21;q21), which results in a chimeric transcript between the AP12 and MLT genes, predicts lymphoma resistance to antibiotic therapy, we screened for the fusion transcript with RT-PCR in ten responsive and 12 non-responsive gastric MALT lymphomas. The AP12-MLT transcript was detected in nine (75%) of 12 patients non-responsive to antibiotic therapy but not in responsive patients. Most H pylori-associated gastric MALT lymphomas that do not respond to antibiotic therapy are associated with t(11;18, q21;q21).