What is MALT lymphoma
MALT lymphoma is an indolent B-cell non-Hodgkin lymphoma (NHL) first described as a separate entity in 1983 by Isaacson and Wright. Accounting for 8% of all NHL, approximately one-third of MALT lymphomas originate in the stomach. MALT lymphoma arises from marginal zone B cells that have undergone post follicular differentiation following chronic antigenic stimulation secondary to persistent infection or autoimmune disease. In the stomach, it is strongly associated with H. pylori infection with 90–95% of patients with gastric MALT lymphoma showing evidence of concurrent or previous infection, compared with 50% of the global population.
Gastrointestinal lymphoma Gastric and intestinal lymphomas are rare and are usually caused by chronic inflammation and activation of the local immune system, as with H. pylori infection, coeliac disease and immunoproliferative small intestinal disease (IPSID), which occurs with chronic intestinal infection . MALT lymphoma is a marginal zone B-cell lymphoma which accounts for 50% of gastric lymphomas, and eradication of H. pylori is effective treatment in the majority of cases. Symptoms of IPSID include weight loss, diarrhoea, malabsorption and abdominal pain. Barium meal and follow-through examination, computed tomography (CT), magnetic resonance imaging (MRI) scanning, capsule endoscopy (CE) and exploratory laparotomy with intestinal biopsy are often used to make the diagnosis .
(a) MALT lymphoma; (b) MALT lymphoma- Helicobacter pylori immunostaining
Other infections that have been linked to MALT lymphoma in nongastric locations include Chlamydia psittaci (ocular adnexa), Borrelia burgdorferi (skin), and Campylobacter jejuni (small bowel). An association with autoimmune diseases is also described including Sjögren’s syndrome (salivary gland MALT lymphoma), Hashimoto’s autoimmune thyroiditis (thyroid MALT lymphoma), Conjunctival Lymphoma (eye MALT lymphoma)and polymyalgia rheumatica. Uncertainty remains as to whether lymphoma outcomes diff er in this population. No inherited component has been identified. Th e median age at presentation is 61 years 12 and prognosis is generally considered good. Poor prognostic features include non-GI or distant nodal involvement, poor WHO performance status, bulky tumor, high beta-2 microglobulin level, high lactate dehydrogenase (LDH), low serum albumin, and anemia.
MALT lymphoma survival rates
Five-year survival ranges from 80% to 95%, despite progression-free survival (PFS) being comparably short in those with advanced stage or poor prognostic features.
Diagnosis and staging MALT lymphoma
Diagnosis and staging MALT lymphoma is oft en multifocal disease in the organ of origin and is frequently macroscopically indistinguishable from other disease processes in the GI tract. 17 Endoscopy is key to diagnosing MALT lymphoma, with multiple biopsies of the visible lesions required, as well as samples of macroscopically normal tissue, termed “gastric mapping.” Histologically, there is expansion of the marginal zone compartment with development of sheets of neoplastic small lymphoid cells . Th e morphology of the neoplastic cells is variable with small mature lymphocytes, cells resembling centrocytes (centrocyte like cells), or marginal zone/monocytoid B cells. Plasmacytoid or plasmacytic differentiation is frequent. Lymphoid follicles are ubiquitous to MALT lymphoma but may be indistinct as they are oft en overrun or colonized by the neoplastic cells. Large transformed B cells are present scattered among the small cell population. If these large cells are present in clusters or sheets, a diagnosis of associated large B-cell lymphoma should be considered. A characteristic feature of MALT lymphoma is the presence of neoplastic cells within epithelial structures with associated destruction of the glandular architecture to form lymphoepithelial lesions.
MALT lymphoma Treatment
Historically, surgical treatment of localized disease was adopted with high cure rates. Distal partial gastrectomy was frequently associated with stump recurrence aft er a disease-free interval and total gastrectomy resulted in significant long-term morbidity. With the advent of stomach conserving therapies with similar outcomes, the role of surgery is restricted to the treatment of rare complications such as perforation or bleeding that cannot be controlled endoscopically.
Association of gastric MALT lymphoma with H. pylori infection
Following the recognition of the association of gastric MALT lymphoma with H. pylori infection, it was established that early-stage gastric disease could be cured by H. pylori eradication, which is now the mainstay of therapy. Fifty to 95% of cases achieve complete response (CR) with H. pylori treatment. H. pylori eradication therapy consists of proton-pump inhibitor (PPI) plus clarithromycin-based triple therapy with amoxicillin or metronidazole for 14 days. Increasing clarithromycin-resistant strains has led to the recommendation that this drug is avoided in areas where resistant strains are prevalent. In these areas, and when second-line therapy is required, quadruple therapy with PPI, colloidal bismuth, tetracycline, and metronidazole is recommended and this is effective even in areas with high prevalence of metronidazole-resistant strains.
radiotherapy is a valid option for MALT lymphoma; however, it is not universally used. It provides local control and potential cure in localized gastric stage IE and II 1E disease with 5-year EFS of 75–90% reported in retrospective studies. However, the irradiation field is potentially large as it must include the whole stomach, which can vary greatly in size and shape. Irradiation techniques have improved considerably in the last 20 years, including treating the patient in a fasting state, decreasing the irradiated field and required dose. Th e moderate dose of 30 Gray (Gy) of involved-field radiotherapy administered in 15 fractions (doses) can be associated with tolerable toxicity and adequate outcomes. Hence, radiotherapy is an acceptable approach for local disease where antibiotic therapy has failed, or is not indicated; however, its use in individuals is determined by the radiation field. Evidence also suggests that radiotherapy can be utilized to control localized relapses outside the original radiation field.
MALT lymphoma is exquisitely chemotherapy sensitive. Chemotherapy is reserved for those with disseminated disease at presentation or lack of response to local treatment. Rituximab, the anti-CD20 chimeric antibody, is a key component of therapy. Responses vary from 55% to 77% with monotherapy and 100% in combination with chemotherapy. Oral alkylating agents such as cyclophosphamide or chlorambucil have been administered for a median duration of 12 months with high rates of disease control (CR up to 75%) but appear not to be active in disease. The purine nucleoside analogs fludarabine and cladribine also demonstrate activity, the latter conferring a CR rate of 84% (100% in those with gastric primaries) in a small study.A pivotal study of rituximab plus chlorambucil compared with chlorambucil alone (IELSG-19 study, n = 227) demonstrated a significantly higher CR rate (78% vs. 65%; p = 0.017) and 5-year EFS (68% vs. 50%; p = 0.024) over chlorambucil alone. However, 5-year OS was not improved (88% in both arms). First-line treatment of choice is generally rituximab in combination with single alkylating agents or fludarabine, or a combination of all three drugs. Th e final results of this study, including the later addition of a rituximab-alone arm, are pending.
Y e, H ., L iu, H ., A ttygalle, A . et al. ( 2003 ) Variable frequencies of t(11;18) (q21;q21) in MALT lymphomas of diff erent sites: signifi cant association with CagA strains of H. pylori in gastric MALT lymphoma . Blood , 102 , 1012 – 1018 . 25. Bayerdorff er , E. , Oertel , H. , Lehn , N. et al. ( 1989 ) Topographic association between active gastritis and Campylobacter pylori colonisation. J Clin Pathol , 42 , 834 – 839 . 26. L ehours, P ., R uskone-Fourmestraux, A ., L avergne, A . et al. ( 2003 ) Which test to use to detect Helicobacter pylori infection in patients with low-grade gastric mucosa-associated lymphoid tissue lymphoma? Am J Gastroenterol , 98 , 291 – 295 . 27. Eck , M. , Greiner , A. , Schmausser , B. et al. (1 999) E valuation of Helicobacter pylori in gastric MALT-type lymphoma: diff erences between histologic and serologic diagnosis . Mod Pathol , 12 , 1148 – 1151 . 28. C arbone, P .P., K aplan, H .S., M usshoff , K. et al. (1 971) R eport of the Committee on Hodgkin’s Disease Staging Classifi cation. Cancer Res , 31 , 1860 – 1861 . 29. M usshoff , K. ( 1977 ) Clinical staging classifi cation of non-Hodgkin’s lymphomas (author’s transl) . Strahlentherapie , 153 , 218 – 221 . 30. A viles, A ., N ambo, M .J., N eri, N . et al. (2 005) M ucosa-associated lymphoid tissue (MALT) lymphoma of the stomach: results of a controlled clinical trial. Med Oncol , 22 , 57 – 62 . 31. F ischbach, W ., G oebeler, M .E., R uskone-Fourmestraux, A . et al. ( 2007 ) Most patients with minimal histological residuals of gastric MALT lymphoma aft er successful eradication of Helicobacter pylori can be managed safely by a watch and wait strategy: experience from a large international series. Gut , 56 , 1685 – 1687 . 32. d e Boer, J .P., H iddink, R .F., R aderer, M . et al. ( 2008 ) Dissemination patterns in non-gastric MALT lymphoma. Haematologica , 93 , 201 – 206 . 33. R aderer, M ., S treubel, B ., W oehrer, S . et al. ( 2005 ) High relapse rate in patients with MALT lymphoma warrants lifelong follow-up . Clin Cancer Res , 11 , 3349 – 3352 .
Incoming search terms:
- capsule endoscopy diagnose ipsid
- MALT gastric lymphoma treatment
- visible evidence of malt lymphoma on endoscopy