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Histopathology of Mucosa-Associated Lymphoid TissueTNO Nutrition and Food Research, 3704 HE Zeist, The Netherlands Correspondence: Address correspondence to: C. Frieke Kuper, TNO Nutrition and Food Research, P.O. Box 360, 3704 HE Zeist, The Netherlands; e-mail:frieke.kuper{at}tno.nl
Mucosa-associated lymphoid tissue (MALT) is a generalized term incorporating a disseminated collection of lymphoid tissues in multiple sites throughout the body. MALT sites that have been/are primarily studied include bronchus-associated lymphoid tissue (BALT), gut-associated lymphoid tissue (GALT), and nasopharynx-associated lymphoid tissue (NALT). Since MALT sites are often under-sampled in conventional toxicity studies, MALT lesions have not been extensively documented in these lymphoid effector sites. Lesions of the nasopharyngeal lymphoid tissue and Peyer’s patches include degeneration, inflammation, and both primary and metastatic neoplasia.
Key Words: Lymphatic ectasia • macrophage aggregates • granulomas • MALT lymphoma
The organized mucosa-associated lymphoid tissues, collectively denoted MALT, and the mucosa-draining lymph nodes are considered to be the inductive sites for mucosal immunity, i.e., trigger the näive immune cells and generate the memory-effector cells (Brandtzaeg and Pabst, 2004; Cesta, 2006). The effector sites are the sites where secretory immunoglobulins are generated and where e.g., allergic inflammation is effectuated. The effector sites consist of histological compartments, which are distinctly different from the inductive sites, including the lamina propria, the stroma of exocrine glands and surface epithelia. It should be acknowledged that the distinction between immune response-induction and effector sites is not strict, for example the lamina propria is also involved in the differentiation of lymphocytes. The focus of the paper is on the histopathology of part of MALT, namely the Peyer’s patches (PP) and nasopharynx-associated lymphoid tissues (NALT), whereas the mucosa-draining lymph nodes are described elsewhere (Willard-Mack, 2006; Elmore, 2006a).
Semi-Quantitative Changes in Cellularity, Compartment Size, and Germinal Center Development
Inflammation, Macrophage Aggregates and Granulomata Macrophage aggregates and granulomatous inflammation (Figures 4 and 5) may be formed in MALT upon uptake of macromolecules and microorganisms by the specialized lymphoepithelium of MALT. Macrophage aggregates and granuloma formation in MALT is reported occasionally. It has been reported for example in PP by intramural injection with bacterial peptidoglucan-polysaccharide complex (Tanaka et al., 1995) and in paratuberculosis infection in goats (Corpa et al., 2000). Macrophage aggregates have been observed in PP and BALT of rats, but not in NALT of Wistar rats (Kuper, unpublished observations).
Degeneration, Necrosis, and Mineralization Several compounds induce necrosis of lymphocytes in PP (the muscle toxin azaspiracid, Ito et al., 2000; Nivalenol, Poapolathep et al., 2002; DMSO, Aita et al., 2005). Degeneration and necrosis are also encountered in inflammation and may lead to mineralization, which has been observed occasionally in PP of rats (Figure 6).
Changes in Lymphoepithelium
MALT Tumors MALT houses subpopulations of T and B lymphocytes and macrophages and thus, theoretically, any type of lymphoma may arise in MALT. In man, a type of lymphoma that has been linked specifically with gut mucosal lymphoid tissues is MALT lymphoma (synonym: maltoma; belonging to the extranodal marginal zone lymphomas; WHO histological classification, Jaffe et al., 2001), which originates from post-germinal center memory B-lymphocytes in the periphery of the mantle zone of germinal centers. This outer zone is sometimes called marginal zone, hence the term marginal zone lymphoma. Infiltration of neoplastic lymphocytes into epithelium and plasma cell differentiation are characteristic findings of this tumor. Chronic inflammation, e.g. due to infection with Helicobacter pylori or to autoimmune-like diseases, are considered to be causative agents. MALT lymphoma is rarely reported in most laboratory species (Figure 9). It has been induced in mice as a model for human disease (Mueller et al., 2005).
Metastasis, Tumor Emboli and Involvement of MALT in Tumorigenesis Dimethylhydrazine (DMH) induces intestinal adenocarcinoma in rats, which is associated regularly with PP. Martin et al. (1986) observed early carcinoma in the interfollicular compartment of PP and hypothesized that the atypical glandular crypts, found often in the interfollicular compartment of PP, were the origin of the PP-associated adenocarcinomas.
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Toxicologic Pathology, Vol. 34, No. 5,
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Abstract
Introduction
