0 3: 436-446 Rev Esp Patot 1999; Vol. 32, N © Prous Science, SA. © Sociedad Espajiola de Anatomia Patot6gica Short Course 10 © Sociedad Espafiola de Citologia

Metaplasia in the gut Chairperson: NA. Wright, UK. Co-chairpersons: G. Coggi, Italy and C. Cuvelier, Belgium.

Overview of gastrointestinal metaplasias only in esophagus but also in the duodenum, intestine, gallbladder and even in the pancreas. Well established is columnar metaplasia J. Stachura of esophageal squamous epithelium. Its association with increased risk of esophageal cancer is widely recognized. Recent develop- Dept. of Pathomorphology, Jagiellonian University ments have suggested, however, that only the intestinal type of Faculty of Medicine, Krakdw, Poland. metaplastic epithelium (classic Barrett’s esophagus) predisposes to cancer. Another field of studies is metaplasia in the short seg- ment at the esophago-cardiac junction, its association with Metaplasia is a reversible change in which one aduit cell type is Helicobacter pylon infection and/or reflux disease and intestinal replaced by another. It is always associated with some abnormal metaplasia in the cardiac and fundic areas. stimulation of tissue growth, tissue regeneration or excessive hor- Studies on gastric mucosa metaplasia could be divided into monal stimulation. Heterotopia, on the other hand, takes place dur- those concerned with pathogenesis and detailed structural/func- ing embryogenesis and is usually supposed not to be associated tional features and those concerned with clinical significance. with tissue damage. Pancreatic acinar cell clusters in pediatric gas- We know now that gastric mucosa may show not only complete tric mucosa form another example of aberrant cell differentiation. and incomplete intestinal metaplasia but also others such as ciliary Metaplasia is usually divided into epithelial and connective tis- and pancreatic metaplasia. We also know that pylorization of oxyn- sue (e.g., osseous metaplasia of fibroblastic stroma or scar tissue). tic mucosa in atrophic gastritis is common. We know that in addi- Metaplasia within a cancer is still another issue. tion to fully differentiated intestinal cells some cells show dual gas- Epithelial metaplasia is thought to arise from reprogramming tric and intestinal or amphocrine features. Subtyping of intestinal stem and reserve epithelial cells. These precursor cells differenti- metaplasia has led to the conclusion that the “gastric and intestinal ate along a new pathway. Metaplasia may represent an adaptive substitution of sensitive cells by other cell types better able to with- mixed” subtype predominates in the antral mucosa while the “sole- stand the adverse environment. This is less clear in connective tis- ly intestinal” subtype predominates in the oxyntic mucosa. sue metaplasia. Metaplasias are patches of ectopic tissue and only Studies on the clinical significance of metaplasia within gastric rarely and in the later stages involve the entire affected structure, mucosa have been heavily affected by the decade of helicobac- e.g., the entire gastric mucosa. terology (2-5). This includes not only the association of metaplasia Metaplasia is caused by malfunction of tissue-specific and dif- with H. pylon infection but also reversibility after H. pylon eradica- ferentiation genes stimulated by cytokines, growth factors and tion as well as the influence of acid suppression therapy on the extracellular matrix components. These external factors trigger the proximal extension of inflammation and renewed recognition of cascade of transcription factors that lead toward the fully differenti- gastric mucosa transitional zones. All this was additionally found in ated cell. experimental conditions by the development of metaplasia and The most common epithelial metaplasia is columnar to squa- cancer in H. pylon infected gerbils. mous. Well known is the example of squamous metaplasia in vita- Now, in the post-Helicobacter era, there can be a return to min A deficiency or metaplasia of bronchial epithelium irritated by Correa’s classic paradigm of gastritis-atrophic gastritis-atrophy- cigarette smoke. metaplasia-dysplasia-carcinoma sequence (at least for gastric ade- Metaplasia from squamous to columnar or may also occur. nocarcinoma). Other environmental and host factors in gastric car- This is the case in Barrett’s esophagus. cinogenesis can also again be appreciated. Epithelial metaplasia is a two-edged sword. Metaplastic cells survive better but some of the functions of the normal epithelium References are lost. In addition, a persistent metaplastic process may predis- 1. Noda M, Poulsom R, Hanby AM et al. Prolongedduodenogastric reflux inthe ret pose to cancer transformation. This is the main area of interest followed by development of newglands resembling the ulcer-associated-cell-lin- even though it is still unclear whether cancer is associated with eage (UACL). Gut 1998; 42: 87A. metaplasia in a causative manner or whether it is simply a 2. Miehlke S, Meining A, Hackeisberger A et al. Prevalence of Helicobaster pylon bystander providing a warning about the riskof cancer, which how- infection, intestinal metaplasia and atrophy in gastric cancer of different clinical ever, develops independently. stages. Gut 1998; 43: 67A. The substantial contribution to our understanding of aberrant 3. Kasem H, Going J, Mackay C at al. Prolonged acid suppression therapy is differentiation of gastrointestinal cells was given by Nick Wright and associated with gastric intestinal metaplasia. Br J Surg 1998; 85: 1573. his hypothesis of ulcer-associated cell lineages (1). 4. Anti M, Armuzzi A, Gasbarrini A et al. Importance of changes in epithelial cell In the gastrointestinal system metaplasia is relatively common. turover during Helicobacterpylon infection in gastric carcinogenesis. Gut 1998; 43: 275. Best recognized is intestinal metaplasia of the gastric mucosa. 5. made K, Nakanishi H, Fuiimitsu Y at al. Gastric and intestinal mixed and solelu Gastric metaplasia is also common, however. The latter occurs not intestinal metaplasia in the human stomach. Pathol mt 1997; 47: 831.

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