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CELLULAR SCIENCE


Barrett’s metaplasia in the upper GI tract: subtyping, stem cells and receptors


Gastroesophageal reflux disease (GERD) is a common condition that, if left untreated, may result in the development of metaplasia, a premalignant condition occurring in areas of the upper gastrointestinal tract.


Intestinal metaplasia (IM) is a form of metaplastic change that can occur in the stomach and the oesophagus (Barrett’s oesophagus). It can only be diagnosed by histological examination, and the presence of acid mucin-containing goblet cells is the hallmark of the condition. Studies suggest that IM of both the stomach and oesophagus may be a risk factor for the development adenocarcinoma at these sites. However, IM is present in about 20% of all gastric biopsies and few of these patients will progress to adenocarcinoma of the stomach. Thus. its specificity as a marker is actually too low to be used in surveillance for cancer. Consequently, in an attempt to


improve the specificity of IM, its subtypes have been examined. Conventionally, three main subtypes (I, II and III) have been recognised and some studies reveal that there may be a strong link between type III IM and both adenocarcinoma of


the oesophagus and intestinal-type gastric adenocarcinoma. The subtypes of IM have been characterised according to their mucin content and morphology (Table 1). Discrimination between type I IM and the other two subtypes is easily made using the alcian blue/periodic acid–Schiff (AB/PAS) technique, as the latter two subtypes express acid mucins in the metaplastic columnar cells, whereas the former type contains no cellular mucin. However, this technique does not allow discrimination between types II and III IM. As type II IM is characterised by the


presence of sialomucin and type III by the presence of sulphomucins within the intervening columnar cells, the high iron diamine/alcian blue (HID/AB) technique has been used to distinguish them. The procedure, however, involves the use of reagents that are toxic if inhaled or come into contact with the skin or eyes, and the technique is potentially carcinogenic.


Table 1. Classification of intestinal metaplasia subtypes. Mucin content


Subtype Morphology I


II III 52 Goblet cells


Virtually identical to the appearance of the small intestine with fully developed goblet cells and absorptive cells


Mild architectural distortion, slightly irregular and lined


by goblet and columnar cells in crypts at various stages of maturation. There are few or no absorptive cells.


As for type II Sialomucins and/or sulphomucins Sulphomucins DECEMBER 2020 WWW.PATHOLOGYINPRACTICE.COM Sialomucins and/or sulphomucins Sialomucins and/or sulphomucins Columnar cells No mucins (absorptive cells) Sialomucins and neutral mucins


Mucin histochemistry A study conducted in Leeds1


evaluated


alternative, non-toxic histochemical staining procedures to the HID/AB technique that can be used to distinguish the IM subtypes.


The histochemical techniques evaluated


were all methods claimed to demonstrate sulphomucins, and included the combined Gomori’s aldehyde fuchsin/alcian blue (GAF/AB) technique, the combined orcein/alcian blue method and the combined alcian blue/ruthenium red technique. Another suggested technique, that of McFadden et al., claimed to discriminate between sulphomucins and sialomucins; however, the use of phenylhydrazine makes it toxic and potentially carcinogenic, and therefore was considered to be an inappropriate alternative to the HID/AB technique. Over 20 years ago, Shah et al. evaluated the GAF/AB technique for the demonstration of IM subtypes and suggested that it was suitable for their routine identification. In that study, the use of Sigma-Aldrich basic fuchsin for the preparation of aldehyde fuchsin was recommended, as other aldehyde fuchsin solutions have given weak, inadequate staining or false staining patterns (ie sulphomucin positivity was observed in goblet cells of the duodenum).


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