Are the histologic changes associated with reflux different in adults and children?

D.A. Antonioli (Boston)

The histologic changes associated with gastroesophageal reflux (GER) are basically similar in children and adults. In well-oriented esophageal mucosal biopsy specimens

taken 2 cm or more above the gastroesophageal junction, a basal zone occupying more than 20% of the thickness of the squamous epithelium and stromal papillae extending more than two-thirds of the distance through the epithelium are excellent markers of GER. However, since most esophageal mucosal biopsies in the pediatric population are obtained using grasp biopsy forceps that result in small, poorly-oriented specimens, basal zone hyperplasia and papillary lengthening cannot be evaluated. Thus, as in adults, detection of intraepithelial inflammation becomes a major component in evaluating GER-related esophagitis in children [1].

Intraepithelial neutrophils are uncommon but are a good indicator of GER, being most often noted in patients with esophageal erosions or ulcers. Intraepithelial eosinophils are more frequent than neutrophils in GER-related injury and they are often the sole marker of injury in children. Even a small number of eosinophils in a specimen taken 2-3 cm above the gastroesophageal junction correlates with GER. Although intraepithelial eosinophils are a very specific indicator of acid reflux, they are not a highly sensitive one [2]. Intraepithelial lymphocytes may be increased in childhood GER [1,3]. Other, nonspecific markers of mucosal injury may be noted; these include increased mitoses in the epithelium, spongiosis and balloon-cell change (swelling) of keratinocytes [4]. Vascular congestion in papillae is a nonspecific response to endoscope trauma.

Like adults, children may develop Barrett's esophagus (BE) as a complication of severe GER. The precise incidence and prevalence of BE in the pediatric population are difficult to determine, because clinical studies in this age group are few in number and typically retrospective in nature. Within these limitations, however, BE has been diagnosed between infancy and age 19 years in 10 to 13% of children with severe GER and/or histologically proven esophagitis [5,6]. These percentages are similar to those for adults with severe GER; also like adults, BE in children has a marked male predominance [6,7].

Barrett's esophagus may be overrepresented in certain subsets of pediatric patients. For example, there may be an excess of BE in children (and adults) who have had an esophageal atresia or tracheoesophageal fistula surgically repaired. These congenital lesions are associated with esophageal dysmotility, resulting in poor esophageal acid clearance and a high prevalence of esophagitis [8]. Likewise, young people who are severely developmentally disabled are numerous in studies of BE in childhood [9], forming up to 40-70% of the BE patients in some series [6,7,10]. Severe GER is common in these patients; however, since they often cannot articulate their symptoms, the diagnosis of esophagitis is often delayed, thus allowing time for BE to develop [10]. The recognition of BE is important in children because of its malignant potential. Although they are rare, 10 cases of adenocarcinoma arising in BE before the age of 25 years have been reported [11].

The histologic features of BE in children are, in many respects, similar to those in adults. Fundic, junctional and specialized columnar epithelium may all be found, with the specialized epithelium typically at the upper end and the fundic and junctional types at the distal end of the BE segment [5-7,9,10]. As in adults, the fundic and junctional variants usually have an atrophic appearance, unlike that of normal stomach [5].

The major histologic difference between pediatric and adult BE is that specialized columnar epithelium is less frequent in children. Whereas specialized columnar epithelium can be identified in over 90% of adults with BE, it has been detected in only 15 to 50% of children with BE [5-7]. Its presence appears to be age related, in that specialized columnar epithelium increases in prevalence in older, as compared to younger, cohorts of children with BE [6].

The relative paucity of specialized epithelium in younger children may make the diagnosis of BE problematic; caution should be exercised if only fundic or junctional tissue is obtained in biopsy specimens, since they may represent normal proximal stomach or gastric mucosa in a hiatal hernia [12]. Multiple biopsies and careful endoscopic measurements of the length of columnar mucosa may aid in determining if BE is present. Alcian blue staining (at pH 2.5) of biopsy specimens may be helpful in detecting otherwise inapparent goblet cells [12].

References

1. Dahms BB, Rothstein FC. Mucosal biopsy of the esophagus in children. In: Rosenberg HS, Bernstein J (eds) Respiratory and Alimentary Tract Diseases (Perspectives in Pediatric Pathology, vol. II). Basel: Karger, 1987;97-123.

2. Winter HS, Madara JL, Stafford RJ et al. Intraepithelial eosinophils: a new diagnostic criterion for reflux esophagitis Gastroenterology 1982:83:818-823.

3. Groben PA, Siegal GP, Shub MD et al. Gastrointestinal reflux and esophagitis in infants and children In: Rosenberg HS, Bernstein J (eds) Respiratory and Alimentary Tract Diseases (Perspectives in Pediatric Pathology, vol II). Basel: Karger, 1987;124-151.

4. Jessurun J, Yardley JH, Giardiello FM, Hamilton SR. Intracytoplasmic plasma proteins in distended esophageal squamous cells (balloon cells). Mod Pathol 1988:1:175-181.

5. Dahms BB, Rothstein FC. Barrett's esophagus in children: a consequence of chronic gastroesophageal reflux. Gastroenterology 1984;86:318-323.

6. Qualman SJ, Murray RD, McClung J, Lucas J. Intestinal metaplasia is age-related in Barrett's esophagus. Arch Pathol Lab Med 1990;114:1236-1240.

7. Hassall E, Weinstein WM, Ament ME. Barrett's esophagus in childhood. Gastroenterology 1985;89:1131-1137.

8. Biller JA, Allen JL, Schuster SR, Treves ST. Winter HS. Long-term evaluation of esophageal and pulmonary function in patients with repaired esophageal atresia and tracheoesophageal fistula. Dig Dis Sci 1987;32:985-990.

9. Roberts IM, Curtis RL, Madara JL. Gastroesophageal reflux and Barrett's esophagus in developmentally disabled patients. Am J Gastroenterol 1986;81:519-523.

10. Snyder JD, Goldman H. Barrett's esophagus in children and young adults: frequent association with mental retardation. Dig Dis Sci 1990:35:1185-1189.

11. Hassall E, Dimmick JE, Magee JF. Adenocarcinoma in childhood Barrett's esophagus: case documentation and the need for surveillance in children Am J Gastroenterol 1993;88:282-288.

12. Hassall E. Barrett's esophagus: congenital or aequired? Am J Gastroenterol 1993:88:819-824.