Abstract
Over the past two decades, evidence has accumulated to challenge the traditional view that cardiac mucosa, which is comprised exclusively of mucus glands, is the normal lining of the most proximal portion of the stomach (the gastric cardia). There is now considerable evidence to suggest that cardiac mucosa develops as a GERD-induced, squamous-to-columnar esophageal metaplasia in some, if not all, cases. Although cardiac mucosa lacks the goblet cells commonly required for a histologic diagnosis of intestinal metaplasia, cardiac mucosa has many molecular features of an intestinal-type mucosa, and appears to be the precursor of intestinal metaplasia with goblet cells. In apparently normal individuals, cardiac mucosa is commonly found in a narrow band, less than 3 mm in extent, on the columnar side of the squamo-columnar junction at the end of the esophagus. A greater extent of cardiac mucosa can be found in GERD patients, and the magnitude of that extent appears to be an index of GERD severity. Presently, the risk of adenocarcinoma imposed by cardiac mucosa is not clear, but appears to be far less than that of intestinal metaplasis with goblet cells. The British Society of Gastroenterology accepts an esophagus lined by cardiac mucosa as a "Barrett's esophagus". However, if one defines Barrett's esophagus as a metaplasia that predisposes to cancer, then only intestinal metaplasia clearly fulfills that criterion at this time. Well-designed, prospective studies are needed to establish the malignant potential of cardiac mucosa.
Similar content being viewed by others
References
Slack JM. Metaplasia and transdifferentiation: from pure biology to the clinic. Nat Rev Mol Cell Biol. 2007;8:369–378.
Spechler SJ, Souza RF. Barrett’s esophagus. N Engl J Med. 2014;371:836–845.
Turner K, Genta RM. The nonneoplastic stomach. In: Noffsinger AE, ed. Fenoglio-Preiser’s Gastrointestinal Pathology. 4th ed. Alphen aan den Rijn: Wolters Kluwer; 2017:136–223.
Hahn HP, Blount PL, Ayub K, et al. Intestinal differentiation in metaplastic, nongoblet columnar epithelium in the esophagus. Am J Surg Pathol. 2009;33:1006–1015.
McClave SA, Boyce HW Jr, Gottfried MR. Early diagnosis of columnar-lined esophagus: a new endoscopic diagnostic criterion. Gastrointest Endosc. 1987;33:413–416.
Ogiya K, Kawano T, Ito E, et al. Lower esophageal palisade vessels and the definition of Barrett’s esophagus. Dis Esophagus. 2008;21:645–649.
Krause WJ, Ivey KJ, Baskin WN, MacKercher PA. Morphological observations on the normal human cardiac glands. Anat Rec. 1978;192:59–71.
Hayward J. The lower end of the oesophagus. Thorax. 1961;16:36–41.
Chandrasoma P. Pathophysiology of Barrett’s esophagus. Semin Thorac Cardiovasc Surg. 1997;9:270–278.
Chandrasoma P, Makarewicz K, Wickramasinghe K, Ma Y, Demeester T. A proposal for a new validated histological definition of the gastroesophageal junction. Hum Pathol. 2006;37:40–47.
Chandrasoma P, Wijetunge S, Demeester SR, Hagen J, Demeester TR. The histologic squamo-oxyntic gap: an accurate and reproducible diagnostic marker of gastroesophageal reflux disease. Am J Surg Pathol. 2010;34:1574–1581.
Park YS, Park HJ, Kang GH, Kim CJ, Chi JG. Histology of gastroesophageal junction in fetal and pediatric autopsy. Arch Pathol Lab Med. 2003;127:451–455.
Kilgore SP, Ormsby AH, Gramlich TL, et al. The gastric cardia: fact or fiction? Am J Gastroenterol. 2000;95:921–924.
Dunn LJ, Burt AD, Hayes N, Griffin SM. Columnar metaplasia in the esophageal remnant after esophagectomy: a common occurrence and a valuable insight into the development of Barrett esophagus. Ann Surg. 2016;264:1016–1021.
Ellison E, Hassall E, Dimmick JE. Mucin histochemistry of the developing gastroesophageal junction. Pediatr Pathol Lab Med. 1996;16:195–206.
Liu W, Hahn H, Odze RD, Goyal RK. Metaplastic esophageal columnar epithelium without goblet cells shows DNA content abnormalities similar to goblet cell-containing epithelium. Am J Gastroenterol. 2009;104:816–824.
Robertson EV, Derakhshan MH, Wirz AA, et al. Central obesity in asymptomatic volunteers is associated with increased intrasphincteric acid reflux and lengthening of the cardiac mucosa. Gastroenterology. 2013;145:730–739.
Robertson EV, Derakhshan MH, Wirz AA, et al. Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux. Gut. 2017;66:1208–1215.
Derakhshan MH, Robertson EV, Lee YY, et al. In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity. Gut. 2015;64:1705–1714.
Joseph A, Ackerman D, Talley JD, Johnstone J, Kupersmith J. Manifestations of coronary atherosclerosis in young trauma victims–an autopsy study. J Am Coll Cardiol. 1993;22:459–467.
Shaheen NJ, Falk GW, Iyer PG, Gerson LB. American College of Gastroenterology. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. Am J Gastroenterol. 2016;111:30–50.
Harrison R, Perry I, Haddadin W, et al. Detection of intestinal metaplasia in Barrett’s esophagus: an observational comparator study suggests the need for a minimum of eight biopsies. Am J Gastroenterol. 2007;102:1154–1161.
Abrams JA, Kapel RC, Lindberg GM, et al. Adherence to biopsy guidelines for Barrett’s esophagus surveillance in the community setting in the United States. Clin Gastroenterol Hepatol. 2009;7:736–742.
Goldblum JR. Current issues in Barrett’s esophagus and Barrett’s-related dysplasia. Mod Pathol. 2015;28:S1–S6.
McDole JR, Wheeler LW, McDonald KG, et al. Goblet cells deliver luminal antigen to CD103 + dendritic cells in the small intestine. Nature. 2012;483:345–349.
Barrett NR. Chronic peptic ulcer of the oesophagus and “oesophagitis”. Br J Surg. 1950;38:175–182.
Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK. The histologic spectrum of Barrett’s esophagus. N Engl J Med. 1976;295:476–480.
Spechler SJ, Fitzgerald RC, Prasad GA, Wang KK. History, molecular mechanisms, and endoscopic treatment of Barrett’s esophagus. Gastroenterology. 2010;138:854–869.
Playford RJ. New British Society of Gastroenterology (BSG) guidelines for the diagnosis and management of Barrett’s oesophagus. Gut. 2006;55:442.
Fitzgerald RC, di Pietro M, Ragunath K, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2014;63:7–42.
Takubo K, Aida J, Naomoto Y, et al. Cardiac rather than intestinal-type background in endoscopic resection specimens of minute Barrett adenocarcinoma. Hum Pathol. 2009;40:65–74.
Kelty CJ, Gough MD, Van Wyk Q, Stephenson TJ, Ackroyd R. Barrett’s oesophagus: intestinal metaplasia is not essential for cancer risk. Scand J Gastroenterol. 2007;42:1271–1274.
Gatenby PA, Ramus JR, Caygill CP, Shepherd NA, Watson A. Relevance of the detection of intestinal metaplasia in non-dysplastic columnar-lined oesophagus. Scand J Gastroenterol. 2008;43:524–530.
Chandrasoma P, Wijetunge S, DeMeester S, et al. Columnar-lined esophagus without intestinal metaplasia has no proven risk of adenocarcinoma. Am J Surg Pathol. 2012;36:1–7.
Bhat S, Coleman HG, Yousef F, et al. Risk of malignant progression in Barrett’s esophagus patients: results from a large population-based study. J Natl Cancer Inst. 2011;103:1049–1057.
Westerhoff M, Hovan L, Lee C, Hart J. Effects of dropping the requirement for goblet cells from the diagnosis of Barrett’s esophagus. Clin Gastroenterol Hepatol. 2012;10:1232–1236.
Khandwalla HE, Graham DY, Kramer JR, et al. Barrett’s esophagus suspected at endoscopy but no specialized intestinal metaplasia on biopsy, what’s next? Am J Gastroenterol. 2014;109:178–182.
American Gastroenterological Association, Spechler SJ, Sharma P, Souza RF, Inadomi JM, Shaheen NJ. American Gastroenterological Association medical position statement on the management of Barrett’s esophagus. Gastroenterology. 2011;140:1084–1091.
Spechler SJ, Sharma P, Souza RF, Inadomi JM, Shaheen NJ. American Gastroenterological Association technical review on the management of Barrett’s esophagus. Gastroenterology. 2011;140:e18–e52.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Dr. Spechler has served as a consultant for Takeda Pharmaceuticals and Ironwood Pharmaceuticals.
Rights and permissions
About this article
Cite this article
Spechler, S.J. Cardiac Metaplasia: Follow, Treat, or Ignore?. Dig Dis Sci 63, 2052–2058 (2018). https://doi.org/10.1007/s10620-018-5063-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-018-5063-y