Morphology of the gastroesophageal reflux disease

Česká verze

Authors: Ondřej Daum ; Bohuslava Kokošková; Marián Švajdler
Authors place of work: Bioptická laboratoř, s. r. o., Plzeň ; Šiklův ústav patologie LF UK a FN Plzeň
Published in the journal: Čes.-slov. Patol., 52, 2016, No. 1, p. 15-22
Category: Přehledový článek

Summary

The present definition of gastroesophageal reflux disease is based on clinical criteria that are difficult to reproduce accurately. Pathologists are supposed to confirm the presence of morphological changes induced by gastroesophageal reflux. Traditional evaluation of injury, inflammatory and reactive changes of esophageal squamous epithelium lacks both sufficient sensitivity and specificity, and thus the modern diagnostic focuses on chronic metaplastic changes of esophageal mucosa defined as any mucosal type proximal to the upper border of oxyntic mucosa (also called fundic mucosa of the stomach). In the setting of gastroesophageal reflux the esophageal mucosa, under normal conditions lined with squamous epithelium, undergoes columnar metaplasia. According to morphology and immunophenotype of columnar cells, the columnar metaplasia may be further subdivided to oxyntocardiac mucosa, cardiac mucosa, intestinal metaplasia, and an intermediate type of cardiac mucosa expressing intestinal transcription factor CDX2, but devoid of goblet cells. The latter two mucosal types are currently thought to represent the most probable candidates for neoplastic transformation, whereas oxyntocardiac mucosa is believed to represent a stable compensatory change with no risk of further progression. An evaluation of dysplastic changes (intraepithelial neoplasia) in the setting of columnar lined esophagus necessitates correlation with the second opinion of a GI expert to prevent potentially harmful under- or over-treatment of the patient. Regarding invasive adenocarcinoma, the pathologist should avoid overdiagnosis of the infiltration of the space between the two layers of columnar lined esophagus - associated split muscularis mucosae as invasion of submucosa, as it is associated with different prognosis. Critical evaluation of the real impact of acid suppression on neoplastic transformation in the setting of gastroesophageal reflux disease may represent the greatest challenge for future studies.

Keywords:
esophagus – reflux – esophagitis – GERD – cardia – Barrett

Zdroje

1. Jackson C. Peptic ulcer of the esophagus. JAMA 1929; 92(5): 369-372.

2. Findlay L, Kelly AB. Congenital shortening of the oesophagus and the thoracic stomach resulting therefrom. Proc R Soc Med 1931; 24(11): 1561-1578.

3. Barrett NR. Chronic peptic ulcer of the oesophagus and ‘oesophagitis’. Br J Surg 1950; 38(150): 175-182.

4. Barrett NR. The lower esophagus lined by columnar epithelium. Surgery 1957; 41(6): 881- 894.

5. 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(9): 476-480.

6. Haggitt RC, Tryzelaar J, Ellis FH, Colcher H. Adenocarcinoma complicating columnar epithelium-lined (Barrett’s) esophagus. Am J Clin Pathol 1978; 70(1): 1-5.

7. Reid BJ, Weinstein WM. Barrett’s esophagus and adenocarcinoma. Annu Rev Med 1987; 38(38): 477-492.

8. Hayward J. The lower end of the oesophagus. Thorax 1961; 16(1): 36-41.

9. Chandrasoma PT, Der R, Ma Y, Dalton P, Taira M. Histology of the gastroesophageal junction: an autopsy study. Am J Surg Pathol 2000; 24(3): 402-409.

10. Chandrasoma PT, Lokuhetty DM, Demeester TR, et al. Definition of histopathologic changes in gastroesophageal reflux disease. Am J Surg Pathol 2000; 24(3): 344-351.

11. Der R, Tsao-Wei DD, Demeester T, et al. Carditis: a manifestation of gastroesophageal reflux disease. Am J Surg Pathol 2001; 25(2): 245-252.

12. Chandrasoma P, Wijetunge S, Ma Y, Demeester S, Hagen J, Demeester T. The dilated distal esophagus: a new entity that is the pathologic basis of early gastroesophageal reflux disease. Am J Surg Pathol 2011; 35(12): 1873-1881.

13. 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(1): 40-47.

14. Chandrasoma PT, Der R, Dalton P, et al. Distribution and significance of epithelial types in columnar-lined esophagus. Am J Surg Pathol 2001; 25(9): 1188-1193.

15. Owen DA. Gastritis and carditis. Mod Pathol 2003; 16(4): 325-341.

16. Kilgore SP, Ormsby AH, Gramlich TL, et al. The gastric cardia: fact or fiction? Am J Gastroenterol 2000; 95(4): 921-924.

17. Zhou H, Greco MA, Daum F, Kahn E. Origin of cardiac mucosa: ontogenic consideration. Pediatr Dev Pathol 2001; 4(4): 358-363.

18. Glickman JN, Fox V, Antonioli DA, Wang HH, Odze RD. Morphology of the cardia and significance of carditis in pediatric patients. Am J Surg Pathol 2002; 26(8): 1032-1039.

19. Derdoy JJ, Bergwerk A, Cohen H, Kline M, Monforte HL, Thomas DW. The gastric cardia: to be or not to be? Am J Surg Pathol 2003; 27(4): 499-504.

20. Sarbia M, Donner A, Gabbert HE. Histopathology of the gastroesophageal junction: a study on 36 operation specimens. Am J Surg Pathol 2002; 26(9): 1207-1212.

21. Hadravská Š, Chlumská A, Boudová L, Mukenšnabl P, Šulc M. The histological findings in the gastroesophageal junction of fetuses. Cesk Patol 2004; 40(1): 7-10.

22. Chandrasoma P. Cardiac mucosal changes in a pediatric population. Am J Surg Pathol 2003; 27(2): 274-275.

23. Chandrasoma PT, Der R, Ma Y, Peters J, Demeester T. Histologic classification of patients based on mapping biopsies of the gastroesophageal junction. Am J Surg Pathol 2003; 27(7): 929-936.

24. 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(4): 451-455.

25. Odze RD. Unraveling the mystery of the gastroesophageal junction: a pathologist’s perspective. Am J Gastroenterol 2005; 100(8): 1853-1867.

26. Chandrasoma P, Wickramasinghe K, Ma Y, DeMeester T. Adenocarcinomas of the distal esophagus and “gastric cardia” are predominantly esophageal carcinomas. Am J Surg Pathol 2007; 31(4): 569-575.

27. Wijetunge S, Ma Y, DeMeester S, Hagen J, DeMeester T, Chandrasoma P. Association of adenocarcinomas of the distal esophagus, “gastroesophageal junction,” and “gastric cardia” with gastric pathology. Am J Surg Pathol 2010; 34(10): 1521-1527.

28. Fiocca R, Mastracci L, Riddell R, et al. Development of consensus guidelines for the histologic recognition of microscopic esophagitis in patients with gastroesophageal reflux disease: the Esohisto project. Hum Pathol 2010; 41(2): 223-231.

29. Chlumská A, Boudová L, Beneš Z, Zámečník M. Histopathologic changes in gastroesophageal reflux disease. A study of 126 bioptic and autoptic cases. Cesk Patol 2007; 43(4): 142-147.

30. Langner C, Schneider NI, Plieschnegger W, et al. Cardiac mucosa at the gastro-oesophageal junction: indicator of gastro-oesophageal reflux disease? Data from a prospective central European multicentre study on histological and endoscopic diagnosis of oesophagitis (histoGERD trial). Histopathology 2014; 65(1): 81-89.

31. Schneider NI, Plieschnegger W, Geppert M, et al. Validation study of the Esohisto consensus guidelines for the recognition of microscopic esophagitis (histoGERD Trial). Hum Pathol 2014; 45(5): 994-1002.

32. Leape LL, Bhan I, Ramenofsky ML. Esophageal biopsy in the diagnosis of reflux esophagitis. J Pediatr Surg 1981; 16(3): 379-384.

33. Knuff TE, Benjamin SB, Worsham GF, Hancock JE, Castell DO. Histologic evaluation of chronic gastroesophageal reflux. An evaluation of biopsy methods and diagnostic criteria. Dig Dis Sci 1984; 29(3): 194-201.

34. 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(11): 1574-1581.

35. Shields HM, Zwas F, Antonioli DA, Doos WG, Kim S, Spechler SJ. Detection by scanning electron microscopy of a distinctive esophageal surface cell at the junction of squamous and Barrett’s epithelium. Dig Dis Sci 1993; 38(1): 97-108.

36. Boch JA, Shields HM, Antonioli DA, Zwas F, Sawhney RA, Trier JS. Distribution of cytokeratin markers in Barrett’s specialized columnar epithelium. Gastroenterology 1997; 112(3): 760-765.

37. Shields HM, Rosenberg SJ, Zwas FR, Ransil BJ, Lembo AJ, Odze R. Prospective evaluation of multilayered epithelium in Barrett’s esophagus. Am J Gastroenterol 2001; 96(12): 3268-3273.

38. Glickman JN, Chen YY, Wang HH, Antonioli DA, Odze RD. Phenotypic characteristics of a distinctive multilayered epithelium suggests that it is a precursor in the development of Barrett’s esophagus. Am J Surg Pathol 2001; 25(5): 569-578.

39. Wieczorek TJ, Wang HH, Antonioli DA, Glickman JN, Odze RD. Pathologic features of reflux and Helicobacter pylori-associated carditis: a comparative study. Am J Surg Pathol 2003; 27(7): 960-968.

40. Glickman JN, Spechler SJ, Souza RF, Lunsford T, Lee E, Odze RD. Multilayered epithelium in mucosal biopsy specimens from the gastroesophageal junction region is a histologic marker of gastroesophageal reflux disease. Am J Surg Pathol 2009; 33(6): 818-825.

41. Krishnamurthy S, Dayal Y. Pancreatic metaplasia in Barrett’s esophagus. An immunohistochemical study. Am J Surg Pathol 1995; 19(10): 1172-1180.

42. Wang HH, Zeroogian JM, Spechler SJ, Goyal RK, Antonioli DA. Prevalence and significance of pancreatic acinar metaplasia at the gastroesophageal junction. Am J Surg Pathol 1996; 20(12): 1507-1510.

43. Takubo K, Vieth M, Honma N, et al. Ciliated surface in the esophagogastric junction zone: a precursor of Barrett’s mucosa or ciliated pseudostratified metaplasia? Am J Surg Pathol 2005; 29(2): 211-217.

44. 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(1): 7-42.

45. 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(1): 65-74.

46. 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(3): 1084-1091.

47. Lukáš K, Bureš J, Drahoňovský V, et al. Refluxní choroba jícnu. Standardy České gastroenterologické společnosti – aktualizace 2009. Vnitr Lek 2009; 55(10): 967-975.

48. Faller G, Borchard F, Ell C, et al. Histopathological diagnosis of Barrett’s mucosa and associated neoplasias: results of a consensus conference of the Working Group for Gastroenterological Pathology of the German Society for Pathology on 22 September 2001 in Erlangen. Virchows Arch 2003; 443(5): 597-601.

49. 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): 1-7.

50. Hahn HP, Blount PL, Ayub K, et al. Intestinal differentiation in metaplastic, nongoblet columnar epithelium in the esophagus. Am J Surg Pathol 2009; 33(7): 1006-1015.

51. McDonald SAC, Graham TA, Lavery DL, Wright NA, Jansen M. The Barrett´s gland in phenotype space. Cell Mol Gastroenterol Hepatol 2015; 1(1): 41-54.

52. Watanabe G, Ajioka Y, Takeuchi M, et al. Intestinal metaplasia in Barrett’s oesophagus may be an epiphenomenon rather than a preneoplastic condition, and CDX2-positive cardiac-type epithelium is associated with minute Barrett’s tumour. Histopathology 2015; 66(2): 201-214.

53. Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999; 340(11): 825-831.

54. Hansel DE, Dhara S, Huang RC, et al. CDC2/ CDK1 expression in esophageal adenocarcinoma and precursor lesions serves as a diagnostic and cancer progression marker and potential novel drug target. Am J Surg Pathol 2005; 29(3): 390-399.

55. Shi XY, Bhagwandeen B, Leong AS. p16, cyclin D1, Ki-67, and AMACR as markers for dysplasia in Barrett esophagus. Appl Immunohistochem Mol Morphol 2008; 16(5): 447- 452.

56. Duits LC, Phoa KN, Curvers WL, et al. Barrett’s oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel. Gut 2015; 64(5): 700-706.

57. Sangle NA, Taylor SL, Emond MJ, Depot M, Overholt BF, Bronner MP. Overdiagnosis of high-grade dysplasia in Barrett’s esophagus: a multicenter, international study. Mod Pathol 2015; 28(6): 758-765.

58. Khor TS, Alfaro EE, Ooi EM, et al. Divergent expression of MUC5AC, MUC6, MUC2, CD10, and CDX-2 in dysplasia and intramucosal adenocarcinomas with intestinal and foveolar morphology: is this evidence of distinct gastric and intestinal pathways to carcinogenesis in Barrett Esophagus? Am J Surg Pathol 2012; 36(3): 331-342.

59. Chlumská A, Mukenšnabl P, Waloschek T, Zámečník M. Dysplázie žaludku. Histologické typy a jejich význam. Kongresové noviny (32 český a slovenský gastroenterologický kongres) 2011; 32(2): 5.

60. Abraham SC, Krasinskas AM, Correa AM, et al. Duplication of the muscularis mucosae in Barrett esophagus: an underrecognized feature and its implication for staging of adenocarcinoma. Am J Surg Pathol 2007; 31(11): 1719-1725.

61. Estrella JS, Hofstetter WL, Correa AM, et al. Duplicated muscularis mucosae invasion has similar risk of lymph node metastasis and recurrence-free survival as intramucosal esophageal adenocarcinoma. Am J Surg Pathol 2011; 35(7): 1045-1053.

62. Holscher AH, Bollschweiler E, Schroder W, Metzger R, Gutschow C, Drebber U. Prognostic impact of upper, middle, and lower third mucosal or submucosal infiltration in early esophageal cancer. Ann Surg 2011; 254(5): 802-807.