Histopathologic Classification of Adenocarcinoma of the Esophagogastric Junction

  • Stephan E. BaldusEmail author
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 182)


In contrast to squamous cell carcinomas of the esophagus as well as adenocarcinomas of the distal or middle third of the stomach, the incidence of adenocarcinomas in the distal esophagus or EG junction increased continuously during the last decades. Initially, most of these cancers were thought to represent either esophageal or gastric carcinomas (especially the so-called “carcinomas of the cardia”). However, it became clear that the pathogenesis of these cancers exhibits differences. While most of the “true” adenocarcinomas of the distal esophagus arise predominantly on the basis of Barrett’s metaplasia developing in the clinical setting of gastroesophageal reflux disease, the etiology of cancers of the cardia and the subcardial stomach remained unclear.


Intestinal Metaplasia Gastroesophageal Reflux Disease Intraepithelial Neoplasia Distal Esophagus Esophagogastric Junction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Antonioli DA, Wang HH (1997) Morphology of Barrett’s esophagus and Barrett’s-associated dysplasia and adenocarcinoma. Gastroenterol Clin North Am 26:495–506PubMedCrossRefGoogle Scholar
  2. Baldus SE, Mönig SP, Schröder W, Metzger R, Lang S, Zirbes TK, Thiele J, Müller RP, Dienes HP, Hölscher AH, Schneider PM (2004) Regression von Ösophaguskarzinomen nach neoadjuvanter Radiochemotherapie. Pathologe 25:421–427PubMedCrossRefGoogle Scholar
  3. Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, Böttcher K, Siewert JR, Höfler H (2003) Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer 98:1521–1530PubMedCrossRefGoogle Scholar
  4. Boyce HW (2000) Endoscopic definitions of the esophagogastric junction regional anatomy. Gastrointest Endosc 51:586–592PubMedCrossRefGoogle Scholar
  5. Chalasani N, Wo JM, Hunter JG, Waring JP (1997) Significance of intestinal metaplasia in different areas of esophagus including esophagogastric junction. Dig Dis Sci 42:603–607PubMedCrossRefGoogle Scholar
  6. Chandrasoma P (1997) Pathophysiology of Barrett’s esophagus. Semin Thorac Cardiovasc Surg 9:270–278PubMedGoogle Scholar
  7. Chandrasoma PT, Der R, Ma Y, Dalton P, Taira M (2000) Histology of the gastroesophageal junction: an autopsy study. Am J Surg Pathol 24:402–409PubMedCrossRefGoogle Scholar
  8. Chandrasoma PT, Der R, Dalton P, Kobayashi G, Ma Y, Peters J, Demeester T (2001) Distribution and significance of epithelial types in columnar-lined esophagus. Am J Surg Pathol 25:1188–1193PubMedCrossRefGoogle Scholar
  9. Chandrasoma P, Makarewicz K, Wickramasinghe K, Ma Y, Demeester T (2006) A proposal for a new validated histological definition of the gastroesophageal junction. Hum Pathol 37:40–47PubMedCrossRefGoogle Scholar
  10. Cunningham D, Allum WH, Stenning SP, Thompson JN, van de Velde CJH, Nicolson M, Scarffe H, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, for the MAGIC trial participants (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. New Engl J Med 355:11–20Google Scholar
  11. De Hertogh G, Van Eyken P, Ectors N, Tack J, Geboes K (2003) On the existence and location of cardiac mucosa: an autopsy study in embryos, fetuses, and infants. Gut 52:791–796PubMedCrossRefGoogle Scholar
  12. DeMeester SR (2006) Adenocarcinoma of the esophagus and cardia: a review of the disease and its treatment. Ann Surg Oncol 13:12–30PubMedCrossRefGoogle Scholar
  13. DeMeester SR, DeMeester TR (2000) Columnar mucosa and intestinal metaplasia of the esophagus: fifty years of controversy. Ann Surg 231:303–321PubMedCrossRefGoogle Scholar
  14. De Nardi FG, Riddell RH (1997) Esophagus. In: Sternberg SS (ed) Histology for Pathologists. Lippincott Raven, Philadelphia, p 461Google Scholar
  15. Derdoy JJ, Bergwerk A, Cohen H, Kline M, Monforte HL, Thomas DW (2003) The gastric cardia: to be or not to be? Am J Surg Pathol 27:499–504PubMedCrossRefGoogle Scholar
  16. Driessen A, Nafteux P, Lerut T, van Raemdonck D, de Leyn P, Filez L, Penninckx F, Geboes K, Ectors N (2004) Identical cytokeratin expression pattern CK7+/CK20- in esophageal and cardiac cancer: etiopathological and clinical implications. Mod Pathol 17:49–55PubMedCrossRefGoogle Scholar
  17. Fléjou JF (2005) Barrett’s esophagus: from metaplasia to dysplasia and cancer. Gut 54(suppl 1)i6–i12Google Scholar
  18. Flucke U, Steinborn E, Dries V, Mönig SP, Schneider PM, Thiele J, Hölscher AH, Dienes HP, Baldus SE (2003) Immunoreactivity of cytokeratins (CK7, CK20) and mucin peptide core antigens (MUC1, MUC2, MUC5AC) in adenocarcinomas, normal and metaplastic tissues of the distal esophagus, oesophago-gastric junction and proximal stomach. Histopathology 43:127–134PubMedCrossRefGoogle Scholar
  19. Fontana MG, La Pinta M, Moneghini D, Villanacci V, Donato F, Rindi G, Paparini S, Baronchelli C, Bertoli G, Alquati P (2003) Prognostic value of Goseki histological classification in adenocarcinoma of the cardia. Br J Cancer 88:401–405PubMedCrossRefGoogle Scholar
  20. Glickman JN, Fox V, Antonioli DA, Wang HH, Odze RD (2002) Morphology of the cardia and significance of carditis in pediatric patients. Am J Surg Pathol 26:1032–1039PubMedCrossRefGoogle Scholar
  21. Goldblum JR (2003) Barrett’s esophagus and Barrett’s-related dysplasia. Mod Pathol 16:316–324PubMedCrossRefGoogle Scholar
  22. Goseki N, Takizawa T, Koike M (1992) Differences in the mode of extension of gastric cancer classified by histological types: new histological classification of gastric carcinoma. Gut 33:606–612PubMedCrossRefGoogle Scholar
  23. Gulmann C, Counihan I, Grace A, Patchett S, Leen E, Leader M, Kay E (2003) Cytokeratin 7/20 and mucin expression patterns in esophageal, cardia and distal gastric adenocarcinomas. Histopathology 43:453–461PubMedCrossRefGoogle Scholar
  24. Halliday BP, Skipworth RJE, Wall L, Philipps HA, Couper GW, de Beaux AC, Paterson-Brown S (2007) Neoadjuvant chemotherapy for carcinoma of the esophagus and oesophago-gastric junction: a six-year experience. Int Semin Surg Oncol 4:24PubMedCrossRefGoogle Scholar
  25. Hamilton SR, Aaltonen LA (eds) (2000) World Health Organization Classification of tumours: tumours of the digestive system. IARC Press, Lyon, pp 9–67Google Scholar
  26. Hirota WK, Loughney TM, Lazas DJ, Maydonovitch CL, Rholl V, Wong RK (1999) Specialized intestinal metaplasia, dysplasia and cancer of the esophagus and esophagogastric junction: prevalence and clinical data. Gastroenterology 116:277–285PubMedCrossRefGoogle Scholar
  27. Jakl RJ, Miholic J, Koller R, Markis E, Wolner E (1995) Prognostic factors in adenocarcinoma of the cardia. Am J Surg 169:316–319PubMedCrossRefGoogle Scholar
  28. Kilgore SP, Ormsby AH, Gramlich TL, Rice TW, Richter JE, Falk GW, Goldblum JR (2000) The gastric cardia: fact or fiction? Am J Gastroenterol 95:921–924PubMedCrossRefGoogle Scholar
  29. Lagergren J, Bergstrom R, Lindgren A, Nyren O (1999) Symptomatic gastroeseophageal reflux as a risk factor for esophageal adenocarcinoma. New Engl J Med 340:825–831PubMedCrossRefGoogle Scholar
  30. Laurén P (1965) The two histological main types of gastric carcinoma. Acta Pathol Microbiol Scand 64:31–49PubMedGoogle Scholar
  31. Malfertheiner P, Peitz PU (2005) The interplay between Helicobacter pylori, gastro-esophageal reflux disease, and intestinal metaplasia. Gut 54(Suppl 1):i13–20PubMedCrossRefGoogle Scholar
  32. Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, Roussel A, Jacob JH, Segol P, Samama G, Ollivier JM, Bonvalot S, Gignoux M (1994) Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Cancer 73:2680–2686PubMedCrossRefGoogle Scholar
  33. Mattioli S, Ruffato A, di Simone MP, Corti B, d’Errico A, Lugaresi ML, Mattioli B, d’Ovidio F (2007) Immunopathological patterns of the stomach in adenocarcinoma of the esophagus, cardia and gastric antrum: gastric profiles in Siewert type I and II tumors. Ann Thorac Surg 83:1814–1819PubMedCrossRefGoogle Scholar
  34. Mueller J, Werner M, Siewert JR (2000) Malignant progression in Barrett’s esophagus: pathology and molecular biology. Recent Results Cancer Res 155:29–41PubMedCrossRefGoogle Scholar
  35. Mulligan RM, Rember RR (1954) Histogenesis and biologic behaviour of gastric carcinoma: study of one hundred thirty-eight cases. AMA Arch Pathol 58:1–25PubMedGoogle Scholar
  36. Nurgalieva Z, Lowrey A, El-Serag HB (2007) The use of cytokeratin stain to distinguish Barrett’s esophagus from contiguous tissues: a systematic review. Dig Dis Sci 52:1345–1354PubMedCrossRefGoogle Scholar
  37. Oberg S, Peters JH, DeMeester TR, Chandrasoma P, Hagen JA, Ireland AP, Ritter MP, Mason RJ, Crookes P, Bremner CG (1997) Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease. Ann Surg 226:522–530PubMedCrossRefGoogle Scholar
  38. Odze RD (2005) Unraveling the mystery of the gastroesophageal junction: a pathologist’s perspective. Am J Gastroenterol 100:1853–1867PubMedCrossRefGoogle Scholar
  39. Odze RD (2006) Diagnosis and grading of dysplasia in Barrett’s esophagus. J Clin Pathol 59:1029–1038PubMedCrossRefGoogle Scholar
  40. Ormsby AH, Goldblum JR, Rice TW, Richter JE, Falk GW, Vaezi MF, Gramlich TL (1999) Cytokeratin subsets can reliably distinguish Barrett’s esophagus from intestinal metaplasia of the stomach. Hum Pathol 30:288–294PubMedCrossRefGoogle Scholar
  41. Ormsby AH, Kilgore SP, Goldblum JR, Richter JE, Rice TW, Gramlich TL (2000) The location and frequency of intestinal metaplasia at the esophagogastric junction in 223 consecutive autopsies: implications for patient treatment and preventive strategies in Barrett’s esophagus. Mod Pathol 13:614–620PubMedCrossRefGoogle Scholar
  42. Ott K, Lordick F, Herrmann K, Krause BJ, Schumacher C, Siewert JR (2008) The new credo: induction chemotherapy in locally advanced gastric cancer: consequences for surgical strategies. Gastric Cancer 11:1–9PubMedCrossRefGoogle Scholar
  43. Pacelli F, Papa V, Caprino P, Sgadari A, Bossola M, Doglietto GB (2001) Proximal compared with distal gastric cancer: multivariate analysis of prognostic factors. Am Surg 67:697–703PubMedGoogle Scholar
  44. Paraf F, Fléjou JF, Pignon JP, Fékété F, Potet F (1995) Surgical pathology of adenocarcinoma arising in Barrett’s esophagus. Analysis of 67 cases. Am J Surg Pathol 19:183–191PubMedCrossRefGoogle Scholar
  45. Pereira AD, Suspiro A, Chaves P, Saraiva A, Gloria L, de Almeida JC, Leitao CN, Soares J, Mira FC (1998) Short segments of Barrett’s epithelium and intestinal metaplasia in normal appearing esophagogastric junctions: the same or two different entities? Gut 42:659–662PubMedCrossRefGoogle Scholar
  46. Sarbia M, Donner A, Franke C, Gabbert HE (2004) Distinction between intestinal metaplasia in the cardia and in Barrett’s esophagus: the role of histology and immunohistochemistry. Hum Pathol 35:371–376PubMedCrossRefGoogle Scholar
  47. Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Fléjou JF, Geboes K, Hattori T, Hirota T, Itabashi M, Iwafuchi M, Iwashita A, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, Offner F, Price A, Rubio CA, Shimizu M, Shimoda T, Sipponen P, Solcia E, Stolte M, Watanabe H, Yamabe H (2000) The Vienna classification of gastrointestinal epithelial neoplasia. Gut 47:251–255PubMedCrossRefGoogle Scholar
  48. Schmidt HG, Riddell RH, Walther B, Skinner DB, Riemann JF (1985) Dysplasia in Barrett’s esophagus. J Cancer Res Clin Oncol 110:145–152PubMedCrossRefGoogle Scholar
  49. Schneider PM, Baldus SE, Metzger R, Kocher M, Bongartz R, Bollschweiler E, Schaefer H, Thiele J, Dienes HP, Mueller RP, Hoelscher AH (2005) Histomorphologic tumor regression and lymph node metastases determine prognosis following neoadjuvant radiochemotherapy for esophageal cancer. Ann Surg 242:684–692PubMedCrossRefGoogle Scholar
  50. Schneider PM, Metzger R, Schaefer H, Baumgarten F, Vallbohmer D, Brabender J, Wolfgarten E, Bollschweiler E, Baldus SE, Dienes HP, Hoelscher AH (2008) Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not accurately predict histopathologic regression after neoadjuvant chemoradiation for esophageal cancer. Ann Surg 248(6):902–908PubMedCrossRefGoogle Scholar
  51. Sharma P, Weston AP, Morales T, Topalovski M, Mayo MS, Sampliner RE (2000) Relative risk of dysplasia for patients with intestinal metaplasia in the distal esophagus and in the gastric cardia. Gut 46:9–13PubMedCrossRefGoogle Scholar
  52. Siewert JR, Stein HJ (1998) Classification of carcinoma of the esophagogastric junction. Br J Surg 85:1457–1459PubMedCrossRefGoogle Scholar
  53. Siewert JR, Hölscher AH, Becker K, Gössner W (1987) Kardiakarzinom: Versuch einer therapeutisch relevanten Klassifikation. Chirurg 58:25–34PubMedGoogle Scholar
  54. Siewert JR, Lordick F, Ott K, Stein HJ, Weber WA, Becker K, Peschel C, Fink U, Schwaiger M (2007) Induction chemotherapy in Barrett cancer: influence on surgical risk and outcome. Ann Surg 246:624–628PubMedCrossRefGoogle Scholar
  55. Sobin LH, Gospodarowicz MK, Wittekind C (2010) TNM classification of malignant tumours, 7th edn. Wiley-Liss, New YorkGoogle Scholar
  56. Stein HJ, Feith M, Siewert JR (2000) Cancer of the esophagogastric junction. Surg Oncol 9:35–41PubMedCrossRefGoogle Scholar
  57. Stein HJ, von Rahden BHA, Höfler H, Siewert JR (2003) Karzinom des ösophagogastralen Übergangs und Barrett-Ösophagus. Chirurg 74:703–708PubMedCrossRefGoogle Scholar
  58. Stubbe Teglbjaerg P, Vetner M (1977) Gastric carcinoma I. The reproducibility of a histogenetic classification proposed by Masson, Rember and Mulligan. Acta Pathol Microbiol Scand A 85:519–527PubMedGoogle Scholar
  59. Taniere P, Borghi-Scoazec G, Saurin JC, Lombard-Bohas C, Boulez J, Berger F, Hainaut P, Scoazec JY (2002) Cytokeratin expression in adenocarcinomas of the esophagogastric junction: a comparative study of adenocarcinomas of the distal esophagus and of the proximal stomach. Am J Surg Pathol 26:1213–1221PubMedCrossRefGoogle Scholar
  60. Torres C, Turner JR, Wang HH, Richards W, Sugarbaker D, Shahsafaei A, Odze RD (1999) Pathologic prognostic factors in Barrett’s associated adenocarcinoma: a follow-up study of 96 patients. Cancer 85:520–528PubMedCrossRefGoogle Scholar
  61. Vigneri S, Termini R, Savarino V, Pace F (2000) Review article: is Helicobacter pylori status ­relevant in the management of GORD? Aliment Pharmacol Ther 14(suppl 3):31–42PubMedCrossRefGoogle Scholar
  62. Voutilainen M, Sipponen P (2001) Inflammation in the cardia. Curr Gastroenterol Rep 3:215–218PubMedCrossRefGoogle Scholar
  63. Wang HH, Antonioli DA, Goldman H (1986) Comparative features of esophageal and gastric adenocarcinomas: recent changes in type and frequency. Hum Pathol 17:482–487PubMedCrossRefGoogle Scholar
  64. Younes M (2005) What is the role of cytokeratins in Barrett/cardia differentiation? Arch Pathol Lab Med 129:181–182PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Institute of PathologyUniversity of DüsseldorfDüsseldorfGermany

Personalised recommendations