Skip to main content
SpringerLink
Log in

Pathology of Premalignant and Malignant Disease of the Esophagus

  • Chapter
  • First Online:
Esophageal Cancer

Abstract

Esophageal adenocarcinoma and squamous cell carcinoma are associated with defined risk factors and tend to develop over time with progression from normal to pre-neoplasia to neoplasia and frank malignancy. In this chapter, we review the pathology of esophageal adenocarcinoma and its precursor lesions, Barrett’s esophagus, and Barrett’s-associated dysplasia. We also review squamous cell carcinoma and squamous dysplasia. We discuss how biopsy, endoscopic mucosal resection, and esophagectomy specimens are assessed, including the challenges in diagnosis and pathologic staging of these specimens. Finally, we touch upon theragnostic tests, including HER2, microsatellite instability, and PD-L1, that are performed in the pathology laboratory and provide information that identified patients who will benefit most from these targeted therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 2013;381(9864):400–12. https://doi.org/10.1016/S0140-6736(12)60643-6.

    Article  PubMed  Google Scholar 

  2. American Cancer Society. Cancer Facts & Figures 2019. Atlanta: American Cancer Society; 2019.

    Google Scholar 

  3. Avidan B, Sonnenberg A, Schnell TG, Chejfec G, Metz A, Sontag SJ. Hiatal hernia size, Barrett’s length, and severity of acid reflux are all risk factors for esophageal adenocarcinoma. Am J Gastroenterol. 2002;97(8):1930–6. https://doi.org/10.1111/j.1572-0241.2002.05902.x.

    Article  PubMed  Google Scholar 

  4. Cheng KK, Sharp L, McKinney PA, Logan RF, Chilvers CE, Cook-Mozaffari P, Ahmed A, et al. A case-control study of oesophageal adenocarcinoma in women: a preventable disease. Br J Cancer. 2000;83(1):127–32. https://doi.org/10.1054/bjoc.2000.1121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cook MB, Kamangar F, Whiteman DC, Freedman ND, Gammon MD, Bernstein L, Brown LM, et al. Cigarette smoking and adenocarcinomas of the esophagus and esophagogastric junction: a pooled analysis from the international BEACON consortium. J Natl Cancer Inst. 2010;102(17):1344–53. https://doi.org/10.1093/jnci/djq289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. de Jonge PJ, van Blankenstein M, Looman CW, Casparie MK, Meijer GA, Kuipers EJ. Risk of malignant progression in patients with Barrett’s oesophagus: a Dutch nationwide cohort study. Gut. 2010;59(8):1030–6. https://doi.org/10.1136/gut.2009.176701.

    Article  PubMed  Google Scholar 

  7. el-Serag HB. The epidemic of esophageal adenocarcinoma. Gastroenterol Clin N Am. 2002;31(2):421–40. viii.

    Article  PubMed  Google Scholar 

  8. Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005;143(3):199–211.

    Article  PubMed  Google Scholar 

  9. Islami F, Kamangar F. Helicobacter pylori and esophageal cancer risk: a meta-analysis. Cancer Prev Res (Phila). 2008;1(5):329–38. https://doi.org/10.1158/1940-6207.CAPR-08-0109.

    Article  CAS  Google Scholar 

  10. Pohl H, Wrobel K, Bojarski C, Voderholzer W, Sonnenberg A, Rosch T, Baumgart DC. Risk factors in the development of esophageal adenocarcinoma. Am J Gastroenterol. 2013;108(2):200–7. https://doi.org/10.1038/ajg.2012.387.

    Article  PubMed  Google Scholar 

  11. Shaheen NJ, Falk GW, Iyer PG, Gerson LB. ACG clinical guideline: diagnosis and Management of Barrett’s Esophagus. Am J Gastroenterol. 2016;111(1):30–50.; quiz 1. https://doi.org/10.1038/ajg.2015.322.

    Article  CAS  PubMed  Google Scholar 

  12. Fitzgerald RC, di Pietro M, Ragunath K, Ang Y, Kang JY, Watson P, Trudgill N, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2014;63(1):7–42. https://doi.org/10.1136/gutjnl-2013-305372.

    Article  PubMed  Google Scholar 

  13. Takubo K, Vieth M, Aida J, Sawabe M, Kumagai Y, Hoshihara Y, Arai T. Differences in the definitions used for esophageal and gastric diseases in different countries: endoscopic definition of the esophagogastric junction, the precursor of Barrett’s adenocarcinoma, the definition of Barrett’s esophagus, and histologic criteria for mucosal adenocarcinoma or high-grade dysplasia. Digestion. 2009;80(4):248–57. https://doi.org/10.1159/000235923.

    Article  PubMed  Google Scholar 

  14. Byrne JP, Bhatnagar S, Hamid B, Armstrong GR, Attwood SE. Comparative study of intestinal metaplasia and mucin staining at the cardia and esophagogastric junction in 225 symptomatic patients presenting for diagnostic open-access gastroscopy. Am J Gastroenterol. 1999;94(1):98–103. https://doi.org/10.1111/j.1572-0241.1999.00778.x.

    Article  CAS  PubMed  Google Scholar 

  15. 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):818–25. https://doi.org/10.1097/PAS.0b013e3181984697.

    Article  PubMed  Google Scholar 

  16. Anders M, Lucks Y, El-Masry MA, Quaas A, Rosch T, Schachschal G, Bahr C, et al. Subsquamous extension of intestinal metaplasia is detected in 98% of cases of neoplastic Barrett’s esophagus. Clinical Gastroenterol Hepatol. 2014;12(3):405–10. https://doi.org/10.1016/j.cgh.2013.07.013.

    Article  Google Scholar 

  17. Yachimski P, Shi C, Slaughter JC, Washington MK. Endoscopic mucosal resection of Barrett’s esophagus detects high prevalence of subsquamous intestinal metaplasia. World J Gastrointest Endosc. 2013;5(12):590–4. https://doi.org/10.4253/wjge.v5.i12.590.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Dunbar KB, Spechler SJ. Controversies in Barrett esophagus. Mayo Clin Proc. 2014;89(7):973–84. https://doi.org/10.1016/j.mayocp.2014.01.022.

    Article  PubMed  Google Scholar 

  19. Edge SB, Byrd DR, Carducci MA, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th ed. New York, NY: Springer; 2009.

    Google Scholar 

  20. Amin MB, Edge SB, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, et al., editors. AJCC cancer staging manual. 8th ed. New York, NY: Springer; 2017.

    Google Scholar 

  21. Chinyama CN, Marshall RE, Owen WJ, Mason RC, Kothari D, Wilkinson ML, Sanderson JD. Expression of MUC1 and MUC2 mucin gene products in Barrett’s metaplasia, dysplasia and adenocarcinoma: an immunopathological study with clinical correlation. Histopathology. 1999;35(6):517–24.

    Article  CAS  PubMed  Google Scholar 

  22. Groisman GM, Amar M, Meir A. Expression of the intestinal marker Cdx2 in the columnar-lined esophagus with and without intestinal (Barrett’s) metaplasia. Mod Pathol. 2004;17(10):1282–8. https://doi.org/10.1038/modpathol.3800182.

    Article  CAS  PubMed  Google Scholar 

  23. Guillem P, Billeret V, Buisine MP, Flejou JF, Lecomte-Houcke M, Degand P, Aubert JP, et al. Mucin gene expression and cell differentiation in human normal, premalignant and malignant esophagus. Int J Cancer. 2000;88(6):856–61.

    Article  CAS  PubMed  Google Scholar 

  24. Phillips RW, Frierson HF Jr, Moskaluk CA. Cdx2 as a marker of epithelial intestinal differentiation in the esophagus. Am J Surg Pathol. 2003;27(11):1442–7.

    Article  PubMed  Google Scholar 

  25. Srivastava A, Appelman H, Goldsmith JD, Davison JM, Hart J, Krasinskas AM. The use of ancillary stains in the diagnosis of Barrett esophagus and Barrett Esophagus-associated dysplasia: recommendations from the Rodger C. Haggitt gastrointestinal pathology society. Am J Surg Pathol. 2017;41(5):e8–e21. https://doi.org/10.1097/pas.0000000000000819.

    Article  PubMed  Google Scholar 

  26. Murray L, Sedo A, Scott M, McManus D, Sloan JM, Hardie LJ, Forman D, et al. TP53 and progression from Barrett’s metaplasia to oesophageal adenocarcinoma in a UK population cohort. Gut. 2006;55(10):1390–7. https://doi.org/10.1136/gut.2005.083295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kaye PV, Haider SA, James PD, Soomro I, Catton J, Parsons SL, Ragunath K, et al. Novel staining pattern of p53 in Barrett’s dysplasia – the absent pattern. Histopathology. 2010;57(6):933–5. https://doi.org/10.1111/j.1365-2559.2010.03715.x.

    Article  PubMed  Google Scholar 

  28. Kerkhof M, van Dekken H, Steyerberg EW, Meijer GA, Mulder AH, de Bruine A, Driessen A, et al. Grading of dysplasia in Barrett’s oesophagus: substantial interobserver variation between general and gastrointestinal pathologists. Histopathology. 2007;50(7):920–7. https://doi.org/10.1111/j.1365-2559.2007.02706.x.

    Article  CAS  PubMed  Google Scholar 

  29. Curvers WL, ten Kate FJ, Krishnadath KK, Visser M, Elzer B, Baak LC, Bohmer C, et al. Low-grade dysplasia in Barrett’s esophagus: overdiagnosed and underestimated. Am J Gastroenterol. 2010;105(7):1523–30. https://doi.org/10.1038/ajg.2010.171.

    Article  PubMed  Google Scholar 

  30. Duits LC, Phoa KN, Curvers WL, Ten Kate FJ, Meijer GA, Seldenrijk CA, Offerhaus GJ, 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):700–6. https://doi.org/10.1136/gutjnl-2014-307278.

    Article  PubMed  Google Scholar 

  31. Alikhan M, Rex D, Khan A, Rahmani E, Cummings O, Ulbright TM. Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice. Gastrointest Endosc. 1999;50(1):23–6.

    Article  CAS  PubMed  Google Scholar 

  32. Abraham SC, Krasinskas AM, Correa AM, Hofstetter WL, Ajani JA, Swisher SG, Wu TT. 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):1719–25. https://doi.org/10.1097/PAS.0b013e318093e3bf.

    Article  PubMed  Google Scholar 

  33. Mandal RV, Forcione DG, Brugge WR, Nishioka NS, Mino-Kenudson M, Lauwers GY. Effect of tumor characteristics and duplication of the muscularis mucosae on the endoscopic staging of superficial Barrett esophagus-related neoplasia. Am J Surg Pathol. 2009;33(4):620–5. https://doi.org/10.1097/PAS.0b013e31818d632f.

    Article  PubMed  Google Scholar 

  34. Kumarasinghe MP, Brown I, Raftopoulos S, Bourke MJ, Charlton A, de Boer WB, Eckstein R, et al. Standardised reporting protocol for endoscopic resection for Barrett oesophagus associated neoplasia: expert consensus recommendations. Pathology. 2014;46(6):473–80. https://doi.org/10.1097/PAT.0000000000000160.

    Article  CAS  PubMed  Google Scholar 

  35. Vieth M, Stolte M. Pathology of early upper GI cancers. Best Pract Res Clin Gastroenterol. 2005;19(6):857–69. https://doi.org/10.1016/j.bpg.2005.02.008.

    Article  PubMed  Google Scholar 

  36. Edge SB, Compton CC, et al., editors. AJCC cancer staging manual. New York: Springer-Verlag; 2009.

    Google Scholar 

  37. Dry SM, Lewin KJ. Esophageal squamous dysplasia. Semin Diagn Pathol. 2002;19(1):2–11.

    PubMed  Google Scholar 

  38. Shimizu M, Ban S, Odze RD. Squamous dysplasia and other precursor lesions related to esophageal squamous cell carcinoma. Gastroenterol Clin N Am. 2007;36(4):797–811., v-vi. https://doi.org/10.1016/j.gtc.2007.08.005.

    Article  Google Scholar 

  39. Daly JM, Fry WA, Little AG, Winchester DP, McKee RF, Stewart AK, Fremgen AM. Esophageal cancer: results of an American College of Surgeons patient care evaluation study. J Am Coll Surg. 2000;190(5):562–72; discussion 72-3

    Article  CAS  PubMed  Google Scholar 

  40. Dawsey SM, Fagundes RB, Jacobson BC, Kresty LA, Mallery SR, Paski S, van den Brandt PA. Diet and esophageal disease. Ann N Y Acad Sci. 2014;1325(1):127–37. https://doi.org/10.1111/nyas.12528.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Prabhu A, Obi KO, Rubenstein JH. The synergistic effects of alcohol and tobacco consumption on the risk of esophageal squamous cell carcinoma: a meta-analysis. Am J Gastroenterol. 2014;109(6):822–7. https://doi.org/10.1038/ajg.2014.71.

    Article  PubMed  Google Scholar 

  42. O’Neill OM, Johnston BT, Coleman HG. Achalasia: a review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol: WJG. 2013;19(35):5806–12. https://doi.org/10.3748/wjg.v19.i35.5806.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Iwaya T, Maesawa C, Ogasawara S, Tamura G. Tylosis esophageal cancer locus on chromosome 17q25.1 is commonly deleted in sporadic human esophageal cancer. Gastroenterology. 1998;114(6):1206–10.

    Article  CAS  PubMed  Google Scholar 

  44. Al-Haddad S, El-Zimaity H, Hafezi-Bakhtiari S, Rajendra S, Streutker CJ, Vajpeyi R, Wang B. Infection and esophageal cancer. Ann N Y Acad Sci. 2014;1325(1):187–96. https://doi.org/10.1111/nyas.12530.

    Article  PubMed  Google Scholar 

  45. Takubo K, Fujii S. Squamous cell carcinoma of the oesophagus. In: WHO Classification of Tumours Editorial Board, editor. WHO classification of tumors: digestive system. 5th ed. Lyon: WHO Press; 2019. p. 36–7.

    Google Scholar 

  46. Ando N, Ozawa S, Kitagawa Y, Shinozawa Y, Kitajima M. Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years. Ann Surg. 2000;232(2):225–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tachimori Y, Nagai Y, Kanamori N, Hokamura N, Igaki H. Pattern of lymph node metastases of esophageal squamous cell carcinoma based on the anatomical lymphatic drainage system. Dis Esophagus. 2011;24(1):33–8. https://doi.org/10.1111/j.1442-2050.2010.01086.x.

    Article  CAS  PubMed  Google Scholar 

  48. Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, et al. SEER cancer statistics review 1975–2010. Bethesda, MD: National Cancer Institute. (http://seer.cancer.gov/csr/1975_2010/, based on November 2012 SEER data submission, posted to the SEER Web site, April 2013)

  49. Shah RD, Cassano AD, Neifeld JP. Neoadjuvant therapy for esophageal cancer. World J Gastrointest Oncol. 2014;6(10):403–6. https://doi.org/10.4251/wjgo.v6.i10.403.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Brucher BL, Becker K, Lordick F, Fink U, Sarbia M, Stein H, Busch R, et al. The clinical impact of histopathologic response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas. Cancer. 2006;106(10):2119–27. https://doi.org/10.1002/cncr.21850.

    Article  PubMed  Google Scholar 

  51. Chang F, Deere H, Mahadeva U, George S. Histopathologic examination and reporting of esophageal carcinomas following preoperative neoadjuvant therapy: practical guidelines and current issues. Am J Clin Pathol. 2008;129(2):252–62. https://doi.org/10.1309/CCR3QN4874YJDJJ7.

    Article  PubMed  Google Scholar 

  52. Wu TT, Chirieac LR, Abraham SC, Krasinskas AM, Wang H, Rashid A, Correa AM, et al. Excellent interobserver agreement on grading the extent of residual carcinoma after preoperative chemoradiation in esophageal and esophagogastric junction carcinoma: a reliable predictor for patient outcome. Am J Surg Pathol. 2007;31(1):58–64. https://doi.org/10.1097/01.pas.0000213312.36306.cc.

    Article  PubMed  Google Scholar 

  53. Hermann RM, Horstmann O, Haller F, Perske C, Christiansen H, Hille A, Schmidberger H, et al. Histomorphological tumor regression grading of esophageal carcinoma after neoadjuvant radiochemotherapy: which score to use? Dis Esophagus. 2006;19(5):329–34. https://doi.org/10.1111/j.1442-2050.2006.00589.x.

    Article  CAS  PubMed  Google Scholar 

  54. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97. https://doi.org/10.1016/S0140-6736(10)61121-X.

    Article  CAS  PubMed  Google Scholar 

  55. Bartley AN, Washington MK, Colasacco C, Ventura CB, Ismaila N, Benson AB 3rd, Carrato A, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35(4):446–64. https://doi.org/10.1200/JCO.2016.69.4836.

    Article  CAS  PubMed  Google Scholar 

  56. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Esophageal and Esophagogastric Junction Cancers. , V.4.2017. http://www.nccn.org. Accessed 10 Feb 2018.

  57. Yoon HH, Shi Q, Sukov WR, Wiktor AE, Khan M, Sattler CA, Grothey A, et al. Association of HER2/ErbB2 expression and gene amplification with pathologic features and prognosis in esophageal adenocarcinomas. Clin Cancer Res. 2012;18(2):546–54. https://doi.org/10.1158/1078-0432.CCR-11-2272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, et al. PD-1 blockade in Tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20. https://doi.org/10.1056/NEJMoa1500596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Meltzer SJ, Yin J, Manin B, Rhyu MG, Cottrell J, Hudson E, Redd JL, et al. Microsatellite instability occurs frequently and in both diploid and aneuploid cell populations of Barrett’s-associated esophageal adenocarcinomas. Cancer Res. 1994;54(13):3379–82.

    CAS  PubMed  Google Scholar 

  60. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–13. https://doi.org/10.1126/science.aan6733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Curea FG, Hebbar M, Ilie SM, Bacinschi XE, Trifanescu OG, Botnariuc I, Anghel RM. Current targeted therapies in HER2-positive gastric adenocarcinoma. Cancer Biother Radiopharm. 2017;32(10):351–63. https://doi.org/10.1089/cbr.2017.2249.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA

    Jessica Tracht, Brian S. Robinson & Alyssa M. Krasinskas

Authors
  1. Jessica Tracht
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian S. Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alyssa M. Krasinskas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alyssa M. Krasinskas .

Editor information

Editors and Affiliations

  1. Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, GA, USA

    Nabil F. Saba

  2. Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, GA, USA

    Bassel F. El-Rayes

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Tracht, J., Robinson, B.S., Krasinskas, A.M. (2020). Pathology of Premalignant and Malignant Disease of the Esophagus. In: Saba, N., El-Rayes, B. (eds) Esophageal Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-29832-6_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-29832-6_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-29831-9

  • Online ISBN: 978-3-030-29832-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation