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Review Article| Volume 32, ISSUE 4, P413-424, November 2022

Barrett’s Esophagus and Esophageal Adenocarcinoma: A Histopathological Perspective

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      References

        • Cattelan L.
        • Ghazawi F.M.
        • Le M.
        • et al.
        Epidemiologic trends and geographic distribution of esophageal cancer in Canada: A national population-based study.
        Cancer Med. 2020; 9: 401-417
        • Hur C.
        • Miller M.
        • Kong C.Y.
        • et al.
        Trends in esophageal adenocarcinoma incidence and mortality.
        Cancer. 2013; 119: 1149-1158
        • Shaheen N.J.
        • Falk G.W.
        • Iyer P.G.
        • et al.
        ACG Clinical Guideline: Diagnosis and management of Barrett’s esophagus.
        Am J Gastroenterol. 2016; 111: 30-50
        • Cook M.B.
        • Thrift A.P.
        Epidemiology of Barrett’s esophagus and esophageal adenocarcinoma - implications for screening and surveillance.
        Gastrointest Endosc Clin N Am. 2021; 31: 1-26
        • Rustgi A.K.
        • El-Serag H.B.
        Esophageal carcinoma.
        N Engl J Med. 2014; 371: 2499-2509
        • Groulx S.
        • Limburg H.
        • Doull M.
        • et al.
        Guideline on screening for esophageal adenocarcinoma in patients with chronic gastroesophageal reflux disease.
        Can Med Assoc J. 2020; 192: E768-E777
        • Then E.O.
        • Lopez M.
        • Saleem S.
        • et al.
        Esophageal cancer: An updated Surveillance Epidemiology and End Results database analysis.
        World J Oncol. 2020; 11: 55-64
        • 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
        • Naini B.V.
        • Souza R.F.
        • Odze R.D.
        Barrett’s esophagus: a comprehensive and contemporary review for pathologists.
        Am J Surg Pathol. 2016; 40: e45-e66
        • Coleman H.G.
        • Xie S.H.
        • Lagergren J.
        The epidemiology of esophageal adenocarcinoma.
        Gastroenterology. 2018; 154: 390-405
        • Desai T.K.
        • Krishnan K.
        • Samala N.
        • et al.
        The incidence of oesophageal adenocarcinoma in non-dysplastic Barrett’s oesophagus: a meta-analysis.
        Gut. 2012; 61: 970-976
        • Singh S.
        • Manickam P.
        • Amin A.V.
        • et al.
        Incidence of esophageal adenocarcinoma in Barrett’s esophagus with low-grade dysplasia: a systematic review and meta-analysis.
        Gastrointest Endosc. 2014; 79 (e4): 897-909
        • Rastogi A.
        • Puli S.
        • El-Serag H.B.
        • et al.
        Incidence of esophageal adenocarcinoma in patients with Barrett’s esophagus and high-grade dysplasia: a meta-analysis.
        Gastrointest Endosc. 2008; 67: 394-398
        • Goldblum J.R.
        Barrett’s esophagus and Barrett’s-related dysplasia.
        Mod Pathol. 2003; 16: 316-324
        • Hopcroft S.A.
        • Shepherd N.A.
        The changing role of the pathologist in the management of Barrett’s oesophagus.
        Histopathology. 2014; 65: 441-455
        • Barrett N.R.
        Chronic peptic ulcers of the œsophagus and ‘œsophagitis.
        Br J Surg. 1950; 38: 175-182
        • Lowes H.
        • Somarathna T.
        • Shepherd N.A.
        Definition, derivation, and diagnosis of Barrett’s esophagus: pathological perspectives.
        in: Jansen M. Wright N.A. Stem cells, Pre-neoplasia, and early cancer of the Upper gastrointestinal tract. Springer International Publishing, Switzerland2016: 111-136
        • Paull A.
        • Trier J.S.
        • Dalton M.D.
        • et al.
        The histologic spectrum of Barrett’s esophagus.
        N Engl J Med. 1976; 295: 476-480
        • 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: 201-214
        • 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
        • Slack J.M.W.
        Metaplasia and transdifferentiation: from pure biology to the clinic.
        Nat Rev Mol Cell Biol. 2007; 8: 369-378
        • Geboes K.
        • Hoorens A.
        The cell of origin for Barrett’s esophagus.
        Science. 2021; 373: 737-738
        • Boch J.
        • Shields H.
        • Antonioli D.
        • et al.
        Distribution of cytokeratin markers in Barrett’s specialized columnar epithelium.
        Gastroenterology. 1997; 112: 760-765
        • Aichler M.
        • Seiler C.
        • Tost M.
        • et al.
        Origin of pancreatic ductal adenocarcinoma from atypical flat lesions: a comparative study in transgenic mice and human tissues.
        J Pathol. 2012; 226: 723-734
        • Barbera M.
        • Pietro M di
        • Walker E.
        • et al.
        The human squamous oesophagus has widespread capacity for clonal expansion from cells at diverse stages of differentiation.
        Gut. 2015; 64: 11-19
        • Sarosi G.
        • Brown G.
        • Jaiswal K.
        • et al.
        Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett’s esophagus.
        Dis Esophagus. 2008; 21: 43-50
        • Aikou S.
        • Aida J.
        • Takubo K.
        • et al.
        Columnar metaplasia in a surgical mouse model of gastro-esophageal reflux disease is not derived from bone marrow-derived cell.
        Cancer Sci. 2013; 104: 1154-1161
        • Leedham S.J.
        • Preston S.L.
        • McDonald S.A.C.
        • et al.
        Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett’s oesophagus.
        Gut. 2008; 57: 1041-1048
        • Owen R.P.
        • White M.J.
        • Severson D.T.
        • et al.
        Single cell RNA-seq reveals profound transcriptional similarity between Barrett’s oesophagus and oesophageal submucosal glands.
        Nat Commun. 2018; 9: 4261
        • Nowicki-Osuch K.
        • Zhuang L.
        • Jammula S.
        • et al.
        Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition.
        Science. 2021; 373: 760-767
        • Riddell R.H.
        • Goldman H.
        • Ransohoff D.F.
        • et al.
        Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications.
        Hum Pathol. 1983; 14: 931-968
        • van der Wel M.J.
        • Jansen M.
        • Vieth M.
        • et al.
        What makes an expert Barrett’s histopathologist?.
        in: Jansen M. Wright N.A. Stem cells, Pre-neoplasia, and early cancer of the Upper gastrointestinal tract. Springer International Publishing, Switzerland2016: 137-159
        • Yin F.
        • Hernandez Gonzalo D.
        • Lai J.
        • et al.
        Histopathology of Barrett’s esophagus and early-stage esophageal adenocarcinoma: an updated review.
        Gastrointest Disord. 2019; 1: 147-163
        • Kumarasinghe M.P.
        • Armstrong M.
        • Foo J.
        • et al.
        The modern management of Barrett’s oesophagus and related neoplasia: role of pathology.
        Histopathology. 2021; 78: 18-38
        • Corsini E.M.
        • Foo W.C.
        • Mitchell K.G.
        • et al.
        Esophageal adenocarcinoma with any component of signet ring cells portends poor prognosis and response to neoadjuvant therapy.
        J Thorac Cardiovasc Surg. 2021; 162: 1404-1412
        • Patel V.R.
        • Hofstetter W.L.
        • Correa A.M.
        • et al.
        Signet ring cells in esophageal adenocarcinoma predict poor response to preoperative chemoradiation.
        Ann Thorac Surg. 2014; 98: 1064-1071
        • Rice T.W.
        • Patil D.T.
        • Blackstone E.H.
        8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice.
        Ann Cardiothorac Surg. 2017; 6: 119-130
        • Bejarano P.A.
        • Berho M.
        Examination of surgical specimens of the esophagus.
        Arch Pathol Lab Med. 2015; 139: 1446-1454
        • Orosey M.
        • Amin M.
        • Cappell M.S.
        A 14-year study of 398 esophageal adenocarcinomas diagnosed among 156,256 EGDs performed at two large hospitals: an inlet patch is proposed as a significant risk factor for proximal esophageal adenocarcinoma.
        Dig Dis Sci. 2018; 63: 452-465
        • Taniere P.
        • Borghi-Scoazec G.
        • Saurin J.C.
        • et al.
        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. 2002; 26: 1213-1221
        • Driessen A.
        • Nafteux P.
        • Lerut T.
        • et al.
        Identical cytokeratin expression pattern CK7+/CK20- in esophageal and cardiac cancer: etiopathological and clinical implications.
        Mod Pathol. 2004; 17: 49-55
        • Shah M.A.
        • Kennedy E.B.
        • Catenacci D.V.
        • et al.
        Treatment of locally advanced esophageal carcinoma: ASCO Guideline.
        J Clin Oncol. 2020; 38: 2677-2694
        • Muir J.A.
        • Marcon N.
        • Aranda-Hernandez J.
        • et al.
        Endoscopic mucosal resection (EMR) in Barrett’s esophagus associated neoplasia: recommendations for pathological evaluation and reporting.
        Can J Pathol. 2015; 7: 25-36
        • Sharma P.
        • Shaheen N.J.
        • Katzka D.
        • et al.
        AGA clinical practice update on endoscopic treatment of Barrett’s esophagus with dysplasia and/or early cancer: expert review.
        Gastroenterology. 2020; 158: 760-769
        • Kumarasinghe M.P.
        • Bourke M.J.
        • Brown I.
        • et al.
        Pathological assessment of endoscopic resections of the gastrointestinal tract: a comprehensive clinicopathologic review.
        Mod Pathol. 2020; 33: 986-1006
        • Othman M.O.
        • Lee J.H.
        • Wang K.
        AGA clinical practice update on the utility of endoscopic submucosal dissection in T1b esophageal cancer: expert review.
        Clin Gastroenterol Hepatol. 2019; 17: 2161-2166
        • Manner H.
        • Pech O.
        • Heldmann Y.
        • et al.
        The frequency of lymph node metastasis in early-stage adenocarcinoma of the esophagus with incipient submucosal invasion (pT1b sm1) depending on histological risk patterns.
        Surg Endosc. 2015; 29: 1888-1896
        • Manner H.
        • Pech O.
        • Heldmann Y.
        • et al.
        Efficacy, safety, and long-term results of endoscopic treatment for early stage adenocarcinoma of the esophagus with low-risk sm1 invasion.
        Clin Gastroenterol Hepatol. 2013; 11: 630-635
        • Nentwich M.F.
        • von Loga K.
        • Reeh M.
        • et al.
        Depth of submucosal tumor infiltration and its relevance in lymphatic metastasis formation for T1b squamous cell and adenocarcinomas of the esophagus.
        J Gastrointest Surg. 2014; 18: 242-249
        • Griffin S.M.
        • Burt A.D.
        • Jennings N.A.
        Lymph node metastasis in early esophageal adenocarcinoma.
        Ann Surg. 2011; 254: 731-737
        • Cen P.
        • Hofstetter W.L.
        • Correa A.M.
        • et al.
        Lymphovascular invasion as a tool to further subclassify T1b esophageal adenocarcinoma.
        Cancer. 2008; 112: 1020-1027
        • Badreddine R.J.
        • Prasad G.A.
        • Lewis J.T.
        • et al.
        Depth of submucosal invasion does not predict lymph node metastasis and survival of patients with esophageal carcinoma.
        Clin Gastroenterol Hepatol. 2010; 8: 248-253
        • Karamchandani D.M.
        • Gonzalez R.S.
        • Westerhoff M.
        • et al.
        Measuring depth of invasion of submucosa – invasive adenocarcinoma in oesophageal endoscopic specimens: how good are we?.
        Histopathology. 2022; 80: 420-429
        • Dunbar K.B.
        • Spechler S.J.
        The risk of lymph node metastases in patients with high grade dysplasia or intramucosal carcinoma in Barrett’s esophagus: a systematic review.
        Am J Gastroenterol. 2012; 107: 850-863
        • Zemler B.
        • May A.
        • Ell C.
        • et al.
        Early Barrett’s carcinoma: the depth of infiltration of the tumour correlates with the degree of differentiation, the incidence of lymphatic vessel and venous invasion.
        Virchows Archiv. 2010; 456: 609-614
        • Estrella J.S.
        • Hofstetter W.L.
        • Correa A.M.
        • 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: 1045-1053
        • Kaneshiro D.K.
        • Post J.C.
        • Rybicki L.
        • et al.
        Clinical significance of the duplicated muscularis mucosae in Barrett esophagus-related superficial adenocarcinoma.
        Am J Surg Pathol. 2011; 35: 697-700
        • Chang F.
        • Deere H.
        • Mahadeva U.
        • et al.
        Histopathologic examination and reporting of esophageal carcinomas following preoperative neoadjuvant therapy: practical guidelines and current issues.
        Am J Clin Pathol. 2008; 129: 252-262
        • Wang K.L.
        • Yang Q.
        • Cleary K.R.
        • et al.
        The significance of neuroendocrine differentiation in adenocarcinoma of the esophagus and esophagogastric junction after preoperative chemoradiation.
        Cancer. 2006; 107: 1467-1474
        • Alnaji R.M.
        • Du W.
        • Gabriel E.
        • et al.
        Pathologic complete response is an independent predictor of improved survival following neoadjuvant chemoradiation for esophageal adenocarcinoma.
        J Gastrointest Surg. 2016; 20: 1541-1546
        • Langer R.
        • Ott K.
        • Feith M.
        • et al.
        Prognostic significance of histopathological tumor regression after neoadjuvant chemotherapy in esophageal adenocarcinomas.
        Mod Pathol. 2009; 22: 1555-1563
        • Groth S.S.
        • Burt B.M.
        • Farjah F.
        • et al.
        Prognostic value of neoadjuvant treatment response in locally advanced esophageal adenocarcinoma.
        J Thorac Cardiovasc Surg. 2019; 157: 1682-1693
        • Mandard A.M.
        • Dalibard F.
        • Mandard J.C.
        • et al.
        Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations.
        Cancer. 1994; 73: 2680-2686
        • Langer R.
        • Becker K.
        Tumor regression grading of gastrointestinal cancers after neoadjuvant therapy.
        Virchows Archiv. 2018; 472: 175-186
        • Takeda F.R.
        • Tustumi F.
        • de Almeida Obregon C.
        • et al.
        Prognostic value of tumor regression grade based on Ryan score in squamous cell carcinoma and adenocarcinoma of esophagus.
        Ann Surg Oncol. 2020; 27: 1241-1247
        • Noble F.
        • Lloyd M.A.
        • Turkington R.
        • et al.
        Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma.
        Br J Surg. 2017; 104: 1816-1828
        • Karamitopoulou E.
        • Thies S.
        • Zlobec I.
        • et al.
        Assessment of tumor regression of esophageal adenocarcinomas after neoadjuvant chemotherapy: comparison of 2 commonly used scoring approaches.
        Am J Surg Pathol. 2014; 38: 1551-1556
        • Hornick J.L.
        • Farraye F.A.
        • Odze R.D.
        Prevalence and significance of prominent mucin pools in the esophagus post neoadjuvant chemoradiotherapy for Barrett’s-associated adenocarcinoma.
        Am J Surg Pathol. 2006; 30: 28-35
        • Spicer J.
        • Benay C.
        • Lee L.
        • et al.
        Diagnostic accuracy and utility of intraoperative microscopic margin analysis of gastric and esophageal adenocarcinoma.
        Ann Surg Oncol. 2014; 21: 2580-2586
        • Chan D.S.Y.
        • Reid T.D.
        • Howell I.
        • et al.
        Systematic review and meta-analysis of the influence of circumferential resection margin involvement on survival in patients with operable oesophageal cancer.
        Br J Surg. 2013; 100: 456-464
        • Thies S.
        • Guldener L.
        • Slotta-Huspenina J.
        • et al.
        Impact of peritumoral and intratumoral budding in esophageal adenocarcinomas.
        Hum Pathol. 2016; 52: 1-8
        • Landau M.S.
        • Hastings S.M.
        • Foxwell T.J.
        • et al.
        Tumor budding is associated with an increased risk of lymph node metastasis and poor prognosis in superficial esophageal adenocarcinoma.
        Mod Pathol. 2014; 27: 1578-1589
        • Lohneis P.
        • Hieggelke L.
        • Gebauer F.
        • et al.
        Tumor budding assessed according to the criteria of the International Tumor Budding Consensus Conference determines prognosis in resected esophageal adenocarcinoma.
        Virchows Archiv. 2021; 478: 393-400
        • Marginean E.C.
        • Dhanpat J.
        Pathologic assessment of endoscopic resection specimens with superficial carcinoma of the esophagus: current practice and practical issues.
        Ann N Y Acad Sci. 2020; 1482: 130-145
        • Nafteux P.R.
        • Lerut A.M.
        • Moons J.
        • et al.
        International multicenter study on the impact of extracapsular lymph node involvement in primary surgery adenocarcinoma of the esophagus on overall survival and staging systems.
        Ann Surg. 2015; 262: 809-816
        • Wang A.
        • Tan Y.
        • Geng X.
        • et al.
        Lymphovascular invasion as a poor prognostic indicator in thoracic esophageal carcinoma: a systematic review and meta-analysis.
        Dis Esophagus. 2019; 32: doy083
        • Lordick F.
        • Mariette C.
        • Haustermans K.
        • et al.
        Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2016; 27: v50-v57
        • Bang Y.J.
        • Van Cutsem E.
        • Feyereislova A.
        • 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: 687-697
        • Hu Y.
        • Bandla S.
        • Godfrey T.E.
        • et al.
        HER2 amplification, overexpression and score criteria in esophageal adenocarcinoma.
        Mod Pathol. 2011; 24: 899-907
        • Yoon H.H.
        • Shi Q.
        • Sukov W.R.
        • et al.
        Association of HER2/ErbB2 expression and gene amplification with pathologic features and prognosis in esophageal adenocarcinomas.
        Clin Cancer Res. 2012; 18: 546-554
        • Bartley A.N.
        • Washington M.K.
        • Ventura C.B.
        • et al.
        HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology.
        Am J Clin Pathol. 2016; 146: 647-669