ESOPHAGUS: Endoscopic Resection, Esophagectomy, or ...



Protocol for the Examination of Specimens From Patients?With Carcinoma of the EsophagusProtocol applies to all carcinomas of the esophagus, including esophagogastric junction carcinomas. Well-differentiated neuroendocrine tumors (carcinoid tumors) are not included.Based on AJCC/UICC TNM, 7th editionProtocol web posting date: October 2013ProceduresEndoscopic ResectionEsophagectomyEsophagogastrectomyAuthorsKay Washington, MD, PhD, FCAP*Department of Pathology, Vanderbilt University Medical Center, Nashville, TNJordan Berlin, MDDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TNPhilip Branton, MD, FCAP Department of Pathology, Inova Fairfax Hospital, Falls Church, VALawrence J. Burgart, MD, FCAPAllina Laboratories, Abbott Northwestern Hospital, Minneapolis, MNDavid K. Carter, MD, FCAPDepartment of Pathology, St. Mary’s/Duluth Clinic Health System, Duluth, MNPatrick Fitzgibbons, MD, FCAPDepartment of Pathology, St. Jude Medical Center, Fullerton, CAWendy L. Frankel, MD, FCAPDepartment of Pathology, Ohio State University Medical Center, Columbus, OHJohn Jessup, MDDivision of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MDSanjay Kakar, MD, FCAPDepartment of Pathology, University of California San Francisco and the Veterans Affairs Medical Center, San Francisco, CABruce Minsky, MDDepartment of Radiation Oncology, University of Chicago, Chicago, ILRaouf Nakhleh, MD, FCAPDepartment of Pathology, Mayo Clinic, Jacksonville, FLLaura H. Tang, MD, PhD, FCAPDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NYCarolyn C. Compton, MD, PhD, FCAP?Critical Path Institute, Tucson, AZFor the Members of the Cancer Committee, College of American Pathologists* Denotes primary author. ? Denotes senior author. All other contributing authors are listed alphabetically. Previous contributors: Randall G. Lee, MD; Leslie H. Sobin, MD; Donald?Antonioli, MD; Harvey?Goldman, MD; Rodger C. Haggitt, MD; Robert V. P. Hutter, MD; Klaus Lewin, MD; Pablo Ross, MD; Heidrun Rotterdam, MD; Stuart?Spechler, MD; Christopher Willett, MD; Donald E. Henson, MD? 2013 College of American Pathologists (CAP). All rights reserved.The College does not permit reproduction of any substantial portion of these protocols without its written authorization. The College hereby authorizes use of these protocols by physicians and other health care providers in reporting on surgical specimens, in teaching, and in carrying out medical research for nonprofit purposes. This authorization does not extend to reproduction or other use of any substantial portion of these protocols for commercial purposes without the written consent of the College.The CAP also authorizes physicians and other health care practitioners to make modified versions of the Protocols solely for their individual use in reporting on surgical specimens for individual patients, teaching, and carrying out medical research for non-profit purposes.The CAP further authorizes the following uses by physicians and other health care practitioners, in reporting on surgical specimens for individual patients, in teaching, and in carrying out medical research for non-profit purposes: (1) Dictation from the original or modified protocols for the purposes of creating a text-based patient record on paper, or in a word processing document; (2) Copying from the original or modified protocols into a text-based patient record on paper, or in a word processing document; (3) The use of a computerized system for items (1) and (2), provided that the protocol data is stored intact as a single text-based document, and is not stored as multiple discrete data fields.Other than uses (1), (2), and (3) above, the CAP does not authorize any use of the Protocols in electronic medical records systems, pathology informatics systems, cancer registry computer systems, computerized databases, mappings between coding works, or any computerized system without a written license from the CAP.Any public dissemination of the original or modified protocols is prohibited without a written license from the CAP.The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations of surgical specimens. The College regards the reporting elements in the “Surgical Pathology Cancer Case Summary” portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice.The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the required data elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of this document.The inclusion of a product name or service in a CAP publication should not be construed as an endorsement of such product or service, nor is failure to include the name of a product or service to be construed as disapproval.CAP Esophagus Protocol Revision HistoryVersion CodeThe definition of the version code can be found at cancerprotocols.Version: Esophagus 3.1.1.2Summary of ChangesThe following changes have been made since the June 2012 release.Endoscopic Resection, Esophagectomy, or EsophagogastrectomyPathologic Staging (pTNM)Primary Tumor (pT)pT4b was changed from an optional to a required data element.Surgical Pathology Cancer Case SummaryProtocol web posting date: October 2013ESOPHAGUS: Endoscopic Resection, Esophagectomy, or Esophagogastrectomy (Note A)Select a single response unless otherwise indicated.Specimen (select all that apply)___ Esophagus___ Proximal stomach___ Other (specify): __________________________ Not specifiedProcedure___ Endoscopic resection___ Esophagectomy___ Esophagogastrectomy___ Other (specify): __________________________ Not specifiedTumor Site (select all that apply) (Note B)___ Cervical (proximal) esophagus___ Midesophagus+ ___ Upper thoracic esophagus+ ___ Midthoracic esophagus___ Distal esophagus (lower thoracic esophagus)___ Esophagogastric junction (EGJ)___ Proximal stomach and esophagogastric junction___ Other (specify): __________________________ Not specified Relationship of Tumor to Esophagogastric Junction (Note B)___ Tumor is entirely located within the tubular esophagus and does not involve the esophagogastric junction___ Tumor midpoint lies in the distal esophagus and tumor involves the esophagogastric junction___ Tumor midpoint is located at the esophagogastric junction___ Tumor midpoint lies in the proximal stomach or cardia and tumor involves the esophagogastric junction___ Not specified___ Cannot be assessedDistance of tumor center from esophagogastric junction (specify, if applicable): ___ cmTumor SizeGreatest dimension: ___ cm+ Additional dimensions: ___ x ___ cm___ Cannot be determined (see “Comment”)Histologic Type (Note C)___ Squamous cell carcinoma___ Adenocarcinoma___ Adenosquamous carcinoma___ High-grade neuroendocrine carcinoma___ Large cell neuroendocrine carcinoma___ Small cell neuroendocrine carcinoma___ Undifferentiated carcinoma___ Other (specify): _____________________________ Carcinoma, type cannot be determinedHistologic Grade (Note D)___ Not applicable___ GX: Cannot be assessed___ G1: Well differentiated___ G2: Moderately differentiated___ G3: Poorly differentiated___ G4: UndifferentiatedMicroscopic Tumor Extension (Note E)___ Cannot be assessed___ No evidence of primary tumor___ High-grade dysplasia (carcinoma in situ) ___ Tumor invades lamina propria___ Tumor invades muscularis mucosae___ Tumor invades submucosa___ Tumor invades muscularis propria___ Tumor invades through the muscularis propria into the periesophageal soft tissue (adventitia)___ Tumor directly invades adjacent structures (specify): ______________________Margins (select all that apply) (Note F)If all margins uninvolved by invasive carcinoma:Distance of invasive carcinoma from closest margin: ___ mm or ___ cmSpecify margin: __________________________Proximal Margin___ Cannot be assessed___ Uninvolved by invasive carcinoma___ Involved by invasive carcinoma___ Uninvolved by dysplasia ___ Involved by dysplasia ___ Squamous dysplasia ___ Low grade ___ High grade___ Intestinal metaplasia (Barrett’s esophagus) with dysplasia___ Low grade ___ High grade___ Involved by intestinal metaplasia (Barrett’s esophagus) without dysplasiaDistal Margin___ Cannot be assessed___ Uninvolved by invasive carcinoma or dysplasia___ Involved by invasive carcinoma___ Involved by dysplasia ___ Squamous dysplasia___ Low grade___ High grade___ Intestinal metaplasia (Barrett’s esophagus) with dysplasia___ Low grade___ High grade___ Involved by intestinal metaplasia (Barrett’s esophagus) without dysplasiaCircumferential (Adventitial) Margin (esophagectomy or esophagogastrectomy specimens) or Deep Margin (endoscopic resection specimens)___ Cannot be assessed___ Uninvolved by invasive carcinoma___ Involved by invasive carcinomaOther Margin(s) (required only if applicable)Specify margin(s): ___________________________ ___ Cannot be assessed___ Uninvolved by invasive carcinoma___ Involved by invasive carcinomaTreatment Effect (applicable to carcinomas treated with neoadjuvant therapy) (select all that apply) (Note G)___ No prior treatment___ Present+ ___ No residual tumor (complete response, grade 0)+ ___ Marked response (grade 1, minimal residual cancer)+ ___ Moderate response (grade 2) ___ No definite response identified (grade 3, poor or no response)___ Treatment history not knownLymph-Vascular Invasion ___ Not identified___ Present___ Indeterminate+ Perineural Invasion + ___ Not identified+ ___ Present+ ___ IndeterminatePathologic Staging (pTNM) (Note H)TNM Descriptors (required only if applicable) (select all that apply)___ m (multiple primary tumors)___ r (recurrent)___ y (posttreatment)Primary Tumor (pT)___ pTX:Cannot be assessed___ pT0:No evidence of primary tumor___ pTis:High-grade dysplasia___ pT1:Tumor invades lamina propria, muscularis mucosae, or submucosa___ pT1a: Tumor invades lamina propria or muscularis mucosae___ pT1b: Tumor invades submucosa___ pT2:Tumor invades muscularis propria___ pT3:Tumor invades adventitia___ pT4:Tumor invades adjacent structures (specify): _________________________ pT4a: Resectable tumor invading pleura, pericardium, or diaphragm___ pT4b: Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etcRegional Lymph Nodes (pN) (Note I)___ pNX:Cannot be assessed___ pN0:No regional lymph node metastasis___ pN1:Regional lymph node metastasis involving 1 to 2 nodes___ pN2:3 to 6 nodes involved___ pN3:7 or more nodes involved___ No nodes submitted or foundNumber of Lymph Nodes ExaminedSpecify: _______ Number cannot be determined (explain): ______________________Number of Lymph Nodes InvolvedSpecify: _______ Number cannot be determined (explain): ______________________Distant Metastasis (pM)___ Not applicable___ pM1:Distant metastasis+ Specify site(s), if known: ____________________________Additional Pathologic Findings (select all that apply) (Note J)___ None identified___ Intestinal metaplasia (Barrett’s esophagus)___ Dysplasia___ Low grade___ High grade+ ___ Esophagitis (type): ___________________________+ ___ Gastritis (type): ___________________________+ ___ Other (specify): ___________________________+ Ancillary Studies + Specify: ___________________________________+ Clinical History (select all that apply) (Note J)+ ___ Barrett’s esophagus+ ___ Other (specify): ______________________________ + ___ Not known+ Comment(s)Explanatory NotesA. Application This protocol applies to all carcinomas arising in the esophagus and to carcinomas involving the esophagogastric junction (EGJ), including tumors that cross the EGJ but are predominantly located in the proximal stomach. Lymphomas, well-differentiated neuroendocrine tumors (carcinoid tumors), and sarcomas are also not included (separate TNM staging systems ADDIN EN.CITE <EndNote><Cite><Author>Edge</Author><Year>2009</Year><RecNum>30</RecNum><record><rec-number>30</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author>Edge, S. E.</author><author>Byrd, D. R.</author><author>Carducci, M. A.</author><author>Compton, C. C.</author></authors></contributors><titles><title>AJCC TNM Staging Manual</title></titles><edition>7th</edition><dates><year>2009</year></dates><pub-location>New York, NY</pub-location><publisher>Springer</publisher><urls></urls></record></Cite></EndNote>1 and CAP protocols apply). B. LocationThe location of the tumor in the esophagus (cervical, upper thoracic, midthoracic, lower thoracic, abdominal) and with respect to the macroscopic EGJ (defined as where the tubular esophagus meets the stomach, as measured from the top of the gastric folds) should be noted whenever possible (Figure 1). The macroscopic EGJ often does not correspond to the junction of esophageal squamous mucosa and columnar mucosa because of the common finding in esophageal resection specimens of glandular mucosa involving the distal esophagus. Because anatomic divisions of the esophagus are defined by anatomic boundaries and relationships to other structures, ADDIN EN.CITE <EndNote><Cite><Author>Edge</Author><Year>2009</Year><RecNum>30</RecNum><record><rec-number>30</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author>Edge, S. E.</author><author>Byrd, D. R.</author><author>Carducci, M. A.</author><author>Compton, C. C.</author></authors></contributors><titles><title>AJCC TNM Staging Manual</title></titles><edition>7th</edition><dates><year>2009</year></dates><pub-location>New York, NY</pub-location><publisher>Springer</publisher><urls></urls></record></Cite></EndNote>1 it may not be possible for the pathologist to determine exact tumor location from the resection specimen. Figure 1. Anatomic subdivisions of the esophagus. From Edge et al.1 Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, 7th edition (2009) published by Springer Science and Business Media LLC, .For tumors involving the esophagogastric junction, specific observations should be recorded in an attempt to establish the exact site of origin of the tumor. The EGJ is defined as the junction of the tubular esophagus and the stomach, irrespective of the type of epithelial lining of the esophagus. The?pathologist should record the maximum longitudinal dimension of the tumor mass, the distance of the tumor midpoint from the EGJ, and the relative proportions of the tumor mass located in the esophagus and in the stomach. Tumors involving the EGJ are classified for purposes of staging as esophageal carcinomas. ADDIN EN.CITE <EndNote><Cite><Author>Edge</Author><Year>2009</Year><RecNum>30</RecNum><record><rec-number>30</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author>Edge, S. E.</author><author>Byrd, D. R.</author><author>Carducci, M. A.</author><author>Compton, C. C.</author></authors></contributors><titles><title>AJCC TNM Staging Manual</title></titles><edition>7th</edition><dates><year>2009</year></dates><pub-location>New York, NY</pub-location><publisher>Springer</publisher><urls></urls></record></Cite></EndNote>1 Although the nature of these tumors (gastric versus esophageal) has been controversial ADDIN EN.CITE <EndNote><Cite><Author>Chandrasoma</Author><Year>2007</Year><RecNum>3</RecNum><record><rec-number>3</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chandrasoma, Parakrama</author><author>Wickramasinghe, Kumari</author><author>Ma, Yanling</author><author>DeMeester, Tom</author></authors></contributors><auth-address>Department of Surgical Pathology, Keck School of Medicine and University of Southern California, Los Angeles, CA 90033, USA. ptchandr@usc.edu</auth-address><titles><title>Adenocarcinomas of the distal esophagus and &quot;gastric cardia&quot; are predominantly esophageal carcinomas</title><secondary-title>American Journal of Surgical Pathology</secondary-title></titles><pages>569-75</pages><volume>31</volume><number>4</number><dates><year>2007</year><pub-dates><date>Apr</date></pub-dates></dates><accession-num>17414104</accession-num><urls></urls></record></Cite><Cite><Author>Mattioli</Author><Year>2007</Year><RecNum>35</RecNum><record><rec-number>35</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mattioli, Sandro</author><author>Ruffato, Alberto</author><author>Di Simone, Massimo Pierluigi</author><author>Corti, Barbara</author><author>D&apos;Errico, Antonietta</author><author>Lugaresi, Maria Luisa</author><author>Mattioli, Benedetta</author><author>D&apos;Ovidio, Frank</author></authors></contributors><auth-address>Division of Esophageal and Pulmonary Surgery, Villa Maria Cecilia Hospital, Cotignola and Faenza (Ravenna), Italy. sandro.mattioli@unibo.it</auth-address><titles><title>Immunopathological patterns of the stomach in adenocarcinoma of the esophagus, cardia, and gastric antrum: gastric profiles in Siewert type I and II tumors</title><secondary-title>Annals of Thoracic Surgery</secondary-title></titles><pages>1814-9</pages><volume>83</volume><number>5</number><dates><year>2007</year><pub-dates><date>May</date></pub-dates></dates><accession-num>17462405</accession-num><urls></urls></record></Cite></EndNote>2,3 (reviewed by Carneiro and Chaves ADDIN EN.CITE <EndNote><Cite><Author>Carneiro</Author><Year>2006</Year><RecNum>37</RecNum><record><rec-number>37</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Carneiro, Fatima</author><author>Chaves, Paula</author></authors></contributors><auth-address>Medical Faculty of the University of Porto and Hospital S.Joao, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal. fcarneiro@ipatimup.pt</auth-address><titles><title>Pathologic risk factors of adenocarcinoma of the gastric cardia and gastroesophageal junction</title><secondary-title>Surgical Oncology Clinics of North America</secondary-title></titles><pages>697-714</pages><volume>15</volume><number>4</number><dates><year>2006</year><pub-dates><date>Oct</date></pub-dates></dates><accession-num>17030268</accession-num><urls></urls></record></Cite></EndNote>4), recent data support their classification as esophageal carcinomas.1 The World Health Organization (WHO) defines esophageal tumors are those located entirely above the EGJ and proximal gastric tumors as those located entirely below the EGJ. ADDIN EN.CITE <EndNote><Cite><Author>Hamilton</Author><Year>2000</Year><RecNum>51</RecNum><record><rec-number>51</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author><style face="normal" font="Helvetica" size="12">Hamilton, S. R.</style></author><author><style face="normal" font="Helvetica" size="12">Aaltonen, L. A.</style></author></authors></contributors><titles><title><style face="normal" font="Helvetica" size="12">World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Digestive System</style></title></titles><dates><year><style face="normal" font="Helvetica" size="12">2000</style></year></dates><pub-location><style face="normal" font="Helvetica" size="12">Lyon</style></pub-location><publisher><style face="normal" font="Helvetica" size="12">IARC Press</style></publisher><urls></urls></record></Cite></EndNote>5 Tumors crossing the EGJ are classified as EGJ tumors. An alternative system proposed by Siewart and colleagues divides adenocarcinomas involving the EGJ into three categories, based upon location of the midpoint of the tumor6:Type I: adenocarcinoma of the distal esophagus, with or without infiltration of the EGJ from aboveType II: true carcinoma of the gastric cardia, arising from the cardiac epithelium or short segments with intestinal metaplasia at the EGJType III: subcardial gastric carcinoma, which infiltrates the EGJ and distal esophagus from belowApplication of the Siewart system is complicated by lack of consensus as to the definition and nature of the gastric cardia, with some investigators regarding it as a normal anatomic finding, ADDIN EN.CITE <EndNote><Cite><Author>Glickman</Author><Year>2002</Year><RecNum>61</RecNum><record><rec-number>61</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Glickman, Jonathan N. </author><author>Fox, Victor </author><author>Antonioli, Donald A. </author><author>Wang, Helen H. </author><author>Odze, Robert D. </author></authors></contributors><auth-address>From the Departments of Pathology (J.N.G., R.D.O.), Brigham and Women&apos;s Hospital, Children&apos;s Hospital (J.N.G., D.A.A.), Beth Israel Deaconess Medical Center (D.A.A., H.H.W.), the Department of Gastroenterology and Nutrition (V.F.), Childrens&apos; Hospital, and Harvard Medical School (J.N.G., V.F., D.A.A., H.H.W., R.D.O.), Boston, Massachusetts, U.S.A.</auth-address><titles><title>Morphology of the Cardia and Significance of Carditis in Pediatric Patients</title><secondary-title>American Journal of Surgical Pathology</secondary-title></titles><pages>1032-1039</pages><volume>26</volume><number>8</number><dates><year>2002</year></dates><urls></urls></record></Cite></EndNote>7 and others as a metaplastic response to injury from esophagogastric reflux. ADDIN EN.CITE <EndNote><Cite><Author>Chandrasoma</Author><Year>2007</Year><RecNum>3</RecNum><record><rec-number>3</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chandrasoma, Parakrama</author><author>Wickramasinghe, Kumari</author><author>Ma, Yanling</author><author>DeMeester, Tom</author></authors></contributors><auth-address>Department of Surgical Pathology, Keck School of Medicine and University of Southern California, Los Angeles, CA 90033, USA. ptchandr@usc.edu</auth-address><titles><title>Adenocarcinomas of the distal esophagus and &quot;gastric cardia&quot; are predominantly esophageal carcinomas</title><secondary-title>American Journal of Surgical Pathology</secondary-title></titles><pages>569-75</pages><volume>31</volume><number>4</number><dates><year>2007</year><pub-dates><date>Apr</date></pub-dates></dates><accession-num>17414104</accession-num><urls></urls></record></Cite></EndNote>2,4 C.Histologic TypeFor consistency in reporting, the histologic classification proposed by the WHO is recommended. ADDIN EN.CITE <EndNote><Cite><Author>Hamilton</Author><Year>2000</Year><RecNum>51</RecNum><record><rec-number>51</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author><style face="normal" font="Helvetica" size="12">Hamilton, S. R.</style></author><author><style face="normal" font="Helvetica" size="12">Aaltonen, L. A.</style></author></authors></contributors><titles><title><style face="normal" font="Helvetica" size="12">World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Digestive System</style></title></titles><dates><year><style face="normal" font="Helvetica" size="12">2000</style></year></dates><pub-location><style face="normal" font="Helvetica" size="12">Lyon</style></pub-location><publisher><style face="normal" font="Helvetica" size="12">IARC Press</style></publisher><urls></urls></record></Cite></EndNote>5 However, this protocol does not preclude the use of other systems of classification or histologic types.Worldwide, squamous cell carcinoma continues to predominant as the most common histologic type, but numerous population-based studies document the increasing incidence of adenocarcinoma of the esophagus and EGJ in Western countries. ADDIN EN.CITE <EndNote><Cite><Author>Keeney</Author><Year>2006</Year><RecNum>38</RecNum><record><rec-number>38</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Keeney, Scott</author><author>Bauer, Thomas L.</author></authors></contributors><auth-address>Department of Surgery, Christiana Care Health System, 4735 Ogletown-Stanton Road, Newark, DE 19713, USA.</auth-address><titles><title>Epidemiology of adenocarcinoma of the esophagogastric junction</title><secondary-title>Surgical Oncology Clinics of North America</secondary-title></titles><pages>687-96</pages><volume>15</volume><number>4</number><dates><year>2006</year><pub-dates><date>Oct</date></pub-dates></dates><accession-num>17030267</accession-num><urls></urls></record></Cite></EndNote>8 More than 50% of esophageal carcinomas diagnosed in the United States since 1900 are adenocarcinomas. Other subtypes, such as adenoid cystic carcinoma and mucoepidermoid carcinoma, which resemble their counterparts arising in salivary gland, are rarely encountered. The revised TNM staging system for esophageal carcinomas incorporates tumor grade and histologic type in the stage groupings (see Note H). Mixed histologic types, such as adenosquamous carcinomas, are staged using the squamous cell carcinoma stage grouping. ADDIN EN.CITE <EndNote><Cite><Author>Edge</Author><Year>2009</Year><RecNum>30</RecNum><record><rec-number>30</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author>Edge, S. E.</author><author>Byrd, D. R.</author><author>Carducci, M. A.</author><author>Compton, C. C.</author></authors></contributors><titles><title>AJCC TNM Staging Manual</title></titles><edition>7th</edition><dates><year>2009</year></dates><pub-location>New York, NY</pub-location><publisher>Springer</publisher><urls></urls></record></Cite></EndNote>1 WHO Classification of Carcinoma of the EsophagusSquamous cell carcinomaVerrucous (squamous) carcinomaSpindle cell (squamous) carcinomaAdenocarcinomaAdenosquamous carcinomaMucoepidermoid carcinoma#Adenoid cystic carcinoma#High-grade neuroendocrine carcinomaLarge cell neuroendocrine carcinomaSmall cell neuroendocrine carcinoma#Undifferentiated carcinoma#Others#These types are not generally graded.The term “carcinoma, NOS (not otherwise specified)” is not part of the WHO classification.D.Histologic GradeThe histologic grades for esophageal squamous cell carcinomas are as follows:Grade X Grade cannot be assessedGrade 1 Well differentiated Grade 2 Moderately differentiated Grade 3 Poorly differentiated If there are variations in the differentiation within the tumor, the highest (least favorable) grade is recorded. In general, mucoepidermoid carcinoma and adenoid cystic carcinoma of the esophagus are not amenable to grading.For adenocarcinomas, a suggested grading system based on the proportion of the tumor that is composed of glands is as follows:Grade X Grade cannot be assessedGrade 1Well differentiated (greater than 95% of tumor composed of?glands) Grade 2 Moderately differentiated (50% to 95% of tumor composed of?glands)Grade 3Poorly differentiated (49% or less of tumor composed of glands)Undifferentiated tumors cannot be categorized as squamous cell carcinoma or adenocarcinoma (or other) type. They are classified as "undifferentiated carcinomas" in the WHO classification of tumor types (see above) and may be assigned grade 4. Small cell carcinomas are not typically graded but are high-grade tumors and would correspond to grade 4.The revised TNM staging system for esophageal carcinomas incorporates tumor grade and histologic type in the stage groupings (see Note H). For purposes of staging, grade 4 carcinomas (undifferentiated carcinomas) are staged as grade 3 squamous cell carcinomas. ADDIN EN.CITE <EndNote><Cite><Author>Edge</Author><Year>2009</Year><RecNum>30</RecNum><record><rec-number>30</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author>Edge, S. E.</author><author>Byrd, D. R.</author><author>Carducci, M. A.</author><author>Compton, C. C.</author></authors></contributors><titles><title>AJCC TNM Staging Manual</title></titles><edition>7th</edition><dates><year>2009</year></dates><pub-location>New York, NY</pub-location><publisher>Springer</publisher><urls></urls></record></Cite></EndNote>1 Grade X tumors are grouped as grade 1 carcinomas. E. Tumor ExtensionFor purposes of data reporting, Barrett’s esophagus with high-grade dysplasia in an esophageal resection specimen is reported as “carcinoma in situ.” The term “carcinoma in situ” is not widely applied to glandular neoplastic lesions in the gastrointestinal tract but is retained for tumor registry reporting purposes as specified by law in many states. Invasion of the lamina propria may be difficult to assess for glandular neoplasms in the esophagus. The muscularis mucosae (Figure 2) is commonly duplicated and thickened in Barrett’s esophagus; invasion of this layer should not be misinterpreted as invasion of the muscularis propria. ADDIN EN.CITE <EndNote><Cite><Author>Abraham</Author><Year>2007</Year><RecNum>62</RecNum><record><rec-number>62</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Abraham, Susan C.</author><author>Krasinskas, Alyssa M.</author><author>Correa, Arlene M.</author><author>Hofstetter, Wayne L.</author><author>Ajani, Jaffer A.</author><author>Swisher, Stephen G.</author><author>Wu, Tsung-Teh</author></authors></contributors><auth-address>Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.</auth-address><titles><title>Duplication of the muscularis mucosae in Barrett esophagus: an underrecognized feature and its implication for staging of adenocarcinoma</title><secondary-title>American Journal of Surgical Pathology</secondary-title></titles><pages>1719-25</pages><volume>31</volume><number>11</number><dates><year>2007</year><pub-dates><date>Nov</date></pub-dates></dates><accession-num>18059229</accession-num><urls></urls></record></Cite></EndNote>9 It should be noted that the muscularis mucosae varies in organization from relatively sparse bundles of smooth muscle in the cervical esophagus to a thickened reticulated network in the distal esophagus. ADDIN EN.CITE <EndNote><Cite><Author>Nagai</Author><Year>2003</Year><RecNum>65</RecNum><record><rec-number>65</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nagai, Kaoruko</author><author>Noguchi, Tsuyoshi</author><author>Hashimoto, Tsuyoshi</author><author>Uchida, Yuzo</author><author>Shimada, Tatsuo</author></authors></contributors><auth-address>Department of Oncological Science, School of Medicine, Oita Medical University, Oita, Japan. knagai@oita-med.ac.jp</auth-address><titles><title>The organization of the lamina muscularis mucosae in the human esophagus</title><secondary-title>Archives of Histology &amp; Cytology</secondary-title></titles><pages>281-8</pages><volume>66</volume><number>3</number><dates><year>2003</year><pub-dates><date>Aug</date></pub-dates></dates><accession-num>14527169</accession-num><urls></urls></record></Cite></EndNote>10Figure 2. Microscopic anatomy of the esophagus. From Edge et al.1 Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, 7th edition (2009) published by Springer Science and Business Media LLC, .F. MarginsMargins include the proximal, distal, and radial margins. The radial margin represents the adventitial soft tissue margin closest to the deepest penetration of tumor. Sections to evaluate the proximal and distal resections margins can be obtained in 2 orientations: (1)?en face sections parallel to the margin, or (2)?longitudinal sections perpendicular to the margin. Depending on the closeness of the tumor to the margin, select the orientation(s) that will most clearly demonstrate the status of the margin. The distance from the tumor edge to the closest resection margin(s) should be measured. Proximal and distal resection margins should be evaluated for Barrett’s esophagus and for squamous and glandular dysplasia. It may be helpful to mark the margin(s) closest to the tumor with ink. Margins marked by ink should be so designated in the macroscopic description.G. Treatment Effect Response of tumor to previous chemotherapy or radiation therapy should be reported. Although grading systems for tumor response have not been established, in general, three-category systems provide good interobserver reproducibility. ADDIN EN.CITE <EndNote><Cite><Author>Ryan</Author><Year>2005</Year><RecNum>59</RecNum><record><rec-number>59</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="Helvetica" size="12">Ryan, R.</style></author><author><style face="normal" font="Helvetica" size="12">Gibbons, D.</style></author><author><style face="normal" font="Helvetica" size="12">Hyland, J. M. P.</style></author><author><style face="normal" font="Helvetica" size="12">Treanor, D.</style></author><author><style face="normal" font="Helvetica" size="12">White, A.</style></author><author><style face="normal" font="Helvetica" size="12">Mulcahy, H. E.</style></author><author><style face="normal" font="Helvetica" size="12">O&apos;Donaghue, D. P.</style></author><author><style face="normal" font="Helvetica" size="12">Moriarty, M.</style></author><author><style face="normal" font="Helvetica" size="12">Fennelly, D.</style></author><author><style face="normal" font="Helvetica" size="12">Sheahan, K.</style></author></authors></contributors><titles><title><style face="normal" font="Helvetica" size="12">Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer</style></title><secondary-title><style face="normal" font="Helvetica" size="12">Histopathology</style></secondary-title></titles><pages><style face="normal" font="Helvetica" size="12">141-146</style></pages><volume><style face="normal" font="Helvetica" size="12">47</style></volume><dates><year><style face="normal" font="Helvetica" size="12">2005</style></year></dates><urls></urls></record></Cite></EndNote>11 The following system is suggested:DescriptionTumor Regression Grade No viable cancer cells0 (Complete response)Single cells or small groups of cancer cells 1 (Moderate response)Residual cancer outgrown by fibrosis2 (Minimal response)Minimal or no tumor kill; extensive residual cancer3 (Poor response)Sizable pools of acellular mucin may be present after chemoradiation but should not be interpreted as representing residual tumor. This protocol does not preclude the use of other systems for assessment of tumor response. ADDIN EN.CITE <EndNote><Cite><Author>Brucher</Author><Year>2006</Year><RecNum>55</RecNum><record><rec-number>55</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Brucher, Bjorn L. D. M.</author><author>Becker, Karen</author><author>Lordick, Florian</author><author>Fink, Ulrich</author><author>Sarbia, Mario</author><author>Stein, Hubert</author><author>Busch, Raymonde</author><author>Zimmermann, Frank</author><author>Molls, Michael</author><author>Hofler, Heinz</author><author>Siewert, Jorg R.</author></authors></contributors><auth-address>Department of Surgery, Technical University of Munich, Munich, Germany. bruecher@chir.med.tu-muenchen.de</auth-address><titles><title>The clinical impact of histopathologic response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas</title><secondary-title>Cancer</secondary-title></titles><pages>2119-27</pages><volume>106</volume><number>10</number><dates><year>2006</year><pub-dates><date>May 15</date></pub-dates></dates><accession-num>16607651</accession-num><urls></urls></record></Cite><Cite><Author>Hermann</Author><Year>2006</Year><RecNum>54</RecNum><record><rec-number>54</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hermann, R. M.</author><author>Horstmann, O.</author><author>Haller, F.</author><author>Perske, C.</author><author>Christiansen, H.</author><author>Hille, A.</author><author>Schmidberger, H.</author><author>Fuzesi, L.</author></authors></contributors><auth-address>Department of Radiooncology and Radiotherapy, University Hospital, University of Gottingen, Gottingen, Germany. ro.hermann@t-online.de</auth-address><titles><title>Histomorphological tumor regression grading of esophageal carcinoma after neoadjuvant radiochemotherapy: which score to use?</title><secondary-title>Diseases of the Esophagus</secondary-title></titles><pages>329-34</pages><volume>19</volume><number>5</number><dates><year>2006</year></dates><accession-num>16984527</accession-num><urls></urls></record></Cite><Cite><Author>Wu</Author><Year>2007</Year><RecNum>5</RecNum><record><rec-number>5</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wu, Tsung-Teh</author><author>Chirieac, Lucian R.</author><author>Abraham, Susan C.</author><author>Krasinskas, Alyssa M.</author><author>Wang, Huamin</author><author>Rashid, Asif</author><author>Correa, Arlene M.</author><author>Hofstetter, Wayne L.</author><author>Ajani, Jaffer A.</author><author>Swisher, Stephen G.</author></authors></contributors><auth-address>Department of Pathology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. twu@mdanderson.edu</auth-address><titles><title>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</title><secondary-title>American Journal of Surgical Pathology</secondary-title></titles><pages>58-64</pages><volume>31</volume><number>1</number><dates><year>2007</year><pub-dates><date>Jan</date></pub-dates></dates><accession-num>17197919</accession-num><urls></urls></record></Cite></EndNote>12-14H.TNM and Anatomic Stage/Prognostic GroupingsThe TNM staging system for esophageal carcinoma of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) is recommended (Figure 3). ADDIN EN.CITE <EndNote><Cite><Author>Edge</Author><Year>2009</Year><RecNum>30</RecNum><record><rec-number>30</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author>Edge, S. E.</author><author>Byrd, D. R.</author><author>Carducci, M. A.</author><author>Compton, C. C.</author></authors></contributors><titles><title>AJCC TNM Staging Manual</title></titles><edition>7th</edition><dates><year>2009</year></dates><pub-location>New York, NY</pub-location><publisher>Springer</publisher><urls></urls></record></Cite></EndNote>1 Figure 3. T, N, and M classifications for esophageal carcinoma. From Edge et al.1 Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, 7th edition (2009) published by Springer Science and Business Media LLC, .According to AJCC/UICC convention, the designation “T” refers to a primary tumor that has not been previously treated. The symbol “p” refers to the pathologic classification of the TNM, as opposed to the clinical classification, and is based on gross and microscopic examination. pT entails a resection of the primary tumor or biopsy adequate to evaluate the highest pT category, pN entails removal of nodes adequate to validate lymph node metastasis, and pM implies microscopic examination of distant lesions. Clinical classification (cTNM) is usually carried out by the referring physician before treatment during initial evaluation of the patient or when pathologic classification is not possible.Pathologic staging is usually performed after surgical resection of the primary tumor. Pathologic staging depends on pathologic documentation of the anatomic extent of disease, whether or not the primary tumor has been completely removed. If a biopsied tumor is not resected for any reason (eg, when technically infeasible) and if the highest T and N categories or the M1 category of the tumor can be confirmed microscopically, the criteria for pathologic classification and staging have been satisfied without total removal of the primary cancer.TNM Descriptors For identification of special cases of TNM or pTNM classifications, the “m” suffix and “y,” “r,” and “a” prefixes are used. Although they do not affect the stage grouping, they indicate cases needing separate analysis.The “m” suffix indicates the presence of multiple primary tumors in a single site and is recorded in parentheses: pT(m)NM.The “y” prefix indicates those cases in which classification is performed during or after initial multimodality therapy (ie, neoadjuvant chemotherapy, radiation therapy, or both chemotherapy and radiation therapy). The cTNM or pTNM category is identified by a “y” prefix. The ycTNM or ypTNM categorizes the extent of tumor actually present at the time of that examination. The “y” categorization is not an estimate of tumor before multimodality therapy (ie, before initiation of neoadjuvant therapy).The “r” prefix indicates a recurrent tumor when staged after a documented disease-free interval and is identified by the “r” prefix: rTNM.The “a” prefix designates the stage determined at autopsy: aTNM.N Category ConsiderationsA mediastinal lymphadenectomy specimen will ordinarily include 7 or more regional lymph nodes. Stage Groupings: Squamous Cell CarcinomaStageTNMG LocationStage 0TisN0M0#1AnyStage IA T1N0 M01AnyStage IB T1N0M02 or 3AnyT2 or T3N0M01LowerStage IIA T2 or T3N0M01Upper, middleT2 or T3N0M02 or 3LowerStage IIB T2 or T3N0M02 or 3Upper, middleT1 or T2N1M0AnyAnyStage IIIAT1 or T2N2M0AnyAnyT3N1M0AnyAnyT4aN0M0AnyAnyStage IIIBT3N2M0AnyAnyStage IIICT4aN1 or N2M0AnyAnyT4bAnyM0AnyAnyAnyN3M0AnyAnyStage IVAny TAny NM1AnyAny# M0 is defined as no distant metastasis.Stage Grouping: AdenocarcinomaStageTNMG Stage 0Tis (HGD#)N0M01Stage IAT1N0M01 or 2Stage IBT1N0 M03T2N0M01 to 2Stage IIA T2N0M03Stage IIBT3N0M0AnyT1 or T2N1M0AnyStage IIIAT1 or T2N2M0AnyT3N1M0AnyT4aN0M0AnyStage IIIBT3N2M0AnyStage IIICT4aN1 or N2M0AnyT4bAnyM0AnyAnyN3M0AnyStage IVAny TAny NM1Any# HGD, high-grade dysplasia.Additional DescriptorsLymph-Vascular InvasionLymph-vascular invasion (LVI) indicates whether microscopic lymph-vascular invasion is identified in the pathology report. LVI includes lymphatic invasion, vascular invasion, or lymph-vascular invasion. By AJCC/UICC convention, LVI does not affect the T category indicating local extent of tumor unless specifically included in the definition of a T category. I.Regional Lymph NodesRegional lymph nodes (Figure 4) extend from periesophageal cervical nodes for the cervical esophagus to celiac lymph nodes for the distal esophagus. ADDIN EN.CITE <EndNote><Cite><Author>Edge</Author><Year>2009</Year><RecNum>30</RecNum><record><rec-number>30</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author>Edge, S. E.</author><author>Byrd, D. R.</author><author>Carducci, M. A.</author><author>Compton, C. C.</author></authors></contributors><titles><title>AJCC TNM Staging Manual</title></titles><edition>7th</edition><dates><year>2009</year></dates><pub-location>New York, NY</pub-location><publisher>Springer</publisher><urls></urls></record></Cite></EndNote>1 Number of involved lymph nodes has consistently emerged as a prognostic indicator on multivariate analysis. ADDIN EN.CITE <EndNote><Cite><Author>Christein</Author><Year>2002</Year><RecNum>58</RecNum><record><rec-number>58</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Christein, John D.</author><author>Hollinger, Edward F.</author><author>Millikan, Keith W.</author></authors></contributors><auth-address>Department of General Surgery, Rush-Presbyterian-St. Luke&apos;s Medical Center, Chicago, Illinois, USA.</auth-address><titles><title>Prognostic factors associated with resectable carcinoma of the esophagus</title><secondary-title>American Surgeon</secondary-title></titles><pages>258-62; discussion 262-3</pages><volume>68</volume><number>3</number><dates><year>2002</year><pub-dates><date>Mar</date></pub-dates></dates><accession-num>11893104</accession-num><urls></urls></record></Cite><Cite><Author>Gu</Author><Year>2006</Year><RecNum>25</RecNum><record><rec-number>25</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gu, Yan</author><author>Swisher, Stephen G.</author><author>Ajani, Jaffer A.</author><author>Correa, Arlene M.</author><author>Hofstetter, Wayne L.</author><author>Liao, Zhongxing</author><author>Komaki, Ritsuko R.</author><author>Rashid, Asif</author><author>Hamilton, Stanley R.</author><author>Wu, Tsung-Teh</author></authors></contributors><auth-address>Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.</auth-address><titles><title>The number of lymph nodes with metastasis predicts survival in patients with esophageal or esophagogastric junction adenocarcinoma who receive preoperative chemoradiation</title><secondary-title>Cancer</secondary-title></titles><pages>1017-25</pages><volume>106</volume><number>5</number><dates><year>2006</year><pub-dates><date>Mar 1</date></pub-dates></dates><accession-num>16456809</accession-num><urls></urls></record></Cite></EndNote>15,16 Extranodal extension may identify a subset of node-positive patients with a particularly poor prognosis.17Figure 4. Regional lymph nodes of the esophagus. From Edge et al.1 Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, 7th edition (2009) published by Springer Science and Business Media LLC, .J. Additional FindingsMost esophageal adenocarcinomas develop in the setting of Barrett’s esophagus, which is defined as alteration of the mucosal lining of the esophagus from the normal squamous epithelium to metaplastic columnar epithelium in response to esophagogastric reflux. Although in some cases the columnar epithelium may resemble gastric oxyntic or cardiac mucosa, only the specialized columnar epithelium with goblet cells is considered to carry significant risk of cancer and is designated as Barrett’s esophagus for diagnostic purposes. References ADDIN EN.REFLIST 1.Edge SB, Byrd DR, Carducci MA, Compton CC, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2009.2.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):569-575.3.Mattioli S, Ruffato A, Di Simone MP, et al. 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. 2007;83(5):1814-1819.4.Carneiro F, Chaves P. Pathologic risk factors of adenocarcinoma of the gastric cardia and gastroesophageal junction. Surg Oncol Clin North Am. 2006;15(4):697-714.5.Bosman FT, Carneiro F, Hruban RH, Theise ND, eds. WHO Classification of Tumours of the Digestive System. Geneva, Switzerland: WHO Press; 2010.6.Feith M, Stein HJ, Siewert JR. Adenocarcinoma of the esophagogastric junction: surgical therapy based on 1602 consecutive resected patients. Surg Oncol Clin North Am. 2006;15(4):751-764.7.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):1032-1039.8.Keeney S, Bauer TL. Epidemiology of adenocarcinoma of the esophagogastric junction. Surg Oncol Clin North Am. 2006;15(4):687-696.9.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):1719-1725.10.Nagai K, Noguchi T, Hashimoto T, Uchida Y, Shimada T. The organization of the lamina muscularis mucosae in the human esophagus. Arch Histol Cytol. 2003;66(3):281-288.11.Ryan R, Gibbons D, Hyland JM, et al. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology. 2005;47(2):141-146.12.Brucher BLDM, Becker K, Lordick F, et al. The clinical impact of histopathologic response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas. Cancer. May 15 2006;106(10):2119-2127.13.Hermann RM, Horstmann O, Haller F, et al. Histomorphological tumor regression grading of esophageal carcinoma after neoadjuvant radiochemotherapy: which score to use? Dis Esoph. 2006;19(5):329-334.14.Wu T-T, Chirieac LR, Abraham SC, 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):58-64.15.Christein JD, Hollinger EF, Millikan KW. Prognostic factors associated with resectable carcinoma of the esophagus. Am Surg. 2002;68(3):258-262; discussion 262-263. 16.Gu Y, Swisher SG, Ajani JA, et al. The number of lymph nodes with metastasis predicts survival in patients with esophageal or esophagogastric junction adenocarcinoma who receive preoperative chemoradiation. Cancer. 2006;106(5):1017-1025.17.Lagarde SM, ten Kate FJW, de Boer DJ, Busch ORC, Obertop H, van Lanschot JJB. Extracapsular lymph node involvement in node-positive patients with adenocarcinoma of the distal esophagus or gastroesophageal junction. Am J Surg Pathol. 2006;30(2):171-176. ................
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