Japanese Classification of Esophageal Cancer, 12th Edition: Part I

1Contents PrefaceGeneral principles of the 12th editionAbbrevi ationTerminology of the lymph nodesGeneral rules

2Preface

3General principles of the 12th edition

4Abbrevi ation

5Terminology of the lymph nodes

6General rules

7General rules 1. Purpose, object, and methods of descriptions1.1. Purpose1.2. Object1.3. Methods of descriptions1.3.1. Principles of descriptions and abbreviations2. Description of primary tumor2.1. Number of primary tumors, size, and circumferential location2.2. Tumor location2.2.1. Anatomical definition of esophagus2.2.2. Anatomical subsites of esophagus2.2.3. Principles of description of tumor location2.3. Macroscopic tumor type2.3.1. Principles of macroscopic tumor type2.3.2. Macroscopic tumor type2.3.3. Subclassification of superficial type (type 0)2.4. Depth of tumor invasion (T)2.4.1. Classification of depth of tumor invasion (T)2.4.2. Diagnostic criteria for depth of superficial esophageal cancer by magnifying endoscopy2.4.3. Diagnosis of cT4 invasion of adjacent organs by CT and other imaging techniques2.4.3.1. Typical CT images: cT3r2.4.3.2. Typical CT images: cT3br2.4.3.3. Typical CT images: cT42.5. Infiltrative growth pattern (INF)2.6. Lymphatic or venous invasion2.6.1. Lymphatic invasion (Ly)2.6.2. Venous invasion (V)2.7. Description of surgical findings2.7.1. Tumor size2.7.2. Distance from surgical margin to the tumor2.7.3. Surgical tumor type2.7.4. Surgical margin2.7.4.1. Proximal margin (PM)2.7.4.2. Distal margin (DM)2.7.4.3. Radial margin (RM)2.8. Description of endoscopic findings2.8.1. Number of tumors and resected specimens2.8.2. Size of resected specimen and size of each tumor lesion2.8.3. Tumor types2.8.4. Resection margin2.8.4.1. Horizontal margin (HM)2.8.4.2. Vertical margin (VM)2.9. Multiple primary cancers2.9.1. Multiple primary cancers of the esophagus2.9.2. Multi-organ primary cancers including the esophagus2.10. Intramural metastasis (IM)3. Description of lymph nodes3.1. Name, number, and extent and boundaries of lymph node station in esophageal cancer3.2. Regional lymph nodes3.3. Grading of lymph node metastasis (N)4. Distant organ and lymph node metastasis (M)5. Stage5.1. Staging of cervical and thoracic esophageal cancer, and squamous cell carcinoma of the esophagogastric junction5.2. Staging of adenocarcinoma of the esophagogastric junction5.3. Degree of lymph node dissection and residual tumor5.3.1. Lymph node dissection5.3.2. Description of lymph node dissection5.3.3. Definition of extent of lymph node dissection (D)5.3.4. Residual tumor after endoscopic and surgical resection (R)6. Handling of endoscopically and surgically resected specimen6.1. Handling of endoscopically resected specimen6.2. Handling of surgically resected specimen (primary tumor)6.3. Sectioning for resected specimen6.3.1. Preparation of resected specimens for sectioning6.3.2. Rule of sectioning for endoscopically resected specimen6.3.3. Rule of sectioning for surgically resected specimen

81. Purpose, object, and methods of descriptions1.1. Purpose1.2. Object1.3. Methods of descriptions1.3.1. Principles of descriptions and abbreviations

91.1. Purpose

101.2. Object

111.3. Methods of descriptions1.3.1. Principles of descriptions and abbreviations

121.3.1. Principles of descriptions and abbreviations

132. Description of primary tumor2.1. Number of primary tumors, size, and circumferential location2.2. Tumor location2.2.1. Anatomical definition of esophagus2.2.2. Anatomical subsites of esophagus2.2.3. Principles of description of tumor location2.3. Macroscopic tumor type2.3.1. Principles of macroscopic tumor type2.3.2. Macroscopic tumor type2.3.3. Subclassification of superficial type (type 0)2.4. Depth of tumor invasion (T)2.4.1. Classification of depth of tumor invasion (T)2.4.2. Diagnostic criteria for depth of superficial esophageal cancer by magnifying endoscopy2.4.3. Diagnosis of cT4 invasion of adjacent organs by CT and other imaging techniques2.4.3.1. Typical CT images: cT3r2.4.3.2. Typical CT images: cT3br2.4.3.3. Typical CT images: cT42.5. Infiltrative growth pattern (INF)2.6. Lymphatic or venous invasion2.6.1. Lymphatic invasion (Ly)2.6.2. Venous invasion (V)2.7. Description of surgical findings2.7.1. Tumor size2.7.2. Distance from surgical margin to the tumor2.7.3. Surgical tumor type2.7.4. Surgical margin2.7.4.1. Proximal margin (PM)2.7.4.2. Distal margin (DM)2.7.4.3. Radial margin (RM)2.8. Description of endoscopic findings2.8.1. Number of tumors and resected specimens2.8.2. Size of resected specimen and size of each tumor lesion2.8.3. Tumor types2.8.4. Resection margin2.8.4.1. Horizontal margin (HM)2.8.4.2. Vertical margin (VM)2.9. Multiple primary cancers2.9.1. Multiple primary cancers of the esophagus2.9.2. Multi-organ primary cancers including the esophagus2.10. Intramural metastasis (IM)

142.1. Number of primary tumors, size, and circumferential location

152.2. Tumor location2.2.1. Anatomical definition of esophagus2.2.2. Anatomical subsites of esophagus2.2.3. Principles of description of tumor location

162.2.1. Anatomical definition of esophagus

172.2.2. Anatomical subsites of esophagus

182.2.3. Principles of description of tumor location

192.3. Macroscopic tumor type2.3.1. Principles of macroscopic tumor type2.3.2. Macroscopic tumor type2.3.3. Subclassification of superficial type (type 0)

202.3.1. Principles of macroscopic tumor type

212.3.2. Macroscopic tumor type

222.3.3. Subclassification of superficial type (type 0)

232.4. Depth of tumor invasion (T)2.4.1. Classification of depth of tumor invasion (T)2.4.2. Diagnostic criteria for depth of superficial esophageal cancer by magnifying endoscopy2.4.3. Diagnosis of cT4 invasion of adjacent organs by CT and other imaging techniques2.4.3.1. Typical CT images: cT3r2.4.3.2. Typical CT images: cT3br2.4.3.3. Typical CT images: cT4

242.4.1. Classification of depth of tumor invasion (T)

252.4.2. Diagnostic criteria for depth of superficial esophageal cancer by magnifying endoscopy

262.4.3. Diagnosis of cT4 invasion of adjacent organs by CT and other imaging techniques2.4.3.1. Typical CT images: cT3r2.4.3.2. Typical CT images: cT3br2.4.3.3. Typical CT images: cT4

272.4.3.1. Typical CT images: cT3r

282.4.3.2. Typical CT images: cT3br

292.4.3.3. Typical CT images: cT4

302.5. Infiltrative growth pattern (INF)

312.6. Lymphatic or venous invasion2.6.1. Lymphatic invasion (Ly)2.6.2. Venous invasion (V)

322.6.1. Lymphatic invasion (Ly)

332.6.2. Venous invasion (V)

342.7. Description of surgical findings2.7.1. Tumor size2.7.2. Distance from surgical margin to the tumor2.7.3. Surgical tumor type2.7.4. Surgical margin2.7.4.1. Proximal margin (PM)2.7.4.2. Distal margin (DM)2.7.4.3. Radial margin (RM)

352.7.1. Tumor size

362.7.2. Distance from surgical margin to the tumor

372.7.3. Surgical tumor type

382.7.4. Surgical margin2.7.4.1. Proximal margin (PM)2.7.4.2. Distal margin (DM)2.7.4.3. Radial margin (RM)

392.7.4.1. Proximal margin (PM)

402.7.4.2. Distal margin (DM)

412.7.4.3. Radial margin (RM)

422.8. Description of endoscopic findings2.8.1. Number of tumors and resected specimens2.8.2. Size of resected specimen and size of each tumor lesion2.8.3. Tumor types2.8.4. Resection margin2.8.4.1. Horizontal margin (HM)2.8.4.2. Vertical margin (VM)

432.8.1. Number of tumors and resected specimens

442.8.2. Size of resected specimen and size of each tumor lesion

452.8.3. Tumor types

462.8.4. Resection margin2.8.4.1. Horizontal margin (HM)2.8.4.2. Vertical margin (VM)

472.8.4.1. Horizontal margin (HM)

482.8.4.2. Vertical margin (VM)

492.9. Multiple primary cancers2.9.1. Multiple primary cancers of the esophagus2.9.2. Multi-organ primary cancers including the esophagus

502.9.1. Multiple primary cancers of the esophagus

512.9.2. Multi-organ primary cancers including the esophagus

522.10. Intramural metastasis (IM)

533. Description of lymph nodes3.1. Name, number, and extent and boundaries of lymph node station in esophageal cancer3.2. Regional lymph nodes3.3. Grading of lymph node metastasis (N)

543.1. Name, number, and extent and boundaries of lymph node station in esophageal cancer

553.2. Regional lymph nodes

563.3. Grading of lymph node metastasis (N)

574. Distant organ and lymph node metastasis (M)

585. Stage5.1. Staging of cervical and thoracic esophageal cancer, and squamous cell carcinoma of the esophagogastric junction5.2. Staging of adenocarcinoma of the esophagogastric junction5.3. Degree of lymph node dissection and residual tumor5.3.1. Lymph node dissection5.3.2. Description of lymph node dissection5.3.3. Definition of extent of lymph node dissection (D)5.3.4. Residual tumor after endoscopic and surgical resection (R)

595.1. Staging of cervical and thoracic esophageal cancer, and squamous cell carcinoma of the esophagogastric junction

605.2. Staging of adenocarcinoma of the esophagogastric junction

615.3. Degree of lymph node dissection and residual tumor5.3.1. Lymph node dissection5.3.2. Description of lymph node dissection5.3.3. Definition of extent of lymph node dissection (D)5.3.4. Residual tumor after endoscopic and surgical resection (R)

625.3.1. Lymph node dissection

635.3.2. Description of lymph node dissection

645.3.3. Definition of extent of lymph node dissection (D)

655.3.4. Residual tumor after endoscopic and surgical resection (R)

666. Handling of endoscopically and surgically resected specimen6.1. Handling of endoscopically resected specimen6.2. Handling of surgically resected specimen (primary tumor)6.3. Sectioning for resected specimen6.3.1. Preparation of resected specimens for sectioning6.3.2. Rule of sectioning for endoscopically resected specimen6.3.3. Rule of sectioning for surgically resected specimen

676.1. Handling of endoscopically resected specimen

686.2. Handling of surgically resected specimen (primary tumor)

696.3. Sectioning for resected specimen6.3.1. Preparation of resected specimens for sectioning6.3.2. Rule of sectioning for endoscopically resected specimen6.3.3. Rule of sectioning for surgically resected specimen

706.3.1. Preparation of resected specimens for sectioning

716.3.2. Rule of sectioning for endoscopically resected specimen

726.3.3. Rule of sectioning for surgically resected specimen

73Preface

74The 12th edition of the Japanese Classification of Esophageal Cancer was published seven years after the publication of the 11th edition in 2015.

75Considering the increasing importance of preoperative treatment, we add and revise the descriptions of preoperative diagnosis, especially T4 and lymph node metastasis diagnoses, which are considered to have a significant impact on the treatment policy, and modify the Response evaluation criteria and also to ensure consistency with the Japanese Cancer Staging Manual, particularly for cancers of the esophagogastric junction. Consistency with the TNM classification of the Union for International Cancer Control (UICC) was aimed as much as possible in the previous revision. However, consistency with the N classification was omitted because our N classification had been based on the site relative to the main tumor and because there had been a complete difference in the view of supraclavicular lymph node metastasis. This new version adopts the classification based on the number of metastases consistent with the TNM classification. Furthermore, by examining both the dissection efficacy index and recurrence frequency, the regional lymph nodes are formulated to be more consistent with actual clinical practice. In accordance with these changes in the staging of lymph node metastasis, we develop a new staging classification system in an era when preoperative treatment has become the standard using prognostic information from the National Comprehensive Registry of Esophageal Cancer.

76The diagnostic criteria for esophagogastric junction cancer were determined, and a booklet consisting of seven pages was added in the previous edition. In this revision, the definition and description of esophagogastric junction cancer are jointly developed by the Japanese Society of Gastric Cancer. In addition, the regional lymph nodes for esophagogastric junction cancer are established, and a description of staging is added. Many discussions were conducted among the committee members that led to this revision. Although there are still some points to be discussed, we appreciate the considerable efforts made by the individual committee members.

77September 2022.

78General principles of the 12th edition “Ae” is eliminated as a subsite of the esophagus, and “Jz” is newly defined as the esophagogastric junction zone. “Jz” is equal to the esophagogastric junction area in Nishi’s classification.We sub-classify cT3 as resectable (cT3 resectable: cT3r) or borderline resectable (cT3 borderline resectable: cT3br) because of the difficulty in determining adjacent organ involvement on imaging. Reference CT images and supporting findings are added to the diagnoses of cT3r, cT3br, and cT4.For the diagnosis of cN, recommended cut-off values are provided, referring to the diagnostic accuracy of lymph node metastasis by size in CT diagnosis. Diagnoses using PET are also included as a reference.To classify the degree of lymph node metastasis, a classification based on the number of metastatic regional lymph nodes is adopted for consistency with the TNM classification. We then abandon the lymph node grouping related to tumor location in thoracic esophageal cancer and newly establish the common regional lymph nodes for thoracic esophageal cancer. Supraclavicular lymph nodes are classified as distant rather than regional. However, it is defined as M1a to distinguish it from other distant metastases (M1b), because dissection efficacy can be expected in some cases. Although 106pre, 106tbR, and 112aoP are often dissected in metastasis-positive cases, they are defined as distant metastasis M1b in this edition because of insufficient data on the dissection efficacy index.The degree of lymph node dissection (D) is determined based on the pattern and extent of lymph node dissection in each type of esophagectomy. For thoracic esophageal cancer, D1: dissection less than D2; D2: two-field lymph node dissection; and D3: D2 + cervical lymph node dissection. We included 106tbL, 111, 8a, and 11p in the standard D2 dissection range but could be omitted.With the prevalence of standard preoperative treatment for locally advanced esophageal cancer, the staging classification is divided into clinical and pathological staging classifications based on the latest data.We jointly establish a definition and description of esophagogastric junction cancer with the Japanese Gastric Cancer Association and organize its management in the nationwide registry of gastric and esophageal cancers to facilitate further surveys in the future.Although primary esophageal cancer is a non-target lesion in the RECIST criteria for determining the treatment efficacy in RECIST, its prognostic impact is significant; therefore, we develop an index for determining the efficacy of CT for primary lesions. Simultaneously, the criteria for determining the treatment efficacy of primary tumors using endoscopy are updated. In addition, the diagnostic criteria for local recurrence after CR, as judged by endoscopy, are established.In line with advances in endoscopic diagnosis and treatment, the classification content (September 2012) established by the Japanese Esophageal Association's Committee for Diagnostic Criteria of Superficial Esophageal Cancer Depth by Enlarged Endoscopy is described in the reference terms.Squamous intraepithelial neoplasia is reevaluated and revised.Previously existing surgical findings [s] (gross surgical findings, intraoperative imaging findings, and gross findings of resection specimens) and findings in the endoscopic treatment [e] (intraoperative and gross findings of resection specimens) are included in the final analysis and deleted from the list.

79“Ae” is eliminated as a subsite of the esophagus, and “Jz” is newly defined as the esophagogastric junction zone. “Jz” is equal to the esophagogastric junction area in Nishi’s classification.

80We sub-classify cT3 as resectable (cT3 resectable: cT3r) or borderline resectable (cT3 borderline resectable: cT3br) because of the difficulty in determining adjacent organ involvement on imaging. Reference CT images and supporting findings are added to the diagnoses of cT3r, cT3br, and cT4.

81For the diagnosis of cN, recommended cut-off values are provided, referring to the diagnostic accuracy of lymph node metastasis by size in CT diagnosis. Diagnoses using PET are also included as a reference.

82To classify the degree of lymph node metastasis, a classification based on the number of metastatic regional lymph nodes is adopted for consistency with the TNM classification. We then abandon the lymph node grouping related to tumor location in thoracic esophageal cancer and newly establish the common regional lymph nodes for thoracic esophageal cancer. Supraclavicular lymph nodes are classified as distant rather than regional. However, it is defined as M1a to distinguish it from other distant metastases (M1b), because dissection efficacy can be expected in some cases. Although 106pre, 106tbR, and 112aoP are often dissected in metastasis-positive cases, they are defined as distant metastasis M1b in this edition because of insufficient data on the dissection efficacy index.

83The degree of lymph node dissection (D) is determined based on the pattern and extent of lymph node dissection in each type of esophagectomy. For thoracic esophageal cancer, D1: dissection less than D2; D2: two-field lymph node dissection; and D3: D2 + cervical lymph node dissection. We included 106tbL, 111, 8a, and 11p in the standard D2 dissection range but could be omitted.

84With the prevalence of standard preoperative treatment for locally advanced esophageal cancer, the staging classification is divided into clinical and pathological staging classifications based on the latest data.

85We jointly establish a definition and description of esophagogastric junction cancer with the Japanese Gastric Cancer Association and organize its management in the nationwide registry of gastric and esophageal cancers to facilitate further surveys in the future.

86Although primary esophageal cancer is a non-target lesion in the RECIST criteria for determining the treatment efficacy in RECIST, its prognostic impact is significant; therefore, we develop an index for determining the efficacy of CT for primary lesions. Simultaneously, the criteria for determining the treatment efficacy of primary tumors using endoscopy are updated. In addition, the diagnostic criteria for local recurrence after CR, as judged by endoscopy, are established.

87In line with advances in endoscopic diagnosis and treatment, the classification content (September 2012) established by the Japanese Esophageal Association's Committee for Diagnostic Criteria of Superficial Esophageal Cancer Depth by Enlarged Endoscopy is described in the reference terms.

88Squamous intraepithelial neoplasia is reevaluated and revised.

89Previously existing surgical findings [s] (gross surgical findings, intraoperative imaging findings, and gross findings of resection specimens) and findings in the endoscopic treatment [e] (intraoperative and gross findings of resection specimens) are included in the final analysis and deleted from the list.

90Abbrevi ations AAnteriorADAdventitiaAIInvasion to the adjacent organsAPCArgon plasma coagulationBABrownish areaBLIBlue laser imagingBrBorderline resectablecClinical findingsCeCervical esophagusCRComplete responseCRTChemoradiotherapyCTChemotherapyCTVClinical target volumeDExtent of lymph node dissectionDMDistal marginDMMDeep muscularis mucosaeEEsophagusEGJEsophagogastric junctionEIEsophageal invasionEMREndoscopic mucosal resectionEPEpitheliumEREndoscopic resectionESDEndoscopic submucosal dissectionfFinal findingsGStomachGIGastric invasionGISTGastrointestinal stromal tumorHHHiatus herniaHMHorizontal marginHTHyperthermiaIMIntramural metastasisINFInfiltrative growth patternIOImmuno-oncology drugJzZone of esophagogastric junctionLaserLaser therapyLPMLamina propria mucosaeLRLocal recurrenceLSBELong-segment Barrett’s esophagusLtLower thoracic esophagusLyLymphatic invasionLy/VLymphatic invasion or venous invasionMDistant organ metastasisMCTMicrowave coagulation therapyMMMuscularis mucosaeMPMuscularis propriaMtMiddle thoracic esophagusNGrading of lymph node metastasisNBINarrow band imagingpPathological findingsPPosteriorPDProgressive diseasePDTPhotodynamic therapyPhPharynxPMProximal marginPRPartial responseRResidual tumorRECISTResponse evaluation criteria in solid tumorsRMRadial marginRRRemarkable responseRTRadiotherapySCESpecialized columnar epitheliumSCJSquamocolumnar junctionSDStable diseaseSINSquamous intraepithelial neoplasiaSMSubmucosal layerSMMSuperficial muscularis mucosaeSSBEShort-segment Barrett’s esophagusTDepth of tumor invasionTeThoracic esophagusTisCarcinoma in situUtUpper thoracic esophagusVVenous invasionVMVertical marginXCannot be assessed

91Anterior

92Adventitia

93Invasion to the adjacent organs

94Argon plasma coagulation

95Brownish area

96Blue laser imaging

97Borderline resectable

98Clinical findings

99Cervical esophagus

100Complete response

101Chemoradiotherapy

102Chemotherapy

103Clinical target volume

104Extent of lymph node dissection

105Distal margin

106Deep muscularis mucosae

107Esophagus

108Esophagogastric junction

109Esophageal invasion

110Endoscopic mucosal resection

111Epithelium

112Endoscopic resection

113Endoscopic submucosal dissection

114Final findings

115Stomach

116Gastric invasion

117Gastrointestinal stromal tumor

118Hiatus hernia

119Horizontal margin

120Hyperthermia

121Intramural metastasis

122Infiltrative growth pattern

123Immuno-oncology drug

124Zone of esophagogastric junction

125Laser therapy

126Lamina propria mucosae

127Local recurrence

128Long-segment Barrett’s esophagus

129Lower thoracic esophagus

130Lymphatic invasion

131Lymphatic invasion or venous invasion

132Distant organ metastasis

133Microwave coagulation therapy

134Muscularis mucosae

135Muscularis propria

136Middle thoracic esophagus

137Grading of lymph node metastasis

138Narrow band imaging

139Pathological findings

140Posterior

141Progressive disease

142Photodynamic therapy

143Pharynx

144Proximal margin

145Partial response

146Residual tumor

147Response evaluation criteria in solid tumors

148Radial margin

149Remarkable response

150Radiotherapy

151Specialized columnar epithelium

152Squamocolumnar junction

153Stable disease

154Squamous intraepithelial neoplasia

155Submucosal layer

156Superficial muscularis mucosae

157Short-segment Barrett’s esophagus

158Depth of tumor invasion

159Thoracic esophagus

160Carcinoma in situ

161Upper thoracic esophagus

162Venous invasion

163Vertical margin

164Cannot be assessed

165Terminology of the lymph nodes RRightLLeftsmSubmandibularspfSuperficialacAccessorytrTrachealupUppermidMiddlerecRecurrent nervetbTracheobronchialprePretrachealaoParaaorticpulPulmonary ligament

166Right

167Left

168Submandibular

169Superficial

170Accessory

171Tracheal

172Upper

173Middle

174Recurrent nerve

175Tracheobronchial

176Pretracheal

177Paraaortic

178Pulmonary ligament

179General rules

180“The Guidelines for Clinical and Pathological Studies on Carcinoma of the Esophagus was originally published in 1969 by the Japanese Society for Esophageal Diseases. Since then, the Society changed its name to the Japan Esophageal Society in 2003 and published the “Japanese Classification of Esophageal Cancer” in the Japanese language with some revisions to treatment results to keep up to date and provide a standard nomenclature. The Society is publishing a handbook in English language, entitled “The Japanese Classification of Esophageal Cancer” to promote the international use of the Guidelines and Classification.

181The term esophageal cancer in the Japanese Classification refers to cancer originating in the esophagus, and cancers metastatic to the esophagus are excluded. All primary malignant tumors of the esophagus should be described according to the Japanese Classification.

182Findings are recorded using the uppercase letters T (depth of tumor invasion), N (lymph node metastasis), and M (distant organ metastasis). The extent of each finding is expressed by Arabic numerals following each uppercase letter. “X” is used in unknown cases. Three categories of findings, namely Clinical, Pathological, and Final findings, are identified using the lowercase “c,” “p,” and “f,” respectively, before each uppercase letter. The “f” of Final findings can be omitted (Tables 1, 2). The checklists describing the Japanese Classification of Esophageal Cancer are shown in Tables 3 and 4.

183The order of clinical description is as follow: Tumor location (including the distance from the incisor), circumferential extent, tumor length, macroscopic tumor type, histological type (when identified), depth of tumor invasion, lymph node metastasis, distant organ metastasis, and stage, e.g., Mt (31–36 cm), 1/2 of circumference and on the anterior wall, 5 cm, type 2, moderately differentiated squamous cell carcinoma, cT3, cN2, cM0, cStage IIIB.

184The order of pathological description is as follow: Tumor location, tumor length, macroscopic tumor type, histological type, depth of tumor invasion, infiltrative growth pattern, lymphatic invasion, venous invasion, intramural metastasis, involvement of resection margins (proximal, distal, and radial margins), multiple primary cancers, histological response of chemotherapy and/or radiation, lymph node metastasis, distant organ metastasis, and stage, e.g., Mt, 5 cm; type 2, moderately differentiated squamous cell carcinoma; pT3, INFa, Ly1a, V1a, pIM0, pPM0, pDM0, pRM0, multiple primary carcinomas (present, two lesions), CRT-Grade 2, pN1 (2/30), sM0, f Stage IIIA.

185Other items to be filled inMetastasis from other organs and cancer invasionNon-cancerous coexisting tumors: leiomyoma and othersOther: Barrett's esophagus, achalasia, and other background lesions

186Metastasis from other organs and cancer invasion

187Non-cancerous coexisting tumors: leiomyoma and others

188Other: Barrett's esophagus, achalasia, and other background lesions

189The maximum length (mm), orthogonally oriented maximum width (mm), the center of circumferential extent, and the proportion of the tumor in the entire circumference should be described. In addition, the diagnostic methods used, such as barium radiography, endoscopy, and EUS, should be recorded.

190The esophagus is anatomically defined as extending from the esophageal orifice to the esophagogastric junction. The esophageal orifice is located at the lower margin of the cricoid cartilage. Identification of the esophagogastric junction (EGJ) is described in Part II (refer to 8.1 in Part II).

191The esophagus lies between the hypopharynx and stomach and can be anatomically divided into the cervical esophagus (Ce), thoracic esophagus (Te), and the zone of the esophagogastric junction (Jz).

192Cervical esophagus (Ce): From the esophageal orifice to the sternal notch.

193Thoracic esophagus (Te): From the sternal notch to 2 cm cephalad of the esophagogastric junction.Upper thoracic esophagus (Ut): From the sternal notch to the tracheal bifurcationMiddle thoracic esophagus (Mt): The proximal half of the two equal portions between the tracheal bifurcation and the esophagogastric junctionLower thoracic esophagus (Lt): The portion between the inferior margin of the Mt and 2 cm cephalad from the esophagogastric junction

194Upper thoracic esophagus (Ut): From the sternal notch to the tracheal bifurcation

195Middle thoracic esophagus (Mt): The proximal half of the two equal portions between the tracheal bifurcation and the esophagogastric junction

196Lower thoracic esophagus (Lt): The portion between the inferior margin of the Mt and 2 cm cephalad from the esophagogastric junction

197Zone of the esophagogastric junction (Jz): The zone of the esophagogastric junction is defined as the region 2 cm above the esophagogastric junction and 2 cm below the esophagogastric junction.Note 1: In the absence of esophagography, the border between the Mt and Lt should be 1 cm distal to the inferior border of the inferior pulmonary vein on CT.Note 2: When Jz shifts into the thoracic cavity due to a hiatal hernia of the esophagus, first, the Jz range should be decided based on the esophagogastric junction. And then, the remaining range is defined as Lt.

198Note 1: In the absence of esophagography, the border between the Mt and Lt should be 1 cm distal to the inferior border of the inferior pulmonary vein on CT.

199Note 2: When Jz shifts into the thoracic cavity due to a hiatal hernia of the esophagus, first, the Jz range should be decided based on the esophagogastric junction. And then, the remaining range is defined as Lt.

200When the tumor location is uncertain because other examinations except endoscopy are yet to be performed, only the distance from the incisor is described.

201When the tumor extends continuously into more than one portion of the esophagus, the main tumor location is the site of the deepest tumor invasion, which should be described first. When it is difficult to determine the site of the deepest tumor invasion, the portion at the central point of the tumor can be recorded as the main tumor location.

202In the case of multiple primary lesions, their locations are described in the order of depth of tumor invasion. The deepest lesion is described first. When it is difficult to determine the order of the depth, then, the order of description depends on the size of the area occupied by the lesion. The largest lesion is described first, e.g., MtLt, LtJzG, CePh.

203Esophagogastric junction cancer (refer to 8.4 in Part II)The location of the lesion should be described depending on the tumor center as follows: E, EG, E = G, GE, or G.The tumor center is recorded as the distance (− 2 cm, 1 cm, and others) from the esophagogastric junction. Minus means that the tumor center is located at the esophagus, and plus means that tumor center is located at the stomach.The lengths of proximal and distal invasions are recorded as the distance from the EGJ (cm).Barrett's esophagus, hiatal hernia, and other coexisting lesions are recorded.

204The location of the lesion should be described depending on the tumor center as follows: E, EG, E = G, GE, or G.

205The tumor center is recorded as the distance (− 2 cm, 1 cm, and others) from the esophagogastric junction. Minus means that the tumor center is located at the esophagus, and plus means that tumor center is located at the stomach.

206The lengths of proximal and distal invasions are recorded as the distance from the EGJ (cm).

207Barrett's esophagus, hiatal hernia, and other coexisting lesions are recorded.

208Tumor type classification is based on macroscopic findings. Radiological findings and endoscopic findings are also defined according to macroscopic findings.

209Tumors confined to the mucosa or submucosa are classified as the superficial type, while tumors whose invasion extends to the muscularis propria or beyond are classified as the advanced type. The superficial types have the prefix ‘0’ and are classified into 0-I, 0-II, or 0-III. The advanced types are divided into four categories:1, 2, 3, or 4. When a tumor cannot be classified into any of these 5 (0–4) categories or consists of their combinations, it is classified as 5.

210Type 0: SuperficialType 1: ProtrudingType 2: Ulcerative and localizedType 3: Ulcerative and infiltrativeType 4: Diffusely infiltrativeType 5: UnclassifiableType 5a: Unclassifiable without treatmentType 5b: Unclassifiable after treatment Notes 1, 2

211Type 0: Superficial

212Type 1: Protruding

213Type 2: Ulcerative and localized

214Type 3: Ulcerative and infiltrative

215Type 4: Diffusely infiltrative

216Type 5: UnclassifiableType 5a: Unclassifiable without treatmentType 5b: Unclassifiable after treatment Notes 1, 2

217Type 5a: Unclassifiable without treatment

218Type 5b: Unclassifiable after treatment Notes 1, 2

219Note 1: Macroscopic tumor type before any treatments is described.

220Note 2: In case with preceding treatments, if the tumor still can be classified into Type 0–4, describe it, otherwise describe it as Type 5b. In either case, all the prefixes indicating the preceding treatments, e.g., CT-, RT-, EMR-, should be marked.

221Type 0-I: Superficial and protrudingType 0-Ip: PedunculatedType 0-Is: Sessile (broad based)Type 0-II: Superficial and flatType 0-IIa: Slightly elevatedType 0-IIb: FlatType 0-IIc: Slightly depressedType 0-III: Superficial and excavatedOther notations

222Type 0-I: Superficial and protrudingType 0-Ip: PedunculatedType 0-Is: Sessile (broad based)

223Type 0-Ip: Pedunculated

224Type 0-Is: Sessile (broad based)

225Type 0-II: Superficial and flatType 0-IIa: Slightly elevatedType 0-IIb: FlatType 0-IIc: Slightly depressed

226Type 0-IIa: Slightly elevated

227Type 0-IIb: Flat

228Type 0-IIc: Slightly depressed

229Type 0-III: Superficial and excavated

230Other notations

231Note 1: Combined type: When multiple macroscopic tumor types are mixed in one lesion, it is called a combined type. The wider tumor is described first, and the smaller one is second. Double quotation marks (“”) are placed around the macroscopic tumor type that has the deepest tumor invasion. The main macroscopic tumor type was the deepest. However, when an advanced type is mixed, the most advanced type is described first and double quotation marks are unnecessary. For example, 0-IIc + “0-Is”, 3 + 0-IIc.

232Note 2: Superficial spreading type: superficial type 0-IIc in which the maximal length of the tumor extends ≥ 5 cm longitudinally. This may also be described in macroscopic tumor types.

233TX: Depth of tumor invasion cannot be assessedT0: No evidence of primary tumorT1a: Tumor invades mucosaNotes 1 and 2T1a-EP: Carcinoma in situ (Tis)T1a-LPM: Tumor invades lamina propria mucosae (LPM)T1a-MM: Tumor invades muscularis mucosae (MM)T1b: Tumor invades submucosa (SM)Notes 1 and 3T1b-SM1: Tumor invades the upper third of the submucosal layerT1b-SM2: Tumor invades the middle third of the submucosal layerT1b-SM3: Tumor invades the lower third of the submucosal layerT2: Tumor invades muscularis propria (MP)T3: Tumor invades adventitia (AD)Note 4T4: Tumor invades adjacent structures (AI)Notes 5, 6, and 7

234TX: Depth of tumor invasion cannot be assessed

235T0: No evidence of primary tumor

236T1a: Tumor invades mucosaNotes 1 and 2T1a-EP: Carcinoma in situ (Tis)T1a-LPM: Tumor invades lamina propria mucosae (LPM)T1a-MM: Tumor invades muscularis mucosae (MM)

237T1a-EP: Carcinoma in situ (Tis)

238T1a-LPM: Tumor invades lamina propria mucosae (LPM)

239T1a-MM: Tumor invades muscularis mucosae (MM)

240T1b: Tumor invades submucosa (SM)Notes 1 and 3T1b-SM1: Tumor invades the upper third of the submucosal layerT1b-SM2: Tumor invades the middle third of the submucosal layerT1b-SM3: Tumor invades the lower third of the submucosal layer

241T1b-SM1: Tumor invades the upper third of the submucosal layer

242T1b-SM2: Tumor invades the middle third of the submucosal layer

243T1b-SM3: Tumor invades the lower third of the submucosal layer

244T2: Tumor invades muscularis propria (MP)

245T3: Tumor invades adventitia (AD)Note 4

246T4: Tumor invades adjacent structures (AI)Notes 5, 6, and 7

247Note 1: Superficial esophageal cancer: T1a and T1b are designated as superficial cancers, regardless of lymph node or distant organ metastases, e.g., superficial esophageal cancer: T1NxMx.

248Note 2: Early esophageal cancer: T1a can be designated as early esophageal cancer regardless of the presence or absence of lymph node or distant organ metastasis, e.g., early esophageal cancer: T1aNxMx.

249Note 3: In endoscopically resected specimens of carcinoma other than adenocarcinoma, a tumor invading the submucosa to a depth of ≤200 μm from the muscularis mucosae is classified as T1b-SM1, while a tumor extending >200 μm is classified as T1b-SM2. Since the true entire thickness of the submucosal layer is unknown, SM3 is not defined.

250In adenocarcinoma arising in the esophagus or esophagogastric junction, all lesions that invaded the submucosa >500 μm from the muscularis mucosae are considered T1b-SM2.

251For pT1b carcinomas, the invasion distance from the lower edge of the muscularis mucosae is also measured. Invasion distance is described only in endoscopically resected specimens, e.g., pT1b-SM2 (600 μm).

252Note 4: The T3 subclassification is used only for clinical diagnosis.

253T3r: Resectable: No evidence of invasion of other organs on imaging

254T3br: borderline resectable: invasion of other organs (trachea, bronchus, or aorta) cannot be ruled out on imaging. Describe organ(s) suspected of invasion, e.g., cT3br(Trachea)

255In this clinical T classification, we abolished the subclassification of cT4. When a tumor is suspected to be resectable without simultaneous resection of adjacent organs, it should be classified as cT3r. When a tumor definitely invades adjacent organs, it is recorded as cT4, even if the adjacent organs are the pleura, pericardium, or diaphragm. When the suspicious target organs of invasion are trachea, bronchus, or aorta, which are usually not resected simultaneously, but no definite findings of cT4 are found, the tumor is classified as cT3br.

256Note 5: T4 subclassification is used only for pathological diagnosis and not for clinical diagnosis.

257pT4a: Pleura, pericardium, diaphragm, lungs, thoracic duct, azygos vein, and nerves

258pT4b: Aorta (great artery), trachea, bronchus, pulmonary vein, pulmonary artery, and vertebral body

259Note 6: Invading organs, such as the pericardium, aorta, vena cava, trachea, lungs, diaphragm, thoracic duct, recurrent laryngeal nerve, and azygos vein, should be recorded, e.g., cT4 (lung), cT4 (aorta), pT4a (lung), pT4b (Trachea).

260Note 7: When a metastatic lymph node additionally invades a surrounding organ other than the esophagus, it should be classified as T4 and recorded as “T4 (metastatic node number - invaded organ)”, e.g., cT4 (No.112aoA-Aorta).

261Note 8: Intraductal involvement is defined as pT1a-EP. If the cancer shows invasion outside the duct of the esophageal glands, the depth is defined by the layer of invasion.

262Note 9: If there are no viable cancer cells capable of proliferating after preoperative treatment, it is classified as T0. In staging, T0 is used equally as T1a.

263e.g.:CRT-pT0, N0, M0, CRT-pStage 0

264Note 10: Depth classification of esophageal adenocarcinoma

265For cervical (Ce) and thoracic (Te) esophageal adenocarcinoma, follow this Depth of tumor invasion (2.4.1.) ".

266Adenocarcinoma of the esophagogastric junction is classified as follows according to the "Gastric Cancer Treatment.”

267TX: Depth of tumor unknown

268T0: No evidence of primary tumor

269T1: Tumor confined to the mucosa (M) or submucosa (SM)

270T1a: Tumor confined to the mucosa (M)

271T1a-SMM: Tumor invading the superficial muscularis mucosae (SMM).

272T1a-LPM: Tumor invading the lamina propria mucosa.

273T1a-DMM: Tumor invading the deep muscularis mucosae (DMM). Note 11

274T1b: Tumor confined to the submucosa (SM)

275T2: Tumor invading muscularis propria (MP)

276T3: Tumor invading the subserosa (SS)

277T4: Tumor invasion is contiguous to or exposed beyond the serosa, or the tumor invading adjacent structures.

278T4a: Tumor invasion is contiguous with the serosa or penetrates the serosa and is exposed in the peritoneal cavity (SE)

279T4b: Tumor invades adjacent structures (AI/SI)

280Note 11: If a new muscularis mucosae (superficial muscularis mucosae (SMM)) is present, the deep muscularis mucosae (DMM) is regarded as the original muscularis mucosae. When a tumor invades the DMM, it is described as T1a-DMM. If a muscularis mucosal duplication is not found in an esophageal adenocarcinoma, it should be described as T1a-MM.

281The Committee for Diagnostic Criteria of Superficial Esophageal Cancer Depth Using Magnifying Endoscopy of the Japanese Esophageal Association (JESA) has been studying to develop a new, simpler classification based on the two existing endoscopic classifications (Inoue and Arima Classifications). Therefore, we develop a new classification based on narrow-band light-based observation (NBI) and blue laser imaging (BLI), which is simple, objective, and useful for differentiating tumors from non-tumors and evaluating tumor depth.

282This classification is based on lesions with territoriality Note 1 that are suspected to be squamous cell carcinomas. Vessels seen in borderline lesions Note 2 are classified as Type A. Vessels seen in carcinomas are classified as Type B, sub-classified as B1, B2, and B3. The subclassification aims to diagnose the depth of the disease, and the findings in squamous cell carcinomas of T1a-EP and -LPM are classified as Type B1, T1a-MM, and T1b-SM1 as Type B2, and those deeper than T1b-SM2 as Type B3.

283Type A: Normal IPCL Note 3 (intraepithelial papillary capillary loop) or abnormal microvessels without severe irregularity (Fig. 9a)

284Type B: Abnormal microvessels with severe irregularities or highly dilated abnormal vessels (Fig. 9b–g)

285B1: Type B vessels with a loop-like formation (Fig. 9b)Note 4

286B2: Type B vessels without a loop-like formation (Fig. 9c)Note 5

287B3: Highly dilated vessels which calibers (Fig. 9d)Note 6Avascular area (AVA): AVA is a certain area without vessels or with sparse vessels surrounded by (any subtypes of) type B microvessels. The AVA is categorized into three types as follows: AVA-small (<0.5 mm in diameter) (Fig. 9e), AVA-middle (0.5 mm or between 0.5 and 3 mm) (Fig. 9f), and AVA-large (≥3 mm) (Fig. 9g). Any type of AVA (small, medium, or large) surrounded by B1 vessels is suggestive of T1a-EP/LPM. An AVA-middle surrounded by B2 or B3 vessels is suggestive of T1a-MM/T1b-SM1. AVA-large surrounded by B2 or B3 vessels is suggestive of T1b-SM2 or deeper.

288Avascular area (AVA): AVA is a certain area without vessels or with sparse vessels surrounded by (any subtypes of) type B microvessels. The AVA is categorized into three types as follows: AVA-small (<0.5 mm in diameter) (Fig. 9e), AVA-middle (0.5 mm or between 0.5 and 3 mm) (Fig. 9f), and AVA-large (≥3 mm) (Fig. 9g). Any type of AVA (small, medium, or large) surrounded by B1 vessels is suggestive of T1a-EP/LPM. An AVA-middle surrounded by B2 or B3 vessels is suggestive of T1a-MM/T1b-SM1. AVA-large surrounded by B2 or B3 vessels is suggestive of T1b-SM2 or deeper.

289Reticular pattern vessels are defined as plexiform microvessels and the term "R" is added. This vascular pattern is often found in invasive SCC or non-SCC types of malignant epithelial neoplasms (such as basaloid squamous carcinoma, adenosquamous carcinoma, and neuroendocrine carcinoma) with an infiltrative growth pattern composed of single cells, small tumor nests, or a trabecular arrangement of tumor cells (such as INFc). (Fig. 9h)

290The coloration of the epithelium between microvessels presenting as a brownish area (BA: brownish epithelium visualized by NBI or BLI) is defined as intervascular background coloration.

291Note 1: Lesions whose borders can be followed by normal or image-enhanced observation (dye, digital, and optical digital methods).

292Note 2: These are mainly squamous intraepithelial neoplasias, but some may include inflammation or carcinoma.

293Note 3: In normal conditions, the diameter of the vessels is approximately 7–10μm.

294Note 4: It shows loop-like morphology such as dotted, spiral, or lint-like, with a vessel diameter of approximately 20–30μm.

295Note 5: Anomalous vessels that do not form loops, such as multilayered (ML) and irregularly branched (IB) vessels.

296Note 6: Irregular vessels that are approximately 3 times larger than B2 vessels and have a vessel diameter greater than approximately 60µm.

297This classification system has abolished subclassification of T4 in the former edition as a clinical diagnosis. However, in practice, it remains unclear whether the tumor is cT3 or cT4, or resectable or unresectable. In cases of obvious adjacent organ involvement, such as an esophagotracheal fistula, the diagnosis of cT4 is easy; however, the involvement of adjacent organ is often difficult to diagnose. Clinically, the question is whether R0 can be achieved without resection of the adjacent organs (trachea, bronchus, and aorta). Therefore, we subclassified cT3 into two, cT3br (borderline resectable), wherein the invasion of adjacent organs cannot be ruled out, and cT3r (resectable), wherein the invasion of adjacent organs can be ruled out. When a tumor is considered to invade the adjacent organs, it is recorded as cT4 even if the adjacent organs are the pleura, pericardium, or diaphragm. When a tumor might invade the adjacent organs (such as the trachea, bronchus, or aorta) wherein the organs are not usually resectable but no definite findings of cT4 are found, the tumor is classified as cT3br.

298Tracheal and bronchial invasion is diagnosed when the stratified structure of the border of contact with the airway by the primary tumor or lymph node metastases is unclear and when the airway is compressed, displaced, or the lumen is narrowed. In addition to CT images, it is also important to evaluate bronchoscopy findings.

299Aortic invasion is diagnosed when the layered structure of the contact border with the aorta by the primary tumor or lymph node metastases is unclear, and the contact angle (Picus angle) at ≥ 110 degrees can be detected with ≥ 10 mm in cephalocaudal length, or the angle of contact (Picus angle) at 90–110 degrees can be detected with ≥ 20 mm in cephalocaudal length. In addition, if the tumor contour collapses and contacts or encircles the aorta, aortic invasion is diagnosed.

300In addition to enhanced CT, upper gastrointestinal endoscopy and esophagography are used to make a cT4 diagnosis, considering the primary tumor's main wall location (such as posterior wall predominant or sub-total) and the gross type of the primary tumor (bulge or ulcer). If necessary, MRI and EUS are used to aid in the diagnosis of the aortic and tracheal wall structures.

301In this chapter, typical CT images of cT3r, cT3br, and cT4 are presented for reference. Regarding each CT image, the rates of agreement of diagnosis among the experts are shown.

302We present typical CT images of cT3r that do not invade the adjacent organs. We provide the rates of agreement of the tumor depth by seven experts who belong to the working group of the Committee of Japanese Classification of Esophageal Cancer as reference data.

303The laterality of the primary lesion on the circumference is significant in the diagnosis of tracheal invasion. Although the tracheal membrane is often compressed by tumors of the upper esophagus, the possibility of tracheal invasion differs between anterior and posterior tumors. In these three figures, the primary lesions (located in the upper esophagus) appear to contact the tracheal membrane or tracheal cartilage. As shown in Fig. 10a and b, the tracheal invasion is not determined because the tumors are located in the posterior wall and low-density layers between the trachea, and an enhanced outline of the tumors can be detected. As shown in Fig. 10c, we determine no tracheal invasion because the boundary of the trachea is clear and no compression, dislocation, or stenosis is observed despite the presence of a left-anterior tumor.

304Agreement of diagnosis of cT3: 10a, 85.7%, 10b, 100%, 10c, 85.7%

305The laterality of the primary lesion in the circumference is also significant for the diagnosis of invasion of the left main bronchus. In these three figures, the primary lesions (located in the middle esophagus) contact the left main bronchial membranes and appear to compress them slightly. However, all three patients are diagnosed as having no main bronchial invasion because low-density layers between the left main bronchus and the enhanced outline of the tumors can be detected, there are no findings of bronchial stenosis or deformity, and the tumors are located in the posterior wall.

306Agreement of diagnosis of cT3: 11a, 100%, 11b, 100%, and 11c, 100%.

307For the diagnosis of aortic invasion, the laterality of the primary lesion in the circumference is also significant. In these three figures, the primary lesions (located in the middle or lower esophagus) are in contact with the descending aorta. All three patients are diagnosed with no aortic invasion because the fat layers between the primary lesions and the aorta can be clearly detected, and their angles of contact (Picus’ angle) are < 90°.

308Agreement of diagnosis of cT3: 12a, 100%, 12b, 71.4%, 12c, 100%

309We present typical CT images of cT3br, which are not ruled out to invade the adjacent organs.

310In this case, the angle of contact (Picus’ angle) ≥ 110 degrees can be detected with ≥ 10 mm in cephalocaudal length and compression to the aorta is also found. However, the outline of the tumor contacting the aorta remains, and a low-density layer between the aorta and the enhanced outline of the tumor can also be detected. Overall, with a suspicion of cT4, this case is diagnosed as cT3br.

311Agreement of diagnosis of cT3: 57.1%

312In this case, the angle of contact (Picus’ angle) ≥ 110 degrees can be detected with ≥ 10 mm in cephalocaudal length and the tumor surrounds the aorta. However, infiltrative shadows are believed to be caused by edema or other effects because most of the esophageal wall is confirmed to be in the arterial phase. Finally, with the suspicion of cT4, this patient is diagnosed as cT3br.

313Agreement of diagnosis of cT3: 57.1%

314In this case, the primary lesion (located in the upper esophagus) was found to be in contact with a large area of the tracheal membrane and cartilage, as well as the surrounding areas; however, there are no findings of tracheal compression, dislocation, stenosis, or deformation. Therefore, with the suspicion of cT4, this case is diagnosed as cT3br.

315Agreement of diagnosis of cT3: 57.1%

316Although the primary lesion in the upper esophagus contacts the left main bronchus, compression, dislocation, stenosis, and deformation of the left main bronchus are relatively mild and smooth. Therefore, with the suspicion of cT4, this case is finally diagnosed as cT3br.

317Agreement of diagnosis of cT3: 57.1%

318We present typical CT images of cT4, which are considered to definitely invade adjacent organs.

319The primary lesions (located in the upper esophagus) are in contact with the tracheal membrane and part of the tracheal cartilage. Based on the findings of tracheal compression, dislocation, stenosis, and deformation, these patients are diagnosed with invasions to the trachea.

320Diagnostic agreement of cT4:17a, 85.7%, 17b, 85.7%

321The primary lesions (located in the middle esophagus) contact the left main bronchus, and compression of the bronchial membrane, bronchial stenosis, and deformation are observed. These patients are diagnosed with invasions to the left main bronchus.

322Agreement of diagnosis of cT4: 18a, 85.7%, 18b, 85.7%, 18c, 85.7%.

323Metastatic nodes of 106recR or 106recL contact the right and left tracheal cartilage and the tracheal membrane widely. Tracheal compression and dislocation are observed. These cases are diagnosed with invasion to the trachea (cT4).

324Agreement of diagnosis of cT4: 19a, 100%, 19b, 100%, 19c, 85.7%, 19d, 100%

325The boundary layers between the primary lesions (located in the lower esophagus) and the aorta are obscure, and the angles of contact (Picus’ angle) are 160° (Fig. 16a) and 110° (Fig. 16b). These lesions appear to surround the aorta, and these findings are confirmed in cranial and caudal images (data not shown). These patients are diagnosed with cT4.

326Agreement of diagnosis of cT4: 20a, 85.7%, 20b, 71.4%

327The metastatic lymph nodes of 108 located between the primary lesions (middle esophagus) and the aorta contact with the aorta, losing the boundary of the nodes. Boundary layers could not be detected. The angles of contact (Picus’ angle) are 100° (Fig. 21a) and 120° (Fig. 21b) and these findings are confirmed in the cranial and caudal images (Figures not shown). These cases are diagnosed with invasion to the aorta.

328Agreement of diagnosis of cT4: 21a, 85.7%, 21b, 71.4%

329Infiltrative growth patterns of tumors can be classified into one of the following three types based on the predominant pattern observed at the tumor margins.

330INFa (expansive type): expansive growth of tumor nests with a well-demarcated border from the surrounding tissue.

331INFb (intermediate type): intermediate growth pattern, between INFa and INFc.

332INFc (infiltrative type): infiltrative growth of tumor nests with an ill-defined border from the surrounding tissue.

333These descriptions (Ly or V) are used only for pathological findings and not for clinical findings.

334Note 1: Indefinite discrimination of lymphatic or venous invasion is described as Ly/V.

335LyX: lymphatic invasion cannot be assessed.Ly0: None.Ly1: Lymphatic invasion is observed.Ly1a: Slight, one or two lymphatic vessels are involved.Ly1b: Moderate.Ly1c: Severe.

336LyX: lymphatic invasion cannot be assessed.

337Ly0: None.

338Ly1: Lymphatic invasion is observed.Ly1a: Slight, one or two lymphatic vessels are involved.Ly1b: Moderate.Ly1c: Severe.

339Ly1a: Slight, one or two lymphatic vessels are involved.

340Ly1b: Moderate.

341Ly1c: Severe.

342Note: A tumor mass found in the thoracic duct is described as positive for lymphatic invasion.

343VX: Venous invasion cannot be assessed.V0: None.V1: Venous invasion is observed.V1a: Slight, one or two veins are involved.V1b: Moderate.V1c: Severe.

344VX: Venous invasion cannot be assessed.

345V0: None.

346V1: Venous invasion is observed.V1a: Slight, one or two veins are involved.V1b: Moderate.V1c: Severe.

347V1a: Slight, one or two veins are involved.

348V1b: Moderate.

349V1c: Severe.

350Note: For endoscopically resected specimens, it is not necessary to evaluate the degree of vascular involvement; only its presence or absence should be described.

351Lymphatic invasion (Ly)LyX: lymphatic invasion could not be assessedLy0: NoneLy1: Lymphatic invasion is observed

352LyX: lymphatic invasion could not be assessed

353Ly0: None

354Ly1: Lymphatic invasion is observed

355Venous invasion (V)VX: Venous invasion could not be assessedV0: NoneV1: Venous invasion is observed

356VX: Venous invasion could not be assessed

357V0: None

358V1: Venous invasion is observed

359Greatest longitudinal dimension (mm)

360Greatest transverse (at 90° to the longitudinal tumor axis) dimension (mm)

361Proximal (oral) margin (PM) (mm)

362Distal (anal) margin (DM) (mm)

363The macroscopic appearance of tumors before and after fixation may differ. Under such circumstances, the surgical tumor type should be described according to pre-fixation observations, and the pathological tumor type should be described based on post-fixation findings. Pathological tumor types can be classified based on cross-sectional observations. Surgical tumor types should be determined regardless of the pathological depth of tumor invasion.

364Note: The presence of preoperative chemotherapy and radiotherapy should be recorded for surgical tumor types.

365Cancer invasion at the resection margin is evaluated pathologically, and a p- is assigned to each finding. The pathological and surgical findings are judged comprehensively as the final findings (f).

366PMX: Proximal margin cannot be assessedPM0: No evidence of tumor invasionPM1: Tumor invasion present at the proximal margin

367PMX: Proximal margin cannot be assessed

368PM0: No evidence of tumor invasion

369PM1: Tumor invasion present at the proximal margin

370Note: The distance from the resection margin to the tumor is recorded in millimeters for the PM0 specimens.

371DMX: Distal Margin cannot be assessedDM0: No evidence of tumor invasionDM1: Tumor invasion present at the distal margin

372DMX: Distal Margin cannot be assessed

373DM0: No evidence of tumor invasion

374DM1: Tumor invasion present at the distal margin

375Note: The distance from the resection margin to the tumor is recorded in millimeters for DM0 specimens.

376RMX: Radial margin cannot be assessedRM0: No evidence of tumor invasionRM1: Tumor invasion present at the radial margin

377RMX: Radial margin cannot be assessed

378RM0: No evidence of tumor invasion

379RM1: Tumor invasion present at the radial margin

380Note: The distance from the resection margin to the tumor is recorded in millimeters for RM0 specimens.

381Number of lesions

382Number of specimens resected from each lesion:

383e.g., 1. en bloc resection; 2. Divided resection (divided resection means that the lesion was resected but not in en bloc fashion. In this case, the number of divided specimens should be recorded.)

384Size is described as the greatest longitudinal dimension in millimeters multiplied by the greatest transverse dimension in millimeters: a × b (mm).

385The tumor types are classified as Type 0-Ip, Type 0-Is, Type 0-IIa, Type 0-IIb, Type 0-IIc, Type 0-III, combined type, and others.

386Cancer invasion at the resection margin is evaluated pathologically, and a p- is assigned to each finding. The pathological and endoscopic findings are judged comprehensively as the final findings (f).

387HMX: The presence or absence of residual tumors in the horizontal margin cannot be assessed.HM0: Non-cancerous squamous epithelium and lamina propria mucosae confirmed on all horizontal resection margins.HM1: The tumor is exposed on any horizontal resection margin.

388HMX: The presence or absence of residual tumors in the horizontal margin cannot be assessed.

389HM0: Non-cancerous squamous epithelium and lamina propria mucosae confirmed on all horizontal resection margins.

390HM1: The tumor is exposed on any horizontal resection margin.

391VMX: Residual tumor in the vertical margin cannot be assessed.VM0: No tumor is exposed on any vertical margin.VM1: The tumor is exposed on any vertical margin.

392VMX: Residual tumor in the vertical margin cannot be assessed.

393VM0: No tumor is exposed on any vertical margin.

394VM1: The tumor is exposed on any vertical margin.

395Note 1: When no tumor is recognized in any resection margin, it is defined as complete resection (pR0); when a tumor is recognized in any resection margin, it is defined as incomplete resection (pR1).

396Note 2: The presence of vascular invasion in the resection margin is defined as a positive resection margin (pHM1 or pVM1).

397Note3: When a lesion is resected in divided fashion, outer margin of the reassembled specimens should be regarded as horizontal margin.

398The term “multiple primary cancers of the esophagus” refers to the presence of two or more primary esophageal cancers that are located separately from each other. They should be described separately from intramural metastatic lesions. If multiple primary cancers are present, the location, size, macroscopic findings, and tumor depth should be described for each lesion. Among multiple lesions, the primary lesion is assigned to the lesion with the deepest depth or the lesion with the largest diameter if the depths are the same.

399Note 1: Descriptions of the locations of multiple primary cancers of the esophagus should be made according to the order of the depth of tumor invasion (deeper to shallower), inserting “/” between the abbreviations for the location of each lesion; the total number of lesions should also be recorded in parentheses. For example, MtUt/Lt/Lt (3 lesions)

400Note 2: Secondary lesions that are clearly histologically different from the main lesion or those with the same histology but with evidence of intraepithelial carcinoma are considered primary lesions and regarded as multiple carcinomas.

401The term “multi-organ primary cancers including the esophagus” refers to the presence of one or more primary malignant diseases other than esophageal cancer in patients with primary esophageal cancer.

402Note 1: In cases of multi-organ primary cancers including the esophagus, organs other than the esophagus should be specified in parentheses.

403Note 2: Whether the multiplicity is synchronous or metachronous should be recorded, e.g., multi-organ primary cancers: stomach (synchronous).

404Cancers diagnosed within a period of <1 year are considered synchronous cancers.

405Cancers diagnosed over a period of ≥1 year are considered metachronous cancers.

406If both simultaneous and metachronous cancers are present, they are considered synchronous and metachronous.

407Metastatic lesions in the esophagus, pharynx, or gastric wall macroscopically (clearly) separated from the primary tumor should be recorded as IM, and the number of such lesions should be described.IMX: Intramural metastasis cannot be assessedIM0: No intramural metastasis.IM1: Intramural metastasis.

408IMX: Intramural metastasis cannot be assessed

409IM0: No intramural metastasis.

410IM1: Intramural metastasis.

411Note: IM in the gastric wall should be recorded as “IM1-St.” This is classified as organ metastasis (M1).

412The names and numbers of lymph nodes are defined in Table 5 and Fig. 23 (refer to 19 in Part II).

413The names and numbers of the abdominal lymph node stations are defined according to the Japanese Classification of Gastric Carcinoma.

414Note 1: The number of lymph node stations should be recorded using “No.” plus a number, e.g., No.106recR.

415Note 2: Imaging criteria for the diagnosis of lymph node metastasis using CT and PET/CT (refer to 20 in Part II)For the diagnosis of lymph node metastasis by CT, the slice size should be ≤ 2.5 mm on contrast-enhanced CT.Based on the analysis limited to lymph nodes of short diameter ≥ 5 mm of patients with cT2-T4, a short diameter of 6 mm on CT is recommended as the cut-off criterion. However, there are limitations to diagnosing lymph node metastases based on size alone, since approximately 1/3 of metastatic lymph node have a short diameter of < 5 mm.Although PET/CT is superior to CT in terms of the positive predictive value of lymph node metastasis, the diagnostic criteria for positive SUV have not yet been standardized due to inter-institutional differences and the likelihood of being affected by many factors (patient’s blood sugar level, type of machine, or protocol).On PET-CT, it should be noted that lymph nodes in the mediastinum, especially those in the hilar region, can accumulate FDG due to inflammation in the lung field or sarcoidosis, resulting in false-positive results.

416For the diagnosis of lymph node metastasis by CT, the slice size should be ≤ 2.5 mm on contrast-enhanced CT.

417Based on the analysis limited to lymph nodes of short diameter ≥ 5 mm of patients with cT2-T4, a short diameter of 6 mm on CT is recommended as the cut-off criterion. However, there are limitations to diagnosing lymph node metastases based on size alone, since approximately 1/3 of metastatic lymph node have a short diameter of < 5 mm.

418Although PET/CT is superior to CT in terms of the positive predictive value of lymph node metastasis, the diagnostic criteria for positive SUV have not yet been standardized due to inter-institutional differences and the likelihood of being affected by many factors (patient’s blood sugar level, type of machine, or protocol).

419On PET-CT, it should be noted that lymph nodes in the mediastinum, especially those in the hilar region, can accumulate FDG due to inflammation in the lung field or sarcoidosis, resulting in false-positive results.

420Note 3: The numbers of metastatic and resected nodes are recorded at each lymph node station, e.g., No.104R (0/10), No.104L (1/13), No.106recL (0/4).

421Note 4: Extralymph node metastasis (tumor nodule), a cancer nest without lymphatic tissue in the fat tissue outside the esophagus or stomach, is confirmed, and its number and station should be recorded as extralymph node metastasis.

422Note 5: Extranodal involvement (direct or vascular invasion) should be recorded.

423Regional lymph nodes are defined according to the location of the tumor (Ce, Te, and Jz), as shown in Table 6 and Figs. 24, 25, 26.Note 1: For multiple esophageal cancers or tumors extending continuously into more than one portion of the esophagus, the regional lymph nodes should be determined based on the location of the deepest tumor invasion or the main tumor location.Note 2: Until the 11th edition of the "Japanese Classification of Esophageal Cancer,” the degree of lymph node metastasis was classified according to the site of metastatic lymph nodes. However, in this edition, the N classification is changed to a system based on the number of metastatic lymph nodes in accordance with the TNM classification of the Union for International Cancer Control (UICC). We decide on the extent of the regional lymph nodes so that patients can be expected to have a survival benefit from the dissection of these nodes. The degree of lymph node metastasis (N1-N3) is determined based on the number of metastatic nodes in the regional lymph nodes.Note 3: The concept of regional lymph nodesThe supraclavicular lymph nodes (No. 104) in thoracic esophageal cancer and No. 101, 104, and 16 in the esophagogastric junction (Jz) cancer are extra-regional lymph nodes; however, we recognize them as M1a to distinguish them from other M1b nodes because some dissection benefit can be expected.The M1a lymph nodes (No.104 for thoracic esophageal cancer and No.101, 104, and 16 for esophagogastric junction cancer) described above and other extra-regional lymph nodes (M1b) are not included in the count of the number of regional lymph node metastases.Lymph nodes 102, 106pre, 106tbR, and 112aoP in thoracic esophageal cancer are classified as extra-regional lymph nodes (M1b) because the effect of prophylactic dissection is unknown, although they are occasionally dissected in metastatic cases.

424Note 1: For multiple esophageal cancers or tumors extending continuously into more than one portion of the esophagus, the regional lymph nodes should be determined based on the location of the deepest tumor invasion or the main tumor location.

425Note 2: Until the 11th edition of the "Japanese Classification of Esophageal Cancer,” the degree of lymph node metastasis was classified according to the site of metastatic lymph nodes. However, in this edition, the N classification is changed to a system based on the number of metastatic lymph nodes in accordance with the TNM classification of the Union for International Cancer Control (UICC). We decide on the extent of the regional lymph nodes so that patients can be expected to have a survival benefit from the dissection of these nodes. The degree of lymph node metastasis (N1-N3) is determined based on the number of metastatic nodes in the regional lymph nodes.

426Note 3: The concept of regional lymph nodes

427The supraclavicular lymph nodes (No. 104) in thoracic esophageal cancer and No. 101, 104, and 16 in the esophagogastric junction (Jz) cancer are extra-regional lymph nodes; however, we recognize them as M1a to distinguish them from other M1b nodes because some dissection benefit can be expected.

428The M1a lymph nodes (No.104 for thoracic esophageal cancer and No.101, 104, and 16 for esophagogastric junction cancer) described above and other extra-regional lymph nodes (M1b) are not included in the count of the number of regional lymph node metastases.

429Lymph nodes 102, 106pre, 106tbR, and 112aoP in thoracic esophageal cancer are classified as extra-regional lymph nodes (M1b) because the effect of prophylactic dissection is unknown, although they are occasionally dissected in metastatic cases.

430NX: Regional lymph node metastasis cannot be assessedN0: No regional lymph node metastasisN1: Metastasis to 1 to 2 regional lymph nodesN2: Metastasis to 3 to 6 regional lymph nodesN3: Metastasis to 7 or more regional lymph nodes

431NX: Regional lymph node metastasis cannot be assessed

432N0: No regional lymph node metastasis

433N1: Metastasis to 1 to 2 regional lymph nodes

434N2: Metastasis to 3 to 6 regional lymph nodes

435N3: Metastasis to 7 or more regional lymph nodes

436For pathological diagnosis of lymph node metastasis, D2 or more lymphadenectomy for cervical and thoracic esophageal cancer and D1 + α or more lymphadenectomy for esophagogastric junction cancer is preferable (refer to 5.3.3).

437MX: Distant organ or extra-regional lymph node metastasis cannot be assessedM0: Neither distant organ nor extra-regional lymph node metastasisM1a: Metastasis in lymph node that is outside the region but can be expected to have some efficacy in dissectionM1b: Metastasis to lymph node that are neither regional lymph node nor M1a, or metastasis to distant organ

438MX: Distant organ or extra-regional lymph node metastasis cannot be assessed

439M0: Neither distant organ nor extra-regional lymph node metastasis

440M1a: Metastasis in lymph node that is outside the region but can be expected to have some efficacy in dissection

441M1b: Metastasis to lymph node that are neither regional lymph node nor M1a, or metastasis to distant organ

442Note: Refer to 3.2 Regional lymph nodes

443Distant organ metastasis should be determined through comprehensive consideration of operative macroscopic findings, intraoperative imaging examinations such as intraoperative ultrasound examination, intraoperative pathological diagnosis with frozen sections, and final pathological findings. Whether distant organ metastases are resected should be recorded.Note 1: The site of distant metastasis should be recorded as follows: lymph node (LYM), skin (SKI), liver (HEP), lung (PUL), bone marrow (MAR), bone (OSS), peritoneum (PER), pleura (PLE), brain (BRA), meninx (MEN), adrenal (ADR), and others (OTH).Note 2: Intramural metastasis to the stomach is regarded as distant metastasis and recorded as M1b (IM1-St).

444Note 1: The site of distant metastasis should be recorded as follows: lymph node (LYM), skin (SKI), liver (HEP), lung (PUL), bone marrow (MAR), bone (OSS), peritoneum (PER), pleura (PLE), brain (BRA), meninx (MEN), adrenal (ADR), and others (OTH).

445Note 2: Intramural metastasis to the stomach is regarded as distant metastasis and recorded as M1b (IM1-St).

446T, N, and M category and stage is recorded, e.g., T2N2M0, Stage IIIA.

447The stages are divided into two categories: clinical stage based on diagnostic imaging and pathological stage based on histological examination of the resected specimen.

448The staging of esophagogastric junction adenocarcinoma should conform to that of the Japanese Classification of Gastric Carcinoma (15th edition) (Tables 9 and 10). In the case of esophagogastric junction squamous cell carcinoma, the stage is used for thoracic esophageal squamous cell carcinoma.

4495.3.2 Description of lymph node dissection

450Two-field dissection:

451Thoracic and abdominal lymph nodes are dissected. The following lymph nodes must be removed: No. 101, 105, 106rec, 106tbl, 107, 108, 109, 110, 111, 112aoA, 112pul, 1, 2, 3, 7, 8a, 9, 11p (Dissection of No. 106tbl, 111, 8a, and 11p can be omitted).

452Three-field dissection:

453Cervical Note 1, thoracic, and abdominal lymph nodes are dissected. This is equivalent to two-field dissection plus cervical lymph node dissection.Note 1: Cervical lymph node dissection refers to the bilateral resection of No. 101, 102, and 104. Dissection No. 102 can be omitted. Dissection No. 101 can be performed from the thorax.Note 2: The extent of lymph node dissection should be described when typical lymph node dissection is not performed, e.g., thoracic and cervical lymph node dissection (in patients undergoing two-stage esophagectomy without abdominal lymph node dissection).

454Note 1: Cervical lymph node dissection refers to the bilateral resection of No. 101, 102, and 104. Dissection No. 102 can be omitted. Dissection No. 101 can be performed from the thorax.

455Note 2: The extent of lymph node dissection should be described when typical lymph node dissection is not performed, e.g., thoracic and cervical lymph node dissection (in patients undergoing two-stage esophagectomy without abdominal lymph node dissection).

456Based on the location of esophageal cancer, the degree of lymph node dissection is defined as follows.

457Cervical esophageal cancer (Ce)DX: Degree of lymph node dissection cannot be assessedD1: Less than D2 lymph node dissection is performedD2: Lymph nodes dissection of 100, 101, 102 mid, 104, 105, and 106rec are performed Note 1, 2D3: not applicable

458DX: Degree of lymph node dissection cannot be assessed

459D1: Less than D2 lymph node dissection is performed

460D2: Lymph nodes dissection of 100, 101, 102 mid, 104, 105, and 106rec are performed Note 1, 2

461D3: not applicable

462Note 1: Regarding nodes 105, 106recR, and 106recL, dissection of the nodes that can be resected from the neck is acceptable.Note 2: Although lymph node 102 is a regional node, lymph node dissection without lymph node 102 can be regarded as D2 lymph node dissection.

463Note 1: Regarding nodes 105, 106recR, and 106recL, dissection of the nodes that can be resected from the neck is acceptable.

464Note 2: Although lymph node 102 is a regional node, lymph node dissection without lymph node 102 can be regarded as D2 lymph node dissection.

465Thoracic esophageal cancer (Te)DX: Extent of lymph node dissection cannot be assessedD1: Incomplete dissection of two-field lymph nodesD2: Complete dissection of two-field lymph nodesD3: Complete dissection of three-field lymph nodes

466DX: Extent of lymph node dissection cannot be assessed

467D1: Incomplete dissection of two-field lymph nodes

468D2: Complete dissection of two-field lymph nodes

469D3: Complete dissection of three-field lymph nodes

470Esophagogastric junctional cancer (Jz)D1: Lymph node dissection of No. 1, 2, 3a, and 7Note 1D1 +: Lymph node dissection of No. 1, 2, 3a, 7, 8a, 9, and 11pNote 2D2: Lymph node dissection of No. 1, 2, 3a, 7, 8a, 9, 11p, 19, 20, and 110Note 3D3: Lymph node dissection of No. 1, 2, 3a, 7, 8a, 9, 11p, 19, 20, 105, 106recL, 106recR, 107, 108, 109L, 109R, 110, 111, 112aoA, and 112pulNote 4Note 1: The extent of D1 equals nodes with a ≥20% incidence of metastasis in a nationwide prospective study.Note 2: The extent of D1+ equals nodes with a ≥10% incidence of metastasis in a nationwide prospective study.Note 3: D2 lymph node dissection is recommended for patients with an esophageal invasion length of 2.1–4.0 cm.Note 4: D3 lymph node dissection is recommended for patients with an esophageal invasion length >4.0 cm.Note 5: When a total gastrectomy is performed, lymph nodes 3b, 4sa, 4sb, 4d, 5, and 6 are added to the extent of the lymph nodes described above.Note 6: In this edition, classification D is based on each surgical procedure. Lymph nodes 4sa and 4sb are excluded from lymph nodes that should be resected because they have a low frequency of metastasis based on a nationwide prospective study.

471D1: Lymph node dissection of No. 1, 2, 3a, and 7Note 1

472D1 +: Lymph node dissection of No. 1, 2, 3a, 7, 8a, 9, and 11pNote 2

473D2: Lymph node dissection of No. 1, 2, 3a, 7, 8a, 9, 11p, 19, 20, and 110Note 3

474D3: Lymph node dissection of No. 1, 2, 3a, 7, 8a, 9, 11p, 19, 20, 105, 106recL, 106recR, 107, 108, 109L, 109R, 110, 111, 112aoA, and 112pulNote 4

475Note 1: The extent of D1 equals nodes with a ≥20% incidence of metastasis in a nationwide prospective study.

476Note 2: The extent of D1+ equals nodes with a ≥10% incidence of metastasis in a nationwide prospective study.

477Note 3: D2 lymph node dissection is recommended for patients with an esophageal invasion length of 2.1–4.0 cm.

478Note 4: D3 lymph node dissection is recommended for patients with an esophageal invasion length >4.0 cm.

479Note 5: When a total gastrectomy is performed, lymph nodes 3b, 4sa, 4sb, 4d, 5, and 6 are added to the extent of the lymph nodes described above.

480Note 6: In this edition, classification D is based on each surgical procedure. Lymph nodes 4sa and 4sb are excluded from lymph nodes that should be resected because they have a low frequency of metastasis based on a nationwide prospective study.

481RX: Presence of residual tumor cannot be assessedNote 5R0: No residual tumorR1: Microscopic residual tumor (resection margin or radial margin)Note 2R2: Macroscopic residual tumor

482RX: Presence of residual tumor cannot be assessedNote 5

483R0: No residual tumor

484R1: Microscopic residual tumor (resection margin or radial margin)Note 2

485R2: Macroscopic residual tumor

486Note 1: Residual tumor should be evaluated for both primary tumor and metastatic lesions.Note 2: The R1 classification includes cases that are highly suspected of having microscopic residual tumors based on frozen sections or exfoliative cytology during the operation.Note 3: When multiple lesions were treated, R classifications are determined separately for each lesion.Note 4: In the case of piecemeal resection, the R classification should be evaluated after restructuring the specimen as much as possible. The pR0 of piecemeal resection is confirmed only when restructuring is possible and non-cancerous tissue is recognized at the resection margins of the restructured specimen.Note 5: RX Non-Cancerous cells cannot be confirmed on the margin because of the crushed or burned effect.Impossible restructuring the specimen because of a piecemeal resection.Suspected residual tumor due to the non-continuous tumor extension in the basal layer of the squamous epithelium.Possible residual tumor in the vertical margin because of intra-ductal spread.Indeterminable residual tumor because of other reasons.

487Note 1: Residual tumor should be evaluated for both primary tumor and metastatic lesions.

488Note 2: The R1 classification includes cases that are highly suspected of having microscopic residual tumors based on frozen sections or exfoliative cytology during the operation.

489Note 3: When multiple lesions were treated, R classifications are determined separately for each lesion.

490Note 4: In the case of piecemeal resection, the R classification should be evaluated after restructuring the specimen as much as possible. The pR0 of piecemeal resection is confirmed only when restructuring is possible and non-cancerous tissue is recognized at the resection margins of the restructured specimen.

491Note 5: RX

492Non-Cancerous cells cannot be confirmed on the margin because of the crushed or burned effect.

493Impossible restructuring the specimen because of a piecemeal resection.

494Suspected residual tumor due to the non-continuous tumor extension in the basal layer of the squamous epithelium.

495Possible residual tumor in the vertical margin because of intra-ductal spread.

496Indeterminable residual tumor because of other reasons.

497The specimen is extended and fixed immediately after resection on a corkboard or polystyrene foam and fixed in a sufficient volume of 10% neutral buffered formalin solution for at least half a day.

498The resected esophagus should be cut open along the longitudinal line on the opposite side of the lesion. Next, it should be gently stretched longitudinally and fixed such that the length of the specimen becomes similar to its size in vivo. Photographic recordings are necessary for both fresh and fixed specimens.

499The specimen is extended after resection on a corkboard or polystyrene foam and fixed in a sufficient volume of 10% neutral buffered formalin solution. The recommended fixation time is < 72 h.

500The formalin-fixed specimen should be treated with an iodine solution to confirm the unstained area and accurately recognize and record the macroscopic findings. This is important for the treatment of superficial carcinomas. Rinsing the sample with tap water for at least 30 min for endoscopically resected specimens and at least 1 h for surgically resected specimens will provide good staining conditions. To increase the contrast between the stained and unstained areas, the sample should be treated with a relatively low concentration (0.1–0.5%) of iodine solution for a long time.

501Cutting lines are defined as crossing lines at right angles to the tangent line at the resection margin closest to the tumor, and a whole resected specimen is cut into slices each at 2–3 mm thick.

502The resected specimen should be cut parallel to the long axis of the esophagus. Whole-step sections should be prepared for superficial cancer. A representative section of an advanced tumor at the site of the deepest invasion, parallel or perpendicular to the esophagus should be blocked and used for microscopic examination. The entire tumor should be cut into sections for macroscopic observation, and the adequate sections must be chosen for microscopic examination. The section of the proximal margin must be made parallel or perpendicular based on macroscopic findings. Schemas or photographs of the cut section sites should be preserved.