SPECIAL ARTICLE

Esophagus (2009) 6:125 Japan Esophageal Society and Springer 2009DOI 10.1007/s10388-009-0169-0

Japan Esophageal Society

Japanese Classifi cation of Esophageal Cancer, tenth edition: part I

PresidentKaiyo Takubo Tokyo Metropolitan Institute of Gerontology

Former PresidentHiroyasu Makuuchi Tokai University

English Edition Committee, ChairmanHiromasa Fujita Kurume University

English Edition Committee MembersTakashi Aikou Kagoshima UniversityYoshiaki Kajiyama Juntendo UniversityTatsuyuki Kawano Tokyo Medical and Dental UniversityHisahiro Matsubara Chiba UniversityKenji Nemoto Yamagata UniversityAtsushi Ohtsu National Cancer Center Hospital EastSoji Ozawa Fujita Health UniversityYutaka Shimada Toyama UniversityTadakazu Shimoda National Cancer Center HospitalYuji Tachimori National Cancer Center HospitalHarushi Udagawa Toranomon Hospital

English EditingJ. Patrick Barron Tokyo Medical University

Editorial AssistantsToshiaki Tanaka Kurume UniversityYukihiro Nakanishi National Cancer Center Research InstituteKazu Kaihara Tokyo Medical University

Japanese Edition Committee, ChairmanHiromasa Fujita Kurume University

Japanese Edition Committee MembersTakashi Aikou Kagoshima UniversityTatsuyuki Kawano Tokyo Medical and Dental University

These guidelines were published by Kanehara & CO., Ltd., Tokyo, copyright 2008 by Kanehara & CO., Ltd., and Japan Esophageal Society. They are reprinted here by permission of the copyright holders.

Japan Esophageal SocietySun-city Inohana B, 3-2-4 Inohana, Chuo-ku, Chiba 260-0856, Japan

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Hisahiro Matsubara Chiba UniversityKenji Nemoto Yamagata UniversityAtsushi Ohtsu National Cancer Center Hospital EastSoji Ozawa Fujita Health UniversityYutaka Shimada Toyama UniversityTadakazu Shimoda National Cancer Center HospitalYuji Tachimori National Cancer Center HospitalMasahiko Tsurumaru Juntendo UniversityHarushi Udagawa Toranomon HospitalMisao Yoshida Foundation for Detection of Early Gastric Carcinoma

Pathological Research Committee, ChairmanTadakazu Shimoda National Cancer Center Hospital

Pathological Research Committee MembersShingo Ishiguro Osaka Medical Center for Cancer and Cardiovascular DiseasesMasayuki Itabashi Ibaraki Prefectural Central HospitalAkinori Iwashita Fukuoka University Chikushi HospitalHiroshi Kato Ishikiriseiki HospitalTouichirou Takizawa Tokyo Medical and Dental UniversityKaiyo Takubo Tokyo Metropolitan Institute of GerontologyTakashi Yao Juntendo UniversityAkio Yanagisawa Kyoto Prefectural University of MedicineSuguru Yonezawa Kagoshima University

Endoscopy Research Committee, ChairmanMisao Yoshida Foundation for Detection of Early Gastric Carcinoma

Endoscopy Research Committee MembersMiwako Arima Saitama Cancer CenterMasayuki Itabashi Ibaraki Prefectural Central HospitalHaruhiro Inoue Showa University Northern HospitalHarushi Udagawa Toranomon HospitalMasamitsu Unakami Watari HospitalTai Ohmori Kawasaki Municipal HospitalTsuneo Oyama Saku Central HospitalHiroshi Kawachi Tokyo Metropolitan Cancer and Infectious Diseases Komagome HospitalTatsuyuki Kawano Tokyo Medical and Dental UniversityMorio Koike Bunkyo Gakuin UniversityHideo Shimada Tokai UniversityKaiyo Takubo Tokyo Metropolitan Institute of GerontologySetsuo Tamai Kanagawa Cancer CenterYukihiro Nakanishi National Cancer Center Research InstituteHiroyasu Makuuchi Tokai UniversityYouko Murata Murata ClinicKumiko Monma Tokyo Metropolitan Cancer and Infectious Diseases Komagome Hospital

Radiotherapy and Chemotherapy Research Committee, ChairmanYasumasa Nishimura Kinki University

Radiotherapy and Chemotherapy Research Committee MembersSatoshi Ishikura National Cancer Center Hospital EastAtsushi Ohtsu National Cancer Center Hospital EastHiroyuki Kato Gunma UniversityMichio Sato Tokyo Dental College Ichikawa General HospitalKenji Nemoto Yamagata UniversityKazuma Fujimoto Saga UniversityMiyako Myojin National Hospital Organization Hokkaido Cancer CenterTakashi Yoshioka Institute of Development, Aging and Cancer, Tohoku University

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Preface

The Japanese Society for Esophageal Diseases (JSED) was founded by Professor Komei Nakayama (19102005) of Tokyo Womens Medical College (now Tokyo Womens Medical University) and his colleagues in 1965 to gain a deeper understanding of esophageal diseases and improve the prognosis of esophageal malignancies. The scientifi c meeting of the JSED has been held usually twice a year for the last 38 years. In 2003, the JSED changed its name and organization to the Japan Esophageal Society (JES). Scien-tifi c meetings of the JES are held annually for 2 days. The JES has 2500 members, of whom about 1000 usually partici-pate in each annual meeting. The Society publishes an offi -cial quarterly English-language journal, Esophagus. Based on discussions at the JES scientifi c meetings, defi nitions of early and superfi cial carcinomas, the esophagogastric junc-tion, and subclassifi cation of the depth of superfi cial carci-noma have been decided. The fi rst edition of the Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esophagus (Guidelines) was published in 1969. In 2001, the 9th Japanese edition was translated into English and pub-lished for the fi rst time. The Japanese 10th edition was pub-lished in 2007 under the guidance of Professor Hiroyasu Makuuchi, the acting president at the 61st Annual Meeting of the JES. The present second English version -Japanese Classifi cation of Esophageal Cancer- (Japanese Classifi ca-tion) is a translation of the Japanese 10th edition.

For about 40 years, the presentations and discussions on esophageal diseases at the meetings of the JSED and JED have always been based on the common rules stipulated in the Guidelines, including stage, tumor type and histological classifi cation, and other criteria of esophageal carcinoma, and these are now the standard criteria used among Japa-nese hospitals. On the basis of the Guidelines, the Compre-hensive Registry was started in 1988, and in 2004 this was made available on the website of the Japan Esophageal Society (http://www.esophagus.jp/). All descriptions in the Comprehensive Registry were recorded on the basis of the Guidelines. The activities of the JES contribute to the well-being of patients with esophageal diseases.

We hope that the Japanese Classifi cation will be used worldwide to bring about improvements in all aspects of diagnosis, treatment and care of patients with esophageal diseases.

Nov. 30, 2007Kaiyo Takubo, MD

PresidentThe 62nd Annual Meeting of the Japan Esophageal Society

Hiroyasu Makuuchi, MDPresident

The 61st Annual Meeting of the Japan Esophageal SocietyHiromasa Fujita, MD

Chairperson Committee of the Guidelines for Clinical and

Pathologic Studies on Carcinoma of the Esophagus, the Japan Esophageal Society

Preface of the Ninth Edition

This edition of the English Version of the Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esoph-agus corresponds to the Japanese Version of the 9th edition published in February 1999.

The major points of emphasis in this edition are:

1) Renewal of the descriptions of lymph node metastases consequently accompanied by modifi cation of stages.

2) Improved compatibility with the TNM classifi cation by changing the abbreviation of the depth of tumor inva-sion from A to T and the term respectability to residual tumor or R

3) Partial revision of the pathological classifi cation accord-ing to the revision of the clinical classifi cation

The English version of the Guidelines is intended mainly for international use. The new Revision may be somewhat too complicated for ready familiarization, especially as to the classifi cation of lymph nodes and related subjects. Along with progress of the treatment for carcinoma of the esopha-gus, however, the anatomical structure and pathophysiolog-ical picture of carcinoma of the esophagus has become clearer in detail. The Guidelines describe these changes as accurately as possible.

Selection of the method of treatment based on the Guidelines should improve treatment results. It is my wish that these Guidelines will become familiar to all esophageal specialists around the world.

Finally, the dedicated efforts of committee members which have made the publication of this Revision possible are deeply appreciated.

July, 2001Kaichi Isono, M.D.

President,Japanese Society for Esophageal Diseases

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Contents

PrefaceGeneral Principles of this EditionAbbreviations

Part I General Rules 1. Purpose, Object, and Methods of Descriptions 1.1. Purpose 1.2. Object 1.3. Methods of Descriptions 2. Clinical Aspects 2.1. Description of Primary Tumor 2.2. Metastatic Lesions from Esophageal Cancer 2.3. Stage 2.4. Multiple Primary Cancers 3. Surgical Aspects 3.1. Handling of the Resected Specimen 3.2. Description of Surgical Findings and Macroscopic Findings of Primary Tumor 3.3. Intramural Metastasis and Multiple Cancers of the Esophagus 3.4. Lymph Nodes 3.5. Distant Organ Metastasis (M) 3.6. Residual Tumor (R) 3.7. Curativity (Cur) 4. Pathological Findings 4.1. Handling of the Surgically Resected Specimens 4.2. Description of Pathological Findings 4.3. Lymph Node Metastasis (pN) 4.4. Distant Organ Metastasis (pM) 4.5. Residual Tumor (pR) 4.6. Curativity (pCur) 5. Endoscopic Treatment 5.1. Handling of Specimens Resected Endoscopically 5.2. Macroscopic Findings 5.3. Preparation for Pathological Examination 5.4. Description of Pathological Findings 5.5. Curativity (Cur) 5.6. Comprehensive Evaluation of Curativity 6. Barrett Esophagus and Adenocarcinoma in Barrett Esophagus 6.1. Defi nition and Methods of Description for Barrett Mucosa, Barrett Esophagus and Adenocarcinoma in Barrett

Esophagus 6.2. Tumor Location 6.3. Description of Tumors 6.4. Stage

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General Principles of this Edition

Since 1969, when the fi rst edition of the Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esoph-agus was published by the Japanese Society for Esophageal Diseases, it has been constantly revised giving consideration to consistency with the TNM classifi cation and Japanese Classifi cation concerning other gastrointestinal cancers along with progress in the diagnosis and treatment of esoph-ageal cancer. The Japan Esophageal Society (formerly the Japanese Society for Esophageal Diseases) continues to publish the Japanese Classifi cation of Esophageal Cancer in English. The major revisions in this 10th Edition are as follows;

This version is divided into two parts; the General Rules and the Explanations

1.3. Methods of DescriptionsAll symbols are described using upper case letters, and the extent is also denoted by largefont Arabic numbers.The clinical, surgical, pathological, and fi nal fi ndings are expressed by c, s, p, and f, respectively.2.1.2. Tumor LocationThe zone of the esophagogastric junction is defi ned, and diagnostic methods at the esophagogastric junction are described.2.1.3. Macroscopic Tumor TypeThe macroscopic tumor types are expressed by the macro-scopic tumor type classifi cation and the sub-classifi cation for the superfi cial types.The unclassifi ed type (type 5) is divided into the unclassifi -able type without treatment (5a), and that after treatment (5b).The superfi cial and protruding type (0-I) is sub-classifi ed into the pedunculated type (0-Ip) and the sessile type (0-Is).In the mixed type, the lesion is described in the order of the size, and the deepest lesion is enclosed by double quotation marks.2.1.4. Depth of Tumor InvasionThe mucosal layer (T1a) is sub-classifi ed into three layers.The submucosal layer (T1b) is sub-classifi ed into three layers.The defi nition of early esophageal cancer is changed. It is defi ned as a lesion localized within the mucosal layer of the esophagus. The presence of metastatic lymph nodes is not referred to.2.2.1. Lymph Node MetastasisThe locations of the cervical and thoracic lymph nodes are the same as those in the English version of the 9th edition.The computed tomography images of the lymph nodes were added.The lymph node grading in the cervical esophagus was changed, and divided into that for cervical esophageal cancer with (CePh) or without (Ce) involvement of the hypopharynx.

The classifi cation of lymph nodes in the abdominal esopha-gus was revised.The lymph node grading for cancers at the esophagogastric junction which has two gradings for the esophagus-dominant tumor (EG) and for stomach-dominant tumor (GE) is established. The lymph node grading for cancer at the esophagogastric junction of the esophagus-dominant tumor (EG) is the same as that for cancer in the abdominal esophagus.2.4. Multiple Primary CancersMultiple primary cancers of the esophagus and multi-organ primary cancers including the esophagus are defi ned.3. Surgical AspectsMacroscopic fi ndings of the resected specimens are included in surgical fi ndings.3.2.5. Radial MarginThe abbreviation for the radial margin of the resected speci-mens is RM.3.4.3. Lymph Node DissectionCervical lymph node dissection only of the cervical parae-sophageal nodes (No. 101) is not included in three-fi eld dissection.3.6. Residual TumorDefi nition of microscopic residual tumor R1 is revised. R1 is not defi ned as histopathologically confi rmed residual tumor, but as suspected or minute residual tumor.3.7. CurativityThe assessment of curativity in transhiatal esophagectomy is revised.4.2.1. Histological Classifi cationAll esophageal tumors and tumor-like lesions, either malig-nant or benign are described.Intraepithelial neoplasia is defi ned. Reactive changes accom-panying infl ammation and regeneration are excluded.Intraepithelial neoplasia is classifi ed into low grade intraep-ithelial neoplasia and high grade intraepithelial neoplasia. The defi nition of high grade intraepithelial neoplasia is almost identical to that of carcinoma in situ.Malignant epithelial tumors are classifi ed into squamous cell carcinoma, basaloid (-squamous) carcinoma, carcinosar-coma, adenocarcinoma, adenosquamous carcinoma, muco-epidermoid carcinoma, adenoid cystic carcinoma, endocrine cell carcinoma, undifferentiated carcinoma, and others.Endocrine cell carcinoma is defi ned. Most small cell carci-nomas are included in this category.Non-epithelial tumors are classifi ed into smooth muscle tumor, gastrointestinal stromal tumor (GIST), neurogenic tumor, and others. The defi nition of GIST is established, and its histological risk criteria presented.5. Endoscopic TreatmentThe methods for handling and excising endoscopically-resected specimens are described.The submucosal layer is classifi ed into two layers: the shal-lower layer up to 200 m from the lower margin of the muscularis mucosa and the layer deeper than 200 m.The assessment of clinical (endoscopically recognizable) residual tumor is defi ned. The abbreviations for the hori-zontal margin (HM) and the vertical margin (VM) are established. The criteria of impossible assessment of the

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residual tumor in the resected margin (pRX) are defi ned.Curativity, and the assessment of curative or non-curative resection in cases of endoscopic treatment are defi ned.6. Barrett Esophagus and Adenocarcinoma in Barrett EsophagusThe assessment methods of the esophagogastric junction are established.Barrett mucosa, Barrett esophagus, and adenocarcinoma in Barrett esophagus are defi ned.The macroscopic tumor types are classifi ed in a manner similar to those of esophageal carcinoma.The method of deciding the depth of tumor invasion for adenocarcinoma in Barrett esophagus is defi ned.7.1. Endoscopic TreatmentsVarious kinds of endoscopic treatments are described.7.2. Surgical TreatmentsPlanned surgery and salvage surgery are defi ned.7.3. StentingVarious types of stenting are described.

7.4. Common Issues for Radiotherapy and ChemotherapyCondition of the target lesion, purpose of treatment, and reasons for selection of method(s) for curative treatment are defi ned.7.7. Multi-modality TreatmentMulti-modality treatments are defi ned.8.8.2. Period and Rate of Esophageal PreservationPeriods and rates of esophageal preservation are defi ned.8.9. Terminology Related to Survival PeriodThe terminology related to survival period is defi ned.PartIII. Response Evaluation Criteria in Radiotherapy and Chemotherapy for Esophageal CancerBased on the Response Evaluation Criteria in Solid Tumors (RECIST), the guidelines to evaluate the response to radio-therapy, chemotherapy and chemoradiotherapy for esopha-geal cancers are established.OthersImportant references, tables of abbreviations and an index are added.

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Abbreviations

AD adventitiaAe abdominal esophagusAI Invasion to the adjacent structuresAPC argon plasma coagulationB tracheal bifurcationc clinical fi ndingsCe cervical esophagusCR complete responseCRT chemoradiotherapyCT chemotherapyCTV clinical target volumeCur curativityD lymph node dissectionDFS disease-free survivalDM distal marginDMM deep muscularis mucosaE esophagusEG tumor located in the esophageal sideEGJ esophagogastric junctionEMR endoscopic mucosal resectionEP epitheliumER endoscopic resectionESD endoscopic submucosal dissectionf fi nal fi ndingsG stomachGE tumor located in the gastric sideGIST gastrointestinal stromal tumorH esophageal hiatusHM horizontal marginIM intramural metastasisINF infi ltrative growth patternIR/SD incomplete response/stable diseaseIT immunotherapyLN lymph nodeLPM lamina propria mucosaLSBE long segment Barrett esophagusLaser laser therapyLt lower thoracic esophagusly lymphatic invasionly/v vascular invasionM distant organ metastasisMCT microwave coagulation therapyMFH malignant fi brous histiocytomaMM muscularis mucosaMP muscularis propriaMST median survival timeMt middle thoracic esophagusN lymph node metastasis

O esophageal orifi ceOS overall survivalp pathological fi ndingsPD progressive diseasePDT photodynamic therapyPFS progression free survivalPh pharynxPM proximal marginPR partial responseR residual tumorRECIST Response Evaluation Criteria in Solid TumorsRFS relapse/recurrence-free survivalRM radial marginRT radiotherapys surgical fi ndingsS superior margin of the sternumSCE specialized columnar epitheliumSCJ squamocolumnar junctionSD stable diseaseSM submucosaSMM superfi cial muscularis mucosaSSBE short segment Barrett esophagusT depth of tumor invasionTe thoracic esophagusTis carcinoma in situTT thermotherapyTTF time to treatment failureTTP time to progressionUt upper thoracic esophagusv venous invasionVM vertical marginX cannot be assessed

Terminology of the lymph nodesR rightL leftsm submandibularspf superfi cialac accessorytr trachealup uppermid middlerec recurrent nervetb tracheobronchialpre pretrachealao paraaorticpul pulmonary ligament

Number of the lymph nodesa: 13, b: 47, c: 8

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Part 1General Rules

1. Purpose, Object, and Methods of Descriptions

1.1. Purpose

The Guidelines for the Clinical and Pathologic Studies on Carcinoma of the Esophagus was originally published in 1969 by the then Japanese Society for Esophageal Diseases. Since then, the Society has changed its name in 2003 to become the Japan Esophageal Cancer Society, and has pub-lished the Japanese Classifi cation of Esophageal Cancer in Japanese with some revisions to keep up to date with treatment results and to provide a standard nomenclature. To promote the international use of the Guidelines and the Classifi cation, the Society is publishing this handbook in English entitled The Japanese Classifi cation of Esopha-geal Cancer.

1.2. Object

The term esophageal cancer in the Japanese Classifi cation refers to cancer originating in the esophagus, and cancer metastatic to the esophagus is excluded.All primary malignant tumors in the esophagus, including cancer, should be described according to the Japanese Classifi cation.

1.3. Methods of Descriptions

1.3.1. Principles of Descriptions and Abbreviations

Findings are recorded using upper-case letters T (depth of tumor invasion), N (lymph node metastasis) and M (distant

organ metastasis). The extent of each fi nding is expressed by Arabic numerals following each upper-case letter. X is used in unknown cases. Four categories of fi ndings, namely Clinical, Surgical, Pathological, and Final fi ndings, are identifi ed using the lower case c, s, p, and f, respectively, before each upper case letter. The f of Final fi ndings can be omitted (Table 1-1, Table 1-2).The order of clinicopathological description is:Tumor location, tumor length, macroscopic tumor type, his-tological type (when identifi ed), depth of tumor invasion, lymph node metastasis, distant organ metastasis and stage.e.g.: Mt, 5 cm, Type 2, moderately differentiated squamous cell carcinoma, pT3, pN2, sM0, fStage III

The order of pathological description is:Tumor location, tumor length, macroscopic tumor type, his-tological type, depth of tumor invasion, pattern of infi ltra-tion, lymphatic invasion, venous invasion, intramural metastasis, involvement of the resection margins (proximal margin, distal margin, and radial margin), multiple primary cancers, effects of radiation and/or anticancer chemother-apy, lymph node metastasis, distant organ metastasis, and stage.e.g.: Mt, 5 cm, Type 2, moderately differentiated squamous cell carcinoma, pT3, INFa, ly1, v1, IM0, pPM0, pDM0, pRM0, multiple primary carcinomas (present, one lesion), CRT-grade 2, pN1 (2/30), sM0, fStage IIIe.g.:Tracheal invasion was observed from clinical fi ndings;cT4, cN2, cM0, cStage IVaAs the tumor responded to chemoradiotherapy, surgery was performed;CRT-sT3, sN2, sM0, sStage IIIAlthough the tumor completely responded to chemoradio-therapy on pathological fi ndings, metastasis to Group 3 lymph nodes was observed;CRT-pT0 (T3), pN3, sM0, pStage IIIFinal fi ndings;(f) T4, (f) N3, (f) M0, (f) Stage IVa

Note: In cases in which any fi ndings are modifi ed by combined treatment, fi ndings should be recorded as the estimated most advanced condition throughout the treatment.

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2. Clinical Aspects

2.1. Description of Primary Tumor

2.1.1. Number of Primary Tumors, Size and Circumferential Location

Maximal longitudinal dimension (mm), transverse dimen-sion (mm) and circumferential ratio of the tumor to the entire esophagus should be described. In addition, the methods of diagnosis such as barium swallow, endoscopy and endoscopic ultrasonography are to be recorded.

2.1.2. Tumor Location

2.1.2.1. Anatomical Defi nition of the EsophagusThe esophagus is defi ned anatomically from the esophageal orifi ce to the esophagogastric junction. The esophageal orifi ce is at the lower margin of the cricoid cartilage. The identifi cation of the esophagogastric junction (EGJ) will be described later.

2.1.2.2. Anatomical Regions (Subsites) of the EsophagusThe esophagus lies between the hypopharynx and stomach, and can be anatomically divided into the following portions; cervical esophagus (Ce), thoracic esophagus (Te) and abdominal esophagus (Ae). The zone of the esophagogas-tric junction is divided into the esophageal side (E) and gastric side (G) (Figure 1-1).Note

Cervical esophagus (Ce): This extends from the esophageal orifi ce to the sternal notch

Thoracic esophagus (Te): From the sternal notch to the superior margin of the esophageal hiatus

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 thoracic part of the distal half of the two equal portions between the tracheal bifurcation and the esophagogastric junctionAbdominal esophagus (Ae): The abdominal part of the distal half of the two equal portions between the tracheal bifurcation and the esophagogastric junction (from the superior margin of the esophageal hiatus to the esopha-gogastric junction)

Note: The zone of the esophagogastric junction is defi ned as the region between 2 cm in esophagus and 2 cm in the stomach from the esophagogastric junction. The abdomi-nal esophagus is included in this zone.

2.1.2.3. Principles of Description of Tumor LocationWhen the tumor extends continuously in more than one portion of the esophagus, the main tumor location is that with the deepest tumor invasion. If it is diffi cult to deter-mine the site of deepest tumor invasion, the portion at the central point of the tumor can be recorded as the main tumor location.In the case of multiple primary lesions, the locations of the lesions are described in the order of depth of tumor inva-

Note: Findings modifi ed by treatment methods other than surgery are abbreviated as follows;Radiotherapy: RT-, Chemotherapy: CT-, Chemoradiotherapy: CRT-, Endoscopic mucosal resection: EMR-, Endoscopic submucosal dissec-tion: ESD-, Laser therapy: Laser-, Photodynamic therapy: PDT-

Fig. 1-1 Tumor location and anatomical esophageal nomenclatureO: esophageal orifi ceS: superior margin of the sternumB: tracheal bifurcationD: diaphragmEGJ: esophagogastric junctionH: esophageal hiatus

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sion. The deepest lesion is described fi rst. If it is diffi cult to determine the order of the depth, the description order depends on the size of the area occupied by the lesion. The largest lesion is described fi rst.e.g.: MtLt, LtAeG

2.1.3. Macroscopic Tumor Type

2.1.3.1. Principles of Tumor Type Classifi cationThe tumor type classifi cation is based on the macroscopic fi ndings. Radiological and endoscopic classifi cations are based on the macroscopic classifi cation.Tumors in which invasion is macroscopically diagnosed to be limited to within the submucosa are classifi ed as super-fi cial type, while tumors in which invasion is diagnosed to extend to the muscularis propria or beyond are classifi ed as advanced type. The superfi cial type has the prefi x 0 and is classifi ed into 0-I, 0-II or 0-III. The advanced type is divided into 4 categories: 1, 2, 3, or 4. When a tumor cannot be classifi ed into any of the 5 (04) categories or their combi-nations, it is classifi ed as 5.

2.1.3.2. Macroscopic Classifi cation (Figure 1-2) Note 1

Type 0 Superfi cial typeType 1 Protruding typeType 2 Ulcerative and localized typeType 3 Ulcerative and infi ltrative typeType 4 Diffusely infi ltrative typeType 5 Unclassifi able type

Type 5a Unclassifi able type without treatmentType 5b Unclassifi able type after treatment Notes 1, 2

Note 1: The macroscopic tumor type before chemother-apy and/or radiotherapy is described. Previous treatment is indicated. Cases with minor changes following treat-ment and which fi t the macroscopic tumor type(s) are classifi ed as type 14 and cases of major changes are designated as unclassifi able type.Note 2: Any former treatment(s) is mentioned before the macroscopic tumor type.e.g.: CT-3, CRT-5b, EMR-0-IIc

2.1.3.3. Subclassifi cation of Superfi cial Type (type 0)

Type 0-I Superfi cial and protruding typeType 0-Ip Pedunculated typeType 0-Is Sessile (broad based) type

Type 0-II Superfi cial and fl at typeType 0-IIa Slightly elevated typeType 0-IIb Flat typeType 0-IIc Slightly depressed type

Type 0-III Superfi cial and excavated type

Other notationsNote 1: Combined type: When multiple macroscopic tumor types are mixed in one lesion, it is called a com-bined type. The wider type is described fi rst and types are connected with+. Double quotation marks ( ) are placed around the macroscopic tumor type that has the deepest tumor invasion. In this case, the main macroscopic tumor type is the deepest one. However, when an advanced type is mixed, the most advanced type is described fi rst and double quotation marks are unnecessary.e.g.: 0-IIc+ 0-Is, 3+0-IIcNote 2: Superfi cial spreading type: superfi cial type 0-IIc which extends 5 cm or more longitudinally. It may be noted additionally in the macroscopic tumor type.

[Reference]Japanese Society for Esophageal Diseases. Guidelines for the Clinical

and Pathologic Studies on Carcinoma of the Esophagus (in Japa-nese). 8th ed. Kanehara Shuppan, Tokyo, 1992; 34.

2.1.4. Depth of Tumor Invasion (T)

TX Depth of tumor invasion cannot be assessedT0 No evidence of primary tumor

T1a Tumor invades mucosa Note 1

T1a-EP Carcinoma in situ (Tis)T1a-LPM Tumor invades lamina propria mucosa (LPM)T1a-MM Tumor invades muscularis mucosa (MM)

T1b Tumor invades submucosa (SM) Notes 2,3,4

SM1 Tumor invades the upper third of the submucosal layer

SM2 Tumor invades the middle third of the submucosal layer

SM Tumor invades the lower third of the submucosal layer

Fig. 1-2 Macroscopic classifi -cation (Type 04)

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T2 Tumor invades muscularis propria (MP)T3 Tumor invades adventitia (AD)T4 Tumor invades adjacent structures (AI) Notes-5,6,7

Note 1: Early esophageal cancer: T1a can be designated as early cancer of the esophagus regardless of the pres-ence or absence of lymph node or distant organ metastasis.e.g.: early esophageal cancer: T1aNxMxNote 2: Superfi cial esophageal cancer: T1a and T1b are designated as a superfi cial cancer regardless of lymph node or distant organ metastasis.e.g.: superfi cial esophageal cancer: T1NxMxNote 3: Formerly-used subclassifi cation of superfi cial type generally corresponds to the following.m1: T1a-EP, m2: T1a-LPM, m3: T1a-MM, sm1: SM1, sm2: SM2, sm3: SM3Note 4: In endoscopically resected specimens, a tumor invading the submucosa to a depth of 200m or less from the lamina muscularis mucosa is classifi ed as SM1, while a tumor extending more than 200m is classifi ed as SM2.Note 5: Lesions invading the mediastinal pleura beyond the extent of the primary tumor are classifi ed as T4.Note 6: Invaded organs such as the pericardium, aorta, vena cava, trachea, lung, diaphragm, thoracic duct, recur-rent laryngeal nerve, azygos vein should be recorded.e.g.: T4 (lung)Note 7: If a metastatic lymph node invades an organ other than the esophagus, that should also be classifi ed as T4, and it should be recorded as T4 (metastatic node number-invaded organ.e.g.: T4 (No. 108-lung)

[Reference]Japan Esophageal Society. Guideline\s for Diagnosis and Treatment

of Esophageal Cancer (in Japanese). 2nd ed. Kanehara Shuppan, Tokyo, 2007.

2.2. Metastatic Lesions from Esophageal Cancer

2.2.1. Lymph Node Metastasis

2.2.1.1. Naming and Numbers of Lymph Node StationsThe names and numbers of lymph nodes are defi ned as shown in Table 1-3 and Figure 1-4.

Fig. 1-3 Subclassifi cation for superfi cial cancer (modifi ed from the Guidelines for Esophageal Cancer Treatment)

Fig. 1-4 Station numbers of regional lymph nodes

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The stations of cervical and thoracic lymph nodes are shown in Figures 1-5 to 1-7.The names and numbers of abdominal lymph node stations are defi ned in the Japanese Classifi cation of Gastric Carcinoma.

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

[Reference]Japanese Gastric Cancer Association. Japanese Classifi cation of

Gastric Carcinoma. 13th ed. Kanehara Shuppan, Tokyo, 1999.

2.2.1.2. Lymph Node GroupsLymph node groups are defi ned according to the location of the tumor as shown in Table 1-4 and Figures 1-8 to 1-14.

Note: In deciding the lymph node group of multiple esophageal cancers and widely extending esophageal cancer, the location of the deepest tumor invasion takes precedence in documentation.

2.2.1.3. Grading of Lymph Node Metastasis (N)

NX Lymph node metastasis cannot be assessedN0 No lymph node metastasisN1 Metastasis involving only Group 1 lymph nodesN2 Metastasis to Group 2 lymph nodes, regardless of

involvement of Group 1 lymph nodesN3 Metastasis to Group 3 lymph nodes, regardless of

involvement of Group 1 or 2 lymph nodesN4 Metastasis to distant (Group 4) lymph nodes, regard-

less of whether any other group(s) of regional lymph nodes are involved or not

Note: The left or right side of lymph nodes location should be recorded using a number plus L or R.

Table 1-3 Numbers and Naming of Regional Lymph Nodes

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Fig. 1-5 Superfi cial cervical lymph nodes Fig. 1-6 Deep cervical lymph nodes(Right view of the trachea) (Posterior view of the trachea)

Fig. 1-7 Tracheobronchial lymph nodes

Note 2: Pleural, peritoneal, and pericardial dissemination should be recorded as M1.

2.3. Stage (Table 1-5)

The stage should be recorded based on the following TNM stage classifi cation.e.g.: T2N2M0, Stage III

2.2.2. Distant Organ Metastasis (M)

MX Distant organ metastasis cannot be assessedM0 No distant organ metastasisM1 Distant organ metastasis

Note 1: Organs with metastasis should be recorded in parentheses.e.g.: M1 (lung), M1 (liver, stomach)

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Note 1: Cancer at the esophagogastric junction should be classifi ed as EG or GE. If the center of a tumor is located exactly at the esophagogastric junction, and if it is squamous cell carcinoma, it is defi ned as EG, and if it is adenocarcinoma it is defi ned as GE.Note 2: Lymph node grading in EG tumors is the same as in Ae tumors.Note 3: The D Category is not affected by excision or non-excision of lymph nodes in parentheses.

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Fig. 1-8 Lymph node groups for tumors located in CePh

Fig. 1-9 Lymph node groups for tumors located in Ce

Fig. 1-10 Lymph node groups for tumors located in Ut

Fig. 1-11 Lymph node groups for tumors located in Mt

Fig. 1-12 Lymph node groups for tumors located in Lt

Fig. 1-13 Lymph node groups for tumors located in Ae (EG)The D category is not affected by excision or non-excision of lymph nodes designated by*.

Fig. 1-14 Lymph node groups for tumors located in GEThe D category is not affected by excision or non-excision of these lymph nodes designated by*.

17

2.4. Multiple Primary Cancers

Multiple primary cancers of the esophagus:The term multiple primary cancers of the esophagus is used to refer to the presence of two or more primary esoph-ageal cancers.

Note: The description of location of multiple primary cancers of the esophagus should be made in the order of the depth of tumor invasion (deeper to shallower) insert-ing / between the abbreviations of the location of each lesion, and the total number of lesions should be recorded in parentheses.e.g.: MtUt/Lt/Lt (3 lesions)

Multi-organ primary cancers including the esophagus:The term multi-organ primary cancers including the esophagus is used to refer to the presence of one or more primary malignant diseases other than esophageal cancer in a patient with primary esophageal cancer.Multiple primary cancers including the esophagus:The term multiple primary cancers including the esopha-gus indicates the concept combining both multiple primary cancers of the esophagus and multi-organ primary cancers including the esophagus.

Note 1: In cases of multi-organ primary cancers including the esophagus, the organ other than the esophagus should be specifi ed in parentheses.Note 2: Whether the multiplicity is synchronous or meta-chronous should be recorded.e.g.: Multi-organ primary cancers: stomach (synchronous)

3. Surgical Aspects

3.1. Handling of the Resected Specimen

The resected esophagus should be cut and opened along the longitudinal line on the side opposite to the lesion. The opened esophagus should be gently stretched longitudinally and fi xed so that the length of the specimen becomes similar to its size in vivo.The specimen should be treated with iodine solution after fi xation in order to accurately describe the macroscopic fi ndings. This is particularly important in superfi cial carci-noma. Photographic recording is recommended for both fresh and fi xed specimens.

3.2. Description of Surgical Findings and Macroscopic Findings of Primary Tumor

Operative fi ndings should be identifi ed in the record putting

18

Fig. 1-16 How to cut specimens surgically resected

Fig. 1-15 Tumor size and the dis-tance from resection margin to tumora. greatest longitudinal dimen-sion (mm)b. greatest transverse dimension (mm)

Fig. 1-17 Histological effi cacy of chemotherapy and/or radiother-apy Japanese Gastric Cancer Association: Japanese Classifi ca-tion of Gastric Carcinoma (in Japanese). 13th ed. Kanehara Shuppan, Tokyo, 1999; 27.

Fig. 1-18 How to cut specimens endoscopically resected

IMX Intramural metastasis cannot be assessed.IM0 No intramural metastasisIM1 Intramural metastasis

Note: IM in the gastric wall should be recorded as IM1-St. It is classifi ed as organ metastasis (M1).

3.3.2. Multiple Cancers of the Esophagus

Multiple cancers are two or more primary cancer lesions separate from each other. Multiple cancers and IM should be clearly differentiated in the description.

3.4. Lymph Nodes

3.4.1. Preparation of Resected Lymph Nodes for Pathological Examination

Surgically dissected lymph nodes are classifi ed according to the defi nition of regional lymph nodes, given individual names or numbers and sent to pathologists. The lymph nodes dissected en bloc with the esophagus should be iso-lated from the specimen before fi xation.

3.4.2. Grading of Lymph Node Metastasis (N)

The surgical diagnosis of the grading of lymph node metas-tasis (sN) should be made comprehensively with intraoper-ative fi ndings of macroscopic observation, imaging examinations, immediate pathological diagnosis with frozen

section, and macroscopic fi ndings obtained during postop-erative preparation.

3.4.3. Lymph Node Dissection (D)

3.4.3.1. Field of Lymph Node Dissection

Three-fi eld dissection Dissection through cervical inci-sion, thoracotomy, and laparot-omy Note

Two-fi eld dissection Dissection through thoracotomy and laparotomy

Dissection through cervical incision and laparotomyDissection through cervical incision and thoracotomyOne-fi eld dissection Dissection through a single

operative fi eld, i. e., cervical incision, thoracotomy or laparotomy

Note: The term three-fi eld dissection should not be applied when only the cervical paraesophageal nodes (101R, 101 L) are dissected in the neck.

3.4.3.2. Extent of Lymph Node Dissection (D)DX Extent of lymph node dissection cannot be assessed.D0 No or incomplete dissection of Group-1 lymph

nodesD1 Complete dissection of Group-1 lymph nodes but no

or incomplete dissection of Group-2 lymph nodesD2 Complete dissection of Group-1 and Group-2 lymph

nodes, but no or incomplete dissection of Group-3 lymph nodes

D3 Complete dissection of Group-1, Group-2 and Group-3 lymph nodes

19

3.5. Distant Organ Metastasis (M)

Surgical fi ndings of distant organ metastasis (sM) should be determined through comprehensive consideration of opera-tive macroscopic fi ndings, intraoperative imaging examina-tions such as intraoperative ultrasound examination, macroscopic observation of resected specimen, and intra-operative immediate pathological diagnosis with frozen section. Whether the distant organ metastasis was resected or not should be recorded.

3.6. Residual Tumor (R) Note 1

RX Residual tumor cannot be assessed.R0 No residual tumorR1 Microscopic residual tumor Note 2

R2 Macroscopic residual tumor Note 3

Note 1: The postoperative state of both primary tumor and metastatic lesions should be evaluated.Note 2: This means that the presence of residual tumor is strongly suspected but very small in amount.Note 3: This means that the amount of residual tumor is macroscopically obvious.

3.7. Curativity (Cur) (Table 1-6)

Cur A Complete removal of the tumor is strongly believed.

sStage 0III, and sR0, and sD > sNCur B Neither Cur A nor Cur C R1 sStage IV (T4, M1) or sDsN, but R0 was

achieved with resection of a T4 tumor or com-plete removal of metastatic tumor (M1) or lymph nodes.

Cur C R2, i. e., M1 evident residual tumor in distant organ(s) (M1), lymph nodes, or surgical margin(s) (PM1, DM1, RM1).

4. Pathological Findings

4.1. Handling of the Surgically Resected Specimens

The resected specimen should be cut parallel along the long axis of the esophagus. Whole step sections are made in superfi cial type cancer. One representative section of an advanced tumor at the site of deepest invasion, parallel or

perpendicular to the esophagus should be blocked and used for microscopic examination. Schemas or photographs of the sites of cut sections should be preserved.

4.2. Description of Pathological Findings

The p (pathology) mark is prefi xed to the pathological fi nd-ings except for vascular invasion as follows.e.g.: p0-Is, pType 2, pT2, pStageII

4.2.1. Histological Classifi cation

4.2.1.1. Benign Epithelial Neoplasms1. Squamous cell papilloma2. Adenoma3. Others

4.2.1.2. Intraepithelial Neoplasias

1. Squamous intraepithelial neoplasiaa. Low grade intraepithelial neoplasiab. High grade intraepithelial neoplasia (Carcinoma in

situ)2. Columnar intraepithelial neoplasia

4.2.1.3. Malignant Epithelial Neoplasms 1. Squamous cell carcinoma

a. well-differentiated typeb. moderately-differentiated typec. poorly-differentiated type

2. Basaloid (-squamous) carcinoma 3. Carcinosarcoma 4. Adenocarcinoma

a. well-differentiated typeb. moderately-differentiated typec. poorly-differentiated type

5. Adenosquamous carcinoma 6. Mucoepidermoid carcinoma 7. Adenoid cystic carcinoma 8. Endocrine cell tumor

a. Carcinoid tumorb. Endocrine cell carcinoma

9. Undifferentiated carcinoma10. Others

4.2.1.4. Non-epithelial Tumors1. Smooth muscle tumor2. Gastrointestinal stromal tumor (GIST)3. Neurogenic tumor

Schwannoma, Neurofi broma, Granular cell tumor

20

4. OthersHemangioma, Lymphangioma, Lipoma, et al.

4.2.1.5. Lymphoid TumorsThe defi nition is according to the WHO classifi cation.

[Reference]Jaffe ES, Harris NL, Stein H, et al. WHO Classifi cation of Tumours.

Pathology and Genetics of Tumours of Haematopoietic and Lym-phoid Tissues. IARC Press, Lyon, 2001.

4.2.1.6. Other Malignant Tumors1. Malignant melanoma2. Others

4.2.1.7. Tumor-like LesionsEctopic gastric mucosaHeterotopic sebaceous glandCowden diseaseGlycogenic acanthosis

4.2.2. Depth of Tumor Invasion (pT) Note 17

Note 1: Intraductal spreading of cancer is categorized as pT1a, and if the tumor invades beyond the duct of the esophageal gland, the depth of tumor invasion is defi ned as the layer presenting extraductal invasion of cancer.Note 2: The vertical depth of sm invasion is measured from the muscularis mucosa, and the depth is recorded in parentheses.e.g.: pSM2 (400m)Note 3: The depth of tumor invasion is defi ned histologi-cally as the point of deepest direct invasion by the primary tumor. Vascular invasion within the confi nes of the primary tumor should be regarded as the depth of direct tumor invasion. However if vascular invasion is found outside the confi nes of the primary tumor, the depth of such invasion should be specifi ed in parentheses after the depth of direct invasion. For example, when a primary tumor has invaded into the submucosa (pT1b) but lym-phatic invasion is found in the muscularis propria outside the main tumor, this is designated as pT1b (ly-T2).Note 4: Cancer macroscopically invading the adjacent organ(s) (sT4), and histologically, malignant tissue recog-nized on the surgical radial margin (pRM1) is pT4.Note 5: Direct invasion of tumor from lymph node metas-tasis to the adjacent organ(s) is categorized as pT4.e.g.: Direct invasion from No. 108 lymph node metastasis to the lung: pN1 (108-lung) T4Note 6: In determining the depth of invasion of an advanced cancer after preoperative treatment, both the depth of invasion by residual tumor and the estimated depth of tumor invasion prior to treatment should be considered. The type of adjuvant therapy (RT-, CT-, CRT-, EMR-), depth of invasion by residual tumor, and estimated depth of tumor invasion prior to treatment should be specifi ed in that order, the last in parentheses.e.g.: RT-pT1b (T4).

Note 7: If no residual tumor is found in an entire speci-men after preoperative treatment, the designation should be pT0, and its stage is recognized as the same as T1a.e.g.: CRT-pT0 (T3), N0, M0, CRT-pStage 0

4.2.3. Infi ltrative Growth Pattern (INF)

The growth and infi ltrative pattern of a tumor can be clas-sifi ed into one of the following three types, with regard to the predominant pattern observed at tumor margins.

INF-a (expansive type) Expansive growth of tumor nests with a well-demarcated border from surrounding tissue

INF-b (intermediate type) Intermediate growth pattern, between INF-a and c

INF-c (infi ltrative type) Infi ltrative growth of tumor nests with an ill-defi ned border from surrounding tissue

4.2.4. Vascular Invasion (ly/v)

4.2.4.1. Lymphatic Invasion (ly) Note 1

ly0 Nonely1 Slightly2 Moderately3 SevereNotes 24

Note 1: Examination by immunohistochemical staining using antibody D240 should be described.e.g.: ly1 (D240)Note 2: The description of wide spreading of tumor through lymphatic vessels should be described as lym-phangitis carcinomatosa.Note 3: Lymphangitis carcinomatosa in distant organ(s) is categorized as T4.Note 4: When the tumor mass is found in the thoracic duct, it is described as lymphatic invasion in the thoracic duct.

4.2.4.2. Venous Invasion (v) Note 1

v0 Nonev1 Slightv2 Moderate Note 2v3 Severe

Note 1: Examination by elastic fi ber staining methods should be described.e.g.: v1 (Victoria blue), v2 (Elastica van Gieson)Note 2: Indefi nite for determination of lymphatic or venous invasion is described as ly/v.

21

4.2.5. Intramural Metastasis (pIM)

4.2.6. Distance from Surgical Margin

4.2.6.1. Proximal and Distal Margin (pPM, pDM) Note

Note: The distance from surgical margin to tumor edge in pPM0 or pDM0 is measured in histological specimens (mm).

4.2.6.2. Radial Margin (pRM)4.2.7. Multiple Primary Cancers

Present (lesions)Absent

Note: Lesions with a histological type different from that of the main tumor, and isolated lesions with an intraepi-thelial component, are defi ned as multiple primary cancers.

4.2.8. Others

1) Metastatic or invasive cancer from other organs2) Co-existing tumor

Leiomyoma etc.3) Other non-neoplastic lesions

Barrett esophagus, Achalasia etc.

4.2.9. Pathological Criteria for the Effects of Radiation and/or Chemotherapy (Figure 1-17)

In cases of preoperative radiation and/or chemotherapy, the radiation dose and method of administration, type and dose of chemotherapy, and time interval between pre-operative therapy and surgical resection of the tumor are described. In cases of preoperative treatment, all the specimens in which the primary tumor is macroscopically possibly present should be examined histologically.Grade 0: IneffectiveNo recognizable cytological or histological therapeutic effectGrade 1: Slightly effectiveApparently viable cancer cells (including cells having eosin-ophilic cytoplasm with vacuolation and swollen nuclei) account for 1/3 or more of tumor tissue, but there is some evidence of degeneration of cancer tissue or cells.

Grade 1a: Viable cancer cells accounting for 2/3 or more tumor tissue

Grade 1b: Viable cancer cells accounting for 1/3 or more, but less than 2/3, of tumor tissue

Grade 2: Moderately effectiveViable cancer cells account for less than 1/3 of tumor tissue, while other cancer cells are severely degenerated or necrotic.Grade 3: Markedly effectiveNo viable cancer cells are evident.

Note: Defi nite re-proliferation of tumor cells in treated cancer lesions, after pre-operative treatment, should be recorded as re-proliferation (+).

4.3. Lymph Node Metastasis (pN)

Note 1: Lymph nodes should be sectioned through the hilum.Note 2: The number of dissected lymph nodes and meta-static lymph nodes should be recorded.Note 3: The metastatic ratio (the number of metastatic lymph nodes/the number of dissected lymph nodes) is described for each lymph node station. The total meta-static ratio is also described in parentheses.e.g.: No. 104R (0/10), No. 104 L (1/13), No. 106recR (1/3), No. 106recL (0/4)Note 4: Metastasis to soft tissue without lymph node structure is described as extra-lymph node metastasis.Note 5: Extranodal invasion including direct invasion and lymphatic invasion is described.Note 6: A lymph node with no viable cancer cells after preoperative treatment is diagnosed as negative for metastasis.Note 7: When the N category (pN) is modifi ed based on the number of the metastatic lymph nodes, refer to the explanation on page 96, then describe as modifi ed pN.

4.4. Distant Organ Metastasis (pM)

4.5. Residual Tumor (pR)

4.6. Curativity (pCur) Table 1-7

Curativity is comprehensively assessed based on both the surgical and pathological fi ndings.Curativity A: Cur ApStage 0III, pR0 and pD > pNCurativity B: Cur B

22

pStage IV (T4, M1) or pDpN, and R0Surgical curativity B or C, but pathologically R0Curativity C: Cur CpR1, pR2: pathologically residual tumor including the primary tumor (pPM1, pDM1, pRM1), lymph node metas-tasis or distant organ metastasis.

5. Endoscopic Treatment

5.1. Handling of Specimens Resected Endoscopically Note

Extending fi xation of the resected specimens: A specimen is extended and fi xed immediately after resection on a cork board or polystyrene foam and is fi xed in formalin solution of suffi cient volume for at least half a day.

Note: As for the extended fi xation of the resected speci-men, it should be done by the doctor or co-worker who carried out endoscopic treatment. Especially in piece-meal resection, fi xation of the specimen should be per-formed by the doctor(s) aware of the actual fi gure of the tumor in vivo to enable more exact restructuring.

5.2. Macroscopic Findings

Findings of iodine staining: The specimen is stained by iodine solution after fi xation with formalin, and the iodine-unstained area is confi rmed as a lesion.Note

Note: Although it takes longer, better fi ndings are obtained in the specimen stained using about 0.6% iodine solution more than shorter staining using more concen-trated iodine solution.

5.2.1. Clinical Assessment of the Residual Tumor (R) Note1,2

RX (non-assessable): it cannot be assessed whether there is an iodine unstained area in the margin of the resected speci-men or notR0 (complete resection): there is no iodine unstained area in any margin of the resected specimenR1 (incomplete resection): there is an iodine unstained area in the margin of the resected specimen

Note 1: A clinical assessment of the residual tumor refer-ring to the iodine staining is done immediately after endoscopic resectionNote 2: This method for assessment is applied to squa-mous cell carcinoma

5.3. Preparation for Pathological Examination (Figure 1-18)

Cutting lines are decided 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 in slice each 23 mm thick.

5.4. Description of Pathological Findings

The pathological diagnosis of an endoscopically resected specimen is summarized by the histological type, depth of tumor invasion, assessment of resection margin (horizontal and vertical), and vascular invasion.

5.4.1. Pathological Diagnosis

The diagnosis is based on the histological classifi cation (4.2.1). Although most esophageal tumors are squamous cell carcinoma, the evaluation of histological differentiation is omitted for intraepithelial carcinoma.

5.4.2. Depth of Tumor Invasion (T)

A mucosal cancer is categorized in three depths of EP, LPM and MM. In a submucosal cancer, the distance from the lamina muscularis mucosa is described because the entire submucosal layer cannot be examined in an endoscopically resected specimen. A submucosal cancer is sub-classifi ed to SM1 (submucosal tumor invasion is limited up to 200m) and SM2 (more than 200m).e.g.: pSM2, 300m

5.4.3. Resection Margin Note1,2

5.4.3.1. Horizontal Margin (HM)pHMX: It cannot be assessed whether there is residual tumor on the horizontal margin or not.pHM0: Non-cancerous squamous epithelium and lamina propria mucosa are confi rmed on all horizontal resection margins.pHM1: The tumor is exposed on any horizontal resection margin.

5.4.3.2. Vertical Margin (VM)pVMX: It cannot be assessed whether there is residual tumor on the vertical margin or not.pVM0: No tumor is exposed on any vertical margin.pVM1: The tumor is exposed on any vertical margin.Note 1: When no tumor is recognized in any resection margin, it is defi ned as a complete resection (pR0), and when a tumor is recognized in any resection margin, it is defi ned as an incomplete resection (pR1).Note 2: When vascular invasion is present in the resection margin, it is defi ned as a positive resection margin (pHM1, pVM1).

5.4.3.3. Non-assessable Resection Margin (pRX)1) Because of crushing injury or the burn effect in the

specimen during endoscopic resection, non-cancerous tissue in the resection margin cannot be confi rmed.

2) Reconstruction after piecemeal resection is impossible.Note

3) Suspected residual tumor in the basal layer because of non-continuous tumor extension.

23

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

5) Indeterminable residual tumor because of other reasons.

Note: In piecemeal resection pR0 is confi rmed only when restructuring is possible and only non-cancerous tissue is recognized in the resection margins of the restructured specimen.

5.4.4. Infi ltrative Growth Pattern (INF)

INFa (expansive type): Tumor extends downward continu-ously and expansively from the epithelium.INFb (intermediate type): Intermediate pattern, between INFa and INFcINFc (infi ltrative type): Tumor infi ltrates in the pattern of single cells, small and large tumor nests or trabecular arrangement of tumor cells in the lamina propria mucosa or submucosa.

5.4.5. Vascular Invasion (ly/v) Note

It is not necessary to evaluate the degree of vascular involve-ment: only its presence or absence should be described.

5.4.5.1. Lymphatic Invasion (ly)ly () No lymphatic invasionly (+) Lymphatic invasion

5.4.5.2. Venous Invasion (v)v () No venous invasionv (+) Venous invasion

Note: Special staining methods for the elastic fi bers of the vascular wall such as EVG and Victoria blue dyeing are necessary in determining the venous invasion. Immunos-taining with D240 is useful for confi rmation of lymphatic invasion. When differentiation between lymphatic and venous invasion is diffi cult, it is described as ly/v.

5.4.6. Report of Pathological Findings

All above mentioned factors should be described, and a fi gure showing a general view of the resected specimen

with depth of tumor invasion and vascular invasion by the part is needed. It is better to attach a schematic fi gure showing pathological fi ndings on the cut surface if necessary.

5.5. Curativity (Cur) Notes 1, 2 (Table 1-8)

When endoscopic resection (EMR: endoscopic mucosal resection or ESD: endoscopic submucosal dissection) is per-formed, a comprehensive evaluation is established, giving a clinical (cR) and pathological assessment (pHM and pVM) of the resection margin. In piecemeal resection, the evalu-ation is made by histological examination after accurate restructuring of the resected specimen.

Note 1: If there are multiple lesions, each lesion is evalu-ated, and the lesion with the lowest possibility of curative resection is used for comprehensive evaluation.Note 2: In cases of clinical and/or histological incomplete resection, if results similar to complete resection can be expected by an additional endoscopic treatment, it is fi nally evaluated as a complete resection.

5.6. Comprehensive Evaluation of Curativity

Curative resection: the complete resection for a cancer invading within the lamina propria mucosa and having no vascular invasionThe situation of EP or LPM at the depth of tumor invasion, Cur A and ly0/v0Non-curative resection: situations other than curative resection

6. Barrett Esophagus and Adenocarcinoma in Barrett Esophagus

6.1. Defi nition and Methods of Description for Barrett Mucosa, Barrett Esophagus and Adenocarcinoma in Barrett Esophagus

6.1.1. Defi nition of the Esophagogastric Junction (EGJ)

Border of esophageal muscle and gastric muscle.

24

6.1.2. Diagnosis of the Esophagogastric Junction (EGJ)

1) Lower margin of the palisading small vessels in the lower esophagus by endoscopic fi ndings (Figure 1-19).

2) Horizontal level at the same level as the angle of His in an upper gastrointestinal series (UGI).

3) Oral margin of longitudinal folds of the greater curva-ture of the stomach by endoscopic fi ndings and UGI (Figure 1-20).

4) Obvious macroscopic caliber change of resected esopha-gus and stomach.

Note: Squamocolumnar junction (SCJ) is not always consis-tent with EGJ.

6.1.3. Barrett Mucosa

The columnar epithelium continuous from the stomach with or without intestinal metaplasia.

6.1.4. Barrett Esophagus < cf. p97 >

The esophagus having Barrett mucosa is designated Barrett esophagus.Note 1

At least one of the following conditions must be satisfi ed.(1) Esophageal glands in the area of columnar epithelium(2) Squamous islands in the columnar epithelium(3) Double layer structure of muscularis mucosa Note 2

Note 1: Circular Barrett mucosa extending longitudinally 3 cm or more is called long segment Barrett esophagus (LSBE) (Figure 1-21). On the other hand, less than 3 cm Barrett mucosa or non-circular Barrett mucosa is desig-nated as short segment Barrett esophagus (SSBE)Note 2: Sometimes there is new muscularis mucosa just under the columnar epithelium. In the Japanese Classifi -cation, the primary muscularis mucosa is called deep muscularis mucosa (DMM), and the new muscularis mucosa is called superfi cial muscularis mucosa (SMM). The identifi cation of SMM and DMM is occasionally dif-fi cult due to fusion of both of the layers, thickness and irregularity.

6.1.5. Adenocarcinoma in Barrett Esophagus

Adenocarcinoma arising in Barrett mucosa

6.2. Tumor Locat ion

Same as esophageal cancer.Note: In the presence of hiatus hernia, the tumor location is diagnosed using barium contrast radiography.

6.3. Description of Tumors

Adenocarcinoma in Barrett Esophagus is described accord-ing to the Japanese Classifi cation for esophageal cancer except for the depth of the tumor invasion.

6.3.1. Primary Tumor

6.3.1.1. Circumferential Location

6.3.1.2. Tumor Size

6.3.1.3. Macroscopic Tumor Types

6.3.1.4. Depth of Tumor Invasion (T)

TX Depth of tumor invasion cannot be assessed.

T0 No evidence of primary tumor

T1a Tumor invades mucosa.

T1a-SMM Tumor invades superfi cial muscularis mucosa (SMM).

T1a-LPM Tumor invades lamina propria mucosa.

T1a-DMM Tumor invades deep muscularis mucosa (DMM).

T1b Tumor invades submucosa (SM).

SM1 Tumor invades the upper third of submucosa.

SM2 Tumor invades the middle third of submucosa.

SM3 Tumor invades the lower third of submucosa.

T2 Tumor invades muscular propria (MP).

T3 Tumor invades adventitia (AD).

T4 Tumor invades adjacent structure(s) (AI).

6.3.2. Intramural Metastasis (IM)

Same as esophageal cancer.

6.3.3. Lymph Node Metastasis (N)

6.3.4. Distant Organ Metastasis (M)

Same as esophageal cancer.

6.4. Stage

Same as esophageal cancer.

25

Fig. 1-19 Esophagogastric junctionThe site of the lower edges of the palisading small vessels is defi ned as EGJ.

Fig. 1-20 Esophagogastric junctionThe site of the oral edges (arrows) of longitudinal gastric folds is defi ned as the EGJ.

Fig. 1-21 Long segment Barrett esophagus (LSBE).

Fig. 1-22 Short segment Barrett esophagus (SSBE)a. Circular SSBE, b. Non-circu-lar SSBE

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