Staging Handbook in Thoracic Oncology, 2nd Edition by IASLC (PDFDrive)

INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER
Conquering Thoracic Cancers Worldwide
SECOND EDITION
Staging Handbook in
Thoracic Oncology
Executive Editor
Ramón Rami-Porta, MD
Developed in
Collaboration with
SECOND EDITION
Staging Handbook in
Thoracic Oncology
SECOND EDITION
Staging Handbook in
Thoracic Oncology
Ramón Rami-Porta, MD, Executive Editor
An International Association for the Study of Lung Cancer Publication
Editorial Rx Press
North Fort Myers, FL
International Association for the Study of Lung Cancer
Aurora, CO, USA
Executive Editor: Ramón Rami-Porta, MD

Chair, IASLC Staging and Prognostic Factors Committee
Hospital Universitari Mútua Terrassa, University of Barcelona, Terrassa, Spain
An IASLC publication published by Editorial Rx Press
Editorial Rx Press, Registered Office: North Fort Myers, FL 33917

www.editorialrxpress.com
First Editorial Rx Press Printing 2016
10 9 8 7 6 5 4 3 2 1
ISBN: 978-0-9832958-6-0
Copyright © 2016 by International Association for the Study of Lung Cancer

All rights reserved
Chapters 1, 2, 7, 9, 12–Used with the permission of the Union for International

Cancer Control (UICC), Geneva, Switzerland. The original source for this
material is the UICC TNM Classification of Malignant Tumours, 8th edition
(2017), published by John Wiley & Sons, Ltd, www.wiley.com.
Chapter 3, 4, 13– Used with the permission of the Union for International
Cancer Control (UICC), Geneva, Switzerland. The original source for this
material is the TNM Supplement: A Commentary on Uniform Use, 4th Edition
(2012) published by John Wiley & Sons Ltd, www.wiley.com.
Cover and interior design by Amy Boches, Biographics.

Use of the AJCC and UICC logos provided.
v
Dedication
To Prof. Peter Goldstraw, MBChB, FRCS
Emeritus Professor of Thoracic Surgery,

National Heart and Lung Institute, Imperial College,
Honorary Consultant in Thoracic Surgery, Royal Brompton Hospital, London,
President (2011-2013), International Association for the Study
of Lung Cancer (IASLC),
Chair (1998-2009) and Past Chair (2009-2016), IASLC Staging and
Prognostic Factors Committee
With gratitude, esteem, and respect

vii
Acknowledgments
The International Association for the Study of Lung Cancer

(IASLC) expresses its most sincere gratitude to all the investiga-
tors and their institutions around the world for their voluntary
contribution to the IASLC, the International Mesothelioma
Interest Group (IMIG), the International Thymic Malignancies
Interest Group (ITMIG) and the Worldwide Esophageal Cancer
Collaboration (WECC) staging projects. Without their collabora-
tion and submission of their cases, the data-based revisions
leading to the 8th edition of the TNM classifications of thoracic
malignancies would have not been possible. The complete list
of contributors is in Rami-Porta R (ed), IASLC Staging Manual
in Thoracic Oncology, 2nd edition; Editorial Rx Press, North
Fort Myers, FL; 2016.
ix
“Nought may endure but mutability!”

—Percy B. Shelley
Contents
Dedication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Epigraph. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Preface to the Second Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
PART I GENERAL
CH 1 The Principles of the TNM System. . . . . . . . . . . . . . . . . . . . . . . . . 35
PART II LUNG CANCER

CH 2 8th Edition of TNM for Lung Cancer. . . . . . . . . . . . . . . . . . . . . . . . 55
3 Site-Specific Explanatory Notes for Lung Tumours. . . . . 65
4 Site-Specific Recommendations for pT and
pN Categories. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
5 New Site-Specific Recommendations Proposed
by the IASLC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
6 Atlas of Lung Cancer Staging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
PART III PLEURAL MESOTHELIOMA

CH 7 8th Edition of TNM for Pleural Mesothelioma . . . . . . . . . . 119
8 Atlas of Pleural Mesothelioma Staging . . . . . . . . . . . . . . . . . . 123
PART IV THYMIC MALIGNANCIES

CH 9 TNM for Thymic Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
10 Site-Specific Explanatory Notes for
Thymic Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .133
11 Atlas of Thymic Malignancies Staging . . . . . . . . . . . . . . . . . . . 143
Contents
PART V CARCINOMA OF THE OESOPHAGUS AND OF
OESOPHAGOGASTRIC JUNCTION
CH 12 8th Edition of TNM for Carcinoma of the Oesophagus
and of the Oesophagogastric Junction . . . . . . . . . . . . . . . . .153
13 Site-Specific Explanatory Notes for Carcinoma
of the Oesophagus and of the
Oesophagogastric Junction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .169
14 Atlas of Oesophagus and of Oesophagogastric
Junction Cancer Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .179

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .183
Contributors
Editorial Committee
Executive Editor
Ramón Rami-Porta
Associate Editors
Hisao Asamura
Frank C. Detterbeck
Peter Goldstraw
Thomas W. Rice Ramón Rami-Porta
Valerie W. Rusch
Members
Alex A. Adjei (Editor-in-Chief, Journal of Thoracic Oncology),
Mayo Clinic, Rochester, MN, USA.
Hisao Asamura (Chair-Elect and Chair, N-Descriptors Subcom-
mittee of the IASLC Staging and Prognostic Factors Committee,
Japan Lung Cancer Society Liaison), Keio University, Tokyo,
Japan.
Eugene H. Blackstone (Member of the Advisory Board of the
IASLC Oesophageal Cancer Domain of the IASLC Staging and
Prognostic Factors Committee, and the Worldwide Esophageal
Cancer Collaboration), Cleveland Clinic, Cleveland, OH, USA.
James Brierley (Co-Chair, Union for International Cancer
Control TNM Committee and UICC Liaison), Princess Margaret
Cancer Centre/University Health Network, University of
Toronto, Toronto, ON, Canada.
David Carbone (IASLC President), Ohio State’s Comprehensive
Cancer Center-James Cancer Hospital and Research Institute,
Columbus, OH, USA.
14 | CONTRIBUTORS
John Crowley (Chief of Strategic Alliances), Cancer Research

And Biostatistics, Seattle, WA, USA.
Frank C. Detterbeck (Chair, Thymic Malignancies Domain and
Chair, Methodology and Validation Subcommittee of the IASLC
Stating and Prognostic Factors Committee, and International
Thymic Malignancies Interest Group Liaison), Yale University,
New Haven, CT, USA.
Wilfried E. E. Eberhardt (Chair, M-Descriptors Subcommittee of
the IASLC Staging and Prognostic Factors Committee), West
German Cancer Centre, University Hospital, Ruhrlandklinik,
Univesity Duisburg-Essen, Essen, Germany.
Pier Luigi Filosso (Member of the Advisory Board of the Thymic
Malignancies Domain of the IASLC Staging and Prognostic
Factors Committee), University of Torino, Torino, Italy.
Dorothy Giroux (Biostatistician), Cancer Research And
Biostatistics, Seattle, WA, USA.
Peter Goldstraw (Past-President IASLC, Past-Chair IASLC
Staging and Prognostic Factors Committee), Royal Brompton
Hospital, Imperial College, London, UK.
Mary K. Gospodarowicz (Immediate Past President of the UICC,
Co-Chair of the UICC TNM Core Group), Princess Margaret
Hospital/University Health Network, University of Toronto,
Toronto, Canada.
Fred R. Hirsch (CEO, IASLC and Board of Directors Liaison),
University of Colorado Health Sciences, Denver, Colorado, USA.
Eng-Siew Koh, Princess Margaret Hospital/University Health
Network, University of Toronto, Toronto, Canada.
Andrew G. Nicholson (Chair, Small Cell Lung Cancer Sub-
committee of the IASLC Staging and Prognostic Factors
Committee), Royal Brompton Hospital and Harefield NHS
CONTRIBUTORS | 15
Foundation Trust and Imperial College, London, UK.

Brian O’Sullivan (Chair, UICC Prognostic Factors Committee,
Member of the UICC TNM Core Group), Princess Margaret
Hospital/University Health Network, University of Toronto,
Toronto, Canada.
Harvey I. Pass (Member of the Advisory Board of the IASLC
Mesothelioma Domain of the IASLC Staging and Prognostic
Factors Committee), New York University, New York, NY, USA.
Ramón Rami-Porta (Chair, IASLC Staging and Prognostic
Factors Committee and Chair, Lung Cancer Domain and
T-Descriptors Subcommittee), Hospital Universitari Mútua
Terrassa, University of Barcelona, and Centros de Investigación
Biomédica en Red de Enfermedades Respiratorias (CIBERES)
Lung Cancer Group, Terrassa, Barcelona, Spain.
Thomas W. Rice (Chair, Carcinoma of the Oesophagus Domain
of the IASLC Staging and Prognostic Factors Committee, and
World Wide Esophageal Collaboration Liaison), Cleveland
Clinic, Cleveland, OH, USA.
Valerie W. Rusch (Chair, Mesothelioma Domain of the IASLC
Staging and Prognostic Factors Committee, and American
Joint Committee on Cancer Liaison), Memorial Sloan-Kettering
Cancer Center, New York, NY, USA.
Nagahiro Saijo (IASLC President 2007-2009), Former Deputy
Director National Cancer Center East, Chiba, Executive Officer
of the Japanese Society of Medical Oncology, Japan.
Jean-Paul Sculier (Chair, Prognostic Factors Subcommittee of
the IASLC Staging and Prognostic Factors Committee), Institut
Jules Bordet, Brussels, Belgium.
Lynn Shemanski (Senior Biostatistician), Cancer Research And
Biostatistics, Seattle, WA, USA.
16 | CONTRIBUTORS
William D. Travis (Chair, Neuroendocrine Tumours Subcom-

mittee of the IASLC Staging and Prognostic Factors Committee),
Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Ming S. Tsao (Chair, Biologic Factors Subcommittee of the
IASLC Staging and Prognostic Factors Committee), The
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
The complete list of members of the IASLC Staging and

Prognostic Factors Committee and of the Advisory Boards is in
Rami-Porta R (ed), IASLC Staging Manual in Thoracic Oncology,
2nd edition; Editorial Rx Press, North Fort Myers, FL; 2016; and
in the Appendix of the Introduction.
Preface to the Second Edition
By David P. Carbone, MD, PhD, IASLC President, 2015-2017,
and Fred R. Hirsch, MD, PhD, Chief Executive Officer
The staging of lung cancer and other thoracic malignan-

cies is important for the treatment decisions. The Union for
International Cancer Control/American Joint Committee on
Cancer/International Association for the Study of Lung Cancer
(UICC/AJCC/IASLC) Staging Classification is used all over the
world and the IASLC is proud of launching the 8th Edition of
the International Staging of Thoracic Malignancies. While the
previous 7th Edition of the staging system was focusing on lung
cancer, the new 8th Edition also includes staging of thymus
cancers, malignant pleural mesothelioma, and carcinoma of
the oesophagus. The new staging system is based on about
100.000 cases collected by international multidisciplinary
investigators from all geographical regions of the world.
For the second consecutive time, the IASLC has been in
charge to provide the UICC and the AJCC with data-based rec-
ommendations to revise the TNM classification of thoracic
malignancies. Both institutions have accepted the IASLC rec-
ommendations and incorporated them in their respective 8th
Edition staging manuals published in 2016.
The IASLC staging project has been performed by the
IASLC Staging and Prognostic Factors Committee under the
leadership of Dr. Ramón Rami-Porta, MD, Spain. This project
could not be performed without the generous unrestricted
support from Lilly Oncology, USA.
The IASLC is proud to serve the international
oncological community and thanks the UICC and
the AJCC for entrusting it with such challenging and
18 | PREFACE TO THE SECOND EDITION
intellectually rewarding responsibility. It is our hope that the

8th Edition of the Staging Classification will be a useful tool for
further research and will serve in the daily lung cancer clinic
to the benefit for the many patients with lung cancer around
the world.
Introduction
By Ramón Rami-Porta, MD, PhD, FETCS, Executive Editor
Chair, IASLC Staging and Prognostic Factors Committee
The second phase of the International Association for the

Study of Lung Cancer (IASLC) Staging Projects culminates
with the publication of the second edition of the IASLC
Staging Manual in Thoracic Oncology and the IASLC Staging
Handbook in Thoracic Oncology. During these eight years since
2009, new datasets have been designed to register data on
patients with lung cancer, malignant pleural mesothelioma
and thymic tumours, and a memorandum of understanding
was agreed with Dr. Thomas W. Rice, from the Cleveland Clinic,
Cleveland, OH, USA, for an educational association to promote
and disseminate the tumour, node and metastasis (TNM) clas-
sification of oesophageal cancer based on a new database
of cases registered by the Worldwide Esophageal Cancer
Collaboration (WECC). The IASLC also has worked in collabo-
ration with the International Thymic Malignancies Interest
Group (ITMIG) regarding the staging data of these tumours and
with the International Mesothelioma Interest Group (IMIG), as
well as with other organizations interested in the staging of
malignant tumours, such as the European Society of Thoracic
Surgeons, the Japanese Association for Research on the
Thymus, and the Japanese Joint Committee for Lung Cancer
Registry, among others. These entities and many institutions
around the world sent data from their databases to Cancer
Research And Biostatistics (CRAB) whose statisticians analysed
and interpreted in close association with the members of the
IASLC Staging and Prognostic Factors Committee and with the
members of the newly created Advisory Boards. The Advisory
20 | INTRODUCTION
Boards consist of additional specialists who contribute their

work and expertise to the IASLC Staging Projects. From the
functional point of view, the members of the IASLC Staging
and Prognostic Factors Committee were distributed in four
different domains according to their areas of interest: Lung
Cancer Domain, Malignant Pleural Mesothelioma Domain,
Thymic Tumours Domain and Oesophageal Cancer Domain.
(Appendix) Each domain has a chair, who is the link with the
members of the Advisory Boards, and may have several sub-
committees for specific tasks. (Figures 1 and 2)
Staging and Prognostic Factors Committee of the IASLC

Past-Chair/Chair/Chair-Elect
Lung Cancer Mesothelioma Thymoma Oesophageal Ca.

Domain Domain Domain Domain
Chairperson Chairperson Chairperson Chairperson
Subcommittees (x n) Subcommittees (x n) Subcommittees (x n) Subcommittees (x n)

– Chairperson (x 1) – Chairperson (x 1) – Chairperson (x 1) – Chairperson (x 1)
– Members (x n) – Members (x n) – Members (x n) – Members (x n)
– Liaison w/AB (x 1) – Liaison w/AB (x 1) – Liaison w/AB (x 1) – Liaison w/AB (x 1)
Advisory Board Advisory Board Advisory Board Advisory Board
Links with
UICC, AJCC, IMIG, ITMIG, WECC, and others
Figure 1. Structure of the International Association for the Study of Lung

Cancer Staging and Prognostic Factors Committee. Notes: n: number; w:
with; AB: Advisory Board; UICC: Union for International Cancer Control; AJCC:
American Joint Committee on Cancer; IMIG: International Mesothelioma
Interest Group; ITMIG: International Thymic Malignancies Interest Group;
WECC: Worldwide Esophageal Cancer Collaboration.
INTRODUCTION | 21
Figure 2. Most members of the International Association for the Study of Lung
Cancer (IASLC) Staging and Prognostic Factors Committee met in Sydney,
Australia, on October 25 and 26, 2013, prior to the 15th World Conference on
Lung Cancer, to discuss the latest analyses of the IASLC database and decide
on the recommendations for changes. This picture was taken at the end of
the sessions on October 25, 2013.
Table 1. Number of Evaluable Patients

The amount of col- Used for Revision of the TNM Classifi-
cations of Thoracic Malignancies.
lected data is huge. Table
Number of
1 shows the number of
Evaluable
evaluable patients used Tumour Patients
for the revision of the TNM
Lung cancer* 77,156
classifications of lung
Malignant 2,460
cancer, malignant pleu- pleural
ral mesothelioma and mesothelioma*
oesophageal carcinoma, Thymic 8,145
and for the development malignancies**
of an internationally Oesophageal 22,654
cancer***
agreed TNM classification
for thymic malignancies. * Registered by the International Association for
The analyses of the lung the Study of Lung Cancer (IASLC) and analysed
by Cancer Research And Biostatistics (CRAB).
cancer database produced
** Registered by the International Thymic
a series of original articles Malignancies Interest Group and the IASLC, and
describing the character- analysed by CRAB.
*** Registered by the World Wide Esophageal
istics of the database1, Cancer Collaboration and analysed at the
the analyses, findings and Cleveland Clinic, Cleveland, OH, USA.
22 | INTRODUCTION
recommendations for changes on the T2, the N3, and the M4

components of the classification, as well as those for the revi-
sion of the stages.5 In addition, the recommended changes,
based on the analyses of non-small cell lung cancer, were
tested in the population of patients with small cell lung cancer.
They were found to be useful in this cancer although the sur-
vival curves reflect the different natural history of small cell
lung cancer and its worse prognosis.6 The issue of how to
classify lung cancers with multiple lesions was thoroughly
discussed in four original papers on different patterns of
disease: simultaneous second primaries,7 separate tumour
nodules,8 multiple adenocarcinomas presenting as ground
glass opacities on computed tomography and showing lepidic
features on pathologic examination,9 and adenocarcinoma
with pneumonic pattern.9 A succinct paper summarises the
rules for classification and provides concise information on
the criteria to classify these lesions at clinical and pathologic
staging.10 One additional article deals with the newly incorpo-
rated tumours into the TNM classification -adenocarcinoma
in situ and minimally invasive adenocarcinoma- and how to
code them in the 8th edition of the TNM classification of lung
cancer.11 Finally, another article discusses in detail the meth-
odological aspects of the different analyses conducted for the
8th edition.12
Although more than a dozen classifications of thymic
malignancies had been proposed during the past few decades,
none was considered official or incorporated into the staging
manuals of the American Joint Committee on Cancer and the
Union for International Cancer Control. For the first time in
the history of anatomic staging, a data-based, internationally
and multidisciplinary agreed classification will be part of the
8th edition of the TNM classification of malignant tumours.
INTRODUCTION | 23
This thymic classification is, indeed, the first TNM-based inter-

nationally approved classification for this tumour site. The
analyses of the IASLC/ITMIG database comprising more than
8,000 evaluable patients generated a series of original articles
on the T13 and the N and M components,14 as well as on the
stages15 that have informed the proposed classification for the
8th edition staging manuals. A new lymph node map for exclu-
sive use in thymic malignancies also has been proposed,16
together with a revision of the mediastinal compartments.17
The analyses of the first IASLC mesothelioma database
pointed out some limitations of the TNM classification.18
Therefore, a call for the submission of more cases was
launched resulting in the registration of 2,460 evaluable cases.
Their analyses have generated four original articles, one on the
database itself,19 one on the T component,20 another on the
N component,21 and another on the M component and stage
grouping.22 Not all limitations have been solved, but changes
in the T and the N components, and in the stages have been
suggested. In addition, an article on recommendations for uni-
form definitions of surgical procedures based on an IASLC/IMIG
consensus was published,23 as well as an article on prognostic
factors.24
For the second consecutive time, the WECC database has
been used to revise the TNM classification of oesophageal car-
cinoma. The initial one, used to inform the 7th edition of the
classification, consisted of 4,627 patients who had undergone
oesophageal resection with no induction therapy. Important
innovations of this classification were the unification of the
classification of oesophageal and oesophago-gastric junction
cancers, and the introduction of non-anatomical parameters,
such as cell type, histopathologic grade and tumour location,
to arrange stage groupings. For the 8th edition, the WECC has
24 | INTRODUCTION
data on 22,654 patients and, among these, there are patients

whose tumours were clinically staged, pathologically staged
and pathologically staged after induction therapy. The analy-
ses of these three populations of patients have been reported
in three articles that inform the 8th edition of the TNM clas-
sification of oesophageal cancer and oesophago-gastric
junction.25, 26, 27
I would like to thank Prof. Peter Goldstraw, Past-Chair of
the IASLC Staging and Prognostic Factors Committee. Far from
retiring to an easy chair, he has actively participated in the
development of all activities that have led to the 8th edition
of the TNM classification of thoracic malignancies, sharing his
knowledge, experience, common sense, diplomacy, political
correctness and time, and contributing the most complex
article in the series, i.e., the lung cancer stages article.5 Ms.
Deb Whippen, our publisher from Editorial Rx Press, already
published the first edition of the IASLC Staging Manual in
Thoracic Oncology28 and the IASLC Staging Handbook in
Thoracic Oncology,29 has managed the production of their
second edition. I thank her for her professionalism, enthusi-
asm, continuous availability and thoughtful suggestions. Dr.
Aletta Anne Frazier, a radiologist by profession and a skillful
medical illustrator, was kind enough to accept again our invi-
tation to contribute her beautiful figures to the atlases of the
different thoracic malignancies. I thank her for her dedication
and good taste, and for devoting many hours of her time to
the IASLC Staging Projects. It has been delightful to discuss
with her over the phone the best options to illustrate the many
categories of the four tumours included in the IASLC staging
books. Nothing would have been possible without the data
from our many contributors around the world. Their generosity
is overwhelming. All are mentioned in the Acknowledgment
INTRODUCTION | 25
section and I wholeheartedly thank them for their time, dedi-

cation and support. Ms. Dolores Martínez, Secretary to our
Service of Thoracic Surgery, and Ms. Pat Vigues Frantzen, my
Personal Assistant, have paid attention to every detail and
have made my life much easier in so many ways that I cannot
thank them enough. Finally, I would like to thank Dr. Fred
Hirsch, IASLC CEO, IASLC presidents for this phase of the
IASLC Staging Projects, Drs. David Gandara, Peter Goldstraw,
Tony Mok and David Carbone, as well as all the IASLC Board
Members, for their continuous support to the activities of the
IASLC Staging and Prognostic Factors Committee.
As with the first edition, the second edition of the IASLC
Staging Manual in Thoracic Oncology and the IASLC Staging
Handbook in Thoracic Oncology has been produced in collabo-
ration with the Union for International Cancer Control and the
American Joint Committee on Cancer. Both institutions have
granted us permission to reprint key chapters from their own
books, which ensures uniformity in the three manuals. Their
cooperation is much appreciated.
The IASLC Staging Projects, conceived in 1996 in London,
during the International Workshop on Intrathoracic Staging,
under the leadership of Prof. Peter Goldstraw and the sponsor-
ship of the IASLC,30 have already spanned for 20 years. After
these two decades of continuous hard work, it is clear that
the era of data-based revisions of the TNM classification of
thoracic malignancies is consolidated. The work is not fin-
ished, though. The challenge of the combination of anatomic
elements and non-anatomic elements, especially molecular
markers, to construct prognostic groups and improve individu-
alized prognosis will be the core activity of the third phase of
the IASLC Staging Projects 2017-2024 that will be led by Dr.
Hisao Asamura as Chair of the IASLC Staging and Prognostic
26 | INTRODUCTION
Factors Committee. We count, once more, on the data sent

by our colleagues around the world to make this third phase,
leading to the 9th edition of the TNM classification of thoracic
malignancies, a scientific success and a useful contribution to
our patients.
References
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Staging Project: the new database to inform the eighth edition
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3. Asamura H, Chansky K, Crowley J et al. The IASLC Lung Cancer Staging
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Staging Project: proposals for the classification of lung cancer with
INTRODUCTION | 27
separate tumor nodules in the forthcoming eighth edition of the TNM

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1204-1223.
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forthcoming (8th) edition of the TNM classification of malignant tumors.
J Thorac Oncol 2014; 9 (suppl 2); s73-s80.
14. Kondo K, Van Schil P, Detterbeck FC at al. The IASLC/ITMIG Thymic
Epithelial Tumors Staging Project: proposals for the N and M components
for the forthcoming (8th) edition of the TNM classification of malignant
tumors. J Thorac Oncol 2014; 9 (suppl 2): s81-s87.
15. Detterbeck FC, Stratton K, Giroux D et al. The IASLC/ITMIG Thymic
Epithelial Tumors Staging Project: proposals for an evidence-based stage
classification system for the forthcoming (8th) edition of the TNM clas-
sification of malignant tumors. J Thorac Oncol 2014; 9 (suppl 2): s65-s72.
16. Bhora FY, Chen DJ, Detterbeck FC et al. The ITMIG/IASLC Thymic Epithelial
Tumors Staging Project: a proposed lymph node map for thymic epithelial
tumors in the forthcoming 8th edition of the TNM classification of malig-
nant tumors. J Thorac Oncol 2014; 9 (suppl 2): s88-s96.
17. Carter BW, Tomiyama N, Bhora FY et al. A modern definition of mediastinal
compartments. J Thorac Oncol 2014; 9 (suppl 2): s97-s101.
28 | INTRODUCTION
18. Rusch VW, Giroux D, Kennedy C et al. Initial analysis of the International
Association for the Study of Lung Cancer Mesothelioma database. J
Thorac Oncol 2012; 7: 1631-1639.
19. Pass H, Giroux D, Kennedy C et al. The IASLC Mesothelioma database:
improving staging of a rare disease through international participation.
J Thorac Oncol 2016; in press.
20. Nowak AK, Chansky K, Rice DC et al. The IASLC Mesothelioma Staging
Project: proposals for revisions of the T descriptors in the forthcoming
eighth edition of the TNM classification for mesothelioma. J Thorac Oncol
2016; in press.
21. Rice D, Chansky K, Nowak A et al. The IASLC Mesothelioma Staging Project:
proposals for revisions of the N descriptors in the forthcoming eighth
edition of the TNM classification for malignant pleural mesothelioma. J
Thorac Oncol 2016; in press.
22. Rusch VW, Chansky K, Kindler HL et al. The IASLC Malignant Pleural
Mesothelioma Staging Project: proposals for the M descriptors and for
the revision of the TNM stage groupings in the forthcoming (eighth) edition
of the TNM classification for mesothelioma. J Thorac Oncol 2016; in press.
23. Rice D, Rusch V, Pass H et al. Recommendations for uniform definitions
of surgical techniques for malignant pleural mesothelioma: a consen-
sus report of the International Association for the Study of Lung Cancer
International Staging Committee and the International Mesothelioma
Interest Group. J Thorac Oncol 2011; 6: 1304-1312.
24. Pass HI, Giroux D, Kennedy C et al. Supplementary prognostic variables
for pleural mesothelioma: a report from the IASLC Staging Committee.
J Thorac Oncol 2014; 9: 856-864.
25. Rice TW, Apperson-Hansen C, DiPaola C et al. Worldwide Esophageal
Cancer Collaboration: clinical staging data. Dis Esophagus 2016; 7: 707-714.
26. Rice TW, Chen L-Q, Hofstetter WL et al. Worldwide Esophageal Cancer
Collaboration: pathologic staging data. Dis Esophagus 2016; 7: 724-733.
27. Rice TW, Lerut TEMR, Orringer MB et al. Worldwide Esophageal Cancer
Collaboration: neoadjuvant pathologic staging data. Dis Esophagus 2016;
7: 715-723.
28. Goldstraw P, ed. IASLC Staging Manual in Thoracic Oncology. Editorial Rx
Press, Orange, FL, USA; 2009.
29. Goldstraw P, ed. IASLC Staging Handbook in Thoracic Oncology. Editorial
Rx Press, Orange, FL, USA; 2009.
30. Goldstraw P. Report on the international workshop on intrathoracic stag-
ing. London, October 1996. Lung Cancer 1997; 18: 107-111.
INTRODUCTION | 29
Appendix. Members and Structure of the IASLC

Staging and Prognostic Factors Committee
Past-chair: Peter Goldstraw
Chair: Ramón Rami-Porta
Chair-elect: Hisao Asamura
LUNG CANCER DOMAIN

Chair: Ramón Rami-Porta
T Descriptors Subcommittee:
Ramón Rami-Porta (chair), David Ball, Vanessa Bolejack, John
Crowley, Dorothy J. Giroux, Jhingook Kim, Gustavo Lyons,
Thomas Rice, Kenji Suzuki, Charles F. Thomas Jr, William D.
Travis, Yi-Iong Wu
N Descriptors Subcommittee:
Hisao Asamura (chair), David Ball, Kari Chansky, John
Crowley, Peter Goldstraw, Valerie Rusch, Paul Van Schil, Johan
Vansteenkiste, Hirokazu Watanabe, Yi-Iong Wu, Marcin Zielinski
M Descriptors Subcommittee:
Wilfried Eberhardt (chair), Kari Chansky, John Crowley, Young
Tae Kim, Haruhiko Kondo, Alan Mitchell, Andrew Turrisi
Validation and Methodology Subcommittee:
Patti Groome (chair 2010-15), Frank Detterbeck (chair 2015-7),
Vanessa Bolejack, John Crowley, Catherine Kennedy, Mark
Krasnik, Michael Peak
Prognostic Factors Subcommittee:
Jean-Paul Sculier (chair), Kari Chansky, John Crowley, Dorothy
J. Giroux, Fergus Gleeson, Jan van Meeerbeeck
Neuroendocrine Tumours Subcommittee:
William D. Travis (chair), Hisao Asamura, Kari Chansky, John
Crowley, Dorothy J. Giroux
30 | INTRODUCTION
Small Cell Lung Cancer Subcommittee:

Andrew Nicholson (chair), Ricardo Beyruti, Kari Chansky, John
Crowley, Kouru Kubota, Andrew Turrisi
Biologic Factors Subcommittee:
Ming S. Tsao (chair), David G. Beer, John Crowley, Yi-Iong Wu
T Coding and Size Measurement in Preinvasive and Lepidic
Adenocarcinoma ad hoc Workgroup:
William D. Travis (chair), Hisao Asamura, Alex Bankier, Mary
Beth Beasley, Frank Detterbeck, Douglas B. Flieder, Jin Mo Goo,
Heber MacMahon, David Naidich, Andrew Nicholson, Charles
A. Powell, Mathias Prokop, Ramón Rami-Porta, Valerie Rusch,
Paul Van Schil, Yasushi Yatabe
Multiple Pulmonary Sites of Involvement ad hoc Workgroup:
Frank Detterbeck (chair), Douglas A. Arenberg, Hisao Asamura,
Vanessa Bolejack, John Crowley, Jessica S. Donington, Wilbur
A. Franklin, Nicolas Girard, Edith M. Marom, Peter J. Mazzone,
Andrew G. Nicholson, Valerie W. Rusch, Lynn T. Tanoue, William
D. Travis
MALIGNANT PLEURAL MESOTHELIOMA DOMAIN

Chair: Valerie Rusch
Hisao Asamura, John Crowley, John G. Edwards, Françoise
Galateau- Sallé, Dorothy J. Giroux, Catherine Kennedy, Jan van
Meerbeeck, Takashi Nakano, Anna Nowack, K. E. Rosenzweig,
William Travis, Johan Vansteenkiste
Mesothelioma Advisory Board:
Liaison with the Malignant Pleural Mesothelioma Domain:
Valerie Rusch
Members: Paul Baas, Seiki Hasegawa, Jeremy Erasmus,
Kouki Inai, Kemp Kernstein, Hedy Kindler, Lee Krug, Kristiaan
Nackaerts, Harvey Pass, David Rice
INTRODUCTION | 31
THYMIC MALIGNANCIES DOMAIN

Chair: Frank Detterbeck
Hisao Asamura, John Crowley, Dorothy Giroux, James
Huang, Jhingook Kim, Mirella Marino, Edith Marom, Anderew
Nicholson, Enrico Ruffini, Paul Van Schil
Thymic Malignancies Advisory Board:
Liaison with the Thymic Malignancies Domain: Frank
Detterbeck
Members: Conrad Falkson, Pier Luigi Filosso, Giuseppe
Giaccone, Kazuya Kondo, Mario Lucchi, Meinoshin Okumura
OESOPHAGEAL CARCINOMA DOMAIN

Chair: Thomas Rice
John Crowley, Toni Lerut, Yuji Tachimori
Oesophageal Carcinoma Advisory Board:
Liaison with the Oesophageal Carcinoma Domain: Thomas
Rice
Member: Eugene Blackstone
PART I
GENERAL
Acknowledgment: Used with the permission
of the Union for International Cancer Control
(UICC), Geneva, Switzerland. The original source
for this material is in Brierley JB, Gospodarowicz
MK, Wittekind C, eds. UICC TNM Classification of
Malignant Tumours, 8th edition (2017), published
by John Wiley & Sons, Ltd, www.wiley.com.
1
The Principles of the
TNM System
The practice of classifying cancer cases into groups according

to anatomical extent, termed ‘stage’, arose from the obser-
vation that survival rates were higher for cases in which the
disease was localized than for those in which the disease had
extended beyond the organ of origin. The stage of disease
at the time of diagnosis is a reflection not only of the rate of
growth and extension of the neoplasm but also the type of
tumour and the tumour–host relationship.
It is important to record accurate information on the
anatomical extent of the disease for each site at the time of
diagnosis, to meet the following objectives:
1. to aid the clinician in the planning of treatment
2. to give some indication of prognosis for survival
3. to assist in evaluation of the results of treatment
4. to facilitate the exchange of information between treat-
ment centres
5. to contribute to the continuing investigation of human
cancer
6. to support cancer control activities.
Cancer staging is essential to patient care, research, and

cancer control. Cancer control activities include direct patient
36 | PART I | GENERAL
care-related activities, the development and implementa-

tion of clinical practice guidelines, and centralized activities
such as recording disease extent in cancer registries for sur-
veillance purposes and planning cancer systems. Recording
of stage is essential for the evaluation of outcomes of clinical
practice and cancer programmes. However, in order to evalu-
ate the long-term outcomes of populations, it is important for
the classification to remain stable. There is therefore a conflict
between a classification that is updated to include the most
current forms of medical knowledge while also maintaining a
classification that facilitates longitudinal studies. The UICC TNM
Project aims to address both needs.
International agreement on the classification of cancer
by extent of disease provides a method of conveying disease
extent to others without ambiguity.
There are many axes of tumour classification: for example,
the anatomical site and the clinical and pathological extent of
disease, the duration of symptoms or signs, the gender and
age of the patient, and the histological type and grade of the
tumour. All of these have an influence on the outcome of the
disease. Classification by anatomical extent of disease is the
one with which the TNM system primarily deals.
The clinician’s immediate task when meeting a patient
with a new diagnosis of cancer is to make a judgment as to
prognosis and a decision as to the most effective course of
treatment. This judgment and this decision require, among
other things, an objective assessment of the anatomical extent
of the disease.
To meet the stated objectives a system of classification is
needed:
1. that is applicable to all sites regardless of treatment; and
2. that may be supplemented later by further informa-
CH 1 | THE PRINCIPLES OF THE TNM SYSTEM | 37
tion that becomes available from histopathology and/or

surgery.
The TNM system meets these requirements.
The General Rules of the TNM Systema,b

The TNM system for describing the anatomical extent of dis-
ease is based on the assessment of three components:
T – the extent of the primary tumour
N – the absence or presence and extent of regional lymph
node metastasis
M – the absence or presence of distant metastasis.
The addition of numbers to these three components indicates

the extent of the malignant disease, thus:
T0, T1, T2, T3, T4, N0, N1, N2, N3, M0, M1
In effect, the system is a ‘shorthand notation’ for describing

the extent of a particular malignant tumour.
The general rules applicable to all sites are as follows:
1. All cases should be confirmed microscopically. Any cases
not so proved must be reported separately.
2. Two classifications are described for each site, namely:
a) Clinical classification: the pretreatment clinical classi-
fication designated TNM (or cTNM) is essential to select
and evaluate therapy. This is based on evidence acquired
before treatment. Such evidence is gathered from physi-
cal examination, imaging, endoscopy, biopsy, surgical
exploration, and other relevant examinations.
b)Pathological classification: the postsurgical histo-
pathological classification, designated pTNM, is used
to guide adjuvant therapy and provides additional data
to estimate prognosis and end results. This is based on
evidence acquired before treatment, supplemented or

modified by additional evidence acquired from surgery
and from pathological examination. The pathologi-
cal assessment of the primary tumour (pT) entails a
resection of the primary tumour or biopsy adequate
to evaluate the highest pT category. The pathological
assessment of the regional lymph nodes (pN) entails
removal of the lymph nodes adequate to validate the
absence of regional lymph node metastasis (pN0) or suf-
ficient to evaluate the highest pN category. An excisional
biopsy of a lymph node without pathological assess-
ment of the primary is insufficient to fully evaluate the
pN category and is a clinical classification. The patho-
logical assessment of distant metastasis (pM) entails
microscopic examination of metastatic deposit.
3. After assigning T, N, and M and/or pT, pN, and pM categories,
these may be grouped into stages.The TNM classification
and stages, are established at diagnosis and must remain
unchanged in the medical records. Only for cancer sur-
veillance purposes, clinical and pathological data may be
combined when only partial information is available either
in the pathological classification or the clinical classifica-
tion.
4. If there is doubt concerning the correct T, N, or M category
to which a particular case should be allotted, then the
lower (i.e., less advanced) category should be chosen. This
will also be reflected in the stage.
5. In the case of multiple primary tumours in one organ, the
tumour with the highest T category should be classified
and the multiplicity or the number of tumours should be
indicated in parenthesis, e.g., T2(m) or T2(5). In simulta-
neous bilateral primary cancers of paired organs, each
tumour should be classified independently. In tumours of

the liver, ovary and fallopian tube, multiplicity is a criterion
of T classification, and in tumours of the lung multiplicity
may be a criterion of the M classification.
6. Definitions of the TNM categories and stage may be tele-
scoped or expanded for clinical or research purposes
as long as the basic definitions recommended are not
changed. For instance, any T, N, or M can be divided into
subgroups.
Notes
a
For more details on classification the reader is referred to the TNM
Supplement.
b
An educational module is available on the UICC website www.uicc.org.
Anatomical Regions and Sites

The sites in this classification are listed by code number of the
International Classification of Diseases for Oncology.1 Each
region or site is described under the following head-
ings:
• Rules for classification with the procedures for assessing
the T, N, and M categories
• Anatomical sites, and subsites if appropriate
• Definition of the regional lymph nodes
• TNM Clinical classification
• pTNM Pathological classification
• G Histopathological grading if different from that
described in the Histopathological Grading section pro-
vided further in this chapter
• Stage and prognostic groups
• Prognostic factors grid
TNM Clinical Classification

The following general definitions are used throughout:
T – Primary Tumour
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Carcinoma in situ
T1–T4 Increasing size and/or local extent of the primary
tumour
N – Regional Lymph Nodes

NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1–N3 Increasing involvement of regional lymph nodes
M – Distant Metastasis*
M0 No distant metastasis
M1 Distant metastasis
Note
*The MX category is considered to be inappropriate as clinical assess-
ment of metastasis can be based on physical examination alone. (The
use of MX may result in exclusion from staging.)
The category M1 may be further specified according to the

following notation:
Pulmonary PUL (C34) Brain BRA (C71)
Bone marrow MAR (C42.1) Adrenals ADR (C74)
Osseous OSS (C40, 41) Lymph nodes LYM (C77)
Pleura PLE (C38.4) Skin SKI (C44)
Hepatic HEP (C22) Others OTH
Peritoneum PER (C48.1,2)
Subdivisions of TNM
Subdivisions of some main categories are available for those
who need greater specificity (e.g., T1a, T1b or N2a, N2b).
pTNM Pathological Classification

The following general definitions are used throughout:
pT – Primary Tumour
pTX Primary tumour cannot be assessed histologically
pT0 No histological evidence of primary tumour
pTis Carcinoma in situ
pT1–4 Increasing size and/or local extent of the primary
tumour histologically
pN – Regional Lymph Nodes

pNX Regional lymph nodes cannot be assessed
histologically
pN0 No regional lymph node metastasis histologically
pN1–3 Increasing involvement of regional lymph nodes
histologically
Notes
• Direct extension of the primary tumour into lymph nodes is clas-
sified as lymph node metastasis.
• Tumour deposits (satellites), i.e., macro- or microscopic nests or
nodules, in the lymph drainage area of a primary carcinoma with-
out histological evidence of residual lymph node in the nodule,
may represent discontinuous spread, venous invasion (V1/2) or
a totally replaced lymph node. If a nodule is considered by the
pathologist to be a totally replaced lymph node (generally having
a smooth contour), it should be recorded as a positive lymph
node, and each such nodule should be counted separately as a
lymph node in the final pN determination.
• Metastasis in any lymph node other than regional is classified as

a distant metastasis.
• When size is a criterion for pN classification, measurement is made
of the metastasis, not of the entire lymph node. The measurement
should be that of the largest dimension of the tumour.
• Cases with micrometastasis only, i.e., no metastasis larger than
0.2 cm, can be identified by the addition of ‘(mi)’, e.g., pN1(mi).
Sentinel Lymph Node

The sentinel lymph node is the first lymph node to receive
lymphatic drainage from a primary tumour. If it contains
metastatic tumour this indicates that other lymph nodes may
contain tumour. If it does not contain metastatic tumour, other
lymph nodes are not likely to contain tumour. Occasionally,
there is more than one sentinel lymph node.
The following designations are applicable when sentinel
lymph node assessment is attempted:
(p)NX(sn) Sentinel lymph node could not be assessed
(p)N0(sn) No sentinel lymph node metastasis
(p)N1(sn) Sentinel lymph node metastasis
Isolated Tumour Cells

Isolated tumour cells (ITC) are single tumour cells or small
clusters of cells not more than 0.2 mm in greatest extent that
can be detected by routine H and E stains or immunohisto-
chemistry. An additional criterion has been proposed in breast
cancer to include a cluster of fewer than 200 cells in a single
histological cross-section. Others have proposed for other
tumour sites that a cluster should have 20 cells or fewer; defini-
tions of ITC may vary by tumour site. ITCs do not typically show
evidence of metastatic activity (e.g., proliferation or stromal
reaction) or penetration of vascular or lymphatic sinus walls.
Cases with ITC in lymph nodes or at distant sites should be

classified as N0 or M0, respectively. The same applies to cases
with findings suggestive of tumour cells or their components
by non-morphological techniques such as flow cytometry or
DNA analysis. The exceptions are in malignant melanoma of
the skin and Merkel cell carcinoma, wherein ITC in a lymph
node are classified as N1. These cases should be analysed
separately.2 Their classification is as follows.
(p)N0 No regional lymph node metastasis histologi-
cally, no examination for isolated tumour cells
(ITC)
(p)N0(i–) No regional lymph node metastasis histologi-
cally, negative morphological findings for ITC
(p)N0(i+) No regional lymph node metastasis histologi-
cally, positive morphological findings for ITC
(p)N0(mol–) No regional lymph node metastasis histologi-
cally, negative non-morphological findings for
ITC
(p)N0(mol+) No regional lymph node metastasis histolog
cally, positive non-morphological findings for
ITC
Cases with or examined for isolated tumour cells (ITC) in sen-

tinel lymph nodes can be classified as follows:
(p)N0(i–)(sn) No sentinel lymph node metastasis histo-
logically, negative morphological findings
for ITC
(p)N0(i+)(sn) No sentinel lymph node metastasis histologi-
cally, positive morphological findings for ITC
(p)N0(mol–)(sn) No sentinel lymph node metastasis histologi-
cally, negative non-morphological findings
for ITC
(p)N0 (mol+)(sn) No sentinel lymph node metastasis histologi-

cally, positive non-morphological findings
for ITC
pM – Distant Metastasis*
pM1 Distant metastasis microscopically confirmed
Note
*pM0 and pMX are not valid categories.
The category pM1 may be further specified in the same way

as M1 (see TNM Clinical Classification section provided earlier
in this chapter).
Isolated tumour cells found in bone marrow with morpho-

logical techniques are classified according to the scheme for
N, e.g., M0(i+). For non-morphological findings ‘mol’ is used
in addition to M0, e.g., M0 (mol+).
Histopathological Grading
In most sites, further information regarding the primary
tumour may be recorded under the following heading:
G – Histopathological Grading
GX Grade of differentiation cannot be assessed
G1 Well differentiated
G2 Moderately differentiated
G3 Poorly differentiated
G4 Undifferentiated
Notes
• Grades 3 and 4 can be combined in some circumstances as ‘G3-4,
poorly differentiated or undifferentiated’.
• Special systems of grading are recommended for tumours of

breast, corpus uteri, and prostate.
Additional Descriptors
For identification of special cases in the TNM or pTNM classifi-
cation, the m, y, r, and a symbols may be used. Although they
do not affect the stage grouping, they indicate cases needing
separate analysis.
m Symbol. The suffix m, in parentheses, is used to indicate

the presence of multiple primary tumours at a single site. See
TNM rule no. 5.
y Symbol. In those cases in which classification is performed

during or following multimodality therapy, the cTNM or pTNM
category is identified by a y prefix. The ycTNM or ypTNM cat-
egorizes the extent of tumour actually present at the time of
that examination. The y categorization is not an estimate of
the extent of tumour prior to multimodality therapy.
r Symbol. Recurrent tumours, when classified after a disease-

free interval, are identified by the prefix r.
a Symbol. The prefix a indicates that classification is first

determined at autopsy.
Optional Descriptors
L – Lymphatic Invasion
LX Lymphatic invasion cannot be assessed
L0 No lymphatic invasion
L1 Lymphatic invasion
V – Venous Invasion
VX Venous invasion cannot be assessed
V0 No venous invasion
V1 Microscopic venous invasion
V2 Macroscopic venous invasion
Note
Macroscopic involvement of the wall of veins (with no tumour within
the veins) is classified as V2.
Pn – Perineural Invasion
PnX Perineural invasion cannot be assessed
Pn0 No perineural invasion
Pn1 Perineural invasion
Residual Tumour (R) Classification*

The absence or presence of residual tumour after treatment
is described by the symbol R. More details can be found in the
TNM Supplement (see Preface, Reference 3).
TNM and pTNM describe the anatomical extent of cancer
in general without considering treatment. They can be supple-
mented by the R classification, which deals with tumour status
after treatment. It reflects the effects of therapy, influences
further therapeutic procedures, and is a strong predictor of
prognosis.
The definitions of the R categories are:

RX Presence of residual tumour cannot be assessed
R0 No residual tumour
R1 Microscopic residual tumour
R2 Macroscopic residual tumour.
Note
*Some consider the R classification to apply only to the primary
tumour and its local or regional extent. Others have applied it more
broadly to include distant metastasis. The specific usage should be
indicated when the R is used.
Stage and Prognostic Groups

The TNM system is used to describe and record the anatomical
extent of disease. For purposes of tabulation and analysis it
is useful to condense these categories into groups. For con-
sistency, in the TNM system, carcinoma in situ is categorized
stage 0; in general, tumours localized to the organ of origin as
stages I and II, locally extensive spread, particularly to regional
lymph nodes as stage III, and those with distant metastasis as
stage IV. The stage adopted is such as to ensure, as far as pos-
sible, that each group is more or less homogeneous in respect
of survival, and that the survival rates of these groups for each
cancer site are distinctive.
For pathological stages, if sufficient tissue has been
removed for pathological examination to evaluate the highest
T and N categories, M1 may be either clinical (cM1) or patho-
logical (pM1). However, if only a distant metastasis has had
microscopic confirmation, the classification is pathological
(pM1) and the stage is pathological.
Although the anatomical extent of disease, as categorized
by TNM, is a very powerful prognostic indicator in cancer, it is
recognized that many factors have a significant impact on pre-
dicting outcomes. This has resulted in different stage groups.
In thyroid cancer there are different stage definitions for dif-
ferent histologies and, new to this edition, in oropharyngeal
cancer HPV-related cancer is staged differently from non-HPV-
related cancer. Some factors have been combined with TNM in
the development of stage groupings; for instance, for different

histologies (thyroid), different major prognostic factor groups
(age in thyroid), and by aetiology (HPV-related oropharyngeal
cancer). In this edition the term stage has been used as defin-
ing the anatomical extent of disease while prognostic group
for classifications that incorporate other prognostic factors.
Historically, age in differentiated thyroid cancer and grade in
soft tissue sarcoma are combined with anatomical extent of
disease to determine stage, and stage is retained rather than
prognostic group in these two sites.
Prognostic Factors Classification

Prognostic factors can be classified as those pertaining to:
• Anatomic extent of disease: describes the extent of dis-
ease in the patient at the time of diagnosis. Classically, this
is TNM but may also include tumour markers that reflect
tumour burden, for instance prostate-specific antigen (PSA)
in prostate carcinoma or carcinoembryonic antigen (CEA)
in colorectal carcinoma.
• Tumour profile: this includes pathological (i.e., grade) and
molecular features of a tumour, and gene expression pat-
terns that reflect behaviour. These can be:
– predictive factors
– prognostic factors
– companion diagnostic marker
• Patient profile: this includes terms related to the host of
the cancer. These can be demographic factors, such as age
and gender, or acquired, such as immunodeficiency and
performance status.
• Environment: this may include treatment-related and
education (expertise, access, ageism, and healthcare deliv-
ery) and quality of management.
When describing prognostic factors it is important to

state what outcome the factors are prognostic for, and at what
point in the patient trajectory. Anatomical extent of disease as
described by TNM stage defines prognosis for survival.
In the second edition of the UICC Prognostic Factors in
Cancer for each tumour site, grids were developed that iden-
tified prognostic factors for survival at time of diagnosis and
whether they were considered to be essential, additional, or
new and promising.3 The grids were updated for the third edi-
tion4 and have been further updated and incorporated into the
ninth edition of the UICC Manual of Clinical Oncology.5 Essential
factors are those that are required in addition to anatomical
extent of disease to determine treatment as identified by
published clinical practice guidelines. The table is a generic
example of the prognostic factors summary grid. The grids
from the ninth edition of the UICC Manual of Clinical Oncology
are reproduced in this eighth edition. Grids are not available
for some of the less common tumours.
Examples of the UICC prognostic factors summary ‘grid’
Prognostic Host Environment
Factors Tumour Related Related Related
Essential* Anatomical disease Age Availability of
extent access to
Histological type radiotherapy
Additional Tumour bulk Race Expertise of a
Tumour marker level Gender treatment at the
Programmed death 1 Cardiac specific level
(PD-1) receptor and its function (e.g., surgery or
ligands (PD-L1) radiotherapy)
New and Epidermal growth Germline Access to
promising factor receptor p53 information
Gene expression patterns
*The origin of essential factors as imperatives for treatment decisions are from known and
available clinical practice guidelines.
Essential TNM
Information on anatomical extent of disease at presentation
or stage is central to cancer surveillance to determine cancer
burden as it provides additional valuable information to inci-
dence and mortality data.6 However, cancer registries in low
and middle income countries frequently have insufficient
information to determine complete TNM data, either because
of inability to perform necessary investigations or because
of lack of recording of information. In view of this, the UICC
TNM Project has with the International Agency for Research
in Cancer and the National Cancer Institute developed a new
classification system ‘Essential TNM’ that can be used to col-
lect stage data when complete information is not available. To
date, Essential TNM schemas have been developed for breast,
cervix, colon, and prostate cancer, and are presented in this
edition and available for download at www.uicc.org.
Paediatric Tumours
Since the fourth edition, the UICC TNM Classification of
Malignant Tumours has not incorporated any classifications
of paediatric tumours. This decision has stemmed from the
lack of an international standard staging system for many
paediatric tumours. To enable stage data collection by pop-
ulation-based cancer registries there needs to be agreement
on cancer staging. Recognition of this led to a consensus
meeting held in 2014 and resulted in the publication of rec-
ommendations on the staging of paediatric malignancies for
the purposes of population surveillance.7 The classifications
published are not intended to replace the classifications used
by the clinician when treating an individual patient but instead
to facilitate the collection of stage by population-based cancer
registries.
Related Classifications
Since 1958, WHO has been involved in a programme aimed at
providing internationally acceptable criteria for the histologi-
cal diagnosis of tumours. This has resulted in the International
Histological Classification of Tumours, which contains, in an
illustrated multivolume series, definitions of tumour types and
a proposed nomenclature. A new series, WHO Classification of
Tumours–Pathology and Genetics of Tumours, continues this
effort. (Information on these publications is at www.iarc.fr).
The WHO International Classification of Diseases for
Oncology (ICD-O-3)1 is a coding system for neoplasms by
topography and morphology and for indicating behaviour
(e.g., malignant, benign). This coded nomenclature is identi-
cal in the morphology field for neoplasms to the Systematized
Nomenclature of Medicine (SNOMED).8
In the interest of promoting national and international
collaboration in cancer research and specifically of facilitating
cooperation in clinical investigations, it is recommended that
the WHO Classification of Tumours be used for classification
and definition of tumour types and that the ICD-O-3 code be
used for storage and retrieval of data.
References
1. Fritz A, Percy C, Jack A, Shanmugaratnam K, Sobin L, Parkin DM, Whelan S,
eds. WHO International Classification of Diseases for Oncology ICD-O, 3rd
edn. Geneva: WHO, 2000.
2. Hermanek P, Hutter RVP, Sobin LH, Wittekind Ch. Classification of isolated
tumour cells and micrometastasis. Cancer 1999; 86: 2668–2673.
3. International Union Against Cancer (UICC) Gospodarowicz MK, Henson
DE, Hutter RVP, et al., eds. Prognostic Factors in Cancer, 2nd edn. New
York: Wiley, 2001.
4. International Union Against Cancer (UICC) Gospodarowicz MK, O’Sullivan B,
Sobin LH, eds. Prognostic Factors in Cancer, 3rd edn. New York: Wiley, 2006.
5. O’Sullivan B, Brierley J, D’Cruz A, Fey M, Pollock R, Vermorken J, Huang S.
Manual of Clinical Oncology, 9th edn. Oxford: Wiley-Blackwell, 2015.
6. The World Health Organization. Cancer Control Knowledge into Action,

Guide for Effective Programs. Available at: www.who.int/cancer/modules/
en/(accessed Aug. 2016).
7. Gupta S, Aitken J, Bartels U, et al. Paediatric cancer stage in population-
based cancer registries: the Toronto consensus principles and guidelines.
Lancet Oncol 2016; 17: e163–172.
8. SNOMED International: The Systematized Nomenclature of Human and
Veterinary Medicine. Northfield, Ill: College of American Pathologists.
Available at: www.cap.org (accessed Aug. 2016).
PART II
LUNG CANCER
MK, Wittekind Ch, eds. UICC TNM Classification of
2
8th Edition of TNM
for Lung Cancer
Introductory Notes
The classification applies to carcinomas of the lung including
non-small cell and small cell carcinomas, and bronchopulmo-
nary carcinoid tumours.
Each site is described under the following headings:
• Rules for classification with the procedures for assess-
ing T, N, and M categories; additional methods may be
used when they enhance the accuracy of appraisal before
treatment
• Anatomical subsites where appropriate
• TNM clinical classification
• pTNM pathological classification
• Stage
Regional Lymph Nodes

The regional lymph nodes extend from the supraclavicular
region to the diaphragm. Direct extension of the primary
tumour into lymph nodes is classified as lymph node
metastasis.
56 | PART II | LUNG CANCER
Lung
(ICD-O-3 C34)
Rules for Classification
The classification applies to carcinomas of the lung includ-
ing non-small cell carcinomas, small cell carcinomas, and
bronchopulmonary carcinoid tumours. It does not apply to
sarcomas and other rare tumours.
Changes in this edition from the seventh edition are based
upon recommendations from the International Association for
the Study of Lung Cancer (IASLC) Staging Project (see refer-
ences).1–6
There should be histological confirmation of the disease
and division of cases by histological type.
The following are the procedures for assessing T, N, and
M categories:
T categories Physical examination, imaging, endoscopy,
and/or surgical exploration
N categories Physical examination, imaging, endoscopy,
M categories Physical examination, imaging, and/or surgical
exploration
Anatomical Subsites
1. Main bronchus (C34.0)
2. Upper lobe (C34.1)
3. Middle lobe (C34.2)
4. Lower lobe (C34.3)

The regional lymph nodes are the intrathoracic nodes (medi-
astinal, hilar, lobar, interlobar, segmental, and subsegmental),
scalene, and supraclavicular lymph nodes.
CH 2 | 8TH EDITION OF TNM FOR LUNG CANCER | 57

TX Primary tumour cannot be assessed, or tumour proven by
the presence of malignant cells in sputum or bronchial
washings but not visualized by imaging or bronchoscopy
Tis Carcinoma in situa
T1 Tumour 3 cm or less in greatest dimension, surrounded
by lung or visceral pleura, without bronchoscopic
evidence of invasion more proximal than the lobar
bronchus (i.e., not in the main bronchus)b
T1mi Minimally invasive adenocarcinomac
T1a Tumour 1 cm or less in greatest dimensionb
T1b Tumour more than 1 cm but not more than 2 cm
in greatest dimensionb
T1c Tumour more than 2 cm but not more than 3 cm
in greatest dimensionb
T2 Tumour more than 3 cm but not more than 5 cm; or
tumour with any of the following featuresd
• Involves main bronchus regardless of distance to the
carina, but without involvement of the carina
• Invades visceral pleura
• Associated with atelectasis or obstructive pneumonitis
that extends to thehilar region either involving part of
or the entire lung
T2a Tumour more than 3 cm but not more than 4 cm
in greatest dimension
T3 Tumour more than 5 cm but not more than 7 cm in
greatest dimension or one that directly invades any of
the following: parietal pleura, chest wall (including
superior sulcus tumours), phrenic nerve, parietal

pericardium; or separate tumour nodule(s) in the same
lobe as the primary
T4 Tumour more than 7 cm or of any size that invades any
of the following: diaphragm, mediastinum, heart, great
vessels, trachea, recurrent laryngeal nerve, oesophagus,
vertebral body, carina; separate tumour nodule(s) in a
different ipsilateral lobe to that of the primary

N1 Metastasis in ipsilateral peribronchial and/or ipsilateral
hilar lymph nodes and intrapulmonary nodes, including
involvement by direct extension
N2 Metastasis in ipsilateral mediastinal and/or subcarinal
lymph node(s)
N3 Metastasis in contralateral mediastinal, contralateral
hilar, ipsilateral or contralateral scalene, or supraclavicular
lymph node(s)
M – Distant Metastasis
M1a Separate tumour nodule(s) in a contralateral lobe;
tumour with pleural or pericardial nodules or malignant
pleural or pericardial effusione
M1b Single extrathoracic metastasis in a single organf
M1c Multiple extrathoracic metastasis in a single or
multiple organs
Notes
a
Tis includes adenocarcinoma in situ and squamous carcinoma in situ.
b
The uncommon superficial spreading tumour of any size with its
invasive component limited to the bronchial wall, which may extend
proximal to the main bronchus, is also classified as T1a.
c
Solitary adenocarcinoma (not more than 3 cm in greatest dimen-
sion), with a predominantly lepidic pattern and not more than 5 mm
invasion in greatest dimension in any one focus.
d
T2 tumours with these features are classified T2a if 4 cm or less, or
if size cannot be determined and T2b if greater than 4 cm but not
larger than 5 cm.
e
Most pleural (pericardial) effusions with lung cancer are due to
tumour. In a few patients, however, multiple microscopic examina-
tions of pleural (pericardial) fluid are negative for tumour, and the
fluid is non-bloody and is not an exudate. Where these elements
and clinical judgment dictate that the effusion is not related to the
tumour, the effusion should be excluded as a staging descriptor.
f
This includes involvement of a single non-regional node.

The pT and pN categories correspond to the T and N catego-
ries. For pM see page 44.
pN0 Histological examination of hilar and mediastinal
lymphadenectomy specimen(s) will ordinarily include 6
or more lymph nodes/stations. Three of these nodes
stations should be mediastinal, including the subcarinal
nodes and three from N1 nodes/stations. Labelling
according to the IASLC chart and table of definitions
given in the TNM Supplement is desirable. If all the lymph
nodes examined are negative, but the number ordinarily
examined is not met, classify as pN0.
Stage
Occult carcinoma TX N0 M0
Stage 0 Tis N0 M0
Stage IA T1 N0 M0
Stage IA1 T1mi N0 M0

T1a N0 M0
Stage IA2 T1b N0 M0
Stage IA3 T1c N0 M0
Stage IB T2a N0 M0
Stage IIA T2b N0 M0
Stage IIB T1a-c, T2a, b N1 M0
T3 N0 M0
Stage IIIA T1a-c, T2a, b N2 M0
T3 N1 M0
T4 N0, N1 M0
Stage IIIB T1a-c, T2a, b N3 M0
T3, T4 N2 M0
Stage IIIC T3, T4 N3 M0
Stage IV Any T Any N M1
Stage IVA Any T Any N M1a, M1b
Stage IVB Any T Any N M1c

Prognostic Factors Grid–Non-Small Cell Lung Carcinoma

Prognostic factors in surgically resected NSCLC
Prognostic Tumour Host Environment
Factors Related Related Related
Essential T category Weight loss Resection margins
N category Performance Adequacy of
Extracapsular nodal status mediastinal
extension dissection
Additional Histological type Gender
Grade Symptom
Vessel invasion burden
Tumour size
New and Molecular/ Quality of life
promising biological markers Marital status
Prognostic risk factors in advanced (locally-advanced or metastatic) NSCLC

Essential Stage Weight loss Chemother-
Superior vena cava Performance apy
obstruction (SVCO) status Targeted
Oligometastatic disease therapy
Number of sites
Additional Number of metastatic sites Gender

Pleural effusion
Liver metastasis
Haemoglobin
Lactate dehydrogenase (LDH)
Albumin
New and Molecular/ Quality of life

promising biological markers Marital status
Anxiety/
depression
Source for both tables: UICC Manual of Clinical Oncology, Ninth Edition. Edited by Brian
O’Sullivan, James D. Brierley, Anil K. D’Cruz, Martin F. Fey, Raphael Pollock, Jan B.
Vermorken and Shao Hui Huang. © 2015 UICC. Published 2015 by John Wiley & Sons, Ltd.
Prognostic Factors Grid–Small Cell Lung Carcinoma

Prognostic risk factors in SCLC
Essential Stage Performance Chemotherapy
status Thoracic
Age radiotherapy
Comorbidity Prophylactic
cranial
radiotherapy
Additional LDH
Alkaline phosphatase
Cushing syndrome
M0 – mediastinal
involvement
M1 – number of sites
Brain or bone
involvement
White blood cell count
(WBC)/platelet count
New and Molecular/

promising biological markers
Source: UICC Manual of Clinical Oncology, Ninth Edition. Edited by Brian O’Sullivan,
James D. Brierley, Anil K. D’Cruz, Martin F. Fey, Raphael Pollock, Jan B. Vermorken and
Shao Hui Huang. © 2015 UICC. Published 2015 by John Wiley & Sons, Ltd.
References
1. Rami-Porta R, Bolejack V, Giroux DJ, et al. The IASLC Lung Cancer Staging
Project: the new database to inform the 8th edition of the TNM classifica-
tion of lung cancer. J Thorac Oncol 2014; 9: 1618–1624.
2. Rami-Porta R, Bolejack V, Crowley J, et al. The IASLC Lung Cancer Staging
Project: proposals for the revisions of the T descriptors in the forthcoming
10: 990–1003.
3. Asamura H, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging
10: 1675–1684.
4. Eberhardt WEE, Mitchell A, Crowley J, et al. The IASLC Lung Cancer Staging
Project: proposals for the revisions of the M descriptors in the forthcoming
10: 1515–1522.
5. Goldstraw P, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging
Project: proposals for the revision of the TNM stage grouping in the forth-
coming (eighth) edition of the TNM classification for lung cancer. J Thorac
Oncol 2016;11: 39–51.
6. Nicholson AG, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging
Project: proposals for the revision of the clinical and pathological staging
classification for lung cancer. J Thorac Oncol 2016;11: 300–311.
Executive Editor’s Note: This chapter has
been reprinted from Wittekind Ch, Compton CC,
Brierley J, Sobin LH (eds) UICC TNM Supplement A
Commentary on Uniform Use, fourth edition, John
Wiley & Sons, Ltd., Oxford, 2012. Where needed, the
text has been updated according to the 8th edition
of the TNM classification of lung cancer.
3
Site-Specific Explanatory Notes
for Lung Tumours

The classification applies to all types of carcinoma including
non-small cell and small cell carcinoma and to broncho-pul-
monary carcinoid tumours. It does not apply to sarcomas and
other rare tumours.
Changes to the 7th edition are based upon recommenda-

tions from the IASLC Lung Cancer Staging Project.1-12
Clinical classification (Pre-treatment clinical classifica-

tion), designated TNM (or cTNM), is essential to select and
evaluate therapy. This is based on evidence acquired before
treatment. Such evidence arises from physical examination,
imaging (e.g., computed tomography and positron emission
tomography), endoscopy (bronchoscopy or oesophagoscopy,
with/without ultrasound directed biopsies (EBUS, EUS)),
biopsy (including mediastinoscopy, mediastinotomy, thoraco-
centesis and video-assisted thoracoscopy), as well as surgical
exploration, and other relevant examinations such as pleural/
pericardial aspiration for cytology.
Pathological classification (post-surgical histopathologi-
cal classification), designated pTNM, provides the most precise
data to estimate prognosis and calculate end results. This is

based on the evidence acquired before treatment, supple-
mented or modified by the additional evidence acquired from
surgery and from pathological examination. The pathological
assessment of the primary tumour (pT) entails a resection of
the primary tumour, or biopsy adequate to evaluate the high-
est pT category. Removal of nodes adequate to validate the
absence of regional lymph node metastasis is required for pN0.
The pathological assessment of distant metastasis (pM) entails
microscopic examination.
Pathologic staging depends on the proven anatomic
extent of disease, whether or not the primary lesion has been
completely removed. If a biopsied primary tumour technically
cannot be removed, or when it is unreasonable to remove it,
the criteria for pathologic classification and staging are satis-
fied without total removal of the primary cancer if: a) biopsy
has confirmed a pT category and there is microscopical con-
firmation of nodal disease at any level (pN1-3), b) there is
microscopical confirmation of the highest N category (pN3),
or c) there is microscopical confirmation of pM1.
General Rule 3 states that clinical and pathological data
may be combined when only partial information is available
in either the pathological classification or the clinical classifi-
cation, e.g. the classification of a case designated as cT1 pN2
cM1 or pT2 cN0 cM1 would be considered a clinical classifica-
tion whilst in a case designated pT2 pN2 cM1, cT2 pN3 cM0
or cT2 cN0 pM1 case it would be appropriate to designate a
pathological classification.
CH 3 | SITE-SPECIFIC EXPLANATORY NOTES FOR LUNG TUMOURS | 67
Histopathologic Type
Table 3.1. 2015 WHO Classification of Lung Tumours a,b,c
Histologic Type and Subtypes ICDO Code
Epithelial tumours
Adenocarcinoma 8140/3
Lepidic adenocarcinomae 8250/3d
Acinar adenocarcinoma 8551/3d
Papillary adenocarcinoma 8260/3
Micropapillary adenocarcinoma e
8265/3
Solid adenocarcinoma 8230/3
Invasive mucinous adenocarcinomae 8253/3d
Mixed invasive mucinous and nonmucinous 8254/3d
adenocarcinoma
Colloid adenocarcinoma 8480/3
Fetal adenocarcinoma 8333/3
Enteric adenocarcinomae 8144/3
Minimally invasive adenocarcinomae
Nonmucinous 8256/3d
Mucinous 8257/3d
Preinvasive lesions
Atypical adenomatous hyperplasia 8250/0d
Adenocarcinoma in situ e
Nonmucinous 8250/2d
Mucinous 8253/2d
Squamous cell carcinoma 8070/3
Keratinizing squamous cell carcinoma e
8071/3
Nonkeratinizing squamous cell carcinomae 8072/3
Basaloid squamous cell carcinoma e
8083/3
Preinvasive lesion
Squamous cell carcinoma in situ 8070/2
continued on next page
Table 3.1. (continued)

Neuroendocrine tumours
Small cell carcinoma 8041/3
Combined small cell carcinoma 8045/3
Large cell neuroendocrine carcinoma 8013/3
Combined large cell neuroendocrine carcinoma 8013/3
Carcinoid tumours
Typical carcinoid tumour 8240/3
Atypical carcinoid tumour 8249/3
Preinvasive lesion
Diffuse idiopathic pulmonary neuroendocrine
8040/0d
cell hyperplasia
Large cell carcinoma 8012/3
Adenosquamous carcinoma 8560/3
Sarcomatoid carcinomas
Pleomorphic carcinoma 8022/3
Spindle cell carcinoma 8032/3
Giant cell carcinoma 8031/3
Carcinosarcoma 8980/3
Pulmonary blastoma 8972/3
Other and unclassified carcinomas
Lymphoepithelioma-like carcinoma 8082/3
NUT carcinoma e
8023/3d
Salivary gland-type tumours
Mucoepidermoid carcinoma 8430/3
Adenoid cystic carcinoma 8200/3
Epithelial-myoepithelial carcinoma 8562/3
Pleomorphic adenoma 8940/0
Neuroendocrine tumours (cont.)

Papillomas
Squamous cell papilloma 8052/0
Exophytic 8052/0
Inverted 8053/0
Glandular papilloma 8260/0
Mixed squamous and glandular papilloma 8560/0
Adenomas
Sclerosing pneumocytomae 8832/0
Alveolar adenoma 8251/0
Papillary adenoma 8260/0
Mucinous cystadenoma 8470/0
Mucous gland adenoma 8480/0
Mesenchymal tumours
Pulmonary hamartoma 8992/0d
Chondroma 9220/0
PEComatous tumours e
Lymphangioleiomyomatosis 9174/1
PEComa, benigne 8714/0
Clear cell tumour 8005/0
PEComa, malignante 8714/3
Congenital peribronchial myofibroblastic tumour 8827/1
Diffuse pulmonary lymphangiomatosis
Inflammatory myofibroblastic tumour 8825/1
Epithelioid hemangioendothelioma 9133/3
Pleuropulmonary blastoma 8973/3
Synovial sarcoma 9040/3
Pulmonary artery intimal sarcoma 9137/3
Pulmonary myxoid sarcoma with EWSR1–CREB1
8842/3d
translocatione
Table 3.1. (continued)

Myoepithelial tumourse
Myoepithelioma 8982/0
Myoepithelial carcinoma 8982/3
Lymphohistiocytic tumours
Extranodal marginal zone lymphomas of muco- 9699/3

sa-associated lymphoid tissue (MALT lymphoma)
Diffuse large cell lymphoma 9680/3

Lymphomatoid granulomatosis 9766/1
Intravascular large B cell lymphomae 9712/3
Pulmonary Langerhans cell histiocytosis 9751/1
Erdheim–Chester disease 9750/1
Tumours of ectopic origin
Germ cell tumours
Teratoma, mature 9080/0
Teratoma, immature 9080/1
Intrapulmonary thymoma 8580/3
Melanoma 8270/3
Meningioma, NOS 9530/0
Metastatic tumours
a
The morphology codes are from the ICDO (Fritz A, Percy C, Jack A, et al. International
Classification of Diseases for Oncology. 3rd ed. Geneva: World Health Organization
(WHO), 2000). Behavior is coded /0 for benign tumors, /1 for unspecified, borderline or
uncertain behavior, /2 for carcinoma in situ and grade III intraepithelial neoplasia, and
/3 for malignant tumors.
b
The classification is modified from the previous WHO classification3 taking into account
changes in our understanding of these lesions.
c
This table is reproduced from the 2015 WHO Classification by Travis WD, Brambilla
E, Burke AP, Marx A, Nicholson AG. WHO Classification of Tumours of the Lung, Pleura,
Thymus and Heart. Lyon: International Agency for Research on Cancer, 2015.
d
These new codes were approved by the International Agency on Cancer Research/WHO
Committee for ICDO.
e
New terms changed or entities added since 2004 WHO Classification by Travis WD,
Brambilla E, Müller-Hermelink HK, Harris CC. Pathology and Genetics: Tumours of the
Lung, Pleura, Thymus and Heart. Lyon: IARC, 2004.’
LCNEC, large cell neuroendocrine carcinoma, WHO, World Health Organization; ICDO
International Classification of Diseases for Oncology.
From: Travis WD, Brambilla E, Nicholson AG et al. The 2015 World Health Organization
Classification of Lung Tumors. Impact of genetic, clinical and radiologic advances since
the 2004 classification. J Thorac Oncol 2015; 10: 1243-1260. Used with permission.13
Summary Lung
TX Primary tumour cannot be assessed, or tumour proven
by the presence of malignant cells in sputum or bronchial
washings but not visualized by imaging or bronchoscopy
Tis Carcinoma in situ: Tis (AIS) for adenocarcinoma in situ;
Tis (SCIS) for squamous cell carcinoma in situ.
T1 Tumour 3 cm or less in greatest dimension, surrounded
by lung or visceral pleura, without bronchoscopic
evidence of invasion more proximal than the lobar bron-
chus (i.e., not in the main bronchus). The uncommon
superficial spreading tumour of any size with its inva-
sive component limited to the bronchial wall, which may
extend proximal to the main bronchus, is also classified
as T1a.
T1mi Minimally invasive adenocarcinoma
T1a Tumour 1 cm or less in greatest dimension
T1c Tumour more than 2 cm but not more than 3 cm
T2 Tumour more than 3 cm but not more than 5 cm; or

tumour with any of the following features. T2 tumours
with these features are classified T2a if 4 cm or less, or
if size cannot be determined; and T2b if greater than 4

cm but not larger than 5 cm.
• Involves main bronchus regardless of dis-
tance to the carina, but without involving
the carina
• Invades visceral pleura
• Associated with atelectasis or obstruc-
tive pneumonitis that extends to the hilar
region, either involving part of the lung or
the entire lung
T2a Tumour more than 3 cm but not more than 4 cm
T3 Tumour more than 5 cm but not more than 7 cm in
greatest dimension or one that directly invades any of
the following: parietal pleura (PL3), chest wall (includ-
ing superior sulcus tumours), phrenic nerve, parietal
pericardium; or associated separate tumour nodule(s)
in the same lobe as the primary
T4 Tumour more than 7 cm or one that invades any of the
following: diaphragm, mediastinum, heart, great ves-
sels, trachea, recurrent laryngeal nerve, oesophagus,
vertebral body, carina; separate tumour nodule(s) in a
different ipsilateral lobe to that of the primary

N1 Metastasis in ipsilateral peribronchial and/or ipsilateral
hilar lymph nodes and intrapulmonary nodes, including
involvement by direct extension
N2 Metastasis in ipsilateral mediastinal and/or subcarinal

lymph node(s)
N3 Metastasis in contralateral mediastinal, contralateral
hilar, ipsilateral or contralateral scalene, or supracla-
vicular lymph node(s)
M1a Separate tumour nodule(s) in a contralateral lobe;
tumour with pleural nodules or malignant pleural
or pericardial effusion. Most pleural (pericardial)
effusions with lung cancer are due to tumour. In a
few patients, however, multiple microscopic exami-
nations of pleural (pericardial) fluid are negative for
tumour, and the fluid is non-bloody and is not an
exudate. Where these elements and clinical judg-
ment dictate that the effusion is not related to the
tumour, the effusion should be excluded as a stag-
ing descriptor.
M1b Single extrathoracic metastasis in a single organ and
involvement of a single distant (non-regional) node
M1c Multiple extrathoracic metastases in one or several
organs
T Classification
1. Invasion of visceral pleura (T2) is defined as “invasion
beyond the elastic layer including invasion to the visceral
pleural surface”. The use of elastic stains is recommended
when this feature is not clear on routine histology.14 See
Atlas of Lung Cancer Staging, page 115, for the definitions
and a graphic description of visceral pleural invasion.
2. Tumour with direct invasion of an adjacent lobe, across the

fissure or by direct extension at a point where the fissure is
deficient, should be classified as T2a unless other criteria
assign a higher T category.
3. Invasion of phrenic nerve is classified as T3.
4. Vocal cord paralysis (resulting from involvement of the
recurrent branch of the vagus nerve), superior vena caval
obstruction, or compression of the trachea or oesophagus
may be related to direct extension of the primary tumour
or to lymph node involvement. If associated with direct
extension of the primary tumour a classification of T4 is
recommended. If the primary tumour is peripheral, vocal
cord paralysis is usually related to the presence of N2 dis-
ease and should be classified as such.
5. T4: the “great vessels” are
• Aorta
• Superior vena cava
• Inferior vena cava
• Main pulmonary artery (pulmonary trunk)
• Intrapericardial portions of the right and left pulmonary
artery
• Intrapericardial portions of the superior and inferior right
and left pulmonary veins
Invasion of more distal branches does not qualify for clas-
sification as T4
6. The designation of “Pancoast” tumour relates to the symp-
tom complex or syndrome caused by a tumour arising in
the superior sulcus of the lung that involves the inferior
branches of the brachial plexus (C8 and/or T1) and, in some
cases, the stellate ganglion. Some superior sulcus tumours
are more anteriorly located, and cause fewer neurological
symptoms but encase the subclavian vessels. The extent
of disease varies in these tumours, and they should be

classified according to the established rules. If there is
evidence of invasion of the vertebral body or spinal canal,
encasement of the subclavian vessels, or unequivocal
involvement of the superior branches of the brachial plexus
(C8 or above), the tumour is then classified as T4. If no crite-
ria for T4 disease are present, the tumour is classified as T3.
7. Direct extension to parietal pericardium is classified T3 and
to visceral pericardium, T4.
8. Tumour extending to rib is classified as T3.
9. The uncommon superficial spreading tumour of any size
with its invasive component limited to the bronchial wall,
which may extend proximal to the main bronchus, is clas-
sified as T1a.
10. The classification of additional tumour nodules in lung
cancer depends upon their histological appearances. a)
In most situations in which additional tumour nodules
are found in association with a lung primary these are
metastatic nodules, with identical histological appear-
ances to that of the primary tumour. If limited to the lobe
of the primary tumour such tumours are classified as T3,
when found in other ipsilateral lobes are designated as T4
and if found in the contralateral lung are designated M1a.
b) Multiple tumours may be considered to be synchronous
primaries if they are of different histological cell types.
Multiple tumours of similar histological appearance should
only be considered to be synchronous primary tumours if
in the opinion of the pathologist, based on features such
as differences in morphology, immunohistochemistry and/
or molecular studies, or, in the case of squamous cancers,
are associated with carcinoma in situ, they represent dif-
fering sub-types of the same histopathological cell type.
Such cases should also have no evidence of mediastinal

nodal metastases or of nodal metastases within a common
nodal drainage. These circumstances are most commonly
encountered when dealing with either bronchioloalveolar
carcinomas or adenocarcinomas of mixed subtype with
a bronchioloalveolar component. Multiple synchronous
primary tumours should be staged separately. The highest
T category and stage of disease should be assigned and the
multiplicity or the number of tumours should be indicated
in parenthesis, e.g. T2(m) or T2. This distinction may require
histopathological confirmation of cell type from more than
one tumour nodule, where clinically appropriate.
Executive Editor’s Note: Please, see Chapter 5 for additional

recommendations on how to classify lung cancers with multiple
lesions.
In the above classification lung differs from other sites in

the application of General Rule 5 as the classification of addi-
tional tumour nodules applies not only to grossly recognizable
tumours but also those that are microscopic or otherwise only
discovered on pathological examination, a not unusual finding
in lung cancer.
11. Invasion into mediastinal fat is T4. However, if such inva-
sion is clearly limited to fat within the hilum, classification
as T2a or T2b is appropriate, depending upon size, unless
other features dictate a higher T category.
N Classification
1. The regional lymph nodes are the intrathoracic, scalene,
and supraclavicular nodes.
2. The International Association for the Study of Lung Cancer
(IASLC) lymph node definitions are now the recommended

means of describing regional lymph node involvement for
lung cancers15 (see Table 3.2 and Figure 3.1). In this nomen-
clature ipsilateral or contralateral node involvement in #1
would be classified as N3. Involvement of mediastinal nodes,
if limited to the midline stations or ipsilateral stations (#2-9),
would be classified as N2. Involvement of #10-14 if ipsilateral
would be classified as N1. Contralateral involvement of # 2,
4, 5, 6, 8, 9, 10-14 would be classified as N3.
3. Direct extension of the primary tumour into lymph nodes
is classified as lymph node metastasis.
4. The IASLC nodal chart has been adopted as the new inter-
national chart for the documentation of nodal stations at
clinical or pathological staging where detailed assessment
of nodes has been made, usually by invasive techniques
or at thoracotomy. The concept of nodal zones was sug-
gested in the 7th edition of the TNM classification of lung
cancer as a simpler, more utilitarian system for clinical
staging where surgical exploration of lymph nodes has
not been performed. An exploratory analysis suggested
that nodal extent could be grouped into three categories
with differing prognoses: i) involvement of a single N1 zone,
designated as N1a, ii) involvement of more than one N1
zone, designated as N1b, or a single N2 zone, designated
N2a, and iii) involvement of more than one N2 zone, desig-
nated as N2b. It was suggested that radiologists, clinicians
and oncologists use the classification prospectively, where
more detailed data on nodal stations is not available, to
assess the utility of such a classification for future revision.
Executive Editor’s Note: For the 8th edition, quantification of

nodal disease has been based on the number of nodal stations
Table 3.2. IASLC Nodal Definitions.

Nodal
station Description Definition
#1 Low cervical, Upper border: lower margin of cricoid
(Left/ supraclavicular cartilage
Right) and sternal Lower border: clavicles bilaterally and,
notch nodes in the midline, the upper border of the
manubrium
#L1 and #R1 limited by the midline of
the trachea.
#2 Upper 2R: Upper border: apex of lung and pleu-
(Left/ paratracheal ral space and, in the midline, the upper
Right) nodes border of the manubrium
Lower border: intersection of caudal
margin of innominate vein with the
trachea
2L: Upper border: apex of the lung and
pleural space and, in the midline, the
upper border of the manubrium
Lower border: superior border of the
aortic arch
As for #4, in #2 the oncologic midline
is along the left lateral border of the
trachea.
#3 Pre-vascular 3a: Prevascular
and On the right
retrotracheal upper border: apex of chest
nodes lower border: level of carina
anterior border: posterior aspect of
sternum
posterior border: anterior border of
superior vena cava
On the left
upper border: apex of chest
lower border: level of carina
anterior border: posterior aspect of
sternum
posterior border: left carotid artery
3p: Retrotracheal
upper border: apex of chest
lower border: carina
#4 Lower 4R: includes right paratracheal nodes,

(Left/ paratracheal and pretracheal nodes extending to the
Right) nodes left lateral border of trachea
upper border: intersection of caudal
margin of innominate vein with the
trachea
lower border: lower border of azygos
vein
4L: includes nodes to the left of the left
lateral border of the trachea, medial to
the ligamentum arteriosum
upper border: upper margin of the
aortic arch
lower border: upper rim of the left main
pulmonary artery
#5 Subaortic Subaortic lymph nodes lateral to the

(aorto- ligamentum arteriosum
pulmonary upper border: the lower border of the
window) aortic arch
lower border: upper rim of the left main
pulmonary artery
#6 Para-aortic Lymph nodes anterior and lateral to
nodes the ascending aorta and aortic arch
(ascending upper border: a line tangential to the
aorta or upper
phrenic) border of the aortic arch
lower border: the lower border of the
aortic arch
#7 Subcarinal upper border: the carina of the trachea
nodes lower border: the upper border of the
lower lobe bronchus on the left; the
lower border of the
bronchus intermedius on the right
Table 3.2. (cont.).

Nodal
station Description Definition
#8 Para- Nodes lying adjacent to the wall of the
(Left/ oesophageal oesophagus and to the right or left of the
Right) nodes (below midline, excluding subcarinal nodes
carina) upper border: the upper border of the
lower lobe bronchus on the left; the
lower border of the
bronchus intermedius on the right
lower border: the diaphragm
#9 Pulmonary liga- Nodes lying within the pulmonary liga-
(Left/ ment nodes ment
Right) upper border: the inferior pulmonary
vein
lower border: the diaphragm
#10 Hilar nodes Includes nodes immediately adjacent
(Left/ to the mainstem bronchus and hilar
Right) vessels including the proximal portions
of the pulmonary veins and main
pulmonary artery
upper border: the lower rim of the
azygos vein on the right; upper rim of
the pulmonary artery on the left
lower border: interlobar region
bilaterally
#11 Interlobar Between the origin of the lobar bronchi
nodes
*#11s: between the upper lobe bronchus
and bronchus intermedius on the right
*#11i: between the middle and lower
lobe bronchi on the right
*
optional sub-categories
#12 Lobar nodes Adjacent to the lobar bronchi
#13 Segmental Adjacent to the segmental bronchi

nodes
#14 Sub-segmental Adjacent to the subsegmental bronchi
nodes
Supraclavicular zone
1 Low cervical, supraclavicular,
and sternal notch nodes
SUPERIOR MEDIASTINAL NODES

Upper zone
2R Upper Paratracheal (right)
2L Upper Paratracheal (left)
3a Prevascular
3p Retrotracheal
4R Lower Paratracheal (right)

4L Lower Paratracheal (left)
AORTIC NODES
AP zone
5 Subaortic
6 Para-aortic (ascending aorta or phrenic)
INFERIOR MEDIASTINAL NODES

Subcarinal zone
7 Subcarinal
Lower zone
8 Paraesophageal (below carina)
9 Pulmonary ligament
N1 NODES
Hilar/Interlobar zone
10 Hilar
11 Interlobar
Peripheral zone
12 Lobar
13 Segmental
14 Subsegmental
Figure 3.1 International Association for the Study of Lung Cancer Nodal Chart
with Stations and Zones. Copyright ©2008 Aletta Ann Frazier, MD.
involved. The survival analyses performed on patients whose

tumours were resected and had an adequate intraoperative
nodal evaluation revealed four categories with different prog-
nosis: i) involvement of a single N1 station, designated as N1a, ii)
involvement of more than one N1 station, designated as N1b, or
involvement of one N2 station without N1 disease (skip metasta-
sis), designated as N2a1, iii) involvement of one N2 station with
N1 disease, designated as N2a2, and iv) involvement of more
than one N2 station, designated N2b. From the analyses of nodal
zones and stations, it is evident that the amount of nodal dis-
ease has prognostic impact. It is suggested that quantification
of nodal disease be made with the available methods at clini-
cal staging, and with systematic nodal dissection at the time of
lung resection, either open or video-assisted. Quantifying nodal
disease assists physicians in refining prognosis, and in planning
therapy and follow-up.
M Classification
1. Pleural/pericardial effusions are classified as M1a, Most
pleural (pericardial) effusions with lung cancer are due to
tumour. In a few patients, however, multiple microscopi-
cal examinations of pleural (pericardial) fluid are negative
for tumour, and the fluid is non-bloody and is not an exu-
date. Where these elements and clinical judgment dictate
that the effusion is not related to the tumour, the effusion
should be excluded as a descriptor.
2. Tumour foci in the ipsilateral parietal and visceral pleura
that are discontinuous from direct pleural invasion by the
primary tumour are classified M1a.
3. Pericardial effusion/pericardial nodules are classified as
M1a, the same as pleural effusion/nodules.
4. Separate tumour nodules of similar histological appear-
ance are classed as M1a if in the contralateral lung (vide

supra regarding synchronous primaries).
5. Distant metastases are classified as M1b if single and M1c
if multiple in one or in several organs.
6. Discontinuous tumours outside the parietal pleura in the
chest wall or in the diaphragm are classified M1b or M1c
depending on the number of lesions.
7. In cases classified as M1b and M1c due to distant metasta-
ses it is important to document all of the sites of metastatic
disease, whether the sites are solitary or multiple and in addi-
tion if the metastases at each site are solitary or multiple.
V Classification
In the lung, arterioles are frequently invaded by cancers. For
this reason the V classification is applicable to indicate vascu-
lar invasion, whether venous or arteriolar.
Small Cell Carcinoma

The TNM classification and stage grouping should be applied to
small cell lung cancer (SCLC). TNM is of significance for progno-
sis of small cell carcinoma,6 and has the advantage of providing
a uniform detailed classification of tumour spread. TNM should
be used when undertaking trials in SCLC. The former categories
“limited” and “extensive” for small cell carcinoma have been
inconsistently defined and used.
Broncho-Pulmonary Carcinoid Tumours

The TNM classification and stage groupings should be applied
to carcinoid tumours, typical and atypical variants.16
Isolated Tumour Cells (ITC)

Isolated tumour cells (ITC) are single tumour cells or small
clusters of cells not more than 0.2 mm in greatest dimension
that are detected by routine histological stains, immunohis-

tochemistry or molecular methods. Cases with ITC in lymph
nodes or at distant sites should be classified as N0 or M0,
respectively. The same applies to cases with findings sugges-
tive of tumour cells or their components by nonmorphologic
techniques such as flow cytometry or DNA analysis.
The following classification of ITC may be used:
N0 No regional lymph node metastasis histologically,
no special examination for ITC
N0(i-) No regional lymph node metastasis histologically,
negative morphological findings for ITC
N0(i+) No regional lymph node metastasis histologically,
positive morphological findings for ITC
N0(mol-) No regional lymph node metastasis histologically,
negative nonmorphological findings for ITC
N0(mol+) No regional lymph node metastasis histologically,
positive nonmorphological findings for ITC
Expansion of the R Classification

RX Presence of residual tumour cannot be assessed
R0 Complete resection
All of the following are satisfied:
a) Resection margins confirmed to be clear on microscopy
b) Six nodes/nodal stations removed/sampled for histological
examination. These should include three nodes/stations
from the mediastinum, one of which should be subcarinal
node #7 and three nodes/stations from the hilum or other
N1 locations*
R1(cy+)
The requirements for R0 have been met, but pleural lavage
cytology (PLC) is positive for malignant cells.
A recent meta-analysis17 has confirmed that PLC, under-

taken immediately on thoracotomy and shown to be positive
for cancer cells, has an adverse and independent prognostic
impact following complete resection. Such patients may be
candidates for adjuvant chemotherapy. Surgeons and pathol-
ogists are encouraged to undertake this simple addition to
intra-operative staging and collect data on PLC+ve and PLC-ve
cases. Where the resection fulfills all of the requirements for
classification as a complete resection, R0, but PLC has been
performed and is positive, the resection should be classified
as R1(cy+).
R1(is)
The requirements for R0 have been met, but in situ carcinoma
is found at the bronchial resection margin.
R1 Microscopic incomplete resection

Microscopic evidence of residual disease at any of the follow-
ing sites:
a) Resection margins
b) Extracapsular extension at margins of resected nodes
c) Positive cytology of pleural/pericardial effusions (R1(cy+))
R2 Macroscopic incomplete resection

Macroscopic evidence of residual disease at any of the fol-
lowing sites:
a) Resection margins
b) Extracapsular extension at margins of resected nodes
c) Positive nodes not resected at surgery
d) Pleural/pericardial nodules
*If all resected/sampled lymph nodes are negative, but the
number ordinarily included in a lymphadenectomy specimen
is not met, classify as pN0. If resection has been performed,

and otherwise fulfils the requirements for complete resection,
it should be classified as R0.
A new category, ‘R0(un)’, is proposed to document those
other features that fall within the proposed category of ‘uncer-
tain resection’, i.e. no macroscopic or microscopic evidence of
residual disease but any of the following reservations applies:
i) Nodal assessment has been based on less than the number
of nodes/stations recommended for complete resection
ii) The highest mediastinal node removed/sampled is positive
References
1. Rami-Porta R, Bolejack V, Giroux DJ et al. The IASLC lung cancer staging
project: the new database to inform the eighth edition of the TNM clas-
sification of lung cancer. J Thorac Oncol 2014; 9: 1618-1624.
2. Rami-Porta R, Bolejack V, Crowley J et al. The IASLC lung cancer staging
project: proposals for the revisions of the T descriptors in the forthcoming
10: 990-1003.
3. Asamura H, Chansky K, Crowley J et al. The IASLC lung cancer staging
project: proposals for the revisions of the N descriptors in the forthcoming
10: 1675-1684.
4. Eberhardt WEE, Mitchell A, Crowley J et al. The IASLC lung cancer staging
project: proposals for the revisions of the M descriptors in the forthcoming
10: 1515-1522.
5. Goldstraw P, Chansky K, Crowley J et al. The IASLC lung cancer staging
project: proposals for the revision of the stage grouping in the forthcom-
2016; 11: 39-51.
6. Nicholson AG, Chansky K, Crowley J et al. The IASLC lung cancer staging
project: proposals for the revision of the clinical and pathologic staging

1204-1223.
Staging Project: proposed criteria to distinguish separate primary lung
cancers from metastatic foci in patients with two lung tumors in the forth-
coming eighth edition of the TNM classification for lung cancer. J Thorac
Oncol 2016; 11: 651-665.
Staging Project: proposals for the classification of lung cancer with
separate tumor nodules in the forthcoming eighth edition of the TNM
Staging Project: proposals for the application of TNM staging rules to
lung cancer presenting as multiple nodules with ground glass or lepidic
features or a pneumonic-type of involvement in the forthcoming eighth
Staging Project: proposals for revisions of the classification of lung cancers
with multiple pulmonary sites of involvement in the forthcoming eighth
12. Detterbeck F, Groome P, Bolejack V et al. The IASLC Lung Cancer Staging
Project: methodology and validation used in the development of propos-
als for revision if the stage classification of non-small cell lung cancer in
the forthcoming (eighth) edition of the TNM classification of lung cancer.
J Thorac Oncol 2016; 11: 1433-1446.
13. Travis WD, Brambilla E, Nicholson AG et al. The 2015 World Health
Organization Classification of Lung Tumors. Impact of genetic,
clinical and radiologic advances since the 2004 classification.
J Thorac Oncol 2015; 10: 1243-1260.
14. Travis WD, Brambilla E, Rami-Porta R, et al. Visceral pleural invasion:
Pathologic criteria and use of elastic stains: Proposals for the 7th edition
of the TNM classification for lung cancer. J Thorac Oncol 2008; 3: 1384-1390.
15. Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw
P. The IASLC Lung Cancer Staging Project. A proposal for a new interna-
tional lymph node map in the forthcoming seventh edition of the TNM
16. Travis WD, Giroux DJ, Chansky K, et al. The IASLC Lung Cancer Project:
proposals for the inclusion of broncho-pulmonary carcinoid tumors in the
forthcoming (seventh) edition of the TNM classification for lung cancer. J

Thorac Oncol 2008; 3: 1213-1223.
17. Lim E, Clough R, Goldstraw P et al. Impact of positive pleural lavage cytol-
ogy on survival of patients having lung resection for non-small-cell lung
cancer: An international individual patient data meta-analysis. J Thorac
Cardiovasc Surg 2010; 139: 1441-1446.
Executive Editor’s Note: This chapter has
been reprinted from Wittekind Ch, Compton CC,
Brierley J, Sobin LH (eds) UICC TNM Supplement A
Commentary on Uniform Use, fourth edition, John
Wiley & Sons, Ltd., Oxford, 2012. Where needed, the
text has been updated according to the 8th edition
of the TNM classification of lung cancer.
4
Site-Specific Recommendations
for pT and pN Categories
pT – Primary Tumour
The pathological assessment of the primary tumour (pT)
entails resection of the primary tumours sufficient to evalu-
ate the highest pT category
pT3 or less
Pathological examination of the primary carcinoma shows
no gross tumour at the margins of resection (with or without
microscopic involvement). pT3 may include additional tumour
nodule(s) of similar histological appearance in the lobe of the
primary tumour.
pT4
Microscopic confirmation of invasion of any of the following:
diaphragm, mediastinum, heart, great vessels, trachea, recur-
rent laryngeal nerve, oesophagus, vertebral body, carina or
microscopic confirmation of separate tumour nodule(s) of
similar histological appearance in another ipsilateral lobe
(not the lobe of the primary tumour)
pN – Regional Lymph Nodes

There are no evidence-based guidelines regarding the number
of lymph nodes to be removed at surgery for adequate stag-

ing. However, adequate N staging is generally considered to
include sampling or dissection of lymph nodes from stations
2R, 4R, 7, 10R and 11R for right-sided tumours, and stations
5, 6, 7, 10L and 11L for left-sided tumours. Station 9 lymph
nodes should also be evaluated for lower lobe tumours. The
more peripheral lymph nodes at stations 12-14 are usually
evaluated by the pathologist in lobectomy or pneumonectomy
specimens but may be separately removed when sublobar
resections (e.g. segmentectomy) are performed. These should
be labelled in accordance with the IASLC chart and table of
definitions1 (see table and map on pages 78-81).
The UICC recommends that at least six lymph nodes/sta-
tions be removed/sampled and confirmed on histology to be
free of disease to confer pN0 status. Three of these nodes/
stations should be mediastinal, including the subcarinal nodes
(#7) and three from N1 nodes/stations.
If all resected/sampled lymph nodes are negative, but the
number recommended is not met, classify as pN0. If resection
has been performed, and otherwise fulfils the requirements
for complete resection, it should be classified as R0.
pN1
Microscopic confirmation of metastasis in ipsilateral peribron-
chial and/or ipsilateral hilar lymph nodes and intrapulmonary
nodes, including involvement by direct extension.
pN2
Microscopic confirmation of metastasis in ipsilateral medias-
tinal and/or subcarinal lymph node(s).
pN3
Microscopic confirmation of metastasis in contralateral medi-
CH 4 | SITE-SPECIFIC RECOMMENDATIONS FOR PT AND PN CATEGORIES | 93
astinal, contralateral hilar, ipsilateral or contraletaral scalene

or supraclavicular lymph node(s).
Reference
1. Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P.
The IASLC lung cancer staging project. A proposal for a new international
lymph node map in the forthcoming seventh edition of the TNM classifica-
tion for lung cancer. J Thorac Oncol 2009; 4: 568-577
5
New Site-Specific Recommendations
Proposed by the IASLC
Ramón Rami-Porta, Frank C. Detterbeck, William D. Travis,
and Hisao Asamura
The following recommendations for lung cancer classification

derive from the analyses of the International Association for
the Study of Lung Cancer (IASLC) database, the review of pub-
lished articles, and a wide international and multidisciplinary
consensus. The new categories for adenocarcinoma in situ and
minimally invasive adenocarcinoma have been accepted by
the Union for International Cancer Control (UICC) and by the
American Joint Committee on Cancer (AJCC), and will appear
in the 8th edition of their respective staging manuals; the other
recommendations are included in the 8th edition of the AJCC
Cancer Staging Manual, but are still under assessment by the
UICC. Presumably, they will appear in the 5th edition of the
UICC TNM Supplement – A Commentary on Uniform Use that
is traditionally published after the UICC TNM Classification of
Malignant Tumours.
New Categories for the New Adenocarcinomas

Adenocarcinoma in situ is classified as Tis (AIS) to differentiate
it from squamous cell carcinoma in situ, which is classified as
Tis (SCIS).1 Tis (AIS) and Tis (SCIS) N0 M0 are stage 0.2
Minimally invasive adenocarcinoma is classified as T1mi.1
T1mi N0 M0 is stage IA1, together with T1a N0 M0.2
Measurement of Tumour Size in Part-Solid

Non-Mucinous Adenocarcinomas
Part-solid adenocarcinomas present with a solid component
and a ground glass opacity on computed tomography (CT). At
pathological examination, the solid component usually cor-
responds to the invasive part; and the ground glass opacity,
to the lepidic part. To define the T category by tumour size,
only the size of the solid component on CT or the size of the
invasive component at pathologic examination are consid-
ered, because it is the size of the solid/invasive component
that determines prognosis. However, documentation of both
the size of the solid component/invasive part and of the
whole tumour including the ground glass and lepidic com-
ponents in radiology and pathology reports, respectively, is
recommended.1
Measurement of Tumour Size after Induction Therapy

This issue has been rarely discussed in depth before. The
recommendation of the IASLC is that tumour size can be mea-
sured by multiplying the percentage of viable tumour cells by
the total size of the tumour.1
Classification of Lung Cancers with Multiple Sites of

Involvement
To avoid ambiguity and to facilitate the homogeneous clas-
sification of lung cancer with multiple sites of disease, an
ad hoc sub-committee of the IASLC Staging and Prognostic
Factors Committee developed the following recommenda-
tions based on the analyses of the IASLC database where data
were available, the review of published reports and a wide
multidisciplinary and international consensus. The following
recommendations apply to grossly identified tumours and
CH 5 | NEW SITE-SPECIFIC RECOMMENDATIONS PROPOSED BY THE IASLC | 97
to those identified at microscopic examination, and differ

depending on the pattern of disease.3
• Synchronous and metachronous primary lung cancers.
Regardless of tumour location, a separate TNM is defined
for each tumour. The clinical and pathological criteria to
differentiate second primary from related tumours are
defined in Table 5.1.4
• Separate tumour nodules with similar histopathologic
features (intrapulmonary metastases). Classification
depends on the location of the separate tumour nodule(s):
T3 if the separate tumour nodule(s) is(are) in the same lobe
of the primary tumour; T4, if located in a different ipsilat-
eral lobe; M1a, if located in the contralateral lung. If there
are additional extrathoracic metastases, the tumour will
be classified as M1b or M1c depending on the number of
metastatic sites. The clinical and pathological criteria to
categorise separate tumour nodules (intrathoracic metas-
tasis) are defined in Table 5.2.5
• Multifocal pulmonary adenocarcinoma with ground
glass/lepidic features. Regardless of the location of the
tumours, the rule of the highest T with the number (#) or
(m) for multiple in parentheses, and an N and an M for
all of the multiple tumours collectively applies for these
tumours. Table 5.3 shows the clinical and pathologic cri-
teria to define these tumours.6
• Diffuse pneumonic-type lung adenocarcinoma. A) Single
focus of disease. The general TNM classification is applied,
with the T category defined by tumour size. B) Multiple foci
of disease. Tumour classification is based on the location
of the involved areas (including miliary involvement): T3, if
located in one lobe; T4, if located in other ipsilateral lobes;
M1a, if the contralateral lung is involved, with the
Table 5.1. Criteria for separate versus related pulmonary tumours.4

Clinical Criteria*
Tumours may be considered separate primary tumours if:
They are clearly of a different histologic type (e.g. squamous
carcinoma and adenocarcinoma) by biopsy
Tumours may be considered to be arising from a single tumour
source if:
Exactly matching breakpoints are identified by comparative genomic
hybridization
Relative arguments that favor separate tumours:
Different radiographic appearance or metabolic uptake
Different biomarker pattern (driver gene mutations)
Different rates of growth (if previous imaging is available)
Absence of nodal or systemic metastases
Relative arguments that favor a single tumour source:
Same radiographic appearance
Similar growth patterns (if previous imaging is available)
Significant nodal or systemic metastases
Same biomarker pattern (and same histotype)
Pathologic Criteria (i.e. after resection)**
Tumours may be considered separate primary tumours if:
They are clearly of a different histologic type (e.g. squamous
carcinoma and adenocarcinoma)
They are clearly different by a comprehensive histologic assessment
They are squamous carcinomas that have arisen from carcinoma in situ
Tumours may be considered to be arising from a single tumour
source if:
Exactly matching breakpoints are identified by comparative |
genomic hybridization
Relative arguments that favor separate tumours (to be considered
together with clinical factors):
Different pattern of biomarkers
Absence of nodal or systemic metastases
Relative arguments that favor a single tumour source (to be
considered together with clinical factors):
Matching appearance on comprehensive histologic assessment
Same biomarker pattern
Significant nodal or systemic metastases
*Note that a comprehensive histologic assessment is not included in clinical staging, as it requires
that the entire specimen has been resected.
**Pathologic information should be supplemented with any clinical information that is available.
Table 5.2. Criteria to categorize a lesion as a separate tumour nodule

(intrapulmonary metastasis)3,5
Clinical Criteria
Tumours should be considered to have a separate tumour
nodule(s) if:
There is a solid lung cancer and a separate tumour nodule(s) with a
similar solid appearance and with (presumed) matching histologic
appearance
• This applies whether or not a biopsy has been performed on the
lesions, provided that there is strong suspicion that the lesions
are histologically identical
• This applies whether or not there are sites of extrathoracic
metastases
AND provided that:

The lesions are NOT judged to be synchronous primary lung cancers
The lesions are NOT multifocal GG/L lung cancer (multiple nodules
with ground glass/lepidic features) or pneumonic-type of lung cancer
Pathologic Criteria
Tumours should be considered to have a separate tumour nodule(s)
(intrapulmonary metastasis) if:
There is a separate tumour nodule(s) of cancer in the lung with a
similar histologic appearance to a primary lung cancer
AND provided that:

The lesions are NOT judged to be synchronous primary lung cancers
The lesions are NOT multiple foci of LPA, MIA, AIS
Note: a radiographically solid appearance and the specific histologic subtype of solid
adenocarcinoma denote different things.
AIS, adenocarcinoma in situ; GG/L, ground glass/lepidic; LPA, lepidic predominant
adenocarcinoma; MIA, minimally invasive adenocarcinoma
Table 5.3. Criteria identifying multifocal ground glass/lepidic lung

adenocarcinoma.6
Clinical Criteria
Tumours should be considered multifocal GG/L lung
adenocarcinoma if:
There are multiple sub-solid nodules (either pure ground glass or
part-solid), with at least one suspected (or proven) to be cancer
• This applies whether or not a biopsy has been performed of the
nodules
• This applies if the other nodules(s) are found on biopsy to be AIS,
MIA, or LPA
• This applies if a nodule has become >50% solid but is judged
to have arisen from a GGN, provided there are other sub-solid
nodules
• GGN lesions <5mm or lesions suspected to be AAH are not
counted
Pathologic Criteria
Tumours should be considered multifocal GG/L lung

adenocarcinoma if:
There are multiple foci of LPA, MIA, or AIS
• This applies whether a detailed histologic assessment
(i.e. proportion of subtypes, etc.) shows a matching or different
appearance
• This applies if one lesion(s) is LPA, MIA or AIS and there are other
sub-solid nodules of which a biopsy has not been performed.
• This applies whether the nodule(s) are identified preoperatively
or only on pathologic examination
• Foci of AAH are not counted
AIS, adenocarcinoma in situ; GG/L, ground glass/lepidic; LPA, lepidic predominant
adenocarcinoma; MIA, minimally invasive adenocarcinoma
T category defined by the largest tumour. C) If tumour size

is difficult to determine: T4 applies if there is evidence
of involvement of another ipsilateral lobe. In all circum-
stances, the N category should apply to all pulmonary
sites and the appropriate M category should be applied
depending on the number and location of metastases. The
clinical and pathological criteria to define these tumours
are shown in Table 5.4.6
The basic radiographic and pathologic features, the rec-
ommended TNM classification and the conceptual view of the
four patterns of lung cancer with multiple sites of involvement
are summarised in Table 5.5.
Quantification of Nodal Disease

Quantification of nodal disease has prognostic impact. For the
7th edition of the TNM classification of lung cancer, quantifica-
tion of nodal disease was based on the number of involved
nodal zones.7 For the 8th edition, it is based on the number
of involved nodal stations.8 Both criteria separate groups of
tumours with statistically significant differences. However,
both were based on pathological findings of the lymphad-
enectomy specimen that could not be validated at clinical
staging. The recommendation from the IASLC is to quantify
nodal disease at pathological staging because it allows the
refinement of postoperative prognosis and assists in making
decisions on adjuvant therapy, but also to try to quantify it at
clinical staging with the available means. The subclassifica-
tion of nodal disease based on the number of involved nodal
stations is as follows:
• N1a: single station N1
• N1b: multiple station N1
• N2a1: single station N2 without N1 disease (skip metastasis)
Table 5.4. Criteria identifying the pneumonic-type of adenocarcinoma.6

Clinical Criteria
Tumours should be considered pneumonic-type of adenocarci-
noma if:
The cancer manifests in a regional distribution, similar to a pneumon-
ic infiltrate or consolidation
• This applies whether there is one confluent area or multiple
regions of disease. The region(s) may be confined to one lobe, in
multiple lobes, or bilateral, but should involve a regional pattern
of distribution.
• The involved areas may appear to be ground glass, solid
consolidation or a combination thereof.
• This can be applied when there is compelling suspicion of
malignancy whether or not a biopsy has been performed of the
area(s).
• This should not be applied to discrete nodules (i.e. GG/L nodules)
• This should not be applied to tumours causing bronchial
obstruction with resultant obstructive pneumonia or atelectasis
Pathologic Criteria
Tumours should be considered pneumonic-type of adenocarci-
noma if:
There is diffuse distribution of adenocarcinoma throughout a
region(s) of the lung, as opposed to a single well-demarcated mass or
multiple discrete well-demarcated nodules
• This typically involves an invasive mucinous adenocarcinoma,
although a mixed mucinous and non-mucinous pattern may
occur.
• The tumour may show a heterogeneous mixture of acinar, papil-
lary and micropapillary growth patterns, although it is usually
lepidic predominant.
GG/L, ground glass/lepidic
Table 5.5. Schematic summary of patterns of disease and TNM classification

of patients with lung cancer with multiple pulmonary sites of involvement.3
Separate
Tumour Pneumonic-
Second Nodule Multifocal Type of
Primary (Intrapulmonary GG/L Adenocarci-
Lung Cancer metastasis) Nodules noma
Imaging Two or more Typical lung Multiple Patchy areas
features distinct cancer ground of ground
masses with (e.g. solid, glass or glass and
imaging spiculated) part-solid consolidation
characteristics with separate nodules
of lung cancer solid nodule
(e.g. spicu-
lated)
Pathologic Different Distinct masses Adenocar- Same

features histotype or with the same cinomas histologic
different mor- morphologic with features
phology by features by prominent throughout
comprehen- comprehensive lepidic (most often
sive histologic histologic ᶜomponent invasive
assessment assessment (typically mucinous
varying adenocarci-
degrees of noma)
AIS, MIA,
LPA)
TNM Separate Location T based on T based on
classifica- cTNM and of separate highest T size or T3 if in
tion pTNM for each nodule relative lesion with single lobe,
cancer to primary site (#/m) T4 or M1a if
determines if indicating in different
T3, T4 or M1a; multiplic- ipsilateral or
single N and M ity; single contralateral
N and M lobes; single N
and M
Concep- Unrelated Single tumour, Separate Single tumour,
tual view tumours with tumours, diffuse
intrapulmonary albeit with pulmonary
metastasis similarities involvement
AIS, adenocarcinoma in situ; GG/L, ground glass/lepidic; LPA, lepidic-predominant adeno-
carcinoma; MIA, minimally invasive adenocarcinoma; p, pathologic; TNM, tumour, node,
metastasis.
• N2a2: single station N2 with N1 disease

• N2b: multiple station N2
Prognosis worsens as the number of involved nodal sta-
tions increases, but N1b and N2a1 have the same prognosis.8
References
1204-1223.
2. Goldstraw P, Chansky K, Crowley J et al. The IASLC Lung Cancer Staging
Project: proposals for the revision of the stage grouping in the forthcom-
2016; 11: 39-51.
Staging Project: summary of proposals for revisions of the classification of
lung cancers with multiple pulmonary sites of involvement in the forthcom-
ing eighth edition of the TNM classification. J Thorac Oncol 2016; 11:539-650.
Staging Project: background data and proposed criteria to distinguish
separate primary lung cancers from metastatic foci in patients with two
lung tumors in the forthcoming eighth edition of the TNM classification
for lung cancer. J Thorac Oncol 2016; 11: 651-665.
Staging Project: background data and proposals for the classification
of lung cancer with separate tumor nodules in the forthcoming eighth
edition of the TNM classification for lung cancer. J Thorac Oncol 2016; 11:
681-692.
Staging Project: background data and proposals for the application of
TNM staging rules to lung cancer presenting as multiple nodules with
ground glass or lepidic features or a pneumonic-type of involvement in
the forthcoming eighth edition of the TNM classification. J Thorac Oncol
2016; 11: 666-680.
7. Rusch VW, Crowley J, Giroux DJ, et al. The IASLC Lung Cancer Staging
Project: proposals for the revision of the N descriptors in the forthcoming
seventh edition of the TNM classifications for lung cancer. J Thorac Oncol
2007; 2: 603-612.
8. Asamura H, Chansky K, Crowley J et al. The IASLC Lung Cancer Staging
10: 1675-1684.
6
Atlas of Lung Cancer Staging
T1a, T1b T1c
Tumour:
Tumour: >2cm, ≤3cm
≤1cm
Tumour ≤3cm;
any associated
bronchoscopic
invasion should
not extend
Tumour: proximal
>1cm, to the lobar
≤2cm bronchus
Superficial spreading tumour of

any size with its invasive component
limited to the bronchial wall, which
may extend proximal to the main
bronchus is T1
Copyright ©2016 Aletta Ann Frazier, MD.

T2a T2b
Tumour:
> 3cm, ≤ 4cm
Tumour ≤ 4cm,
invasion of the
visceral pleura
Tumour involves
main bronchus,
regardless of Tumour:
distance from > 4cm, ≤ 5cm
carina but (with or
without carinal
without
involvement
other T2
descriptors)
Associated
atelectasis or
obstructive pneumonitis that extends
to the hilar region, either involving
part of the lung or the entire lung
Tumour in the main bronchus

< 2cm from the carina (without
involvement of the carina)
and/or associated atelectasis or
obstructive pneumonitis of
the entire lung
Note: if the tumour is associated with atelectasis or pneumonitis,

it is T2a if lesion ≤ 4cm or if tumour size cannot be measured; it is
T2b if lesion > 4cm, ≤ 5cm.

CH 6 | ATLAS OF LUNG CANCER STAGING | 107
Chest wall invasion, including

Pancoast tumours without invasion
of vertebral body or spinal canal,
encasement of the subclavian
vessels, or unequivocal involvement
of the superior branches of the
brachial plexus (C8 or above)
T3
Tumour:
> 5cm, ≤ 7cm
Invasion of
parietal pleura
Phrenic
nerve
or parietal
pericardium
invasion
Separate tumour
nodule(s) in the
lobe of the primary
T4
Tumour invades Tumour invades
trachea and/ aorta and/or
or SVC or other recurrent
great vessel laryngeal nerve
Tumour
involves
carina
Tumour > 7cm
Diaphragmatic
invasion Tumour invades oesophagus,
Tumour invades mediastinum and/or heart
adjacent vertebral body
Pancoast tumours with

invasion of one or more of
the following structures:
- vertebral body or spinal
canal
- brachial plexus
(C8 or above)
- subclavian vessels
Tumour accompanied
by ipsilateral,
separate tumour
nodules, different lobe

N0 N1
Metastasis
No regional
in ipsilateral
lymph node
intrapulmonary/
metastases
peribronchial/
hilar lymph
node(s),
including nodal
involvement by
direct extension
N2
Metastasis in
ipsilateral
mediastinal
and/or
subcarinal
lymph node(s), Metastasis in
including “skip” ipsilateral
metastasis mediastinal
without N1 and/or
involvement subcarinal
lymph node(s)
associated
with N1
disease
N3
Metastasis in
contralateral hilar/ Metastasis in ipsilateral
mediastinal/scalene/ scalene/supraclavicular
supraclavicular lymph node(s)
lymph node(s)

M1a
Primary Contralateral,
tumour separate
tumour nodule(s)
Malignant Malignant
pleural effusion/nodule(s) pericardial effusion/nodule(s)
Note: when the pleural (pericardial) effusions are negative after

multiple microscopic examinations, and the fluid is non-bloody and
not an exudate, they should be excluded as a staging descriptor.
M1b
Single
extrathoracic
Liver metastasis

M1b
This includes
involvement of
a single distant
(non-regional)
lymph node
M1c
Brain
This includes
multiple extrathoracic
Lymph metastases in one
nodes or several organs
Bone
Adrenal
Liver

Visceral Pleural Invasion
PL0
PL0
PL1
PL2
PL3
PL0 tumour within the subpleural lung parenchyma or invades superficially

into the pleural connective tissue beneath the elastic layer*
PL1 tumour invades beyond the elastic layer
PL2 tumour invades to the pleural surface
PL3 tumour invades into any component of the parietal pleura.
* Note: In the TNM 7th and 8th editions, PL0 is not regarded as a T descriptor
and the T category should be assigned on other features. PL1 or PL2 indi-
cate “visceral pleural invasion” i.e. T2a. PL3 indicates invasion of the parietal
pleura, i.e. T3.
PART III
PLEURAL
MESOTHELIOMA
7
8th Edition of TNM for
Pleural Mesothelioma
Introductory Notes
The classification applies to malignant mesothelioma of
pleura.
treatment
• Stage

region to the diaphragm. Direct extension of the primary tumour
into lymph nodes is classified as lymph node metastasis.
Pleural Mesothelioma
(ICD-O C38.4)
120 | PART III | PLEURAL MESOTHELIOMA

The classification applies only to malignant mesothelioma
of the pleura.
There should be histological confirmation of the disease.
Changes in this edition from the seventh edition are based
upon recommendations from the International Association for
the Study of Lung Cancer (IASLC) Staging Project.1-5
M categories:
exploration

The regional lymph nodes are the intrathoracic, internal mam-
mary, scalene, and supraclavicular nodes.

TX Primary tumour cannot be assessed.
T1 Tumour involves ipsilateral parietal or visceral pleura
only, with or without involvement of visceral, mediastinal
or diaphragmatic pleura.
T2 Tumour involves the ipsilateral pleura (parietal or visceral
pleura), with at least one of the following:
• invasion of diaphragmatic muscle
• invasion of lung parenchyma
T3 Tumour involves ipsilateral pleura (parietal or visceral
CH 7 | 8TH EDITION OF TNM FOR PLEURAL MESOTHELIOMA | 121

• invasion of endothoracic fascia
• invasion into mediastinal fat
• solitary focus of tumour invading soft tissues of the
chest wall
• non-transmural involvement of the pericardium
T4 Tumour involves ipsilateral pleura (parietal or visceral
• chest wall, with or without associated rib destruction
(diffuse or multifocal)
• peritoneum (via direct transdiaphragmatic extension)
• contralateral pleura
• mediastinal organs (oesophagus, trachea, heart, great
vessels)
• vertebra, neuroforamen, spinal cord
• internal surface of the pericardium (transmural invasion
with or without a pericardial effusion)

N1 Metastases to ipsilateral intrathoracic lymph nodes
(includes ipsilateral bronchopulmonary, hilar, subcarinal,
paratracheal, aortopulmonary, paraesophageal,
peridiaphragmatic, pericardial fat pad, intercostal and
internal mammary nodes)
N2 Metastases to contralateral intrathoracic lymph nodes.
Metastases to ipsilateral or contralateral supraclavicular
lymph nodes

Stage – Pleural Mesothelioma

Stage IA T1 N0 M0
Stage IB T2, T3 N0 M0
Stage II T1, T2 N1 M0
Stage IIIA T3 N1 M0
Stage IIIB T1. T2, T3 N2 M0

T4 Any N M0
Stage IV Any T Any N M1
References
1. Rusch VW, Giroux D, Kennedy C et al. Initial analysis of the International
Association for the Study of Lung Cancer Mesothelioma database.
J Thorac Oncol 2012; 7: 1631-1639.
2. Pass H, Giroux D, Kennedy C et al. The IASLC Mesothelioma database:
improving staging of a rare disease through international participation.
3. Nowak AK, Chansky K, Rice DC et al. The IASLC Mesothelioma Staging
Project: proposals for revisions of the T descriptors in the forthcoming
eighth edition of the TNM classification for mesothelioma. J Thorac Oncol
2016; in press.
4. Rice D, Chansky K, Nowak A et al. The IASLC Mesothelioma Staging Project:
proposals for revisions of the N descriptors in the forthcoming eighth
edition of the TNM classification for malignant pleural mesothelioma.
5. Rusch VW, Chansky K, Kindler HL et al. The IASLC Malignant Pleural
Mesothelioma Staging Project: proposals for the M descriptors and for
the revision of the TNM stage groupings in the forthcoming (eighth) edition
of the TNM classification for mesothelioma. J Thorac Oncol , 2016; in press.
8
Atlas of
Pleural Mesothelioma Staging
T1 T2
Involves ipsilateral
parietal or visceral Involves ipsilateral
pleura only pleura with invasion
of lung and/or
diaphragmatic muscle

T3 T4
Involves ipsilateral pleura Involves ipsilateral pleura

with invasion of the with diffuse, multifocal
endothoracic fascia, the invasionof the chest wall,
chest wall (solitary, invasion of the contralateral
resectable focus extending pleura, peritoneum,
into soft tissue),mediastinal mediastinal organs, spine,
fat and/or non-transmural transmural invasion of the
invasion of the pericardium pericardium (with or
without pericardial effusion)
and/or myocardium

CH 8 | ATLAS OF PLEURAL MESOTHELIOMA STAGING | 125
N1
Metastases to ipsilateral intrathoracic

lymph nodes (includes ipsilateral
bronchopulmonary, hilar, subcarinal,
paratracheal, aortopulmonary,
para-oesophageal, peridiaphragmatic,
pericardial, intercostal and internal
mammary lymph nodes)
N2
Metastases to Metastases to
contralateral ipsilateral or
intrathoracic contralateral
lymph nodes supraclavicular
lymph nodes

PART IV
THYMIC
MALIGNANCIES
9
TNM for Thymic Malignancies
Introductory Notes
The classification applies to thymic tumours.
treatment
• Stage

region to the diaphragm. Direct extension of the primary tumour
into lymph nodes is classified as lymph node metastasis.
Thymic Tumours
ICD-0-3 C37.9
130 | PART IV | THYMIC MALIGNANCIES

The classification applies to epithelial tumours of the thymus,
including thymomas, thymic carcinomas and neuroendocrine
tumours of the thymus. It does not apply to sarcomas, lym-
phomas and other rare tumours.
This classification is new to the 8th edition and is based
upon recommendations from the International Association
for the Study of Lung Cancer (IASLC) Staging Project and the
International Thymic Malignancies Interest Group (ITMIG) (see
references).1–3
There should be histological confirmation of the disease
and division of cases by histological type.
M categories:
exploration

The regional lymph nodes are the anterior (perithymic) lymph
nodes, the deep intrathoracic lymph nodes and the cervical
lymph nodes.

TX Primary tumour cannot be assessed.
T1 Tumour encapsulated or extending into the mediastinal
fat, may involve the mediastinal pleura.
CH 9 | TNM FOR THYMIC MALIGNANCIES | 131
T1a No mediastinal pleural involvement

T1b Direct invasion of the mediastinal pleura
T2 Tumour with direct involvement of the pericardium
(partial or full thickness).
T3 Tumour with direct invasion into any of the following;
lung, brachiocephalic vein, superior vena cava, phrenic
nerve, chest wall, or extrapericardial pulmonary artery
or vein.
T4 Tumour with direct invasion into any of the following;
aorta (ascending, arch or descending), arch vessels,
intrapericardial pulmonary artery, myocardium, trachea,
or oesophagus

N1 Metastasis in anterior (perithymic) lymph nodes
N2 Metastasis in deep intrathoracic or cervical lymph nodes
M0 No pleural, pericardial or distant metastasis
M1a Separate pleural or pericardial nodule(s)
M1b Distant metastasis beyond the pleura or
pericardium
TNM Pathological Classification

Stage –Thymic Tumours
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage IIIA T3 N0 M0
Stage IIIB T4 N0 M0
Stage IVA Any T N1 M0

Any T N0, N1 M1a
Stage IVB Any T N2 M0, M1a
Any T Any N M1b
References
1. Nicholson AG, Detterbeck FC, Marino M, et al. The IASLC/ITMIG thymic
epithelial tumors staging project: proposals for the T component for the
J Thorac Oncol 2014; 9: s73–s80.
2. Kondo K, Van Schil P, Detterbeck FC, et al. The IASLC/ITMIG thymic epi-
thelial tumors staging project: proposals for the N and M components
for the forthcoming (8th) edition of the TNM classification of malignant
tumors. J Thorac Oncol 2014; 9: s81–s87.
3. Detterbeck FC, Stratton K, Giroux D, et al. The IASLC/ITMIG thymic epi-
thelial tumors staging project: proposal for an evidence-based stage
classification system for the forthcoming (8th) edition of the TNM clas-
sification of malignant tumors. J Thorac Oncol 2014; 9: s65–s72.
10
Site-Specific Explanatory Notes
for Thymic Malignancies
Frank Detterbeck
Clinical Stage Classification

1. The reliability of imaging characteristics in predicting
actual invasion of mediastinal structures has generally not
been defined. One must rely on the radiologist’s best judg-
ment. An elevated hemidiaphragm should be considered
evidence of phrenic nerve involvement.
2. Lymph nodes ≥ 1cm in short axial dimension should be
considered involved for purposes of clinical staging; simi-
larly, nodes with PET uptake (if available) should also be
considered involved.
3. A surgical exploration without microscopic confirmation
of levels of invasion or the nodal status defines the clini-
cal stage. Pathologic stage can be defined if a tumour is
completely resected or if invasion of the highest T category
is microscopically confirmed along with node sampling.
Pathologic Stage Classification

T Component
1. For pathologic T classification involvement of a particular
tissue must be microscopically confirmed. Surgically iden-
tified adhesion of the tumour to an adjacent structure does
not affect the T classification if no actual invasion of the

adjacent structure is present on microscopic examination.
2. The presence or absence of a capsule or invasion thereof
is not a descriptor in the T classification. The International
Association for the Study of Lung Cancer-International
Thymic Malignancies Interest Group (IASLC-ITMIG) analy-
sis of a large global database demonstrated that these
descriptors have no impact on outcomes.1 This also con-
firms other studies.2
3. The impact of invasion of the mediastinal pleura is
unclear. The IASLC-ITMIG database did not demonstrate
a difference,1 but a possible difference is suggested in the
Japanese Association for Research on the Thymus (JART)
database.1 A problem with the analysis is that recognition
of the mediastinal pleura can be difficult grossly as well as
microscopically in the resected specimen. ITMIG recom-
mends routine marking of the mediastinal pleura by the
surgeon at the time of resection,3 and the use of elastin
stains is recommended when the mediastinal pleural layer
is unclear microscopically.
4. Invasion of the pericardium is classified as T2 whether this
is partial or full thickness.1 The classification is the same
whether there is involvement of the parietal and visceral
pericardium. (There is no data suggesting a difference in
outcomes, and no ability to make this distinction in clinical
staging.)
5. While it is recommended that tumour size be recorded,
it does not affect the T classification. In the IASLC-ITMIG
global database the largest dimension of tumour size had
no prognostic impact.
6. The T category is determined by the “level” of invasion.
Invasion of structures of a particular T level is counted
CH 10 | SITE-SPECIFIC EXPLANATORY NOTES FOR THYMIC MALIGNANCIES | 135
regardless whether or not there is invasion of structures

of a lower level.
7. While the number of invaded mediastinal structures (of a
particular level) appears to affect outcomes, this is not a
factor in determining the T category. This is due to some
inconsistency and a suspected variable amount of miss-
ing information regarding all of the invaded structures in
the available data for analysis. It is recommended that not
only is the T category recorded, but also all of the specific
structures that are invaded.
8. Direct invasion of the pleura or pericardium is distinguished
from pleural or pericardial nodules that are separated from
the primary tumour mass (see M category notes).
N Component
1. Direct extension of the primary tumour into a lymph node
is counted as nodal involvement.4
2. During resection of a thymoma with invasion of other struc-
tures (i.e. ≥ T2) it is recommended that anterior mediastinal
nodes are routinely removed with the specimen, and sys-
tematic sampling of deep nodes in encouraged. During
resection of a thymic carcinoma systematic resection of
both N1 and N2 nodes is recommended. The pathologists
should specifically examine and report on the presence of
nodal involvement.3-5 Furthermore, removal and specific
notation of any suspicious nodes (either by imaging or
intraoperative assessment) is recommended.
3. Nodal involvement is divided into an anterior (perithymic,
N1) and deep (N2) category, as detailed in the ITMIG-IASLC
node map (Table 10.1, 10.2 and Figures 10.1-10.6).4,6
Table 10.1. Anterior Region [N1] (Anterior Mediastinal & Anterior Cervical Nodes).
Region Node Group
Boundaries Node Groups14, 16 Boundaries
Sup: hyoid bone Low Ant Cervical: Sup: inferior border
Lat (Neck): medial pretracheal, paratra- of cricoid
border of carotid cheal, peri-thyroid, Lat: common carotid
sheaths precricoid/delphian arteries
Lat (Chest): (AAO-HNS / ASHNS Inf: superior border
mediastinal level 6 / IASLC level 1) of manubrium
pleura
Peri-thymic Proximity to thymus
Ant: sternum
Post (Medially): Prevascular Sup: apex of chest
great vessels, (IASLC level 3a) Ant: posterior sternum
pericardium Post: anterior SVC
Post (Laterally): Inf: carina
phrenic nerve
Paraaortic, Sup: line tangential
Inf: xiphoid,
ascending aorta, to sup border of
diaphragm
superior phrenic aortic arch
(IASLC level 6) Inf: inf border of
aortic arch
Supradiaphragmatic/ Sup: inf border of
inferior phrenic/ aortic arch
pericardial (along Ant: post sternum
inferior poles of
Post: phrenic
thymus)
nerve (laterally) or
pericardium (medially)
Inf: diaphragm
Region and node group boundaries adapted directly from definitions established by
AAO-HNS, ASHNS and IASLC.
AAO-HNS, American Academy of Otolaryngology - Head and Neck Surgery; ASHNS,
American Society for Head and Neck Surgery; IASLC, International Association for the
Study of Lung Cancer. Sup, Superior; Ant, Anterior; Inf, inferior; Lat, lateral; Post, posterior;
SVC, superior vena cava.
Table 10.2. Deep Region [N2] (Middle Mediastinal and Deep Cervical Nodes.
Region Node Group
Sup: level of Lower jugular Sup: level of lower border
lower border of (AAO-HNS / ASHNS of cricoid cartilage
cricoid cartilage level 4) Anteromedial: lat border
Anteromedial of sternohyoid
(neck): Posterolateral: lat border
lateral border of sternocleidomastoid
of sternohyoid,
Inf: clavicle
medial border of
carotid sheath Supraclavicular/ Sup: level of lower border
Posterolateral venous angle: of cricoid cartilage
(neck): anterior confluence of Anteromedial: post border
border of internal jugular & of sternocleidomastoid
trapezius subclavian vein
Posterolateral: ant border
Ant (chest): (AAO-HNS / ASHNS of trapezius
aortic arch, level 5b)
Inf: clavicle
aortopulmonary
window–anterior Internal mammary Proximity to internal
border of SVC nodes mammary arteries
Post (chest):
Upper paratracheal Sup: sup border of manu-
oesophagus
(IASLC level 2) brium, apices of lungs
Lat (chest):
Inf: intersection of lower
pulmonary hila
border of innominate
Inf: diaphragm vein with trachea; sup
border of aortic arch
Lower paratracheal Sup: intersection of lower
(IASLC level 4) border of innominate vein
with trachea; sup border
of aortic arch
Inf: lower border of azygos
vein, sup border of left
main pulmonary artery
Table 10.2. (cont.)

Region Node Group
Subaortic/aortopul- Sup: inf border of aortic
monary window arch
(IASLC level 5) Inf: sup border of left main
pulmonary artery
Subcarinal Sup: carina
(IASLC level 7) Inf: upper border of lower
lobe bronchus on the left;
lower border of the
bronchus intermedius on
the right
Hilar Sup: lower rim of azygos
(IASLC level 10) vein on right, upper rim of
pulmonary artery on left
Inf: interlobar region
bilaterally
Region and node group boundaries adapted directly from definitions established by AAO-HNS,
ASHNS and IASLC.
AAO-HNS, American Academy of Otolaryngology - Head and Neck Surgery; ASHNS, American
Society for Head and Neck Surgery; IASLC, International Association for the Study of Lung Cancer.
Sup, Superior; Ant, Anterior; Inf, inferior; Lat, lateral; Post, posterior; SVC, superior vena cava.
Figure 10.1. Mediastinum, Sagittal Section. Tr=trachea; E=esophagus;

LPA=left pulmonary artery; A=aorta; D=diaphragm.
Figure 10.2. Thoracic Inlet, Axial Section.

CCA=common carotid artery; IJV=internal jugular vein; Tr=trachea;
Clav=clavicle; E=esophagus.
Figure 10.3. Paraaortic Level, Axial Section.

SVC=superior vena cava; E=esophagus; Tr=trachea.
Figure 10.4. AP Window Level, Axial Section.

Note: deep region includes aortopulmonary window nodes.
AA=ascending aorta; DA=descending aorta; LPA=left pulmonary artery;
SVC=superior vena cava; Az=azygos vein; RB=right main bronchus;
LB=left main bronchus.
Figure 10.5. Carina Level, Axial Section.

Note: deep region includes aortopulmonary window nodes.
AA=ascending aorta; DA=descending aorta; PT=pulmonary trunk; LPA=left
pulmonary artery; RPA=right pulmonary artery; SVC=superior vena cava;
LSPV=left superior pulmonary vein; BR=bronchus; E=esophagus.
Figure 10.6. Diaphragm Level, Axial Section.

RV=right ventricle; LV=left ventricle; IVC=inferior vena cava; DA=descending
aorta; E=esophagus.
M Component
1. Pleural or pericardial nodules that are separate from the
primary tumor mass are classified as M1a.4
2. Discrete intraparenchymal nodules in the lung are classified
as M1b. These are nodules of tumor that are surrounded
by normal lung (i.e. not contiguous with the visceral pleura
or intraparenchymal tumor that represents direct invasion
by the primary tumor mass).4
Resection (R) Status

The thymus is generally surrounded by loose areolar tissue,
which is prone to disruption either during resection or during
handling of the specimen. Furthermore, a thymectomy
specimen often includes no tissues that inherently orient
the specimen. Therefore, specific attention is necessary to
intraoperative marking, specimen handling and orientation,
and communication between the surgeon and pathologists
in order to accurately report the margin status of resected
tumors.3
1. It is suggested that immediate intraoperative marking of

the specimen be performed to define areas of concern,
areas of tissue disruption during handling that do not rep-
resent true margins, and specific surfaces (e.g. the right or
left mediastinal pleura, areas adjacent to the innominate
vein or pericardium)
2. It is recommended that the resected specimen be clearly
oriented and that the margin status of specific surfaces
be examined and reported (e.g. anterior, posterior, right,
left, adjacent to pericardium etc.).3 ITMIG suggests placing
the specimen on a “mediastinal board” that makes the
relationship of different parts of the specimen to adjacent
structures clear (Figure 10.7).
3. It is recommended that the surgeon and the pathologist
communicate at the time of resection about orientation
and areas of particular concern
4. The distance to the nearest margin should be reported in
mm whenever the margin is ≤ 3mm.
A B
Figure 10.7. A) Mediastinal board and B) example of specimen orientation.
References
1. Nicholson A, Detterbeck C, Marino M, et al. The ITMIG/IASLC Thymic
Epithelial Tumors Staging Project: proposals for the T component for the
J Thorac Oncol. 2014; 9 (9, Suppl 2):S73-S80.
2. Marchevsky AM, McKenna Jr RJ, Gupta R. Thymic epithelial neoplasms: a
review of current concepts using an evidence-based pathology approach.
Hematol Oncol Clin North Am. 2008;22(3):543-562.
3. Detterbeck F, Moran C, Huang J, et al. Which way is up? Policies and
procedures for surgeons and pathologicsts regarding resection
specimens of thymic malignancy. J Thorac Oncol. 2011; 6(7 Suppl 3):
S1730-S1738.
4. Kondo K, Van Schil P, Detterbeck F, et al. The IASLC/ITMIG Thymic Epithelial
Tumors Staging Project: proposals for the N and M components for the
forthcoming (8th) edition of the TNM classification of malignant tumors
J Thorac Oncol. 2014; 9(9, Suppl 2):S81-S87.
5. Park IK, Kim YT, Jeon JH, et al. Importance of lymph node dissection in
thymic carcinoma. Ann Thorac Surg. 2013; 96(3):1025-1032.
6. Bhora F, Chen D, Detterbeck F, et al. The ITMIG/IASLC Thymic Epithelial
Tumors Staging Project: a proposed lymph node map for thymic epithe-
lial tumors in the forthcoming (8th) edition of the TNM classification for
malignant tumors. J Thorac Oncol. 2014; 9 (9, Suppl 2):S88-S96.
11
Atlas of
Thymic Malignancies Staging
Axial #1 Axial #2
Ao: aorta
Prevascular compartment PA: pulmonary artery
SVC: superior vena cava
Visceral compartment T: trachea
Az: azygos vein
Paravertebral compartment
Oes: oesophagus
Visceral-paravertebral boundary RMB: right main bronchus
LMB: left main bronchus
Axial #3 Sagittal
Prevascular compartment Ao: aorta

PA: pulmonary artery
Visceral compartment
LA: left atrium
Paravertebral compartment RV: right ventricle
Visceral-paravertebral boundary
CH 11 | ATLAS OF THYMIC MALIGNANCIES STAGING | 145
Stage I
T1N0M0
Encapsulated
tumour
Invasion of
mediastinal
fat (T1a)
Tumour
Invasion of
mediastinal
pleura (T1b)
Fibrous
compartment
Pericardium
Lung
Visceral pleura
Stage II
T2N0M0
Mediastinal
fat
Invasion of
pericardium
Tumour
Fibrous
compartment
Pericardium
Lung
Visceral pleura
Stage IIIA
T3N0M0
Vessels
Invasion of lung,
phrenic nerve,
brachiocephalic vein,
superior vena cava,
extrapericardial
pulmonary artery
and veins, chest wall
Tumour
Pericardium
Lung
Visceral pleura
Stage IIIB
T4N0M0
Vessels
Invasion of aorta,arch
vessels, myocardium,
intrapericardial Tumour
pulmonary artery,
trachea, oesophagus
Lung
Visceral pleura Myocardium
Stage IVA
Any T N1M0;
any T N0-1 M1a
Vessels
Anterior mediastinal
nodal involvement
Tumour
Tumour with pleural

or pericardial nodules
Pericardium
Lung
Visceral pleura
Stage IVB
Any T N2 M0-1a;
any T, any N, M1b
Vessels
Tumour
Tumour with deep region
node involvement or distant
metastases, including
pulmonary nodules
Lung
Visceral pleura
PART V
CARCINOMA OF THE
OESOPHAGUS AND OF
OESOPHAGOGASTRIC
JUNCTION
by John Wiley & Sons, Ltd, www.wiley.com. There
are some differences between the published 8th
editions of the TNM classification of carcinoma of
the oesophagus and of the oesophagogastric junc-
tion published by the UICC and the American Joint
Committee on Cancer. The Editorial Addendum
following this chapter explains these differences.
12
8th Edition of TNM for Carcinoma
of the Oesophagus and of the
Oesophagogastric Junction

The classification applies only to carcinomas and includes
adenocarcinomas of the oesophagogastric/gastroesopha-
geal junction. There should be histological confirmation
of the disease and division of cases by topographic local-
ization and histological type. A tumour the epicentre of
which is within 2 cm of the oesophagogastric junction
and also extends into the oesophagus is classified and
staged using the oesophageal scheme. Cancers involv-
ing the oesophagogastric junction (OGJ) whose epicentre
is within the proximal 2 cm of the cardia (Siewert types
I/II) are to be staged as oesophageal cancers.
M categories:
(including bronchoscopy), and/or surgical
exploration
N categories Physical examination, imaging, and/or surgical
exploration
exploration
154 | PART V | CARCINOMA OF THE OESOPHAGUS AND OF OESOPHAGOGASTRIC JUNCTION
Anatomical Subsites
1. Cervical oesophagus (C15.0): this commences at the lower
border of the cricoid cartilage and ends at the thoracic inlet
(suprasternal notch), approximately 18 cm from the upper
incisor teeth.
2. Intrathoracic oesophagus
a) The upper thoracic portion (C15.3) extending from the
thoracic inlet to the level of the tracheal bifurcation,
approximately 24 cm from the upper incisor teeth.
b) The mid-thoracic portion (C15.4) is the proximal half of
the oesophagus between the tracheal bifurcation and
the oesophagogastric junction. The lower level is approx-
imately 32 cm from the upper incisor teeth.
c) The lower thoracic portion (C15.5), approximately 8 cm
in length (includes abdominal oesophagus), is the distal
half of the oesophagus between the tracheal bifurcation
and the oesophagogastric junction. The lower level is
approximately 40 cm from the upper incisor teeth.
3. Oesophagogastric junction (C16.0). Cancers involving the
oesophagogastric junction (OGJ) whose epicentre is within
the proximal 2 cm of the cardia (Slewert types I/II) are to be
staged as oesophageal cancers. Cancers whose epicentre is
more than 2 cm distal from the OGJ will be staged using the
Stomach Cancer TNM and Stage even if the OGJ is involved.

The regional lymph nodes, irrespective of the site of the pri-
mary tumour, are those in the oesophageal drainage area
including coeliac axis nodes and paraesophageal nodes in
the neck but not the supraclavicular nodes.
CH 12 | 8TH EDITION OF TNM FOR CARCINOMA OF THE OESOPHAGUS AND OGJ | 155

TX Primary tumour cannot be assessed
Tis Carcinoma in situ/high-grade dysplasia
T1 Tumour invades lamina propria, muscularis mucosae, or
submucosa
T1a Tumour invades lamina propria or muscularis
mucosae
T1b Tumour invades submucosa
T2 Tumour invades muscularis propria
T3 Tumour invades adventitia
T4 Tumour invades adjacent structures
T4a. Tumour invades pleura, pericardium, azygos vein,
diaphragm, or peritoneum
T4b. Tumour invades other adjacent structures such
as aorta, vertebral body, or trachea

N1 Metastasis in 1 to 2 regional lymph nodes
N2 Metastasis in 3 to 6 regional lymph nodes
N3 Metastasis in 7 or more regional lymph nodes

pN0 Histological examination of a regional lymphadenectomy
specimen will ordinarily include 7 or more lymph nodes.
If the lymph nodes are negative, but the number ordinarily
examined is not met, classify as pN0.
Stage and Prognostic Group – Carcinomas of the

Oesophagus and Oesophagogastric Junction*
Squamous Cell Carcinoma

Clinical Stage
Stage 0 Tis N0 M0
Stage I T1 N0, N1 M0
Stage II T2 N0, N1 M0
T3 N0 M0
Stage III T1, T2 N2 M0
T3 N1, N2 M0
Stage IVA T4a, T4b N0, N1, N2 M0
Any T N3 M0
Stage IVB Any T Any N M1
Pathological Stage
Stage 0 Tis N0 M0
Stage IA T1a N0 M0
Stage IB T1b N0 M0
Stage IIA T2 N0 M0
Stage IIB T1 N1 M0
T3 N0 M0
Stage IIIA T1 N2 M0
T2 N1 M0
Stage IIIB T2 N2 M0
T3 N1, N2 M0
T4a N0, N1 M0
Stage IVA T4a N2 M0
T4b Any N M0
Any T N3 M0
Pathological Prognostic Group

Group T N M Grade Location
Group 0 Tis N0 M0 N/A Any
Group IA T1a N0 M0 1, X Any
Group IB T1a N0 M0 2–3 Any
T1b N0 M0 Any Any
T2 N0 M0 1 Any
Group IIA T2 N0 M0 2–3, X Any
T3 N0 M0 Any Lower
Upper,
T3 N0 M0 1
middle
Group IIB Upper,
T3 N0 M0 2–3
middle
T3 N0 M0 Any X
T3 N0 M0 X Any
T1 N1 M0 Any Any
Group IIIA T1 N2 M0 Any Any
T2 N1 M0 Any Any
Group IIIB T2 N2 M0 Any Any
T3 N1, N2 M0 Any Any
T4a N0, N1 M0 Any Any
Group IVA T4a N2 M0 Any Any

T4b Any N M0 Any Any
Any T N3 M0 Any Any
Group IVB Any T Any N M1 Any Any
Adenocarcinoma
Clinical Stage
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage IIA T1 N1 M0
Stage IIB T2 N0 M0
Stage III T2 N1 M0
T3, T4a N0, N1 M0
Stage IVA T1–T4a N2 M0
T4b N0, N1, N2 M0
Any T N3 M0
Pathological Stage
Stage 0 Tis N0 M0
Stage IA T1a N0 M0
Stage IB T1b N0 M0
Stage IIA T2 N0 M0
Stage IIB T1 N1 M0
T3 N0 M0
Stage IIIA T1 N2 M0
T2 N1 M0
Stage IIIB T2 N2 M0
T3 N1, N2 M0
T4a N0, N1 M0
Stage IVA T4a N2 M0
T4b Any N M0
Any T N3 M0
Pathological Prognostic Group

Group T N M Grade
Group 0 Tis N0 M0 N/A
Group IA T1a N0 M0 1, X
Group IB T1a N0 M0 2
T1b N0 M0 1, 2, X
Group IC T1a, T1b N0 M0 3
T2 N0 M0 1, 2
Group IIA T2 N0 M0 3, X
Group IIB T1 N1 M0 Any
T3 N0 M0 Any
Group IIIA T1 N2 M0 Any
T2 N1 M0 Any
Group IIIB T2 N2 M0 Any
T3 N1, N2 M0 Any
T4a N0, N1 M0 Any
Group IVA T4a N2 M0 Any
T4b Any N M0 Any
Any T N3 M0 Any
Group IVB Any T Any N M1 Any
Note
*The AJCC publishes prognostic groups for adenocarcinoma and squamous
cell carcinoma after neoadjuvant therapy (categories with the prefix “y”). See
the Executive Editor’s Note at the end of this chapter.
Prognostic Factors Grid – Oesophagus

Prognostic factors for survival in oesophageal cancer
Essential Depth of invasion Performance Quality of
Lymph node status surgery
involvement Age Multimodality
Presence of Nutritional approach
lymphovascular status
invasion (LVI)
Additional Tumour grading Economic Nutritional

Tumour location status support
New and CEA, VEGF-C, HER 2

promising
Source: UICC Manual of Clinical Oncology, Ninth Edition. Edited by Brian O’Sullivan,
James D. Brierley, Anil K. D’Cruz, Martin F. Fey, Raphael Pollock, Jan B. Vermorken and
Shao Hui Huang. © 2015 UICC. Published 2015 by John Wiley & Sons, Ltd.
Editorial Addendum
By Thomas W. Rice, MD, and Eugene H. Blackstone, MD
The 8th editions of the cancer staging manuals for carcinoma
of the oesophagus and of the oesophagogastric junction1,2
are based on modern machine learning analyses of 22,654
patients registered by the Worldwide Esophageal Cancer
Collaboration (WECC).3–8 The Union for International Cancer
Control (UICC) definitions vary somewhat from those used to
develop the staging recommendations and some categories
are undefined by the UICC.
Location (Anatomic Subsites)

The definitions of anatomic subsites (location) used by the
UICC differ from that used by the American Joint Committee
on Cancer (AJCC) and WECC to develop the staging recom-
mendations. The boundaries used to define the cervical, upper
thoracic, middle thoracic and lower thoracic esophagus are
defined in Table 1. The AJCC Upper GI Task Force consensus
redefined the oesophagogastric junction, such that tumours
with epicentres no more than 2 cm into the proximal stomach
are staged as oesophageal cancers.
Histologic Grade
Crucial to pathological staging of early squamous cell car-
cinoma and adenocarcinoma of the oesophagus is the
non-anatomic cancer category histologic grade. The defini-
tions suggested for use with these staging recommendations
are listed in Tables 2 and 3.
Stage Groups
Analyses of WECC data6–8 demonstrated the need for sepa-
rate stage groupings based on AJCC defined classifications
Table 1. Anatomic subsites (location category), defined by the position of the

epicentre of the tumour in the oesophagus1
Location
Category Definition
X Location unknown
Cervical Inferior border of the hypopharynx to sternal notch, 15
cm to 20 cm#
Upper Sternal notch to lower border of azygos vein, >20 cm to
25 cm#
Middle Lower border of azygos vein to lower border of inferior
pulmonary veins, >25 cm to 30 cm#
Lower Lower border of inferior pulmonary vein to stomach,
including gastroesophageal junction, >30 cm to 40 cm#
# Typical measurements from the incisor teeth.
Table 2. Histologic grade (G category) for squamous cell carcinoma*

G
Category Criteria
G1 Well-differentiated. Prominent keratinization with
pearl formation and a minor component of nonkera-
tinizing basal-like cells. Tumour cells are
arranged in sheets, and mitotic counts are low.
G2 Moderately differentiated. Variable histologic features,
ranging from parakeratotic to poorly keratinizing le-
sions. Generally, pearl formation is absent.
G3 Poorly differentiated. Consists predominantly of basal-
like cells forming large and small nests with frequent
central necrosis. The nests consist of sheets or pave-
ment-like arrangements of tumour cells, and occasion-
ally are punctuated by small numbers of parakeratotic
or keratinizing cells. If further testing of “undifferenti-
ated” cancers reveals a squamous cell component, or
if after further testing they remain undifferentiated,
categorize as squamous cell carcinoma, G3.
*Reproduced with permission and adapted from Rice TW, Ishwaran H, Ferguson MK,
Blackstone EH, Goldstraw P. Cancer of the esophagus and esophagogastric junction:
an 8th edition staging primer. J Thorac Oncol 2016; in press.9
Table 3. Histologic grade (G category) for adenocarcinoma*

G Category Criteria
G1 Well differentiated. >95% of tumour is composed of
well-formed glands.
G2 Moderately differentiated. 50% to 95% of tumour
shows gland formation.
G3 Poorly differentiated. Tumours composed of nest
and sheets of cells with <50% of tumour demon-
strating glandular formation. If further testing of
“undifferentiated” cancers reveals a glandular com-
ponent, categorize as adenocarcinoma G3.
*Reproduced with permission and adapted from Rice TW, Ishwaran H, Ferguson MK,
Blackstone EH, Goldstraw P. Cancer of the esophagus and esophagogastric junction:
an 8th edition staging primer. J Thorac Oncol 2016; in press.9
(clinical, pathological, and postneoadjuvant therapy). 1

Additionally separate groupings for histopathologic cell type
were required for clinically staged and pathologically staged
tumours. UICC adopted Clinical Stage Groups in an unaltered
state. The UICC listing of Pathologic Stage Groups for squamous
cell carcinoma and adenocarcinoma without histologic grade
and location, which are identical for both histopathologic cell
types in this analysis, produced inferior stage grouping of early
stage cancers (stage 0–IIB squamous cell carcinoma and stage
0–IIA adenocarcinoma) because of inhomogeneity.6 Superior
pathological grouping with improved homogeneity is afforded
by the use of Pathologic Prognostic Groups and setting the
unknown histologic grade or location to X.
Unique TNM categories (ypTisN1-3M0 and ypT0N0-3M0),
dissimilar stage group compositions and markedly different
survival profiles compared to clinical and pathological staged
patients necessitated separate stage groups, identical for
both histopathologic cell types, for those patients who have

received neoadjuvant therapy (Postneoadjuvant Therapy).
UICC failed to list these groups.
Table 4. Post neoadjuvant therapy stage groups (ypTNM)

for squamous cell carcinoma and adenocarcinoma*
Stage T N M
Stage I T0–2 N0 M0
Stage II T3 N0 M0
Stage IIIA T0–2 N1 M0
Stage IIIB T3 N1 M0
T0–3 N2 M0
T4a N0 M0
Stage IVA T4a N1–2 M0
T4a NX M0
T4b N0-2 M0
Any T N3 M0
*Reproduced with permission and adapted from Rice TW, Ishwaran
H, Ferguson MK, Blackstone EH, Goldstraw P. Cancer of the esopha-
gus and esophagogastric junction: an 8th edition staging primer.
J Thorac Oncol 2016; in press.9
References
1. Rice TW, Kelsen D, Blackstone EH, Ishwaran H, Patil DT, Bass AJ, Erasmus
JJ, Gerdes H, Hofstetter WL. Esophagus and esophagogastric junction. In:
Amin MB, Edge SB, Greene FL, et al., eds. AJCC Cancer Staging Manual. 8th
ed. New York, NY: Springer; 2017:185-202.
2. Oesophagus including oesophagogastric junction. In: Brierley JD,
Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant
Tumors. International Union Against Cancer. 8th ed. Oxford, England: Wiley;
2017:57-62.
3. Rice TW, Apperson-Hansen C, DiPaola LM, et al. Worldwide Esophageal
Cancer Collaboration: clinical staging data. Dis Esophagus.2016;7:707-14.
4. Rice TW, Lerut TEMR, Orringer MB, et al. Worldwide Esophageal Cancer
Collaboration: neoadjuvant pathologic staging data. Dis Esophagus
2016;7:715-23.
5. Rice TW, Chen L-Q, Hofstetter WL, et al. Worldwide Esophageal Cancer
Collaboration: pathologic staging data. Dis Esophagus 2016;7:724-33.
6. Rice TW, Ishwaran H, Hofstetter WL, Kelsen DP, Blackstone EH.
Recommendations for pathologic staging (pTNM) of cancer of the esopha-
gus and esophagogastric junction for the 8th edition AJCC/UICC staging
manuals. Dis Esophagus 2016 (in press).
7. Rice TW, Ishwaran H, Kelsen DP, Hofstetter WL, Blackstone EH.
Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer
of the esophagus and esophagogastric junction for the 8th edition AJCC/
UICC staging manuals. Dis Esophagus 2016 (in press).
8. Rice TW, Ishwaran H, Blackstone EH, Hofstetter WL, Kelsen DP.
Recommendations for clinical staging (cTNM) of cancer of the esopha-
9. Rice TW, Ishwaran H, Ferguson MK, Blackstone EH, Goldstraw P. Cancer
of the esophagus and esophagogastric junction: an 8th edition staging
primer. J Thorac Oncol 2016 (in press).
Executive Editor’s Note: This chapter has been
reprinted from Wittekind Ch, Compton CC, Brierley J,
Sobin LH (eds) UICC TNM Supplement A Commentary
on Uniform Use, fourth edition, John Wiley & Sons,
Ltd., Oxford, 2012. The explanatory notes in this
chapter are based on the 7th edition of the TNM
classification of carcinoma of the oesophagus and
of the oesophagogastric junction. There are impor-
tant changes in the 8th edition of the classification,
mainly in the definition of the oesophagogastric
junction, in the classification of regional lymph
nodes and in the stages. An Editorial Addendum to
this chapter explains the novelties in the 8th edition,
but the 7th edition text is included here to facilitate
comparison between both editions.
13
Site-Specific Explanatory Notes for
Carcinoma of the Oesophagus and
of the Oesophagogastric Junction

The classification applies to all types of carcinoma. Gastro-
intestinal stromal tumours and neuroendocrine tumours
(carcinoids) have their own classifications. The changes in
the 8th edition derive from the analyses of the Worldwide
Esophageal Cancer Collaboration (WECC).1-6
Oesophagus
Summary – Oesophagus (includes oesophagogastric junction)
T1 Lamina propria, muscularis mucosae (T1a), submucosa
(T1b)
T2 Muscularis propria
T3 Adventitia
T4a Pleura, pericardium, diaphragm
T4b Aorta, vertebral body, trachea
N1 1-2 regional
N2 3-6 regional
N3 7 or more regional
A tumour the epicentre of which is in the stomach within

5 cm of the oesophagogastric junction and also extends into
the oesophagus is classified and staged using the oesophageal
scheme. Tumours with an epicentre in the stomach greater

than 5 cm from the oesophagogastric junction or those within
5 cm of the oesophagogastric junction without extension in
the oesophagus are classified and staged using gastric carci-
noma scheme.
There is a proposal to divide carcinomas of the oesopha-
gogastric junction region into three entities:7-9
• Adenocarcinoma of the distal oesophagus (AEG I, so-called
Barrett carcinoma)
• ‘Real’ carcinoma of the cardia (AEG II)
• Subcardial carcinoma of the stomach, infiltrating the distal
oesophagus (AEG III)
These proposals give some indication of the epidemiology

and biology of the tumours. By sampling worldwide data on
oesophageal and oesophagogastric junction cancers, it has
been shown that patients with all types of Siewert’s carcinoma
have a similar poor prognosis to patients with oesophageal
cancer.10,11 Therefore, these different types are classified
according to tumours of the oesophagus.
The presence of additional synchronous primary carcino-
mas that are only histologically demonstrable is classified as
multifocality and is not considered in the TNM classificaton.
For the separation of these carcinomas from skip metastasis
(intramural metastasis), the configuration of tumour cells as
well as the presence of intraepithelial neoplasia are consid-
ered. In contrast to multi-focality, multiplicity, i.e. the presence
of additional macroscopically detectable synchronous pri-
mary carcinomas is indicated in brackets, e.g. T2(m) or pT2(3).
So-called skip metastasis (intramural metastasis) are
tumour foci (orally or abo-rally) separate from the primary
carcinoma in the wall of the oesophagus or stomach particu-
CH 13 | SITE-SPECIFIC NOTES FOR CARCINOMA OF THE OESOPHAGUS AND OGJ | 171
larly in the submucosa. Such skip metastasis can be found in

10-15% in oesophageal tumour resection specimen. They are
considered the result of lymphatic spread in the oesophageal
wall. These ‘skip metastasis’ are not considered in the TNM/
pTNM classification and are not considered metastasis.
Invasion of adventitia (cT3/pT3) corresponds to invasion
of perioesophageal soft tissue. This is not considered invasion
of the mediastinum or invasion of adjacent structures (T4).
Invasion of pleura, percardium or diaphragm (structures
that are usually considered resectable) are classified as T4a.
A carcinoma of the oesophagus that has invaded the
stomach and shows a perforation there is classified as pT4a
(equivalent to tumours of the stomach). Invasion of bronchi,
lung, heart, aorta, V. cava, V. azygos and invasion of recurrent
nerve(s) or phrenic or sympathetic nerves (structures that are
usually considered unresectable) are classified as T4b.
Invasion in fistulas between oesophagus and trachea
or oesophagus and bronchus or compression of V. cava or V.
azygos is classified T4b.
Lymph Nodes (Oesophagus)

The definition of the regional lymph nodes of the oesophagus
has been simplified in the 7th edition.
The regional lymph nodes, irrespective of the site of the
primary tumour, are those in the oesophageal drainage area
including coeliac axis nodes and paraoesophageal nodes in
the neck.
Paraoesophageal lymph nodes within the neck are con-
sidered regional. All other involved lymph nodes above the
clavicles (supraclavicular) are classified as distant metastasis.
In the AJCC Cancer Staging Manual 2009 the regional
lymph nodes are listed in detail:

Zone Number Site
Supraclavicular 1 Supraclavicular
Upper 2 Upper paratracheal
3p Posterior mediastinal/upper
4 (R, L) paraoesophageal
Lower paratracheal (right, left)
AP (aortopulmo- 5 Subaortic aortopulmonary
nary) 6 Anterior mediastinal (anterior to
ascending aorta
ascendens or innominate artery)
Subcarinal 7 Subcarinal
Lower 8 (L,R) Middle paraoesophageal (left,
9 (L, R) right)
Pulmonary ligament (left, right)
Hilar 10 (R, L) Tracheobronchial (hilar) (right,
left)
Thoracal 15 Diaphragmatic
Abdominal 16 Paracardial
17 Along arteria gastric sinistra
18 Along arteria hepatica communis
19 Along arteria lienalis
20 At the basis of arteria coeliaca
There is a difference in classification of supraclavicular

lymph nodes: they are considered as regional in the AJCC
Manual, but not in the UICC booklet, where they are desig-
nated as distant metastasis.
Another problem arises by the general rule of the TNM
system if a tumour involves more than one site or subsite, e.g.
contiguous extension to another site or subsite, the regional
lymph nodes include those of all involved sites and subsites.
According to this rule, all nodes regional for the stomach have
to be considered as regional for tumours of the oesophagus
and oesophagogastric junction, too. However, in the AJCC list
the following stations are missing: perigastric/lesser curvature,
perigastric/greater curvature, suprapyloric, infrapyloric, at the
splenic hilum.
Stage Grouping and Prognostic Grouping

The T, N and M categories used by the UICC and the AJCC are
identical. The UICC presents two options for stage groupings:
1) A purely anatomical approach that applies to all histological
types, and
2) A prognostic AJCC approach that has two separate classi-
fications for squamous cell and adenocarcinoma, with the
former taking histological grade and subsite into consider-
ation and the latter including histological grade only. The
definitions of the prognostic grouping for squamous cell
and adenocarcinoma of UICC and AJCC are identical. The
AJCC Manual has only the prognostic scheme.
See Chapter 12 for stage grouping and prognostic groups

tables.
References
1. Rice TW, Apperson-Hansen C, DiPaola C et al. Worldwide Esophageal
Cancer Collaboration: clinical staging data. Dis Esophagus 2016;7: 707-14.
2. Rice TW, Chen L-Q, Hofstetter WL et al. Worldwide Esophageal Cancer
Collaboration: pathologic staging data. Dis Esophagus 2016;7: 724-33.
3. Rice TW, Lerut TEMR, Orringer MB et al. Worldwide Esophageal Cancer
Collaboration: neoadjuvant pathologic staging data. Dis Esophagus
2016;7: 715-23.
4. Rice TW, Ishwaran H, Hofstetter WL, Kelsen DP, Blackstone EH.
Recommendations for pathologicstaging (pTNM) of cancer of the
esophagus and esophagogastric junction for the 8th edition AJCC/

5. Rice TW, Ishwaran H, Kelsen DP, Hofstetter WL, Blackstone EH.
Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer
of the esophagus and esophagogastric junction for the 8th edition AJCC/
6. Rice TW, Ishwaran H, Blackstone EH, Hofstetter WL, Kelsen DP.
Recommendations for clinical staging (cTNM) of cancer of the esopha-
7. Hermanek P, Henson DE, Hutter RVP, Sobin LH, eds. UICC TNM Supplement
1993. A Commentary on Uniform Use, 1st ed. New York, Wiley; 1993.
8. Sobin LH, Wittekind Ch, eds. UICC TNM Classification of Malignant
Tumours, 6th ed. New York, Wiley; 2002.
9. Wittekind Ch, Henson DE, Hutter RVP, Sobin LH, eds. UICC TNM
Supplement. A Commentary on Uniform Use, 3rd ed, New York, Wiley;
2003.
10. Rosenberg P, Friederichs J, Schuster T et al. Prognosis of patients with
colorectal cancer is associated with lymph node ratio. A single-center
analysis of 3026 patients over a 25-year time period. Ann Surg 2008; 248:
968-978.
11. Derwinger K, Carlsson G, Gistavsson B. Stage migration in colorectal
cancer related to improved lymph node assessment. Eur J Surg Oncol
2007; 33: 849-853.
Editorial Addendum
By Thomas W. Rice, MD, and Eugene H. Blackstone, MD
This reprinted manuscript, published in 2012, references mate-
rial from the UICC 7th edition staging manual. Although some
of the material is pertinent today, there are many important
changes in the 8th edition.
The Oesophagogastric Junction

The oesophagogastric junction (OGJ) has been redefined
for the 8th edition. Use of a simple measurement to define
whether a cancer is oesophageal or gastric has impeded OGJ
cancer staging since the 1980’s. Conflicting statistical analyses
necessitated a “place card” consensus decision for the 8th
edition. Cancers involving the OGJ that have their epicenter
within the proximal 2 cm of the cardia are to be staged as
oesophageal cancers. Cancers whose epicenter is more than
2 cm distal from the OGJ, even if the OGJ is involved, will be
staged using the stomach cancer TNM and stage groupings.1
Early work suggests genetic signature of OGJ cancers will be
much more useful in appropriate cancer staging by identifying
cell of origin rather than relying on gross location.2,3 A “genetic”
definition of the OGJ will obviate the need for further dividing
it into thirds (AEG I-III, Siewert I–III). This redefinition of the
OGJ will be a focus of the 9th edition staging.

The regional lymph node map has been refined in the 8th edi-
tion AJCC staging manual (Figure 22.2).1 The regional lymph
node stations are listed in Table 1. Supraclavicular, perigastric/
greater curvature, suprapyloric, infrapyloric, and splenic hilum
lymph nodes are non regional lymph nodes in the AJCC 8th
edition Cancer Staging Manual.
Stage Grouping and Prognostic Grouping

The recent (7th edition) separation of pathologic groupings
into Pathological Stage and Pathological Prognostic Group
by the UICC contradicts the stated purposes of TNM classi-
fications and stage groupings originally set out by the UICC,
“Classification is a means of recording facts observed by the
clinician whereas staging implies interpretation of these facts
regarding prognosis.”4 This superfluous distinction unneces-
sarily produces confusion and inferior stage grouping (see
Chapter 20 Editorial Addendum). With publication of the
AJCC 8th edition Cancer Staging Manual and the data-driven
placement of oesophageal and OGJ cancers with unknown
histologic grade or location the statement “the AJCC manual
has only the prognostic scheme” is irrelevant.
References
1. Rice TW, Kelsen D, Blackstone EH, Ishwaran H, Patil DT, Bass AJ, Erasmus
JJ, Gerdes H, Hofstetter. Esophagus and esophagogastric junction. In:
Amin MB, Edge SB, Greene FL, et al. (Eds.) AJCC Cancer Staging Manual.
8th Ed. New York:Springer; 2017:185-202.
2. Cancer Genome Atlas Research Network. Comprehensive molecular char-
acterization of gastric adenocarcinoma. Nature. 2014 Sep 11;513:202-9.
3. Hayakawa Y, Sethi N, Sepulveda AR, Bass AJ, Wang TC. Oesophageal
adenocarcinoma and gastric cancer: should we mind the gap? Nat Rev
Cancer. 2016 Apr 26;16:305-18.
4. International Union Against Cancer (UICC). TNM Classification of Malignant
Tumors. Geneva; 1968.
Table 1. Regional lymph node stations for staging cancer of the oesophagus
and oesophagogastric junction
Lymph
Node
Station Name Location
1R Right lower cervical Between supraclavicular paratra-
paratracheal nodes cheal space and apex of lung
1L Left lower cervical Between supraclavicular paratra-
paratracheal nodes cheal space and apex of lung
2R Right upper Between intersection of caudal
paratracheal nodes margin of brachiocephalic artery
with trachea and apex of lung
2L Left upper Between top of aortic arch and
paratracheal nodes apex of lung
4R Right lower Between intersection of caudal
paratracheal nodes margin of brachiocephalic
artery with trachea and cephalic
border of azygos vein
4L Left lower paratra- Between top of aortic arch and
cheal nodes carina
7 Subcarinal nodes Caudal to carina of trachea
8U Upper thoracic From apex of lung to tracheal
paraesophageal bifurcation
lymph nodes
8M Middle thoracic From tracheal bifurcation to
paraesophageal caudal margin of inferior
lymph nodes pulmonary vein
8Lo Lower thoracic From caudal margin of inferior
paraesophageal pulmonary vein to oesophago-
lymph nodes gastric junction
9R Pulmonary ligament Within right inferior pulmonary
nodes ligament
9L Pulmonary ligament Within left inferior pulmonary
nodes ligament

15 Diaphragmatic On dome of diaphragm and

nodes adjacent to or behind its crura
16 Paracardial nodes Immediately adjacent to gastro-
esophageal junction
17 Left gastric nodes Along course of left gastric artery
18 Common hepatic Immediately on proximal com-
nodes mon
hepatic artery
19 Splenic nodes Immediately on proximal splenic
artery
20 Celiac nodes At base of celiac artery
Note: Cervical periesophageal level VI and level VII lymph nodes are named as per the
head and neck map.
14
Atlas of Oesophagus and of
Oesophagogastric Junction
Cancer Staging
Figure 14.1. Eighth edition TNM categories. T is categorized as Tis: high-grade

dysplasia; T1: cancer invades lamina propria, muscularis mucosae, or submu-
cosa and is subcategorized into T1a (cancer invades lamina propria or mus-
cularis mucosae) and T1b (cancer invades submucosa); T2: cancer invades
muscularis propria; T3: cancer invades adventitia; T4: cancer invades local struc-
tures and is subcategorized as T4a: cancer invades adjacent structures such as
pleura, pericardium, azygos vein, diaphragm, or peritoneum and T4b: cancer
invades major adjacent structures, such as aorta, vertebral body, or trachea. N is
categorized as N0: no regional lymph node metastasis; N1: regional lymph node
metastases involving 1 to 2 nodes; N2: regional lymph node metastases involv-
ing 3 to 6 nodes; and N3: regional lymph node metastases involving 7 or more
nodes. M is categorized as M0: no distant metastasis; and M1: distant metastasis.
Copyright ©2016 Cleveland Clinic Foundation, courtesy of Thomas W. Rice, MD.
A B
Figure 14.2. Lymph node maps for oesophageal cancer. Regional lymph node
stations for staging oesophageal cancer from left A), right B), and anterior
C). 1R: Right lower cervical paratracheal nodes, between the supraclavicular
paratracheal space and apex of the lung. 1L: Left lower cervical paratracheal
nodes, between the supraclavicular paratracheal space and apex of the lung.
2R: Right upper paratracheal nodes, between the intersection of the caudal
margin of the brachiocephalic artery with the trachea and apex of the lung.
2L: Left upper paratracheal nodes, between the top of the aortic arch and
apex of the lung. 4R: Right lower paratracheal nodes, between the intersec-
tion of the caudal margin of the brachiocephalic artery with the trachea and
cephalic border of the azygos vein. 4L: Left lower paratracheal nodes, between
the top of the aortic arch and the carina. 7: Subcarinal nodes, caudal to the
carina of the trachea. 8U: Upper thoracic paraoesophageal lymph nodes,
from the apex of the lung to the tracheal bifurcation. 8M: Middle thoracic
CH 14 | ATLAS OF OESOPHAGUS AND OF OGJ CANCER STAGING | 181
paraoesophageal lymph nodes, from the tracheal bifurcation to the caudal

margin of the inferior pulmonary vein. 8Lo: Lower thoracic paraoesophageal
lymph nodes, from the caudal margin of the inferior pulmonary vein to the
esophagogastric junction. 9R: Pulmonary ligament nodes, within the right
inferior pulmonary ligament. 9L: Pulmonary ligament nodes, within the left
inferior pulmonary ligament. 15: Diaphragmatic nodes, lying on the dome
of the diaphragm and adjacent to or behind its crura. 16: Paracardial nodes,
immediately adjacent to the gastrooesophageal junction. 17: Left gastric
nodes, along the course of the left gastric artery. 18: Common hepatic nodes,
immediately on the proximal common hepatic artery. 19: Splenic nodes,
immediately on the proximal splenic artery. 20: Celiac nodes, at the base of
the celiac artery. Cervical perioesophageal level VI and level VII lymph nodes
are named as per the head and neck map. Copyright ©2016 Cleveland Clinic
Foundation, courtesy of Thomas W. Rice, MD.
Figure 14.3. Location of oesophageal cancer primary site, including typical

endoscopic measurements of each region measured from the incisors. Exact
measurements depend on body size and height. Location of cancer primary
site is defined by cancer epicenter. Cancers involving the oesophagogastric
junction (EGJ) that have their epicenter within the proximal 2 cm of the cardia
(Siewert types I/II) are to be staged as oesophageal cancers. Cancers whose
epicenter is more than 2 cm distal from the EGJ, even if the EGJ is involved, will
be staged using the stomach cancer TNM and stage groups. Key: LES, lower
oesophageal sphincter; UES, upper oesophageal sphincter. Copyright ©2016
Cleveland Clinic Foundation, courtesy of Thomas W. Rice, MD.
Index
A International Association for the
Adenocarcinoma in situ, 22 Study of Lung Cancer Staging
Adenocarcinoma, minimally Project, 19
invasive, 22 International Mesothelioma
American Joint Committee on Interest Group, 19
Cancer, 22, 25 International Thymic Malignancies
Asamura, Hisao, 25 Interest Group, 19
B Isolated tumour cells, 42, 83
Broncho-pulmonary carcinoid J
tumours, 83 Japanese Association for Research
C on the Thymus, 19
Cancer Research And Biostatistics Japanese Joint Committee for Lung
(CRAB), 19 Cancer Registry, 19
Carcinoma of the oesophagus, 8th L
edition of TNM for, 152 Lung cancer domain, 20
Carcinoma of the oesophagus, Lung cancer, IASLC nodal
anatomical subsites, 154 definitions, 78
Carcinoma of the oesophagus, Lung cancer, pTNM pathological
rules for classification, 153, 169 classification, 59
Carcinoma of the oesophagus, site- Lung cancer, rules for classification,
specific explanatory notes for, 169 56
Clinical classification, definition, 37 Lung cancer, TNM clinical
E classification, 57
Essential TNM, 50 Lung cancers with multiple sites of
European Society of Thoracic involvement, classification of, 96
Surgeons, 19 Lung tumours, histopathologic
Expansion of the R classification, 84 type, 67
Lung tumours, site-specific
G explanatory notes, 65
General Rules of the TNM System, 37
Goldstraw, Peter, 25 M
Malignant pleural mesothelioma
H domain, 20
Histopathological grading, 44 Mesothelioma domain, 20
I N
IASLC mesothelioma database, 23 New adenocarcinomas, new
IASLC Staging and Prognostic categories, 95
Factors Committee, 19, 25 Nodal chart with stations and
IASLC/ITMIG database, 23 zones, 81
184 | INDEX
Nodal disease, quantification of, 101 T

Non-small cell lung carcinoma, Thymic malignancies, clinical stage
prognostic factors, 61 classification, 133
O Thymic malignancies, pathologic
Oesophageal cancer domain, 20 stage classification, 133
Oesophagus, prognostic factors, 161 Thymic malignancies, rules for
classification, 130
P Thymic malignancies, site-specific
Paediatric tumours, 50 explanatory notes for, 133
Part-solid adenocarcinoma, 96 Thymic malignancies, TNM for, 129
Pathological classification, Thymic tumours domain, 20
definition, 37 Thymoma domain, 20
Pleural mesothelioma, 8th edition TNM clinical classification, 40
of TNM, 119 TNM for lung cancer, 8th edition, 55
Pleural mesothelioma, rules of TNM or pTNM classification,
classification, 120 additional descriptors, 45
Prognostic factors classification, 48
pT and pN categories, site-specific U
recommendations, 90 Union for International Cancer
pTNM pathological classification, 41 Control, 22, 25
R V
Residual tumour (R) classification, 46 Visceral pleural invasion, 115
Rice, Thomas, 19 W
S WECC database, 23
Small cell carcinoma, 83 Worldwide Esophageal Cancer
Small cell lung carcinoma, Collaboration, 19
prognostic factors, 62
Stage and prognostic groups, 47
The second phase of the International Association
for the Study of Lung Cancer (IASLC) Staging Projects
culminates with the publication of the second edition of
the IASLC Staging Manual in Thoracic Oncology and the
IASLC Staging Handbook in Thoracic Oncology.
The IASLC is proud to serve the international oncological

community and thanks the Union for International
Cancer Control and the American Joint Committee on
Cancer for entrusting it with such challenging and
intellectually rewarding responsibility.
This project could not be performed without the gener-

ous unrestricted support from Lilly Oncology, USA.
It is our hope that the 8th Edition of the Staging Clas-

sification will be a useful tool for further research and
will serve in the daily lung cancer clinic to the benefit for
the many patients with lung cancer and other thoracic
malignancies around the world.
North Fort Myers, FL

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INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER

Conquering Thoracic Cancers Worldwide

An International Association for the Study of Lung Cancer Publication

Executive Editor: Ramón Rami-Porta, MD

An IASLC publication published by Editorial Rx Press

Editorial Rx Press, Registered Office: North Fort Myers, FL 33917

First Editorial Rx Press Printing 2016

Copyright © 2016 by International Association for the Study of Lung Cancer

Chapters 1, 2, 7, 9, 12–Used with the permission of the Union for International

Cover and interior design by Amy Boches, Biographics.

To Prof. Peter Goldstraw, MBChB, FRCS

Emeritus Professor of Thoracic Surgery,

With gratitude, esteem, and respect

The International Association for the Study of Lung Cancer

“Nought may endure but mutability!”

PART II LUNG CANCER

PART III PLEURAL MESOTHELIOMA

PART IV THYMIC MALIGNANCIES

John Crowley (Chief of Strategic Alliances), Cancer Research

Foundation Trust and Imperial College, London, UK.

William D. Travis (Chair, Neuroendocrine Tumours Subcom-

The complete list of members of the IASLC Staging and

The staging of lung cancer and other thoracic malignan-

intellectually rewarding responsibility. It is our hope that the

The second phase of the International Association for the

Boards consist of additional specialists who contribute their

Staging and Prognostic Factors Committee of the IASLC

Lung Cancer Mesothelioma Thymoma Oesophageal Ca.

Subcommittees (x n) Subcommittees (x n) Subcommittees (x n) Subcommittees (x n)

Advisory Board Advisory Board Advisory Board Advisory Board

Figure 1. Structure of the International Association for the Study of Lung

Table 1. Number of Evaluable Patients

recommendations for changes on the T2, the N3, and the M4

This thymic classification is, indeed, the first TNM-based inter-

data on 22,654 patients and, among these, there are patients

section and I wholeheartedly thank them for their time, dedi-

Factors Committee. We count, once more, on the data sent

separate tumor nodules in the forthcoming eighth edition of the TNM

Appendix. Members and Structure of the IASLC

LUNG CANCER DOMAIN

Small Cell Lung Cancer Subcommittee:

MALIGNANT PLEURAL MESOTHELIOMA DOMAIN

THYMIC MALIGNANCIES DOMAIN

OESOPHAGEAL CARCINOMA DOMAIN

The practice of classifying cancer cases into groups according

Cancer staging is essential to patient care, research, and

care-related activities, the development and implementa-

tion that becomes available from histopathology and/or

The General Rules of the TNM Systema,b

The addition of numbers to these three components indicates

In effect, the system is a ‘shorthand notation’ for describing

evidence acquired before treatment, supplemented or

tumour should be classified independently. In tumours of

Anatomical Regions and Sites

TNM Clinical Classification

N – Regional Lymph Nodes

The category M1 may be further specified according to the

pTNM Pathological Classification

pN – Regional Lymph Nodes