TNM Classification of Malignant Tumours E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Serie: UICC
• Sprache: Englisch

Seitenzahl: 303

Veröffentlichungsjahr: 2025

Beschreibung

The essential reference on cancer stage returns as a fully revised edition

Describing cancer stage is one of the most important elements of oncological practice. Clinical research and clinical care depend on an accurate assessment of cancer stage and prognostic factors. The TNM Classification of Malignant Tumours serves as the globally recognised standard reference for describing cancer stage and assessing treatment results. Now fully updated to reflect the results of the latest clinical research, it is indispensable for all clinicians, cancer registrars and researchers who work with malignant tumours.

Readers of the ninth edition of TNM Classification of Malignant Tumours will find:

• Updates in many tumour sites including, nasopharynx, HPV associated oropharynx, lung, thymus, mesothelioma, appendix, anal canal, cervix, vulva and prostate carcinoma;
• Revised and updated sections on Essential TNM and paediatric cancer staging;
• New classifications for medulloblastoma, cutaneous lymphoma, parathyroid carcinoma, adrenal medulla and extra-adrenal paraganglia tumours;
• Revised classification of prognostic factors for many malignancies.

TNM Classification of Malignant Tumours is an essential resource for anyone involved in cancer care, research or cancer control.

Leseprobe

Table of Contents

Cover

Table of Contents

Title Page

Copyright Page

Dedication Page

Editors‐in‐Chief

Editors

Preface

Acknowledgements

Organisations Associated with the TNM System

Members of UICC Committees Associated with the TNM System

Introduction

Head and Neck Tumours

Oral Cavity and Mucosal Lip

Pharynx

Larynx

Nasal Cavity and Paranasal Sinuses

Unknown Primary – Cervical Nodes

Malignant Melanoma of Upper Aerodigestive Tract

Salivary Glands

Thyroid Gland

Parathyroid Gland

Digestive System Tumours

Oesophagus

Stomach

Small Intestine

Appendix

Colon and Rectum

Anal Canal and Perianal Skin

Liver

Intrahepatic Bile Ducts

Gallbladder

Perihilar Bile Ducts

Distal Extrahepatic Bile Duct

Ampulla of Vater

Pancreas

Well‐Differentiated Neuroendocrine Tumours of the Gastrointestinal Tract

Lung, Pleural and Thymic Tumours

Lung

Pleural Mesothelioma

Thymus Tumours

Tumours of Bone and Soft Tissues

Bone

Soft Tissues

Gastrointestinal Stromal Tumour (GIST)

Skin Tumours

Carcinoma of Skin (excluding eyelid, head and neck, perianal, vulva and penis)

Carcinoma of Skin of the Head and Neck Region

Carcinoma of Skin of the Eyelid

Melanoma of Skin

Merkel Cell Carcinoma of Skin

Breast Tumours

Gynaecological Tumours

Vulva

Vagina

Cervix Uteri

Uterus – Endometrium

Uterine Sarcomas

Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma

Gestational Trophoblastic Neoplasms

Urological Tumours

Penis

Prostate

Testis

Kidney

Renal Pelvis and Ureter

Urinary Bladder

Urethra

Adrenal Cortex

Adrenal Medulla and Extra‐Adrenal Paraganglia Tumours

Ophthalmic Tumours

Carcinoma of Conjunctiva

Melanoma of Conjunctiva

Melanoma of Uvea

Retinoblastoma

Sarcoma of Orbit

Carcinoma of Lacrimal Gland

Brain and Spinal Cord

Hodgkin Lymphoma

Non‐Hodgkin Lymphomas

Essential TNM

Paediatric Tumours

Gastrointestinal Tumours

Bone and Soft Tissue Tumours

Gynaecological Tumours

Urological Tumours

Ophthalmic Tumours

Lymphoma

Leukaemia

Central Nervous System

End User License Agreement

List of Illustrations

Chapter 4

Figure 1 The International Association for the Study of Lung Cancer (IASLC) ...

Figure 2 (A) Coronal and sagittal images of patients with pleural mesothelio...

Chapter 5

Figure 1 The five vertebral segments: right pedicle, right body, left body, ...

Figure 2 The four pelvic segments: sacrum segment, iliac wing segment, pubic...

Chapter 12

Figure 1 Classification for ciliary body and choroid uveal melanoma based on...

Guide

Cover Page

Table of Contents

Title Page

Copyright Page

Dedication Page

Editors‐in‐Chief

Editors

Preface

Acknowledgements

Organisations Associated with the TNM System

Members of UICC Committees Associated with the TNM System

Begin Reading

Wiley End User License Agreement

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TNM Classification of Malignant Tumours

Ninth Edition

Editors‐in‐Chief

James Brierley, BSc, MB, FRCP, FRCR, FRCPC

Meredith Giuliani, MB, FRCPC

Brian O’Sullivan, MB, BCh, FRCPC, FRCPI, FFRRCSI (Hon)

Brian Rous, MA (Cantab), MB BChir, PhD, FRCPath

Elizabeth Van Eycken, MD

Section Editors

General Rules

J. Brierley

Thyroid and Parathyroid

J. Brierley

E. Van Eycken

Gastrointestinal Tract

J. Brierley

B. O’Sullivan

Lung, Pleura and

H. Asamura

B. A. Rous

Lung, Pleura andThymic Tumours

H. AsamuraM. Giuliani

Head and Neck

B. O’Sullivan

Bone and Soft Tissues

B. O’Sullivan

S. Huang

A. Lee

Skin

J. Brierley, B. O’Sullivan

W.M. Lydiatt

Breast

E. Van Eycken

Nasopharynx

Gynaecological

B. A. Rous

M. Chua Lee Kiang

Genitourinary

A. Berlin

P. Blanchard

M.K. Gospodarowicz

S. Huang

Ophthalmic Tumours

J. Brierley

A. Lee

A. Mallipatna

B. O’Sullivan

Malignant Lymphoma

D. Hodgson

Oropharynx

S. Huang

CNS

B. A. Rous

M. Evans

Paediatric Tumours

J. Aitken

W.M. Lydiatt

D. Youlden

H. Mehanna

E. Van Eycken

B. O’Sullivan

Essential TNM

M. Piñeros

Salivary Gland

J. Brierley

Vincent Vander Poorten

AJCC Liaison

K. Washington

A. Hosni

E. Asare

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Cover Design: UICC & Motherbird

They are called wise

who put things in their right order

    Thomas Aquinas

Editors‐in‐Chief

James Brierley, BSc, MB, FRCP, FRCR, FRCPCEmeritus Professor, Department of Radiation Oncology, University of Toronto; Princess Margaret Cancer Centre, Toronto, Ontario, Canada

Dr. Brierley was trained in Clinical Oncology in the UK and developed his interest in cancer staging and surveillance while moving to Canada. He has been involved in cancer surveillance at local, national and international levels. He is Co‐Chair of the UICC TNM Prognostic Factors Project. He has co‐edited the TNM Classification of Malignant Tumours, eighth edition (Wiley 2017). In addition he was co‐editor of the TNM Supplement, fifth edition (Wiley 2019), the UICC Manual of Clinical Oncology (Wiley 2015) and the UICC TNM Atlas, seventh edition (Wiley 2020). He is co‐editor of the UICC Cancer Systems and Control for Health Professionals (Wiley 2025).

Meredith Giuliani, MB, FRCPCAssociate Professor, Department of Radiation Oncology, University of Toronto; Director of Education, Princess Margaret Cancer Centre; Associate Dean of Postgraduate Medical Education, University of Toronto.

Dr. Giuliani received her MBBS from the University of London, England, and then completed her residency training in radiation oncology at the University of Toronto. She received her Master’s of Education from the Ontario Institute of Sciences in Education at the University of Toronto and her PhD from the School of Health Professions Education at Maastricht University. Her PhD focused on globalisation and the influence of neocolonialism on curricula. She has an active education research lab that focuses on globalisation, the influence of education on health systems and the intersection of education and health disparities. She is co‐editor of UICC Cancer Systems and Control for Health Professionals (Wiley 2025).

Brian O’Sullivan, MB, BCh, FRCPC, FRCPI, FFRRCSI (Hon)Professor, Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto; Member of the faculty at Centre Hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Canada

Dr. O’Sullivan is a graduate of the National University of Ireland at University College Dublin and trained in medical oncology in Dublin and Toronto, and in radiation oncology in Toronto which has been his medical specialty throughout his career. He has been almost continually involved with the UICC TNM Prognostic Factors Project since the fifth edition of TNM in 1997. He served as a member of the core Committee during most of this time and chaired the Prognostic Factors Subcommittee of the Project. He was also co‐editor of the UICC Prognostic Factors in Cancer, second edition (Wiley 2001) and third edition (Wiley 2006), and was co‐editor of the UICC Manual of Clinical Oncology, seventh edition (Wiley 1999) and eighth edition (Wiley 2004). He served as the Editor‐in‐Chief for the ninth edition of the Manual of Clinical Oncology (Wiley 2015).

Brian Rous, MA (Cantab), MB, BChir, PhD, FRCPathConsultant Histopathologist, Cambridge University Hospitals NHS Foundation Trust

Dr. Rous received his MB BChir and PhD from the University of Cambridge. His PhD studies focussed on the intracellular trafficking of lysosomal proteins. He has worked for many years as a Clinical Lead for the National Disease Registration Service in England, advising on coding and classification of neoplasms. He was a co‐editor of the UICC TNM Atlas, seventh edition (Wiley 2020).

Elizabeth Van Eycken, MDDirector of the Belgian Cancer Registry, Brussels, Belgium

Dr. Van Eycken was trained as a Radiation Oncologist at the University Hospital of Leuven (Belgium) and received the qualification of Physician Expert Health Data Management. She moved from clinical practice to cancer registration with a focus on the use of tumour stage. Her main objective is to promote the crucial role of cancer registries in cancer control activities. She is Co‐Chair of the UICC TNM Prognostic Factors Project, responds to the UICC TNM helpdesk questions and has co‐edited the UICC TNM Supplement, fifth edition (Wiley 2019), and the UICC TNM Atlas, seventh edition (Wiley 2020).

Editors

H. Asamura, MDProfessor of Surgery, Chief, Division of Thoracic Surgery, Keio University School of Medicine, Tokyo, Japan

E. Asare, MD, MS, CMQ, FACSAssistant Professor, Section of Surgical Oncology, Division of General Surgery, University of Utah, Salt Lake City, UT, USA

J. AitkenProfessor, Cancer Council Queensland, Brisbane, Australia

A. Berlin, MD, MSc, FRCPCAssociate Professor, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

M. Gospodarowicz, MD, FRCPC, FRCR (Hon)Emeritus Professor, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

D. Hodgson, MD, MPH, FRCPCProfessor, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

S. Huang, MD, MSc, MRT(T)Associate Professor, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

A. Lee, MD, FRCRProfessor and Head, Department of Clinical Oncology, The University of Hong Kong and the University of Hong Kong‐Shenzhen Hospital, Hong Kong, China

A. Mallipatna, MDAssistant Professor, SickKids Hospital, Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada

M. Piñeros, MD, MScCancer Surveillance Section, International Agency for Research on Cancer, Lyon, France

M.K. Washington, MD, PhDProfessor of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA

D. YouldenBiostatistician, Cancer Alliance Queensland, Queensland, Australia

Preface

In this ninth edition of the TNM Classification of Malignant Tumours, many of the tumour sites are unchanged from the eighth edition.1 However, some tumour entities and anatomic sites have been newly introduced and some tumours contain modifications: this follows the basic philosophy of maintaining stability of the classification over time. The modifications and additions reflect new data on prognosis as well as new methods for assessing prognosis.2 Some changes had already appeared in the TNM Supplement3 as proposals. Subsequent support warrants their incorporation into the classification.

In the seventh edition, a new approach was adopted to separate stage groupings from prognostic groupings in which other prognostic factors are added to T, N and M categories. These new prognostic groupings were presented for oesophagus and prostate. In this ninth edition, as in the eighth edition, the term ‘stage’ is used when only descriptions of anatomic extent of disease are used and ‘prognostic group’ is used when additional prognostic factors are incorporated.

Changes made between the eighth and ninth editions are indicated by a bar at the left‐hand side of the text. To avoid ambiguity, users are encouraged to cite the edition and year of the TNM publication they have used in their list of references.

A TNM web page with Frequently Asked Questions (FAQs) and a form for submitting questions or comments on the TNM can be found at: http://www.uicc.org. Readers are also encouraged to visit http://www.uicc.org for updates and errata. Evidence‐based proposals for changes can be submitted for assessment. More details and a checklist that will facilitate the formulation of proposals can be obtained at http://www.uicc.org.

The AJCC is no longer publishing a Manual alongside this ninth edition of TNM Classification of Malignant Tumours, instead it will publish a series of rolling updates. In line with FIGO and the corresponding UICC update available at http://www.uicc.org, it started with carcinoma of the cervix in 2021.

As with carcinoma of the cervix, changes in this ninth edition result from consultations between the UICC TNM project, the AJCC and other expert groups such as FIGO and IASLC for thoracic tumours, and other global tumour groups, consortia and national TNM committees.

Union for International Cancer Control (UICC)31‐33 Avenue Giuseppe Motta1202 Geneva, Switzerlandhttps://www.uicc.org/

References

1 Brierley, J.D., Gospodarowicz, M.K., and Wittekind, C. (ed.) (2017).

International Union Against Cancer (UICC). TNM Classification of Malignant Tumours

, 8the. New York: Wiley.

2 Gospodarowicz, M.K., O’Sullivan, B., and Sobin, L.H. (ed.) (2006).

International Union Against Cancer (UICC): Prognostic Factors in Cancer

, 3rde. New York: Wiley.

3 Ch, W., Brierley, J.D., Lee, A., and van Eycken (ed.) (2019).

International Union Against Cancer (UICC): TNM Supplement. A Commentary on Uniform Use

, 5the. Oxford: Wiley Blackwell Publications.

Acknowledgements

The Editors have much pleasure in acknowledging the great help received from the members of the TNM Prognostic Factors Project Committee, the National Staging Committees Global Representatives and the international organisations listed on pages XVII, all of whom volunteered their time.

The ninth edition of the TNM Classification is the result of a number of consultative meetings organised and supported by the UICC and AJCC secretariats, with particular thanks to Zuzanna Tittenbrun.

Organisations Associated with the TNM System

CDC

Centers for Disease Control and Prevention (USA)

FIGO

International Federation of Gynaecology and Obstetrics

IACR

International Association of Cancer Registries

IARC

International Agency for Research on Cancer

IASLC

International Association for the Study of Lung Cancer

ICCR

International Collaboration on Cancer Reporting

WHO

World Health Organization

Members of UICC Committees Associated with the TNM System

In 1950, the UICC appointed a Committee on Tumour Nomenclature and Statistics. In 1954, this Committee became known as the Committee on Clinical Stage Classification and Applied Statistics, and, in 1966, it was named the Committee on TNM Classification. Taking into consideration new prognostic factors the Committee was named in 1994 the TNM Prognostic Factors Project Committee, and in 2003 the main committee was named ‘TNM Prognostic Factors Core Group’. A list of members who have served on these committees is available at: www.uicc.org

UICC TNM Prognostic Factors Core Group 2024

Asamura, H.

Japan

Brierley, J

Canada

Brookland, R. Guiliani, M.

USA Canada

Gospodarowicz, M.K.

Canada

Lee, A.

China

O’Sullivan, B. Rous, B.

Canada UK

Van Eycken, E.

Belgium

Ex‐officio members Tittenbrun, Z. Johnson, S.

Switzerland Switzerland

In addition, the Editors wish to acknowledge the invaluable contributions of:

Gastrointestinal Tract

J. Connor, R. Kirsch, R. Jiang

Genitourinary Tumours

P. Chung, P. Cornfeld

Thorax

F. Detterback, E. Ruffini, V. Rusch, R. Ramon Porta

Hodgkin and Non‐Hodgkin Lymphoma

Ying Ying Sum

Essential TNM

M. Parkin, Biying Liu

Paediatric Tumours

L. Frazier, S. Gupta

Global Advisory Group Members

See

www.uicc.org

Introduction

The History of the TNM System*

The TNM system for the classification of malignant tumours was developed by Pierre Denoix (France) between the years 1943 and 1952.1

In 1950, the UICC appointed a Committee on Tumour Nomenclature and Statistics. As a basis for its work on clinical stage classification, it adopted the general definitions of local extension of malignant tumours suggested by the World Health Organization (WHO) Sub‐Committee on The Registration of Cases of Cancer as well as Their Statistical Presentation.2

In 1958, the Committee published the first recommendations for the clinical stage classification of cancers of the breast and larynx and for the presentation of results.3

A second publication in 1959 presented revised proposals for the breast, for clinical use and evaluation over a 5‐year period (1960–1964).4 In 1968, a booklet, the Livre de Poche,5 and, a year later, a complementary booklet were published detailing recommendations for the setting‐up of field trials, for the presentation of end results, and for the determination and expression of cancer survival rates.6 The Livre de Poche was subsequently translated into 11 languages. In 1974 and 1978, second and third editions7,8 were published containing new site classifications, and the fourth edition of TNM was published in 1987.9

In 1993, the project published the TNM Supplement10 to promote the uniform use of TNM by providing detailed explanations of the TNM rules with practical examples. Second, third, fourth and fifth editions appeared in 2001, 2003, 2012 and 2019, respectively.11–14

The project also publishes the TNM Atlas: Illustrated Guide to the TNM Classification of Malignant Tumours; the seventh edition was published in 2021 as a companion to the eighth edition of the TNM Classification.15

In 1995, the project published Prognostic Factors in Cancer,16 a compilation and discussion of prognostic factors in cancer, both anatomical and non‐anatomical, at each of the body sites. This was expanded in the second edition in 200117 and the third edition in 2006.18

The current ninth edition of TNM contains rules of classification and staging that correspond with those appearing in the eighth edition of the AJCC Cancer Staging Manual (2017) and subsequent version 9 series.19,20 While the aim of the UICC and AJCC is to have identical classifications, small differences exist and are identified as footnotes to the text. Wherever possible, the classifications are based on published evidence‐based recommendation and analysis of databases that reflect contemporary management.

To develop and sustain a classification system acceptable to all requires the closest liaison between national and international organisations. As noted, while the classification is based on published evidence, in areas where high‐level evidence is not available, it is based on international consensus. The continuing objective of the UICC is to present the classification of anatomical extent of cancer for global use in high‐, middle‐ and low‐income countries.

Note

* A more detailed history is available on the website at www.uicc.org.

The Principles of the TNM System

The determination of the extent of any malignancy is a prerequisite to determine both prognosis and appropriate treatment for any patient with cancer. The practice of classifying cancer cases into groups according to anatomical extent, termed ‘stage’, arose from the observation that survival rates were higher for cases in which the disease was localised 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 of not only 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:

to aid the clinician in the planning of treatment

to give some indication of prognosis for survival

to assist in the evaluation of the results of treatment

to facilitate the exchange of information between treatment centres and regions

to contribute to the continuing investigation of human cancer

to support cancer control activities.

Cancer staging is essential to patient care, research and cancer control. Cancer control activities include direct patient‐care‐related activities, the development and implementation of clinical practice guidelines and centralised activities such as recording disease extent in cancer registries for surveillance purposes and planning cancer systems. Recording of stage is essential for the evaluation of outcomes of clinical practice and cancer programmes, including screening. However, in order to evaluate the long‐term outcomes of populations, it is ideal if the classification remains stable. There is therefore a conflict between a classification that is updated to include the most current forms of medical knowledge and a classification that facilitates longitudinal studies. The UICC TNM Project aims to address both needs.

International agreement on the classification of cancer by the 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, age, comorbidities and performance status of the patient, and the histological type and grade of the tumour and relevant molecular and genetic markers. All of these have an influence on the outcome of the disease and need to be considered in tailoring the treatment for an individual patient. Classification by the anatomical extent of disease is the one with which the UICC TNM system primarily deals.

The clinician’s immediate task when meeting a patient with a new diagnosis of cancer is to make a judgement as to prognosis and decide on the most effective course of treatment. This judgement and decision require, among other things, an objective assessment of the anatomical extent of the disease.

The General Rules of the TNM System*

The TNM system for describing the anatomical extent of disease 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, extent and the site of distant metastasis

The addition of Arabic numerals determines the categories for each of these three components, which indicate the extent of the malignant disease:

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:

All cases should be confirmed microscopically. Any cases not so proved must be analysed and reported separately.

Two classifications are described for each site.

Clinical classification:

the pre‐treatment clinical classification, designated

cTNM

, is essential to select and evaluate therapy. This is based on evidence acquired before any treatment. Such evidence is gathered from physical examination, imaging, endoscopy, biopsy, surgical exploration and other relevant examinations.

Pathological classification:

the postsurgical histopathological classification, designated

pTNM

, is based on evidence acquired before treatment, supplemented or modified by additional evidence acquired from surgery and from pathological examination. It is used to provide additional data to estimate prognosis and assessment for any additional treatment. The pathological assessment of the primary tumour (pT) entails resection of the primary tumour or biopsy adequate to confirm the highest pT category. Following two surgical procedures for a single lesion, the pTNM classification should be a composite of the histological examination of the specimens from both operations.

 The pathological assessment of regional lymph nodes requires examination of at least one lymph node and the pathological assessment of the primary tumour (pT), except in cases of unknown primary (T0). If a biopsy confirms the highest N category, the use of pN is appropriate. An excisional biopsy of a lymph node without pathological assessment of the primary tumour (pT) is insufficient to fully evaluate the pN category and is a clinical N category and stage, except in the case of an unknown primary (T0). The pathological assessment of distant metastasis (pM) entails microscopic examination of metastatic deposit. However, if both the highest T and N categories or the M1 category are confirmed microscopically including biopsy without removal of the primary, the criteria for pathological staging are considered satisfied.

After assigning cT, cN and cM and/or pT, pN and pM categories, these may be grouped into stages, which are designated by Roman numerals.

The TNM classification and stages, once established, must remain unchanged in the medical records. For cancer surveillance purposes, clinical and pathological data may be combined when only partial information is available in either the pathological classification or the clinical classification; this should be noted. How stage grouping is determined should be recorded.

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; however, the treating physician may recommend treatment as for the higher stage. This rule does not apply to situations where there is insufficient information to stage, where TX or NX should be used, nor does this rule apply to cancer registries interpreting apparently conflicting information.

In the case of multiple primary tumours in one organ of the same histology, the tumour with the highest T category should be classified and the multiplicity or the number of tumours should be indicated in parentheses, e.g., T2(m) or T2(5). In simultaneous bilateral primary cancers of paired organs, each tumour should be classified independently. Exceptions include tumours where bilaterality or multiplicity is a component of the T or M category definitions and in malignant melanoma for which, when patients present with multiple primaries, each anatomical skin site is considered a different primary and should be classified separately.

Definitions of the TNM categories and stage may be telescoped 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 subcategories, such as T1a and T1b.

Previously the UICC did not specify a specific time frame within which staging information should be obtained. The AJCC recommends that staging should be complete within 4 months of the original diagnosis. Exceptionally, the presence of metastases may be confirmed after 4 months from diagnosis, and if the treating physician is of the opinion that they were present but unconfirmed at diagnosis, that data may be used; otherwise, staging should be complete within 4 months of original diagnosis and remain unchanged.

Note

* An educational module on the general principles is available on the UICC website at 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.21 Each region or site is described under the following headings:

Anatomical sites, and subsites if appropriate

Definition of the regional lymph nodes

cTNM clinical classification

pTNM pathological classification

G histopathological grading if different from that described on page 8

Stage and prognostic groups

Prognostic factors grid

cTNM Clinical Classification

The following general definitions are used throughout:

cT – Primary Tumour

cTX

Primary tumour cannot be assessed

cT0

No evidence of primary tumour

cTis

Carcinoma in situ

cT1–T4 

Increasing size

*

and/or local extent of the primary tumour

Note

* The UICC does not prescribe the way to measure tumour size for pT classification; however, the AJCC Cancer Staging Manual 2017 [19] recommends that pT is derived from the actual measurement of the unfixed tumour in the surgical specimen. It should be noted, however, that up to 30% shrinkage of soft tissues may occur in the resected specimen. Thus, in cases of discrepancies of clinically and pathologically measured tumour size, the clinical measurement should also be considered for the pT classification.

N – Regional Lymph Nodes

cNX

Regional lymph nodes cannot be assessed

cN0

No regional lymph node metastasis

cN1–N3

Increasing involvement of regional lymph nodes

M – Distant Metastasis*

cM0 

No distant metastasis

cM1

Distant metastasis

Note

* The MX category is considered to be inappropriate as clinical assessment 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)

Bone marrow

MAR (C42.1)

Osseous

OSS (C40, 41)

Pleura

PLE (C38.4)

Hepatic

HEP (C22)

Peritoneum

PER (C48.1,2)

Brain

BRA (C71)

Adrenals

ADR (C74)

Lymph nodes

LYM (C77)

Skin

SKI (C44)

Others

OTH

Subdivisions of TNM

Subdivisions of some main categories are available for those who need greater specificity (e.g., cT1a, cT1b or cN2a, cN2b).

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–N3 

Increasing involvement of regional lymph nodes histologically

Notes

Direct extension of the primary tumour into lymph nodes is classified as lymph node metastasis.

Tumour deposits (TD) represent discrete tumour nodules of any shape, contour or size in peri‐rectal and peri‐colonic fat, away from the leading edge of the tumour, within the lymph drainage area of the primary carcinoma. TD can originate from different histological structures, including lymph nodes, vessels and nerves. Therefore, TD may contain foci of extramural vascular invasion (EMVI) and perineural invasion (PNI). The feature distinguishing a TD from EMVI and PNI is the presence of unequivocal tumour extension from the vessel or nerve into the surrounding fat or fibroconnective tissue.

When tumour outgrowth from EMVI and/or PNI is present, the diagnosis of TD and EMVI/PNI should be denoted separately in the report. If the tumour involves an identifiable lymph node, it is considered as lymph node metastasis and not as tumour deposit even if the tumour extends into the perinodal fat.

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 within the node, 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 2 mm, 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)N0(sn)

No sentinel lymph node metastasis

(p)N1(sn)

Sentinel lymph node metastasis

Isolated Tumour Cells

Isolated tumour cells (ITCs) 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 immunohistochemistry [22]. An additional criterion has been proposed in breast cancer to include a cluster of fewer than 200 cells in a single histological cross‐section. Definitions of ITCs 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 ITCs in lymph nodes should be classified as N0. 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 ITCs in a lymph node are classified as N1a (clinically occult) or N2a. These cases should be analysed separately.20 Their classification is as follows:

N0

No regional lymph node metastasis histologically, no examination for isolated tumour cells (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 non‐morphological findings for ITC

N0(mol+)

No regional lymph node metastasis histologically, positive non‐morphological findings for ITC

Cases with or examined for ITCs in sentinel lymph nodes can be classified as follows:

N0(i–)(sn)