TNM Classification Help

About the TNM System

2005-02-20T14:48:00.000-08:00

The TNM system is the most widely used means for classifying the extent of cancer spread. TNM Classification of Malignant Tumours, Seventh Edition provides the new, internationally agreed-upon standards to describe and categorize cancer stages and progression. This guide contains important new and updated organ-specific classifications that oncologists and other professionals who treat patients with cancer must use to adequately classify tumours for prognosis and treatment.

This introduction provides a history of the TNM system, the principles of the classification of cancers and general rules of the TNM system applicable to all sites. Headings used in the TNM system to classify tumours for specific anatomical regions and sites are also provided with definitions.

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 1952¹.

In 1950, the UICC appointed a Committee on Tumour Nomenclature and Statistics and adopted, as a basis for its work on clinical stage classification, 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 Presentation².

In 1953, the Committee held a joint meeting with the International Commission on Stage-Grouping in Cancer and Presentation of the Results of Treatment of Cancer appointed by the International Congress of Radiology. Agreement was reached on a general technique for classification by anatomical extent of the disease, using the TNM system.

In 1954, the Research Commission of the UICC set up a special Committee on Clinical Stage Classification and Applied Statistics to "pursue studies in this field and to extend the general technique of classification to cancer at all sites." 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 results³.

A second publication in 1959 presented revised proposals for the breast, for clinical use and evaluation over a 5-year period (1960-1964)⁴.

Between 1960 and 1967, the Committee published nine brochures describing proposals for the classification of 23 sites. It was recommended that the classification proposals for each site be subjected to prospective or retrospective trial for a 5-year period.

In 1968, these brochures were combined in a booklet, the Livre de Poche⁵ and a year later, a complementary booklet was 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 rates⁶. The Livre de Poche was subsequently translated into 11 languages.

In 1974 and 1978, second and third editions⁷ were published containing new site classifications and amendments to previously published classifications. The third edition was enlarged and revised in 1982. It contained new classifications for selected tumours of childhood. This was carried out in collaboration with La Société Internationale d'Oncologie Pédiatrique (SIOP). A classification of ophthalmic tumours was published separately in 1985.

Over the years some users introduced variations in the rules of classification of certain sites. In order to correct this development, the antithesis of standardization, the national TNM committees in 1982 agreed to formulate a single TNM. A series of meetings was held to unify and update existing classifications as well as to develop new ones. The result was the fourth edition of TNM⁹.

In 1993, the project published the TNM Supplement¹⁰. The purpose of this work was to promote the uniform use of TNM by providing detailed explanations of the TNM rules with practical examples. It also included proposals for new classifications, and optional expansions of selected categories. A second edition appeared in 2001.¹¹.

In 1995, the project published Prognostic Factors in Cancer¹², a compilation and discussion of prognostic factors in cancer, both anatomic and nonanatomic, at each of the body sites. This was expanded in the second edition in 2001 with emphasis on the relevance of different prognostic factors. The subsequent third edition in 2006 attempted to refine this by providing evidence-based criteria for relevance.

The present seventh edition of TNM Classification contains rules of classification and staging that correspond with those appearing in the seventh edition of the AJCC Cancer Staging Manual (2009) and have approval of all national TNM committees. The UICC recognizes the need for stability in the TNM classification so that data can be accumulated in an orderly way over reasonable periods of time. Accordingly, it is the intention that the classifications published in this booklet should remain unchanged until some major advances in diagnosis or treatment relevant to a particular site requires reconsideration of the current classification.

To develop and sustain a classification system acceptable to all requires the closest liaison between national and international committees. Only in this way will all oncologists be able to use a ‘common language’ in comparing their clinical material and in assessing the results of treatment. While the classification is based on published evidence, in areas of controversy it is based on international consensus.

The continuing objective of the UICC is to achieve common consent in the classification of anatomical extent of disease.

1. The General Rules of the TNM System^1,2

1.1. General Rule No. 1

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

Microscopically unconfirmed cases can be staged, but should be analyzed separately.

Microscopic confirmation of choriocarcinoma is not required if the hCG is abnormally elevated.

1.2. General Rule No. 2

Two classifications are described for each site, namely:

Clinical classification

(Pretreatment clinical classification), designated TNM (or cTNM). This is based on evidence acquired before treatment. Such evidence arises from physical examination, imaging, endoscopy, biopsy, surgical exploration and other relevant examinations.

Pathological classification

(Postsurgical histopathological classification), designated pTNM. This is based on the evidence acquired before treatment, supplemented 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 highest pT category. The pathological assessment of the regional lymph nodes (pN) entails removal of nodes adequate to validate the absence of regional lymph node metastasis (pN0) and sufficient to evaluate the highest pN category. The pathological assessment of distant metastasis (pM) entails microscopic examination.

TNM is a dual system that includes a clinical (pretreatment) and a pathological (postsurgical histopathological) classification. It is imperative to differentiate between these classifications because they are based on different methods of examination and serve different purposes. The clinical classification is designated TNM or cTNM; the pathological, pTNM. When the abbreviation TNM is used without a prefix, it implies the clinical classification (cTNM). Microscopic confirmation does not in itself justify the use of pTNM. The requirements for pathological classification are described in site-specific Recommendations for pT and pN.

Biopsy provides the diagnosis, including histological type and grade. The clinical assessment of tumour size should not be based on the biopsy.

In general, the cTNM is the basis for the choice of treatment and the pTNM is the basis for prognostic assessment. In addition, the pTNM may determine adjuvant treatment. Comparison between cTNM and pTNM can help in evaluating the accuracy of the clinical and imaging methods used to determine the cTNM. Therefore, it is important to retain the clinical as well as the pathological classification in the medical record.

A tumour is primarily described by the clinical classification before treatment or before the decision not to treat. In addition, a pathological classification is performed if specific requirements are met (see Introduction). Therefore, for an individual patient there may be a clinical classification, e.g., T2N1M0 and a pathological classification, e.g., pT2pNXpMX.

1.3. General Rule No. 3

After assigning T, N and M and/or pT, pN and pM categories, these may be grouped into stages. The TNM classification and stage grouping, once established, must remain unchanged in the medical records. The clinical stage is essential to select and evaluate therapy, while the pathological stage provides the most precise data to estimate prognosis and calculate end results.

The rule that the TNM classification, once established, must remain unchanged in the patient's record applies to the definitive TNM classification determined just before initiation of treatment or before making the decision not to treat. If, for instance, the initial classification T2N0M0 is made in one hospital and is later updated to T2N1M0 after the patient is referred to another center where special imaging techniques are available, then the latter classification, based on a special examination, is considered the definitive one.

After two surgical procedures for a single lesion, the pTNM classification should be a composite of the histological examination of the specimens from both operations.

Example. Initial endoscopic polypectomy of a carcinoma of the ascending colon is classified pT1pNXpMX; the subsequent right hemicolectomy contains two lymph nodes with tumour, and a suspicious metastatic focus in the liver, later found to be a haemangioma, is excised-pT0pN1pM0. The definitive pTNM classification consists of the results of both operative specimens-pTlpN1pM0 (stage III).

For final stage grouping clinical and pathological data may be combined when only partial information is available in either the pathological classification or the clinical classification. The example on p. 2 is expressed as pT2cN1cM0 (stage III). For further discussion on the meaning and application of X (e.g. NX, MX).

1.4. General Rule No. 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 grouping.

Example. Sonography of the liver: suspicious lesion but no definitive evidence of metastasis-assign M0 (not M1).

If there are different results from different methods, the classification should be based on the most reliable method of assessment.

Example. Colorectal carcinoma, preoperative examination of the liver: sonography, suspicious, but no evidence of metastasis; CT, evidence of metastasis. The results of CT determine the classification-Ml. However, if CT were negative, the case would be classified M0.

1.5. General Rule No. 5

In the case of multiple simultaneous 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 parentheses, e.g., T2(m) or T2(5). In simultaneous bilateral cancers of paired organs, each tumour should be classified independently. In tumours of the thyroid, liver, ovary, and fallopian tube, multiplicity is a criterion of T classification.

The following apply to grossly recognizable multiple primary simultaneous carcinomas at the same site. They do not apply to one grossly detected tumour associated with multiple separate microscopic foci.

Multiple synchronous tumours in one organ may be:

a.	Multiple noninvasive tumours
b.	Multiple invasive tumours
c.	Multiple invasive tumours with associated carcinoma in situ
d.	A single invasive tumour with associated carcinoma in situ

For (a) the multiplicity should be indicated by the suffix "(m)", e.g. Tis(m).

For (b) and (c) the tumour with the highest T category is classified and the multiplicity or the number of invasive tumours is indicated in parentheses, e.g., T2(m) or T2(4).

For (c) and (d) the presence of associated carcinoma in situ may be indicated by the suffix "(is)", e.g., T3(m, is) or T2(3, is) or T2(is).

For classification of multiple simultaneous tumours in "one organ", the definitions of one organ listed in Table 1 should be applied. The tumours at these sites 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).

Combining multiple carcinomas of skin should be done only within subsites (C44.1,2, etc). A carcinoma of the skin in subsite C44.3 and a synchronous one in subsite C44.6 and C44.7 should be classified as separate synchronous tumours.

Examples of sites for separate classification of two tumours are:

·	Oropharynx and hypopharynx
·	Submandibular gland and parotid gland
·	Urinary bladder and urethra (separate tumours)
·	Skin carcinoma of eyelid and neck

Examples for classification of the tumour with the highest T category and indication of multiplicity (m symbol) or numbers of tumours:

·	Two separate tumours of the hypopharynx
·	Carcinoma of the caecum and the transverse colon
·	Skin carcinoma of the trunk and the arm
·	Carcinoma of renal pelvis and ureter
·	See item No. 1 of M classification

If a new primary cancer is diagnosed within 2 months in the same site this new cancer is considered synchronous (based on criteria used by the SEER Program of the National Cancer Institute, USA).

Table 1. Definition of "one organ" for the classification of multiple simultaneous primary tumours: the listed sites/subsites are considered as "one organ"

	ICD-O Code^a
Lip	C00.0,1,2,6
Oral cavity	C00.3-5, C02.0-3, C03, C04, C05.0, C06
Oropharynx	C01, C05.1,2, C09, C10.0,2,3
Nasopharynx	C11
Hypopharynx	C12, C13
Larynx	C10.1, C32.0-2
Maxillary sinus	C31.0
Ethmoid sinus	C31.1
Parotid gland	C07
Submandibular (submaxillary gland)	C08.0
Sublingual gland	C08.1
Thyroid^b	C73
Oesophagus	C15
Stomach	C16
Small intestine	C17
Colon and rectum	C18-C20
Anal canal	C21.1,2
Liver^b	C22
Gallbladder	C23
Extrahepatic bile ducts	C24.0
Ampulla of Vater	C24.1
Pancreas	C25
Lung	C34
Pleura	C38.4
Bones	C40, C41
Soft tissues, peripheral	C47, C49
Retroperitoneum	C48
Mediastinum	C38.1-3
Skin (subsite(s) only) except eyelid, anal margin, and perianal skin	C44.0,2-4, 6-9
Eyelid	C44.1
Anal margin and perianal skin	C44.5
Breast	C50
Vulva	C51
Vagina	C52
Cervix uteri	C53
Corpus uteri	C54
Ovary^b	C56
Fallopian tube^b	C57
Gestational trophoblastic tumours	C58.9
Nose	C60
Prostate	C61
Testis	C62
Scrotum	C63.2
Kidney	C64
Renal pelvis and ureter	C65, C66
Urinary bladder	C67
Urethra	C68.0
Conjunctiva	C69.0
Uvea	C69.3,4
Retina	C69.2
Orbit	C69.6
Lacrimal gland	C69.5

^aICD-O Topography code, 3^rd edition, 2000, WHO, Geneva

^bIn this organ multiplicity is a criterion of T classification

2. The Principles of the TNM System

The practice of dividing cancer cases into groups according to so-called stages arose from the fact 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. These groups were often referred to as early cases and late cases, implying some regular progression with time. Actually, the stage of disease at the time of diagnosis may be a reflection not only of the rate of growth and extension of the neoplasm but also of the type of tumour and of the tumour-host relationship.

The staging of cancer is hallowed by tradition, and for the purpose of analysis of groups of patients it is often necessary to use such a method. The UICC believes that it is important to reach agreement on the recording of accurate information on the extent of the disease for each site, because the precise clinical description of malignant neoplasms and histopathological classification may serve a number of related objectives, namely

To aid the clinician in the planning of treatment
To give some indication of prognosis
To assist in evaluation of the results of treatment
To facilitate the exchange of information between treatment centres
To contribute to the continuing investigation of human cancer

The principal purpose to be served by international agreement on the classification of cancer cases by extent of disease is to provide a method of conveying clinical experience to others without ambiguity.

There are many bases or axes of tumour classification: for example, the anatomical site and the clinical and pathological extent of disease, the reported duration of symptoms or signs, the gender and age of the patient, and the histological type and grade. All of these bases or axes represent variables that are known to have an influence on the outcome of the disease. Classification by anatomical extent of disease as determined clinically and histopathologically (when possible) is the one with which the TNM system primarily deals.

The clinician's immediate task 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. In accomplishing this, the trend is away from "staging" to meaningful description, with or without some form of summarization.

To meet the stated objectives a system of classification is needed

whose basic principles are applicable to all sites regardless of treatment; and
which may be supplemented later by information that becomes available from histopathology and/or surgery.

The TNM system meets these requirements.

3. 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 of distant metastasis.
The addition of numbers to these three components indicates the extent of the malignant disease, thus:

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 (Pre-treatment clinical classification), designated TNM (or cTNM). This is based on evidence acquired before treatment. Such evidence arises from physical examination, imaging, endoscopy, biopsy, surgical exploration, and other relevant examinations.

(b) Pathological classification (Post-surgical histopathological classification), designated pTNM. This is based on the evidence acquired before treatment, supplemented 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 highest pT category. The pathological assessment of the regional lymph nodes (pN) entails removal of nodes adequate to validate the absence of regional lymph node metastasis (pN0) and sufficient to evaluate the highest pN category. The pathological assessment of distant metastasis (pM) entails microscopic examination.

3. After assigning T, N, and M and/or pT, pN, and pM categories, these may be grouped into stages. The TNM classification and stage grouping, once established, must remain unchanged in the medical records. The clinical stage is essential to select and evaluate therapy, while the pathological stage provides the most precise data to estimate prognosis and calculate end results.

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 grouping.

5. In the case of multiple simultaneous 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 parentheses, e.g., T2 (m) or T2 (5). In simultaneous bilateral 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.

6. Definitions of TNM categories and stage grouping may be telescoped or expanded for clinical or research purposes as long as basic definitions recommended are not changed. For instance, any T, N, or M can be divided into subgroups.

4. Anatomical Regions and Sites

The sites in this classification are listed by code number of the International Classification of Diseases for Oncology¹⁵.

Each region or site is described under the following headings:

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
Stage grouping
Summary for the region or site

5. TNM Clinical Classification

The following general definitions are used throughout: 5.1. T - Primary Tumour

TX. Primary tumour cannot be assessed
T0. No evidence of primary tumour
Tis. Carcinoma in situ
T1, T2, T3, T4. Increasing size and/or local extent of the primary tumour

5.2. N - Regional Lymph Nodes

NX. Regional lymph nodes cannot be assessed
N0. No regional lymph node metastasis
N1. Regional lymph node metastasis

5.3. M - Distant Metastasis

MX. Distant metastasis cannot be assessed
M0. No distant metastasis
M1. Distant metastasis

The categories M1 and pM1 may be further specified according to the following notation:

Pulmonary	PUL	Bone marrow	MAR
Osseous	OSS	Pleura	PLE
Hepatic	HEP	Peritoneum	PER
Brain	BRA	Adrenals	ADR
Lymph nodes	LYM	Skin	SKI
Others	OTH

6. pTNM Pathological Classification

The following general definitions are used throughout:

6.1. pT - Primary Tumour

pTX. Primary tumour cannot be assessed histologically
pT0. No histological evidence of primary tumour
pTis. Carcinoma in situ
pT1, pT2, pT3, pT4. Increasing size and/or local extent of the primary tumour histologically

6.2. pN - Regional Lymph Nodes

pNX. Regional lymph nodes cannot be assessed histologically
pN0. No regional lymph node metastasis histologically
pN1, pN2, pN3. Increasing involvement of regional lymph nodes histologically

Notes:

Direct extension of the primary tumour into lymph nodes is classified as lymph node metastasis.
A tumour nodule in the connective tissue of a lymph drainage area without histologic evidence of residual lymph node is classified in the pN category as a regional lymph node metastasis if the nodule has the form and smooth contour of a lymph node. A tumour nodule with an irregular contour is classified in the pT category, i.e., discontinuous extension. It may also be classified as venous invasion (V classification).
When size is a criterion for pN classification, measurement is made of the metastasis, not of the entire lymph node.
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) or pN2(mi)

6.3. 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:

pNX (sn). Sentinel lymph node could not be assessed
pN0 (sn). No sentinel lymph node metastasis
pN1 (sn). Sentinel lymph node metastasis

6.4. Isolated Tumour Cells
Isolated tumour cells (ITC) are single tumour cells or small clusters of cells not more than 0.2 mm in greatest dimension that are usually detected by immunohistochemistry or molecular methods, but which may be verified with H and E stains. 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-morphologic techniques such as flow cytometry or DNA analysis. These cases should be analysed separately¹⁶. Their classification is as follows.

pN0. No regional lymph node metastasis histologically, no examination for isolated tumour cells (ITC)
pN0(i-). No regional lymph node metastasis histologically, negative morphological findings for ITC
pN0(i+). No regional lymph node metastasis histologically, positive morphological findings for ITC
pN0(mol-). No regional lymph node metastasis histologically, negative non-morphological findings for ITC
pN0(mol+). No regional lymph node metastasis histologically, positive non-morphological findings for ITC

Cases with or examined for isolated tumour cells (ITC) in sentinel lymph nodes can be classified as follows:

pN0 (i-)(sn). No sentinel lymph node metastasis histologically, negative morphological findings for ITC
pN0 (i+)(sn). No sentinel lymph node metastasis histologically, positive morphological findings for ITC
pN0 (mol-)(sn). No sentinel lymph node metastasis histologically, negative non-morphological findings for ITC
pN0 (mol+)(sn). No sentinel lymph node metastasis histologically, positive non-morphological findings for ITC

6.5. pM - Distant Metastasis

pMX. Distant metastasis cannot be assessed microscopically
pM0. No distant metastasis microscopically
pM1. Distant metastasis microscopically
The category pM1 may be further specified in the same way as M1 (see M - Distant Metastasis).

Isolated tumour cells found in bone marrow with morphological techniques are classified according to the scheme for N, e.g., M0(i+). For non-morphologic findings "mol" is used in addition to M0, e.g., M0(mol+).

6.6. Subdivisions of pTNM
Subdivisions of some main categories are available for those who need greater specificity (e.g., pT1a, 1b or pN2a, 2b).

7. 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."
The bone and soft tissue sarcoma classifications also use "high grade" and "low grade."
Special systems of grading are recommended for tumours of breast, corpus uteri, and liver.

8. Additional Descriptors

For identification of special cases in the TNM or pTNM classification, the m, y, r, and a symbols are 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 initial multimodality therapy, the cTNM or pTNM category is identified by a y prefix. The ycTNM or ypTNM categorizes 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.

9. Optional Descriptors

9.1. L - Lymphatic Invasion

LX. Lymphatic invasion cannot be assessed
L0. No lymphatic invasion
L1. Lymphatic invasion

9.2. 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.

9.3. C-Factor

The C-factor, or certainty factor, reflects the validity of classification according to the diagnostic methods employed. Its use is optional.

The C-factor definitions are:

C1. Evidence from standard diagnostic means (e.g., inspection, palpation, and standard radiography, intraluminal endoscopy for tumours of certain organs)
C2. Evidence obtained by special diagnostic means (e.g., radiographic imaging in special projections, tomography, computerized tomography [CT], ultrasonography, lymphography, angiography; scintigraphy; magnetic resonance imaging [MRI]; endoscopy, biopsy, and cytology)
C3. Evidence from surgical exploration, including biopsy and cytology
C4. Evidence of the extent of disease following definitive surgery and pathological examination of the resected specimen
C5. Evidence from autopsy

Example: Degrees of C may be applied to the T, N, and M categories. A case might be described as T3C2, N2C1, M0C2.

The TNM clinical classification is therefore equivalent to C1, C2, and C3 in varying degrees of certainty, while the pTNM pathological classification generally is equivalent to C4.

10. 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 footnote 11).

TNM and pTNM describe the anatomical extent of cancer in general without considering treatment. They can be supplemented 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

11. Stage Grouping

Classification by the TNM system achieves reasonably precise description and recording of the apparent anatomical extent of disease. A tumour with four degrees of T, three degrees of N, and two degrees of M will have 24 TNM categories. For purposes of tabulation and analysis, except in very large series, it is necessary to condense these categories into a convenient number of TNM stage groups.

Carcinoma in situ is categorized stage 0; cases with distant metastasis stage IV (except at certain sites, e.g., papillary and follicular carcinoma of thyroid).

The grouping adopted is such as to ensure, as far as possible, 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 stage grouping, if sufficient tissue has been removed for pathologic examination to evaluate the highest T and N categories, M1 may be either clinical (cM1) or pathologic (pM1). However, if only a distant metastasis has had microscopic confirmation, the classification is pathologic (pM1) and the stage is pathologic.

12. Site Summary

As an aide-mémoire or as a means of reference, a simple summary of the chief points that distinguish the most important categories is added at the end of each site. These abridged definitions are not completely adequate, and the full definitions should always be consulted.

13. Related Classifications

Since 1958, WHO has been involved in a programme aimed at providing internationally acceptable criteria for the histologic 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. The publications can be ordered online at www.iarc.fr/who-bluebooks/ or by email, iarcpress@who.int.

The WHO International Classification of Diseases for Oncology (ICD-O) (see footnote 15) s a coding system for neoplasms by topography and morphology and for indicating behaviour (e.g., malignant, benign). This coded nomenclature is identical in the morphology field for neoplasms to the Systematized Nomenclature of Medicine (SNOMED)¹⁷.

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 code be used for storage and retrieval of data.

End Notes

1.	Denoix PF: Bull Inst Nat Hyg (Paris) 1944;1:69. 1944;2:82. 1950;5:81. 1952;7:743.
2.	World Health Organization Technical Report Series, number 53, July 1952, pp. 47–48
3.	International Union Against Cancer (UICC), Committee on Clinical Stage Classification and Applied Statistics: Clinical stage classification and presentation of results, malignant tumours of the breast and larynx. Paris; 1958.
4.	International Union Against Cancer (UICC), Committee on Stage Classification and Applied Statistics: Clinical stage classification and presentation of results, malignant tumors of the breast. Paris; 1959.
5.	International Union Against Cancer (UICC): TNM Classification of malignant tumours. Geneva; 1968.
6.	International Union Against Cancer (UICC): TNM General Rules. Geneva; 1969.
7.	International Union Against Cancer (UICC): TNM Classification of malignant tumours. 2nd ed. Geneva; 1974.
8.	International Union Against Cancer (UICC): TNM Classification of malignant tumours. 3rd ed. Harmer MH, ed. Geneva; 1978. Enlarged and revised 1982.
9.	International Union Against Cancer (UICC): TNM Classification of malignant tumours. 4th ed. Hermanek P, Sobin LH, eds. Berlin, Heidelberg, New York: Springer Verlag; 1987. Revised 1992.
10.	International Union Against Cancer (UICC): TNM Supplement 1993. A commentary on uniform use. Hermanek P, Henson DE, Hutter RVP, Sobin LH, eds. Berlin, Heidelberg, New York: Springer Verlag; 1993.
11.	International Union Against Cancer (UICC): TNM Supplement. A commentary on uniform use. 2nd ed. Wittekind Ch, Henson DE, Hutter RVP, Sobin LH, eds. New York: Wiley; 2001.
12.	International Union Against Cancer (UICC): Prognostic factors in cancer. Hermanek P, Gospodarowicz MK, Henson DE, Hutter RVP, Sobin LH, eds. Berlin, Heidelberg, New York: Springer Verlag; 1995.
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17.	SNOMED International: The systematized nomenclature of human and veterinary medicine, Northfield, Ill: College of American Pathologists, `http://snomed.org`

TNM 7 - Introduction

Explanatory Notes - Specific Anatomical Sites

2005-02-20T14:14:00.000-08:00

Abstract

This chapter provides additional explanatory information for the general application of TNM providing more precise definitions for anatomical sites/subsites, regional lymph nodes and T, N, and M categories that are generic or ambiguous.

1. Head and Neck Tumours

1.1. General

1.1.1. Anatomy

A uniform topographic terminology should be used for classification, and the "sites, subsites, adjacent sites and adjacent structures" should be used as defined in the text.

Tumours involving two anatomical sites are classified according to the site in which the greater part of the tumour is located. In invasive tumours with an associated carcinoma in situ, only the invasive component is considered for classification.

Example. Carcinoma with two-thirds in the hypopharynx and one-third in the supraglottis is classified as hypopharynx carcinoma.

1.1.2. Extension to Adjacent Sites

In tumours extending to an adjacent site, differentiation between superficial extension and deep extension is necessary. In superficial extension, the involvement is limited to the mucosa; in deep extension, muscles, bones or other deep structures are invaded.

Superficial extension to adjacent sites is not considered invasion of adjacent structures (T4).

Example. A tumour extending from the oropharynx to nasopharynx or hypopharynx or to oral cavity and limited to the mucosa (without invasion of muscles, bones or other deep structures) is classified only according to size. The involvement of nasopharynx or hypopharynx or oral cavity is not considered invasion of adjacent structures as long as the tumour is limited to the mucosa.

Deep extension to an adjacent site can be the result of vertical invasion of adjacent structures (see above) or the result of horizontal spread not limited to the mucosa but also involving muscles or bones. Such extension is classified as invasion of adjacent structures (T4).

Example. Base of tongue carcinoma invading the preepiglottic space is classified as T4.

1.1.3. Adjacent Structures

Adjacent structures refer to organs and tissues that can be deeply invaded by a tumour, e.g., extension of a glottis carcinoma through thyroid cartilage into soft tissues of the neck or extension of a carcinoma of the maxillary sinus into the orbit.

1.1.4. Regional Lymph Nodes

According to the TNM Atlas [31] the cervical lymph nodes include the following groups (Figs. 2 and 3. See also Fig. 1, p. 22 of the AJCC manual [1]): The first 8 groups are commonly referred to by levels:

1.	Submental nodes (Level IA)
2.	Submandibular nodes (syn. submaxillary nodes) (Level IB)
3.	Cranial jugular (deep cervical) nodes (Level II)
4.	Medial jugular (deep cervical) nodes (Level III)
5.	Caudal jugular (deep cervical) nodes (Level IV)
6.	Dorsal cervical (superficial cervical) nodes along the spinal accessory nerve (Level V)
7.	Supraclavicular nodes (Level IV and, uncommonly, Level V)
8.	Prelaryngeal and paratracheal (syn. anterior cervical) nodes (Level VI)
9.	Retropharyngeal nodes
10.	Parotid nodes
11.	Buccal nodes (syn. facial nodes)
12.	Retroauricular (syn. mastoid, posterior auricular) and occipital nodes


	Figure 2. Cervical lymph node groups [31] [Full View]

	Figure 3. Subdivision of prelaryngeal and paratracheal (anterior cervical) lymph nodes (group 8). [Full View]

In 1991, a standardized neck dissection terminology was published by a Committee for Head and Neck Surgery and Oncology of the American Academy for Otolaryngology-Head and Neck Surgery [24]. In October 1992, at an international symposium in Göttingen, Germany, this terminology was accepted by representatives of various European cancer centers (Villejuif, Milan, Amsterdam). We support the use of this terminology [24]. The lymph node groups 1-8 are defined as follows:

Submental group (Level IA):

Lymph nodes within the triangular boundary of the anterior belly of the digastric muscle and the hyoid bone.

Submandibular group (Level IB):

Lymph nodes within the boundaries of the anterior and posterior bellies of the digastric muscle and the body of the mandible.

Upper jugular group (Level II):

Lymph nodes located around the upper third of the internal jugular vein and adjacent spinal accessory nerve, extending from the hyoid bone (clinical landmark) to the skull base. The posterior boundary is the posterior border of the sternocleidomastoid muscle, and the anterior boundary is the lateral border of the sternohyoid muscle. This group includes the jugulodigastric node, which is the most cranial jugular node.

Middle jugular group (Level III):

Lymph nodes located around the middle third of the internal jugular vein, extending from the carotid bifurcation superiorly to the omohyoid muscle (surgical landmark) or cricothyroid notch (clinical landmark) inferiorly. The posterior boundary is the posterior border of the sternocleidomastoid muscle, and the anterior boundary is the lateral border of the sternohyoid muscle. This group includes the juguloomohyoid node located between omohyoid muscle and internal jugular vein.

Lower jugular group (Level IV):

Lymph nodes located around the lower third of the internal jugular vein, extending from the omohyoid muscle superiorly to the clavicle inferiorly. The posterior boundary is the posterior border of the sternocleidomastoid muscle, and the anterior boundary is the lateral border of the sternohyoid muscle.

Dorsal cervical nodes along the spinal accessory nerve (Level V) and

Supraclavicular nodes (mostly Level IV):

The two groups are combined and called the "posterior triangle group": This comprises predominantly the lymph nodes located along the lower half of the spinal accessory nerve and the transverse cervical artery. The supraclavicular nodes are also included. The posterior boundary is the anterior border of the trapezius muscle, the anterior boundary is the posterior border of the sternocleidomastoid muscle, and the inferior border is the clavicle. Most are in Level IV; some may occupy the most caudal component of Level V.

Anterior compartment group (Level VI):

Lymph nodes surrounding the midline visceral structures of the neck, extending from the level of the hyoid bone superiorly to the suprasternal notch inferiorly. On each side, the lateral boundary is the medial border of the carotid sheath. Located within this compartment are the perithyroidal lymph nodes, paratracheal lymph nodes, lymph nodes along the recurrent laryngeal nerves and precricoid lymph nodes.

Node group 8 (prelaryngeal and paratracheal nodes) may be further subdivided as follows (Figure 3):

8a: cranial paratracheal (suprathyroidal)

8b: thyroidal (perithyroidal)

8c: caudal paratracheal (infrathyroidal, lateral tracheal)

8d: prelaryngeal

8e: pretracheal near the thyroid isthmus (delphian)

Retropharyngeal nodes

10.

The parotid nodes may be subdivided into superficial (in front of tragus on top of parotid fascia) and deep parotid nodes. The latter are located underneath the parotid fascia and include intraglandular nodes directly in parotid gland. The preauricular and infra-auricular (infra- or subparotid) nodes are assigned to the parotid nodes.

11.

The buccal (facial) nodes include the buccinator nodes located deep on buccinator muscle, the nasolabial nodes located underneath nasolabial groove, the molar nodes located in the surface of cheek and the mandibular nodes located outside the lower jaw.

For thyroid surgery, a distinction between a central and a lateral compartment is of interest for treatment planning [5]. The central compartment includes groups 1, 2 and 8, the lateral compartment groups 3-7.

The regional lymph nodes for thyroid include the upper mediastinal lymph nodes, which may be subdivided into tracheo-oesophageal (posterior mediastinal) and upper anterior mediastinal nodes. Cervical and mediastinal lymph nodes are not divided by a fascia; the left brachiocephalic vein is considered to be the boundary [5].

1.1.5. N Classification

Size of Lymph Nodes: In advanced lymphatic spread, one often finds perinodal tumour and the confluence of several lymph node metastases into one large tumour conglomerate. In the definition of the N classification, the perinodal component should be included in the size for isolated lymph node metastases; for conglomerates, the overall size of the conglomerate should be considered and not only the size of the individual lymph nodes.

1.2. Lip and Oral Cavity

Summary Lip, Oral Cavity

T1	≤2 cm
T2	>2-4 cm
T3	>4 cm
T4	Adjacent structures

1.2.1. Lip

Tumours that affect the vermilion surface as well as the skin are assigned to the lip when 50% or more of the tumour is within the vermilion surface.

The vermilion surface is demarcated from the mucosal surface by the line of contact of the opposing lips.

Skin of face is not classified as an adjacent structure.

Invasion up to cortical bone or erosion of the bone is not classified T4. There must be invasion through the cortical bone into the spongiosa.

1.2.2. Oral Cavity

T4 definitions:

a.	The deep (extrinsic) muscle of the tongue includes musculi hyo-, stylo-, genio- and palatoglossus. Invasion indicates T4. Generally, deep muscle invasion is associated with restriction of mobility of the tongue when examined clinically.
b.	The intrinsic muscle of the tongue includes musculi longitudinalis superior and inferior, transversus linguae and verticalis linguae. Invasion of the intrinsic muscle alone or the submandibular gland is not classified T4.
c.	Invasion up to cortical bone or erosion of the bone is not classified T4. There must be invasion through the cortical bone into the spongiosa.
d.	Invasion of the sublingual gland by a carcinoma of the floor of mouth does not qualify for T4 and is not considered in the T classification.

A tumour extending from the oral cavity to the oropharynx and limited to the mucosa (without invasion of muscles, bones or other deep structures) is classified only according to size. The involvement of oropharynx is not considered invasion of adjacent structures as long as the tumour is limited to the mucosa.

1.3. Pharynx

1.3.1. Oropharynx

Summary Oropharynx

T1	≤2 cm
T2	>2-4 cm
T3	>4 cm
T4	Adjacent structures

A tumour extending from the oropharynx to the nasopharynx or to the hypopharynx or to the oral cavity or larynx and limited to the mucosa (without invasion of muscles, bones or other deep structures) is classified only according to size up to T3. The involvement of nasopharynx or hypopharynx or oral cavity or larynx is not considered invasion of adjacent structures provided that the tumour is limited to the mucosa.

A tumour invading soft tissue of neck and paravertebral fascia/muscles is classified as T4.

Definition of invasion of the larynx: Invasion of outer framework (thyroid cartilage, cricoid cartilage, preepiglottic space) or internal structures such as arytenoid and epiglottic cartilages.

1.3.2. Nasopharynx

Summary Nasopharynx

T1		Nasopharynx
T2		Soft tissue of oropharynx and/or nasal fossa
	T2a	Without parapharyngeal extension
	T2b	With parapharyngeal extension
T3		Invades bony structures and/or paranasal sinuses
T4		Intracranial extension, involvement of cranial nerves, infratemporal fossa, hypopharynx, orbit

Tumours not involving the oropharynx and/or nasal fossa but with parapharyngeal extension are classified T2b.

The term "postnasal space" corresponds to nasopharynx (C11). Invasion of vertebral bodies is classified T3.

The terms masticator space and infratemporal fossa are considered synonymous here.

1.3.3. Hypopharynx

Summary Hypopharynx

T1	≤2 cm and limited to one subsite
T2	>2 to 4 cm or more than one subsite
T3	>4 cm or with larynx fixation
T4	Invades adjacent structures

The term "laryngopharynx" corresponds to hypopharynx (C13.9).

For classification, the hypopharyngeal surface of the aryepiglottic fold (C13.1) belongs to the hypopharynx, whereas the laryngeal aspect of the aryepiglottic fold (C32.1) is part of the supraglottis.

Fixation of hemilarynx is diagnosed endoscopically by immobility of the arytenoid or vocal cord.

The uncommon tumours limited to one subsite but with vocal cord fixation should be classified as T3.

Involvement of the arytenoid cartilage is classified as T3, not T4.

Invasion of adjacent structures (T4) includes

·	Invasion of the thyroid cartilage or cricoid cartilage (involvement of perichondrium only is not invasion of the cartilage)
·	Invasion of the soft tissues of the neck
·	Invasion of vertebral bodies

A tumour extending from the hypopharynx to oesophagus and limited to the mucosa (without invasion of muscles, bones or other deeper structures) is classified only according to size up to T3.

A tumour of the sinus piriformis (C12.9) with invasion of the thyroid cartilage should not be classified as T4 but rather as T3.

1.3.4. Larynx

Summary Larynx

*Summary Supraglottis*
T1	One subsite, normal mobility
T2	Involving mucosa of more than one adjacent subsite of supraglottis or glottis or adjacent region outside the supraglottis, without fixation
T3	Limited to the larynx with vocal cord fixation or invades postcricoid area, pre-epiglottic tissues, base of tongue
T4	Extends beyond the larynx
*Summary Glottis*
T1	Limited to vocal cord(s), normal mobility
T2	Supraglottis, subglottis, impaired cord mobility
T3	Cord fixation
T4	Extends beyond larynx
*Summary Subglottis*
T1	Limited to the subglottis
T2	Extends to vocal cord(s) with normal/impaired mobility
T3	Cord fixation
T4	Extends beyond larynx

1.3.5. Anatomical Definitions

1.3.5.1. Superior and Inferior Boundaries of the Glottis

According to the AJCC Cancer Staging Manual [1], the inferior boundary of the supraglottis is the horizontal plane passing through the lateral margin of the ventricle at its junction with the superior surface of the vocal cord. Kleinsasser [19, 20] emphasized embryological and functional reasons for the following definition of the boundary between supraglottis and glottis:

A plane running horizontally through the opening of the ventricle, posteriorly over the vocal process of the arytenoid cartilage and then rising between the cuneiform and the corniculate cartilage to end over the upper edge of the posterior commissure.

According to the AJCC Cancer Staging Manual [1], the lower boundary of the glottis is the horizontal plane 1 cm below the lateral margin of the ventricle.

According to Alberti u. Boyce [2] the following definition is recommended: The inferior boundary of the glottis is a horizontal plane 1 cm inferior to the level of the upper surface of the vocal cords, which divides supraglottis and glottis (Fig. 54 TNM Atlas 1997 [31]).

1.3.6. Pathological Criteria of Impaired Vocal Cord Mobility or Vocal Cord Fixation

1.3.6.1. Impaired Mobility or Fixation

For pathological classification concerning impaired mobility or fixation of vocal cords the information from the clinical T is used for the pathologic T. This is in accordance with TNM rule No. 2, pathological classification "is based on the evidence acquired before treatment, supplemented or modified by the additional evidence acquired from surgery and from pathological examination".

1.3.7. Associated Carcinoma In Situ

1.	For invasive carcinoma, the classification according to horizontal spread is based only on the invasive component.
2.	To indicate the presence of associated carcinoma in situ (adjacent or separate) the suffix "(is)" may be added to the respective T category of the invasive carcinoma, e.g., T2(is). The presence of an associated carcinoma in situ influences treatment of the invasive carcinoma and needs identification and separate analysis of such cases.

1.3.8. Paranasal Sinuses

Summary Maxillary Sinus

T1	Antral mucosa
T2	Bone destruction
T3	Posterior wall maxillary sinus, subcutaneous tissues, skin of cheek, floor/medial wall of orbit, infratemporal fossa, pterygoid plates, ethmoid sinus(es)
T4	Orbital contents, cribriform plate, base of skull, nasopharynx, sphenoid, frontal sinus

Summary Ethmoid Sinus

T1	Ethmoid (with or without bone erosion)
T2	Nasal cavity
T3	Anterior orbit, maxillary sinus
T4	Intracranial cavity, orbital apex, sphenoid, frontal sinus, skin of nose

Erosion of bone indicates that the tumour invades the cortex only; invasion of bone indicates that the spongiosa is involved.

1.3.9. Salivary Glands

Summary Salivary Glands

T1	≤2 cm, without extraparenchymal extension
T2	>2 to 4 cm, without extraparenchymal extension
T3	Extraparenchymal extension, and/or >4 to 6 cm
T4	Base of skull, seventh nerve, and/or >6 cm

Tumours arising in minor salivary glands localized to the mucous membrane of the upper aerodigestive tract are classified according to the rules for tumours of the oral cavity or pharynx.

Designation by histological type should be done to permit separation of squamous mucosal tumours from salivary gland tumours.

2. Digestive System Tumours

2.1. Rules for Classification

The classification applies to all types of carcinoma including small cell carcinoma. It does not apply to carcinoids.

2.2. Oesophagus

Summary Oesophagus

T1	Lamina propria, submucosa
T2	Muscularis propria
T3	Adventitia
T4	Adjacent structures
N1	Regional
M1	Distant metastasis
	Tumour of lower thoracic oesophagus
	M1a	Coeliac nodes
	M1b	Other distant metastasis
	Tumour of upper thoracic oesophagus
	M1a	Cervical nodes
	M1b	Other distant metastasis
	Tumour of mid-thoracic oesophagus
	M1b	Distant metastasis including nonregional nodes

There is a proposal to divide carcinomas of the oesophago-gastric junction region into three entities [27, 28]:

·	adenocarcinoma of the distal oesophagus (adenocarcinoma of the esophagogastric junction = AEG I, Barrett)
·	"real" carcinoma of the cardia (AEG II)
·	subcardial carcinoma of the stomach, infiltrating the distal oesophagus (AEG III)

Nevertheless, there exists no separate TNM classification for tumours of the cardia. For discussion of tumours of the cardia, see below, stomach anatomy.

For tumours of the lower and upper oesophagus, the categories M1a and M1b are provided:

Lower thoracic oesophagus:
M1a	Metastasis in coeliac lymph nodes
M1b	Other distant metastasis

Upper thoracic oesophagus:
M1a	Metastasis in cervical lymph nodes
M1b	Other distant metastasis

In contrast, for tumours of mid-thoracic oesophagus, any distant metastasis is classified as M1b. For tumours of cervical oesophagus only the category M1 (without subdivision) is used.

2.3. Stomach

2.3.1. Anatomy

Gastric tumours located in the cardiac area may involve the distal oesophagus and primary oesophageal tumours may involve the cardiac area of the stomach. For differentiation between oesophageal and gastric carcinomas the following may be considered:

·	If more than 50% of the tumour involves the oesophagus, the tumour is classified as oesophageal; if less than 50%, as gastric
·	If the tumour is equally located above and below the oesophagogastric junction or is designated as being at the junction, squamous cell, small cell and undifferentiated carcinomas are classified as oesophageal, adenocarcinoma and signet ring cell carcinoma as gastric
·	In the presence of Barrett oesophagus, an adenocarcinoma in both cardia and lower oesophagus is most likely to be oesophageal. In the absence of Barrett oesophagus such an adenocarcinoma is most likely to be gastric.

2.3.2. Regional Lymph Nodes

The regional lymph nodes are:

The perigastric nodes along the lesser curvature

1	Right cardiac
3	Lesser curvature
5	Suprapyloric

The perigastric nodes along the greater curvature

2	Left cardiac
4a	Greater curvature left
4b	Greater curvature right
6	Infrapyloric

The nodes located along the main trunks of the following arteries

7	Left gastric
8	Common hepatic
9	Coeliac
10	Splenic/at the splenic hilum
11	Splenic/along trunk
12	Nodes in the hepatoduodenal ligament

Note. The numerical order corresponds to the proposals of the Japanese Research Society for Gastric Cancer [17].

2.3.3. Nomenclature of the 2nd ed. Japanese Classification [18]

2.3.3.1. Perigastric Lymph Nodes

No. 1	Right paracardial
No. 2	Left paracardial
No. 3	Along the lesser curvature
No. 4	Along the greater curvature (According to the TNM Atlas this station may be subdivided into 4a left and 4b right)
No. 5	Suprapyloric
No. 6	Infrapyloric

2.3.3.2. Lymph Nodes of the Gastric Bed

No. 7	Along the left gastric artery
No. 8	Along the common hepatic artery
No. 9	Around the celiac artery
No. 10	At the splenic hilum
No. 11	Along the splenic artery
No. 12	In the hepatoduodenal ligament

Note. The numerical order corresponds to the proposals of the Japanese Gastric Cancer Association [18].

Stations 7, 8, 9 and 11 include only lymph nodes along the main trunk of the mentioned arteries. Lymph nodes along the ramifications of the left gastric artery are classified as perigastric nodes.

In case of gastric stump carcinoma (after previous distal gastrectomy and localized at the anastomosis), lymph nodes in the mesentery of the intestinal loop used for anastomosis are classified as gastric regional nodes.

In case of invasion of the oesophagus the infradiaphragmatic lymph nodes (no. 19) and the lymph nodes of the oesophageal hiatus (no. 20) are considered as additional regional lymph nodes [18].

2.3.4. T Classification

Summary Stomach

T1	Lamina propria, submucosa
T2	Muscularis propria
T3	Penetrates serosa
T4	Adjacent structures

Invasion of the transverse mesocolon is considered analogous to invasion of the gastrocolic ligament and is therefore classified T2 if the covering visceral peritoneum is not perforated (see TNM Classification 1997 [30], Note 1, p. 60). The same applies to direct invasion of the greater omentum. Tumour nodules in the greater omentum that are separate from the primary tumour are classified as distant (peritoneal) metastasis (M1 PER).

2.4. Small Intestine

Summary Small Intestine

T1	Lamina propria, submucosa
T2	Muscularis propria
T3	Subserosa, nonperitonealized perimuscular tissues (mesentery, retroperitoneum) ≤2 cm
T4	Visceral peritoneum, other organs/structures (including mesentery, retroperitoneum >2 cm)

The very uncommon carcinoma in a Meckel diverticulum may be classified according to the classification for small intestine carcinoma, although supporting data are not available.

Intramural extension of an ileal carcinoma directly into the caecum (not by way of the serosa) does not affect the T classification, in particular does not qualify for T4.

2.5. Colon and Rectum

2.5.1. Anatomical Sites and Subsites

A tumour located at the border between two subsites is registered as a tumour of the subsite that is more involved.

Example. Carcinoma with a longitudinal diameter of 6 cm, 2 cm in the caecum, 4 cm in the ascending colon, is classified as a carcinoma of the ascending colon (C18.2).

If two subsites are involved to the same extent, the lesion is classified as an overlapping lesion.

Example. If the carcinoma involves 2 cm of the caecum and 2 cm of the ascending colon, the code C18.8 (overlapping lesion of the colon) is used.

The rectum is defined as the distal large intestine commencing opposite the sacral promontory and ending at the upper border of the anal canal. When measured from below with a rigid sigmoidoscope, it extends 16 cm from the anal verge. A tumour is classified as rectal if its lower margin lies 16 cm or less from the anal verge [6, 29]. A tumour is considered rectal if any part is located at least partly within the supply of the superior rectal artery. Tumours are classified as rectosigmoid when differentiation between rectum and sigmoid according to the above rules is not possible.

2.5.2. Local Recurrence

A local recurrence after previous colon resection should be classified with the prefix "r" (for recurrence); the recurrent tumour is topographically assigned to the proximal segment of the anastomosis.

2.5.3. Regional Lymph Nodes

For each anatomical subsite the nodes along the following vessels (trunks and branches) are regional nodes:

Appendix	Ileocolic
Caecum	Ileocolic and right colic
Ascending colon	Ileocolic, right colic and middle colic
Hepatic flexure	Middle colic and right colic
Transverse colon	Right colic, middle colic, left colic and inferior mesenteric
Splenic flexure	Middle colic, left colic and inferior mesenteric
Descending colon	Left colic and inferior mesenteric
Sigmoid colon and rectosigmoid	Sigmoid, left colic, superior rectal (haemorrhoidal) and inferior mesenteric
Rectum	Superior rectal (haemorrhoidal), inferior mesenteric and internal iliac

Metastasis in nodes other than those listed above is classified as distant metastasis, e.g., metastasis in a node along the trunk of the middle colic artery and/or its ramification in a case of rectal carcinoma is M1. However, in case of direct (intramural) extension of the primary tumour to an adjacent subsite, the lymph nodes of the latter subsite are also considered regional lymph nodes.

Perirectal nodes include the mesorectal (paraproctal), lateral sacral, presacral, sacral promotory (Gerota), middle rectal (haemorrhoidal) and inferior rectal (haemorrhoidal) nodes. Metastasis in the external iliac or common iliac nodes is classified as distant metastasis (M1).

The pericolic nodes correspond to "epicolic," "paracolic" and "intermediate" nodes according to the division of Jamieson and Dobson [16] ("epicolic," and the colon itself; "paracolic" along the marginal artery and between it and the colon; "intermediate" nodes on the branches of the major colic vessels as well as nodes along the trunks of these vessels). The "principal glands" of Jamieson and Dobson include the nodes on the inferior mesenteric artery and on the superior mesenteric artery, the latter to be classified as nonregional.

In case of direct invasion of the small intestine, lymph nodes in the mesentery of the invaded intestinal loop are classified as regional lymph nodes.

2.5.4. T/pT Classification

Summary Colon and Rectum

T1	Submucosa
T2	Muscularis propria
T3	Subserosa, nonperitonealized pericolic/perirectal tissues
T4	Other organs or structures/visceral peritoneum

Tumours of the appendix are classified using the TNM scheme for colon and rectum, but are analyzed separately.

According to a proposal of the AJCC (Yarbro et al., AJCC on Cancer Prognostic Factors Consensus Conference. Cancer 1999; 86: 2436-2446) the classification should not be applied to tumours of the appendix.

1.	For colon and rectum only, Tis/pTis (carcinoma in situ) includes cases with invasion of the lamina propria (including the muscularis mucosae but not of the submucosa), i.e., intramucosal, as well as intraepithelial carcinoma.
2.	T3/pT3: The perirectal tissue includes the mesorectum (paraproctium).
3.	Tumour extension into the peritoneal cavity is classified as T4. Perforation of the visceral peritoneum at the microscopic level requires identification of tumour directly extending to and growing on the peritoneal surface and/or positive cytology on specimens obtained by scraping the serosa overlying the primary tumour [32].
4.	Intramural direct extension from one subsite (segment) of the colon to an adjacent one is not considered in the T classification. The same applies to intramural direct extension from the rectum to the sigmoid colon and vice versa and from the rectum to the anal canal.
5.	Intramural extension of a caecal carcinoma directly into the ileum (not by way of serosa) does not affect the T classification, in particular does not qualify for T4. In contrast, direct extension via serosa or via mesocolon is classified T4, e.g., extension of a sigmoid colon carcinoma to caecum.
6.	Tumour cells in veins or lymphatics do not affect the pT classification. The L and V classifications can be used to record such spread (see also N/pN classification). Example. Carcinoma with continuous local spread into the submucosa, tumour cells in a small vein within the muscularis propria - pT1, V1 (muscularis propria).
7.	Invasion of the external sphincter should be classified as pT3.
8.	Invasion of levator muscle(s) is classified as T4.
9.	A tumour nodule in the soft tissues beneath a perineal operation skin scar after abdominoperineal resection for rectal carcinoma after a disease-free interval is classified as rT(+) not M1.

2.5.5. N/pN Classification

A tumour nodule greater than 3 mm in the perirectal or pericolic adipose tissue of a primary carcinoma without histological evidence of residual lymph node in the nodule is classified in the pN category as a regional lymph node metastasis if the nodule has the form and smooth contour of a lymph node. If the nodule has an irregular contour, it should be classified in the T or pT category and also coded as V1 (microscopic venous invasion) or V2, if it was grossly evident, because there is a strong likelihood that it arises from venous invasion. [12-14].

Involvement of the apical node(s) does not influence the N/pN classification.

2.5.6. M Classification

Tumour nodule(s) in an abdominal scar after removal of an intraabdominal tumour (with a disease-free interval) should be classified as M1, e.g., rT0 N0 M1 SKI.

2.6. Anal Canal

2.6.1. Rules for Classification

The classification applies to all types of carcinoma including those arising within an anorectal fistula as well as squamous cell (cloacogenic) carcinoma.

2.6.2. T Classification

Summary Anal Canal

T1	≤2 cm
T2	>2 to 5 cm
T3	>5 cm
T4	Adjacent organs

Involvement of the sphincter muscle(s) alone is not classified as T4.

Direct invasion of rectal wall or perirectal skin or subcutaneous perianal tissue is not considered T4. The tumour is classified by size.

2.7. Liver

2.7.1. Rules for Classification

The classification applies to intrahepatic cholangiocarcinoma (peripheral bile duct carcinoma) as well as hepatocellular carcinoma and combined hepatocellular and cholangiocarcinoma.

2.7.2. Regional Lymph Nodes

The regional lymph nodes are the hilar, hepatic (along the proper hepatic artery) and periportal (along the portal vein) nodes. In addition, the nodes along the abdominal inferior vena cava above the renal veins, except the inferior phrenic nodes are considered regional. Involvement of the inferior phrenic nodes (lymph nodes in the oesophageal hiatus of the diaphragm) should be considered M1. This expands the definition of regional nodes described in the original printing of the 5^th edition of TNM and corresponds to the definition in the AJCC Cancer Staging Manual. It is supported by a study of Nozaki et al. [22].

2.7.3. T/pT Classification

Summary Liver

T1	Solitary, ≤2 cm, without vascular invasion
T2	Solitary, ≤2 cm, with vascular invasion
	Multiple, one lobe, ≤2 cm, without vascular invasion
	Solitary, >2 cm, without vascular invasion
T3	Solitary, >2 cm, with vascular invasion
	Multiple, one lobe, ≤2 cm, with vascular invasion
	Multiple, one lobe, >2 cm, with or without vascular invasion
T4	Multiple, more than one lobe
	Invasion of major branch of portal or hepatic veins
	Invasion of adjacent organs other than gallbladder
	Perforation of visceral peritoneum

1.	"Multiplicity" includes multiple nodules representing multiple, independent primary tumours and intrahepatic metastasis from a single primary hepatic carcinoma
2.	"Vascular invasion" is diagnosed clinically by imaging procedures. In the pathological assessment it includes gross and/or histological involvement of vessels including invasion of adventitia of major branches of vessels,
3.	T4: "major branches of the portal or hepatic veins" are the right and left branches of the portal vein and the corresponding hepatic veins (not segmental or subsegmental branches). Involvement of the right, left and (not always existent) intermediate branches of the hepatic artery is also classified T4.

2.8. Gallbladder

Summary Gallbladder

T1		Lamina propria and muscle
	T1a	Lamina propria
	T1b	Muscle
T2		Perimuscular connective tissue
T3		Serosa and/or one organ, liver ≤2 cm
T4		Two or more organs, liver >2 cm

Carcinoma of the cystic duct is classified as a tumour of the extrahepatic bile ducts.

2.9. Extrahepatic Bile Ducts

Summary Extrahepatic Bile Ducts

T1		Ductal wall
	T1a	Subepithelial connective tissue
	T1b	Fibromuscular layer
T2		Perifibromuscular connective tissue
T3		Adjacent structures

Carcinoma of the cystic duct and carcinoma in a choledochal cyst are classified as extrahepatic bile duct tumours.

This classification does not apply to carcinomas of the ampulla of Vater.

2.9.1. Anatomical Subsites

The extrahepatic bile ducts include:

·	Left and right hepatic ducts (tumours arising here are often referred to as hilar carcinomas of the liver, also named Klatskin tumours)
·	Common hepatic duct
·	Cystic duct
·	Common bile duct (choledochus)

Direct invasion of the portal vein or the hepatic artery is classified T3.

2.10. Ampulla of Vater

The ampulla opens into the duodenum through a small mucosal elevation, the duodenal papilla or papilla of Vater. Tumours of the ampulla of Vater include tumours arising in the ampulla, tumours arising on the papilla and tumours arising at the junction of the mucosa of the ampulla with that of the papilla.

2.11. Pancreas (Exocrine Tumours Only)

This classification is not applicable to tumours in aberrant pancreatic tissue.

Summary Pancreas

T1	Limited to the pancreas ≤2 cm
T2	Limited to the pancreas >2 cm
T3	Duodenum bile duct, peripancreatic tissues
T4	Stomach, spleen, colon, large vessels

2.11.1. T Classification

T3	Peripancreatic tissues include the surrounding retroperitoneal fat (retroperitoneal soft tissue or retroperitoneal space), including the mesentery (mesenteric fat), mesocolon, greater and lesser omentum and peritoneum.Direct invasion to bile ducts and duodenum includes involvement of the ampulla of Vater.
T4	Adjacent large vessels are the portal vein, the coeliac artery and the superior mesenteric and common hepatic arteries and veins.

2.11.2. Regional Lymph Nodes

There are some differences in the designation of regional lymph nodes between the UICC and AJCC classifications, see appendix.

3. Lung

3.1. Rules for Classification

The classification applies to all types of carcinoma including small cell carcinoma. It does not apply to carcinoids.

3.2. T Classification

Summary Lung

T1	≤3 cm
T2	>3 cm, main bronchus ≤2 cm from carina, invades visceral pleura, partial atelectasis
T3	Chest wall, diaphragm, pericardium, mediastinal pleura
T3	Main bronchus <2 cm from carina, total atelectasis
T4	Mediastinum, heart, great vessels, carina, trachea, oesophagus, vertebra; separate nodules in same lobe, malignant effusion

Tumour with local invasion of another lobe without tumour on the pleural surface should be classified as T2.

Invasion of phrenic nerve is classified as T3.

Vocal cord paralysis (resulting from invasion of the recurrent branch of the vagus nerve), superior vena caval obstruction or compression of the trachea or oesophagus is classified as T4.

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 classification as T4.

Direct extension to parietal pericardium is classified T3 and to visceral pericardium, T4.

Pleural effusion is classified as T4, unless there are multiple negative cytological examinations.

Tumour foci in the ipsilateral parietal and visceral pleura that are discontinuous from direct pleural invasion by the primary tumour are classified T4.

Invasion of visceral pleura (T2) includes not only perforation of the mesothelium but also invasion of the lamina propria serosae.

Tumour extending to rib is classified as T3.

10.

Pericardial effusion is classified the same as pleural effusion.

11.

Multiple tumours of the same histological type in the same lobe is T4, but in different lobes is M1.

12.

Multiple tumours of different histologic type in the same lobe or in different lobes should be classified as T1-4(m).

3.3. M Classification

Discontinuous tumours outside the parietal pleura in the chest wall or in the diaphragm are classified M1.

3.4. Small Cell Carcinoma

The TNM classification and stage grouping should be applied to small cell carcinoma. TNM is of significance for prognosis of small cell carcinoma [21], and has the advantage of providing a uniform detailed classification of tumour spread. The former categories "limited" and "extensive" for small cell carcinoma have been inconsistently defined and used.

The category "limited disease"" as used in the Veterans Administration Lung Cancer Study Group system for classification of small cell carcinoma [15] corresponds to stages I to III A and "extensive disease" to stages III B ("extensive disease I") and IV ("extensive disease II").

4. Tumours of the Bone and Soft Tissue

4.1. Bone Tumours

Summary Bone

T1	Within cortex
T2	Beyond cortex

"Skip" metastasis in the same bone as the primary is not considered in the TNM classification. Metastasis in another bone is classified as distant metastasis.

4.2. Soft Tissue Tumours

Summary Soft Tissue Sarcoma

T1	≤5 cm
	T1a	Superficial
	T1b	Deep
T2	>5 cm
	T2a	Superficial
	T2b	Deep

A TNM classification and stage grouping of Kaposi sarcoma are not provided. The prognosis of Kaposi sarcoma associated with AIDS is determined by AIDS.

5. Skin Tumours

5.1. Carcinoma of Skin

Summary Skin Carcinoma

T1	≤2 cm
T2	>2 to 5 cm
T3	>5 cm
T4	Deep extradermal structures (cartilage, skeletal muscle, bone)

1.	The classification applies to any type of skin carcinoma including squamous cell, basal cell, skin appendages (e.g. sweat glands), Merkel cell.
2.	The classification does not apply to carcinomas of the eyelid, vulva and penis, which have separate classifications.
3.	In carcinoma of the perianal skin (anal margin), direct invasion of the mucosa or submucosa of the anal canal does not affect the T/pT classification. The tumour is classified by size.
4.	Invasion of the galea aponeurotica (aponeurosis epicranialis) is classified as T4.
5.	Metastastic involvement of iliac and other pelvic, abdominal or intrathoracic lymph nodes is classified as Ml.

5.2. Malignant Melanoma of Skin

Summary Malignant Melanoma

T1	≤0.75 mm	Level II
T2	>0.75 to 1.5 mm	Level III
T3	>1.5 to 4.0 mm	Level IV
T4	>4.0 mm/satellites	Level V

5.2.1. Rules for Classification

The classification applies to malignant melanoma of skin of all sites, including eyelid, vulva, penis and scrotum. It does not apply to melanomas arising in mucous membranes (oral cavity, nasopharynx, vagina, urethra, anal canal) or to melanomas of the conjunctiva and uvea. The last two sites have separate classifications. There is no classification for melanoma of the oral cavity, nasopharynx or other visceral sites.

5.2.2. pT Classification of Malignant Melanoma

Three histological criteria are considered:

·	Maximum tumour thickness (Breslow) according to the largest vertical dimension of the tumour in millimetres. Maximum thickness of the tumour is measured with an ocular micrometer after embedding in paraffin at right angles to the adjacent normal skin. The upper reference point is the top of the granular cell layer of the epidermis of the overlying skin or the base of the ulcer if the tumour is ulcerated. The lower reference point is usually the deepest point of invasion. It may be the invading edge of a single tumour mass or an isolated cell or group of cells deep to the main mass. Melanoma cells within the epithelium of structures such as hair follicles and sebaceous glands of the skin are not taken into consideration.
·	Clark levels.
·	Absence or presence of satellites within 2 cm of the primary tumour. "Satellites" include tumour nests and nodules not only in the dermis but also in the subcutaneous tissue.

The definitive pT category is based on these three criteria.

In case of discrepancy between tumour thickness and level, the pT category is based on the less favourable finding.

5.2.3. N Classification

In-transit metastases with regional lymph node metastasis 3 cm or less in greatest dimension are classified N2b.

A completely different TNM classification and stage grouping have been proposed by the AJCC. It cannot be directly compared with the present classification because different criteria for T, N, and M are used. Comparative testing is recommended.

6. Breast Tumours

6.1. Rules for Classification

1.	The classification applies to carcinomas of the male as well as of the female breast.
2.	The rules for multiple simultaneous primary cancers in one breast (general rule No. 5, p. 3) do not apply to a single grossly detected tumour associated with multiple separate microscopic foci (satellites).
3.	According to the proposals of the AJCC (Yarbro et al., see p. 38) LCIS should be dropped from Tis.

6.2. Regional Lymph Nodes

Intramammary lymph nodes are coded as axillary lymph nodes level I.

6.3. T Classification

Summary Breast

Tis		In situ
T1		≤2 cm
	T1mic	≤0.1 cm
	T1a	>0.1 to 0.5 cm
	T1b	>0.5 to 1 cm
	T1c	>1 to 2 cm
T2		>2 to 5 cm
T3		>5 cm
T4		Chest wall/skin
	T4a	Chest wall
	T4b	Skin oedema/ulceration, satellite skin nodules
	T4c	Both 4a and 4b
	T4d	Inflammatory carcinoma

The clinical estimation of tumour size by physical examination and mammography frequently give different results [4, 8, 23].

Accuracy can be improved by using the following formula:

Only clinically/grossly detected satellite skin nodules are classified T4b (histologically detected foci are not considered).

Dimpling of the skin, nipple retraction, nipple involvement or other skin changes, except those in T4b and T4d, may occur in Tl, T2 or T3 without affecting the classification. This also applies to microscopic invasion of the skin (dermis) without changes of T4b or T4d.

On mastectomy specimens oedema of the skin (T4b) may be inapparent at the time of pathological examination. Therefore, the surgeon should inform the pathologist of such a clinical finding to guarantee its consideration and to prevent pathological understaging.

Invasion of lymphatic vessels is not considered in the T category.

If there is a clinical picture of inflammatory carcinoma (cT4d), but a biopsy of the skin is negative for tumour and a measurable breast cancer is present, the pT category is based on the size of the tumour (pT1, 2, or 3).

Microscopic involvement of dermal lymphatic vessels by tumour without the clinical picture of inflammatory carcinoma is classified by the size of the tumour.

For T classification the size of a tumour in a biopsy should be added to the size of the tumour in the definitive resection specimen, if the biopsy specimen has a positive margin.

6.4. N/pN Classification

The N classification is done by the clinical and imaging methods usually applied for examination of the axilla. At the present time, special efforts are not required for evaluation of internal mammary lymph nodes (N3).

pN1 (movable nodes) and pN2 (nodes that are fixed to one another or to other structures) are differentiated by macroscopic findings of the pathologist during dissection of the axillary specimen.

Multiple micrometastasis in one axillary lymph node, e.g., 0.09 cm + 0.07 cm + 0.06 cm, should be added up (0.22 cm) and not be considered micrometastasis if larger than 0.2 cm.

Invasion of lymph vessels in the axillary fatty tissue is not considered in the N classification. It can be classified in the L- Lymphatic invasion classification (p. 12, TNM 5th edition).

For axillary nodal metastasis, the size of the metastasis, not the size of the lymph node, determines pN. If the size of the metastasis is unknown or not reported, then the pN subclassification should not be used.

7. Gynaecological Tumours

7.1. Vulva

Summary Vulva

T1		Confined to vulva/perineum,≤2 cm
	T1a	Stromal invasion ≤1.0 mm
	T1b	Stromal invasion >1.0 mm
T2		Confined to vulva/perineum, >2 cm
T3		Lower urethra/vagina/anus
T4		Bladder mucosa/rectal mucosa/upper urethral mucosa/bone

Invasion of the rectal wall or bladder wall (not mucosa) is classified as T3. Mucosal involvement is T4.

Invasion of the wall (not mucosa) of the upper and lower urethra is classified as T3.

Invasion of the mucosa: Lower urethra	T3
Invasion of the mucosa: Upper urethra	T4

Upper urethra corresponds to the proximal half, lower urethra to the distal half.

7.2. Vagina

Summary Vagina

T1	Vaginal wall
T2	Paravaginal tissue
T3	Extends to pelvic wall
T4	Mucosa of bladder/rectum, beyond pelvis
N1	Upper two thirds of vagina: pelvic lymph nodes
N1	Lower third of vagina: inguinal lymph nodes

"Frozen pelvis" is a clinical term which means that tumour extends to the pelvic wall(s). It is classified as T3.

Invasion of the rectal wall or bladder wall (not mucosa) is classified as T2. Mucosal involvement is T4.

A tumour of the upper two thirds of the vagina with inguinal lymph node metastases, is classified as M1 (Stage IV).

A tumour of the lower third of the vagina with pelvic lymph node metastasis is classified M1 (Stage IV).

7.3. Cervix Uteri

Summary Cervix Uteri

TNM		FIGO
Tis	In situ	0
T1	Confined to uterus	I
T1a	Diagnosed only by microscopy	IA
T1a1	Depth ≤3 mm, horizontal spread ≤7 mm	IA1
T1a2	Depth 3-5 mm, horizontal spread ≤7 mm	IA2
T1b	Clinically visible, greater than T1a2	IB
T1b1	≤4 cm	IB1
T1b2	>4 cm	IB2
T2	Beyond uterus but not pelvic wall or lower third vagina	II
T2a	No parametrium	IIA
T2b	Parametrium	IIB
T3	Lower third vagina/pelvic wall/ hydronephrosis	III
T3a	Lower third vagina	IIIA
T3b	Pelvic wall/hydronephrosis	IIIB
T4	Mucosa of bladder/rectum/beyond true pelvis	IVA
M1	Distant metastasis	IVB

The FIGO stages are based on clinical staging. TNM categories are based on clinical and/or pathological classification.

In the rare multifocal T1a tumours for the horizontal spread FIGO classifies by the largest focus. This is in accordance with TNM rule No. 5.

The presence of tumour cells in lymphatics (lymph vessels) or veins of the parametrium does not qualify for T2b. T2b is used only for grossly or histologically evident continuous invasion beyond the myometrium.

"Frozen pelvis" is a clinical term which means that tumour extends to the pelvic wall(s), i.e., T3b.

Invasion of the rectal wall or bladder wall (not mucosa) is classified as T3a. Mucosal involvement is T4.

Microscopic lesion greater than T1a2 (FIGO IA2) is classified as T1b1 (FIGO IB1).

Tumour-positive peritoneal fluid, e.g., in the pouch of Douglas, is not considered in the TNM or FIGO classification but should be documented.

7.4. Corpus Uteri

Summary Corpus Uteri

TNM			FIGO
Tis		In situ	0
T1		Confined to corpus	I
	T1a	Tumour limited to the endometrium	IA
	T1b	≤ 1/2 myometrium	IB
	T1c	>1/2 myometrium	IC
T2		Extension to cervix	II
	T2a	Endocervical glandular only	IIA
	T2b	Cervical stroma	IIB
T3 and/or N1		Local and/or regional as specified below	III
	T3a	Serosa/adnexa/positive peritoneal cytology	IIIA
	T3b	Vaginal involvement	IIIB
	N1	Regional lymph node metastasis	IIIC
T4		Mucosa of bladder/bowel	IVA
M1		Distant metastasis	IVB

T1b is "invades up to or less than one half of myometrium" (FIGO IB "invasion less than half of the myometrium").

T3a or FIGO IIIA includes discontinuous involvement of adnexae or serosa within the pelvis. Invasion of parametria is classified as T3a (FIGO IIIA).

Invasion of the rectal wall or bladder wall (not mucosa) is classified as T3b. Mucosal involvement is T4.

"Frozen pelvis" is a clinical term which means that tumour extends to the pelvic wall(s), i.e., T3b.

There may be a small number of patients with T1 corpus carcinoma who will be treated primarily with radiation therapy. For these cases FIGO recommends clinical classification according to the former FIGO schedule (IA, uterine cavity ≤8 cm in length; IB, uterine cavity >8 cm in length); the use of this staging system must be stated.

7.4.1. Grading

Further notes about grading appeared in the 23rd Annual Report of the FIGO [7].

7.5. Ovary

The classification applies to malignant surface epithelial-stromal tumours including those of borderline malignancy or of low malignant potential (WHO Classification, 2nd edition, Scully 1999 [26]) (corresponding to "common epithelial tumours" according to the terminology of the first edition of the WHO classification [7,25]).

Cases should be separated by histologic type and borderline or invasive nature.

The FIGO stages are based on surgical staging. TNM stages are based on clinical and/or pathological classification.

7.5.1. T Classification

Summary Ovary

TNM			FIGO
T1		Limited to the ovaries	I
	T1a	One ovary, capsule intact	IA
	T1b	Both ovaries, capsule intact	IB
	T1c	Capsule ruptured, tumour on surface, malignant cells in ascites or peritoneal washing	IC
T2		Pelvic extension	II
	T2a	Uterus, tube(s)	IIA
	T2b	Other pelvic tissues	IIB
	T2c	Malignant cells in ascites or peritoneal washings	IIC
T3 and/or N1		Peritoneal metastasis beyond pelvis and/or regional lymph node metastasis	III
	T3a	Microscopic peritoneal metastasis	IIIA
	T3b	Macroscopic peritoneal metastasis ≤2 cm	IIIB
	T3c and/or N1	Peritoneal metastasis >2 cm and/ or regional lymph node metastasis	IIIC
M1		Distant metastasis (excludes peritoneal metastasis)	IV

Tlc	Rupture of the capsule includes spontaneous rupture as well as rupture caused by the surgeon.
T2,3	The "pelvis" includes the true or minor or small as well as the false major or large or false pelvis.
T3	Peritoneal metastasis outside the pelvis includes involvement of the omentum. T3 includes multifocal involvement of the peritoneum in borderline tumours.

In case of peritoneal metastasis the greatest horizontal diameter is considered in classification, not the thickness of metastasis.

Microscopic confirmation of a single peritoneal metastasis outside the pelvis, irrespective of the size of the metastasis, is required for T3. For the subdivision, size alone is relevant. Therefore, T3c is appropriate based on the macroscopic assessment by the surgeon even if microscopic confirmation was of a smaller metastasis only.

Primary extraovarian peritoneal carcinoma with or without ovarian involvement is not classified by TNM.

7.5.2. N Classification

Involvement of lymph nodes draining a peritoneal metastasis (T3) (e.g., mesocolic) can be considered regional lymph node metastasis (N1) rather than distant metastasis (M1).

7.5.3. M Classification

In ovary, peritoneal metastasis is not considered distant metastasis, it is classified as T3.

7.6. Fallopian Tube

Rules for ovary apply to fallopian tube.

7.7. Gestational Trophoblastic Tumours

Histopathological grading is not applicable.

Risk Factors Affecting Staging Include the Following
1.	Urinary hCG > 100,000 mIU/ml or serum -hCG > 40,000 mIU/ml)
2.	Detection of disease >6 months from termination of antecedent pregnancy

Serum hCG could be used as well as urinary hCG.

The following factors should be considered and noted in reporting:

1.	Prior chemotherapy for known gestational trophoblastic disease
2.	Placental site tumours should be reported separately
3.	Histological verification of the disease is not required, if the hCG is abnormally elevated

8. Urological Tumours

8.1. Penis

Erythroplasia of Queyrat is classified as carcinoma in situ (Tis).

8.2. Prostate

8.2.1. T Classification

Summary Prostate

T1		Not palpable or visible
	T1a	≤5%
	T1b	>5%
	T1c	Needle biopsy
T2		Confined within prostate
	T2a	One lobe (Unilateral)^*
	T2b	Both lobes (Bilateral)^*
T3		Through prostatic capsule
	T3a	Extracapsular
	T3b	Seminal vesicle(s)
T4		Fixed or invades adjacent structures: bladder neck, external sphincter, rectum, levator muscles, pelvic wall

^*Note. The prostate includes a right lobe, a left lobe, and a middle lobe according to the anatomic nomenclature. Therefore "unilateral" and "bilateral" are equivalent to "one lobe" and "both lobes". Involvement of the lateral lobe and the middle lobe can be considered T2a (according to TNM rule No. 4).

The prostate capsule is a network of smooth muscle and collagen-rich soft tissue around the prostate. There is no clear fascia.

There is no pT1 category because there is insufficient tissue to assess the highest pT category.

The presence of fatty or skeletal muscle tissue in a needle biopsy is not in itself evidence of invasion through the capsule into adjacent fatty tissue and thus may not be classified as T3.

Prostate carcinoma with invasion of M. sphincter urethrae internus is classified as T4.

According to newer anatomical results there are two sphincters:

	M.sphincter urethrae externus = M. sphincter urethrae (diaphragmaticae)
	M.sphincter urethrae internus = M. sphincter vesicae

The invasion of the M.sphincter urethrae as well as the invasion of the M.sphincter vesicae would be equivalent to an invasion of the bladder neck and should be classified as T4.

When a tumour is an incidental finding in transurethral resection (TUR) and after the first TUR a repeated TUR (re-TUR) is performed within 2 months as part of the definitive primary treatment (without following radical prostatectomy), the subdivision into Tla and Tlb should be based on the findings of both TURS.

Examples

1.	First TUR: <5% of tissue resected involved by carcinoma. re-TUR with the same amount of tissue: 10% of tissue involved. Classify Tlb.
2.	First TUR: 10% of tissue resected involved by carcinoma. re-TUR including a threefold amount of tissue: no further tumour found. Classify Tla.

Transitional cell carcinoma of the prostate (prostatic urethra) is classified under urethra, see p. 192 of TNM 5th edition [30].

If a prostate resection specimen is limited to the prostate and does not include the capsule or parts of the capsule (in the apex region), the pT classification cannot be used unless the tumour is clearly surrounded by nontumourous prostate tissue.

Involvement of the prostatic urethra is not considered in the T classification.

"Frozen pelvis" is a clinical term which means that tumour extends to the pelvic wall(s) and is fixed. It is classified as T4.

8.2.2. Histopathological Grading

The Gleason score and Gleason pattern [9] correspond to the grading recommended here as follows:

Gleason score	Gleason pattern	TNM histopathological grade

2-4	1,2	1
5-7	3	2
8-10	4,5	3-4

8.3. Testis

8.3.1. pT Classification

Summary Testis

pTis	Intratubular
pT1	Testis and epididymis, no vascular/lymphatic invasion
pT2	Testis and epididymis with vascular/lymphatic invasion
	or tunica vaginalis
pT3	Spermatic cord
pT4	Scrotum

In case of mixed germ cell tumours, the pT classification is determined by the total tumour. The different components should not be classified separately.

Synchronous bilateral tumours should be staged separately as independent primary tumours.

pT2: Invasion beyond the tunica albuginea includes invasion of any of the following-cremaster muscle, cremaster fascia, testicular portion of the internal or external spermatic fascia, i.e., invasion of the scrotum without the skin. Invasion beyond these structures into the subcutis or cutis of the scrotum is classified as pT4.

pT3: Invasion of the spermatic cord refers to direct extension.

Invasion of lymph vessels or blood vessels means unequivocal vessels lined by an endothelium.

The plexus pampiniformis belongs to the spermatic cord, so invasion should be classified as pT3.

Invasion of spermatic cord can be diagnosed, if tumour is found beyond rete testis and/or epididymis on horizontal cross sections.

8.4. Kidney

8.4.1. T Classification

Summary Kidney

T1	≤7.0 cm; limited to kidney
T2	>7.0 cm; limited to kidney
T3	Into major veins; adrenal or perinephric invasion
T4	Invades beyond Gerota fascia

Invasion of ipsilateral adrenal gland (T3a) refers to direct invasion.

Invasion of "perinephric tissues" (T3a) includes perirenal fat and/or renal sinus (peripelvic) fat [11].

Involvement of the renal vein (T3b) entails tumour grossly extending into the renal vein or its segmental (muscle-containing) branches, or vena cava below diaphragm [11].

Gross invasion of the wall of the vena cava above diaphragm is T3c [11].

Gerota fascia (renal fascia) includes the pre- and retrorenal fascia. Invasion of the peritoneum is invasion beyond the Gerota fascia (prerenal fascia) and is classified as T4.

Bulging of a tumour in the sense of changing the contour of the kidney is not sufficient to be classified as T3 or pT3. Penetration of the kidney capsule is needed to classify as T3 or pT3, which should be particularly searched for in the peripelvic fatty tissue.

Invasion (direct spread) of the contralateral adrenal gland is extremely rare and should be classified as M1.

8.5. Renal Pelvis and Ureter

Summary Renal Pelvis, Ureter

Ta	Noninvasive papillary
Tis	In situ
T1	Subepithelial connective tissue
T2	Muscularis
T3	Beyond muscularis
T4	Adjacent organs, perinephric fat

1.	Direct extension into the urinary bladder in the region of the ostium is classified by the depth of greatest invasion in any of the involved organs.
2.	In tumours of the ureter, adjacent organs include parietal peritoneum.
3.	The prognosis of T3 in ureter is worse than in renal pelvis and corresponds approximately to T4 renal pelvis tumours. Therefore, separate analysis of ureter and renal pelvis carcinoma is recommended [10].
4.	For classification of multiple synchronous primary tumours renal pelvis and ureter are considered a single organ. Therefore, in cases of synchronous tumours in the renal pelvis and the ureter, 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 T3(2). In case of multifocal tumours of renal pelvis and ureter with Ta and Tis tumours, Tis(m) should be classified. In contrast, in case of synchronous tumours in the renal pelvis and the urinary bladder both tumours should be classified independently.

8.6. Urinary Bladder

The classification applies not only to carcinomas (noninvasive or invasive) but also to the newly introduced "Papillary urothelial (transitional cell) neoplasm of low malignant potential." (see: Mostofi FK, Davis CJ, Sesterhenn IA (eds) Histological Typing of Bladder Tumours. 2nd ed. (World Health Organization [WHO] International Histological Classification of Tumours). Springer: Berlin Heidelberg New York, 1999)

Summary Urinary Bladder

Ta		Noninvasive papillary
Tis		In situ: flat tumour
T1		Subepithelial connective tissue
T2		Muscularis
	T2a	Inner half
	T2b	Outer half
T3		Beyond muscularis
	T3a	Microscopically
	T3b	Extravesical mass
T4		Prostate, uterus, vagina, pelvic wall, abdominal wall
	T4a	Prostate, uterus, vagina
	T4b	Pelvic wall, abdominal wall

1.	In case of multifocal tumours of urinary bladder with Ta and Tis tumours, Tis(m) should be classified.
2.	If the pathology specimen does not contain muscle, the category T1 is applicable (see TNM Classification 1997 [30], General rule No. 4). However, the pathology report should state the absence of muscle to allow the clinician to consider repeating the biopsy.
3.	In case of transurethral resection, differentiation between T2a and T2b is possible only if the surgeon submits the material as superficial (inner) and deep (outer) portions and histological examination is performed separately. Otherwise, the case is classified as T2.
4.	In some cases (up to 50%) a lamina muscularis mucosae has been described. Invasion of muscularis means lamina muscularis propria.
5.	Direct invasion of the distal ureter is classified by the depth of greatest invasion in any of the involved organs.
6.	Uncommonly, carcinomas of the bladder show an associated in situ component extending into the prostatic ducts and sometimes into the prostatic glands (or ureter) without any invasion in the prostate. Such cases are classified according to the depth of bladder wall invasion. The extension of the associated in situ component into the prostate does not qualify for classification as T4. It may be indicated by the suffix "(is)", e. g., T2(is). It may be further indicated by the suffix "(is pu)" (extension into the prostatic urethra) or "(is pd)" (extension into the prostatic ducts), e. g., T2(is pu) or T2 (is pd).
7.	Invasion of prostatic urethra (extension of invasive urinary bladder carcinoma into the prostatic urethra with invasion of the latter) is included in prostatic invasion and therefore classified as T4a.
8.	Direct invasion of the large or small intestine should be classified as T4a. The same applies to invasion through the peritoneum covering the bladder.
9.	Invasion of seminal vesicles by bladder tumours should be classified as T4a.

8.6.1. Recurrent Carcinoma After Cystectomy and Ureterosigmoidostomy

A recurrent transitional carcinoma in the region of a ureterosigmoidostomy may invade only the subepithelial connective tissue of the ureter and the adjacent mucosa and submucosa of the sigmoid colon. In this case, the invasion of the colon should not be considered as invasion of an adjacent organ. For the T classification the rules for ureter and colon should be applied, i.e., rT1 is the correct classification.

8.7. Urethra

8.7.1. T Classification

Summary Urethra

Ta	Noninvasive papillary, polypoid, or verrucous
Tis	In situ
T1	Subepithelial connective Tissue
T2	Corpus spongiosum, prostate, periurethral muscle
T3	Corpus cavernosum, beyond prostatic capsule anterior vagina, bladder neck
T4	Other adjacent organs

In urethral diverticular carcinoma, a differentiation between T2 and T3 is not possible [3]. In this case T2 is used (according to TNM rule No. 4).

9. Ophthalmic Tumours

9.1. Carcinoma of Eyelid

The eyelids are covered externally by epidermis (anterior surface of the eyelid) and internally by conjunctiva (posterior surface). This classification applies only to the carcinomas of the anterior surface of the eyelid and the eyelid margin. Carcinomas of the posterior surface of the eyelid are considered under tumours of the conjunctiva.

9.2. Carcinoma of Conjunctiva

This classification applies to carcinoma of the palpebral and bulbar conjunctiva and the conjunctival fornix.

9.3. Malignant Melanoma of Conjunctiva

This classification applies to malignant melanoma of the palpebral and bulbar conjunctiva and the conjunctival fornix.

Involvement of eyelid is defined as invasion beyond the tarsal plate into the anterior part of the eyelid.

9.4. Sarcoma of Orbit

In tumours of the orbital soft tissues T3 is used for those with diffuse invasion of the orbit and/or with invasion of the bony walls. In tumours of the orbital bones T3 is used for invasion of the orbital soft tissues.

10. Hodgkin and Non-Hodgkin Lymphomas

Right or left neck are separate lymph node regions.

Single lymph node regions are:

·	Lymph nodes of head, face and neck
·	Intrathoracic lymph nodes
·	Intra-abdominal lymph nodes
·	Lymph nodes of axilla or arm
·	Lymph nodes of inguinal region or leg
·	Pelvic lymph nodes

Bilateral involvement of axilla/arm lymph nodes is considered as involvement of two separate regions. The same applies to bilateral involvement of inguinal lymph nodes.

Examples

Involvement	Classification

Parotid and jugular	Single node region
Jugular and tracheal	Two regions, same side of diaphragm
Tracheal, hilar, para-aortic abdominal	Two regions, both sides of diaphragm
Axillary, bilateral	Two regions, same side of diaphragm
Inguinal bilateral	Two regions, same side of diaphragm

Direct spread of a lymphoma into adjacent tissues or organs does not influence classification.

Examples

·	Lymphoma of a cervical lymph node with pericapsular extension into adjacent muscle-stage I
·	Gastric lymphoma with direct spread to pancreas and involvement of perigastric lymph nodes-stage IIE
·	Lymphoma involving the ascending colon, caecum and ileocaecal valve with direct extension to the terminal ileum-stage IE

Involvement of two or more segments of the gastrointestinal tract, isolated and not in continuity, is classified as stage IV (disseminated involvement of one or more extralymphatic organs).

Example. Involvement of stomach and of ileum-stage IV.

For classification of extranodal lymphomas, involvement of both organs of a paired site is considered as involvement of a single organ.

Example. Extranodal lymphoma involving both lungs is classified stage IE.

Multifocal involvement of a single extralymphatic organ is classified stage IE and not stage IV.

Primary Extranodal Lymphomas, Stage IIE: The definitions of regional lymph nodes given for the individual tumour sites apply to extranodal lymphomas, too, e. g., for primary gastric lymphomas the regional lymph nodes are the perigastric nodes along the lesser and greater curvatures and the nodes located along the left gastric, common hepatic, splenic and coeliac arteries.

11. Appendix

Comparison of the regional lymph nodes listed in the UICC [30] and the AJCC TNM 5th editions [1]

SITE	UICC	AJCC
Lip and oral cavity	Cervical	Submental

		Submandibular

		Jugular, upper, mid, lower

		Posterior triangle (spinal accessory) upper, lower

		Prelaryngeal (Delphian)

		Pretracheal

		Paratracheal

		Upper mediastinal

		Buccinator (facial)

		Intraparotid

		Preauricular

		Postauricular

		Suboccipital
Pharynx	Cervical	Submental

		Submandibular

		Jugular, upper, mid, lower

		Posterior triangle (spinal accessory) upper, lower

		Prelaryngeal (Delphian)

		Pretracheal

		Paratracheal

		Upper mediastinal

		Buccinator (facial)

		Intraparotid

		Preauricular

		Postauricular
Larynx	Cervical	Submental

		Submandibular

		Jugular, upper, mid, lower

		Posterior triangle (spinal accessory) upper, lower

		Prelaryngeal (Delphian)

		Pretracheal

		Paratracheal

		Upper mediastinal

		Buccinator (facial)

		Intraparotid

		Preauricular

		Postauricular

		Suboccipital
Paranasal sinuses	Cervical	Submental

		Submandibular

		Jugular, upper, mid, lower

		Posterior triangle (spinal accessory) upper, lower

		Prelaryngeal (Delphian)

		Pretracheal

		Paratracheal

		Upper mediastinal

		Buccinator (facial)

		Intraparotid

		Preauricular

		Postauricular

		Suboccipital
Salivary glands	Cervical	Submental

		Submandibular

		Jugular, upper, mid, lower

		Posterior triangle (spinal accessory) upper, lower

		Prelaryngeal (Delphian)

		Pretracheal

		Paratracheal

		Upper mediastinal

		Buccinator (facial)

		Intraparotid

		Preauricular

		Postauricular

		Suboccipital
Thyroid	Cervical	Suboccipital

		Submandibular

		Jugular, upper, mid, lower

		Posterior triangle (spinal accessory) upper, lower

		Prelaryngeal (Delphian)

		Pretracheal

		Paratracheal

	Upper mediastinal	Upper mediastinal

		Buccinator (facial)

		Intraparotid

		Preauricular

		Postauricular

		Suboccipital
Cervical oesophagus	Cervical, including supraclavicular	Scalene

		Internal jugular

		Upper cervical

		Perioesophageal

		Supraclavicular

		Cervical, NOS
Intrathoracic oesophagus, upper, middle, lower	Mediastinal Perigastric (excluding celiac)	Tracheobronchial

		Superior mediastinal

		Peritracheal

		Carinal

		Hilar (pulmonary roots)

		Perioesophageal

		Perigastric

		Paracardial

		Mediastinal NOS
Stomach	Perigastric along lesser and greater curvatures	Perigastric along lesser and greater curvatures

	Nodes along left gastric, common hepatic, splenic, and celiac arteries	Nodes along left gastric, common hepatic, splenic, and celiac arteries

		Greater Curvature of Stomach:

		Greater curvature

		Greater omental

		Gastroduodenal

		Gastroepiploic, rights or NOS

		Gastroepiploic, left Pyloric, including subpyloric and infra pyloric

		Pancreaticoduodenal (anteriorly along first part of the duodenum)

		Pancreatic and splenic area:

		Pancreaticolienal

		Peripancreatic

		Splenic hilum

		Lesser curvature of Stomach:

		Lesser curvature

		Lesser omental

		Left gastric

		Paracardial; cardial

		Cardioesophageal

		Perigastic, NOS

		Common hepatic

		Celiac

		Hepatoduodenal

		All other lymph nodes are considered distant. They include: Retropancreatic Para-aortic Portal Retroperitoneal Mesenteric
Small intestine, duodenum	Pancreaticoduodenal	Duodenal

	Pyloric	Hepatic

	Hepatic (pericholedochal, cystic, hilar)	Pancreaticoduodenal

	Superior mesenteric	Infrapyloric

		Gastroduodenal

		Pyloric

		Superior mesenteric

		Pericholedochal

		Regional lymph nodes, NOS
Small intestine, ileum and jejunum	Mesenteric nodes, Superior mesenteric Ileocolic (terminal ileum only)	Posterior cecal (terminal ileum only)

	Mesenteric, NOS	Ileocolic (terminal ileum only)

		Superior mesenteric

		Mesenteric, NOS

		Regional lymph nodes, NOS
Cecum and appendix	Nodes along the ileocolic, and right colic arteries	Anterior cecal

		Posterior cecal

		Ileocolic

		Right colic
Ascending colon	Nodes along the ileocolic, right colic, and middle colic arteries	Ileocolic

		Right colic

		Middle colic
Colon Hepatic flexure	Nodes along the right colic, and middle colic arteries	Middle colic

		Right colic
Transverse colon	Nodes along the right colic, middle colic, and left colic arteries and inferior mesenteric	Middle colic
Colon Splenic flexure	Nodes along the middle colic, left colic, and inferior mesenteric arteries	Middle colic

		Left colic

		Inferior mesenteric
Descending colon	Nodes along the left colic, inferior mesenteric	Left colic

		Inferior mesenteric

		Superior rectal (hemorrhoidal)

		Sigmoidal

		Sigmoid mesenteric
Sigmoid colon	Sigmoid nodes, left colic	Inferior mesenteric

	Nodes along the inferior mesenteric, and superior rectal arteries	Superior rectal (hemorrhoidal)

		Sigmoidal

		Sigmoid mesenteric
Colon Rectosigmoid	Sigmoid nodes, left colic node	Perirectal

	Nodes along the left colic, inferior mesenteric, and superior rectal (hemorrhoidal) arteries Pericolic, Perirectal	Left colic

		Sigmoid mesenteric

		Sigmoidal

		Inferior mesenteric

		Superior rectal (hemorrhoidal)

		Middle rectal (hemorrhoidal)
Rectum	Nodes along the superior rectal (hemorrhoidal), inferior mesenteric, and internal iliac arteries	Perirectal

	Perirectal	Sigmoid mesenteric

		Inferior mesenteric

		Lateral, sacral, presacral

		Internal iliac

		Sacral promontory (Gerota')

		Superior rectal (hemorrhoidal)

		Middle rectal (hemorrhoidal)

		Inferior rectal (hemorrhoidal)
Anal canal	Perirectal	Perirectal (anorectal, perirectal, lateral sacral)

	Internal iliac	Internal iliac (hypogastric)

	Inguinal	Inguinal (superficial, deep femoral)
Liver	Hilar (those in the hepatoduodenal ligament)^*	Hilar nodes¹ (those in the hepatoduodenal ligament)

		Hepatic

		Periportal including those along the hepatic artery, portal vein, and inferior vena cava
Gallbladder	Superior mesenteric

	Peripancreatic (head only)

	Cystic duct node	Cystic duct

	Pericholedochal	Pericholedochal

	Hilar	Hilar

	Celiac	Celiac

	Periduodenal	Periduodenal

	Periportal	Periportal
Extrahepatic bile ducts	Celiac

	Cystic duct	Cystic

	Hilar	Hilar

	Superior mesenteric	Superior mesenteric

	Periduodenal	Periduodenal

		Posterior

		pancreaticoduodenal

	Peripancreatic (head only)	Peripancreatic

	Periportal	Periportal

	Pericholedochal	Pericholedochal

		Celiac
Ampulla of Vater	Superior: Lymph nodes superior to the head and body of the pancreas.	Superior: Lymph nodes superior to the head and body of the pancreas

	Inferior: Lymph nodes inferior to the head and body of the pancreas	Inferior: Lymph nodes inferior to the head and body of the pancreas

	Anterior: Anterior pancreaticoduodenal, pyloric and proximal mesenteric	Anterior: Anterior pancreaticoduodenal, pytonic proximal mesenteric

	Posterior: Posterior pancreaticoduodenal, common bile duct, and proximal mesenteric	Posterior: Posterior pancreatoduodenal common bite duct mesenteric lymph

		Others:

		Pancreaticoduodenal, NOS

		Peripancreatic

		Infrapyloric

		Hepatic

		Subpyloric

		Celiac

		Superior mesenteric

		Retroperitoneal

		Lateral aortic
Exocrine pancreas	Celiac (for tumours of head only)

	Superior: Lymph nodes superior to the head and body of the pancreas	Superior: Lymph nodes superior to the head and body of the pancreas

	Inferior: Lymph nodes inferior to the head and body of the pancreas	Inferior: Lymph nodes inferior to the head and body of the pancreas

	Anterior: Anterior pancreaticoduodenal, pyloric (for the tumours of head only) and proximal mesenteric lymph nodes	Anterior: Anterior pancreaticoduodenal, proximal mesenteric lymph nodes

	Posterior: Posterior pancreaticoduodenal, common bile duct or pericholedochal and proximal mesenteric lymph nodes	Posterior: Posterior pancreaticoduodenal, bile duct or pericholedochal and proximal mesenteric lymph nodes

	Splenic: hilum of spleen and tail of pancreas (for tumours in the body and tail only)	Splenic: (for tumours in the body and tail only)

		Retroperitoneal
Vagina	Pelvic nodes (upper 2/3 of vagina)	Pelvic, NOS (upper 2/3 only)

	Inguinal nodes (lower 1/3 of vagina)	Inguinal nodes (lower 1/3 of vagina)

		Iliac, common, internal, external

		Hypogastric (obturator)

		Pelvic, NOS (upper 2/3 only)
Cervix uteri	Paracervical	Paracervical

	Parametrial	Parametrial

	Hypogastric (internal iliac obturator)	Hypogastric (obturator)

	Iliac, common and external	Common iliac

	Iliac, common and external	Common iliac

		External iliac

		Internal iliac

	Presacral	Presacral

	Lateral sacral	Sacral
Corpus uteri	Pelvic (hypogastric [obturator, internal iliac] common and external iliac, parametrial, and sacral)	Hypogastric (obturator)

	Para-aortic nodes	Internal iliac

		Common iliac

		External iliac

		Parametrial

		Sacral
Ovary	Hypogastric (obturator)	Hypogastric (obturator)

	Common iliac	Common iliac

	External iliac	External iliac

	Lateral sacral	Lateral sacral

	Para-aortic	Para-aortic

	Inguinal	Inguinal

		Pelvic, NOS

		Retroperitoneal, NOS
Fallopian tube	Hypogastric (obturator)	Hypogastric (obturator)

	Common iliac	Common iliac

	External iliac	External iliac

	Lateral sacral	Lateral sacral

	Para-aortic	Para-aortic

	Inguinal	Inguinal

		Internal iliac
Penis	Superficial and deep inguinal	Single superficial inguinal (femoral)

		Multiple or bilateral superficial inguinal

		Deep inguinal: Rosenmüller or Cloque

		External iliac

		Internal iliac (hypogastric)

	Pelvic nodes	Pelvic nodes, NOS
Prostate	Pelvic nodes below bifurcation of common iliac arteries	Pelvis, NOS

		Hypogastric Obturator

		Iliac (internal, external, NOS)

		Sacral (lateral, presacral, promontory (NOS)
Testis	Abdominal para-aortic, preaortic, interaortocaval, precaval, paracaval, retrocaval, retroaortic nodes.	Interaortocaval, para-aortic, paracaval, preaortic, precaval retroaortic, retrocaval nodes.

	Nodes along the spermatic vein.	Nodes along the spermatic vein

	After scrotal or inguinal surgery: inguinal nodes.	After scrotal or inguinal surgery: intrapelvic, external iliac, inguinal nodes.
Kidney	Hilar, abdominal para-aortic, paracaval nodes.	Renal hilar, paracaval, Aortic (para-aortic, periaortic, lateral aortic), retroperitoneal, NOS
Renal Pelvis and Ureter	Hilar, addominal para-aortic, paracaval nodes.	For renal pelvis: Renal hilar, paracaval, retroperitoneal, NOS

	For ureter:	For ureter:

	Intrapelvic nodes.	Renal hilar, Iliac (common, internal [hypogastric], external), paracaval, peri-ureteral, pelvic, NOS
Urinary Bladder	Pelvic nodes below the bifurcation of the common iliac arteries. (Nodes of the true pelvis).	Nodes below the bifurcation of the common iliac arteries: Hypogastric, obdurator, iliac (internal, external, NOS), perivesical, pelvic, NOS, Sacral (lateral, sacral promontory [Gerota's]), Presacral
Urethra	Inguinal and pelvic nodes.	Inguinal (superficial or deep), Iliac (common, internal hypogastric], obdurator, external), presacral, Sacral, NOS, pelvic, NOS

^*Note that the UICC adopted the AJCC regional lymph node list in May 1999 based on studies by Nozaki et al. [22]

¹Regional nodes include those along the hepatic artery, portal vein, and inferior vena cava.

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Explanatory Notes-General

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TNM Classification Help

About the TNM System

The History of the TNM System

1. The General Rules of the TNM System1,2

2. The Principles of the TNM System

3. The General Rules of the TNM System

4. Anatomical Regions and Sites

5. TNM Clinical Classification

6. pTNM Pathological Classification

7. Histopathological Grading

8. Additional Descriptors

9. Optional Descriptors

10. Residual Tumour (R) Classification

11. Stage Grouping

12. Site Summary

13. Related Classifications

End Notes

TNM 7 - Introduction

Explanatory Notes - Specific Anatomical Sites

Explanatory Notes - Specific Anatomical Sites

Abstract

1. Head and Neck Tumours

1. The General Rules of the TNM System^1,2