Principles of Cancer Staging

Principles of Cancer Staging
1
Donna M. Gress, Stephen B. Edge, Frederick L. Greene,
Mary Kay Washington, Elliot A. Asare, James D. Brierley,
David R. Byrd, Carolyn C. Compton, J. Milburn Jessup,
David P. Winchester, Mahul B. Amin,
and Jeffrey E. Gershenwald
INTRODUCTION AND OVERVIEW hilosophy of Revisions to the TNM Staging

P
System
The extent or stage of cancer at the time of diagnosis is a key
factor that defines prognosis and is a critical element in The AJCC and UICC periodically modify the AJCC TNM
determining appropriate treatment based on the experience staging system in response to newly acquired clinical and
and outcomes of groups of previous patients with similar pathological data and an improved understanding of can-
stage. In addition, cancer stage often is a key component of cer biology and other factors affecting prognosis. Periodic
inclusion, exclusion, and stratification criteria for clinical tri- and, to the extent possible, evidence-based revision is a
als. Indeed, accurate staging is necessary to evaluate the key feature that makes this staging system the most clini-
results of treatments and clinical trials, to facilitate the cally useful among staging systems and accounts for its
exchange and comparison of information across treatment widespread use worldwide. However, because changes in
centers and within and between cancer-specific registries, staging systems may make it difficult to compare out-
and to serve as a basis for clinical and translational cancer comes of patients over time, evidence-based changes to
research. At the national and international levels, a cohesive this staging system are made with deliberate care.
approach to the classification of cancer provides a method of In general, the revision cycle for AJCC TNM staging has
clearly conveying clinical experience to others without historically been 5 to 7 years. This approach provides suffi-
ambiguity. cient time for implementation of changes in clinical manage-
Cancer treatment requires assessment of the extent and ment and cancer registry operations and for relevant
behavior of the tumor and patient-related factors. Several examination and discussion of data supporting changes in
cancer staging systems are used worldwide. Differences staging. Table 1.1 shows the publication year for each ver-
among these systems stem from the needs and objectives of sion of the AJCC TNM system up through this current AJCC
users in clinical medicine and in population surveillance. Cancer Staging Manual, 8th Edition. The AJCC Cancer
The most clinically useful staging system is the tumor, node, Staging Manual, 7th Edition was used for cancer patients
and metastasis (TNM) staging system developed by the diagnosed on or after January 1, 2010. The 8th Edition pub-
American Joint Committee on Cancer (AJCC) in collabora- lished in this manual is effective for cancer patients diag-
tion with the Union for International Cancer Control (UICC), nosed on or after January 1, 2018. The AJCC recognizes that
herein referred to as the AJCC TNM staging system. The rapidly evolving evidence may necessitate more frequent
AJCC TNM system classifies cancers by the size and extent updates of AJCC TNM staging in the future, and anticipates
of the primary tumor (T), involvement of regional lymph providing more frequent updates for disease sites as new and
nodes (N), and the presence or absence of distant metastases validated evidence becomes available. Moreover, the AJCC
(M), supplemented in recent years by evidence-based prog- also recognizes that as clinical cancer care continues to
nostic and predictive factors. There is a TNM staging algo- evolve and incorporates factors that are not used to deter-
rithm for cancers of virtually every anatomic site and mine stage but that provide key information on specific out-
histology, with the primary exception of pediatric cancers. comes and/or expected benefit from specific therapies, new,
To access the AJCC cancer staging forms, please visit www.cancerstaging.org.
© American College of Surgeons 2017 3

M.B. Amin et al. (eds.), AJCC Cancer Staging Manual, Eighth Edition, DOI 10.1007/978-3-319-40618-3_1
4 American Joint Committee on Cancer • 2017
Table 1.1 AJCC Cancer Staging Manual editions extent possible, ambiguities have been resolved. Although
Edition Publication Effective dates for cancer diagnoses the rules generally apply across all disease sites, there are
1st 1977 1978–1983 some exceptions as to how these rules are applied to specific
2nd 1983 1984–1988 disease sites. Wherever possible, such exceptions are noted,
3rd 1988 1989–1992 both in this chapter and in the appropriate disease site
4th 1992 1993–1997 chapters.
5th 1997 1998–2002
6th 2002 2003–2009
7th 2009 2010–2017 Assigning Stage: Role of the Managing
8th 2016 2018– Physician
Staging requires the collaborative effort of many profes-

validated clinical tools will be needed to help clinicians effi- sionals, including the managing physician, pathologist,
ciently and accurately use these important data to enhance radiologist, cancer registrar, and others. The pathologist
clinical care (see Anatomic Staging and the Evolving Use of plays a central role. An accurate microscopic diagnosis is
Nonanatomic Factors). essential to the evaluation and treatment of cancer.
Pathologists must also accurately report several anatomic,
histologic, and morphologic characteristics of tumors, as
Comprehensive Analysis of Staging Rules well as key biologic features. Pathological reporting is best
and Nomenclature accomplished by using standardized nomenclature in a
structured report, such as the synoptic reports or cancer pro-
In January 2012, the AJCC and UICC initiated a comprehen- tocols defined by the College of American Pathologists
sive analysis of staging nomenclature: the AJCC–UICC (CAP). In addition, for some cancers, measurements of
Lexicon Project. This effort focused on harmonization of other factors, including biochemical, molecular, genetic,
their collective staging taxonomies with each other and with immunologic, or functional characteristics of the tumor or
international standards. This group concluded that terminol- normal tissues have become important or essential elements
ogy should be categorized into four main groups: (1) ana- to improve tumor classification. Some of the growing reper-
tomic stage—disease extent and timing/classification; (2) toire of techniques that supplement standard histologic eval-
tumor profile—characterization of tumor (e.g., biomarkers, uation used to characterize tumors and their potential
viral load); (3) patient profile—age, gender, race, and health behavior and response to treatment include immunohisto-
status; and (4) environment—availability of treatment and chemistry (IHC), cytogenetic analysis, and genetic charac-
quality of imaging. This joint project thus far has encom- terization in the form of mutational analysis. Similarly,
passed two working groups—anatomic stage and tumor pro- imaging specialists must provide concise and unambiguous
file—to thoroughly review the existing nomenclature and reports on the extent of cancer as identified on a variety of
standard definitions. The patient profile and environment imaging studies.
categories will be addressed in future work. Although the pathologist and the radiologist provide
The Content Harmonization Core (CHC) is one of seven important staging information, and may provide important
AJCC “cores” developed to inform a more uniform 8th T-, N-, and/or M-related information, stage is defined ulti-
Edition effort. The CHC had its first meeting in August 2014. mately from the synthesis of an array of patient history and
Building upon the work of the AJCC–UICC Lexicon Project, physical examination findings supplemented by imaging and
its charge was to review and update the general staging rules pathology data. Only the managing physician can assign the
and nomenclature (published in Chapter 1 of the 7th Edition) patient's stage, because only (s)he routinely has access to all
and to develop a more precise language of cancer to enhance the pertinent information from physical examination, imag-
the accuracy of the staging system. A goal of this effort is to ing studies, biopsies, diagnostic procedures, surgical find-
standardize technical terms and concepts as well as conflict- ings, and pathology reports.
ing terms and usage. Once it identified key issues, the CHC
worked with thought leaders and organizations to clarify and
ensure precise, standardized, and clear definitions and rules Related Publications to Facilitate Staging
for staging to the extent possible; for some terms and con-
cepts, however, unequivocal clarity could not be achieved In the interest of promoting high-quality care, and to facili-
(and is noted in the chapter). The work product of the CHC tate international collaboration in cancer research and com-
is reflected in this chapter, and provides overall rules for parison of data among different clinical studies, the AJCC
staging that apply across all tumor sites. In most cases, the uses information from other organizations and publications
rules are unchanged from previous versions of TNM; to the to facilitate staging, including:
1 Principles of Cancer Staging 5
• World Health Organization Classification of Tumours, anatomic cancer- and host-related factors provide critical
Pathology and Genetics. Since 1958, the World Health prognostic information and may predict the benefit of specific 1
Organization (WHO) has had a program aimed at pro- therapies. Among factors shown to affect patient outcome and/
viding internationally accepted criteria for the histo- or response to therapy are the clinical and pathological ana-
logic classification of tumors. The series contains tomic extent of disease; the reported duration of signs or
definitions, descriptions, and illustrations of tumor symptoms; the gender, age, and health status of the patient; the
types and related nomenclature (WHO: World Health tumor type and grade; and specific biological properties of the
Organization Classification of Tumours. Various edi- cancer and host. Clinicians often use pure anatomic extent of
tions. Lyon, France: IARC Press, 2000–2016). disease in defining treatment, but in many cases, they supple-
• WHO International Classification of Diseases for ment TNM-based staging with other factors to counsel patients
Oncology (ICD-O), 3rd edition. ICD-O is a numeric clas- and offer specific treatment recommendations. As more of
sification and coding system by topography and morphol- these and other factors are embraced, applying them in prac-
ogy (WHO: ICD-O-3 International Classification of tice will become increasingly complex. This will make it
Diseases for Oncology. 3rd ed. Geneva: WHO, 2000). essential to initiate strategies to develop clinically validated
• American College of Radiology Appropriateness prognostic tools and incorporate them into practice to enhance
Criteria®. The American College of Radiology patient management and overall clinical decision making, ide-
(ACR) maintains guidelines and criteria for use of ally while maintaining a core anatomic-based structure of
imaging and interventional radiology procedures for staging. Such an integrated approach may reduce the potential
many aspects of cancer care. This includes the extent for the de facto anatomically constrained TNM system to be
of imaging recommended for the diagnostic evalua- rendered obsolete by fostering incorporation of an unprece-
tion of the extent of disease of the primary tumor, dented and rapidly evolving understanding of the biology of
nodes, and distant metastases for several cancer human cancer. See also Chapter 4, Risk Assessment Models,
types. The ACR Appropriateness Criteria® are for more information on AJCC-initiated efforts to embrace
updated regularly (http://www.acr.org/ac). development of clinically validated tools.
• CAP Cancer Protocols. CAP publishes standards for As introduced in this chapter and detailed throughout this
pathology reporting of cancer specimens for all cancer cancer staging manual, in many of the revised AJCC staging
types and cancer resection types. These specify the algorithms, prognostic factors have been incorporated into
elements necessary for the pathologist to report the stage groupings for specific disease sites where indicated.
extent and characteristics of cancer specimens (http:// Because this practice was initiated in a limited fashion in
www.cap.org). previous editions, most prognostic factors in use, if vali-
• National Comprehensive Cancer Network Clinical dated, have been done so only for patients with specific
Practice Guidelines in Oncology (NCCN Guidelines®). types of disease stratified largely by anatomic stage (e.g.,
The National Comprehensive Cancer Network (NCCN) Gleason score in early-stage prostate cancer and genomic
provides practice guidelines for most types of cancer. profiles in women with node-negative breast cancer). It is
These guidelines are updated at least annually. They important to recognize that even with these advances, ana-
include recommendations for diagnostic evaluation and tomic extent of disease remains central to defining cancer
imaging of the primary tumor and screening for metasta- prognosis. Inclusion of anatomic extent also maintains the
ses for each cancer type that may be useful to guide stag- ability to compare patients in a similar fashion across both
ing (http://www.nccn.org). contemporary and historical treatment regimens and eras, as
• American Society of Clinical Oncology (ASCO) well as patient populations for whom new prognostic factors
Guidelines. ASCO develops guidelines and technical cannot be obtained because of cost, available expertise,
assessments for an array of clinical situations and reporting systems, and/or other logistical issues.
tools. These include disease- and modality- specific
guidelines and assessments of tools, such as the use of
biomarkers in certain cancers. These guidelines may
be found at the ASCO website: www.asco.org. JCC TNM STAGING SYSTEM:
A
CLASSIFICATIONS, CATEGORIES,
AND RULES FOR STAGING
Anatomic Staging and the Evolving Use
of Nonanatomic Factors The AJCC TNM stage for each cancer type is built by defin-
ing the anatomic extent of cancer for the tumor (T), lymph
Historically, cancer staging has been based solely on the ana- nodes (N), and distant metastases (M), supplemented in
tomic extent of cancer, and the 8th Edition approach remains some cases with nonanatomic factors. For each of the T, N,
primarily anatomic. However, an increasing number of non- and M, there is a set of categories, most often defined by a
number (e.g., T1, N2). The description of the anatomic treatment. Imaging study information may be used for clini-
factors is specific for each disease site. These descriptors and cal staging, but clinical stage may be assigned based on
the nomenclature for TNM have been developed and refined whatever information is available. No specific imaging is
over many editions of the AJCC Cancer Staging Manual by required to assign a clinical stage for any cancer site. When
experts in each disease and by cancer registrars who collect performed within this framework, biopsy information on
the information, taking into consideration the behavior and regional lymph nodes and/or other sites of metastatic disease
natural history of each type of cancer. These elements are may be included in the clinical classification.
then combined, in a fashion set forth for each cancer type, Clinical evaluation by physical examination often under-
into prognostic stage groups (often called “stage groups”). estimates the extent of cancer burden at the time of patient
Importantly, the term stage should be used only to presentation. Although imaging is not required to assign
describe the aggregate information resulting from T, N, and clinical stage, clinical imaging has become increasingly
M category designations (i.e., based on T, N, and M classifi- important, and for many cancer sites, imaging is essential to
cations) combined with any prognostic factors relevant to the stage solid tumors accurately. Imaging allows assessment of
specific disease. The term stage should not be used to the tumor's size, location, and relationship to normal ana-
describe individual T, N, or M category designations that tomic structures, as well as the existence of nodal and/or dis-
often are mistakenly referred to as “stage.” tant metastatic disease. Computed tomography (CT) and
Assigning the T, N, and M categories follows general rules magnetic resonance (MR) imaging are the most commonly
described in the tables in this chapter. These rules apply to all used imaging modalities, although positron emission tomog-
cancer sites, with relatively few exceptions. These exceptions raphy (PET; often combined with CT), ultrasound, and plain
are defined in the relevant disease-specific chapters. film radiography also have important roles in various clinical
Rules are repeated throughout this chapter to facilitate situations. Thus, a new section was added to the disease site
easy reference based on the topic. chapters to provide context-specific imaging information. To
Before delineating the specific rules for T, N, and M cat- adequately and comprehensively communicate essential
egorization and for generating prognostic stage groups, it is information, radiologists should use standardized nomencla-
important to first delineate the time points, termed classifica- ture and structured report formats, such as those recom-
tions, at which staging information is collected and reported. mended by the Radiological Society of North America
(RSNA) reporting initiative (http://www.rsna.org/Reporting_
Initiative.aspx). In addition to providing key information for
NM Staging Classification: Clinical,
T assigning the T, N, and M categories, clinical imaging is
Pathological, Posttherapy, Recurrence, invaluable for guiding biopsies and surgical resections. Later
and Autopsy in the course of a patient's treatment, imaging also often
plays an important role in monitoring response to treatment.
Stage may be defined at several time points in the care of the
cancer patient. To properly stage a patient's cancer, it is athological Classification (pTNM)
P
essential to first determine the time point in a patient's care. Pathological stage classification is based on clinical stage
These points in time are termed classifications, and are based information supplemented/modified by operative findings
on time during the continuum of evaluation and management and pathological evaluation of the resected specimens. This
of the disease. Then, T, N, and M categories are assigned for classification is applicable when surgery is performed before
a particular classification (clinical, pathological, posttherapy, initiation of adjuvant radiation or systemic therapy.
recurrence, and/or autopsy) by using information obtained
during the relevant time frame, sometimes also referred to as osttherapy or Post Neoadjuvant Therapy
P
a staging window. These staging windows are unique to each (ycTNM and ypTNM)
particular classification and are set forth explicitly in the fol- Stage determined after treatment for patients receiving sys-
lowing tables. The prognostic stage groups then are assigned temic and/or radiation therapy alone or as a component of their
using the T, N, and M categories, and sometimes also site- initial treatment, or as neoadjuvant therapy before planned
specific prognostic and predictive factors. surgery, is referred to as posttherapy classification. It also may
Among these classifications, the two predominant are be referred to as post neoadjuvant therapy classification.
clinical classification (i.e., pretreatment) and pathological
classification (i.e., after surgical treatment). ecurrence or Retreatment (rTNM)
R
Staging classifications at the time of retreatment for a recur-
linical Classification (cTNM)
C rence or disease progression is referred to as recurrence clas-
Clinical stage classification is based on patient history, phys- sification. It also may be referred to as retreatment
ical examination, and any imaging done before initiation of classification.
Autopsy (aTNM) information, supplemented by selected prognostic factors in

Staging classification for cancers identified only at autopsy some disease sites. Stage groups are defined for each of the 1
is referred to as autopsy classification. classifications: clinical stage group and pathological stage
group.
Defining T, N, M, and Prognostic Factor

Categories Documenting Cancer Stage in the Medical
Record
The T, N, and M designations are referred to as categories.
The category criteria for defining anatomic extent of dis- All staging classifications—and, most importantly, clini-
ease are specific for tumors at different anatomic sites and cal and pathological classifications—should be docu-
sometimes for tumors comprising different histologic mented in the medical record. The documentation in the
types arising from similar anatomic sites. For example, the record should include the type of classification (e.g., clin-
size of the tumor is a key factor in breast cancer but has no ical or pathological); T, N, and M categories; relevant
impact on prognosis in colorectal cancer, in which the prognostic factor categories; and the stage grouping.
depth of invasion or extent of the cancer is the primary Clinical stage generally is used to define primary therapy.
prognostic feature. In summary, the T, N, and M category TNM-based clinical stage also is important because it
criteria are defined separately for each tumor and histo- may be the only common denominator across all cancers
logic type. of a certain anatomic site and histology. Examples include
In addition to anatomic-based T, N, and M information, lung cancer, advanced gastrointestinal tumors, and head
the AJCC recommends collection of key prognostic factors and neck cancers, for which surgery may not be per-
for specific cancer sites (as detailed in each site chapter) formed, and others, such as prostate cancer, for which sur-
that in some cases are used to define T, N, or M and/or may gical resection for limited disease may not be applicable.
be used to define stage groupings critical to prognosis and/ In such scenarios, it may be impossible to compare
or helpful to guide patient care and to ensure uniformity in patients for whom information is obtained solely by clini-
comparative research and reporting environments. cal staging strategies with those undergoing surgical
The AJCC includes additional factors that play a role in resection and for whom pathological staging is performed.
the calculation of the AJCC Prognostic Stage Group for a The importance of clinical stage was reinforced in 2008
disease site. If available and applicable to the disease site, when the American College of Surgeons Commission on
so-called Prognostic Factors Required for Stage Grouping Cancer (CoC) introduced the requirement that clinical
can modify the calculation of stage based only on TNM. These stage be documented in all cancer patients as part of its
factors are involved in the calculation of stage in several dis- cancer program standards, as a key determinant of treat-
ease sites, such as breast and prostate. ment choice. Pathological staging is used to define a more
A different system for designating the extent of disease precise prognosis and to plan other therapies as required.
and prognosis is necessary for certain types of tumors, such Many options exist for documenting staging data in the
as Hodgkin and other lymphomas. In these circumstances, medical record. Examples of source documents in the medi-
other categories are used instead of T, N, and M, and for cal record that may contain patient-specific cancer staging
lymphoma, only the stage group is defined. General staging information include initial clinical evaluations and consulta-
rules are presented in this chapter, and the specifics for each tions, operative reports, imaging studies, pathology reports,
type of disease are detailed in the respective disease site–spe- discharge summaries, and follow-up reports. Physicians are
cific chapters. encouraged to enter the stage of cancer in every record of
clinical encounters with the cancer patient. Paper or
electronic staging forms may be useful to record stage in the
AJCC Prognostic Stage Groups medical record as well as to facilitate communication of
staging data to a cancer registry. A form for recording cancer
For the purposes of tabulation and to analyze the care of staging data will be made available for each disease site on
patients who generally have a similar prognosis, T, N, and M www.cancerstaging.org.
are grouped into prognostic stage groups, commonly referred T, N, and M category information as well as disease
to as stage groups. As introduced earlier, a stage group is site-specific prognostic factor data should be included in
determined from aggregate information on the primary pathology reports whenever these data are available.
tumor (T), regional lymph nodes (N), and distant metastases Pathologists should use the appropriate AJCC-specified data
(M), as well as any specified prognostic factors for certain elements as defined by the CAP Cancer Protocols. However,
cancer types. Stage groups are based primarily on anatomic the determination of stage usually involves synthesis of
information from multiple sources, including clinical data, Elements of

imaging studies, and pathology reports. Because all this TNM tables Description
information may not be available to the reporting patholo- AJCC AJCC prognostic stage groups are assigned based
prognostic on disease site–specific T, N, and M categories and
gist, final T, N, and M categories and stage may not be fully
stage groups relevant prognostic factors to group patients with
assessed from pathology reports alone and should be (stage groups) similar prognosis and/or treatment approach. For
assigned by the managing physician(s). each cancer type in which prognostic factors are
used to assign stage groups, a separate stage group
may be assigned based solely on anatomic
categories so as to allow stage group comparisons
TNM and Prognostic Stage Group Tables among patients who have and do not have available
prognostic factor information.
TNM information in each chapter provides precise criteria
and rules for categorizing the T, N, or M of a patient for the
relevant classification (e.g., clinical, pathological). This T, N, M and Prognostic Factor Category Criteria
information is used to assign prognostic stage groups
based on the assigned T, N, and M categories (with other The three categories—T, N, and M—and the prognostic
prognostic factors if required for that specific cancer type). factors collectively describe, with rare exceptions, the
extent of tumor, including local spread, regional nodal
involvement, and distant metastasis. It is important to stress
Elements of
TNM tables Description that each component (T, N, and M) is referred to as a cate-
Classification A lower case prefix describes the time point in a gory. The term stage is used when T, N, and M and cancer
patient's cancer continuum when stage is assigned, site–specific required prognostic factors are combined. The
including: criteria for T, N, and M are defined separately for cancers in
• c: clinical
• p: pathological
different anatomic locations and/or for different histologic
• yc: post neoadjuvant (radiation or systemic) types.
therapy—clinical
• yp: post neoadjuvant (radiation or systemic) This category… Is defined by…
therapy—pathological T The size and/or contiguous extension of the
• r: recurrence or retreatment primary tumor.
• a: autopsy Note: The roles of the size component and
Category T-, N-, and M-specific data are used to assign a cancer the extent of contiguous spread are
site–specific T, N, and M category for a patient at a specifically defined for each cancer site.
given classification. Generally, the higher the T, N, or N Cancer in the regional lymph nodes as
M category, the greater the extent of the disease and defined for each cancer site, including
generally the worse the prognosis. • absence or presence of cancer in
Note: Exceptions exist in which T-, N-, or regional node(s), and/or
M-specific category elements may represent unique • number of positive regional nodes, and/or
characteristics of the cancer but not necessarily • involvement of specific regional nodal
worse prognosis. For example, N1c in colon cancer groups, and/or
does not represent greater nodal disease burden • size of nodal metastasis or extension
than N1a or N1b, but rather a unique situation. through the regional node capsule, and/or
Subcategory Some disease sites have subcategories devised to • In-transit and satellite metastases,
facilitate reporting of more detailed information somewhat unique manifestations of
and often more specific prognostic information. nonnodal intralymphatic regional disease,
Examples: usually found between the primary tumor
• breast cancer: T1mi, T1a, T1b, T1c site and draining nodal basins.
• breast cancer: N2a, N2b Note: For melanoma and Merkel cell
• prostate cancer: M1a, M1b, M1c carcinoma, nonnodal regional metastasis,
Note: If there is uncertainty in assigning a such as satellites and in-transit metastases,
subcategory, the patient is assigned to the general may be included in the N categorization (see
category. For example, a breast cancer reported the melanoma and Merkel cell carcinoma
clinically as <2 cm without further specification is chapters for specifics). For colorectal
assigned T1 and cannot be assigned T1a, T1b, or carcinoma, mesenteric tumor deposits
T1c. without remaining nodal architecture are
If uncertain or incomplete information precludes included in the N category.
subcategory assignment, which may result in M The absence or presence of distant
different stage groups or management paradigms, a metastases in sites and/or organs outside the
subcategory assignment may still be required. In local tumor area and regional nodes as
that case, the general category, the physician/ defined for each cancer site. For some cancer
managing team categorization, or the lower or less sites, the location and volume or burden of
advanced subcategory should be used. distant metastases are included.
This category… Is defined by… Distant Metastasis (M) Categories

Prognostic factors
required for stage
The prognostic factors required for stage
grouping have such a strong correlation with
1
The distant metastasis category specifies whether distant
grouping prognosis that they are included in the AJCC
metastasis is present.
Prognostic Stage Groups table. It is
important to collect these factors in cancer
registries and databases to measure their Distant metastasis category… Is assigned when there is…
impact on prognosis. M0 No evidence of distant metastasis
M1 Distant metastasis
Notes: There is no designation of MX. The absence of any clinical his-
tory or physical findings suggestive of metastases in a patient who has
Primary Tumor (T) Categories not undergone any imaging is sufficient to assign the clinical M0 cate-
gory (cM0).
Primary tumor categories have specific notations to describe There is no designation of pM0. Biopsy or other pathological information
the existence, size, or extent of the tumor. is required to assign the pathological M1 category. Patients with a negative
biopsy of a suspected metastatic site are classified as clinical M0 (cM0).
Tumor category… Is assigned when there is…
TX No information about the T category for the Distant Metastasis: Selected Locations
primary tumor, or it is unknown or cannot be
assessed The M1 category may be specified further according to the
Note: Use of the TX category should be
minimized. location of distant metastases.
T0 No evidence of a primary tumor
Location Notation
Tis Carcinoma in situ
Examples of exceptions include: Tis for Pulmonary PUL
in situ melanoma of the skin, germ cell Osseous OSS
neoplasia in situ for testis, and high-grade Hepatic HEP
dysplasia in colorectal carcinoma. Brain BRA
T1, T2, T3, or T4 Primary invasive tumor, for which a higher Distant lymph nodes LYM
category generally means Bone marrow MAR
• an increasing size
Pleura PLE
• an increasing local extension, or
• both Peritoneum PER
Adrenal ADR
Distant skin SKI
Other OTH
Regional Lymph Node (N) Categories
Categorizing regional lymph node involvement depends on Unknown Designation: X

its existence and extent.
The X designation is used if information on a specific T or N
Regional node category… Is assigned when there is… category is unknown; such cases usually cannot be assigned
NX No information about the N a stage. Therefore, TX and NX should be used only if
category for the regional lymph
nodes, or it is unknown or cannot absolutely necessary. Of note, there is no MX category.
be assessed
Note: Use of NX should be Exceptions: TX
minimized. Stage may be assigned when the TNM stage group results in
N0 No regional lymph node
Any T or Any N with M1, which includes TX or NX. These
involvement with cancer and for
some disease sites, nonnodal are classified as Stage IV. Examples include:
regional disease as noted earlier
N1, N2, or N3 Evidence of regional node(s) • TX NX M1, or
containing cancer, with • TX N3 M1.
• an increasing number, and/or
• regional nodal group
involvement, and/or Stage may be assigned when the TNM stage group results
• size of the nodal metastatic in Any T or Any N with M0, which includes TX or
cancer deposit, or NX. Examples include:
• non-nodal regional disease as
noted earlier for melanoma
and Merkel cell carcinoma, • TX N1 M0 Stage III in melanoma clinical stage
and for colorectal carcinoma • T4 NX M0 Stage III in pancreas
MX is Not a Valid M Category many patients with Stage IIIA disease have a prognosis more
The MX category was eliminated from the AJCC and UICC favorable than that of patients with Stage IIC disease.
TNM systems in the AJCC Cancer Staging Manual, 6th Stage groups are denoted by Roman numerals from I to IV
Edition. Unless there is clinical or pathological evidence of with increasing extent of disease and generally with worsen-
distant metastases, the patient is classified as clinical M0 and ing overall prognosis. Stage I generally indicates cancers that
denoted as cM0. It is not necessary to perform any imaging are smaller or less deeply invasive without regional disease or
or invasive studies to categorize a patient as cM0. A history nodes, Stages II and III define patients with increasing tumor
and physical examination are all that is needed to assign or nodal extent, and Stage IV identifies those who present
cM0. The M category must always be known and reported to with distant metastases (M1) at diagnosis.
assign a stage group. The term Stage 0 is used to denote carcinoma in situ (or
Pathologists should not report an M category unless melanoma in situ for melanoma of the skin or germ cell neo-
appropriate for the specimen evaluated. CAP Cancer plasia in situ for testicular germ cell tumors) and generally is
Protocols require documentation of distant metastases as considered to have no metastatic potential. Stage 0 is deter-
pM1 only if present in the specimen(s) provided to the mined by microscopic examination of the primary tumor.
pathologist. If the pathologist does not review and report on Stage I through Stage IV subgroups are denoted by capital
a metastatic specimen, or if a biopsy is performed of a pos- letters—for example, A, B, or C—according to cancer site
sible distant metastasis and the biopsy does not show cancer, stage grouping definitions and are used to expand the main
then there should be no mention of the M category in the groupings to provide more refined prognostic information.
pathology report, or the pathologist should designate the M
category as “not applicable.” The term MX should not be
used in the pathology report. Prognostic Factors Required for Stage
The managing physician should stage a patient for whom Grouping
a biopsy performed for possible distant metastasis does not
demonstrate cancer as cM0; there is no pM0 designation. For some cancer types, in addition to T, N, and M categories,
Only the managing physician can assign cM0 after taking prognostic factors are required to assign a stage group.
into account physical examination, imaging, and other Examples include tumor grade, age at diagnosis, histologic
information. type, mitotic rate, serum tumor markers, hormone receptors,
hereditary factors, prostate-specific antigen, and Gleason
score. Specifically, cancer site–specific prognostic factors
AJCC Prognostic Stage Groups populate nonanatomic categories and are defined clearly if
required for a particular disease site.
The purpose of defining and assigning stage groups is to gen- These factors generally constitute categories used with
erate a reproducible and easily communicated summary of the TNM categories to assign prognostic stage groups. In
staging information. The staging tables generally group some cases in which factors are used in stage groups, an X
patients with similar prognoses, usually with a statistically category is provided for use by the managing physician if the
significant separation in outcomes between stage groups. factor is not available. Generally, in cases in which the factor
Patients within a stage group generally have similar out- is absent and X is not provided as an option, the physician's
comes, even though their burden of disease may vary. determination or lowest category (best prognosis) of the fac-
Exceptions to this general stage group convention are noted tor is used to assign the stage group.
in each chapter where relevant. For example, to retain an In contrast, cancer registry data collection should record
anatomic- and TNM-based staging system in melanoma, X or unknown if the prognostic factor is not available, and
some prognostic overlap was allowed between patients with should not use the lowest category. This allows for accurate
Stage IIC melanoma and those with Stage IIIA melanoma; analysis of the data.
GENERAL STAGING RULES

1
These general rules apply to the application of T, N, and M categories for all anatomic sites and classifications.
Topic Rules
Microscopic confirmation • Microscopic confirmation is necessary for TNM classification, including clinical classification (with rare
exception).
• In rare clinical scenarios, patients who do not have any biopsy or cytology of the tumor may be staged. This
is recommended in rare clinical situations, only if the cancer diagnosis is NOT in doubt. In the absence of
histologic confirmation, survival analysis may be performed separately from staged cohorts with histologic
confirmation. Separate survival analysis is not required if clinical findings support a cancer diagnosis and
specific site.
Example: Lung cancer diagnosed by CT scan only, that is, without a confirmatory biopsy
Time frame/staging Information gathered about the extent of the cancer is part of clinical classification:
window for determining • from date of diagnosis before initiation of primary treatment or decision for watchful waiting or supportive
clinical stage care to one of the following time points, whichever is shortest:
○ 4 months after diagnosis
○ to the date of cancer progression if the cancer progresses before the end of the 4 month window; data on
the extent of the cancer is only included before the date of observed progression
Time frame/staging Information including clinical staging data and information from surgical resection and examination of the
window for determining resected specimens—if surgery is performed before the initiation of radiation and/or systemic therapy—from the
pathological stage date of diagnosis:
• within 4 months after diagnosis
• to the date of cancer progression if the cancer progresses before the end of the 4-month window; data on the
extent of the cancer is included only before the date of observed progression
• and includes any information obtained about the extent of cancer up through completion of definitive surgery
as part of primary treatment if that surgery occurs later than 4 months after diagnosis and the cancer has not
clearly progressed during the time window
Note: Patients who receive radiation and/or systemic therapy (neoadjuvant therapy) before surgical resection are
not assigned a pathological category or stage, and instead are staged according to post neoadjuvant therapy
criteria.
Time frame/staging After completion of neoadjuvant therapy, patients should be staged as:
window for staging post • yc: posttherapy clinical
neoadjuvant therapy or After completion of neoadjuvant therapy followed by surgery, patients should be staged as:
posttherapy • yp: posttherapy pathological
The time frame should be such that the post neoadjuvant surgery and staging occur within a time frame that
accommodates disease-specific circumstances, as outlined in the specific chapters and in relevant guidelines.
Note: Clinical stage should be assigned before the start of neoadjuvant therapy.
Progression of disease If there is documented progression of cancer before therapy or surgery, only information obtained before the
documented progression is used for clinical and pathological staging.
Progression does not include growth during the time needed for the diagnostic workup, but rather a major change
in clinical status.
Determination of progression is based on managing physician judgment, and may result in a major change in the
treatment plan.
Uncertainty among T, N, If uncertainty exists regarding how to assign a category, subcategory, or stage group, the lower of the two possible
or M categories, and/or categories, subcategories, or groups is assigned for
stage groups: rules for • T, N, or M
clinical decision making • prognostic stage group/stage group
Stage groups are for patient care and prognosis based on data. Physicians may need to make treatment decisions if
staging information is uncertain or unclear.
Note: Unknown or missing information for T, N, M or stage group is never assigned the lower category,
subcategory, or group.
Uncertainty rules do not If information is not available to the cancer registrar for documentation of a subcategory, the main (umbrella)
apply to cancer registry category should be assigned (e.g., T1 for a breast cancer described as <2 cm in place of T1a, T1b, or T1c).
data If the specific information to assign the stage group is not available to the cancer registrar (including
subcategories or missing prognostic factor categories), the stage group should not be assigned but should be
documented as unknown.
Prognostic factor category If a required prognostic factor category is unavailable, the category used to assign the stage group is:
information is unavailable • X, or
• If the prognostic factor is unavailable, default to assigning the anatomic stage using clinical judgment.
Grade The recommended histologic grading system for each disease site and/or cancer type, if applicable, is specified in
each chapter and should be used by the pathologist to assign grade.
The cancer registrar will document grade for a specific site according to the coding structure in the relevant
disease site chapter.
Topic Rules
Synchronous primary If multiple tumors of the same histology are present in one organ:
tumors in a single organ: • the tumor with the highest T category is classified and staged, and
(m) suffix • the (m) suffix is used
• An example of a preferred designation is: pT3(m) N0 M0.
• If the number of synchronous tumors is important, an acceptable alternative designation is to specify the
number of tumors. For example, pT3(4) N0 M0 indicates four synchronous primary tumors.
Note: The (m) suffix applies to multiple invasive cancers. It is not applicable for multiple foci of in situ cancer or
for a mixed invasive and in situ cancer.
Synchronous primary Cancers occurring at the same time in each of paired organs are staged as separate cancers. Examples include
tumors in paired organs breast, lung, and kidney.
Exception: For tumors of the thyroid, liver, and ovary, multiplicity is a T-category criterion, thus multiple
synchronous tumors are not staged independently.
Metachronous primary Second or subsequent primary cancers occurring in the same organ or in different organs outside the staging
tumors window are staged independently and are known as metachronous primary tumors.
Such cancers are not staged using the y prefix.
Unknown primary or no If there is no evidence of a primary tumor, or the site of the primary tumor is unknown, staging may be based on
evidence of primary tumor the clinical suspicion of the organ site of the primary tumor, with the tumor categorized as T0. The rules for
staging cancers categorized as T0 are specified in the relevant disease site chapters.
Example: An axillary lymph node with an adenocarcinoma in a woman, suspected clinically to be from the
breast, may be categorized as T0 N1 (or N2 or N3) M0 and assigned Stage II (or Stage III).
Examples of exception: The T0 category is not used for head and neck squamous cancer sites, as such patients
with an involved lymph node are staged as unknown primary cancers using the “Cervical Nodes and Unknown
Primary Tumors of the Head and Neck” system (T0 remains a valid category for human papillomavirus [HPV]-
and Epstein–Barr virus [EBV]-associated oropharyngeal and nasopharyngeal cancers).
Date of diagnosis It is important to document the date of diagnosis, because this information is used for survival calculations and
time periods for staging.
The date of diagnosis is the date a physician determines the patient has cancer. It may be the date of a diagnostic
biopsy or other microscopic confirmation or of clear evidence on imaging. This rule varies by disease site and
shares similarities with the earlier discussion on microscopic confirmation.
STAGE CLASSIFICATIONS
Stage classifications are determined according to the point in time of the patient's care in relation to diagnosis and treatment.
The five stage classifications are clinical, pathological, posttherapy/post neoadjuvant therapy, recurrence/retreatment, and
autopsy.
Classification Designation Details

Clinical cTNM or TNM Criteria: used for all patients with cancer identified before treatment
It is composed of diagnostic workup information, until first treatment, including:
• clinical history and symptoms
• physical examination
• imaging
• endoscopy
• biopsy of the primary site
• biopsy or excision of a single regional node or sentinel nodes, or sampling of regional
nodes, with clinical T
• biopsy of distant metastatic site
• surgical exploration without resection
• other relevant examinations
Note: Exceptions exist by site, such as complete excision of primary tumor for melanoma.
Pathological pTNM Criteria: used for patients if surgery is the first definitive therapy
It is composed of information from:
• diagnostic workup from clinical staging combined with
• operative findings, and
• pathology review of resected surgical specimens
Classification Designation Details

Posttherapy or post
neoadjuvant therapy
ycTNM and ypTNM For purposes of posttherapy or post neoadjuvant therapy, neoadjuvant therapy is defined as
systemic and/or radiation therapy given before surgery; primary radiation and/or systemic
1
therapy is treatment given as definitive therapy without surgery.
yc
The yc classification is used for staging after primary systemic and/or radiation therapy, or
after neoadjuvant therapy and before planned surgery
Criteria: First therapy is systemic and/or radiation therapy
yp
The yp classification is used for staging after neoadjuvant therapy and planned post
neoadjuvant therapy surgery.
Criteria: First therapy is systemic and/or radiation therapy and is followed by surgery.
Recurrence or retreatment rTNM This classification is used for assigning stage at time of recurrence or progression until
treatment is initiated.
Criteria: Disease recurrence after disease-free interval or upon disease progression if
further treatment is planned for a cancer that:
• recurs after a disease-free interval or
• progresses (without a disease-free interval)
rc
Clinical recurrence staging is assigned as rc.
rp
Pathological staging information is assigned as rp for the rTNM staging classification.
This classification is recorded in addition to and does not replace the original previously
assigned clinical (c), pathological (p), and/or posttherapy (yc, yp) stage classifications, and
these previously documented classifications are not changed.
Autopsy aTNM This classification is used for cancers not previously recognized that are found as an
incidental finding at autopsy, and not suspected before death (i.e., this classification does
not apply if an autopsy is performed in a patient with a previously diagnosed cancer).
Criteria: No cancer suspected prior to death
Both clinical and pathological staging information is used to assign aTNM.
Clinical Classification therapy, and response to treatment varies. Differences in

primary therapy make comparing groups of patients difficult
Classification of T, N, and M during the diagnostic workup if that comparison is based on pathological assessment. For
time frame is denoted by use of a lower case c prefix: cT, cN, example, it is difficult to compare patients treated with pri-
and cM0, cM1 or pM1, or the use of no prefix: T, N, M. mary surgery with those treated with chemotherapy or radio-
Clinical stage is important to record for all patients therapy without surgery or neoadjuvant therapy.
because: Time frame: Clinical classification is based on any infor-
mation gathered about the extent of the cancer from the time
• clinical stage is essential for selecting initial therapy, of diagnosis until the initiation of primary treatment or the
and decision for watchful waiting or supportive care, and is based
• clinical stage is critical for comparison across patient on the shorter of two periods of time:
cohorts when some have surgery as a component of
initial treatment and others do not. • within 4 months after diagnosis, or
• the time of cancer progression if the cancer progresses
Clinical stage may be the only stage classification by before the end of the 4-month window; data on the
which comparisons can be made across all patients, because extent of the cancer is included only before the date of
not all patients will undergo surgical treatment before other observed progression
Criteria: All patients with cancer identified before linical T (T or cT)

C
treatment. Assessment of the primary tumor is necessary to determine
Clinical classification is based on: the cT category.
• clinical history and symptoms

• physical examination Component of cT Details
• imaging Tumor size and extent Based on physical examination,
imaging, endoscopy, biopsy of the
• endoscopy or surgical exploration without resection primary site (core through long axis),
• biopsy of the primary site, biopsy or excision of a single surgical exploration, or other relevant
regional node or sentinel nodes, sampling of regional examinations.
nodes with clinical T, or biopsy of a distant metastatic site The most accurate size should be used,
as some methods may overestimate the
size. Therefore, the largest size may not
Clinical classification is based on evidence acquired from be the most accurate and should not be
the date of diagnosis until initiation of primary treatment. used automatically. Guidance on which
Examples of primary treatment include definitive surgery, imaging technique(s) may be most
accurate is discussed in site-specific
radiation therapy, systemic therapy, and neoadjuvant radia- chapters. Physicians should document
tion and systemic therapy. the most accurate tumor size used for
Importantly, clinical stage groups cannot be assigned for staging.
some cancer sites if the necessary minimum information to Tumor size in Primary tumor size is the most
millimeters and accurate/largest dimension and is
assign a clinical stage group is not available. Although this
rounding for T-category • measured to the nearest whole
scenario is quite uncommon, it may occur—for example, if assignment millimeter, unless a smaller unit is
lymph nodes cannot be examined before surgical resection specified in a specific disease site,
or if a cancer is identified and resected incidentally during and
• rounded up or down as appropriate
surgery for another medical condition.
for assigning T category:
○ down when the numerals are
Component of clinical between 1 and 4
staging Details ○ up when the numerals are
Assignment of stage by Clinical stage is assigned based on a between 5 and 9.
managing physician synthesis of clinical data from multiple Examples:
sources and only by the managing • Tumor measured as 2.2 mm is
physician, usually a surgical or medical recorded as 2 mm.
oncologist. As noted earlier, the assignment • Tumor measured as 1.7 mm is
of clinical stage also may include recorded as 2 mm.
pathological data from biopsies. • Tumor measured as 2.04 cm is
Known or suspected Tumor must be known or suspected and recorded as 20 mm and would be
tumor have a diagnostic workup including at least grouped with ≤2 cm and not
a history and physical examination to >2 cm.
assign a clinical stage. Nonexhaustive exceptions:
Incidental findings at the time of surgical • Melanoma: primary tumor
treatment may not be assigned a clinical measured to nearest 0.1 mm
stage retrospectively. • Breast cancer: primary tumor
Imaging studies Imaging may be of value and useful, but >1.0 mm to 1.4 mm rounded to
imaging is not necessary to assign a 2 mm (this avoids assigning the
clinical stage. “microinvasion” category to
Guidelines for diagnostic evaluation of cancer >1.0 mm)
individual cancer types are found in these Surgical exploration Observations made at surgical
publications: exploration without resection are used
• ACR Appropriateness Criteria® http:// to assign clinical categories. Biopsies
www.acr.org/ac of the primary site during surgical
• NCCN Guidelines® http://www.nccn. exploration without resection of the
org. primary tumor are used for clinical
Impact of subsequent The clinical stage should not be changed categorization.
information based on: Exception: This information also may
• subsequent information obtained from be used for pathological T
the pathological examination of categorization if the biopsy provides
resected tissue, or histologic material corresponding to
• information obtained after initiation of the highest possible T category for the
definitive therapy. specific cancer type, and if it meets
other criteria described in stage group.
Component of cT Details linical N (N or cN)

C
Synchronous primary For multiple tumors in a single organ, Assessment of the regional lymph nodes is necessary to 1
tumors in a single organ: T is assigned to the highest T category; determine the cN category.
(m) suffix the preferred designation is:
• m suffix; for example, pT3(m) N0
M0
If the number of tumors is important, Component of cN Details
an acceptable alternative is: Lymph node Clinical regional lymph node assessment may
• number of tumors; for example, assessment be performed by physical examination and
pT3(4) N0 M0 imaging. Clinical nodal category cN0 may be
Note: The (m) suffix applies to assigned based solely on physical examination.
multiple invasive cancers. It is not Imaging to assess regional lymph nodes is not
applicable to multiple foci of in situ required to assign clinical stage.
cancer or a mixed invasive and in situ Node status not For some cancer sites in which lymph node
cancer. required in rare involvement is rare, patients whose nodal
Direct extension into an Direct extension of a primary tumor circumstances status is not determined to be positive for
organ into a contiguous or adjacent organ is tumor should be designated as cN0. These
classified as part of the tumor (T) circumstances are identified in specific
classification and is not classified as disease chapters for these sites; NX is not
metastasis (M). listed as a category.
Example: Direct extension into the Example: Bone and soft tissue sarcoma may
liver from a primary colon cancer use cN0 to assign the clinical stage group,
would be in the T category and not in that is, cT1 cN0 cM0.
the M category. Microscopic Microscopic examination of regional nodes
Microscopic assessment of If microscopic assessment of the assessment for cN during the diagnostic workup is included in the
highest T category primary site or regional tissue clinical classification as cN.
establishes the highest T category, it is: Microscopic examination or assessment may
• assigned as cT, and be by:
• it also may be used for assignment • fine-needle aspiration (FNA),
of pT ONLY if there is • core biopsy,
microscopic confirmation of the • incisional biopsy,
highest pN. • excisional biopsy, or
There must be microscopic • sentinel node biopsy/procedure.
confirmation of both the highest T and This information also is included in the
the highest N in order to assign a pathological staging if the patient has surgical
pathological stage group without resection as the first course of therapy.
resection of the primary site. Example: Sentinel node biopsy performed
Unknown primary or no If there is no evidence of a primary before neoadjuvant therapy in breast cancer is
evidence of primary tumor tumor, or the site of the primary designated as clinical (cN).
tumor is unknown, staging may be Sentinel lymph node A sentinel lymph node (SLN) is a regional
based on the clinical suspicion of the lymph node that receives direct afferent
primary tumor, with the tumor lymphatic drainage from a primary tumor site
categorized as T0. The rules for (e.g., breast, melanoma), and in many solid
staging cancers categorized as T0 are tumors it represents the regional lymph node(s)
specified in the relevant disease site most likely to contain metastatic disease, if any
chapters. are involved. More than one SLN may be
Examples of exception: The T0 present in a regional nodal basin, and some
category is not used for head and neck primary tumors (e.g., melanoma) may drain to
squamous cancer sites, as such more than one regional nodal basin.
patients with an involved lymph node Sentinel nodes are identified by lymphatic
are staged as unknown primary mapping as evidenced by nodes that
cancers using the cervical lymph node concentrate a colloidal material injected near
system (T0 remains a valid category the primary tumor or in the involved organ
for HPV- and EBV-associated (the most commonly used agents for sentinel
oropharyngeal and nasopharyngeal node biopsy are vital stains such as isosulfan
cancers). blue and/or radiotracers such as technetium-99
Tis In situ neoplasia identified during the (99Tc)-sulfur colloid). In some circumstances,
diagnostic workup on a core or the managing physician also may label
incisional biopsy is assigned cTis. regional lymph nodes that are palpably
abnormal during surgery as sentinel nodes.
Any T Any T includes all T categories except
Nodes that do not concentrate colloidal material
Tis. This includes TX and T0.
and are resected along with other sentinel nodes
are nonsentinel nodes and are considered as part
of the sentinel node procedure. Their resection
is not coded as a separate nodal procedure or a
lymph node dissection.
Component of cN Details Component of cN Details

Sentinel node (sn) To distinguish lymph nodes identified during Nonmorphologic Nonmorphologic techniques, including flow
and FNA or core diagnostic evaluation by sentinel node biopsy techniques for cytometry and reverse transcriptase polymerase
biopsy (f) or FNA or core biopsy from those identified identifying ITCs: use chain reaction studies, may identify minimal
by physical examination and imaging, the of the (mol+) deposits of cancer in lymph nodes.
following suffixes are used in assigning the designator These deposits usually are classified as
clinical N (cN) category: clinically node negative and are identified
If SLN biopsy is performed as part of the with the (mol+) designator: for example,
diagnostic workup: cN0(mol+).
• the cN category should have the sn The concepts regarding this staging rule
suffix; for example, cN1(sn). continue to evolve, and further study is
If an FNA or a core biopsy is performed on warranted.
lymph nodes as part of the diagnostic Micro-metastases: Lymph node micro-metastases are defined as
workup: use of the mi tumor deposits >0.2 mm but ≤2.0 mm. For
• the cN category should have the f suffix; designator certain disease sites, micro-metastases are
for example, cN1(f). denoted by using the mi designator: for
Isolated tumor cells ITCs include single tumor cells or small example, cN1mi.
(ITCs): use of the clusters of cells ≤0.2 mm in greatest Further studies are needed to determine the
(i+) designator diameter, generally without stromal significance of micro-metastases across many
response in the lymph node. Such cells cancer sites.
usually are found in the subcapsular nodal The concepts regarding this staging rule
sinuses but may be seen within the nodal continue to evolve, and further study is
parenchyma. Because ITCs may represent warranted.
in-transit tumor cells that are not Extranodal extension Extranodal extension (ENE) is defined as the
proliferating within the node, lymph nodes extension of a nodal metastasis through the
with only ITCs usually are categorized as lymph node capsule into adjacent tissues.
N0, with some exceptions. They are ENE is the preferred terminology. It also is
denoted as N0(i+). termed extranodal spread, extracapsular
The concepts regarding this staging rule extension, or extracapsular spread.
continue to evolve, and further study is Regional node A regional node extending into a distant
warranted. In the meantime, the staging rule metastasis invading a structure or organ is categorized as ENE and
serves as a guideline for uniformity and distant organ is ENE is not considered distant metastatic disease.
consistency in practice in recording
Regional nodes when In rare cases in which a tumor involves more
information, and clinical judgment by the
tumor involves more than one organ or structure, the regional
managing physician prevails.
than one organ or nodes include the nodes of all involved
Exception: In melanoma and Merkel cell
structure structures, even if the nodes of the primary
carcinoma, tumor cell deposits defined here
site are not involved.
as ITCs are considered positive nodes and are
Example: If a primary transverse colon
designated as N1 or higher.
cancer invades the stomach, for staging
Note: Cancer site–specific designators have
purposes, the gastric regional nodes are
been developed to identify ITCs in nodes. For
considered regional for the transverse colon,
example, N0(i+) in breast and gynecologic
even if the regional nodes of the colon are not
cancers applies to nodes with ITCs only.
involved.
Pathological ITCs or lymph node micro-metastases may
Microscopic If microscopic assessment of the regional
techniques for ITCs be identified in lymph nodes by hematoxylin
assessment of node is the highest N category, it is
or detection of and eosin staining or by specialized
regional node is the • assigned as cN, and
micro-metastasis pathological techniques, such as IHC for
highest N category • also may be used for the assignment of
cytokeratin proteins for carcinomas.
pN ONLY if there is microscopic
Specialized pathology techniques, such as
confirmation of the highest pT.
IHC and molecular techniques, are not
There must be microscopic evidence of both
recommended for routine examination of
highest T and highest N to assign a
lymph nodes.
pathological stage group without surgical
The concepts regarding this staging rule
resection of the primary site.
continue to evolve, and further study is
warranted. Any N Any N includes all N categories, including
NX and N0.
linical M Classification (cM and pM)

C Component of
Assignment of the M category for clinical classification may clinical M Details
pM1, both clinical and pM1
1
be cM0, cM1, or pM1. The M category is based on clinical
pathological Stage IV A patient may be staged as both clinical
history, physical examination, any imaging results, and
and pathological Stage IV if:
whether there is microscopic confirmation of the distant • there is confirmatory microscopic
metastasis during the diagnostic workup. The terms pM0 and evidence of a distant metastatic site
MX are NOT valid categories in the TNM system. during the diagnostic workup, which
is categorized as pM1, and
• T and N are categorized only
clinically.
Example: cT3 cN1 pM1 clinical Stage IV
Component of and cT3 cN1 pM1 pathological Stage IV
clinical M Details Circulating tumor cells cM0(i+)
No distant metastasis cM0 and disseminated Patients with:
If there are no symptoms or signs of distant tumor cells: cM0(i+) • Circulating tumor cells (CTCs) in
metastasis, M is categorized as clinically category blood, or
M0 (cM0). Evaluation methods include: • Disseminated tumor cells (DTCs) in
• history and physical examination organs and micro-metastasis in bone
• imaging studies marrow detected by IHC or molecular
Note: Imaging studies may be used in techniques
assigning the M category but are not are categorized as cM0(i+).
required to assign the cM0 category. The cM0(i+) category denotes the uncertain
Clinical evidence of cM1 prognostic significance of these findings.
distant metastasis If there is clinical evidence of distant The concepts regarding this staging rule
metastases on physical examination, continue to evolve, and further study is
imaging studies, or invasive procedures, but warranted.
no microscopic evidence of the presumed Clinical suspicion and If there is clinical suspicion for distant
distant metastases, M is categorized as biopsy does not metastases and a biopsy or excision does
clinically M1 (cM1). Examination methods confirm distant not confirm metastatic cancer, M is
include: metastatic disease categorized as clinically M0 (cM0) or
• physical examination clinically M1 (cM1) based on the
• imaging (if performed) evaluation of other possible sites of distant
• exploratory surgery and/or endoscopy metastatic disease. There is no TNM pM0
(if performed) designation.
Microscopic evidence pM1 Note: pM0 is not a valid category.
of distant metastasis If there is microscopic evidence of distant If clinical evidence of distant metastasis
metastatic disease, M is categorized as remains in other areas that are not or cannot
pathological M1 (pM1). be confirmed microscopically, cM1 is
Microscopic evidence includes: assigned.
• cytology from FNA Unknown distant MX does not exist
• core biopsy metastasis status MX is not a valid category and cannot be
• incisional biopsy assigned. Unless there is clinical or
• excisional biopsy pathologic evidence of metastases, M is
• resection categorized as clinically negative: cM0.
Use of pM1 for pM1 Direct extension into Direct extension from the primary tumor or
multiple distant In patients who have distant metastases in an organ not M lymph nodes into a contiguous or adjacent
metastases multiple sites and have a cancer type for category organ is not included in the M category but
which M subcategories distinguish between is used in the T and N category assignments
one or more metastatic sites, microscopic as noted earlier.
evidence of one of these sites is necessary Example: Direct extension of a colon
to assign the higher pM subcategory. cancer into the liver is categorized as pT4
In general, metastases to both sides of a and cM0.
paired organ are considered a single Definition of Metastases defined during the relevant time
metastatic site of involvement (e.g., metastases timing frame/staging window are classified as
metastases to both lungs are designated metastases (cM1/pM1) and are considered
metastasis to one distant site—lung). synchronous with diagnosis of the primary
If clinical evidence of distant metastasis cancer.
remains in other areas that are not or cannot Metastases detected after the relevant time
be microscopically confirmed, cM1 is frame/staging window are not included in
assigned. the initial staging and generally are
considered recurrent cancer.
Pathological Classification Criteria for assigning pathological stage

Component of
Classification of T, N, and M after surgical treatment is pathological staging Details
denoted by use of a lowercase p prefix: pT, pN, and cM0, Unresectable tumor and If the highest T and N categories or the
assignment of M1 category of the tumor are confirmed
cM1, or pM1. pathological stage microscopically, even if a primary tumor
Time frame: From date of diagnosis through surgical technically cannot be removed or if it is
resection in the absence of cancer progression unreasonable to remove it, the criteria for
Criteria: Surgery is first therapy pathological staging are considered
satisfied without total removal of the
Pathological classification is based on the: primary tumor.
Note: Microscopic confirmation of the
• clinical stage information (acquired before treatment), highest T and N does not necessarily
and supplemented/modified by require removal of that structure and may
entail biopsy or FNA only.
• operative findings, and Example: Supraclavicular node
• pathological evaluation of the resected specimen(s). involvement in inflammatory breast
cancer in which inflammatory carcinoma
Pathological stage is assigned for patients first treated was identified on the core needle breast
biopsy and the supraclavicular node
with surgery. The surgical resection required for assignment involvement is documented by FNA
of this classification is specified for each disease site, and
ranges from resection of the tumor to complete resection of
the organ and usually includes resection of at least some of
the regional lymph nodes. Pathological T (pT)
The purpose of pathological classification is to provide The pathological assessment of the primary tumor generally
additional precise and objective data: is based on resection of the primary tumor.
• for prognosis and outcomes, and

• to guide subsequent therapy. Component of pT Description
Tumor size and Primarily based on size and local extension of
extent the resected specimen
The pathologist provides information to assign
Criteria for assigning pathological stage
the pT category based on the specimen
Component of received, but this may not be the final pT used
pathological staging Details for staging assignment. Final pT is assigned by
Assignment of Pathological stage is based on a the managing physician and also may include
pathological stage by synthesis of clinical and pathological clinical stage information and operative
managing physician findings and is assigned only by the findings.
managing physician, such as a surgical, Tumor size in Primary tumor size is the most accurate/largest
radiation, or medical oncologist. millimeters and dimension and is:
Primary tumor surgical The surgical resection criteria in the rounding for • measured to the nearest whole millimeter,
resection for pathological disease site must be met in order to T-category unless a smaller unit is specified in a
staging assign a pathological stage. The extent of assignment specific disease site, and
primary tumor surgical resection ranges • rounded up or down as appropriate for
from: assigning T category:
• resection of the tumor, up to ○ down when the numerals are between 1
• complete resection of the organ, and and 4
• usually includes resection of at least ○ up when the numerals are between 5
some regional lymph nodes and 9
Note: Surgical resection criteria depend Examples:
on the cancer site–specific information • Tumor measured as 2.2 mm is recorded as
necessary to determine the need for 2 mm.
adjuvant therapy and the patient's • Tumor measured as 1.7 mm is recorded as
prognosis, including tumor (T) and 2 mm.
regional nodes (N). • Tumor measured as 2.04 cm is recorded
Basis of pathological Pathological staging encompasses: as 20 mm, and would be grouped with
staging • clinical staging information ≤2 cm and not >2 cm
• the surgeon's operative findings Nonexhaustive exceptions:
• pathological evaluation of the • Melanoma: primary tumor measured to
resected specimen(s) nearest 0.1 mm
Imaging studies used in Imaging studies performed after surgery • Breast cancer: primary tumor >1.0 mm to
assigning pathological are included in the pathological staging 1.4 mm rounded to 2 mm (this avoids
stage if they are within the time frame or assigning the “microinvasion” category to
staging window. cancer >1.0 mm)
Component of pT Description Component of pT Description

Resection specimen pT category optimally is based on
role in pT category resection of a single specimen. If resected
Unresected tumor
and highest T
The pathological T (pT) category may be
assigned without tumor resection if:
1
in several partial specimens at the same or category • a biopsy of the primary tumor (cT) is
separate operative setting, a reasonable performed and is adequate to evaluate the
estimate of size and extension should be highest pT category.
made. Other criteria, such as microscopic
The estimate of multiple specimens may be confirmation of the highest pN, must be met in
based on the best combination of gross and order to assign pathological staging.
microscopic findings, and may include Disease sites have Some disease sites have specific rules to guide
reconstruction of the tumor with the assistance specific rules assignment of pT. Refer to specific disease site
of the radiologist and surgeon. See CAP chapters for further guidance.
Protocols for tumor-specific Unknown primary If there is no evidence of a primary tumor, or
recommendations. or no evidence of the site of the primary tumor is unknown,
Impact on pT The presence of microscopic cancer at the primary tumor staging may be based on clinical suspicion of
category of positive resection margin does not affect the the primary tumor, with the tumor categorized
resection margins assignment of the pT category, which is as T0. The rules for staging cancers categorized
assigned based on findings in the resection as T0 are specified in the relevant disease site
specimen and at operation. chapters.
In situations in which the surgeon has left Examples of exception: The T0 category is not
behind grossly identified tumor in performing used for head and neck squamous cancer sites,
a noncurative resection, the T category should as such patients with an involved lymph node
be based on all available clinical and are staged as unknown primary cancers using the
pathological information. system for cervical nodes and unknown primary
Pathological tumor Tumor size may vary based on whether it is tumors of the head and neck (T0 remains a valid
size variance based measured on an unfixed or a fixed category for HPV- and EBV-associated
on assessment specimen. Size is often reported on the oropharyngeal and nasopharyngeal cancers).
approach fixed specimen, and gross impression of Tis In situ neoplasia identified from a surgical
tumor size may be adjusted based on and surgical resection, as specified in the disease site
microscopic examination. The pathologist resection criteria pathological criteria, is assigned pTis.
should note potential alteration in tumor In situ neoplasia identified microscopically
size caused by fixation if it might affect during the diagnostic workup may be used to
staging. assign the pathological stage pTis if the patient
Synchronous For multiple tumors in a single organ, T is had a surgical resection and no residual tumor
primary tumors is a assigned to the highest T category; the was identified.
single organ: (m) preferred designation is: Use of pTX Since pathological assessment is generally based
suffix • m suffix; for example, pT3(m) N0 M0 on resection of the primary tumor, pTX is rarely
If the number of tumors is important, an appropriate. It may be assigned when relevant
acceptable alternative is: specimens are not available for examination by
• number of tumors; for example, pT3(4) the pathologist. It may also be assigned by the
N0 M0 pathologist for a subsequent resection or
Note: The (m) suffix applies to multiple multiple partial resections when tumor
invasive cancers. It is not applicable for fragmentation precludes assessment of the pT
multiple foci of in situ cancer, or for a mixed category. In such cases, the managing physician
invasive and in situ cancer. should assign the pT and the stage based on the
Direct extension If a primary tumor directly extends into a other available information.
into regional node regional lymph node, it is: pTX may not be assigned if the pathological
• included in the N category as a positive classification criteria of surgical resection,
regional lymph node specified in each chapter, has not been met.
• not included as a criterion for assigning Any T Any T includes all T categories except Tis.
the T category This includes TX and T0.
Tumor nodule in Rounded tumor nodules with smooth-
node area not contoured capsules in the regional nodal
considered in T drainage area generally represent lymph
category nodes completely replaced with cancer and athological N (pN)
P
are classified as lymph nodes, unless there is Pathological assessment of regional node involvement (pN)
clear evidence of residual blood vessel wall is necessary.
to justify classification as vascular
involvement. They are not considered in the
Component of pN Details
T category.
Microscopic Microscopic assessment of a regional node
Direct extension Direct extension of a primary tumor into a
assessment for pN includes:
into an organ contiguous or adjacent organ is classified as
• FNA cytology
part of the tumor (T) classification and is not
• Core biopsy
classified as metastasis (M).
• Incisional biopsy
Example: Direct extension of a primary colon
• Excisional biopsy
cancer into the liver is categorized as T4 and is
• SLN biopsy/procedure
not in the M category.
• Regional lymph node dissection
Component of pN Details Component of pN Details

Requirements for To assign a pN category, there must be: Tumor nodule in Rounded tumor nodules with smooth-
assigning pN • pathological documentation of the node area not contoured capsules in the regional nodal
category presence or absence of cancer in at least considered in T drainage area generally represent lymph
one node, and category nodes completely replaced with cancer and
• pathological assessment of the primary are classified as lymph nodes, unless there is
tumor (pT), except in cases of an clear evidence of residual blood vessel wall
unknown primary (T0) to justify classification as vascular
Note: It is not necessary to pathologically involvement. They are not considered in the
confirm the status of the highest N category to T category.
assign the pN. If pT is available (resection), Sentinel node or Microscopic examination of regional nodes
then any microscopic evaluation of nodes is regional node without resection of the primary site (during
classified as pN. For example, assessment of excision the diagnostic workup) is included in the
the axillary nodes is sufficient to assign pN for clinical classification as cN.
breast cancer, and it is not necessary to Microscopic examination of regional
microscopically confirm the status of nodes with surgical resection of the
supraclavicular nodes. primary site (surgical treatment) is
Many cancer sites have specific categorized as pN.
recommendations regarding the minimum Example: Sentinel node biopsy performed
number of lymph nodes to be removed during at the time of wide re-excision for
lymph node dissection to provide optimal melanoma (surgical treatment) is
prognostic information. However, pathological pathological (pN).
categorization (pN) still applies even in cases in SLN An SLN is a regional lymph node that
which fewer than the recommended number of receives direct afferent lymphatic drainage
lymph nodes are resected (e.g., a colon cancer from a primary tumor site (e.g., breast,
resection specimen with only four melanoma), and in many solid tumors
pathologically negative lymph nodes is represents the regional lymph node(s) most
categorized as pN0). likely to contain metastatic disease, if any
FNA and core needle biopsy of a node both are involved. More than one SLN may be
satisfy the requirement that at least one present in a regional nodal basin, and some
regional node be microscopically examined. primary tumors (e.g., melanoma) may
Categorize N pN generally is categorized by disease- drain to more than one regional nodal
specific rules based on: basin.
• number and/or Sentinel nodes are identified by lymphatic
• location of positive regional nodes and/ mapping, as evidenced by nodes that
or concentrate a colloidal material injected
• size of the largest deposit of tumor cells near the primary tumor or in the involved
in the node(s) organ (the most commonly used agents for
Size of regional Size of regional nodal metastasis generally is sentinel node biopsy are vital stains such as
nodal metastasis specified in disease site chapters and may be isosulfan blue and/or radiotracers such as
based on:
99
Tc-sulfur colloid). In some
• size of metastasis in the node, circumstances, the managing physician
• size of the lymph node, or also may label regional lymph nodes that
• size of the nodal mass, which may be a are palpably abnormal during surgery as
mass of matted nodes sentinel nodes.
For some disease sites, the size of tumor Nodes that do not concentrate colloidal
metastasis within the regional lymph node is material and are resected along with other
a criterion for the N category. If the size of sentinel nodes are nonsentinel nodes, and are
the tumor in the regional nodal metastasis is considered part of the sentinel node
unknown, the size of the involved lymph procedure. Their resection is not coded as a
node may be used. separate nodal procedure or a lymph node
The size of any mass, from a single node to a dissection.
conglomerate mass of matted nodes, is used Sentinel node (sn) If SLN biopsy is performed in the absence of
to determine the N category for some disease and FNA or core complete dissection of the nodal basin:
sites, such as head and neck. biopsy (f) • the N category should have the sn suffix;
Note: Please refer to disease site chapters for for example, pN0(sn).
specific criteria on assessment of size of If FNA or core biopsy is performed in the
regional nodal metastasis. absence of a complete dissection of the nodal
Direct extension into If a primary tumor directly extends into a basin:
regional node is N regional lymph node, it is: • the N category should have the f suffix;
category • included in the N category as a positive for example, pN0(f).
regional lymph node Note: This distinguishes it from a complete
• not included as a criterion for assigning nodal dissection, for which the pN is
the T category assigned without the (sn) or (f) suffix.
Component of pN Details Component of pN Details

ITCs: use of the (i+) ITCs include single tumor cells or small Regional node A regional node extending into a distant
designator clusters of cells ≤0.2 mm in greatest structure or organ is categorized as ENE and is
metastasis invading a
1
diameter, generally without stromal response distant organ is ENEnot considered distant metastatic disease.
in the lymph node. These cells usually are Recommended As noted in previous editions of the AJCC
found in the subcapsular nodal sinuses but minimum number of Cancer Staging Manual, as well as this 8th
may be seen within the nodal parenchyma. lymph nodes Edition, several cancer sites contain a
Because ITCs may represent tumor cells that recommendation regarding the minimum
are in transit that are not proliferating within number of regional nodes to be surgically
the node, lymph nodes with only ITCs resected and pathologically analyzed for
usually are categorized as N0, with some determination of the N category.
exceptions. They are denoted as N0(i+). These recommendations are offered as
The concepts regarding this staging rule metrics for evaluation of quality review of
continue to evolve, and further study is the extent of surgical resection and
warranted. In the meantime, the staging resultant pathological analysis. These
rule serves as a guideline for uniformity minimum benchmarks should not be
and consistency in practice in recording construed as unique indicators for
information, and clinical judgment by the additional surgical resection or adjuvant
managing physician prevails. therapy if the recommended nodal count
Exception: In melanoma and Merkel cell has not been met.
carcinoma, ITCs are considered positive In cases in which fewer than the
nodes and are designated as N1 or higher. recommended optimal number of lymph
Note: There are cancer site–specific nodes are removed, pathological node
designators to identify ITCs in nodes. category (pN) should be assigned and
Example: N0(i+) in breast and gynecologic complete pathological staging applied
cancers applies to nodes with ITCs only. based on whatever number of nodes are
Pathological ITCs or lymph node micro-metastases may reported. A suboptimal node count may
techniques for ITCs be identified in lymph nodes by hematoxylin lead to further dialogue between the
or detection of and eosin staining or by specialized surgeon and pathologist to support the
micro-metastasis pathological techniques, such as IHC for opportunity for further evaluation (e.g., fat
cytokeratin proteins for carcinomas. clearance techniques) of the node-bearing
Specialized pathology techniques such as specimen to assure that a maximum node
IHC and molecular techniques are not assessment is reached; however, this is not
recommended for routine examination of necessary to assign the pathological node
lymph nodes. category.
The concepts regarding this staging rule Node status not For some cancer sites in which lymph node
continue to evolve, and further study is required in rare involvement is rare, patients whose nodal
warranted. circumstances status is not determined to be positive for
Nonmorphologic If used, nonmorphologic techniques, tumor should be designated as cN0. These
techniques for including flow cytometry and reverse circumstances are identified in specific
identifying ITCs: use transcriptase polymerase chain reaction disease site chapters for these sites; NX may
of (mol+) designator studies, may identify minimal deposits of not be listed as a category.
cancer in lymph nodes. The assignment of cN0 will ensure it is not
These usually are classified as clinically node confused with a case in which the nodes were
negative and identified with the (mol+) microscopically proven to not contain tumor,
designator: for example, cN0(mol+). that is, pN0.
The concepts regarding this staging rule Examples: For bone and soft tissue sarcoma,
continue to evolve, and further study is cN0 may be used to assign the pathological
warranted. stage group—that is, pT1 cN0 cM0.
Micro-metastases: Lymph node micro-metastases are defined as For melanoma, cN0 may be used to assign a
use of mi designator tumor deposits >0.2 mm but ≤2.0 mm. For pathological stage group for T1 melanoma.
certain disease sites, micro-metastases are Regional node Tumor involving a regional node and
denoted by using the mi designator: for invading a distant extending into a distant structure or organ is
example, cN1mi. Further studies are needed organ categorized as ENE and is not considered
to determine the significance of micro- metastatic disease.
metastases across many cancer sites. Regional nodes when In the rare occurrence in which a tumor
The concepts regarding this staging rule a tumor involves involves more than one organ or structure,
continue to evolve, and further study is more than one organ the regional nodes include those of all
warranted. or structure involved structures, even if the nodes of the
Extranodal extension ENE is defined as the extension of a nodal primary site are not involved.
(ENE) metastasis through the lymph node capsule Example: If a transverse colon cancer
into adjacent tissues. ENE is the preferred invades the stomach, the gastric regional
terminology. It is sometimes also termed nodes would be considered regional for the
extranodal spread, extracapsular extension, transverse colon, even if the colon regional
or extracapsular spread. nodes were not involved.
Component of pN Details Component of M for

Unresectable tumor If the primary tumor and/or regional lymph pathological staging Details
and highest N nodes technically cannot be removed or it is In general, metastases to both sides
category clinically not indicated to remove them, the of a paired organ are considered a
following criteria may be used to assign single metastatic site of involvement
pathological stage: (e.g., metastases to both lungs are
• microscopically confirmed highest T assigned as metastasis to one distant
category, and site—lung).
• microscopically confirmed single node or If clinical evidence of distant
nodes in the highest N category metastasis remains in other areas that
Note: Microscopic confirmation of the are not or cannot be microscopically
highest T and N categories may use biopsy or confirmed, cM1 is assigned.
FNA only. pM1 may be used for both pM1
Any N Any N includes all N categories. This clinical and pathological A patient may be staged as both
includes NX and N0. Stage IV clinical and pathological Stage IV if
there is:
• confirmatory microscopic
athological M Categorization (cM and pM)
P evidence of a distant metastatic
Any of the M categories (cM0, cM1, or pM1) may be used site during the diagnostic workup,
which is categorized as pM1, and
with pathological stage grouping. The terms pM0 and MX • T and N may be categorized only
are NOT valid categories in the TNM system. clinically.
Example: cT3 cN1 pM1 clinical Stage
IV, and cT3 cN1 pM1 pathological
Component of M for Stage IV
pathological staging Details Circulating tumor cells and cM0(i+)
No distant metastasis cM0 disseminated tumor cells: Patients with
If there are no symptoms or signs of cM0(i+) category • CTCs, or
distant metastasis, the case is classified • DTCs in organs and micro-
as clinically M0 (cM0). Evaluation metastasis in bone marrow, detected
includes: by IHC or molecular techniques,
• history and physical examination are categorized as cM0(i+).
• imaging studies performed The cM0(i+) category denotes the
Note: Imaging studies are NOT uncertain prognostic significance of
required to assign cM0. these findings.
The concepts regarding this staging
Clinical evidence of distant cM1
rule continue to evolve, and further
metastasis Patients with clinical evidence of
study is warranted.
distant metastases by history, physical
examination, imaging studies, or Clinical suspicion of If there is clinical suspicion of
invasive procedures, but without metastasis, but biopsy does distant metastases and a biopsy or
microscopic evidence of the presumed not confirm distant excision does not confirm metastatic
distant metastases, are categorized as metastatic disease cancer, M is classified as clinically
clinically M1 (cM1). Examination M0 (cM0) or clinically M1 (cM1)
methods include: based on the evaluation of other
• physical examination possible sites of distant metastatic
• imaging disease. There is no TNM pM0
• exploratory surgery or endoscopy designation.
Note: pM0 is not a valid category
Microscopic evidence of pM1
If clinical evidence of distant
distant metastasis Patients in whom there is microscopic
metastasis remains in other areas that
evidence confirming distant metastatic
are not or cannot be microscopically
disease are categorized as
confirmed, cM1 is assigned.
pathologically M1 (pM1).
Microscopic evidence includes: Unknown distant metastasis MX does not exist
• cytology from FNA status MX is not a valid category and cannot
• core biopsy be assigned. Unless there is clinical or
• incisional biopsy pathologic evidence of metastases, M
• excisional biopsy is categorized as clinically negative:
• resection cM0.
Use of pM1 if there are pM1 No direct extension in M Direct extension from the primary
multiple distant metastases In patients who have distant metastases category tumor or lymph nodes into a contiguous
in multiple sites, and have a cancer or adjacent organ is not included in the
type for which M subcategories M category but is used in the T and N
distinguish between one or more category assignments as noted earlier.
metastatic sites, microscopic evidence Example: Direct extension of a colon
of one of these sites is necessary to cancer into the liver is categorized as
assign the higher pM subcategory. pT4 and cM0.
osttherapy or Post Neoadjuvant Therapy

P apy, hormone therapy, and immunotherapy. Not all medica-
Classification (yTNM) tion given to a patient meets the criteria for neoadjuvant
1
therapy (e.g., a short course, such as a few days of endocrine
For purposes of posttherapy or post neoadjuvant therapy therapy in breast cancer or prostate cancer that is provided
classification, neoadjuvant therapy is defined as systemic for variable and often unconventional reasons, should not be
and/or radiation therapy given before surgery; primary radia- categorized as neoadjuvant therapy).
tion and/or systemic therapy is treatment given as definitive The time frame should be such that the post neoadjuvant
therapy without surgery. therapy surgery and staging occur within a period that
Classification of T, N, and M after systemic or radiation accommodates disease-specific circumstances, as outlined in
treatment intended as definitive therapy, or after neoadjuvant the specific chapters and in relevant guidelines.
therapy followed by surgery, is denoted by use of a lower- The post neoadjuvant therapy assessment of the T and N
case yc or yp prefix, respectively: ycT, ycN, c/pM, and ypT, (yTNM) categories uses specific criteria. In contrast, the M
ypN, c/pM, respectively. The c/pM category may include category for post neoadjuvant therapy classification remains
cM0, cM1, or pM1. the same as that assigned in the clinical stage before initia-
tion of neoadjuvant therapy (e.g., if there is a complete clini-
yc cal response to therapy in a patient previously categorized as
Time frame: After primary systemic and/or radiation cM1, the M1 category is used for final yc and pc staging).
therapy without subsequent surgical resection, or after neo-
adjuvant and before planned surgical resection
Criteria: First therapy is systemic and/or radiation therapy.
y-clinical (yc) classification is based on the: Component of
posttherapy staging Details
Assignment of stage Posttherapy or post neoadjuvant therapy stage
• clinical history and physical examination and by managing is based on a synthesis of clinical and
• any imaging studies, if performed physician pathological findings and is assigned only by
the managing physician, such as a surgical,
Note: imaging studies may be considered standard prac- radiation, or medical oncologist.
Pathologists may provide T, N, and M
tice, but are NOT required to assign yc categories. information based on the specimens received
to assist the managing physician in assigning
yp the final stage.
Time frame: The yp classification is used when staging Radiologists may provide T, N, and M
information based on imaging studies to assist
after neoadjuvant therapy and planned post neoadjuvant the managing physician in assigning the final
therapy surgery. The time frame should be such that the post stage.
neoadjuvant therapy surgery and staging occur within a Use of yTNM To use the yTNM classification, the extent of
period that accommodates disease-specific circumstances, as disease is assessed:
• after systemic and/or radiation therapy as
outlined in the specific chapters and in relevant guidelines.
the primary treatment, and
Criteria: First therapy is systemic and/or radiation ther- • after surgery when it follows the
apy followed by surgery. systemic and/or radiation therapy
y-pathological (yp) classification is based on the: Use of y prefix The y prefix is always combined with either a
clinical or pathological prefix, that is, ycTNM
or ypTNM.
• y-clinical stage information, and supplemented/modified by
Time frame in the • ycTNM denotes information gathered
• operative findings, and patient's care for use using clinical classification rules and
• pathological evaluation of the resected specimen. of yc and yp methods:
○ after neoadjuvant systemic and/or
Observed changes between the clinical classification and radiation therapy, and
○ before surgical resection or if no
the posttherapy classification may provide clinicians with
surgery is performed.
information regarding the response to therapy. The clinical • ypTNM denotes information gathered
extent of response to therapy may guide the scope of planned using pathological classification rules and
surgery, and the clinical and pathological extent of response methods:
○ after neoadjuvant systemic and/or
to therapy may provide prognostic information and guide the
radiation therapy, and
use of further adjuvant radiation and/or systemic therapy. ○ after the surgical resection.
Examples of treatments that satisfy the definition of neo- Examples:
adjuvant therapy for a disease site may be found in sources • ycT and ycN with cM or pM
• ypT and ypN with cM or pM.
such as the NCCN Guidelines, ASCO guidelines, or other
treatment guidelines. Systemic therapy includes chemother-
Component of been considered cancer-free (disease-free interval), or if the

posttherapy staging Details cancer progresses and the patient has never been disease-free
Distant metastasis The presence of distant metastases is (even if no retreatment is planned).
classified by the M status defined during the
Assessment of recurrence and retreatment follows spe-
clinical classification, cM or pM, before
initiation of neoadjuvant radiation and/or cific criteria.
systemic therapy.
Note: Once distant metastasis is identified, that Recurrence/retreatment staging assessment criteria
M category designation always remains, even Component of
if there no longer is evidence of the metastasis recurrence/
after neoadjuvant therapy. In this situation, the retreatment staging Details
yc and yp stages always maintain the M1 Stage at initial The initially assigned clinical and
category. diagnosis is not pathological stages at diagnosis do not
Complete If a complete pathological response has affected by recurrence change if a cancer recurs or progresses.
pathological occurred and the ypTNM is ypT0 ypN0 cM0, Use of r prefix In staging for recurrence or retreatment, the
response no stage group is assigned. r prefix is applied.
Note: This situation is not classified as Stage
Information included: r All information available at the time of
0, because such a designation would denote
classification recurrence or retreatment should be used to
in situ neoplasia. Nonetheless, the individual
determine the rTNM stage, including
T, N, and M categories should be documented
clinical and pathological information.
as T0, N0, M0.
Important: Biopsy confirmation is not
The complete pathological response also may
required but is encouraged if clinically
be documented by using the response
feasible.
designation.
Response to It is important to record the response to rc
neoadjuvant therapy neoadjuvant therapy. Consult disease site The r-clinical (rc) classification is based on:
chapters for specific systems. • clinical history and physical
For example, some disease sites include examination and
“complete,” “partial,” and “no response,” • any imaging studies, if performed
whereas others consist of a numerical scoring Note: Imaging studies may be considered
system or a “regression score.” standard practice but are NOT required to
If surgery is performed, it is critical to also assign rc categories.
assign the ypT and ypN for analysis of
rp
response to neoadjuvant therapy.
The r-pathological (rp) classification is
Mucin pools, Histologic confirmation of residual cancer based on:
necrosis, and other requires identification of non-necrotic tumor • r-clinical stage information, and
reactive changes not cells. supplemented/modified by
included in the Mucin pools, necrosis, and other degenerative • operative findings, and
assessment of and reactive changes without viable-appearing • pathological evaluation of the resected
residual cancer tumor cells are insufficient for a diagnosis of specimen.
residual cancer. Mucin pools and necrotic
cells currently play no role in assigning the
ypT and ypN.
Autopsy Classification (aTNM)
Classification of T, N, and M at autopsy is denoted by use of

the lowercase a prefix: aT, aN, aM.
ecurrence or Retreatment Classification
R Time frame: At death
(rTNM) Criteria: Incidental finding of cancer at autopsy; cancer
not suspected or evident before death (i.e., classification
Classification of T, N, and M for recurrence or retreatment is does not apply if autopsy is performed in a patent with a
denoted by use of the lowercase r prefix: rcT, rcN, rc/rpM, known cancer before death).
and rpT, rpN, rc/rpM. The rc/rpM may include rcM0, rcM1, Autopsy assessment has specific criteria.
or rpM1.
Time frame: From identification of recurrence or pro- Component of autopsy
gression until treatment is initiated for rc, and from identifi- staging Details
cation of recurrence or progression through surgical resection Diagnosis at autopsy Cancer must be diagnosed at autopsy.
for rp No prior suspicion or evidence of cancer
before death.
Criteria: Disease recurrence after disease-free interval,
Information included All clinical and pathological information
or disease progression is included. It is obtained:
The recurrence or retreatment classification is assigned if • at time of death, and
a cancer recurs after an interval during which the patient has • through postmortem examination.
AJCC PROGNOSTIC STAGE GROUPS Rules for assigning prognostic stage groups (stage groups)
Component of
prognostic stage
1
Cancer patients with similar prognoses are grouped by using
group Rule(s)
prognostic stage group tables. Clinical and pathological
Assigning stage with A presumptive stage to facilitate patient
stage groups are defined for each case as appropriate. These incomplete management may be used by the treating
disease-specific groups are composed of the following information physician/management team. This is not a
categories: formal stage classification type in the TNM
system. It is only for physician use in patient
care. It should never be documented by
• cT, cN, and cM or pM cancer registries.
• pT, pN, and cM or pM During the diagnostic workup, the managing
• factors for both groups, if applicable physician may assign a preliminary clinical
stage based on the information known at that
time, and may continually update the stage as
Stage group assignment follows specific rules. the workup progresses. This approach
commonly is used for cancer conferences
(tumor boards) and other medical conversations.
Once the final clinical stage is determined, these
Rules for assigning prognostic stage groups (stage groups)
preliminary stages no longer are used and are
Component of replaced by the clinical stage. The stage(s)
prognostic stage provisionally assigned during the diagnostic
group Rule(s) workup may be referred to as the presumptive
Prognostic stage Prognostic stage groups are based on stage(s).
groups combinations of T, N, M, and relevant In patient care, it may be appropriate for the
prognostic factors and usually define groups managing physician to combine clinical and
of patients with similar outcomes to help pathological T and N categories if only partial
define prognosis and appropriate treatment, information is available in the pathological
as well as to enable comparisons of similar classification. Although this strategy may be
groups of patients between institutions and used to plan treatment and to provide the
over time. patient with a stage group and prognosis, it
Categories and When a category (e.g., T1) is identified in the does not represent the actual TNM stage and
subcategories stage group table, it includes all subcategories therefore is not used to assign a stage group.
(e.g., for T1, this may include T1mi, T1a, Missing/unknown If a required prognostic factor category is
T1b, etc.). prognostic factor unavailable, the patient may still be staged.
However, If the specific subcategories are The stage group assigned is the:
listed separately (e.g., T1a, T1b, N1mi), only • group containing the prognostic factor X
the specific subcategory is included in the category, or
stage group. • anatomic stage, assigned by default
Unknown T or N A stage group cannot be assigned if X is used using clinical judgment
for either T or N. If a prognostic factor is X, pM1 in stage groups If a patient has microscopic confirmation of
it should be assigned based on TNM. distant metastases (pM1) during the
Exception: Stage IV is always assigned if diagnostic workup, the patient may be
there is: classified as clinical Stage IV and
• evidence of distant metastasis (cM1 or pathological Stage IV, regardless of whether
pM1), even if the T or N category is the T and N are classified by clinical or
unknown (TX or NX). pathological means.
Stage may be assigned if the TNM stage Example: For pM1 and cT and cN, the
group results in Any T or Any N with patient may be assigned both:
M0, which includes TX or NX. Examples • clinical stage group, and
include: • pathological stage group
• TX N1 M0 Stage III in melanoma Note: This rule does not apply to patients
clinical stage with clinical metastases without microscopic
• T4 NX M0 Stage III in pancreatic cancer confirmation. These patients may be staged
Stage documentation The patient's medical record should be only clinically.
in the medical record updated with any applicable stage group cM or pM used in all cM0, cM1, or pM1 may be used in any of the
information as it is available, including: stage groups following stage groups:
• clinical • clinical stage group
• pathological • pathological stage group
• posttherapy or post neoadjuvant therapy • post neoadjuvant therapy or primary
• recurrence or retreatment radiation/systemic therapy clinical stage
• autopsy group
Once assigned according to the appropriate • post neoadjuvant therapy pathological
rules and timing, the documented stage group stage group
does not change. • recurrence or retreatment stage group
Rules for assigning prognostic stage groups (stage groups) Rules for assigning prognostic stage groups (stage groups)
Component of Component of
prognostic stage prognostic stage
group Rule(s) group Rule(s)
Microscopic If the highest T and N categories of the tumor In melanoma, patients with histologically
evaluation without are confirmed microscopically, the criteria for documented melanoma in situ disease only
resection for pathological staging have been satisfied. may develop regional metastasis.
assigning This may occur if a primary tumor Biologically, this may represent melanoma
pathological technically cannot be removed or if it is metastasis associated with a regressed
classification unreasonable to remove it, but the criteria for primary, which may be associated with the
pathological staging have been satisfied Tis lesion or may be a completely regressed
without total removal of the primary tumor. tumor (i.e., unknown primary). The stage
Note: Microscopic confirmation of the may be assigned by the managing physician
highest T and N does not necessarily require as Tis N1-3 M0 with a stage group based on
removal of that structure and may include the N category as available for patient care.
biopsy or FNA only. Please refer to disease Note: Rarely, patients with a resected cancer
sites for specific guidelines. showing only in situ disease (Tis) have
In situ neoplasia, In situ neoplasia identified microscopically metastatic cancer in regional lymph nodes.
Stage 0 for clinical during the diagnostic workup is assigned as This mostly involves breast cancer (ductal
classification cTis cN0 cM0 clinical Stage 0. carcinoma in situ), although it is still rare.
In situ neoplasia, In situ neoplasia is an exception to the stage The common theory is that the node
Stage 0 does not grouping guidelines that otherwise require metastases come from an unidentified occult
require node regional lymph node evaluation for invasive cancer. For clarity in registry
evaluation for pathological classification. By definition, operations and to allow study of these
pathological in situ neoplasia has not involved any patients in the future, such cases should be
classification structures in the primary organ that would categorized as:
allow tumor cells to spread to regional nodes • Tis N1 (or N2/N3 as appropriate).
or distant sites. • These cases cannot be assigned a stage
The primary tumor surgical resection criteria group in the registry database.
for pathological stage must be met in order to Clinicians should use careful judgment in
assign pathological Stage 0. counseling patients with this unusual finding.
Lymph node microscopic assessment is not Uncertainty in If uncertainty exists regarding the stage
necessary to assign pathological Stage 0 for assigning stage group, the lower or less advanced of two
in situ neoplasia; for example, pTis cN0 cM0 group possible stage groups should be assigned.
is staged as pathological Stage 0. Note: This rule does not apply to situations in
Notes: which not enough information is available to
• In situ neoplasia includes carcinoma allow staging, such as cases with unknown T
in situ (CIS) and other in situ neoplasia. (TX) or unknown N (NX).
• Disease sites having two Stage 0 groups Complete If a complete pathological response has
usually are denoted as 0is and 0a. pathological occurred and the ypTNM is ypT0 ypN0 cM0,
Noninvasive, Stage Ta is assigned for noninvasive papillary response no stage group is assigned.
0a carcinoma in the renal pelvis and ureter, Note: This situation is not classified as Stage
urinary bladder, and urethra. The stage group 0, because such a designation would denote
usually is 0a. in situ neoplasia. Nonetheless, the individual
The same rules apply to noninvasive tumors T, N, and M categories should be documented
as those for in situ neoplasia. as T0, N0, M0
Noninvasive papillary carcinoma identified
microscopically during the diagnostic workup
is assigned as cTa cN0 cM0 clinical Stage 0a.
Noninvasive papillary carcinoma identified
on surgical resection meeting the criteria for DDITIONAL STAGING DESCRIPTORS
A
pathological stage is assigned as pTa cN0
cM0 pathological Stage 0a.
AND GUIDELINES
Tis N1–3 In rare situations, whenever the pathology
fails to reveal invasive cancer and shows Tis N Suffixes: Sentinel Node Suffix (sn) and FNA
only with nodal involvement, the stage group or Core Biopsy (f)
may be assigned by the managing physician
based on the N category as available for
patient care. The cancer registry should
Node category suffixes are used to indicate the method of
document Tis with the appropriate N category assessment, which may have implications for the complete-
and no stage group. ness of the pathological review.
Component of N suffix Description Component of N suffix Description

Sentinel node procedure
indication (sn)
If a regional lymph node metastasis is
identified by SLN biopsy only, and
• surgical resection with lymph node
dissection performed, it is assigned
1
additional surgery in the form of a pN1.
completion lymph node dissection is not • diagnostic workup, it is assigned
performed, the N category is assigned cN1(f) for clinical stage; if lymph
with the addition of the (sn) suffix: for node dissection is performed as a
example, cN1(sn) or pN1(sn). component of the surgical resection
Time frame for cN(sn) If the sentinel node procedure is of the primary site, it is assigned
and pN(sn) performed as: pN1 for pathological stage.
• part of the diagnostic workup and
before definitive surgical treatment,
in which case the proper assignment Guidelines for Primary Cancers
is cN1–3(sn), or
• part of initial surgical management,
in which case the proper assignment
Multiple Primary Tumors
is pN1–3(sn). Multiple cancers may occur in the same organ and may be
Note: If the patient has a completion diagnosed at or about the same time (synchronous) or at sep-
lymph node dissection performed as a arate time points (metachronous). For the purpose of staging,
component of the initial surgical
management, the suffix is not used.
the following definitions apply.
(sn) suffix in clinical and If a sentinel node biopsy is performed as
pathological a component of the: Synchronous Primary Cancers
classifications • diagnostic workup, it is assigned
cN1(sn).
• surgical resection procedure and no Component of synchronous
additional (e.g., completion) lymph cancers Description
node dissection is performed, it is
Timing for synchronous Cancers occurring in the same organ
assigned pN1(sn).
cancers (including paired organs) that are
• surgical resection procedure and a
identified with a diagnosis date
completion lymph node dissection
≤4 months apart, or that are
is performed, it is assigned pN1.
identified at the time of surgery for
• diagnostic workup, it is assigned
the first cancer if that surgery is part
cN1(sn) for clinical stage, and if
of the planned first course of therapy
completion lymph node dissection is
performed during surgical resection Multiple synchronous tumors Multiple synchronous tumors:
of primary site, it is assigned pN1 • are cancers of the same histology
for pathological stage. • occur in one organ
FNA or core biopsy An FNA or core needle biopsy is Synchronous primary tumors For multiple tumors in a single
indication (f) denoted by the (f) suffix, if no further in a single organ organ, T is assigned to the highest T
resection of the nodes is performed. category; the preferred designation
FNA or core biopsy meets the criterion is:
for microscopic examination of one node • m suffix; for example, pT3(m)
for assigning the pN category. N0 M0.
If the number of tumors is
Time frame for use of (f) If the FNA/biopsy procedure is
important, an acceptable alternative
suffix performed as:
is:
• part of the diagnostic workup before
• number of tumors; for example,
treatment, it is assigned cN1–3(f).
pT3(4) N0 M0.
• part of primary site surgical resection,
Note: The (m) suffix applies to
then it is assigned pN1–3(f).
multiple invasive cancers. It is not
Note: If the patient subsequently
applicable to multiple foci of in situ
undergoes a completion lymph node
cancer or to mixed invasive and
dissection as a component of the initial
in situ cancer.
surgical management, the suffix is not
used. Synchronous primary tumors Cancers occurring at the same time
in paired organs in each of paired organs are staged
(f) suffix in clinical and If FNA or core biopsy of regional lymph
as separate cancers. Examples
pathological nodes is performed as a component of:
include breast, lung, and kidney.
classifications • diagnostic workup, it is assigned
Exception: For tumors of the
cN1(f).
thyroid, liver, and ovary, multiplicity
• surgical resection of primary with
is a criterion of the T category and is
no lymph node dissection
not independently staged.
performed, it is assigned pN1(f).
Multiple Synchronous Tumors, Suffix (m) Component of T0 Description

• metastatic melanoma is found in lymph
Component of T suffix Description nodes with no apparent primary skin lesion.
(m) suffix for For multiple tumors in a single organ, T is Note: The T0 category was eliminated for
synchronous primary assigned to the highest T category; the head and neck squamous cell cancer, except
tumors in single organ preferred designation is: that T0 remains a valid category for HPV-
• m suffix; for example, pT3(m) N0 and EBV-associated oropharyngeal and
M0. nasopharyngeal cancers.
If the number of tumors is important, an cT0 and pT0 cT0
acceptable alternative is: If physical examination, imaging, endoscopy,
• number of tumors; for example, and other diagnostic procedures do not
pT3(4) N0 M0. identify a primary tumor:
Note: The (m) suffix applies to multiple • the T category is assigned as cT0.
invasive cancers. It is not applicable to
multiple foci of in situ cancer or to mixed pT0
invasive and in situ cancer. If after surgical resection of a suspected primary
tumor no evidence of tumor is identified, and it
was never identified on biopsy:
• the T category is assigned as pT0.
No information on T0 is not used for a cancer whose site of
Metachronous Primary Cancers primary tumor site of origin cannot be determined.
origin Example: Poorly differentiated carcinoma
Component of with histology that is not specific for a
metachronous cancers Description particular primary, and for which no actual
Timing for metachronous Cancers occurring in the same organ site is identified. This is designated as an
cancers system that are identified with unknown primary and cannot be staged.
diagnosis dates >4 months from each
other, except for cancers identified at
the time of surgery for the first cancer Histologic and Specimen Descriptors
occurring >4 months after the
diagnosis of the first cancer if that
surgery is part of the planned first Histopathologic Type
course of therapy Histopathologic type is determined by microscopic assess-
Metachronous primaries Metachronous primaries are primary ment whereby a tumor is categorized according to the normal
cancers:
tissue type or cell type it most closely resembles (e.g., hepa-
• occurring at different times in the
same or different organs. tocellular or cholangiocarcinoma, osteosarcoma, squamous
Staging A metachronous primary is staged as a cell carcinoma).
new cancer by using the applicable
TNM disease site system. Component of histology Description
Previous treatment of the Second cancers in the same organ Resource The World Health Organization
organ occurring after treatment of the original Classification of Tumours, published in
cancer are staged as new cancers and numerous anatomic site-specific
are not staged using the y prefix. editions, is used most commonly for
histopathologic typing.
Histology codes for Each chapter in the AJCC Cancer
staging Staging Manual includes the applicable
WHO and ICD-O-3 histology codes. If
ancers of Unknown Primary Site
C a specific histology is not listed, the case
There is no evidence of a primary tumor, but the anatomic should not be staged using the AJCC
site is suspected. classification in that chapter.
Histologies appropriate for clinical use in
patient care, using current preferred
Component of T0 Description terminology from the WHO and ICD-O-3,
T0 T0 is assigned if there is clinical suspicion of are listed in each chapter. Also included are
a primary tumor, with evidence of regional histologies requested by the surveillance
or distant metastases, but there is: community to reduce the number of
• no evidence of a primary tumor, or unstaged cases in population-based data.
• the site of the primary tumor remains These are denoted with an asterisk and
unknown. italicized in the histology code table. These
Example: T0 N1 M0 is assigned if: additional histologies represent vague or
• metastatic adenocarcinoma in axillary non-specific information such as
lymph nodes is pathologically carcinoma, NOS; more specific terms using
consistent with breast cancer, and there features no longer part of current
is no apparent primary breast tumor or terminology; and other non-standard or
other primary tumor site outdated histologic terms.
Caution should be used when analyzing
data using these different histologies.
Component of histology Description Lymphovascular Invasion

Behavior The behavior code is appended to the This descriptor indicates whether microscopic lympho- 1
histology code based on the vascular invasion (LVI) is identified in the cancer as
pathologist’s determination of benign
recorded in the pathology report. LVI includes lymphatic
(/0), malignant (/3), in situ (/2), or
uncertain malignant potential (/1). invasion, vascular invasion, and lymphovascular invasion.
This coding convention has been developed and
implemented for use in the 8th Edition for appropriate dis-
Grade (G) ease sites.
The grade of a cancer is a qualitative assessment of the
degree of differentiation of the tumor. It may reflect the Component of LVI coding Description
extent to which a tumor resembles the normal tissue at that 0 LVI not present (absent)/not
identified
site. Grade may provide important information on the risk of
1 LVI present/identified, NOS
cancer metastasis and prognosis.
2 Lymphatic and small vessel invasion
only (L)
Component of grade Description
3 Venous (large vessel) invasion
Histologic grade Historically, stratification of solid only (V)
stratification tumors has sometimes included an
4 BOTH lymphatic and small vessel
assessment of the overall histologic
AND venous (large vessel)
differentiation of the cancer. The most
invasion
common grading schema uses numeric
grades from the most or well 9 Presence of LVI unknown/
differentiated (grade 1) to the least indeterminate
differentiated (grade 3 or 4). This system
is still used in some cancer types, The concepts regarding this staging rule continue to evolve, and further
although site-specific grading systems study is warranted.
are used more commonly.
Disease site–specific The recommended grading system for
histologic grade each cancer type is specified in each
stratification chapter and is the grading system to be esidual Tumor and Surgical Margins
R
used by the pathologist and documented The absence or presence of residual tumor after treatment is
in the cancer registry. described by the symbol R (capital R). cTNM and pTNM
For many cancer types, more precise and
describe the extent of cancer in general without consider-
reproducible grading systems have been
developed beyond the standard systems, ation of treatment. cTNM and pTNM may be supplemented
and these may incorporate more specific by the R designation to categorize the absence or presence of
and objective criteria based on single or residual tumor status after treatment.
multiple characteristics of the cancers.
It is important to note that the R designation is not incor-
These factors include nuclear grade,
number of mitoses identified porated into TNM staging itself. However, the absence or
microscopically (mitotic count), and presence of residual tumor and status of the margins may
measures of histologic differentiation provide important information that affects subsequent treat-
(e.g., tubule formation in breast cancer),
ment and prognosis and may be recorded in the medical
among others.
For some cancer types, these systems record and cancer registry.
have been fully validated and largely The absence or presence of residual tumor at the pri-
implemented worldwide. Examples mary tumor site after treatment is denoted by the symbol
include the Gleason scoring system and
R. The R categories for the primary tumor site are as
the grade grouping for prostate cancer
and the Scarff–Bloom–Richardson follows:
(Nottingham) grading system for breast
cancer.
Histologic grade if more If there is evidence of more than one R R Definition
than one grade is noted grade or level of differentiation of the RX Presence of residual tumor cannot be assessed
tumor, the highest grade is recorded, R0 No residual tumor
assuming that the recommended grading
R1 Microscopic residual tumor
system was used for both biopsy and
resection. R2 Macroscopic residual tumor at the primary cancer site or
regional nodal sites (This designation is not used to indicate
Cancer registry The cancer registry must record the
metastatic disease identified but not resected at surgical
documentation grade as specified in the disease site
exploration.)
chapter, according to the rules only
in this chapter and the disease site
chapter.
Component of residual esponse to Neoadjuvant Therapy Assessment

R
tumor and margins Description Specific guidance for pathologists may assist in determining
Causes of residual tumor In some patients treated with surgery the response to neoadjuvant therapy. Additional information
and/or neoadjuvant therapy, residual
on reporting the response to therapy for some specific cancer
tumor may persist at the primary site
and/or regional sites of disease after types is provided in the respective disease site chapters.
such treatment as a result of
incomplete resection (i.e., the tumor Component of response
may extend beyond the limit or to therapy Description
ability of resection). Response to neoadjuvant It is important to record the response to
Indications of residual tumor The presence of residual tumor may: therapy neoadjuvant therapy. Consult disease site
• indicate the effect of therapy chapters for specific systems.
• influence further therapy For example, some disease sites include
• be a strong predictor of prognosis “complete,” “partial,” and “no response,”
Indicator of risk The presence or absence of disease whereas others consist of a numeric
at the margin of resection may be a scoring system or a “regression score.”
predictor of the risk of recurrent If surgery is performed, it is critical to
cancer. also assign the ypT and ypN for analysis
The presence of residual disease or of response to neoadjuvant therapy.
positive margins may be more likely Mucin pools, necrosis Histologic confirmation of residual
with more advanced T- or and reactive changes not cancer requires identification of
N-category tumors. included in the non-necrotic tumor cells.
Margin status following tumor Margin status after tumor resection assessment of residual Mucin pools, necrosis, or degenerative
resection is based on the pathology report cancer and reactive changes without viable-
(and correlation with the operative appearing tumor cells are insufficient
report if necessary) and should be for a diagnosis of residual cancer.
recorded by using the following Mucin pools and necrotic cells
categories: currently play no role in assigning the
• negative margins (tumor not ypT and ypN.
present at the surgical margin)
• microscopic positive margin
(tumor not identified gvrossly at
the margin, but present
microscopically at the margin).
For rare sites, definitions of
margin positivity may vary, and
relevant interpretation is specified
in the respective chapter.
• macroscopic positive margin
(tumor identified grossly at the
margin)
• margin not assessed

Principles of Cancer Staging

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Principles of Cancer Staging

INTRODUCTION AND OVERVIEW  hilosophy of Revisions to the TNM Staging

To access the AJCC cancer staging forms, please visit www.cancerstaging.org.

© American College of Surgeons 2017 3

Staging requires the collaborative effort of many profes-

Autopsy (aTNM) information, supplemented by selected prognostic factors in

Defining T, N, M, and Prognostic Factor

information from multiple sources, including clinical data, Elements of

This category… Is defined by… Distant Metastasis (M) Categories

Categorizing regional lymph node involvement depends on Unknown Designation: X

GENERAL STAGING RULES

Classification Designation Details

Classification Designation Details

Clinical Classification therapy, and response to treatment varies. Differences in

Criteria: All patients with cancer identified before  linical T (T or cT)

• clinical history and symptoms

Component of cT Details  linical N (N or cN)

Component of cN Details Component of cN Details

 linical M Classification (cM and pM)

Pathological Classification Criteria for assigning pathological stage

• for prognosis and outcomes, and

Component of pT Description Component of pT Description

Component of pN Details Component of pN Details

Component of pN Details Component of pN Details

Component of pN Details Component of M for

 osttherapy or Post Neoadjuvant Therapy

Component of been considered cancer-free (disease-free interval), or if the

Classification of T, N, and M at autopsy is denoted by use of

Component of N suffix Description Component of N suffix Description

Multiple Synchronous Tumors, Suffix (m) Component of T0 Description

Component of histology Description Lymphovascular Invasion

Component of residual  esponse to Neoadjuvant Therapy Assessment

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INTRODUCTION AND OVERVIEW hilosophy of Revisions to the TNM Staging

Autopsy (aTNM) information, supplemented by selected prognostic factors in

Defining T, N, M, and Prognostic Factor

This category… Is defined by… Distant Metastasis (M) Categories

Categorizing regional lymph node involvement depends on Unknown Designation: X

GENERAL STAGING RULES

Clinical Classification therapy, and response to treatment varies. Differences in

Criteria: All patients with cancer identified before linical T (T or cT)

Component of cT Details linical N (N or cN)

linical M Classification (cM and pM)

Pathological Classification Criteria for assigning pathological stage

osttherapy or Post Neoadjuvant Therapy

Component of histology Description Lymphovascular Invasion

Component of residual esponse to Neoadjuvant Therapy Assessment