世界卫生组织TNM分期更新内容

TNM Seventh Edition:What’s New,What’s Changed

Communication From the International Union Against Cancer and the American Joint Committee on Cancer

Leslie H Sobin,MD 1and Carolyn https://www.360docs.net/doc/7515719370.html,pton,MD,PhD 2,3

The seventh edition of the TNM Classification of Malignant Tumors (TNM-7)1,2contains several new and modified

component classifications.The purpose of this communication was to briefly summarize these changes,which became effective in January 2010.Among the new classifications are adrenal cortical carcinoma,appendiceal carcinoma,extrahe-patic bile duct carcinoma,esophagogastric junction carcinoma,gastrointestinal stromal tumors (GISTs),intrahepatic cholangiocarcinoma,melanoma of the upper aerodigestive tract,Merkel cell carcinoma,neuroendocrine tumors of the lung and gastrointestinal tract,and uterine sarcomas.Among the classifications with major alterations are carcinomas of the esophagus,stomach,lung,skin,vulva,and prostate.In addition,there are several general rules that have been modified or established.

MX

The category ‘‘MX:Distant metastasis cannot be assessed’’has been a source of misinterpretation and its use,3especially by pathologists (ie,pMX),has had the unintended consequence of preventing stage grouping by cancer registries.Cancer regis-trars do not stage a case if distant metastasis cannot be assessed.Surgical pathologists,when assessing a resected specimen,usually have sufficient information to provide a pT and a pN classification,but rarely have information regarding distant metastasis.Consequently,they may assign MX,meaning that they cannot assess distant metastasis.However,it is the patient’s clinician,not the pathologist,who is in the position to make this assessment,usually by clinical examination.If there are no obvious signs of metastasis,M0or cM0classifications are appropriate.In other words,once clinically examined,a patient is M0until proven otherwise.If a liver nodule is detected radiographically in a patient with colon carcinoma,the disease may be considered cM1.If the nodule is biopsied and proven malignant,it is pM1;if it is found to be a hemangioma,it is classified as cM0,not pM0,pMX,or cMX.pM0indicates there is no pathological evidence of cancer in the patient,a situation that occurs only after a complete autopsy (and then would be designated as aM0,not pM0).To prevent patholo-gists and clinicians from using MX or pMX,these designations have been deleted from TNM-7,thereby encouraging the assignment of M0and facilitating stage grouping.Cancer registries will be the immediate beneficiaries of this change.Pn:Perineural Invasion

This optional descriptor had been in the TNM Supplement since 2001.4Although it does not affect stage grouping,it is considered in some situations to be an independent prognostic factor.

Isolated Tumor Cells

The subject of isolated tumor cells (ITCs)in regional lymph nodes and distant sites,which originally referred to single cells and small clusters,5has now evolved into a proposal to include a single cluster of <200cells in a single histological

DOI:10.1002/cncr.25537,Received:May 25,2010;Accepted:June 21,2010,Published online July 21,2010in Wiley Online Library (https://www.360docs.net/doc/7515719370.html,)

Corresponding author:Leslie H Sobin,MD,UICC TNM Committee,4280Massachusetts Avenue NW,Washington,DC 20016-5558;Fax:(301)480-1069;sobin@https://www.360docs.net/doc/7515719370.html,

1

International Union Against Cancer TNM Prognostic Factors Project,Geneva,Switzerland;2American Joint Committee on Cancer,Chicago,Illinois;3Office of Bio-repositories and Biospecimen Research,National Cancer Institute,Bethesda,Maryland

cross section.ITCs still refer to single tumor cells or small clusters of cells measuring 0.2mm in greatest extent that can be detected by routine hematoxylin and eosin stains or immunohistochemistry.ITCs do not typically demonstrate evidence of metastatic activity(eg,prolifera-tion or stromal reaction)or penetration of vascular or lymphatic sinus walls.Cases with ITC in lymph nodes or at distant sites are considered to be a subset of N0or M0. Stage Grouping and Prognostic Grouping The International Union Against Cancer(UICC)TNM-7edition has taken a new approach to separate anatomical stage groupings from prognostic groupings,in which other prognostic factors are added to the T(tumor),N (lymph node),and M(metastasis)categories.These new prognostic groupings,as well as the traditional anatomical groupings,are presented for esophageal and prostate carci-nomas in the UICC TNM system;only prognostic group-ings(termed anatomical prognostic groupings)appear in the American Joint Committee on Cancer(AJCC)TNM system.Except for this dual presentation,the UICC TNM Classification of Malignant Tumors2is identical to that published in the AJCC Cancer Staging Manual.1As more nonanatomical prognostic factors become available, this approach may provide a means of separating extent of disease staging from prognostic grouping.

Head and Neck Tumors

Mucosal melanoma

A major addition to this chapter is the introduction of a new classification for malignant melanoma of the upper aerodigestive tract.These highly malignant tumors are now classified in a manner similar to anaplastic thy-roid carcinoma(ie,omitting the T1and T2classifications and keeping only stages III and IV).

Except for changes in the T1and T2categories of nasopharyngeal carcinoma,the other head and neck sec-tions of TNM-7are essentially unchanged.

Esophagus

Carcinoma of the esophagus has undergone a major mod-ification between the sixth edition(TNM-6)and TNM-7.T1and T4have been subdivided to provide greater detail,regional lymph nodes(N)are subdivided by the number of involved lymph nodes,and distant metastasis (M)has been simplified to M1rather than subdivided by location.Stage grouping has been divided into:1)purely anatomical stages applicable to all types of carcinomas and2)prognostic groups that separate squamous from ad-enocarcinoma and add histological grade and tumor loca-tion to the T,N,and M categories.The first approach (appearing only in the UICC TNM classification)pre-serves the pure anatomic extent of disease concept and allows direct stage-by-stage comparisons of behavior between tumors of different histological types and loca-tion;the second recognizes the prognostic influence of grade and tumor location.6The use of the terms stage grouping and prognostic grouping distinguishes the2. Stomach

Similar to carcinoma of the esophagus,carcinoma of the stomach also has undergone modifications between the TNM-6and TNM-7.T1was subdivided so that mucosal and submucosal depth of invasion could be delineated. T2a and T2b were separated into T2(muscularis propria) and T3(subserosa).The former T3and T4categories were changed to T4a(perforates serosa)and T4b(invades adjacent structures).The division of regional lymph node metastasis by number of involved lymph nodes conforms to that of the esophagus.Thus,the gastric T,N,and M categories are now essentially identical to those of the esophagus(and esophagogastric junction). Esophagogastric(Gastroesophageal)

Junction

The staging of carcinomas of the esophagogastric/gastro-esophageal(GE)junction has been addressed.It is based on the following new TNM rule:a tumor in which the epicenter is within5cm of the GE junction and also extends into the esophagus is classified and staged using the esophageal carcinoma scheme,whereas tumors with an epicenter in the stomach that are>5cm from the GE junction or those within5cm of the GE junction without extension into the esophagus are classified and staged using the gastric carcinoma scheme.

GISTs

These gastrointestinal sarcomas are now classified based on their3major prognostic factors:site,size,and mitotic rate.The categorization is the result of studies of>2000 cases by Miettinen et al.7,8

Appendix

Carcinoma of the appendix had been included in the stag-ing of colorectal carcinoma in TNM-6.In TNM-7,it is staged separately.The basic T and N categories are essen-tially similar to those of the colon.The separation of mucinous from nonmucinous carcinomas is required and

T4and M1are modified to address the particular nature of mucinous carcinomas.Grading has been introduced to distinguish between low-grade and high-grade mucinous carcinomas because of differences in their behavior and management.Stage IV subgroups are dependent on these grades.The carcinoma staging scheme also applies to gob-let cell carcinoids,but not to typical carcinoids. Carcinoids/Well-Differentiated Neuroendocrine Tumors

For the first time,the TNM classification has addressed carcinoids and other neuroendocrine tumors(NETs).In the lung and pancreas,NETs are covered by the same cri-teria as carcinomas.Gastrointestinal carcinoids/NETs (appendiceal,gastric,small bowel,and large bowel)have separate classifications.Merkel cell carcinoma also has a separate classification.

Large Intestine

Carcinoma of the large intestine has undergone relatively few basic modifications between the TNM-6and TNM-7,and therefore the main T,N,and M categories and stages I,II,III,and IV can be compared with those of the previous2editions.Except for the subdivision of T4 (T4a indicates perforation of the visceral peritoneum and T4b indicates direct invasion of other organs or struc-tures),the T categories remain unchanged.The2N cate-gories,with their breakpoint between3and4lymph nodes,remain unchanged,but there is an expansion of each category for those who wish a finer distinction.An important change concerns the categorization of tumor deposits,or satellites,in the mesentery of T1or T2tumors without positive lymph nodes that simulate lymph node metastasis without histological evidence of residual lymph node in the nodule.These may represent discontinuous (possibly lymphatic)spread,venous invasion with extrava-scular spread,or a totally replaced lymph node.If such deposits are observed in the absence of other lymph node metastasis,then the nodule(s)is recorded as N1c.This was an attempt to not deprive such patients of adjuvant chemotherapy by classifying them as having stage III dis-ease.It also was aimed at identifying such cases to provide data to study their frequency and significance.The M cat-egory was subdivided into those cases with distant metas-tasis confined to1organ(ie,those that might be amenable to surgical resection)versus those with metasta-sis in>1organ or the peritoneum.The subdivisions of the T,N,and M categories are expressed in subdivisions of the stage groupings.Despite this expansion,all the sub-stages can be collapsed back into the original4stages of previous TNM classifications covering a30-year span and are compatible with the original Dukes classification,thus ensuring backwards compatibility.

Intrahepatic Cholangiocarcinoma Intrahepatic bile duct carcinomas were included with he-patocellular carcinomas in TNM-6.In TNM-7,there is a separate classification.The staging system applies to intrahepatic cholangiocarcinoma,cholangiocellular carcinoma,and combined hepatocellular and cholan-giocarcinoma(mixed hepatocellular/cholangiocellular carcinoma).

Extrahepatic Bile Ducts

The extrahepatic bile duct carcinoma classification of TNM-6has been divided into perihilar and distal bile duct classifications in TNM-7.The perihilar classification applies to carcinomas of the right,left,and common he-patic ducts(ie,those proximal to the origin of the cystic duct[Klatskin tumor]).The distal classification applies to carcinomas of the extrahepatic bile ducts distal to the insertion of the cystic duct.

Lung

A major revision of the lung carcinoma classification appears in TNM-7.It is the result of a retrospective study of>80,000cases performed by a committee of the Inter-national Association for the Study of Lung Cancer (IASLC)working closely with the UICC and the AJCC. The lung classification provides a single scheme that is ap-plicable to all histological types of lung carcinoma and carcinoids,all histological grades,and central versus pe-ripheral sites based on a purely anatomical(TNM)for-mat.There are important changes in the T3,T4,and M categories as well as with regard to stage grouping.9

Bone and Soft Tissue

Although there were differences between the AJCC and the UICC regarding the stage grouping of bone and soft tissue tumors in the first printing of TNM-7,both have agreed to follow the AJCC formulation.

Skin

For skin carcinoma,there are changes in T categories and especially in the regional lymph node classification to spe-cifically accommodate skin tumors of the head and neck. The AJCC has added several high-risk factors that could change T1/stage I tumors to T2/stage II.Initial

differences between the AJCC and the UICC regarding the subdivision of pT1in the classification of cutaneous melanoma have been resolved;both the AJCC and the UICC now will follow the AJCC subdivision based on ulceration and mitotic rate.If the mitotic rate cannot be accurately determined,Clark level can be used.A new classification for Merkel cell carcinoma also has been introduced.

Breast

There are no basic changes in this classification. Gynecologic Tumors

Major changes concern the classification of vulvar carci-noma and the introduction of classifications for uterine sarcomas(adenosarcoma,leiomyosarcoma,and endome-trial stromal sarcoma).10,11The classification of gyneco-logical tumors corresponds to that of the International Federation of Gynecology and Obstetrics(FIGO).

Penis

Separate cN and pN classifications have been introduced. Prostate

A dual(anatomic vs prognostic)approach to staging is available in the classification of prostate carcinoma,in which there is a purely TNM-based stage grouping and a prognostic grouping that combines TNM classification, prostate-specific antigen values,and Gleason score.The AJCC classification presents the prognostic grouping, whereas the UICC classification presents both the ana-tomical and prognostic options.A correction to Prognos-tic Group IIA in both the UICC and AJCC publications is shown in Table1.

Adrenal Cortex

A new classification of adrenal cortical carcinoma has been introduced in TNM-7,one that had been previously proposed in the TNM Supplement.12Ophthalmic Tumors

Major changes have been made in the classifications of malignant melanoma of the conjunctiva and uvea as well as retinoblastoma and carcinoma of the lacrimal gland.

Specific questions regarding the TNM classification can be addressed at https://www.360docs.net/doc/7515719370.html, and http:// https://www.360docs.net/doc/7515719370.html,.

CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures.

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Table1.Correction to Prognostic Group IIA

T1a–cN0PSA<20ng/mL Gleason score7 T1a–cN0PSA 10to<20ng/mL Gleason score 6 T2aN0PSA 10to<20ng/mL Gleason score 6 T2aN0PSA<20ng/mL Gleason score7 T2bN0PSA<20ng/mL Gleason score 7

PSA indicates prostate-specific antigen.