AMA Manual of Style - Stacy L. Christiansen, Cheryl Iverson 2020

Cancer
Nomenclature

14.2.1 Cancer Stage.

Cancer stages are expressed with the use of capital roman numerals, with higher numbers indicating increasing extent of disease:

stage I

stage II

stage III

stage IV

The term “stage 0” usually indicates carcinoma in situ, with no spread of disease beyond the primary site.

Letter and numerical suffixes, usually set on the line, may be added to subdivide individual cancer stages, as in the following examples:

stage 0a

stage 0is

stage IA

stage IE

stage IB2

stage IIIE+S

stage IVA

stage IVB

Note: E indicates extralymphatic spread; S, splenic involvement (as seen in Hodgkin disease); is, in situ.

Histologic grades are expressed with arabic numerals (eg, grade 2). For some anatomical sites, grade 3 and grade 4 are combined into a single grade: grade 3-4 (for poorly differentiated to undifferentiated).^1(p13)

14.2.2 The TNM Staging System.

The TNM (tumor, node, metastasis) staging system^{1,2,3,4,5,6,7,8} is an internationally standardized system for the staging of cancer and is in its eighth decade of continuing formulation. The TNM classification is put forth by the American Joint Committee on Cancer (AJCC; https://cancerstaging.org) and the Union for International Cancer Control (UICC; https://www.uicc.org).² The AJCC’s Cancer Staging Manual¹ and the UICC’s TNM Classification of Malignant Tumours³ present the stages of cancer as defined by TNM classifications. The TNM definitions and stage groupings are based on prognostic outcome. Information about TNM may be accessed at the UICC website. The TNM symbols follow.

■T: tumor (indicates size, extent, or depth of penetration of the primary tumor)

T is followed by numerical or other suffixes set on the line, for example:

TX: primary tumor cannot be assessed

T0: no evidence of a primary tumor

Tis: carcinoma in situ

T1, T2, T3, T4: increasing size and/or local extent or other characteristics of the primary tumor

Note: The number following T does not refer to an absolute size. For example, for one type of tumor, T1 may indicate a size of 2 cm or less; for another, a depth (or thickness) of 0.75 mm or less; and for another, tumor confinement within the underlying mucosa.

■N: node (indicates the absence or presence and extent of regional lymph node involvement)

NX: regional lymph nodes cannot be assessed

N0: no regional lymph node metastasis

N1, N2, N3: increasing metastatic involvement of regional lymph nodes according to criteria that vary for different anatomical sites

■M: metastasis (indicates absence or presence of distant metastasis)

M0: no metastasis

M1: distant metastasis

Note: MX (distant metastasis cannot be assessed) has been eliminated from the seventh edition of the TNM classification because “clinical assessment of metastasis can be based on physical examination alone.”^3(p11) This change will encourage the assignment of M0 and facilitate stage grouping.⁶

Site of metastasis may be indicated with parenthetic 3-letter abbreviations, for example, M1(PUL):

14.2.2.1 The TNM System and Cancer Staging.

Various combinations of the T, N, and M categories are used to define cancer stages (consult the AJCC¹ or UICC² manual for specifics). For example, a TNM stage grouping that defines stage I for many types of cancer is as follows:

T1N0M0

The combinations that define individual stages differ among anatomical sites, for example:

More than one combination of the T, N, and M categories may constitute the definition of a single stage; for example, in a given cancer, stage III may be defined as T1N1M0 or T2N1M0 or T3N0M0 or T3N1M0.

14.2.2.2 Optional Descriptors.

Additional descriptors, although not part of the TNM staging system, may be used as adjuncts to the T, N, and M categories for defining the extent of disease; these are indicated by capital letters as follows:

C-factor terms may be used together with T, N, and M categories (eg, T3C2, N2C1, M0C2).^3(p18)

Lowercase prefixes to the T, N, M, and other symbols may be used to indicate the mode of determining criteria for tumor description and staging or other attributes (eg, cTNM, pT3) as follows:

The T, N, M, and other symbols used in cancer staging may be followed by suffixes in addition to the common X, 0, and numerals, which further specify qualities, such as size, invasiveness, and extent of metastasis, eg:

Note: m indicates the presence of multiple primary tumors at a single site; mi, micrometastasis; sn, sentinel node status; i, isolated tumor cells; mol, isolated tumor cells demonstrated by nonmorphologic (eg, molecular) techniques.

Examples of such combined terms are as follows:

pN0(i−)(sn)

pT2cN1cM0

14.2.2.3 Usage.

Terms such as stage I cancer, TNM staging system, and T1N1M0 are widely recognized and may be used in articles without expansion. However, authors should specify the clinical and/or pathologic criteria that define any stage (optionally but preferably citing the staging system of the AJCC or UICC manual).

Use terms as given in Table 14.2-1 (see 11.1, Correct and Preferred Usage of Common Words and Phrases [Case, Client, Consumer, Patient, Subject]).

Table 14.2-1. Correct and Incorrect Usage of TNM Cancer Staging Terms

For some sites, the histologic grade has been integrated into the staging system.

14.2.2.4 Other Staging Systems and the TNM System.

The AJCC-UICC TNM classification and stage grouping is not the only system used for staging cancer, and equivalency of the same stage number among different systems cannot be assumed. However, 2 cancer staging systems, the International Federation of Gynecology and Obstetrics (FIGO; http://www.figo.org) staging system for gynecologic cancers^9,10,11 and the Dukes stage system (expressed with letters: Dukes stages A through D) for colon and rectal cancers, have virtual equivalence with the AJCC-UICC stage. The AJCC-UICC system contains subsets of TNM classifications within stage groups that provide greater prognostic precision within each stage for colorectal cancer than does the Dukes system. The Dukes system has largely been replaced by the TNM system.^1(p143)

FIGO stages are expressed similarly to TNM stages:

14.2.3 Bethesda System for Cervical Cytology.

The Bethesda System for Reporting Cervical Cytology, dating to 1988, is a standardized, systematic means of reporting Papanicolaou test results.¹² Resources are the published handbook (the “blue book”)¹² and the website (https://bethesda.soc.wisc.edu).¹³

Expand the following abbreviations at first mention, and punctuate as shown (Table 14.2-2).

Table 14.2-2. Bethesda System for Reporting Cervical Cytology Abbreviations

In the following examples, unexpanded abbreviations are assumed to have been previously defined in the text:

Low-grade squamous intraepithelial lesions (LSILs) have been described as a benign cytologic consequence of active human papillomavirus (HPV) replication. Several studies have reported that certain behavioral and biological risks exist for LSILs, suggesting that HPV alone is not sufficient for the development of LSILs.

AIS (CP)

ASC-H (CP)

exfoliated endometrial cells (liquid-based preparation [LBP])

atrophy (LBP)

glandular cells post hysterectomy (CP)

Grades are expressed as follows:

CIN 1, CIN 2, CIN 3

VAIN 1, VAIN 2, VAIN 3

14.2.4 Multiple Endocrine Neoplasia.

Abbreviations for types of multiple endocrine neoplasia (MEN) feature arabic numerals and a space, as follows:

MEN 1

MEN 2

MEN 2A

MEN 2B

MEN 3

Gene terms are italicized with spaces closed up (see 14.6.2, Human Gene Nomenclature):

MEN1

MEN2

MEN3

14.2.5 Molecular Cancer Terminology.

See Table 14.10-2 in 14.10, Molecular Medicine. The style for the cell cycle is given in Table 14.2-3.

Table 14.2-3. Cell Cycle Abbreviations

Miscellaneous molecular terms that are frequently seen are styled as detailed in Table 14.2-4^14,15 (see 14.6.3, Oncogenes and Tumor Suppressor Genes).

Table 14.2-4. Miscellaneous Molecular Terms

^a Although these gene symbol aliases or “nicknames” may still be used by some, use of the approved gene symbol, not the alias, is strongly preferred. Use of the approved gene symbol will minimize confusion and make it possible to provide links to genome databases for online versions of the article and to facilitate data retrieval in a number of databases. If an author insists on using an alias, provide the alias parenthetically after the approved gene symbol at first mention in the text and abstract. This practice will link the two and provide a learning experience for those not yet familiar with the approved gene symbol.

Note: Gene terms follow standard gene nomenclature style (see 14.6.2, Human Gene Nomenclature).

Principal Author: Cheryl Iverson, MA

Acknowledgment

Thanks to Boris C. Pasche, MD, PhD, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina; Mary L. Disis, MD,  JAMA Oncology, and University of Washington, Seattle; Carissa A. Gilman, MA, American Cancer Society, Atlanta, Georgia; and John J. McFadden, MA, JAMA Network, for reviewing and providing comments.

References

1.Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III, eds; American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th ed. Springer; 2010.

2.International Union Against Cancer/Union Internationale Contre le Cancer website. Accessed March 20, 2019. https://www.uicc.org

3.Sobin LH, Gospodarowicz MK, Wittekind C, eds; International Union Against Cancer. TNM Classification of Malignant Tumours. 7th ed. Wiley-Blackwell; 2009.

4.Wittekind C, Compton CC, Brierley J, Sobin LH, eds. TNM Supplement: A Commentary on Uniform Use. 4th ed. Wiley-Blackwell; 2012.

5.Gospodarowicz MK, O’Sullivan B, Sobin LH, eds. Prognostic Factors in Cancer. 3rd ed. Wiley-Liss; 2006.

6.Sobin LH, Compton CC. TNM Seventh Edition: what’s new, what’s changed. Cancer. 2010;116(22):5336-5339. doi:10.1002/cncr.25537

7.Greene FL, Sobin LH. A worldwide approach to the TNM staging system: collaborative efforts of the AJCC and UICC. J Surg Oncol. 2009;99(5):269-272. doi:10.1002/jso.21237

8.Gospodarowicz MK, Miller D, Groome PA, Greene FL, Logan PA, Sobin LH; UICC TNM Project. The process for continuous improvement of the TNM classification. Cancer. 2004;100(1):1-5. doi:10.1002/cncr.11898

9.Benedet JL, Bender H, Johnes H III, Pecorelli S; the FIGO Committee on Gynecologic Oncology. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. Int J Gynaecol Obstet. 2000;70(2):209-262. doi:10.1016/S0020-7292(0 0)90001-8

10.Kim HS, Song YS. International Federation of Gynecology and Obstetrics (FIGO) staging system revised: what should be considered critically for gynecologic cancer? J Gynecol Oncol. 2009;20(3):135-136. doi:10.3802/jgo.2009.20.3.135

11.International Federation of Gynecology and Obstetrics. Accessed March 20, 2019. https://www.figo.org

12.Nayar R, Wilbur D, eds. The Bethesda System for Reporting Cervical Cytology: Definitions, Criteria, and Explanatory Notes. 3rd ed. Springer; 2015. Accessed February 23, 2017. https://www.springer.com/us/book/9783319110738

13.Solomon D, Davey D, Kurman R. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287(16):2114-2119. doi:10.1001/jama.287.16.2114

14.HUGO Gene Nomenclature Committee. FAQ about gene nomenclature. Accessed March 19, 2019. https://www.genenames.org/help/faq/

15.Nayar R, Wilbur DC. The Pap test and Bethesda 2014. Acta Cytol. 2015;59(2):121-132. doi:10.1159/000381842