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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 28  |  Issue : 1  |  Page : 65-73

Changes to skin cancer staging in American Joint Committee on Cancer 8th edition


1 Department of Plastic, Reconstructive and Aesthetic Surgery, Antalya Training and Research Hospital, Antalya, Turkey
2 Department of Plastic, Reconstructive and Aesthetic Surgery, Derince Training and Research Hospital, Kocaeli, Turkey

Date of Submission23-Dec-2018
Date of Acceptance01-Feb-2019
Date of Web Publication31-Dec-2019

Correspondence Address:
Dr. Ahmet Demir
Department of Plastic, Reconstructive and Aesthetic Surgery, Antalya Training and Research Hospital, Varlik Mah Kazim Karabekir Cad 07100 Muratpasa, Antalya
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/tjps.tjps_99_18

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  Abstract 


The American Joint Committee on Cancer (AJCC) has an irreplaceable importance with its guidelines for cancer staging. These staging procedures are carried out with retrospective and prospective analysis studies. In the light of the new data, there may be an increase or decrease in the staging of some skin cancer lesions, while some concepts are completely eliminated. In the 8th Edition of the AJCC Manual, which is published approximately 7 years after the previous edition, changes were made in line with the new data on skin cancers. The most prominent change for squamous cell carcinoma of the skin is the discrimination between “clinical (cN)” and “pathological (pN)” staging. The most prominent change for Merkel cell carcinoma is that “cN” and “pN” distinction has been introduced for both regional lymph node and distant metastasis. In terms of melanoma, it can be said that everything related to a tumor, a regional lymph node, and a distant metastasis have been changed. Given the fact that the next edition will not be released earlier than at least another 7 years, it is necessary to quickly become acquainted with this new edition for the benefit of treating and monitoring patients with skin cancer.

Keywords: American Joint Committee on Cancer, melanoma, Merkel cell carcinoma, skin cancer staging, squamous cell cancer


How to cite this article:
Demir A, Unverdi OF. Changes to skin cancer staging in American Joint Committee on Cancer 8th edition. Turk J Plast Surg 2020;28:65-73

How to cite this URL:
Demir A, Unverdi OF. Changes to skin cancer staging in American Joint Committee on Cancer 8th edition. Turk J Plast Surg [serial online] 2020 [cited 2020 Jul 12];28:65-73. Available from: http://www.turkjplastsurg.org/text.asp?2020/28/1/65/274448




  Introduction Top


Cancer staging provides many practical uses. Modern medicine aims at offering individualized treatment options to each specific patient. These staging algorithms make it easier to first group cancer patients according to their common characteristics, and then to evaluate, in line with the guidelines, the treatment options that can be given to each individual. These guidelines further hold an important place in terms of a common scientific language and the management of patients in different clinics.

Among the cancer staging guidelines, the Cancer Staging Manual published by the American Joint Committee on Cancer (AJCC) is the most popular. This manual is being published for almost 42 years.[1] Having periodically updated the edition over ≥4 decades, the AJCC released the 8th Edition of the manual in 2017.[2] This edition introduces some criteria and classification updates to the tumor-node-metastasis (TNM) staging system, which has been used as a guideline in every edition for cancer staging, in line with the current developments and advancements. Although the edition has been released in 2017, the updates to the guidelines are indicated to be effective as of January 01, 2018. Given the almost 10 years' time between the last two editions, a review of the updates will allow us to modify our clinical (cN) practices and possibly require us to revise our staging approach, and the treatments currently offered to newly diagnosed patients.

In this study, we examined the changes made in the manual for skin cancers, which hold an extensive place in the cN practice of plastic surgery. Another aspect to note is that readers who refer to the original source for the type of cancers mentioned here or for any other types of cancers should use the “AJCC Cancer Staging Manual 8th Edition, Corrected at 3rd Printing in 2018” that includes further changes and updates after the original printing.


  Squamous Cell Carcinoma of the Skin Top


The annual incidence of squamous cell carcinoma (SCC) of the skin increases by 3%–8%, and this type is responsible for almost 20% of all skin cancer-related deaths.[3],[4] This type of cancer is thought to cause between 3900 and 8800 deaths in the USA every year.[5]

In the AJCC 7th Edition published in 2010, the “Skin Cancers” chapter included three sections, namely for “SCC of the Skin and Other Skin Carcinomas,” “Merkel Cell Carcinoma (MCC),” and “Melanoma of the Skin.” In the 8th Edition, SCC of the skin has been moved under the heading “Skin Carcinomas of the Head and Neck” in the “Cancers of the Head and Neck” chapter, and the “Skin Cancers” chapter has been reduced to two sections.[2],[6] No staging algorithms are given in the new guidelines for the SCC, and the basal cell carcinoma of the skin at anatomic sites other than the head and neck region. Accordingly, also changes have been made in the topographical codes listed in the 8th Edition. The changes made in the topographical codes are given in [Table 1]. Another point worth noting is that lesions on the dry vermilion border have been moved under the “external lip” section since dry vermilion is embryologically more similar to the skin and etiologically not exposed to ultraviolet radiation.[2]
Table 1: Comparison of topographical codes listed in American Joint Committee on Cancer 7th and 8th editions

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The most prominent change in the T (tumor) definitions for SCC is the absence of “T0” in the latest edition. Further, “high-risk features” used in the “T1” and “T2” definitions have been excluded as criteria and also worth noting are the changes in the anatomic definitions of “T3” and “T4.” The differences between the T definitions given for SCC in the latest and the previous editions are given in [Table 2].
Table 2: Comparison of squamous cell carcinoma tumor criteria in American Joint Committee on Cancer 7th and 8th editions

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While in the 7th Edition, TNM cN and TNM pathological (pN) classifications of SCC definitions were indicated to be the same; in the 8th Edition, evaluation of the lymph nodes has been separated as cN and pN. The single lymph node (N) evaluation description for SCC in the 7th Edition was compared with the clinical lymph node (cN) and the pathological lymph node (pN) descriptions in the last edition as given in [Table 3]. In lymph node evaluations, using the “U” marker is recommended for metastases localized at the level of the lower border of the cricoid cartilage, and the “L” marker for metastases localized below this border.[2]
Table 3: Comparison of the evaluation of the regional lymph nodes in the American Joint Committee on Cancer 7th and 8th editions

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There are no differences in the 7th and 8th Editions with respect to the definitions of distant SCC metastasis. As in the previous edition, the same criteria are given for M0-no distant metastasis, and M1-distant metastasis categories [Table 4]. Histologic evaluation subheadings remain unchanged [Table 5]. Likewise, there are no differences between the two editions in terms of actual TNM staging [Table 6].
Table 4: Definition of metastasis in the American Joint Committee on Cancer 8th edition

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Table 5: Histologic evaluation in American Joint Committee on Cancer 8th edition

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Table 6: Staging system of skin carcinomas of the head and neck in the American Joint Committee on Cancer 8th edition

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  Merkel Cell Carcinoma (Primary Cutaneous Neuroendocrine Carcinoma) Top


MCC is a rare but aggressive neuroendocrine carcinoma that was first described by Tang and Toker in 1978.[7] MCC has an incidence of 1600–2500 in the USA.[8],[9] Mortality rate in MCC (33%) is almost twice as that of skin melanoma (15%).[10],[11] There are studies that show the oncological role Merkel cell polyomavirus plays in tumor development.[12],[13]

As is the case for squamous cell cancer, a specific staging profile is given for the MCC of the eyelid, and this profile is different from the overall staging system. Whereas in the first six editions, MCC was included under the same staging system as for nonmelanocytic skin cancers, a specific staging system was introduced for MCC as of the 7th Edition.[6]

A comparison of MCC classifications in the 7th and 8th Editions reveals that all evaluations except for T have been changed. These changes are based on the analysis data obtained from the study performed by Harms et al. with 9387 patients with MCC.[14]

Even though there is no change in the tumor dimensions defined for MCC in the T evaluation, the term “cN” has been emphasized in the criteria description. Maximum tumor sizes remain unchanged [Table 7].
Table 7: Merkel cell carcinoma definitions in tumor evaluation in the American Joint Committee on Cancer 8th edition

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With regard to regional lymph nodes of MCC, the new edition is seen to introduce a discrimination between cN and pN evaluation. Accordingly, the descriptions of “micrometastasis” and “macrometastasis” in the “N1” subgroup have been discriminated as cN and pN. “In transit” metastases described in the evaluation of “N2” has been discriminated based on the presence and absence of a metastasis in the lymph nodes, and thereby a new “N3” definition has been added in the 8th Edition. [Table 8] shows a comparison of the 7th and 8th Editions in terms of the changes and additions to the definitions of metastases in regional lymph nodes.
Table 8: Comparison of the descriptions given for regional Merkel cell carcinoma lymph nodes in the American Joint Committee on Cancer 7th and 8th Editions

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The same discrimination of “cN” and “pN” has also been introduced for MCC metastases. The evaluation of cN metastasis remains similar to the description given in the 7th Edition. The metastasis evaluation described in the 8th Edition is given in [Table 9].
Table 9: Description of metastasis of Merkel cell carcinoma in the American Joint Committee on Cancer 8th edition

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There is no histologic grading system recommended for MCC. Although subtypes have been described for MCC, i.e., “intermediate” (most common type), “small cell” (second-most common type), and “trabecular” (least common, but most characteristic type of MCC), these have no effect on the prognosis of the disease (AJCC 8th Edition). The staging system of MCC has been revised as clinical TNM and pathological TNM. The new clinical and pathological systems are described in [Table 10].
Table 10: Merkel cell carcinoma staging in the American Joint Committee on Cancer 8th edition

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  Melanoma of the Skin Top


Melanoma of the skin is not a common type of skin cancer, but responsible for a majority of the mortalities caused by skin cancers.[15] In the recent years, however, its annual incidence increases by about 3%.[16],[17] Ongoing research for new medication and vaccination strive to diversify patient-specific treatment options. The description of melanoma has been undergoing major changes in almost every new AJCC Edition based on the data obtained in the treatment and follow-up processes of the disease.

In addition to the topographical codes listed in the previous edition, new codes have been added for the external upper lip (C00.0), the external lower lip (C00.1), the external lip (NOS) (C00.2), and the commissure of the lip (C00.6) in the 8th Edition. Changes to the descriptions, as well as the staging system of primary tumors, regional lymph node metastases and distant metastases have also been introduced in the 8th Edition.

Dr. Wallace Clark's level of invasion classification has been used for almost 40 years.[18] Although the Breslow index developed by Dr. Alexander Breslow was introduced with the intention to support the Clark's system, Clark's level was the last included in the 6th Edition together with ulceration in the T1 subgroup description.[19],[20] In the next (7th) edition, Clark's invasion level was replaced by the Breslow index, and in addition by ulceration and mitotic rate in the T1 description. Tumor thickness is measured from the top of the granular layer of the epidermis (from the base of the ulcer, if ulcerated) over the base diameter of the tumor to the deepest invasive cell (to where it is localized in the dermis or the subcutaneous tissue).[21],[22] In the latest edition, the mitotic rate has been excluded from the description of the T1 subgroup, because rather than evaluating the mitotic rate, using a cutoff value of 0.8 mm for subgroup discrimination is more relevant in terms of process than a mitotic presence or absence.[2] Even though presently not used in staging, mitotic rate maintains its predictive role and importance in individualized prognostic estimates.[23] [Table 11] shows the description of a primary melanoma tumor given in AJCC 8th Edition.
Table 11: Description of primary tumor in the melanoma of the skin in the American Joint Committee on Cancer 8th edition

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Review of the changes made with respect to the regional lymph node metastasis in the melanoma of the skin showed that the number of the metastatic nodes indicated in the previous edition has been replaced with micro/macro metastasis definitions. While the “N3” value included one group in the previous edition, “N1” has been divided into two and “N2” into three subgroups in the 8th Edition. In the new edition, however, each “N” value has been divided into three subgroups based on the presence of microsatellite lesions, and the number of metastatic lymph nodes in addition to the “in-transit” and “satellite” descriptions given for the “N3” value. A comparison of the changes made in terms of the conditions of regional lymph nodes is given in [Table 12].
Table 12: Comparison of the descriptions given for regional lymph nodes in melanoma of the skin in the American Joint Committee on Cancer 7th and 8th editions

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Major changes have been introduced in the 8th Edition with respect to the evaluation of the melanoma of the skin. However, the “M1” value, which traditionally indicated a metastatic presence, was divided into three subgroups in the previous edition; in the latest edition, the “M1” value has been divided into four subgroups by separating the central nervous system from the other visceral systems such as the lungs. Furthermore, lactate dehydrogenase, which was used in the description of “M1c” in the previous edition, has been introduced as a second subgrouping criterion based on the serum level. For instance, a distant skin metastasis that was previously defined as “M1c” is defined as “M1a (1)” in the new edition. [Table 13] shows the differences with respect to metastasis between the 7th and the 8th Editions.
Table 13: Comparison of the descriptions given for distant metastasis in melanoma of the skin in the American Joint Committee on Cancer 7th and 8th editions

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No changes have been introduced in AJCC 8th Edition for the TNM criteria in the cN staging of the melanoma of the skin. There are, however, some changes regarding pN staging. T1N0M0 staging has been lowered from IB in the previous edition to IA in the new edition. Other major changes have been introduced to Stage III, and a fourth subgroup has been added to the previous three subgroups described in Stage III. No changes have been made related to the definitions of Stage II and Stage III. The cN staging of melanoma is given in [Table 14], and the comparisons of the changes introduced in the pN staging of melanoma are given in [Table 15].
Table 14: Clinical staging of melanoma of the skin in the American Joint Committee on Cancer 8th edition

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Table 15: Comparison of pathological staging in melanoma of the skin described in the American Joint Committee on Cancer 7th and 8th editions

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  Conclusion Top


The 8th Edition of the AJCC Manual is yet another link in the series describing the approach to cancers. The AJCC Manual was first published in 1977 and will be republished as long as cancer remains a common disease. New diagnostic procedures and treatment approaches allow for changes in the classification of cancer cases as well as patient survival. Treatment options are being revised, as we gain deeper knowledge about the oncogenetic development and the association with environmental factors of some types of cancers. We are going through a period in which a society-based cancer approach is being replaced by a person-based approach. The contents introduced in this edition may, perhaps, be rendered invalid by the contents of the future AJCC 9th Edition.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Beahrs OH, Carr DT, Rubin P, editors. Manual for Staging of Cancer. Chicago (IL): National Cancer Institute; 1977.  Back to cited text no. 1
    
2.
Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al., editors. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017.  Back to cited text no. 2
    
3.
Diepgen TL, Mahler V. The epidemiology of skin cancer. Br J Dermatol 2002;146 Suppl 61:1-6.  Back to cited text no. 3
    
4.
Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol 1992;26:976-90.  Back to cited text no. 4
    
5.
Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: Estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol 2013;68:957-66.  Back to cited text no. 5
    
6.
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010.  Back to cited text no. 6
    
7.
Tang CK, Toker C. Trabecular carcinoma of the skin: An ultrastructural study. Cancer 1978;42:2311-21.  Back to cited text no. 7
    
8.
Fitzgerald TL, Dennis S, Kachare SD, Vohra NA, Wong JH, Zervos EE, et al. Dramatic increase in the incidence and mortality from Merkel cell carcinoma in the United States. Am Surg 2015;81:802-6.  Back to cited text no. 8
    
9.
Lemos B, Nghiem P. Merkel cell carcinoma: More deaths but still no pathway to blame. J Invest Dermatol 2007;127:2100-3.  Back to cited text no. 9
    
10.
Lemos BD, Storer BE, Iyer JG, Phillips JL, Bichakjian CK, Fang LC, et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: Analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol 2010;63:751-61.  Back to cited text no. 10
    
11.
Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N, et al. Prognostic factors analysis of 17,600 melanoma patients: Validation of the American Joint Committee on cancer melanoma staging system. J Clin Oncol 2001;19:3622-34.  Back to cited text no. 11
    
12.
Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008;319:1096-100.  Back to cited text no. 12
    
13.
Verhaegen ME, Mangelberger D, Harms PW, Vozheiko TD, Weick JW, Wilbert DM, et al. Merkel cell polyomavirus small T antigen is oncogenic in transgenic mice. J Invest Dermatol 2015;135:1415-24.  Back to cited text no. 13
    
14.
Harms KL, Healy MA, Nghiem P, Sober AJ, Johnson TM, Bichakjian CK, et al. Analysis of prognostic factors from 9387 Merkel cell carcinoma cases forms the basis for the new 8th edition AJCC staging system. Ann Surg Oncol 2016;23:3564-71.  Back to cited text no. 14
    
15.
American Cancer Society. Cancer Facts and Figures 2018. Atlanta: American Cancer Society; 2018.  Back to cited text no. 15
    
16.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7-30.  Back to cited text no. 16
    
17.
Whiteman DC, Green AC, Olsen CM. The growing burden of invasive melanoma: Projections of incidence rates and numbers of new cases in six susceptible populations through 2031. J Invest Dermatol 2016;136:1161-71.  Back to cited text no. 17
    
18.
Clark WH Jr., From L, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 1969;29:705-27.  Back to cited text no. 18
    
19.
Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 1970;172:902-8.  Back to cited text no. 19
    
20.
Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, et al., editors. AJCC Cancer Staging Manual. 6th ed. Chicago, IL: Springer; 2002.  Back to cited text no. 20
    
21.
Breslow A. Tumor thickness, level of invasion and node dissection in stage I cutaneous melanoma. Ann Surg 1975;182:572-5.  Back to cited text no. 21
    
22.
Breslow A. Problems in the measurement of tumor thickness and level of invasion in cutaneous melanoma. Hum Pathol 1977;8:1-2.  Back to cited text no. 22
    
23.
Thompson JF, Soong SJ, Balch CM, Gershenwald JE, Ding S, Coit DG, et al. Prognostic significance of mitotic rate in localized primary cutaneous melanoma: An analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. J Clin Oncol 2011;29:2199-205.  Back to cited text no. 23
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13], [Table 14], [Table 15]



 

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  In this article
Abstract
Introduction
Squamous Cell Ca...
Merkel Cell Carc...
Melanoma of the Skin
Conclusion
References
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