Fellow-in-Training Perspectives

Staging of Melanoma and SCC in the AJCC 8th Edition Cancer Staging Manual

By Jeffrey F. Scott, MD

As Micrographic Surgery and Dermatologic Oncology fellows-in-training, we are tasked not only with developing our surgical skills, but also with learning to accurately stage skin cancers and staying up-to-date on advances in cutaneous oncology. The Accreditation Council for Graduate Medical Education (ACGME) regards these skills as essential to our training, as they have designated “Mastery of Cutaneous Oncologic Curriculum” as a Milestone for fellows to work towards during their ACGME-accredited procedural dermatology fellowships.

Recently, the American Joint Committee on Cancer (AJCC) published the 8^th Edition of their Cancer Staging Manual, which will be implemented on January 1^st, 2018. The AJCC cancer staging system has numerous functions, including standardizing nomenclature, advising clinicians in staging, prognosis, and treatment recommendations, determining patient eligibility and stratification for clinical trials, guiding research, and facilitating population-based reporting.

Here, we review key changes to the staging of melanoma and cutaneous squamous cell carcinoma (SCC) found in the AJCC 8^th Edition Cancer Staging Manual. This is not meant to be a comprehensive review of the new staging systems, and fellows are encouraged to regularly reference the staging manual as part of their training.¹

Melanoma

Two important changes in the 8^th Edition staging for melanoma involve the definition of primary tumor (T) classifications. Mitoses have been removed, and the T1a category now includes a 0.8 mm cutoff for Breslow’s thickness. Similar to the 7^th Edition, the presence of ulceration upstages the primary tumor from an “a” to “b” classification for each corresponding T stage (i.e. T1b, T2b, etc).² Thus, the 8^th Edition designates melanomas <0.8 mm in thickness without ulceration as T1a tumors, and melanomas <0.8 mm in thickness with ulceration as T1b tumors. The 8^th Edition, however, also designates melanomas between 0.8 and 1.0 mm in thickness as T1b tumors, regardless of ulceration status. The thickness cutoffs for T2, T3, and T4 tumors remain the same as in the 7^th Edition (>1.0 to 2.0 mm, >2.0 to 4.0 mm, and >4.0 mm, respectively). This is a significant change for thin melanomas, as tumors between 0.8 and 1.0 mm in thickness without ulceration are now classified as T1b tumors and clinically staged as IB in the absence of regional or distant metastases, whereas these same tumors would have previously been classified as T1a tumors and clinically staged as IA in the 7^th Edition. Finally, for a given T stage without regional or distant metastases, clinical and pathological staging of IA-IIC disease remains the same as in the 7^th Edition.

Regarding regional lymph node (N) status, the 8^th Edition removes the terms “microscopic” and “macroscopic” disease, and now refers to disease in lymph nodes as “clinically occult” (i.e. detected by sentinel lymph node biopsy only) and “clinically detected” (i.e. palpable). The 8^th Edition also includes new “c” sub-classifications for each N stage (N1c, N2c, N3c), which take into account the presence of in-transit, satellite, and/or microsatellite metastases. As a reminder, in-transit metastases are located >2 cm away from the primary tumor, but before the nearest lymph node, and satellite metastases (macro- and microsatellite metastases) are located within 2 cm of the primary tumor. In contrast, the 7^th Edition considered in-transit or satellite metastases without metastastic nodes as N2c disease, and with metastatic nodes as N3 disease. Fellows should consult the staging manual to reference how the extent of regional lymph node and/or lymphatic metastases influences pathological staging (IIIA-IIID).

Finally, regarding distant metastases (M), the 8^th Edition designates a new category for distant metastases to the CNS (M1d), which was previously combined with all other visceral sites as M1c disease in the 7^th Edition. Moreover, unlike the 7^th Edition, an elevated LDH level does not immediately upstage to M1c disease in the 8^th Edition. Rather, each M category now includes a separate suffix (1) for an elevated LDH level (M1a(1), M1b(1), etc). All M1 categories result in clinical and pathological stage IV disease.

Cutaneous SCC

A major goal of the 8^th Edition staging for cutaneous SCC was to improve risk stratification. The T3 and T4 tumor classifications in the 7^th Edition were reserved for rare cases of tumors with bony invasion. As such, the vast majority of high-risk tumors were classified as T2 tumors, limiting the prognostic utility of the staging system. Of note, the 8^th Edition staging for cutaneous SCC only applies to head and neck tumors (“Cutaneous Squamous Cell Carcinoma of the Head and Neck”), and cutaneous SCC arising on skin outside the head and neck do not have a dedicated AJCC staging system.¹ This is in contrast to the 7^th Edition, which included a now-removed chapter encompassing all cutaneous SCCs (“Cutaneous Squamous Cell Carcinoma and Other Cutaneous Carcinomas for All Topographies”).²  Finally, SCC of the eyelid, vulva, penis, perianal skin, and anus all have unique staging systems, and will not be discussed below.¹

Similar to the 7^th Edition, the 8^th Edition designates a clinical size of 2 cm as the cutoff for T1 and T2 tumors. The 7^th Edition also identified various high-risk features which upstaged tumors from T1 to T2,  including >2 mm depth of invasion, perineural invasion (PNI), ear or non-hair bearing lip anatomic location, and poorly differentiated or undifferentiated histology. The 8^th Edition has modified these high-risk features in a number of important ways, and now only incorporates them into the classification of T3 tumors. T3 tumors are classified as tumors with a clinical size ≥4 cm, or tumors with deep invasion (>6 mm or involvement beyond the subcutaneous fat, rather than the >2 mm cutoff used in the 7^th Edition), large-caliber PNI (≥0.1 mm rather than the small-caliber PNI used in the 7^th Edition), involvement of named nerves without skull base invasion or transgression, or minor bone erosion. The T4 category is now reserved for tumors with bony invasion, with sub-classifications for gross cortical bone or bone marrow invasion (T4a), and skull base invasion or foramen involvement (T4b). Of note, aggressive histologic features and anatomic site are no longer included in the T classification. Importantly, immunosuppression still does not affect the T classification in the 8^th Edition. In summary, T1 and T2 tumors are defined by size alone (<2 cm and between 2 and 4 cm in greatest dimension, respectively), size ≥4 cm and/or high-risk features upstage to T3, and bony involvement upstages to T4.

The regional lymph node (N) status is also significantly modified in the 8^th Edition, however a detailed discussion of the revised N staging is beyond the scope of this article. In summary, the 8^th Edition considers extracapsular extension, lymph node size (with cutoffs of 3 cm and 6 cm), and laterality (ipsilateral or contralateral lymph node involvement) as critical features of N staging (all of which were not included in the 7^th Edition). Finally, all distant metastases are now staged as M1 disease, regardless of the visceral site.

T1, T2, and T3 tumors, without regional or distant metastases, are classified as stage I, II, and III disease, respectively. Stage III disease also includes T1, T2, or T3 tumors with N1 disease, defined as metastasis in a single ipsilateral lymph node, <3 cm in greatest dimension, and without extracapsular extension.  Finally, stage IV disease is reserved for higher burdens of nodal disease (N2-N3), T4 tumors, or any distant metastatic disease (M1).

References

1. Amin MB, Edge SB, Greene FL, et al. eds. AJCC Cancer Staging Manual. 8^th ed.  New York, NY: Springer; 2017.
2. Edge SB, Byrd DR, Compton CC, et al. eds.  AJCC Cancer Staging Manual. 7^th ed. New York, NY: Springer; 2010.