AJCC Classification

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The American Joint Committee on Cancer (AJCC) Melanoma Expert Panel introduced recently several major changes to the Tumor, Nodes, Metastasis (TNM) classification and stage system based on the analysis of a large database comprising of >46.000 stage I-III melanoma patients diagnosed since 1998 from 10 centers worldwide (1).


MAJOR CHANGES The key changes as introduced in the AJCC 8th edition are summarized here: • Definitions of T1 tumors are revised with 0.8mm as threshold and mitotic rate being no longer a T category criterion; T1a is defined as non-ulcerated melanomas <0.8mm and T1b as melanomas 0.8-1.00 mm in thickness regardless of ulceration or ulcerated melanomas <0.8mm • Tumor thickness measurements are recorded to the nearest 0.1 mm, not 0.01 mm • The N category descriptors “microscopic” and “macroscopic” for regional node metastasis are redefined as “clinically occult” and “clinically apparent” • Prognostic stage III groups are currently based on not only N category criteria but also T category criteria (ie, primary tumor thickness and ulceration) resulting in 4 subgroups (stages IIIA-IIID) (Figure 2) • N category is revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes • Central nervous system involvement is designated as M1d • Descriptors (0 or 1) are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c)


THE T CATEGORY In the eighth edition, the T-category thresholds of melanoma thickness continue to be defined at 1, 2 and 4mm (Table 1); however, T1 is now subcategorized by tumor thickness cut off of 0.8mm. As a result, patients with primary melanoma with no evidence of metastasis are stratified into 8 categories (Table 1). Mitotic rate is not included as a T1 staging criterion, since a multivariate analysis model suggested that it is weak predictor of survival compared to ulceration and tumor thickness (p=0.57) (1). Similar to the seventh edition, the presence or absence of ulceration of the primary tumor is designated “a” or “b” in each T subcategory respectively. Generally, ulceration represents an impaired prognostic factor for survival, with similar survival to that of a patient with non-ulcerated tumor in the next highest tumor thickness category (2-5). Patients with melanoma in situ are instantly categorized as Tis and patients with unknown primary as T0. T category should be recorded as Tx if the tumor thickness cannot be assessed e.g. in cases of incomplete excision or missing epidermal fragments. Lastly and on the basis of consensus recommendations, thickness measurements should be recorded to the nearest 0.1mm, not the nearest 0.01mm due to impracticality and imprecision, especially for tumors >1mm.


THE N CATEGORY N category defines metastatic disease either in regional lymph nodes and/or in non-nodal loco-regional sites (eg microsatellites, satellites or intransit metastasis). The term microscopic and macroscopic disease are replaced by “clinically occult” and “clinically detected” respectively. “Clinically occult” nodal metastasis describes patients with only microscopically identified disease detected by sentinel lymph node biopsy (SLN). In contrast, “clinically detected” nodal metastasis describes patients with regional node metastasis identified by clinical, or radiological examination. If microsatellites, satellites or in transit metastasis are present, then patients are automatically subcategorized as N1c, N2c, N3c according to the number of tumor-involved loco-regional lymph-nodes independently of whether being clinically occult or detected (Table 2).


THE M CATEGORY For the eighth edition, the M-category was refined by including also patients with central nervous system (CNS) involvement (M1d). M1 category is currently defined by both anatomic site of distant disease and LDH levels for all subcategories. Analytically and for each M1 subcategory, descriptors, designated as “[0]” for not elevated LDH and “[1]” for elevated, were additionally added (Table 3).

AJCC pathological staging of the primary melanoma is shown in Figure 1. Figure 2 shows the AJCC stage III subgroups based on T and N categories. Original and primary source of this information is the AJCC Cancer Staging Manual, eight edition (2017) published by Springer International (Gershenwald JE et al)(6).


REFERENCES


  1. Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472-92.
  2. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199-206.
  3. Bach CM, Murad TM, Soong SJ, Ingalls AL, Halpern NB, Maddox WA. A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark's and Breslow's staging methods. Ann Surg. 1978;188(6):732-42.
  4. Charles M. Balch, Jeffrey E. Gershenwald, Seng-jaw Soong, John F. Thompson, Shouluan Ding, David R. Byrd, et al. Multivariate Analysis of Prognostic Factors Among 2,313 Patients With Stage III Melanoma: Comparison of Nodal Micrometastases Versus Macrometastases. J Clin Oncol. 2010;28(14): 2452–2459. .
  5. Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Nieweg OE, Roses DF, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7):599-609.
  6. JE G, RA S, KR H, al e. Melanoma of the skin. In: Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York: Springer International Publishing; 2017:563-85.