In 2010, the seventh edition of the AJCC TNM staging manual incorporated significant novelties in NMSC classification.24 For the first time, a separate staging system was introduced for Merkel cell carcinoma (MCC), which until then had been classified with the same staging system as other NMSC. This means that all forms of NMSC other than MCC should be classified according to the criteria for SCC. TNM classification for MCC has been modified in the most recent edition2 in light of a study that assessed clinical outcomes in a large series of patients.25 In reality, T categorization has not been changed, but there are significant changes in N categorization and stratification of stages I-IV.2,25 Furthermore, clinical and pathologic staging are separated out in this eight edition of the manual.2,25 In the T category, MCC is classified as T1 if it measures 2cm or less in the largest dimension, T2 if it measures between 2 and 5cm in the largest dimension, T3 if it measures more than 5cm, and T4 if it invades deep structures (bone, muscle, fascia, or cartilage).2,25

Within the N category, a tumor is considered N1 if metastasis to the regional lymph nodes is present, N2 if in transit metastasis is present without metastasis to the regional lymph nodes, and N3 if both in transit and lymph node metastases are present. With regards the corresponding pathologic staging within the N category, a distinction is made between the N1a subtype (clinically occult, detected by lymph node dissection), N1a(sn) subtype (clinically occult, detected by selective lymph node biopsy), and N1b subtype (detected clinically and radiologically and confirmed by biopsy). In the case of the M category, M1a is used for skin or distant subcutaneous involvement (not in transit metastasis, which would be covered within the N category) or involvement of distant lymph nodes (not regional ones); category M1b refers to lung involvement and M1c to involvement of viscera other than the kidney. If microscopic confirmation is obtained, the tumor is considered pM1, with its corresponding subclassification. Table 1 summarizes the current staging system for MCC.

In the case of the staging system for SCC, the seventh edition included a series of high risk factors that permitted modification of the T category of a primary tumor regardless of the horizontal size (this represented an important advance compared with previous editions) (Table 2).24 Specifically, the manual recognized poor degree of histological differentiation, perineural infiltration, vertical depth of more than 2mm, Clark levels iv and v, and the involvement of the ear or lower lip, along with the horizontal size of the tumor as risk factors defining the T category of the primary tumor: a) a tumor measuring <2cm with <2 risk factors was T1; b) a tumor measuring >2cm or measuring <2cm with 2 or more risk factors was considered T2; c) T3 or T4 corresponded to bone invasion: T3 corresponded to invasion of the maxillary, mandibular, orbital, or temporal bones, while T4 corresponded to invasion of other bones or perineural infiltration of the base of the cranium.24 However, not all risk factors were included and, as validation studies were performed, deficiencies emerged. The main criticism was that the T2 category encompassed a range of heterogeneous patients in terms of risk and prognosis.26–31 The seventh edition of the staging manual seemed to focus on the poor prognosis of SCC in T2 tumors.32,33 In fact, in a cohort of 1818 patients, only 6 cases of T3-T4 tumors were detected and most adverse outcomes occurred in tumors classified as T2 (72% of local relapses, 82% of lymph node metastases, and 67% of disease-specific deaths).32

The eight edition of the AJCC2 seems to have taken into account some studies that had focused, on the one hand, on assessing the influence of thickness on prognosis,21 and on the other the influence of thickness of the involved nerve branch that infiltrates the tumor and the depth of invasion of the SCC32 for stratification of the T category (Table 2). N stratification is based on the system shared with other head and neck tumors. Moreover, for the first time, SCC of the head and neck is given its own independent section (in previous editions, NMSC referred in general to any site) and includes SCC of the lower lip given its relationship with UV radiation. However, it excludes a site on the eyelid and all tumors located outside the head and neck. Although for the special sites of the eyelid, vulva, penis, and perineal region, the AJCC manual offers solutions, it does not define any system for classification of tumors located outside the area of the head and neck, and so does not cover these particular sites. This is clearly a drawback and means, for example, that an SCC on the dorsum of the hand cannot be classified according to the eighth edition of the AJCC TNM staging manual. On the other hand, forms of NMSC other than SCC and MCC follow the same criteria as SCC (as was the case in previous editions).

Regarding the T category, the eighth edition of the AJCC considers a tumor measuring less than 2cm in greatest dimension as T1, one measuring 2 to 4cm as T2, and one greater than 4cm as T3. So far, this category is similar to editions prior to 2010. However, a tumor is also T3 if it has a thickness greater than 6cm, if it shows perineural infiltration of nerve branches of more than 0.1cm, if invasion extends beyond the fatty tissue, or if it shows minimal bone erosion. The tumor is classified as T4 if it invades the bone more extensively, as well as if it invades the base or foramen of the cranium.2 Thus, tumors with poor prognosis should tend to be categorized as T3. In view of the study by O’Brien et al,34 the expert panel of the AJCC considered staging patients also in accordance with progressive lymph node involvement. The N category is based on a system shared with other tumors of the head and neck. A tumor is considered N1 if it involves an isolated ipsilateral lymph node, is less than 3cm in diameter, and is without extracapsular extension, N3 if there is metastasis to a major lymph node and it is more than 6cm in diameter or any size if there is extracapsular extension. N2 is used for intermediate situations between N1 and N3 (Table 3). On the other hand, involvement of other organs is defined as M1 (without establishing any subgroups). Table 3 summarizes classification of SCC of the head and neck according to the latest edition of the TNM AJCC staging manual.

The following criticisms could be made: 1) Omission of certain risk factors; 2) lack of a specific staging system for basal cell carcinoma or for other forms of NMSC (excluding MCC, which has its own staging system since 2010); 3) exclusion of sites other than the head and neck, which means that some cases cannot be staged according to the eighth edition of TNM of the AJCC. However, the system seems to have improved significantly compared with previous editions and at least considers relevant factors that had been ignored in the past, although validation series would be necessary for confirmation.

The authors declare that no experiments were performed on humans or animals for this investigation.

The authors declare that they have followed their hospital's protocol on the publication of data concerning patients.

The authors declare that patient data do not appear in this article.