Prognostic Predictors of Thin Melanoma in Clinico-Pathological Practice

The latest reviews on thin melanoma (TM) continue to consider it a melanoma within 1 mm in thickness, but no consensus exists as to which patients with TM are at risk for lymph node metastases (1). Numerous studies have evaluated the impact of various predictors (Breslow thickness, Clark level, ulceration, regression, vascular invasion, mitotic activity, location, sex) for nodal disease in melanoma, but the conclusions have not been homogenous (2,3). For this reason, we read the paper by Homolak et al. with great interest, where the authors examine the sentinel lymph node biopsies (SLNB) of 184 patients affected by melanoma of thickness less than 1.5 mm, defined as thin (4). SLNB was positive in 22 patients (12%), and 30 patients (7.65%) developed metastatic disease. The group of thinnest tumors (<0.50 mm) had the highest proportion of positive nodes (33%); the group of thickest tumors (1.26-1.50 mm) had the highest proportion of patients with metastatic disease (23%). The authors divided TM into 5 groups: 1) <0.50 mm (15 patients, 5 with positive SLNB); 2) 0.50-0.75 mm (18 patients, 3 with positive SLNB); 3) 0.76-1.00 mm (67 patients, 7 with positive SLNB); 4) 1.01-1.25 mm (45 patients, 4 with positive SLNB); 5) 1.26-1.50 mm (36 patients, 3 with positive SLNB). The current staging system of the American Joint Committee on Cancer (AJCC) uses Breslow thickness as the primary attribute, and up to 1 mm thick melanoma is defined as 'thin' because it shows a good prognosis after surgical excision, with a 10-year survival rate of 85-90% in case of a tumor-free margin of at least 1 cm (5). Based on our experience, this limit should be maintained at 1 mm because TM includes four main histological subtypes, which reflect specific biological attitudes: the intra-epidermal (in situ) radial growth phase (RGP), the non-tumorigenic micro-invasive radial growth phase without regression, the micro-invasive radial growth phase with regression (>75%) of uncertain tumorigenic potential, and the tumorigenic early (≤1 mm) invasive vertical growth phase (VGP) (6-10). This proposed sub-typing fits better with the AJCC staging system, as elucidated below and in Table 1: intra-epidermal radial growth phase (pTis), micro-invasive radial growth phase without regression (pT1), micro-invasive radial growth phase with regression (pT1), early invasive vertical growth phase (pT1), invasive vertical growth phase >1 mm, ≤2 mm (pT2), invasive vertical growth phase >2 mm, ≤4 mm (pT3), invasive vertical growth phase >4 mm (pT4). The in situ RGP and micro-invasive RGP without regression are biologically indolent if completely removed, and SLNB is not necessary in these cases (6). In micro-invasive RGP with regression, performing SLNB is prudent, in particular if accompanied by high mitotic rates, while it is mandatory in early invasive VGP (7). Therefore, the prognostic predictors of nodal and distant metastases require further research in the four above-mentioned histological subtypes of thin melanoma.