Critical points of T1 stage in primary melanoma

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In the eighth edition (2017) of the American Joint Committee on Cancer (AJCC) staging system, T1 (≤1 mm) melanoma (M) has been splitted into two subcategories: T1a (<0.8 mm) without ulceration and T1b (<0.8 mm) with ulceration or T1b (0.8–1 mm) with or without ulceration 1. Mitotic rate is no longer considered as a subcategorization criterion, but it remains a major prognostic determinant 1; in fact, mitogenicity should be assessed and reported in all primary Ms 2. The recommended approach to mitotic evaluation is to find the region containing the highest number of mitoses, the so-called ‘hot-spot’ 1. We are prone to support that the new T1 stage proposed by the AJCC does not fully respect the biology of the lesion. The M growth consists of two phases: the radial growth phase (RGP) and the vertical growth phase (VGP) 3. Clinically, RGP manifests itself as a patch or plaque that expands along the radii of an imperfect circle. On the contrary, VGP refers to growth of an expandable papule within the confines of a previously indolent plaque, which grows in three dimensions, like a balloon to form a nodule 4. The RGP may be intraepidermal or microinvasive. The intraepidermal RGP corresponds to Tis (in-situ M), according to the AJCC, and thickness or ulceration criteria are not applicable. The lesion is characterized by epidermal malignant melanocytes, which proliferate above the basement membrane, and may show pagetoid (superficial spreading M) or lentiginous (acral lentiginous M, lentigo maligna M, mucosal M) proliferative patterns 3. The nontumorigenic microinvasive RGP is characterized by invasion into the papillary dermis (Clark’s levels II or III) of single M cells or into small nests in the absence of nodule or papule. The dermal nests are invariably smaller than junctional ones; the cytological features of the junctional and dermal components are overlapping 3. In the nontumorigenic microinvasive RGP, the absence of mitoses and of regression are absolute criteria, while lymphohistiocytic infiltrate may be present. The nontumorigenic microinvasive RGP can be detected in less than 0.8 mm T1 M, as in 0.8–1 mm T1 M. If the epidermal or microinvasive RGP cells are not adequately removed, they can evolve into VGP cells. This tumorigenic phase is characterized by the presence of a cluster of dermal malignant cells that is larger than the epidermal largest cluster (tumorigenicity); mitoses are found in the dermal M cells (mitogenicity) 5. VGP signifies the point at which M becomes biologically capable of producing metastatic events; it can be present in less than 0.8 mm T1 M, as in 0.8–1 mm T1 M. Therefore, serial histological sections of the lesion are always indicated. We have previously suggested that the tumorigenic potential of microinvasive RGP is uncertain, when extensive regression is present, because it could contain a VGP clone 5–7. In conclusion, we believe that T1 stage in primary microinvasive M include three histological subtypes, which should always be accompanied by the Breslow’s depth specification: (i) nontumorigenic microinvasive RGP M; (ii) microinvasive RGP M with uncertain tumorigenic potential at diagnosis, due to extensive regression (>75%) of the lesion; (iii) submillimetric tumorigenic VGP M. A statement in the sign-out, such as ‘T1 M in RGP’, or ‘T1 M in RGP (>75% regression present)’, or ‘T1 M in VGP’, is recommended.

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