ABSTRACT

First described by Sophie Spitz, 1 epithelioid and/ or spindled cell nevi share some clinical and histologic features with melanomas. Subsequently, a deeply pigmented melanocytic lesion, predominantly in young adults on the lower extremities, was described. 2 Since the clinicopathologic distinction between pigmented Spitz nevus and Reed nevus is highly controversial, 3 the term spindle and/or epithelioid cell nevus 4 and the term Spitz nevus have been employed as unifying definitions for this diagnostic category. Usually, Spitz nevi appear clinically as solitary, firm, dome-shaped, round-to-oval papules or nodules, in a wide spectrum of colors, including red, tan, or dark brown, located on the lower extremities and the face ( Figures 4.158 , 4.164). 5 The lesion is frequently observed in children, although more than half of the cases occur in patients > 14 years old. 6 Dermoscopy, which enables the in-vivo observation of subsurface structures, increases the diagnostic accuracy for Spitz nevi, identifying characteristic features which correlate with specific histologic findings ( Figures 4.159 , 4.165 ). 7,8 However, some cases are still impossible to distinguish from dysplastic nevi or melanomas. 9,10 Histologically, these lesions are defined by a set of characteristic features, including several features which overlap with melanoma. In spite of their bizarre histology, Spitz nevi can usually be differentiated from melanomas by well-demarcated lateral margins, the presence of a distinctive, symmetrical pattern of growth, maturation of cells with increasing depth, uniform nuclei, and by the absence of atypical mitoses and deep dermal invasion. 11

Findings on reflectance confocal microscopy (RCM) of Spitz nevi 12,13 include the presence of ‘pagetoid’ cells within the superficial layers of the epidermis in approximately half of the cases. In comparison to melanoma, pagetoid melanocytosis is usually less abundant, predominantly located in the center of the lesion, and constituted by small, elongated cells with short dendritic-like branches. 14 Moreover, thin elongated cells with peripheral dendritic processes at the extremities are frequently observed in the basal and suprabasal layers, corresponding to spindle cells on histology ( Figures 4.162 , 4.163 ). A rim of dense nests regularly distributed at the lesion’s perimeter is observed in many cases and directly correlates with the peripheral globules seen on dermoscopy and the peripheral melanocytic nests sharply demarcating the lesion’s border on histology ( Figures 4.160, 4.161, 4.165 – 4.169 ). Numerous large melanocytic dense clusters are found throughout the whole lesion in Spitz nevi, showing a globular appearance on dermoscopy ( Figures 4.165-4.171 ). 15 Spitz nevi presenting a homogeneous diffuse pigmentation and/or pigment network on dermoscopy are predominantly characterized by non-edged papillae at the dermal-epidermal junction (DEJ), sometimes with the presence of atypical cells within the epidermal basal layer. 16 In a small proportion of cases, the lesions show roundish rings of refractive cells surrounding dermal papillae, called edged papillae, corresponding to regular rete ridges with elongated cristae on histology. 16 Numerous plump bright cells, corresponding to melanophages, may be seen in the

dermis and blood vessels and are frequently observable in the upper dermis. 17 The asymmetric silhouette, which usually makes distinction from melanoma impossible on dermoscopy, corresponds in some cases to melanophages aggregated at one pole of the lesion. In nodular lesions, large confluent irregular clusters of cells, non-homogeneous in shape and reflectivity, are observed in the upper dermis and correspond to ovoid nests composed of densely clustered large epithelioid cells on histology. In conclusion, RCM enables the in-vivo evaluation of cytologic and architectural features of Spitz nevi, which correlate with histology. Nevertheless, the limited imaging depth prevents complete examination of the dermal component for features such as deep mitoses and cellular maturation, and does not permit a definite differentiation from melanoma in most cases.