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Verrucous seborrheic keratosis with keratoacanthoma‐like features, a pitfall in differential diagnosis

Keratoacanthoma (KA) is a follicular lesion clinically characterized by rapid (1–2 cm within few weeks), abundant, sometimes considerably destructive growth. After a subsequent stationary period, the tumor frequently spontaneously resolves within 4–6 months [1, 2]. Typically arising on hair-bearing, sun-exposed skin in middle-aged and elderly fair-skinned individuals, the lesion clinically presents as a pink to flesh-colored, dome-shaped nodule with a central keratin plug. Rare clinical variants include giant (diameter > 2–3 cm) and abortive KA (lichenoid infiltrate with concurrent involution), keratoacanthoma centrifugum marginatum (progressive peripheral growth, concomitant central healing), non-follicular (subungual, palmar) or syndromic occurrence (for example, Ferguson-Smith, Witten-Zak, Grzybowski, Muir-Torre syndromes) as well as variants with perineural and vascular invasion [3]. Besides its defining clinical growth pattern, characteristic histologic features include an almost symmetric exophytic-endophytic, cup-shaped architecture with a central, Clinical Letter often multilobulated crater filled with an invaginating mass of keratinizing, well-differentiated squamous epithelium (keratin plug); overhanging perforated epithelial lips (collarette) at the edges of the lesion; a well-differentiated epidermis with pale-staining, slightly eosinophilic, glassy keratinocytes with intracytoplasmic glycogen; and a low, usually basal mitotic activity accentuated in the periphery of the squamous nests [3, 4]. Moreover, intraepithelial elastic fibers within the lesional center and a surrounding polymorphous nuclear infiltrate may be found. In this study, we reviewed a total of 1 949 biopsies with histologic characteristics of KA (crateriform architecture, epithelial lip, sharp demarcation) that had been worked up at our institutions since May 2000. Based on histopathologic features and corroborative in-situ hybridization studies, 1 547 specimens (79.3 %) were classified as “classic” squamous cell carcinoma (SCC) with KA-like features and irregular keratocytic bulbs, nests or sheets. Another 389 cases (19.9 %) were diagnosed as human papilloma virus (HPV) papilloma with KA-like features, showing a regular growth pattern with keratocytic lobules oriented towards an imaginary central point above the lesion. These lesions rarely exhibited invasion beyond the depth of sweat glands. Relevant epithelial atypia and stromal desmoplasia were absent, and there was a sharp delimitation between lesional nests and the surrounding stroma. These lesions typically showed positive in-situ hybridization for low-risk HPV subtypes (Figure 1h). In addition, 15 cases (0.8 %) were reported as “verrucous seborrheic keratosis (VSK) with KA-like features” (Figure 1a–g, Table 1). Besides typical KA findings (Figure 1b, d, f) and a well-differentiated epidermis (Figure 1 c, e, g), histopathologic hallmarks of this distinct variant primarily included