Abstract

The conventional morphological characteristics of Wnt-activated deep penetrating melanocytic nevi/melanocytomas (DPN) are those of large spindled or epithelioid melanocytes with distinctive voluminous amphophilic cytoplasm, fine pigmented granules, and surrounding melanophages. The central molecular hallmark is the activation of the Wnt-pathway predominantly driven by mutations in the CTNNB1 gene. Although typically lacking a junctional component, a lesser-known superficial subset with a junctional component has been identified, which could potentially lead to diagnostic challenges. This study presents a cohort of ten cases displaying a junctional component of DPN from nine patients (5 females, 4 males; age range: 27-79; median age: 46). The nevi were distributed as follows: one conjunctival, one scalp, two lower limb, and six truncal lesions. Eight cases were combined with a conventional nevus, two cases displayed pure DPN cytology exhibiting only a junctional element, and nine cases exhibited some degree of lentiginous architecture. All cases demonstrated a low mitotic index (<1 mitosis/mm²). Immunohistochemistry revealed positive BRAF staining in 5 cases (5/7), while all cases tested (7/7) were PRAME negative. Nuclear beta-catenin and LEF staining were consistently strong in most cells with DPN cytology (10/10), along with robust cyclin-D1 staining in all cases tested (7/7). In contrast, all 8 conventional nevi showed an absence of nuclear beta-catenin staining (0/8) and weaker, mosaic-type LEF and cyclin-D1 staining was observed in eight and four cases, respectively. This study emphasizes the diagnostic challenge these nevi can pose in the absence of a conventional, deeper DPN component, which can potentially be misdiagnosed as melanoma.