Superficial Wnt-Activated Melanocytic Nevi/Melanocytomas With a Junctional Component: A Case Series

Abstract

The conventional morphological characteristics of Wnt-activated deep penetrating/plexiform melanocytomas/nevi (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 beta-catenin ( CTNNB1 ) gene. Although typically lacking a junctional component, a lesser-known superficial variant with a junctional component has been identified, which could potentially lead to diagnostic challenges. This study presents a cohort of 11 such cases displaying a junctional component of DPN from 10 patients (5 women and 5 men; age range: 27-78 years; median age: 51 years). The nevi were distributed as follows: 1 conjunctival, 1 scalp, 2 lower limb, and 6 truncal lesions. Eight cases were combined with a conventional nevus, 2 cases displayed pure DPN cytology exhibiting only a junctional element, and 9 cases exhibited some degree of lentiginous architecture. All cases demonstrated a low mitotic index (<1 mitosis/mm 2 ). Immunohistochemistry revealed positive BRAF V600E staining in 8 cases (8/11), whereas all cases tested (11/11) were PRAME negative. Nuclear beta-catenin and LEF1 staining was consistently strong and diffuse with DPN cytology (11/11), along with robust cyclin D1 staining in all cases tested (11/11). By contrast, all 9 conventional nevi showed an absence of nuclear beta-catenin staining (0/9) and weaker, mosaic-type LEF1 and cyclin D1 staining was observed. 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.

Figure 1

Figure 1A–1H: A conjunctival melanocytic lesion removed from a 64-year-old man composed of conventional (right black arrows) and Wnt-activated components (left red arrows) with voluminous finely pigmented cytoplasm (1A, 20x). In the Wnt-activated cytology, there is strong, diffuse nuclear staining with LEF1 (1B, 20x) and Cyclin D1 (1E, 40x) with less more variable weaker staining in the conventional area (1B & 1F, 40x). Beta-catenin shows strong nuclear and cytoplasmic staining in the Wnt-activated nest (1C, 40x) compared to weaker more variable cytoplasmic staining in the conventional nests (1D, 40x). PRAME is negative (1G, 20x). BRAF is positive in both areas (1H, 20x).

Figure 2

Fig. 2A–2F: An acral combined melanocytic lesion removed from a 27-year-old female composed of Wnt-activated (red arrows; 2A, 20x) and a conventional component in a separate part of the nevus (black arrows; 2B, 20x). There is some lentiginous growth in Wnt-activated cells with strong nuclear Beta-catenin (2C, 40x) staining while the conventional cells show weak or no nuclear staining (2D, 40x). LEF1 and Cyclin D1 show strong nuclear staining in the nested areas with Wnt activated cytology (2E & 2F, 40x, respectively).

Figure 3

Fig. 3A–3F: This junctional nevus was from a 31-year-old male’s back with pure Wnt-activated cytology. Nevus nests are expansile with bridging with adjacent rete ridges. However, the cytology is similar to that seen in other Wnt-activated lesions with the voluminous amphophilic dusty cytoplasm and small nuclei with pin-point nucleoli (3A, 40x). Strong nuclear LEF1 (3B, 40x), beta-catenin (red arrows; 3C, 40x), and Cyclin D1 (3D, 40x) staining can be seen. BRAF V600E is positive in this lesion (3E, 40x), and PRAME is negative (3F, 40x).

Figure 4

Fig. 4A–4D: A compound melanocytic lesion removed from the lower back of a 55-year-old male with combined conventional and Wnt-activated morphology. The cells with Wnt-activated cytology can be seen as nests and lentiginous single cells at the junction. (4A, 20x). There is strong, nuclear LEF1 (4B, 40x) and Cyclin D1 (4D, 40x) staining in the nested and lentiginous Wnt-activated junctional component. Beta-catenin strong nuclear staining further highlights lentiginous portion of the lesion with Wnt-activated cytology (4C, 40x).