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Case Reports

Abstract

Malignant melanoma (MM) shows a wide variety of morphological subtypes in which architectural and cytological diversity is attributed to clinical and genetic features. Plexiform MM is characterized genetically by WNT-activation, and morphologically by heavily pigmented dermal fascicles. It usually mimics deep penetrating/plexiform nevus (DPN) with malignant features. We report 3 cases of hypopigmented plexiform MM with a myxoid background. All were male (median age 63.4 years) with tumors located on the back, ankle, and arm. The tumors presented as amelanotic nodules (average size 1.2cm). Morphologically, all cases displayed a massive infiltration of the dermis by fascicles arranged in a plexiform architecture. There was an important myxoid background, but limited or absent pigment load. Melanocytes were epithelioid and spindle-shaped. Cellular atypia was mild. Mitoses were scant. Breslow thickness ranged from at least 2.7 to 8.7mm (median of 7.1 mm). Alcian blue stain highlighted the myxoid background. The genetic analysis identified a BRAF V600E mutation in 2 cases and a NRAS Q61K in 1 case mutation, and WNT activation with respectively CTNNB1 exon 3 (p.G34E), APC exon 16 (p.Q999*), and APC exon 5 (p.D170fs*4) mutations by whole-exome RNA sequencing. Immunohistochemical analysis confirmed aberrant nuclear accumulation of beta-catenin in all cases. This report indicates a novel morphological variation in WNT-activated MM, increasing diagnostic difficulties in such cases. Supplementary molecular anomalies could be responsible for the myxoid background but remain to be identified.