Giant congenital melanocytic nevus with vascular malformation and epidermal cysts associated with a somatic activating mutation in BRAF

Heather C. Etchevers (1, 2) , Christian Rose (3) , Birgit Kahle (4) , Helmuth Vorbringer , Frederic Fina (5, 6) , Pauline Heux (1, 2) , Benjamin Schwarz (1) , Stéphane Zaffran (2, 1) , Nicolas Macagno (5, 7) , Sven Krengel (3)

1 GMGF - Génétique Médicale et Génomique Fonctionnelle
2 AMU MED - Aix-Marseille Université - Faculté de médecine
3 Dermatological group practice, Lübeck
4 Universitätsklinikum Schleswig-Holstein
5 TIMONE - Hôpital de la Timone [CHU - APHM]
6 ACPNP - Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM]
7 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie

Giant congenital melanocytic nevi may be symptomatically isolated, or syndromic. Associations with capillary malformations are exceptional, and development of epidermal cysts has not been described. A 71-year old patient with a giant congenital melanocytic nevus of the lower back, buttocks and thighs was asymptomatic except for unexpected hemorrhage during partial surgical excision years before. Blunt trauma at age 64 initiated recurrent, severe pain under the nevus; multiple large epidermal cysts developed within it. Imaging and biopsy showed a large, non-pulsatile venous malformation intermingled with the deep nevus. A low-abundance, heterozygous BRAF c.1799T>A (p.V600E) mutation was present in both the gluteal and occipital “satellite” nevi; additional mutations in NRAS, GNAQ, GNA11, HRAS and PIK3CA were undetectable. This is the first demonstration of an identical BRAF mutation in multiple congenital nevi from the same individual, confirming genetic heterogeneity in giant nevi. This exceptional case indicates that constitutive activation of BRAF can be an underlying cause of unusual associations of giant nevi with vascular malformations, and that the latter may be included among the somatic RASopathies.

Mots clés: congenital; nevus; melanocyte; malformation; venous; BRAF

Domaines: Génétique humaine; Dermatologie; Physiologie [q-bio.TO]

Heather C. Etchevers, Christian Rose, Birgit Kahle, Helmuth Vorbringer, Frederic Fina, et al.. Giant congenital melanocytic nevus with vascular malformation and epidermal cysts associated with a somatic activating mutation in BRAF. 2017. ⟨hal-01613153v1⟩