Agminated blue nevus with a GNAQ mutation: A case report and review of the literature

Abstract

Agminated blue nevi are dermal melanocytic proliferations that classically present as dark blue macules or papules in a grouped, linear, or blaschkoid distribution. In their more common sporadic form, blue nevi manifest in young adulthood as solitary blue papules or macules on the scalp, face, hands, or feet. By contrast, agminated blue nevi tend to manifest earlier in life, and are distributed more evenly across anatomic sites. Recent studies have identified mutations in sporadic blue nevi in the genes encoding G Protein subunit alpha Q and G protein subunit alpha 11 (GNAQ and GNA11). It is unknown whether agminated blue nevi share the same genetic changes. In the present paper, we present a case of agminated blue nevus on the wrist, and identify an activating mutation (c.626A > T, p.Glu209Leu) in GNAQ. We hypothesize that GNAQ/GNA11 activating mutations arising earlier during development may trigger agminated blue nevi, explaining the broader field of involvement in these cutaneous lesions.

Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular Malformations

“…In a biopsy from a patient who had a capillary–venous malformation near an eyebrow [ 20 , 21 ] we found a mutation in GNAQ (NM_002072.4), p.(Gln209Arg). As far as we know, this is the first time that this mutation has been linked to a capillary–venous malformation.…”

GNAQ Q209R Mutations Are Highly Specific for Circumscribed Choroidal Hemangioma

“…Congenital hemangioma of the skin (RICH and NICH), which also cluster within this group, are an exception [10]. Other neoplasms that belong to this cluster are melanocytic tumors, specifically melanocytoma, nevus of the skin, blue nevus, choroidal nevus, choroidal melanoma, and vascular tumors like congenital hemangioma, hepatic small vessel neoplasia, anastomosing hemangioma, cherry angioma, and circumscribed choroidal hemangioma [9,10,12,13,14,15,16,17,18,29,30,31,32,33]. It is common for these tumors that make up this cluster to show continuous cell proliferation.…”

“…GNAQ and its paralogue GNA11 each encode an alpha subunit of a heterotrimeric G protein, a binding protein that remains in its active GTP-bound state when mutated [7,8,9]. Both genes have been reported to be mutated in several vascular malformations such as congenital hemangioma of the skin and cherry angioma and in melanocytic tumors (choroidal nevus, uveal melanoma, melanocytoma, blue nevus) [6,9,10,11,12,13,14,15,16,17,18]. Moreover, GNAQ or GNA11 mutations have been detected in several neural crest disorders such as Sturge Weber Syndrome (SWS).…”

Agminated blue nevi: a case series and updated dermoscopic review

“…The term "agminate" derives from the Latin word "agminis" and indicates the army or troop [3]. ABN can be congenital or acquired, but they tend to occur earlier in life compared to blue nevi, which present most frequently in the second decade of life [1]. The occurrence of reported ABN is nearly identical in females and males.…”

“…Blue nevi (BN), usually presenting as solitary, bluish, asymptomatic macules or nodules, are formed by collections of dermal melanocytes that failed to complete their migration from the neural crest to the dermo-epidermal junction. The term "agminated blue nevi" refers to multiple lesions grouped, linear, or arranged in a blashkoid distribution [1]. It is a relatively rare phenomenon with less than 35 cases reported in the literature, but only 14 cases with dermoscopic features.…”