Patient with confirmed LEOPARD syndrome developing multiple melanoma

Abstract

LEOPARD syndrome, also known as Gorlin syndrome II, cardiocutaneous syndrome, lentiginosis profusa syndrome, Moynahan syndrome, was more recently coined as Noonan syndrome with multiple lentigines (NSML), inside the RASopathies. Historically, the acronym LEOPARD refers to the presence of distinctive clinical features such as: lentigines (L), electrocardiographic/conduction abnormalities (E), ocular hypertelorism (O), pulmonary stenosis (P), genital abnormalities (A), retardation of growth (R), and sensorineural deafness (D). This condition is identified in 85% of patients with phenotype hallmarks caused by presence a germline point mutation in PTPN11 gene. Association of melanoma to NSML seems to be rare: to our knowledge, two patients so far were reported in the literature. We herein present a patient diagnosed with LEOPARD syndrome, in whom molecular investigation confirmed the presence of the c.1403C>T mutation in exon 12 of the PTPN11 gene, who developed four superficial spreading melanomas and three atypical lentiginous hyperplasias. Three of the melanomas were achromic or hypochromic, three were in situ, and one had a Breslow index under 0.5 mm. Dermoscopic examination showed some characteristic white structures in most of the lesions, which were a signature pattern and a key for the diagnosis.

Keywords: LEOPARD syndrome; dermoscopy; melanomas.

Figure 1

First melanoma of the foot: clinical aspect and dermoscopical aspect. Aspect of eczema. On dermoscopy, shiny white strands, dotted vessels and a structureless pink and brown-gray background (polarized dermoscopy, DermLite Foto, [3Gen, San Juan Capistrano, CA, USA]). Pathology: superficial spreading melanoma developed on nevus, Clark’s level II, a Breslow index of 0.42 mm, and regression phenomenon in the papillary dermis. [Copyright: ©2018 Colmant et al.]

Figure 2

First and second melanoma of the back: clinical aspect and dermoscopical aspect. (A) First melanoma of the back: on dermoscopy white lines with thickening at their crossings (white arrows) (polarized dermoscopy, DermLite Foto). Pathology: lentigo maligna in situ arising on a nevus, with regression phenomenon. (B) Second melanoma of the back: on dermoscopy, classic negative pigment network (black arrow); negative pigment network with thickening at the crossings of some white lines (white arrows) (polarized dermoscopy, DermLite Foto). Pathology: lentigo maligna with regression. . [Copyright: ©2018 Colmant et al.]

Figure 3

Dermoscopy of the four last lesions (A) Not well defined white lines, (B) and (C) Signature pattern: in the negative pigment network, the white lines show thickening at their crossings (white arrows). (D) Shiny white strands and dotted vessels (polarized dermoscopy DermLite Foto). Pathology: (A,) (B), (D) atypical lentiginous hyperplasia; (C) lentigo maligna. [Copyright: ©2018 Colmant et al.]