Page 22 - SPD Review Winter 2014

Literature Review - Winter 2014

Blatt J, Powell CM, Burkhart CN, Stavas J, Aylsworth AS. Genetics of Heman- variant of CMN. Furthermore, these are distinct from common nevi spilus, which

giomas, Vascular Malformations, and Primary Lymphedema. J Pediatr Hema- are secondary to mutations in HRAS. (Submitted by Markus Boos, MD PhD)

tol Oncol. 2014:36;587-593.

Ehrhardt MJ, Humphrey SR, Kelly ME, Chiu YE, Glabraith SS. The Natural His-

For the majority of vascular tumors and malformations, the underlying genetic tory of Skin-limited Langerhans Cell Histiocytosis: A Single-institution Experi-

etiology has not been found. However, in the past few years, there has been a ence. J Pediatr Hematol Oncol. 2014:36;613-616.

dramatic increase in the genetic understanding of many vascular anomalies.

This article nicely summarizes the forty genes and genetic loci that have been This retrospective chart review study from the Medical College of Wisconsin

associated with various vascular tumors and malformations. In addition, the examined the natural history of isolated skin-only Langerhans cell histiocytosis

authors review important concepts pertinent to vascular anomalies including (LCH), and speciically addressed how often skin-limited disease progressed to

allelic heterogeneity (i.e., that different mutations in a given gene can give rise systemic disease. Prior descriptions have generally concluded that skin-limited

to the same anomaly), phenotypic heterogeneity (i.e. that mutations in a single disease often progresses to systemic disease. Of 16 patients with skin-limited

gene can give rise to more than type of vascular anomaly), and lastly, locus LCH identiied at Children’s Hospital of Wisconsin from 2001-20012, one patient

heterogeneity (i.e., similar vascular anomalies can be associated with multiple went on to develop pituitary disease and 1 patient had persistent/refractory cu-

causative genes.) (Submitted by Deborah Goddard, MD)
taneous disease. The remaining 14 patients had complete resolution, and on

average, experienced resolution of cutaneous features within 7 months from

disease onset. The authors conclude that progression from skin-limited LCH to

 TUMORS AND NEOPLASIA
multisystem LCH may occur less frequently than previously thought.

(Submitted by Deborah Goddard, MD)

Kinsler V, Krengel S, Riviere J, et al. Next-Generation Sequencing of Nevus

Spilus–Type Congenital Melanocytic Nevus: Exquisite Genotype–Phenotype Simko SJ, Garmezy B, Abhyankar H, et al. Differentiating skin-limited and mul-

Correlation in Mosaic RASopathies. J. Invest. Dermatol. 2014; 134: 2658-2660.
tisystem Langerhans cell histiocytosis. J Pediatr. 2014;165(5):990-996.

In this study, Kinsler and colleagues use whole exome sequencing to determine The authors performed a 6-year retrospective review of 71 patients with Lang-

the genetic basis of nevus-spilus type congenital melanocytic nevi (CMN). From erhans cell histiocytosis (LCH) at a single center to identify features of LCH that

three patients they obtained blood and skin samples of both the café-au-lait are associated with multisystem involvement and therapeutic failure. When

portion of the lesion and a superimposed CMN. After analysis, the authors de- patients were older than 18 months of age at the time of diagnosis, there was

termined that the mutation present in each patient’s café-au-lait and its overlay- an odds ratio of 9.65 of multisystem LCH. Also, 40% of patients referred for

ing CMN was a single missense mutation in NRAS, without an accompanying skin-limited LCH to oncology had underlying multisystem involvement, with half

“second hit.” The authors note that the mutations identiied have never before involving risk-organs (predictive of increased mortality) such as liver, spleen

been described in CMN and conclude that nevus-spilus type CMN are distinct
or bone marrow. Those with skin-limited LCH in this center had a 3-year, pro-

22 SOCIETY FOR PEDIATRIC DERMATOLOGY  www.pedsderm.net