title: Costello Syndrome and Umbilical Ligament Rhabdomyosarcoma in Two Pediatric Patients: Case Reports and Review of the Literature.
abstract: Costello syndrome is caused by heterozygous de novo missense mutations in the protooncogeneHRASwith tumor predisposition, especially rhabdomyosarcoma. We here report two pediatric patients with Costello syndrome and umbilical ligament rhabdomyosarcoma. A review of the literature published in English in MEDLINE from January 1971 to June 2016 using the search terms "Costello syndrome" and "rhabdomyosarcoma" was performed, including two new cases that we describe. Twenty-six patients with Costello syndrome and rhabdomyosarcoma were recorded with mean age of diagnosis of 2 years and 8 months. The most common tumor location was the abdomen/pelvis, including four out of ten of those in the umbilical ligament. The most common histological subtype was embryonal rhabdomyosarcoma. Overall survival was 43%. A total of 17 rhabdomyosarcomas in pediatric patients arising in the umbilical ligament were recorded with mean age of diagnosis of 3 years and 4 months. Overall survival was 69%. Costello syndrome is a poorly known disorder in pediatric oncology but their predisposition to malignancies implies the need for a new perspective on early diagnosis and aggressive medical and surgical treatment.
authors.affiliation: Pediatric Surgical Oncology Section, Oncology Service, Department of Hematology-Oncology, Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera", Paseo Colón, 1654-1000 San José, Costa Rica; Oncology Section, Department of Pediatric Surgery, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
authors.forename: Carlos
authors.identifier: 0000-0002-1488-0382
authors.initials: C
authors.lastname: Sánchez-Montenegro
authors.affiliation: Oncology Section, Department of Pediatric Surgery, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Vilanova-Sánchez
authors.affiliation: Oncology Section, Department of Pediatric Surgery, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
authors.forename: Saturnino
authors.initials: S
authors.lastname: Barrena-Delfa
authors.affiliation: Institute of Medical and Molecular Genetics (INGEMM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Paseo de la Castellana 261, 28046 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Calle Sinesio Delgado 4, 28029 Madrid, Spain.
authors.forename: Jair
authors.initials: J
authors.lastname: Tenorio
authors.affiliation: Institute of Medical and Molecular Genetics (INGEMM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Paseo de la Castellana 261, 28046 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Calle Sinesio Delgado 4, 28029 Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Santos-Simarro
authors.affiliation: Institute of Medical and Molecular Genetics (INGEMM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Paseo de la Castellana 261, 28046 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Calle Sinesio Delgado 4, 28029 Madrid, Spain.
authors.forename: Sixto
authors.initials: S
authors.lastname: García-Miñaur
authors.affiliation: Institute of Medical and Molecular Genetics (INGEMM), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Paseo de la Castellana 261, 28046 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Calle Sinesio Delgado 4, 28029 Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.affiliation: Oncology Section, Department of Pediatric Surgery, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Martínez-Martínez