Revisiting a series of epithelial salivary gland tumors in children and adolescents in southern Portugal

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014Introduction: Salivary gland tumors in pediatric population are extremely rare. Most papers are case reports or small series of cases. Objective: To analyze the clinical, epidemiological and histopathological features and outcomes of epithelial salivary gland tumors occurring in the pediatric population. Methods: During a 50-year period, a total of 54 epithelial salivary gland tumors were diagnosed in patients less than 19 years at Instituto Português de Oncologia de Lisboa Francisco Gentil. Demographic, clinical and follow-up data were obtained from medical records and histopathological features were reviewed. Results: The mean of age of the patients was 13.4 years. One case was congenital and the male to female ratio was 1:1.1. Thirty-seven tumors (68.5%) were benign and 17 (31.5%) malignant. Pleomorphic adenoma was the most common tumor type (61.1%), followed by mucoepidermoid carcinoma (22.2%). The parotid gland was affected in most cases (77.8%), followed by minor glands involvement (14.8%). All tumors in submandibular gland were benign. The recurrence rate was 21.6% for benign tumors and the 5-year survival rate was 82.4% for malignant tumors. Conclusions: Epithelial salivary gland tumors in southern Portugal pediatric patients are rare, specialy malignant tumors. Parotid gland is the most common involved site and pleomorphic adenoma and mucoepidermoid carcinoma are the most common benign and malignant tumor, respectively. There is a slight female predominance.Introdução: Os tumores das glândulas salivares são extremamente raros na população pediátrica. A maioria dos artigos científicos publicados são casos clínicos ou pequenas séries de casos. Objetivo: Análise das características clínicas, epidemiológicas e histopatológicas e dos resultados terapêuticos dos casos de tumores epiteliais das glândulas salivares na população pediátrica. Métodos: Durante um período de 50 anos, 54 tumores epiteliais das glândulas salivares foram diagnosticados no Instituto Português de Oncologia de Lisboa Francisco Gentil em doentes com idade inferior a 19 anos. Os dados demográficos, clínicos e de follow-up foram obtidos a partir dos processos clínicos e as características histopatológicas foram revistas. Resultados: A média de idade dos doentes foi de 13,4 anos. O ratio masculino/feminino foi de 1:1,1 e um dos casos era congénito. Trinta e sete tumores (68.5%) eram benignos e 17 (31.5%) malignos. O adenoma pleomórfico foi o tipo histológico mais frequente (61.1%), seguido do carcinoma mucoepidermóide (22,2%). A glândula parótida foi o local afetado na maioria dos casos (77,8%), seguida pelo envolvimento das glândulas salivares minor (14.8%). Todos os tumores da glândula submandibular eram benignos. A taxa de recorrência foi de 21.6% para os tumores benignos e a taxa de sobrevida aos 5 anos foi de 82.4% para os tumores malignos.Conclusões: Os tumores epiteliais das glândulas salivares são raros na população pediátrica do sul de Portugal. A glândula parótida é o local afetado na maioria dos casos; o adenoma pleomórfico e o carcinoma mucoepidermóide são os tumores benigno e maligno mais comuns, respetivamente. Verifica-se uma pequena predominância feminina

Unraveling the genetic background of individuals with a clinical familial hypercholesterolemia phenotype

Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism caused by pathogenic/likely pathogenic variants in LDLR, APOB, and PCSK9 genes. Variants in FH-phenocopy genes (LDLRAP1, APOE, LIPA, ABCG5, and ABCG8), polygenic hypercholesterolemia, and hyperlipoprotein (a) [Lp(a)] can also mimic a clinical FH phenotype. We aim to present a new diagnostic tool to unravel the genetic background of clinical FH phenotype. Biochemical and genetic study was performed in 1,005 individuals with clinical diagnosis of FH, referred to the Portuguese FH Study. A next-generation sequencing panel, covering eight genes and eight SNPs to determine LDL-C polygenic risk score and LPA genetic score, was validated, and used in this study. FH was genetically confirmed in 417 index cases: 408 heterozygotes and 9 homozygotes. Cascade screening increased the identification to 1,000 FH individuals, including 11 homozygotes. FH-negative individuals (phenotype positive and genotype negative) have Lp(a) >50 mg/dl (30%), high polygenic risk score (16%), other monogenic lipid metabolism disorders (1%), and heterozygous pathogenic variants in FH-phenocopy genes (2%). Heterozygous variants of uncertain significance were identified in primary genes (12%) and phenocopy genes (7%). Overall, 42% of our cohort was genetically confirmed with FH. In the remaining individuals, other causes for high LDL-C were identified in 68%. Hyper-Lp(a) or polygenic hypercholesterolemia may be the cause of the clinical FH phenotype in almost half of FH-negative individuals. A small part has pathogenic variants in ABCG5/ABCG8 in heterozygosity that can cause hypercholesterolemia and should be further investigated. This extended next-generation sequencing panel identifies individuals with FH and FH-phenocopies, allowing to personalize each person’s treatment according to the affected pathway