Ovarian Yolk Sac Tumor in a 13-year-old Girl with McCune-Albright Syndrome

Abstract

Background MacCune-Albright Syndrome (MAS) is typically characterized by the triad of café-au-lait spots, fibrous dysplasia, and peripheral precocious puberty, along with variety of phenotypes including cancers. Patient and Methods: We report a 13-year-old girl who was found to have both MAS triad and an ovarian yolk sac tumor. Clinical features and follow-up information was documented. Peripheral blood, tumor tissue and biopsy from the benign ovarian were collected for the molecular analysis, DNA samples were extracted from the three kinds of samples. RNA molecules were extracted from tumor biopsy specimen to analyze the expression profile including metabolic and immune characteristics through nanostring. Results Beside the classic triad of MAS, the patient presented with other unique clinical conditions including ovarian yolk sac tumor and autoimmune related thrombocytopenia. Whole exosome sequencing revealed germline pathogenic missense mutation of TP53 and PRSS1. GNAS variations noticed on 5’UTR were likely benign variant. Gene expression profiling suggested the upregulated KRAS and NRAS and down-regulated PTEN in yolk-sac tumor cells as compared to normal tissue. Metabolic analysis of tumor showed weak activity of vitamins metabolism and significantly elevated activity of the tricarboxylic acid cycle. Conclusions This is the first report wherein a patient with MAS was found to have a yolk sac tumor with sequencing demonstrating the germline TP53 mutation. The unusual genetic and expression findings raise the questions in understanding MAS and appropriate longtime surveillance for these patients.