Endometrial Carcinoma as the Presenting Malignancy in a Teenager With a Pathogenic TP53 Germline Mutation: A Case...

Patients with germline TP53 mutations are characterized by the occurrence of multiple early-onset malignancies. The characteristic syndrome is Li-Fraumeni syndrome (OMIM # 151623), an autosomal dominant disorder typified by premenopausal breast carcinoma, adrenal cortical tumors, bone and soft tissue sarcomas, leukemias, and tumors of the brain and spinal cord. Gynecologic malignancies are uncommonly reported in families harboring TP53 mutations, and the predominant tumor type reported is ovarian. Uterine carcinoma has been reported only a handful of times in patients with germline TP53 mutations, none as a presenting tumor in a teenager. We report on an 18-year-old patient who presented with grade 3, high-stage endometrioid endometrial carcinoma. Sequencing detected a single-nucleotide substitution in the TP53 gene (NM_000546.6:c.818G>A), encoding the missense substitution p.Arg273His (R273H) in both the tumor and normal tissue, consistent with a germline mutation. We discuss the biology of the TP53 gene and p53 protein, with emphasis on the R273H mutation. We also review the literature on endometrial carcinoma in patients with germline TP53 mutations.