ESPE Abstracts (2016) 86 P-P1-41

RET and TP53 Concomitant Mutations: A Challenging Approach to a Unique Association of High Tumor Predisposing Conditions

Matilde Calanchinia,b, Andrea Fabbrib, Ashley Grossmana & Bahram Jafar-Mohammadia


aOxford Center for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK; bDepartment of Endocrinology, University of Tor Vergata Rome, Rome, Italy


Background: A 33-year-old woman with a history of adrenocortical carcinoma (ACC), surgically treated aged 4, presented for prenatal screening at 20 weeks gestation. Ultrasound examination identified that the female foetus had a 3-cm adrenal lesion. She had a positive family history for multiple-endocrine-neoplasia-type 2/MEN2 (paternal grandmother) and her father’s cousin was diagnosed with ACC and Li-Fraumeni syndrome (LFS) at 30 year old. Calcitonin, PTH and cathecholamine were in the normal limits. The rest of pregnancy and delivery were uneventful and two months later her daughter’s CT confirmed an unchanged adrenal mass with predominantly low attenuation. No evidence of cathecholamine excess, neither increased urinary steroid metabolites, precursors of androgens or glucocorticoids were identified.

Objective and hypotheses Method: Aged 2 months, she underwent an adrenalectomy and no histopathological feature of malignancy were reported.

Results: Genetic testing confirmed that the mother was RET (Val804Met) and p53 (Arg158His) mutation positive. The daughter, accordingly with mother’s informed decision, was tested only for RET and the same RET mutation was found. The mother had a prophylactic thyroidectomy. Daughter’s suggested management was thyroidectomy before age 5 years; clinical examination, abdomen ultrasound and hormone evaluation every 6 months.

Conclusion: LFS is an autosomal dominant disorder associated with abnormalities in the p53 oncosuppressor gene. It is characterized by a wide range of malignancies, often at a young age. ACC is one of the LFS core tumors. 68% of individuals with p53 germline mutation develop an ACC before age 4 and before age 20 in about 90%. Any individuals with ACC or family history should be considered for testing for p53 mutations. RET Val804Met mutation is correlated with the MEN2 familiar-medullary-thyroid-cancer phenotype and with low tumor aggressiveness. This is the first case of a concomitant carriage of RET and p53 mutations, both high tumor predisposing conditions. Due to this unique association, a safe, appropriate and effective screening program is mandatory.

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