Endocrine Abstracts

Objectives: BRAFV600E mutation is present in 50% of aggressive papillary thyroid carcinoma(PTC). TERT promoter (pTERT) mutations (C228T, C250T) are related to cancer growth and reduced overall- and disease-free survivals in differentiated thyroid carcinomas(DTC). We report a patient with an extremely aggressive PTC presenting in the primary lesion two pTERT mutations (C228T and C250T), and absence of BRAFV600E.

Case Report: Female, 39-year-old, euthyroid patient referred a 10-year multinodular goiter, developed compressive symptoms during last year. Cytology of largest nodule was not suggestive of malignancy. Total thyroidectomy was performed due to compression. Histopathology revealed multifocal PTC follicular variant with areas of classic form within the hyperplasic nodules (5.3 cm in right lobe; 3.5 cm in left lobe; two 0.9 cm foci in isthmus) (pT3N0M0). Patient received adjuvant radioiodine ablation therapy(RIT); 150mCi 131I; Tg=68ng/dL, anti- TgAb undetectable, TSH=73mUI/dL. Two years later, a whole-body 131I scintigraphy(WBS) demonstrated diffuse iodine-avid pulmonary metastases; Tg=1,100ng/dL, negative TgAb. After five years, 18F-FDG PET/CT images revealed hypermetabolism in cervical lymph node metastases bilaterally and in pulmonary nodules; Tg=2,991ng/dL; TgAb undetectable. After seven years, patient presented pathological fractures (humerus, right tibia), soft tissues infiltration. 18F-FDG-PET/CT revealed widespread lungs metastases, cervical lymph nodes, left breast, gluteus maximus, mediastinal, axillary, and inguinal lymph nodes. Hypermetabolic metastatic lytic bone lesions were noted in skull, mandible, clavicle, ribs, humerus, femur, pelvis, T2 vertebra. Patient received three adjuvant RIT (1223mCi), without response. Palliative radiotherapy was performed in skull, humerus, left leg with partial reduction. There was lung metastases reduction with sorafenib, and progression of the other. Patient progressed with bronchial obstruction from lung metastases and died from respiratory failure eight years after the initial diagnosis. Molecular analysis of primary tumor tissue revealed absence of BRAF V600E mutation, evaluated by qPCR in COBAS Z 480 System (Roche) and presence of both pTERT C228T and C250T mutation, detected by pyrosequencing and validated by droplet digital PCR.

Conclusions: The pTERT mutations C228T and C250T have been described as mutually exclusive, indicating that one mutation is enough for telomerase activation and exert its action on thyroid tumorigenesis. However, in this case report we observed the presence of both pTERT mutations.