Abstract

Brogna Marianna60593*, Francesca Collina60596, Simona Losito60597, Eduardo Clery60598, Angela Montone60599, Michele Del Sesto60600 and Gerardo Ferrara60601

Background: Papillary Thyroid Cancer (PTC) is the most common type of well differentiated endocrine malignancy. Generally thyroid nodules with multiple oncogenic mutations are uncommon with an occurrence which may be related to more aggressive biological behavior of tumors. Rearranged in Transformation/ Papillary Thyroid Carcinomas (RET/PTC) rearrangement, RAS and BRAF mutations are considered to be mutually exclusive in PTC. Concomitant RET/PTC, RAS, or BRAF mutations have been documented, although the impact of these mutations for tumor growth and survival is debated.

Case presentation: Here, we present a rare case of woman 46 years old with a neck mass and thyroid nodule classified as Toll-Like Receptor 5 (TIR5) on cytological examination. We found contemporary BRAF p.(Val600Glu) (p. (V600E); c. 1799T>A) and NRAS p. (Gln61Arg) (p. (Q61R); c.182A>G) mutations in morphologically different areas within the same lobe (the right one). Two lesions show different morphology. The mutated BRAF lesion showed morphological characteristics compatible with classic papillary carcinoma while the mutant NRAS lesion shows morphological features compatible with follicular variant papillary carcinoma.

Results and conclusion: To the best of our knowledge, this is the first time that such mutations, which are normally mutually exclusive, have been detected at the same time. The findings of synchronous mutations are rare occurrence, suggesting for Intratumoral Heterogeneity (ITH) even in PTC. Patients with multiple mutations have a clinical worse prognosis, generally characterized by an aggressive thyroid cancer, which may influence the surgical treatment, chemotherapy, and BRAF V600E mutation-targeting therapy.