Molecular Alterations in Relation to Histopathological Characteristics in a Large Series of Pediatric Papillary Thyroid Carcinoma from a Single Institution

SIMPLE SUMMARY: Papillary thyroid carcinoma (PTC) in pediatric patients shows different characteristics compared with PTC in adults. In this large mono-institutional cohort of pediatric PTCs, tumor tissue samples have been analyzed for point mutations and fusions. Overall, molecular alterations were detected in 131 out of 163 PTCs (80%). Fusion-driven PTCs showed more aggressive clinico-pathological features compared to mutation-driven and wild-type cases. These results highlight the importance of testing pediatric PTCs for gene rearrangement in routine characterization of tumors. ABSTRACT: Papillary thyroid carcinoma (PTC) presents distinct clinico-pathological and molecular differences in children compared with adult patients. Whether the presence of rearrangements or point mutations is associated with aggressive PTC clinical presentation is still controversial. In this study, PTCs diagnosed in patients aged less than 18 years were retrospectively searched from the institutional archive and tumor tissue was tested for point mutations in BRAF and RAS genes and for rearrangements in RET, NTRK1, NTRK3, ALK, PPARG, BRAF and THADA. A total of 163 PTCs were analyzed. Point mutations were found in 83 (51%) and gene fusions in 48 cases (30%). The most frequent alteration was the BRAF(V600E) mutation (36.8%), followed by NTRK3 fusion (11%), NRAS mutation (10.4%) and RET fusion (10.4%). Fusion-driven PTCs showed more frequently infiltrative growth, larger tumors, extrathyroidal extension and N1b disease. PTCs showing solid growth pattern were significantly enriched in gene fusions. This is one of the largest cohorts of pediatric PTCs. Fusion-driven tumors most frequently show aggressive pathological features; the search for rearrangements, especially in tumors with solid areas, could improve the characterization of pediatric PTCs and offer possible therapeutic options.