Clinicopathological Characteristics of Papillary Thyroid Cancer in Children with Emphasis on Pubertal Status and Association with BRAFV600E Mutation

Abstract

Objective:

Papillary thyroid cancer (PTC) may behave differently in prepubertal children as compared to pubertal children and adults. BRAF gene activating mutations may associate with PTC by creating aberrant activation. We aimed to evaluate the clinicopathological characteristics of PTC patients with emphasis on the pubertal status and also to investigate the association of BRAF ^V600E mutation with disease characteristics.

Methods:

The medical records of 75 patients with PTC were reviewed retrospectively. BRAF ^V600E mutation status was available only in the medical records of 56 patients.

Results:

Mean age at diagnosis was 12.4±3.8 years. There was no difference in sex, initial signs, tumor histopathology, and pathological evidence of tumor aggressiveness between prepubertal and pubertal children. Although not statistically significant, lateral neck nodal metastasis and lung metastasis at diagnosis were more prevalent in prepubertal children. After excluding patients with microcarcinoma, prepubertal children were found to require lateral neck dissection and further doses of radioactive iodine more frequently than pubertal patients. Recurrence was also more frequent in prepubertal children (p=0.016). Frequency of BRAF ^V600E mutation was similar in prepubertal and pubertal patients. BRAF ^V600E mutation was found in 14/56 (25%) patients and was high in the classic variant PTC (p=0.004). Multicentricity was high in BRAF ^V600E mutation (p=0.01). There was no relation between BRAF ^V600E mutation and lymph node and pulmonary metastasis at diagnosis, or between BRAF ^V600E mutation and pathological evidence of tumor aggressiveness.

Conclusion:

PTC is more disseminated in prepubertal children. BRAF ^V600E mutation does not correlate with a more extensive or aggressive disease. BRAF ^V600E mutation is not the cause of the differences in the biological behavior of PTC in prepubertal and pubertal children.