Morphological features predictive for BRAF(V600E) mutation in papillary thyroid microcarcinomas.

BACKGROUND: The B-Raf proto-oncogene serine∕threonine kinase (BRAF) V600E (BRAF(V600E)) mutation represents a very specific marker for papillary thyroid carcinoma (PTC), including microcarcinomas (PTMCs). However, assessment of the BRAF(V600E) mutational status is expensive and not available in all pathology laboratories.

AIM: We aimed to evaluate if we can identify those morphological features that could predict the presence of the BRAF(V600E) mutation in a series of PTMCs.

MATERIALS AND METHODS: Nineteen PTMCs with analysis of 25 tumor foci were included. The following histological features were evaluated: size of the tumor, multifocality, extrathyroidal extension, tumor's border, characteristic PTC nuclear features, tumor-associated stromal reaction and histological variant. All PTMCs foci were subject to real-time polymerase chain reaction (RT-PCR) amplification targeting the BRAF gene. BRAF(V600E) mutation was assessed by high resolution melting (HRM) analysis and confirmed by Sanger sequencing. Morphological features associated with BRAF(V600E) positive and BRAF(V600E) negative PTMCs were compared using the two-tailed Fisher's exact test, with α set at ≤0.05.

RESULTS: Out of the 25 PTMC foci, 16 (64%) were BRAF(V600E) negative, whereas nine (36%) were BRAF(V600E) positive. Our data showed that subcapsular localization (p=0.013), conventional histological type (p=0.05) and tumor-associated stromal reaction (moderate∕extensive fibrosis) (p=0.032) were significantly associated with the mutation.

CONCLUSIONS: We have demonstrated the value of several morphological features in predicting a BRAF(V600E) mutation profile in PTMCs. All these parameters should be documented in the histopathological report, as they seem to be associated with this mutation and could serve as a risk stratification tool in the selection of patients in need for adjuvant post-surgery therapy.