Nuclear morphometric findings in undetermined cytology: A possible clue for prediction of BRAF mutation in papillary thyroid carcinomas.

PURPOSE: To investigate the possible relationship between the nuclear morphometric characteristics (nuclear perimeter, roundness, nuclear area, and nuclear shape) and BRAF mutation status in papillary thyroid carcinoma cases with a prior diagnosis of undetermined cytology.

MATERIALS AND METHODS: Total thyroidectomy specimens obtained from 48 patients with papillary thyroid carcinoma with a prior diagnosis of undetermined cytology were included. Morphometric analysis under light microscopy included measurements of the perimeter, shape factor, nuclear area, and roundness of thyrocyte nuclei from the cytological smear preparations. Mutational analysis, including immunohistochemistry and polymerase chain reaction, was performed in formalin fixed paraffin embedded tissue blocks.

RESULTS: BRAF V600E mutation was detected in 7 of 48 cases (14.5%). The nuclear perimeter and nuclear area in mutated cases were significantly higher than the wild type (p = 0.005). Shape factor (p = 0.681) and roundness (p = 0.752) values did not significantly differ between the wild-type and mutant groups. No significant relationship was evident between BRAF expression and BRAF point mutation.

CONCLUSION: In cases with positivity for BRAF mutation, the nuclear perimeter and nuclear area were significantly increased. These findings suggest that morphometric variables are predictive markers for papillary thyroid carcinoma cases with positivity for BRAF mutation. However, further trials on larger series are warranted to understand the significance and predictive value of nuclear morphometric analysis in these circumstances.