BRAF status of follicular variant of papillary thyroid carcinoma and its relationship to its clinical and cytological features.
BACKGROUND
The cytological discrimination between benign and malignant follicular-patterned lesions of the thyroid can represent a diagnostic challenge, even for experienced pathologists. To attempt to clarify this diagnostic problem, we analyzed the BRAF status of thyroid tumors in a group of patients with follicular variant of papillary thyroid carcinoma (FVPTC) and its correlation with cytomorphological features.


METHODS
The BRAF status was evaluated in a total of 187 patients in whom FVPTC was consecutively diagnosed by histology between January 2006 and January 2009. Each case had a previous fine-needle aspiration diagnosis classified according to the British Thyroid Association Guidelines categorized as inadequate (Thy1) (n = 19), benign (Thy2) (n = 19), follicular lesion and follicular lesion with atypia (Thy3) (n = 109), suspicious of PTC (Thy4) (n = 29), or malignant (Thy5) (n = 11). The first 68 cases were selected for a morphological study by a quantitative analysis of four cytological features (grooves, intranuclear cytoplasmatic inclusions, number of cells per high power field (400 ×), and mean nuclear diameter) of the carcinomas.


RESULTS
The BRAF status of each tumor was correlated with the cytological classes. 54.5% and 27.6% of Thy5 and Thy4, respectively, were BRAF-mutated, against 12.1% of follicular lesions and 9.3% of follicular lesion with atypia (Thy3). This comparison was statistically significative (p = 0.0017). Among the 68 cases selected for the cyto-morphological study, the BRAF status frequency was similar to that of the total case series. No significant differences were found correlating the cytological classes with the number of cells, the number of grooves, and the mean cell diameters. Only the number of intranuclear cytoplasmatic inclusions were associated (p < 0.05) with the Thy5 cytological class.


CONCLUSIONS
BRAF is mutated in a low percentage of FVPTC, and most of these mutated cases are suspicious or positive on fine-needle aspiration. BRAF analysis is of limited value in the preoperative diagnosis of FVPTC.
Division of Pathology, Department of Surgery, University of Pisa, Pisa, Italy.
Agnese
A
Proietti
Riccardo
R
Giannini
Clara
C
Ugolini
Mario
M
Miccoli
Gabriella
G
Fontanini
Giancarlo
G
Di Coscio
Rossana
R
Romani
Piero
P
Berti
Paolo
P
Miccoli
Fulvio
F
Basolo
D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D016606:Thyroid Nodule / Q000473:pathology; D055815:Young Adult
D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf