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Uncommon BRAF mutations in the follicular variant of thyroid papillary carcinoma: New insights
Author(s) -
Rossi Esther Diana,
Martini Maurizio,
Bizzarro Tommaso,
Capodimonti Sara,
Cenci Tonia,
Lombardi Celestino Pio,
Pontecorvi Alfredo,
Fadda Guido,
Larocca Luigi Maria
Publication year - 2015
Publication title -
cancer cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.29
H-Index - 57
eISSN - 1934-6638
pISSN - 1934-662X
DOI - 10.1002/cncy.21586
Subject(s) - v600e , medicine , thyroid carcinoma , malignancy , pathology , thyroid , cancer research , mutation , thyroid cancer , biology , gene , genetics
BACKGROUND Mutational analysis is reshaping the practice of fine‐needle aspiration cytology for the diagnosis of thyroid nodules. The v‐Raf murine sarcoma viral oncogene homolog B1 ( BRAF ) valine (V) to glutamic acid (E) substitution at codon 600 ( BRAF V600E ) is the most effective diagnostic/prognostic marker and is used mainly for papillary thyroid carcinomas (PTCs). Although BRAF V600E represents 95% of all BRAF mutations, uncommon BRAF mutations have been identified in thyroid carcinomas. For the current study, the authors evaluated morphologic (plump pink cells and sickle‐shaped nuclei) anti‐ BRAF V600E antibody (VE1) immunocytochemical and molecular findings of BRAF mutations in PTCs and in the follicular variant of PTC (FVPC). METHODS Between January 2013 and June 2014, there were 150 cytologic samples with surgical follow‐up at the authors' institution. BRAF mutations, which were identified using liquid‐based cytology, were classified into wild‐type BRAF , BRAF V600E , and uncommon BRAF mutations. All clinicopathologic correlations between BRAF and FVPCs were analyzed. RESULTS Forty‐four of 150 samples were identified as benign histologic lesions, and the authors focused on the 106 cytologic samples from patients who had malignant outcomes (60 PTCs and 46 FVPCs). The series included 16 follicular neoplasms, 36 samples diagnosed as suspicious of malignancy, and 54 samples diagnosed as positive for malignancy. The BRAF V600E mutation was detected in 17.4% of FVPCs and in 66.6% of PTCs, whereas uncommon BRAF mutations were detected only in FVPCs. Plump pink cells and VE1 expression were not identified in samples that had uncommon BRAF mutations. VE1 immunocytochemistry yielded positive results in all 36 samples that had the BRAF V600E mutation. CONCLUSIONS Uncommon BRAF mutations were observed only in FVPCs and were linked to less aggressive behavior. Negative/weak VE1 expression was observed in both wild‐type and uncommon BRAF mutations. The current investigation did not reveal any plump cells or morphologic BRAF findings in samples that had uncommon BRAF mutations. In the authors' experience, BRAF mutations detected by DNA methods were more accurate in identifying FVPCs. Cancer (Cancer Cytopathol) 2015;123:593–602 . © 2015 American Cancer Society .