title: Morphological parameters able to predict BRAF(V600E) -mutated malignancies on thyroid fine-needle aspiration cytology: Our institutional experience.
abstract: BACKGROUND
  The BRAF(V600E) mutation is the most common diagnostic/prognostic marker in papillary thyroid carcinoma (PTC). Its evaluation is typically performed with DNA-based techniques; nonetheless, a few articles have recently proposed the morphological prediction of BRAF(V600E) in histological PTCs. We investigated this morphological parameter in our cytological series.
  
  
  METHODS
  We re-analyzed all 72 cytohistological samples diagnosed as positive for malignancy (favoring PTC) on fine-needle aspiration cytology from January 2012 to December 2013. We included 22 male patients and 50 female patients. The cytological cases were processed with liquid-based cytology. We performed molecular analysis and immunocytochemistry for the VE1 BRAF(V600E) antibody.
  
  
  RESULTS
  We reported 47 mutated cases and 25 wild-type (WT) cases with 100% cytohistological concordance. The cytological evaluations revealed plump cells (abundant eosinophilic cytoplasm and PTC nuclei) in all 47 mutated cases, with only 6 having a focal plump cell component (≤20% cells). Furthermore, 5 of the 25 WT cases showed focal plump cells. A distinctive sickle nuclear shape was found only in the mutated cases. VE1 yielded 100% positivity for all 24 mutated cases that were tested, including 3 cases with focal plump cells.
  
  
  CONCLUSIONS
  We demonstrated that the BRAF(V600E) mutation might be predicted in cytological samples on the basis of some specific morphological features. Although the detection of plump cells (mainly focal) was also observed in WT cases, the detection of sickle-shaped nuclei provided the highest specificity and sensitivity as a predictive mutational parameter. These morphological features might be a valid tool for selecting cases for molecular analysis.
authors.affiliation: Division of Anatomic Pathology and Histology of the Catholic University of the Sacred Heart, Agostino Gemelli School of Medicine, Rome, Italy.
authors.forename: Esther Diana
authors.initials: ED
authors.lastname: Rossi
authors.forename: Tommaso
authors.initials: T
authors.lastname: Bizzarro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Sara
authors.initials: S
authors.lastname: Capodimonti
authors.forename: Guido
authors.initials: G
authors.lastname: Fadda
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D044963:Biopsy, Fine-Needle; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003581:Cytodiagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF mutation; liquid-based cytology; plump cells; thyroid carcinoma; thyroid lesions