title: Papillary Thyroid Carcinoma With Rare Exon 15 BRAF Mutation Has Indolent Behavior: A Single-Institution Experience.
abstract: Approximately 40% of papillary thyroid carcinomas (PTCs) harbor the BRAF V600E mutation, which is significantly associated with the advanced clinicopathological features of PTC at diagnosis, a higher recurrence rate, and disease-related mortality. BRAF alterations other than V600E are less common in PTC, and their clinical significance remains to be established.
  
  
  
  The aim of the study was to describe a large cohort of rare exon 15 BRAF alterations (r-BRAF) and the clinicopathological features of PTC harboring these alterations and to clarify their clinical significance.
  
  
  
  A total of 2961 PTCs were collected from 2006 to 2013 and screened for exon 15 BRAF alterations.
  
  
  
  Exon 15 BRAF alterations were found in 1186 of 2961 PTC cases (40.0%). In particular, we found the BRAF V600E mutation in 95.3% (1131 of 1186) and r-BRAF in 4.7% (55 of 1186) of the cases. r-BRAF were found in 18 microcarcinomas, 33 follicular variants, one classic variant, and one trabecular/solid variant. The most frequent r-BRAF was BRAF K601E (35 of 55; 63.6%), followed by BRAF V600_K601delinsE (seven of 55; 12.7%) and BRAF T599I-V600_R603del (two of 55; 3.6%). The remaining 11 alterations were found in one case only. The large majority of these tumors were unifocal (34 of 55; 61.8%), completely encapsulated (46 of 55; 83.6%), and intrathyroidal (53 of 55; 96.4%) with a low prevalence of lymph node metastases (one of 55; 1.8%) and a less advanced tumor stage at diagnosis (American Joint Commission on Cancer stage I/II, 51 of 55; 92.7%).
  
  
  
  r-BRAF are very uncommon in PTC and are found almost exclusively in PTC with low-risk clinicopathological features.
authors: Unit of Surgical Pathology (L.T., E.S., M.G., F.B.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine; Endocrine Section (D.V., P.P., C.R., R.E.), Department of Clinical and Experimental Medicine, World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders; and Endocrine Surgery Unit (G.M., P.M.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy.
authors: Liborio
authors: L
authors: Torregrossa
authors: Unit of Surgical Pathology (L.T., E.S., M.G., F.B.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine; Endocrine Section (D.V., P.P., C.R., R.E.), Department of Clinical and Experimental Medicine, World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders; and Endocrine Surgery Unit (G.M., P.M.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy.
authors: David
authors: D
authors: Viola
authors: Unit of Surgical Pathology (L.T., E.S., M.G., F.B.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine; Endocrine Section (D.V., P.P., C.R., R.E.), Department of Clinical and Experimental Medicine, World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders; and Endocrine Surgery Unit (G.M., P.M.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy.
authors: Elisa
authors: E
authors: Sensi
authors: Unit of Surgical Pathology (L.T., E.S., M.G., F.B.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine; Endocrine Section (D.V., P.P., C.R., R.E.), Department of Clinical and Experimental Medicine, World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders; and Endocrine Surgery Unit (G.M., P.M.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy.
authors: Mirella
authors: M
authors: Giordano
authors: Unit of Surgical Pathology (L.T., E.S., M.G., F.B.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine; Endocrine Section (D.V., P.P., C.R., R.E.), Department of Clinical and Experimental Medicine, World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders; and Endocrine Surgery Unit (G.M., P.M.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy.
authors: Paolo
authors: P
authors: Piaggi
authors: Unit of Surgical Pathology (L.T., E.S., M.G., F.B.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine; Endocrine Section (D.V., P.P., C.R., R.E.), Department of Clinical and Experimental Medicine, World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders; and Endocrine Surgery Unit (G.M., P.M.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy.
authors: Cristina
authors: C
authors: Romei
authors: Unit of Surgical Pathology (L.T., E.S., M.G., F.B.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine; Endocrine Section (D.V., P.P., C.R., R.E.), Department of Clinical and Experimental Medicine, World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders; and Endocrine Surgery Unit (G.M., P.M.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy.
authors: Gabriele
authors: G
authors: Materazzi
authors: Unit of Surgical Pathology (L.T., E.S., M.G., F.B.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine; Endocrine Section (D.V., P.P., C.R., R.E.), Department of Clinical and Experimental Medicine, World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders; and Endocrine Surgery Unit (G.M., P.M.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy.
authors: Paolo
authors: P
authors: Miccoli
authors: Unit of Surgical Pathology (L.T., E.S., M.G., F.B.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine; Endocrine Section (D.V., P.P., C.R., R.E.), Department of Clinical and Experimental Medicine, World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders; and Endocrine Surgery Unit (G.M., P.M.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy.
authors: Rossella
authors: R
authors: Elisei
authors: Unit of Surgical Pathology (L.T., E.S., M.G., F.B.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine; Endocrine Section (D.V., P.P., C.R., R.E.), Department of Clinical and Experimental Medicine, World Health Organization Collaborating Center for the Study and Treatment of Thyroid Diseases and Other Endocrine and Metabolic Disorders; and Endocrine Surgery Unit (G.M., P.M.), Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy.
authors: Fulvio
authors: F
authors: Basolo
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy*; D002291:Carcinoma, Papillary; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf