Clinical Study BRAF Testing in Multifocal Papillary Thyroid Carcinoma Hillary Z. Kimbrell, 1 Andrew B. Sholl, 1 Swarnamala Ratnayaka, 1 Shanker Japa, 1 Michelle Lacey, 2 Gandahari Carpio, 3 Parisha Bhatia, 4 and Emad Kandil 4 1 Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Avenue SL-79, New Orleans, LA 70112, USA 2 Department of Mathematics, Tulane University, 6823 St. Charles Avenue, New Orleans, LA 70118, USA 3 Department of Medicine, Tulane University, 1430 Tulane Avenue SL-12, New Orleans, LA 70112, USA 4 Department of Surgery, Tulane University, 1430 Tulane Avenue SL-22, New Orleans, LA 70112, USA Correspondence should be addressed to Hillary Z. Kimbrell; hillarykimbrell@gmail.com Received 6 January 2015; Revised 3 March 2015; Accepted 8 March 2015 Academic Editor: Aurelio Ariza Copyright © 2015 Hillary Z. Kimbrell et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. BRAF V600E mutation is associated with poor prognosis in patients with papillary thyroid carcinoma (PTC). PTC is oten multifocal, and there are no guidelines on how many tumors to test for BRAF mutation in multifocal PTC. Methods. Fity- seven separate formalin-ixed and parain-embedded PTCs from twenty-seven patients were manually macrodissected and tested for BRAF mutation using a commercial allele-speciic real-time polymerase chain reaction-based assay (Entrogen, Woodland Hills, CA). Data related to histologic characteristics, patient demographics, and clinical outcomes were collected. Results. All mutations detected were BRAF V600E. Seventeen patients (63%) had concordant mutation status in the largest and second-largest tumors (i.e., both were positive or both were negative). he remaining ten patients (37%) had discordant mutation status. Six of the patients with discordant tumors (22% overall) had a BRAF-negative largest tumor and a BRAF-positive second-largest tumor. No histologic feature was found to help predict which cases would be discordant. Conclusions. Patients with multifocal PTC whose largest tumor is BRAF-negative can have smaller tumors that are BRAF-positive. herefore, molecular testing of more than just the dominant tumor should be considered. Future studies are warranted to establish whether inding a BRAF mutation in a smaller tumor has clinical signiicance. 1. Introduction Papillary thyroid carcinoma (PTC) is oten a multifocal disease, with rates as high as 80% in the literature [1]. Despite multiple studies using diferent methodologies [1– 11] it remains an unsettled question as to whether the mul- tifocality represents separate primary tumors or intraglan- dular metastasis, or a combination of both. It seems likely from prior studies that a subset of cases represent separate primaries, or at the very least have molecularly distinct tumors. he question then arises, how many tumors should be tested for BRAF mutation in multifocal PTC? A recent very large retrospective study found that patients with multifocal disease and a BRAF V600E mutation had a signiicantly higher rate of mortality than patients with multifocal disease without a BRAF mutation, but the study did not elaborate on how many or which tumors were tested for each patient [12]. Our study attempts to further the data on BRAF mutation status in patients with multifocal disease and to ind the optimal strategy for BRAF testing in these patients. 2. Materials and Methods he study protocol was approved by the IRB at Tulane University. he laboratory information system was searched for cases of multifocal papillary thyroid carcinoma in patients with all thyroid tissue removed, either as a single surgery or two separate surgeries, since January 1, 2006. hirty- three cases were identiied, and the slides from each case were reviewed by the study pathologists (H.Z.K. and A.B.S.). In all but one case, the entire thyroid was submitted. he following histologic features were recorded for each tumor: size, laterality, histologic variant, and the presence or absence Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 486391, 7 pages http://dx.doi.org/10.1155/2015/486391