Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation

Yip, Linwah; Nikiforova, Marina N.; Carty, Sally E.; Yim, John H.; Stang, Michael T.; Tublin, Mitchell J.; LeBeau, Shane O.; Hodak, Steven P.; Ogilvie, Jennifer B.; Nikiforov, Yuri E.

doi:10.1016/j.surg.2009.09.011

« Previous Next »Surgery
Volume 146, Issue 6 , Pages 1215-1223, December 2009

Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation

Linwah Yip, MD
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA
- Reprint requests: Linwah Yip, MD, Kaufmann Building, Suite 101, 3471 Fifth Avenue, Pittsburgh, PA 15213.
Marina N. Nikiforova, MD
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
Sally E. Carty, MD
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA
John H. Yim, MD
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA
Michael T. Stang, MD
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA
Mitchell J. Tublin, MD
- Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA
Shane O. LeBeau, MD
- Department of Endocrinology, University of Pittsburgh School of Medicine, Pittsburgh, PA
Steven P. Hodak, MD
- Department of Endocrinology, University of Pittsburgh School of Medicine, Pittsburgh, PA
Jennifer B. Ogilvie, MD
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA
Yuri E. Nikiforov, MD
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA

Accepted 17 September 2009.

Background

To date, a mutation of the BRAF oncogene is the most common genetic alteration found in papillary thyroid carcinoma (PTC) and is associated with extrathyroidal extension, lymph node metastasis, and tumor recurrence. It is not known whether pre-operative identification of BRAF mutations in cytologic specimens should alter surgical management.

Methods

From 2006 to 2008, the clinical, cytologic, and pathologic parameters of 106 consecutive surgically treated patients with BRAF-positive PTC were compared with a concurrent cohort of 100 patients with BRAF-negative PTC.

Results

In all, 99 BRAF-positive PTC patients underwent initial treatment, and 7 BRAF-positive patients had surgical resection of recurrent/persistent PTC. BRAF mutations were identified on preoperative cytologic samples (31 patients) or after thyroidectomy (75 patients). All 31 patients with BRAF-positive fine-needle aspiration (FNA) had PTC at thyroidectomy (specificity 100%). At short-term follow-up, 11/106 BRAF-positive patients have required reoperation for recurrent/persistent disease compared with 3 BRAF-negative patients (P = .04). Preoperative knowledge of BRAF mutation positivity could have productively altered initial PTC surgical management in 24% of patients.

Conclusion

In PTC, BRAF mutations are associated with cervical recurrence and with reoperation. Pre-operative cytologic identification of BRAF mutation has high specificity and may guide the initial extent of thyroidectomy and node dissection.