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A Clinical Algorithm for Fine-Needle Aspiration Molecular Testing Effectively Guides the Appropriate Extent of Initial Thyroidectomy

Yip, Linwah MD*; Wharry, Laura I. MD*; Armstrong, Michaele J. PhD*; Silbermann, Ari BS*; McCoy, Kelly L. MD*; Stang, Michael T. MD*; Ohori, Nobuyuki P. MD; LeBeau, Shane O. MD; Coyne, Christopher MD; Nikiforova, Marina N. MD; Bauman, Julie E. MD§; Johnson, Jonas T. MD; Tublin, Mitch E. MD; Hodak, Steven P. MD; Nikiforov, Yuri E. MD, PhD; Carty, Sally E. MD*

doi: 10.1097/SLA.0000000000000215
Original Articles

Objective: To test whether a clinical algorithm using routine cytological molecular testing (MT) promotes initial total thyroidectomy (TT) for clinically significant thyroid cancer (sTC) and/or correctly limits surgery to lobectomy when appropriate.

Background: Either TT or lobectomy is often needed to diagnose differentiated thyroid cancer. Determining the correct extent of initial thyroidectomy is challenging.

Methods: After implementing an algorithm for prospective MT of in-house fine-needle aspiration biopsy specimens, we conducted a single-institution cohort study of all patients (N = 671) with nonmalignant cytology who had thyroidectomy between October 2010 and March 2012, cytological diagnosis using 2008 Bethesda criteria, and 1 or more indications for thyroidectomy by 2009 American Thyroid Association guidelines. sTC was defined by histological differentiated thyroid cancer of 1 cm or more and/or lymph node metastasis. Cohort 2 patients did not have MT or had unevaluable results. In cohort 1, MT for a multigene mutation panel was performed for nonbenign cytology, and positive MT results indicated initial TT.

Results: MT guidance was associated with a higher incidence of sTC after TT (P = 0.006) and a lower rate of sTC after lobectomy (P = 0.03). Without MT results, patients with indeterminate (follicular lesion of undetermined significance/follicular or oncocytic neoplasm) cytology who received initial lobectomy were 2.5 times more likely to require 2-stage surgery for histological sTC (P < 0.001). In the 501 patients with non-sTC for whom lobectomy was the appropriate extent of surgery, lobectomy was correctly performed more often with routine preoperative MT (P = 0.001).

Conclusions: Fine-needle aspiration biopsy MT for BRAF, RAS, PAX8-PPARγ, and RET-PTC expedites optimal initial surgery for differentiated thyroid cancer, facilitating succinct definitive management for patients with thyroid nodules.

Single-institution cohort study to determine whether prospective routine cytological molecular testing (MT) correctly guides the extent of initial thyroidectomy. MT guidance was associated with a higher incidence of initial total thyroidectomy for clinically significant thyroid cancer and limited surgery to lobectomy when indicated. Thus, MT optimizes surgery for patients with thyroid nodule.

Departments of *Surgery





Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA.

Reprints: Linwah Yip, MD, Division of Endocrine Surgery, University of Pittsburgh Medical Center, 3471 Fifth Ave, Kauffman Bldg, Ste 101, Pittsburgh, PA 15213. E-mail

Disclosure: L.Y. received a grant from the University of Pittsburgh Medical Center. N.P.O. received an honorarium for speaking at the 2013 Texas Society of Pathologists Annual Meeting. J.E.B. is a consultant for AVEO. S.P.H. received an honorarium for speaking at a 2012 Association for Molecular Pathology lecture. S.E.C. is a section editor for UptoDate, Inc. The remaining authors declare no conflicts of interest.

© 2014 by Lippincott Williams & Wilkins.