David S Cohen1, Jane E Tongson-Ignacio2, Christopher M Lolachi1, Vanessa S Ghaderi3, Babak Jahan-Parwar4, Lester D R Thompson5. 1. 1 Department of Head and Neck Surgery, Southern California Permanente Medical Group, Harbor City, California, USA. 2. 2 Department of Cytopathology, Southern California Permanente Medical Group, North Hollywood, California, USA. 3. 3 Department of Endocrinology, Southern California Permanente Medical Group, Harbor City, California, USA. 4. 4 Department of Head and Neck Surgery, Southern California Permanente Medical Group, Baldwin Park, California, USA. 5. 5 Department of Pathology, Southern California Permanente Medical Group, Woodland Hills, California, USA.
Abstract
OBJECTIVES: To recognize that thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; Bethesda III) have different risks of malignancy based on genetic mutation and to consider molecular testing of nodules with AUS/FLUS to help avoid unnecessary morbidity or cost. STUDY DESIGN: Retrospective cohort study. SETTING: Multiple locations within Southern California Permanente Medical Group. SUBJECTS AND METHODS: Patients included those with indeterminate thyroid nodules and AUS/FLUS on 2 separate fine-needle aspirations with positive ThyGenX testing from 2014 to 2017 who underwent thyroid surgery. Patients were classified as having benign or malignant disease. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features was considered benign. RESULTS: A total of 231 patients had repeat AUS/FLUS with positive molecular testing and surgery. The most frequent type of malignancy was papillary carcinoma, followed by follicular carcinoma. The overall prevalence of malignancy in nodules with mutations was 74.0%, although there was considerable variation: BRAF = 100%, RET = 100%, PAX8-PPARγ = 84.6%, HRAS = 70.7%, NRAS = 63.4%, and KRAS = 33%-a statistically significant finding (P < .001). CONCLUSIONS: Not all molecular mutations in thyroid nodules with AUS/FLUS have a high risk of malignancy. Of note, patients with BRAF and RET mutations in our population had a 100% risk of malignancy. Patients with PAX, HRAS, or NRAS mutations had a high risk of malignancy, while patients with KRAS mutations had a lower risk of malignancy. Further studies are needed to determine if the presence of certain molecular mutations can help personalize care and aid in the decision for thyroid surgery.
OBJECTIVES: To recognize that thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; Bethesda III) have different risks of malignancy based on genetic mutation and to consider molecular testing of nodules with AUS/FLUS to help avoid unnecessary morbidity or cost. STUDY DESIGN: Retrospective cohort study. SETTING: Multiple locations within Southern California Permanente Medical Group. SUBJECTS AND METHODS: Patients included those with indeterminate thyroid nodules and AUS/FLUS on 2 separate fine-needle aspirations with positive ThyGenX testing from 2014 to 2017 who underwent thyroid surgery. Patients were classified as having benign or malignant disease. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features was considered benign. RESULTS: A total of 231 patients had repeat AUS/FLUS with positive molecular testing and surgery. The most frequent type of malignancy was papillary carcinoma, followed by follicular carcinoma. The overall prevalence of malignancy in nodules with mutations was 74.0%, although there was considerable variation: BRAF = 100%, RET = 100%, PAX8-PPARγ = 84.6%, HRAS = 70.7%, NRAS = 63.4%, and KRAS = 33%-a statistically significant finding (P < .001). CONCLUSIONS: Not all molecular mutations in thyroid nodules with AUS/FLUS have a high risk of malignancy. Of note, patients with BRAF and RET mutations in our population had a 100% risk of malignancy. Patients with PAX, HRAS, or NRAS mutations had a high risk of malignancy, while patients with KRAS mutations had a lower risk of malignancy. Further studies are needed to determine if the presence of certain molecular mutations can help personalize care and aid in the decision for thyroid surgery.
Authors: Sara Jackson; Gyanendra Kumar; Anna B Banizs; Nicole Toney; Jan F Silverman; Christina M Narick; Sydney D Finkelstein Journal: Diagn Cytopathol Date: 2019-11-01 Impact factor: 1.582
Authors: Mark A Lupo; Ann E Walts; J Woody Sistrunk; Thomas J Giordano; Peter M Sadow; Nicole Massoll; Ryan Campbell; Sara A Jackson; Nicole Toney; Christina M Narick; Gyanendra Kumar; Alidad Mireskandari; Sydney D Finkelstein; Shikha Bose Journal: Diagn Cytopathol Date: 2020-08-07 Impact factor: 1.582