Features of Cytologically Indeterminate Molecularly Benign Nodules Treated With Surgery

Abstract

Background Most cytologically indeterminate thyroid nodules (ITN) with benign molecular testing do not undergo surgery. The data on clinical outcomes of these nodules are limited. Methods We retrospectively analyzed all ITN that underwent molecular testing with either Afirma Gene Expression Classifier (GEC) or Afirma Gene Sequencing Classifier (GSC) between 2011 and 2018 at a single institution. Results Thirty-eight out of 289 molecularly benign ITN were ultimately resected. The most common reason for surgery was compressive symptoms (39%). In multivariable modeling, patients <40 years old, nodules > 3 cm, presence of Afirma suspicious nodule other than the index nodule and compressive symptoms were associated with higher surgery rates with hazard ratios (HR) for surgery of 3.5 (p<0.001), 3.2 (p<0.001), 16.8 (p<0.001) and 7.31 (p<0.001), respectively. Of resected nodules, 5 were malignant. False-negative rate (FNR) was 1.7% presuming all unresected nodules were truly benign and 13.2% restricting analysis to resected cases. FNR was significantly higher in nodules with a high-risk sonographic appearance for cancer (American Thyroid Association (ATA) high risk classification and American College of Radiology Thyroid Imaging Reporting And Data Systems (ACR-TIRADS) score of 5) compared to nodules with all other sonographic categories (11.8% vs 1.1%, p=0.03 and 11.1% vs. 1.1%, p=0.02, respectively). Conclusions Younger age, larger nodule size, presence of Afirma suspicious nodule other than the index nodule and compressive symptoms were associated with a higher rate of surgery. False-negative rate of benign Afirma was significantly higher in nodules with high-risk sonographic features.

[18F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial

“…Whether any very slow-growing malignant or borderline thyroid tumours in these nodules will lower diagnostic accuracy of [ 18 F]FDG-PET/CT and limit the [ 18 F]FDG-PET/CT-driven reduction in futile diagnostic surgeries remains to be established. Similarly, additional long-term false-negative results were recently reported for a well-known molecular classifier [40]. It seems clinically unlikely that a delayed diagnosis of any missed slow-growing malignancies or borderline tumours following [ 18 F]FDG-PET/CT-driven management will alter the patients' prognosis, as such tumours are likely indolent in nature.…”

Development and validation of an RNA sequencing–based classifier for medullary thyroid carcinoma on thyroid FNA

“…There have yet to be any false negatives or false positives. [24][25][26][27][28][29][30][31][32][33][34][35][36] In summary, the article by Randolph et al 11 provides insight into the development and validation of the Afirma RNA sequencing-based classifier for distinguishing MTC from non-MTC samples on thyroid FNAC. It presents a fascinating look into the complex process of machine learning and statistical models used to create such a test.…”

“…The Afirma RNA sequencing–based MTC classifier described in this text has also been performed on thyroid FNAC specimens from various independent institutions, with more than 2100 thyroid nodules reported in the literature. There have yet to be any false negatives or false positives 24–36 …”

Differential Diagnosis of Clinical, Imaging and Pathological Features Between Focal Nodular Hyperplasia and Hepatocellular Carcinoma

“…It is brown on the section and lighter in color than that of the adjacent normal liver. The central stellate scar with radial fibrous septum divides the mass into several small nodules as one of its characteristics [21]. Typical FNH generally has three characteristics: abnormal nodular structure, malformed blood vessels and bile duct hyperplasia, but atypical FNH generally has no central scar and is easy to be misdiagnosed as HCC.…”