A Genomic Alternative to Preoperatively Identify Medullary Thyroid Cancer in Thyroid Nodules with Indeterminate Cytology.

A Genomic Alternative to Preoperatively Identify Medullary Thyroid Cancer in Thyroid Nodules with Indeterminate Cytology.

Thyroid. 2016 Mar 18;

Authors: Kloos RT, Monroe RJ, Traweek ST, Lanman RB, Kennedy GC

Abstract
BACKGROUND: The use of calcitonin screening for the rare medullary thyroid cancer (MTC) is controversial due to questions of efficacy, accuracy, and cost-effectiveness. We report the results of a large prospective validation using a machine-trained algorithm (MTC Classifier) to pre-operatively identify MTC in fine-needle aspiration biopsies in lieu of calcitonin measurements.
METHODS: Cytology analysis on a prospective consecutive series of 50,430 thyroid nodule biopsies yielded a total of 7,815 indeterminate (Bethesda categories III/IV) cases which were tested with the MTC classifier. A prospective, consecutively submitted series of 2,673 Bethesda III-VI cases with cytology determined locally was also evaluated. RNA was isolated and tested for the MTC Classifier using microarrays.
RESULTS: Forty-three cases were positive by the MTC Classifier among 10,488 tested nodules (0.4%), consistent with the low prevalence of MTC. Of these, all but one was histologically or biochemically confirmed as MTC, yielding a positive predictive value (PPV) of 98%. Of the positive cases, only 19 (44%) had been specifically suspected of MTC by cytology, highlighting the limitations of light microscopy to detect this disease. Three surgically confirmed MTC cases that were detected by the MTC Classifier had low basal serum calcitonin values, indicating these would have been missed by traditional calcitonin screening methods. A pooled analysis of 3 independent validation sets demonstrates high test sensitivity (97.9%), specificity (99.8%), PPV (97.9%), and negative predictive value (99.8%).
CONCLUSIONS: We propose a clinical paradigm whereby cytologically indeterminate thyroid nodules being tested for common malignancies using gene expression can be simultaneously tested for MTC using the same genomic assay, at no added cost.

PMID: 26992356 [PubMed - as supplied by publisher]

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