2018-19 Section 7-Neoplastic and Inflammatory Diseases of the Head and Neck eBook

Review Article

TABLE 1. “Rule-In” Testing

Test

ThyroSeq v2.1 (Nikiforov 2014 16 , Nikiforov 2015 17 )

Seven-Gene Mutation Panel (Nikiforov 2011 22 )

Rosetta GX Reveal (Lithwick-Yanai 2016 23 )

ThyGenX/ThyraMIR (Labourier 2015 21 )

Afirma (Alexander 2012 14 )

Result

AUS/FLUS, % Prevalence

32 80 68 32 91 82

23 92 77 27 93 83

24 52 38 25 52 37

14 99 88 27 97 87

21 74 43 21 74 43

Specificity

PPV

FN/SFN. %

Prevalence Specificity

PPV

Abbreviations: AUS, atypia of undetermined significance; FLUS, follicular lesion of undetermined significance; FN, follicular neoplasm; PPV, positive predictive value; SFN, suspicious for follicular neoplasm.

TABLE 2. “Rule-Out” Testing

Test

ThyroSeq v2.1 (Nikiforov 2014 16 , Nikiforov 2015 17 )

Seven-Gene Mutation Panel (Nikiforov 2011 22 )

Rosetta GX Reveal (Lithwick-Yanai 2016 23 )

ThyGenX/ThyraMIR (Labourier 2015 21 )

Afirma (Alexander 2012 14 )

Result

AUS/FLUS, % Prevalence

32 94 97 32 82 91

23 90 97 27 90 96

24 92 95 25 92 94

14 63 94 27 57 86

21 74 92 21 74 92

Sensitivity

NPV

FN/SFN, %

Prevalence Sensitivity

NPV

Abbreviations: AUS, atypia of undetermined significance; FLUS, follicular lesion of undetermined significance; FN, follicular neoplasm; NPV, negative predictive value; SFN, suspicious for follicular neoplasm.

total thyroidectomy may not be the recommended initial surgery even for confirmed thyroid malignancies that are clinically considered low risk. 3 Early studies with the 7- gene mutation panel indicated that rat sarcoma (RAS) (a family of small guanosine triphosphate hydrolases) muta- tions were most common but were not highly specific for thyroid cancer, thereby limiting the PPV of the test. Recent studies have demonstrated that RAS mutations also can be identified in up to 48% of benign nodules; therefore, the type of RAS mutation and the degree of alle- lic frequency can be used to guide decision-making. 24 Similarly, many thyroid nodules with RAS and PAX8/ PPAR c mutations are the histologically noninvasive encapsulated follicular variant of PTC, 10 now reclassified as NIFTP. 9 The definition of NIFTP was only recently published and reclassified to highlight the limited malig- nant potential of these precancerous lesions. However,

nodules with both cytology and histologic follow-up. The investigators reported 63% sensitivity and 99% specificity for Bethesda III nodules and 57% sensitivity and 97% specificity for Bethesda IV nodules. A positive test result (the PPV) increased the cancer risk to 88% for Bethesda III nodules and 87% for Bethesda IV nodules, whereas the absence of a mutation or fusion was associated with a cancer risk of 6% (NPV, 94%) and 14% (NPV, 86%), respectively. 22 Although the early adoption of the 7-gene mutation panel to guide surgery was very positive, 22 with a signifi- cant decrease in the number of patients requiring a com- pletion thyroidectomy, several changes in the overall approach to thyroid cancer treatment may limit this early promise. A more judicious approach to thyroid surgery has been recommended, as described in the 2015 Ameri- can Thyroid Association guidelines, recognizing that a

Cancer

March 1, 2018

146