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

Molecular Test Performance in Thyroid Nodules/Jug et al

TABLE 4. Resected Nodules by Whether They Met Criteria for Biopsy by ATA 2015 Guidelines, Stratified by Results of ThyroSeq and Afirma GEC

ThyroSeq Resected Nodules by Whether ATA Criteria for Biopsy Were Met (N 5 26)

Nodule Histology on Resection

Benign

Malignant or NIFTP

Total

ATA criteria for biopsy met

17 14

77.2% 93.3% 42.9% 75.0% 100.0%

5 1 4 1

22.7%

22 15

No HR mutations HR mutations found

6.7%

3 3 3

57.1% 25.0%

7 4 3 1

Did not meet ATA criteria for biopsy

No HR mutations HR mutations found

0.0%

0.0%

1 6

100.0% 23.1%

Total

20

76.9%

26

Afirma GEC Resected Nodules by Whether ATA Criteria for Biopsy Were Met (N 5 70)

Nodule Histology on Resection

Benign

Malignant or NIFTP

Total

ATA criteria for biopsy met

45

75.0% 100.0% 70.6% 70.0% 100.0% 66.7% 74.3%

15

25.0%

60

GEC “benign”

9

0.0%

9

GEC “suspicious”

36

15

29.4% 30.0%

51 10

Did not meet ATA criteria for biopsy

7 1 6

3

GEC “benign”

0.0%

1 9

GEC “suspicious”

3

33.3% 25.7%

Total

52

18

70

Abbreviations: ATA 2015, 2015 American Thyroid Association guideline; GEC, gene expression classifier; HR, high risk; NIFTP, noninvasive thyroid neoplasm with papillary-like nuclear features.

performance of ThyroSeq with regard to NIFTP. 16 Although that study had a PPV for HR mutations that was similar to our experience if NIFTP was included in the malignant group (42.4% vs 42.9%), when NIFTP was removed, the PPV in the current study dropped much more, to 14.3% versus 33.3%. Both studies were limited by the relatively small numbers of patients who had HR mutations on ThyroSeq. The differences in the impact of the NIFTP classification on the PPV across studies most likely is due to several factors, including variations in the institutional prevalence of malignancy as well as NIFTP. To the best of our knowledge, none of these other studies compared molecular testing modalities within the same institution, which we have done herein. It is interest- ing to note that in our experience, the impact of the NIFTP reclassification was greater in the ThyroSeq cohort compared with the Afirma GEC cohort, with the majority of the “malignancies” fitting the criteria for reclassification as NIFTP. This most likely is due to the fact that, as we and others have previously described, 2,15,17 NIFTPs often demonstrate RAS mutations, which were categorized as HR by the ThyroSeq panel. In addition, because the choice of molecular testing platform was not randomized

NPVs of the molecular panels. The impact of the improved predictive values hopefully will contribute to improved prognostication for patients in whom thyroidec- tomy is being considered. The findings of the current study support predictions that NIFTP decreases the risk of malignancy for a “positive” result for both the Afirma GEC and ThyroSeq, thereby adding to the limited literature regarding this topic. Table 5 summarizes the distribution of cases with “suspicious” Afirma GEC or HR mutations on ThyroSeq in the current study alongside the existing literature. 11,13-15 The PPV of a “suspicious” Afirma GEC if NIFTP is not removed from the malignant category ranges from 30.1% to 39.3% for studies that specifically looked at GEC results in the context of NIFTP. If NIFTP is removed from the malignant category, the PPV ranges from 12.7% to 29.9%, with absolute decreases in PPV ranging from 4.8% to 22.2%. The decrease in PPV for a “suspicious” Afirma GEC result in our experience was lower than in other stud- ies at 4.8%, which reflects the smaller number of NIFTPs in the current study cohort. To our knowledge, independent studies of ThyroSeq are limited, with only 1 other published study assessing the

Cancer Cytopathology

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