The impact of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features on the performance of the Afirma gene expression classifier

Abstract

BACKGROUND: A recent revision in thyroid tumor nomenclature has resulted in a change from a malignant diagnosis (noninvasive follicular variant of papillary thyroid carcinoma) to one that is nonmalignant (noninvasive follicular thyroid neoplasm with papillary-like nuclear features [NIFTP]). The objective of the current study was to evaluate the impact of this change on the performance of the Afirma gene expression classifier (GEC). METHODS: The authors retrospectively analyzed consecutive thyroid fine-needle aspiration specimens with indeterminate diagnoses on which GEC was performed. Surgical pathology material was reviewed with the reclassification of nodules into NIFTP. RESULTS: GEC testing was performed on 384 fine-needle aspiration specimens diagnosed as atypia of undetermined significance (AUS) (304 cases) and suspicious for a follicular neoplasm (SFN) (80 cases) and yielded a suspicious result in 152 of the AUS cases (50%) and 50 of the SFN cases (63%). Thyroidectomy was performed on 177 patients. After reclassifying NIFTP, the positive predictive value of GEC decreased from 42% (95% confidence interval [95% CI], 39%-45%) to 24% (95% CI, 22%-26%) in the AUS group and from 23% (95% CI, 19%-27%) to 13% (95% CI, 9%-18%) in the SFN group. Total thyroidectomy was performed more frequently than a partial thyroidectomy in patients with AUS with a suspicious GEC result compared with pre-GEC controls (68% vs 49%; P 5.037). CONCLUSIONS: Reclassification of NIFTP significantly decreases the positive predictive value of GEC in indeterminate thyroid nodules. Nevertheless, the majority of patients with indeterminate thyroid nodules with a suspicious GEC result in the study institution have undergone total thyroidectomy. This finding raises concerns over reliance on a suspicious GEC result by clinicians to justify total thyroidectomy. Cancer Cytopathol 2017;125:683-91.

Outcomes of Bethesda categories III and IV thyroid nodules over 5 years and performance of the Afirma gene expression classifier: A single‐institution study

“…Two of these cases had undergone preoperative molecular testing, both with GEC Suspicious results. The current use of NIFTP nomenclature appears to lower the positive predictive value (PPV) as previously published by Hang et al; they observed a reduction in PPV to identify malignancy from 23% to 13% in the FN/SFN group. Recent publication from Jug et al also noted a reduction in PPV for both the Afirma GEC and ThyroSeq v2 when accounting for nonmalignant NIFTP lesions, from 30.1% to 25.3% and 42.9% to 14.3%, respectively.…”

Ancillary molecular testing of indeterminate thyroid nodules

“…The initial prospective validated GEC study did not consider NIFTP, and only few papers have evaluated the impact of NIFTP on the performance of GEC. The diagnostic role of the Afirma test to detect NIFTP has been controversial . As reported in different series, NIFTP is associated with suspicious Afirma GEC results .…”

“…This recent acknowledgement of the role of molecular testing formalizes their use in defining risk stratification of patients with thyroid nodules. In this review, we discuss the clinical implications of the different molecular tests in the indeterminate Bethesda categories . It is important to note that the literature to date generally supports employing a combination of morphology and molecular testing to best guide the clinical or surgical approach for patients diagnosed with indeterminate thyroid nodules (Table ).…”

“…Wong et al reported that the Afirma GEC is a useful aid to detect NIFTP and that many of the carcinomas detected by Afirma are in fact noninvasive FVPTCs. Hang et al evaluated the impact of the introduction of NIFTP on the performance of the Afirma GEC. The investigators studied 384 indeterminate thyroid nodules (including AUS/FLUS and SFN/FN) where 177 had surgical follow‐up.…”

Hurthle cell predominance impacts results of Afirma gene expression classifier and ThyroSeq molecular panel performance in indeterminate thyroid nodules

“…Hang et al suggested that separating lesions with and without Hurthle cell features may be helpful to maximize the benefit of Afirma GEC in the latter group 19. Hang et al suggested that separating lesions with and without Hurthle cell features may be helpful to maximize the benefit of Afirma GEC in the latter group 19.…”