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

Molecular Test Performance in Thyroid Nodules/Jug et al

diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance on the same nodule. In the Afirma GEC cohort, of the 207 nodules that were tested, approximately one-half (105 nodules; 51%) were “benign” by GEC and the other one-half (102 nod- ules; 49%) were “suspicious” on GEC. The majority of patients with the Afirma GEC “benign” nodules did not undergo surgery, and all 13 cases (12%) that underwent surgical excision demonstrated benign findings. There were no cases of NIFTP in the Afirma GEC “benign” cohort

that went to surgical resection. The majority of patients with the Afirma GEC “suspicious” cases (81%) underwent surgical resection. Of the Afirma GEC “suspicious” cases that went to surgery, the majority (70%) demonstrated benign findings. A total of 21 cases (21%) demonstrated malignancy, and 4 cases (4%) met the criteria for NIFTP (Fig. 1). In the ThyroSeq cohort, of the 97 nodules that were tested, the majority (83%) did not demonstrate high-risk (HR) mutations. The majority of the patients with these nodules without HR mutations (59%) did not undergo surgery. Of the HR mutation-negative cases that went to surgery, there were no NIFTPs and only 1 case demon- strated a malignancy, which was a minimally invasive fol- licular carcinoma. The majority of the patients with nodules that were positive for HR mutations (82%) under- went surgical resection. Of these surgically resected cases, the majority (57%) demonstrated benign findings. Two cases (14%) demonstrated malignancy, and 4 cases (29%) met the criteria for NIFTP (Fig. 2). Table 2 shows the distribution of TBSRTC diagnos- tic categories, surgical follow-up, and PPV with and with- out cases of NIFTP for cases with a “positive” test result (either a HR mutation identified on ThyroSeq or a “suspicious” Afirma GEC result). All of the cases that were found on surgical resection to meet the criteria for NIFTP either had a “suspicious” Afirma GEC result or a Thyro- Seq panel demonstrating HR mutations. All cases of

TABLE 1. Patient Demographics and Cytological Diagnoses of the Afirma GEC and ThyroSeq Cohorts

Afirma GEC Cohort N 5 207

ThyroSeq Cohort N 5 97

Characteristics

Sex

Female

155 (78%) 43 (22%)

73 (80%) 18 (20%)

Male

Age, y

Mean Range

57

59

20-87

19-85

Bethesda category Nondiagnostic

2 (1%) 3 (1%)

NA

Benign

8 (8%)

AUS/FLUS

178 (86%) 23 (11%)

71 (73%) 14 (14%)

SFN/FN

Suspicious Malignant

1 (1%)

4 (4%)

NA

NA

Abbreviations: AUS/FLUS, atypia of undetermined significance/follicular lesion of undetermined significance, GEC, gene expression classifier; NA, not applicable; SFN/FN, suspicious for follicular neoplasm/follicular neo- plasm; Suspicious, suspicious for malignancy.

Figure 1. Flow diagram of Afirma gene expression classifier (GEC) results with percentage of patients who were treated surgically and results on surgical resection. NIFTP indicates noninvasive thyroid neoplasm with papillary-like nuclear features.

Cancer Cytopathology

155