Faculty Bibliography

Introduction: The Thyroid Imaging Reporting and Data System (TI-RADS) was designed to standardize risk stratification of thyroid nodules by ultrasonographic criteria and categorize nodules as TR1-TR5 to designate nodules for fine needle aspiration (FNA) or surveillance. Thyroid FNAs are classified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) (categories TBS I-VI) with an associated risk of malignancy and management guideline. We utilize Thyroseq-V3 molecular testing for indeterminate cytology cases (TBS III- V). Our aim was to correlate indeterminate thyroid FNAs with TI-RADS scores and molecular results to determine if TI-RADS is accurately identifying nodules for biopsy.
Material(s) and Method(s): A retrospective review of thyroid nodules from 1/1/2018-8/30/2018 was performed. Patients with ultrasound (US) reports including TI-RADS scores, FNA reports with indeterminate cytology (TBS-III, TBS-IV and TBS-V) and molecular testing were included.
Result(s): 370 of 1000 thyroid nodules had US reports with TI-RADS scoring and concurrent cytology. 47 cases had indeterminate cytology (TBS-III n=37, TBS-IV n=7 and TBS-V n=3) and reflex molecular testing. Majority were TR4 (31/47;65.97%) and TR5 (10/47;21.27%) (Table1). 23/47 (48.94%) showed no alteration. NRAS was the most common alteration (8 cases), followed by Copy Number Alterations (CNA) (6 cases) (Figure 1). Three TBS-III cases showed dual alterations (NRAS/CNA x2 and HRAS/CNA). Two TBS-IV cases had multiple alterations (EIF1AX/NRAS/TP53 and NRAS/PTEN).
Conclusion(s): While majority of thyroid nodules had a high TI-RADS score (TR4 or TR5), most cases fell into the atypical category (TBS III). Almost half of the thyroid nodules lacked any molecular alterations thereby suggesting an over-classification by TI-RADS. Further refinement of the TI-RADS criteria may be warranted. [Figure presented] [Figure presented]
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Introduction: TBS diagnostic category rates, ASCUS/(+)hrHPV (high risk HPV) ratio, and cytotechnologist's (CT'S) concordance with the CP's final diagnosis are used as common quality monitors in gyn cytology. Additionally, extending monitoring of the hrHPV (+) rate to NILM and SIL cases has been proposed as quality indicators for cytopathologist's (CP's) performance. At our institution, Pap tests are finalized without the knowledge of hrHPV status. We investigated the impact of known hrHPV status on CPs' interpretation of cases previously screened as NILM, and stipulated its potential consequence on quality metrics. Material(s) and Method(s): 60 Pap tests previously resulted as NILM, half hrHPV (+) and half hrHPV (-), were reviewed blindly by 5 CPs in two rounds at 4 months interval. At first round, correct hrHPV results were provided to the CPs. At second round, incorrect (reversed) hrHPV results were given. McNemar chi-squared test was used to analyze the impact of knowing the hrHPV test result on Pap test interpretation. Kappa coefficient was calculated to test intra-observer agreement between the first and second review of the same slides for each CP. Result(s): ASCUS (13%) was the most upgraded diagnosis followed by 12 LSILs (2%) and 2 HSILs (0.3%). There were no significant differences in Pap test interpretation based on hrHPV status for 3 CPs and marked differences for 2 CPs (Table 1). Intra-observer agreement between round 1 and round 2 diagnoses varied from moderate to poor (Table 2). Conclusion(s): Knowledge of hrHPV status significantly biases some but not all CPs. hrHPV (+) to NILM, ASCUS and SIL ratios may not be the most objective parameters for evaluation of CP performance under these circumstances. This bias has further implications for CT performance evaluation because it impacts CT discordance rate measured against CPs final diagnosis. [Figure presented] [Figure presented]

Objectives/UNASSIGNED:To evaluate whether non-small cell lung carcinoma (NSCLC) cytology specimens are reliable for programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) testing. Methods/UNASSIGNED:Fifty-two cell blocks (CBs) with corresponding surgical pathology PD-L1 IHC testing were stained with a Dako PD-L1 pharmDX antibody (clone-22C3). Tumor cellularity was recorded as <100 or ≥100 cells. PD-L1 IHC was scored by percentage of tumor cells staining (<1%, ≥1%-49%, ≥50%) and compared between matched cases. Results/UNASSIGNED:Substantial agreement (κ = 0.63; 95% CI, 0.53-0.73) was reached between matched CB and surgical cases in CBs with ≥100 tumor cells compared to CBs with <100 tumor cells (slight agreement, κ = 0.19; 95% CI, 0.04-0.35). Overall, there was 67% agreement among paired cases (35/52 cases, κ = 0.51; 95% CI, 0.42-0.60). Conclusions/UNASSIGNED:CBs can be utilized for PD-L1 IHC testing, as illustrated by the 67% agreement between CB and surgical cases in our study. Disagreement is attributable to intratumoral heterogeneity and CB cellularity.

OBJECTIVE:Because of the indolent nature of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) and potential requisite for conservative treatment, it is crucial to identify features of this entity pre-operatively. Our group recently published our findings that there are several cytomorphologic features that may be used as clues to distinguish NIFTP, PTC and follicular adenoma (FA) on fine-needle aspiration (FNA). Therefore, we aimed to determine the interobserver reproducibility of these findings. METHODS:Pre-surgical FNA slides from NIFTP (n=30), classic PTC (n=30) and FA (n=30) collected from 1/2013-8/2016 were reviewed by 7 cytopathologists blindly. Presence of selected cytomorphologic features was recorded and compared to determine percent agreement and inter-rater reliability among study cytopathologists using Gwet's AC1 statistics. RESULTS:For all the cytomorphologic features, the overall percent agreement amongst the pathologists ranged between 65.1% and 86.8% (Gwet's AC1 0.30 to 0.80). There was substantial or almost perfect agreement (Gwet's AC1 >0.60) in seven cytomorphologic features in the classic PTC group, in six features in the NIFTP group, and in five features in the FA group. There were no features with poor agreement (Gwet's AC1<0.0). CONCLUSIONS:The current study supports the reproducibility of our previous findings. The high level of agreement amongst pathologists for these groups, and particularly the NIFTP group, supports the notion that when viewed in combination as a cytologic profile, these cytomorphologic features may assist the cytopathologist in raising the possibility of NIFTP pre-operatively. This can potentially aid clinicians in deciding whether more conservative treatment may be appropriate.

Objectives/UNASSIGNED:Recognizing preoperative characteristics of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is important for clinical management. Therefore, we assessed presurgical NIFTP molecular profiles using fine-needle aspiration (FNA) material. Methods/UNASSIGNED:Presurgical FNA reports of 39 surgically confirmed NIFTP cases from January 2013 through May 2017 were assessed for Afirma and ThyroSeq results. Results/UNASSIGNED:Twenty-one of 39 NIFTP nodules were preoperatively tested with Afirma with two benign and 19 suspicious results. Twenty-seven of 39 nodules were tested with ThyroSeq (nine of 39 had both Afirma and Thyroseq): 18 (67%) had RAS mutations (13 NRAS, four HRAS, one KRAS), and three of 18 had multiple alterations (NRAS + TP53, n = 1; NRAS + PTEN, n = 2). BRAF T599_R603 + EIF1AX mutation (n = 1), PTEN mutation (n = 1), MET overexpression (n = 1), PAX8/PPARG fusion (n = 3), and THADA/IGF2BP3 fusion (n = 3) comprised the remainder. Conclusions/UNASSIGNED:NIFTP cases most commonly displayed suspicious Afirma results and RAS mutations on ThyroSeq, lacking aggressive/BRAF-V600E-like mutations. While NIFTP remains a surgical entity, the lack of aggressive/BRAF-V600E-like mutations can aid in determining the extent of surgery.