Faculty Bibliography

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.

BACKGROUND: The noninvasive encapsulated follicular variant of papillary carcinoma (nEFVPTC) has recently been reclassified to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)," removing this entity from the malignant category. This re-categorization has had major implications for clinical management. NIFTP has overlapping cytohistologic features with papillary thyroid carcinoma (PTC) and with follicular adenomas (FA), but sonographic data comparing NIFTP to PTC and FA is lacking. Our study examines the sonographic features of NIFTP as compared with PTC and FA. METHODS: Ultrasound scans and Doppler blood flow from subjects who had pre-surgical sonograms and fine needle aspiration biopsies with final surgical pathology diagnoses of NIFTP/nEFVPTC, classical PTC, and FA between 01/2013-08/2016 were assessed. Sonographic and Doppler features as well as Bethesda System (TBS) diagnoses were recorded and analyzed. RESULTS: 40 NIFTP, 58 classical PTC, and 23 FA cases were included. The most common NIFTP pre-surgical TBS cytology diagnosis was Atypia of Undetermined Significance (AUS/FLUS) (40%). NIFTP cases predominantly displayed wider-than-tall shape (100%), smooth borders (75%), occurrence in multinodular glands (82.5%), heterogeneous echogenicity (50%), both perinodular and intranodular Doppler flow patterns (70%), minimal Doppler flow grade (62.5%), and no calcifications (90%). CONCLUSIONS: Our study demonstrates that NIFTP, PTC, and FA display several distinguishing and overlapping sonographic and Doppler features. Sonographic features appear to complement cytology findings and may help raise pre-operative concern for NIFTP in the proper clinical setting, potentially leading to a more conservative management approach.

BACKGROUND: Differentiating parathyroid and thyroid lesions can be challenging because of considerable morphologic overlap and anatomic proximity. Therefore, the authors sought to identify characteristic morphologic patterns and useful adjunct tests to distinguish these 2 entities. METHODS: A search was conducted in the study institution database for clinically indeterminate thyroid nodules from 2000 through 2016 with an emphasis on confirmed parathyroid nodules. Pathology reports, slides, ancillary studies, molecular analysis, and clinical and radiologic data were retrieved. RESULTS: A total of 143 cases of clinically indeterminate thyroid nodules were identified; 34 of these were confirmed parathyroid nodules. Three cytologic patterns were identified: 1) oncocytic cell pattern (9 cases; 26%); 2) follicular lesion of undetermined significance-like/papillary-like pattern (14 cases; 41%); and 3) nonspecific endocrine cell clusters (11 cases; 32%). Bare oval nuclei (100%), nuclear overlap (88%), crowded sheets (88%), and intracytoplasmic vacuoles (62%) were observed. Ten cases (29%) demonstrated positive immunostaining for parathyroid hormone (PTH), 7 cases (21%) demonstrated a positive PTH assay, and 9 cases (26%) had PTH detected by ThyroSeq v.2. The remaining 8 cases were morphologically either indeterminate or suggestive of parathyroid origin. The cytologic diagnosis was confirmed clinically (20 cases) or surgically (14 cases). Based on cytology alone, 8 cases initially were diagnosed as thyroid tissue and amended to parathyroid lesion after ancillary studies were performed, including 5 cases based on ThyroSeq v.2 results alone. CONCLUSIONS: Lesions with follicular lesion of undetermined significance-like or oncocytic features are prone to misdiagnosis. The current study identified distinct cytologic patterns in parathyroid lesions suggestive of parathyroid origin, which, together with PTH immunostains or assay, molecular studies, or sestamibi scans, aid in distinguishing parathyroid from thyroid lesions. Cancer (Cancer Cytopathol) 2017. (c) 2017 American Cancer Society.

BACKGROUND: Noninvasive encapsulated follicular variant of papillary thyroid carcinoma, a diagnosis implying malignancy as a variant of papillary thyroid carcinoma (PTC), has recently been reclassified to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on surgical pathology. Due to the effects of such a recategorization on rate of malignancy and clinical management algorithms, it is imperative that we explore whether presurgical fine-needle aspiration can differentiate NIFTP from PTC and follicular adenoma (FA). METHODS: Cytology slides from subjects with final surgical pathology resection diagnoses of NIFTP/encapsulated follicular variant of papillary thyroid carcinoma, classic PTC, and FA made between January 2013 and August 2016 were assessed. The Bethesda System diagnoses were tabulated and cytomorphologic features were analyzed for an association with surgical pathology diagnoses. RESULTS: A total of 56 NIFTP, 67 classic PTC, and 30 FA cases were included. The presurgical NIFTP diagnosis according to The Bethesda System was most often atypia of undetermined significance (37.5%) followed by suspicious for follicular neoplasm/follicular neoplasm (26.8%), suspicious for malignancy (17.9%), benign (10.7%), and positive for malignancy (7.1%). The most common NIFTP cytomorphologic features were nuclear enlargement (83.9%), nuclear crowding (82.1%), nuclear clearing (69.6%), and microfollicles (73.2%). All cytomorphologic features demonstrated statistically significant associations (P value range, <.001-.002) between NIFTP and PTC, whereas select cytomorphologic features demonstrated significant associations between NIFTP and FA. CONCLUSIONS: Several statistically significant associations appear to be present between cytomorphologic features and surgical diagnosis that may be used as clues to distinguish NIFTP, PTC, and FA on fine-needle aspiration. Although diagnostic confirmation of NIFTP must occur at the time of excision, similar to follicular neoplasms, the possibility of NIFTP may be raised preoperatively on cytology. Cancer Cytopathol 2017;125:378-88. (c) 2017 American Cancer Society.