Faculty Bibliography

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.

Objectives/UNASSIGNED:Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (NEFVPTC) was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Excluding "carcinoma" from the new terminology shifted NIFTP out of the malignant category and altered Bethesda System for Reporting Thyroid Cytopathology (BSRTC) rates of malignancy (ROMs) on thyroid fine-needle aspiration (FNA). Because of potential effects on management guidelines, we examined our ROM data. Methods/UNASSIGNED:In total, 750 thyroid FNAs with surgical resections from January 2013 to June 2016 were reviewed (including 87 NIFTPs). ROM was recorded for each BSRTC category: classifying NEFVPTC/NIFTP as "malignant" and reclassifying NEFVPTC/NIFTP as "nonmalignant." Results/UNASSIGNED:ROM changes were as follows: nondiagnostic (ND), no change; benign, 5.5% to 2.5%; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 42.3% to 22.3%; follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 48.7% to 17.9%; suspicious for malignancy (SFM), 93.6% to 61.7%; and positive for malignancy, 100% to 97%. Conclusions/UNASSIGNED:Decreased ROM was seen in most BSRTC categories, most significantly in AUS/FLUS, FN/SFN, and SFM categories.

Introduction: Because of the indolent nature and potentially conservative treatment of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)- an entity recently removed from the malignant papillary thyroid carcinoma (PTC) category, it is crucial to identify features of this entity pre-operatively. Our group has recently published our findings that 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 follicular adenoma (FA) on fine-needle aspiration (FNA). Therefore, we set out to determine the reproducibility of these results. Materials and Methods: Pre-surgical FNA slides from NIFTP (n=30), classical PTC (n=30) and FA (n=30) collected from 1/2013-8/2016 were reviewed by 7 cytopathologists blind and independently. Presence of cytomorphologic features was recorded and compared to determine concordance amongst cytopathologists. For each feature, the concordance was compared between NIFTP, PTC and FA by Fisher's Exact Test. Utilizing the majority consensus for presence or absence of each cytomorphologic feature, differences amongst NIFTP, PTC and FA presurgical FNAs were assessed for each feature by Fisher's Exact Test. Results: For all the cytomorphologic features, the concordance rates amongst the pathologists ranged between 78 to 93%. The concordance rates were similar between the NIFTP, PTC and FA groups (Table 1). Comparing each cytomorphologic feature (present/absent determined by majority consensus) amongst the NIFTP, PTC and FA groups displayed statistically significant differences for all features (Table 2). Conclusions: The current study supports our previous findings that there are cytomorphologic differences between the three surgical pathology groups-NIFTP, PTC and FA, and shows that these results are reproducible. The presence or absence of each feature viewed in combination as a profile may assist the cytopathologist in raising the possibility of NIFTP pre-operatively, potentially aiding clinicians in deciding whether a more conservative treatment plan is appropriate. (Table Presented)

Objectives: Differentiating squamous cell carcinoma from adenocarcinoma (ACA) in cytology specimens can be challenging. Recent literature showed p40 had higher specificity than p63 for this purpose. Methods: We identified 190 cytology cases with p40 (polyclonal) and p63 (monoclonal clone 4A4) immunohistochemistry, including specimens from fine-needle aspirations (FNAs) and effusions. Results: ACAs of lung origin stained for p40 and p63 in 21% and 20% of cases, respectively, regardless of specimen site. Among lung FNAs of primary pulmonary ACAs (n = 42), 14% were positive for p40 and 24% were positive for p63. Of the 20 pulmonary ACAs in effusions, more cases showed p40 positivity (40%) compared with FNAs, whereas p63 were positive in 15%. Among metastatic ACAs from other sites (n = 14), more cases were positive for p40 than p63. Conclusions: Polyclonal p40 yields a level of false positivity in ACAs similar to p63, which is highest in effusions and is not limited to lung origin.

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.