Faculty Bibliography

Background & Objectives: Ciliated muconodular papillary tumour (CPMT) is a rare benign lesion, which occurs in the periphery of the lung and is characterised by papillary architecture, intra-alveolar mucin and the presence of non-atypical ciliated-columnar, basal and mucous cells. Since its introduction in 2002 by Ishikawa et al, this entity counts a few reports in the literature, which have primarily occurred in East Asia. Although not in the 2015WHO classification, CPMT represents a frank neoplastic process, harbouring genetic alterations including BRAF and EGFR mutations. The goal of this study was to characterise the clinicopathologic features of CPMT diagnosed at a tertiaty care institution in the U.S.
Method(s): Nine cases with characteristic features of classic and nonclassic CPMT from New York University Tisch Hospital and Bellevue Hospital from 2016 to 2019 were identified. Clinical and pathologic data were reviewed.
Result(s): CPMTs were identified in 3 Male and 6 Female patients, whose age ranged from 47 to 82 years old. The lesions were predominantly found in the right lung and had a median size of 6 mm. Six (6) cases represented classic CPMTs, while 3 cases lacked the full spectrum of CPMT diagnostic features, and were classified as non-classic CPMTs. While in 7 cases, surgical resection was performed due to radiologic diagnosis of a peripheral nodule, in 2 cases, small CPMTs were incidental findings in resections performed for a dominant lesion, which was either adenocarcinoma, non-mucinous type (case 2) or atypical carcinoid (case 8). All lesions showed the characteristic immunohistochemical TTF-1 stain of columnar cells and p63 or p40 stain of basal cells. Two out of four (2/4) cases stained for BRAF-V600E showed uniform staining of all 3 cellular components of the lesion. The data are summarized on Table 1.
Conclusion(s): CPMTs although infrequent are now increasingly recognized and their incidence appears higher than reported in western literature. Interestingly, this self-limited tumour shares similar driver mutations with lung adenocarcinoma. Further studies will include a comprehensive immunohistochemical and molecular characterization of these nine cases and comparison with morphologically similar non-neoplastic processes, like bronchiolar metaplasia

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: Encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), formerly a malignant diagnosis and variant of PTC, has recently been reclassified to NIFTP on surgical pathology. Because of the indolent nature and potentially conservative treatment of NIFTP, it is crucial to identify features early on during patient evaluation which may suggest the possibility of this entity. One such feature is the molecular profile of thyroid nodules determined preoperatively utilizing fine-needle aspiration (FNA) cellular material. Design: Pre-surgical FNA Cytopathology reports of 41 confirmed cases of NIFTP from 1/2013-8/2016 were assessed for molecular testing (Afirma and/or ThyroSeq) results. Results: Bethesda System cytology diagnoses were: Benign (n=1), Atypia of Undetermined Significance (n=24), Follicular Neoplasm (n=14), and Suspicious for Malignancy (n=2). Of the 41 NIFTP cases, 22 nodules were pre-operatively tested with Afirma: 2 were benign; 20 were suspicious. 12 cases were Afirma MTC negative; 4 were BRAF negative. 27 nodules were pre-operatively tested with ThyroSeq: 2 had insufficient material; 15 cases (55.6%) had RAS mutations (11 NRAS, 4 HRAS); 3 of the 15 had two mutations [NRAS and TP53 (n=1); NRAS and PTEN (n=2)]. One additional case with 2 mutations showed BRAF T599-R603 and EIF1AX mutations (n=1). Other isolated molecular changes included PTEN mutation (n=1), MET overexpression (n=1), PAX8/PPARG fusion (n=4), and THADA/IGF2BP3 fusion (n=3). Conclusions: While NIFTP remains a surgical entity, the molecular profile of thyroid nodules can be analyzed pre-operatively in order to determine appropriate treatment. Our findings demonstrate that NIFTP cases most commonly displayed Suspicious Afirma results and RAS mutations on ThyroSeq, and several molecular alterations not characteristic of classical PTC or poorly differentiated/anaplastic thyroid carcinomas. The molecular profile of thyroid nodules must be considered together with the patients' clinical, sonographic and cytologic results in order to raise the possibility of NIFTP early on in determining proper management

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)