Objectives: To assess the cytological findings of noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), conventional papillary thyroid carcinomas (C-PTC), and invasive follicular variants of papillary thyroid carcinomas (IFV-PTC) to determine if there are cytological differences between groups. Study Design: We have reviewed all thyroid fine-needle aspiration cytology samples diagnosed between 2000 and 2017. We have included all NIFTP cases (n = 6) and randomly selected cases of C-PTC (n = 14) and IFV-PTC (n = 8). Results: Comparing NIFTP and C-PTC cases, NIFTP cases showed significantly less papillary or pseudopapillary architecture, more bidimensional groups and microfollicles, and less tridimensionality, giant cells, and nuclear folds. We observed a trend towards significance for smear cellularity and amount of cytoplasm. Presence of nuclear folds was the only significant difference between NIFTP and IFV-PTC cases. The differences between groups in percent papillary or pseudopapillary architecture, cellularity, and tridimensionality showed a trend towards significance. Amount of colloid, dirty background, pleomorphism or atypia, nuclear pseudoinclusions, type of chromatin, and nucleolus were not significant. Conclusions: No cytopathological feature can differentiate between invasive and encapsulated IFV-PTC. In accordance with the recently accepted category, PTC smears with cells arranged in a predominantly follicular architecture should be reported as Bethesda IV category with descriptive terms to avoid false-positive cases.

Keywords:
Thyroid, Fine needle aspiration cytology, Noninvasive follicular thyroid neoplasm, Papillary-like nuclear features, Papillary thyroid carcinoma, Cytology
1.
Vivero M, Kraft S, Barletta JA: Risk stratification of follicular variant of papillary thyroid carcinoma. Thyroid 2013; 23: 273–279.
2.
Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LDR, et al: Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma. JAMA Oncol 2016; 2: 1023.
3.
Hung YP, Barletta JA: A user’s guide to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Histopathology 2018; 72: 53–69.
4.
Mainthia R, Wachtel H, Chen Y, Mort E, Parangi S, Sadow PM, et al: Evaluating the projected surgical impact of reclassifying noninvasive encapsulated follicular variant of papillary thyroid cancer as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Surgery 2018; 163: 60–65.
5.
Jung CK, Little MP, Lubin JH, Brenner AV, Wells SA, Sigurdson AJ, et al: The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. J Clin Endocrinol Metab 2014; 99:E276–E285.
6.
Jug R, Jiang X: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: an evidence-based nomenclature change. Patholog Res Int 2017; 2017: 1–6.
7.
Maletta F, Massa F, Torregrossa L, Duregon E, Casadei GP, Basolo F, et al: Cytological features of “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” and their correlation with tumor histology. Hum Pathol 2016; 54: 134–142.
8.
Cho U, Mete O, Kim M-H, Bae JS, Jung CK: Molecular correlates and rate of lymph node metastasis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive follicular variant papillary thyroid carcinoma: the impact of rigid criteria to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features. Mod Pathol 2017; 30: 810–825.
9.
Haugen BR, Sawka AM, Alexander EK, Bible KC, Caturegli P, Doherty GM, et al: American Thyroid Association guidelines on the management of thyroid nodules and differentiated thyroid cancer task force review and recommendation on the proposed renaming of encapsulated follicular variant papillary thyroid carcinoma without invasion to noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Thyroid 2017; 27: 481–483.
10.
Wartofsky L: A rose by any name surely does smell just as sweetly: the controversy over revised nomenclature for encapsulated follicular variant papillary carcinoma. J Transl Intern Med 2016; 4: 55–57.
11.
Xu B, Tallini G, Scognamiglio T, Roman BR, Tuttle RM, Ghossein RA: Outcome of large noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Thyroid 2017; 27: 512–517.
12.
Cibas ES, Ali SZ: The Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol 2009; 132: 658–665.
13.
Baloch ZW, Harrell RM, Brett EM, Randolph G, Garber JR, AACE Endocrine Surgery Scientific Committee and Thyroid Scientific Committee: American Association of Clinical Endocrinologists and American College of Endocrinology Disease state commentary: managing thyroid tumors diagnosed as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Endocr Pract 2017; 23: 1153–1158.
14.
Zhao L, Dias-Santagata D, Sadow PM, Faquin WC: Cytological, molecular, and clinical features of noninvasive follicular thyroid neoplasm with papillary-like nuclear features versus invasive forms of follicular variant of papillary thyroid carcinoma. Cancer Cytopathol 2017; 125: 323–331.
15.
Strickland KC, Howitt BE, Marqusee E, Alexander EK, Cibas ES, Krane JF, et al: The impact of noninvasive follicular variant of papillary thyroid carcinoma on rates of malignancy for fine-needle aspiration diagnostic cate gories. Thyroid 2015; 25: 987–992.
16.
Ibrahim AA, Wu HH: Fine-needle aspiration cytology of noninvasive follicular variant of papillary thyroid carcinoma is cytomorphologically distinct from the invasive counterpart. Am J Clin Pathol 2016; 146: 373–377.
17.
Yang GCH, Fried K, Yakoushina TV, Schrei-ner AM: Encapsulated follicular variant of papillary thyroid carcinoma: fine-needle aspiration with ultrasound and histologic correlation of 41 cases. Acta Cytol 2013; 57: 26–32.
18.
Bizzarro T, Martini M, Marrocco C, D’Amato D, Traini E, Lombardi CP, et al: The role of CD56 in thyroid fine needle aspiration cytology: a pilot study performed on liquid based cytology. PLoS One 2015; 10:e0132939.
19.
Fu G, Polyakova O, MacMillan C, Ralhan R, Walfish PG: Programmed death – ligand 1 expression distinguishes invasive encapsulated follicular variant of papillary thyroid carcinoma from noninvasive follicular thyroid neoplasm with papillary-like nuclear features. EBioMedicine 2017; 18: 50–55.
20.
Armstrong MJ, Yang H, Yip L, Ohori NP, McCoy KL, Stang MT, et al: PAX8/PPARγ rearrangement in thyroid nodules predicts fol-licular-pattern carcinomas, in particular the encapsulated follicular variant of papillary carcinoma. Thyroid 2014; 24: 1369–1374.
21.
Hwang TS, Kim WY, Han HS, Lim SD, Kim W-S, Yoo YB, et al: Preoperative RAS mutational analysis is of great value in predicting follicular variant of papillary thyroid carcinoma. Biomed Res Int 2015; 2015: 1–8.
22.
Borrelli N, Denaro M, Ugolini C, Poma AM, Miccoli M, Vitti P, et al: miRNA expression profiling of “noninvasive follicular thyroid neoplasms with papillary-like nuclear features” compared with adenomas and infiltrative follicular variants of papillary thyroid carcinomas. Mod Pathol 2017; 30: 39–51.
23.
Jug R, Jiang X: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: an evidence-based nomenclature change. Patholog Res Int 2017; 2017: 1057252.
24.
Yang GCH, Fried KO: Pathologic basis of the sonographic differences between thyroid cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Ultrasonography 2018; 37: 157–163.
25.
Yang GCH, Fried KO, Scognamiglio T: Sonographic and cytologic differences of NIFTP from infiltrative or invasive encapsulated follicular variant of papillary thyroid carcinoma. Diagn Cytopathol 2017; 45: 533–541.
26.
Jang EK, Kim WG, Choi YM, Jeon MJ, Kwon H, Baek JH, et al: Association between neck ultrasonographic findings and clinico-pathological features in the follicular variant of papillary thyroid carcinoma. Clin Endocrinol (Oxf) 2015; 83: 968–976.
27.
Rosario PW: Ultrasonography and cytology as predictors of noninvasive follicular thyroid (NIFTP) neoplasm with papillary-like nuclear features: importance of the differential diagnosis with the invasive encapsulated follicular variant of papillary thyroid cancer. Clin Endocrinol (Oxf) 2017; 87: 635–636.
28.
Brandler TC, Yee J, Zhou F, Cho M, Can-giarella J, Wei X-J, et al: Does noninvasive follicular thyroid neoplasm with papillary-like nuclear features have distinctive features on sonography? Diagn Cytopathol 2018; 46: 139–147.
© 2018 S. Karger AG, Basel
2018
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