2018 Jun;29(3):233-240. doi: 10.1111/cyt.12537. (2016) Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in the Bethesda System for reporting thyroid cytopathology. 1). Therefore, approximately 58% (74/128) of conventional PTC patients with two or three parameters can be diagnosed as malignant PTC, not NIFTP. – NIFTP had more subtle features, whereas FVPTC had more diffuse atypia • Classic PTC vs. NIFTP – Classic PTC: papillary structures, nuclear inclusions, psammoma bodies PTC nuclei were diffusely present in 88.6% and focally present in 11.4%. Invasive FVPTC vs NIFTP (NI-FVPTC) • Cytology can not distinguish between them • NIFTP has more subtle features, whereas inv. It has a higher rate of central nodal metastasis and BRAF V600E mutation in comparison with EFVPTC and Cytological findings of invasive FVPTC and NIFTP were very similar to each other but differed from those of conventional PTC. FNA diagnosis of NIFTP; impact on ROM Microfollicular vs sheet, papillae, pseudoinclusions SM cPTC:) 96% sheets) 79% Abstract. They are not characteristic signs of conventional PTC. Therefore, RAS and BRAF gene analysis may help in the differential diagnosis between NIFTP and invasive FVPTC. (2017) Low rate of NIFTP in Asian practice. Updates in the Pathologic Classification of Thyroid Neoplasms: A Review of the World Health Organization Classification. doi: 10.1530/EC-19-0566. 2021 Jan;10(1):307-318. doi: 10.21037/gs-20-612. To semi-quantitatively distinguish NIFTP from conventional PTC, we examined the scoring of their cytological characteristics. (2016) Cytological features of “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” and their correlation with tumor histology. Higuchi M, et al. The differences, except for psammoma bodies, were considered significant (p < 0.001, p < 0.001, and p = 0.007, respectively; Table 2). NIFTP cases are diagnosed histologically according to Nikiforov’s criteria [1, 2]. The ultrasound findings for IFVPTC group showed at least one of the malignant gray-scale features: markedly hypoechoic, taller-than-wide, microcalcifications or blurred margins. In: Ali SZ, Cibas ES (eds) The Bethesda System for reporting thyroid cytopathology. Ther Adv Endocrinol Metab. Three nuclear features alone cannot differentiate between conventional PTC and invasive FVPTC or NIFTP. Clin Endocrinol (Oxf), Higuchi M, Hirokawa M, Kanematsu R, Tanaka A, Suzuki A, et al. Cytopathol. (2017) Can noninvasive follicular thyroid neoplasm with papillary-like nuclear features be distinguished from classic papillary thyroid carcinoma and follicular adenomas by fine-needle aspiration? Those without a fibrovascular core are pseudo-papillary cell clusters. Online ahead of print. Wang H, Correa H, Sanders M, Neblett WW, Liang J. Pediatr Dev Pathol. This renaming has had a huge impact on the histological and cytological diagnosis of PTC. Cytological specimens in Aichi Cancer Center Hospital were stained using both Papanicolaou and Diff-Quik methods, and those in Kuma Hospital were stained only using the Papanicolaou method. Of 128 patients with conventional PTC, 122 (95%) were diagnosed with malignant PTC. About distinguishing conventional PTC from NIFTP, we previously reported that cytological findings other than the nuclear features would be useful markers [12]. A recent review reported that ≤1 cm behaved in an identical fashion to NIFTP, 32 but nearly all microscopic tumors behave in an indolent fashion already. Mahajan S, Agarwal S, Kocheri N, Jain D, Mathur SR, Iyer VK. Results of scoring using eight cytological parameters for distinction of NIFTP, FVPTC, and conventional PTC, Nikiforov YE, Ghossein RA, Kakudo K, LiVolsi V, Papotti M, et al. Cancer Cytopathol, Canberk S, Gunes P, Onenerk M, Erkan M, Kilinc E, et al. Karger, Basel: 126–153. True nuclear inclusions contain cytoplasmic content and are surrounded by aggregated chromatin. Diffuse FVPTC seems to present and behave in a more aggressive fashion. Thus, the differentiation of conventional PTC from NIFTP and FVPTC is crucial in the cytological diagnosis of PTC. We reclassified 179 cases of the follicular variant (FV) of papillary thyroid carcinoma (PTC) into 72 (40.2%) noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP), 37 (20.7%) encapsulated FVPTC with These cell types can be distinguished because the cytoplasm of multinucleate giant cells is smooth and homogeneous, not foamy as in foamy macrophages. Unable to load your collection due to an error, Unable to load your delegates due to an error. Hirokawa and colleagues [ 21 ] found that NIFTP nodules had higher rates of low suspicion ATA Category on ultrasound and lower rates of high suspicion ATA category than non-NIFTP. The 43 patients with invasive FVPTC comprised 35 women and eight men. A considerable number of NIFTPs and invasive FVPTCs, however, were classified as malignant in our study (Table 1). Gland Surg. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a problematic entity. This is an indolent, low risk tumour that likely represents the preinvasive stage of invasive FVPTC. Therefore, true papillary cell clusters and monolayered cell sheets are characteristic features of conventional PTC, whereas microfollicular cell clusters are characteristic features of NIFTP or invasive FVPTC. Conclusion Nuclear grooves are also typical cytological features of PTC, but are not specific and are not useful if their numbers are small. Cancer Cytopathol, Diaz Del Arco C, Fernandez Acenero MJ (2018) Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: can cytology face the challenge of diagnosis in the light of the new classification? Monolayered cell sheets are the most frequent cell clusters in PTC smears. (2017) Non-invasive follicular thyroid neoplasm with papillary-like nuclear features. Especially, true papillae and psammoma type calcification were described as exclusion criteria for histological diagnosis of NIFTP [2, 20]. The Doppler in this group was mostly avascular. Cytopathology of non-invasive follicular thyroid neoplasm with papillary-like nuclear features: A comparative study with similar patterned papillary thyroid carcinoma variants. No statistically significant difference was found for HBME1 in NIFTP vs PTC (conventional and FVPTC), p>/= 0.2. Therefore, patients with possible NIFTP or invasive FVPTC should be differentiated from those with conventional PTC and excluded from malignant diagnosis. Cytological characteristics of NIFTP, invasive FVPTC, and conventional PTC are shown in Table 2. 2017 , Rosario 2018 b ), histogram analysis of greyscale sonograms ( Kwon et al. In the pre-NIFTP era, Vanzati et al. Pathol Int, Gallagher EM, Oertel YC, Oertel JE (1997) Follicular variant of papillary carcinoma of the thyroid: fine-needle aspirates with histologic correlation. The architectural atypia was not significantly different between the benign and malignancy/NIFTP groups (72% vs. 71.8%). 2021 Apr 12;12:20420188211000500. doi: 10.1177/20420188211000500. In the EFVPTC group, 8.1% cytology were hypercellular and the reminder low to moderate cellularity. We previously reported that conventional PTC can be distinguished from FVPTC and NIFTP based on the cytological findings of cell clusters and smear backgrounds, rather than nuclei [12]. Non-invasive follicular thyroid neoplasm with papillary-like nuclearfeatures (NIFTP): a review and update. National Library of Medicine 62% NIFTP) 12.5% FVPTC) 25% FA cPTC can be separated from NIFTP/FVPTC on FNA Howitt et al. Eight cytological parameters for scoring, Table 5 Orell SR, Sterrett GF, Walters MN-I, Whitaker D (1999) Papillary carcinoma. They look like papillary cell clusters and are sometimes difficult to distinguish. Thus, we evaluated the presence of these parameters. © 2017 Wiley Periodicals, Inc. Keywords: We did not conduct gene analysis. Papillary fibrovascular stroma (Fig. 1) are true papillary cell clusters. (2017) Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a single-institutional experience in Japan. CK19 was also highly expressed in FVPTC and NIFTP (Table I, Fig. All cases were histologically confirmed after undergoing surgical procedures in Aichi Cancer Centre Hospital, Nagoya, Japan. NONINVASIVE FOLLICULAR VARIANT PAPILLARY THYROID CARCINOMA (FVPTC), recently renamed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs), is considered an indolent thyroid tumor because of its better clinical course relative to conventional papillary thyroid carcinoma (PTC) [1-5]. 2) is another distinctive characteristic and often forms a fingerlike radial structure. Approximately 98% (126/128) of patients with conventional PTC and 63% (22/35) of those with NIFTP had at least one of these parameters. We would like to thank Editage (www.editage.jp) for English language editing. Significance of nuclear inclusions, true papillary clusters, and psammoma bodies for differentiation between NIFTP, FVPTC, and conventional PTC, Table 4 FVPTC/NIFTP –Based on microfollicle predominance without papillae, pseudoinclusions or psammomatous calcifications. PTC nuclei were absent in 18%, focally present in 37.5%, and diffusely present in 44.4%. Definitions, criteria and explanatory notes (2, Hirokawa M, Higuchi M, Suzuki A, Hayashi T, Kuma S, et al. More information from NIFTP and FVPTC cases are needed to confirm this finding. Epub 2019 Sep 4. Microfollicular cell clusters were not frequently seen in conventional PTC. (2016) Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. 2020 May-Jun;9(3):159-165. doi: 10.1016/j.jasc.2020.01.002. For this reason, we used a total of eight parameters to differentiate conventional PTC from invasive FVPTC or NIFTP. No statistically significant difference was found for HBME1 in NIFTP vs PTC (conventional and FVPTC), p ≥ 0.2. Many foamy macrophages are seen in the background. Please enable it to take advantage of the complete set of features! When noniEFVPTC and iEFVPTC were separately compared, the noninvasive form showed no propensity for invasive growth (T3 staging: 0/4 vs. 2/6), lymph node metastasis (N1: 0/3 vs. 2/5) or extranodal recurrence. Cancer Cytopathol. Therefore, we have add other 5 parameters for clear differentiation in this study and obtained results that 87.5% of conventional PTCs were definitely diagnosed as malignant. Overall, samples from 128 patients with conventional PTC, 43 with invasive FVPTC, and 35 with NIFTP were used in this study. Nuclear inclusions (intranuclear cytoplasmic inclusions) are one of the most typical cytological characteristics of PTC. Powdery chromatin, an important characteristic of PTC, refers to very fine, watery nuclear chromatin in cytological smears, identical to Orphan Annie eye nuclei in histology. By ultrasonography, NIFTP appears as a well-demarcated benign-looking nodule, while invasive FVPTC appears as a vague nodule with an indistinct border because of the associated invasion. To investigate the cytological features of FVPTC, including NIFTP and conventional PTC, we reviewed the cytological smears of 60 patients with conventional PTC, five with invasive FVPTC, and two with NIFTP. 6) are concentric calcified bodies and are highly suggestive of PTC, but they are not frequently observed in individuals with PTC. Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features in Children: An Institutional Experience and Literature Review. In such cases, if the BRAF V600E mutations are present, it is best not to diagnose the tumor as a NIFTP but rather a FVPTC. To date, there is no reliable method to distinguish NIFTP from invasive FVPTC by cytology. Zajkowska K, Kopczyński J, Góźdź S, Kowalska A. Endocr Connect. Using these parameters, NIFTP and invasive FVPTC can be clearly distinguished from conventional PTC. NIFTP patients (50 and 16.4% respectively, p< 0.0001). There is a tendency toward higher prevalence in Western countries and lower prevalence in Asian countries. FVPTC is the most common subtype of PTC [18]. Department of Pathology, Shubun University Faculty of Nursing, Ichinomiya 491-0938, Japan Department of Clinical Laboratories, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan, Department of Clinical Laboratories, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan, Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan, Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan, Department of Laboratory Medicine, Kuma Hospital, Kobe 856-8562, Japan, Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe 856-8562, Japan, Department of Surgery, Kuma Hospital, Kobe 856-8562, Japan, (EndNote、Reference Manager、ProCite、RefWorksとの互換性あり). In this study, we focused on five non-nuclear features, which were observed in conventional PTC, but not in NIFTP, in addition to three nuclear features. 2020 Dec;35(4):696-715. doi: 10.3803/EnM.2020.807. The differences were considered significant by Pearson’s chi-square test (p < 0.001, Table 2). Thyroid, Kakudo K, Bychkov A, Bai Y, Li Y, Liu Z, et al. Cytopathology. Any capsular or vascular invasion but if the whole capsule has not been examined thoroughly then the default diagnosis is still noninvasive encapsulated FVPTC (EFVPTC) and it is NOT a NIFTP True papillary structures in more than 1% of tumor volume, psammoma bodies, infiltrative border Papillary cell clusters are the most essential signs of PTC. J Am Soc Cytopathol. Consequently, it is better to not classify FVPTC cases into the malignant category to avoid false-positive diagnosis. In contrast, the frequency of nuclear grooves and powdery chromatin were almost identical among these three groups. Such cases are classified as indeterminate Thyroid Bethesda System categories of atypia of undetermined significance or follicular lesion of undetermined significance, follicular neoplasm or suspected follicular neoplasm, or suspicious for malignancy. J Basic Clin Med. The results of routine cytological diagnosis based on the Thyroid Bethesda System [6] are shown in Table 1. However, this result is not sufficient, because more than 40% of conventional PTCs were diagnosed as indeterminate. The difference was considered significant (p < 0.001, Table 2). Although psammoma bodies were not significant statistically (p = 0.088, Table 2), they were still considered a useful finding for conventional PTC because they were not observed in patients with NIFTP and invasive FVPTC. Clinicopathological parameters for predicting non-invasive follicular thyroid neoplasm with papillary features (NIFTP). Of the 17 FVPTC cases, 12% were diagnosed as FLUS, 53% as FN/SFN and 35% as SPTC. The difference was considered significant (p < 0.001, Table 2). Also important in the definitive diagnosis of PTC are the appearance of cell clusters and smear background [5, 13-17]. NIFTP is related to RAS gene mutation, like follicular adenoma and carcinoma. Hence, in this study, we added 71 patients with NIFTP and invasive FVPTC, examined their nuclear findings, confirmed that the nuclear findings were very similar, and that there was nearly no difference between NIFTP and invasive FVPTC. In: Gray W, Mckee GT (eds) Diagnostic cytopathology (2, Rosai J, Albores Saavedra J, Asioli S, Baloch ZW, Bogdanova T, et al. Additionally, we also reviewed the cytological smears of 68 patients with conventional PTC, 38 with invasive FVPTC, and 33 with NIFTP, which were also histologically confirmed after surgical procedures in Kuma Hospital, Kobe, Japan. The prospects of NIFTP for thyroid cytology: The ROM for indeterminate diagnostic categories of TBSRTC will change. The 2nd edition monograph of the Thyroid Bethesda System recommends that a definitive malignant diagnosis of PTC should be reserved in patients who present, in addition to other characteristics, at least one of the following features: papillary architecture, psammoma bodies, and intranuclear inclusions [5]. confirmed that NIFTP larger than 4 cm shows the same low risk of recurrence.
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