Clinical-Pathological and Molecular Evaluation of 451 NIFTP Patients from a Single Referral Center

Background: Non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were introduced in thyroid pathology in 2016. NIFTPs are a group of follicular neoplasm with an indolent behaviour. In this study, we gathered a large retrospective cohort of NIFTPs and compared those presenting as solitary lesions and NIFTPs found in multifocal setting. Methods: A retrospective search of NIFTPs was performed, and the clinico-pathological features were recorded. For a subgroup of patients, pre-surgical ultrasound (US) evaluation, cytological diagnosis, and molecular analysis were available. Results: We collected 451 NIFTPs; 254 (56.3%) were truly solitary tumours, while 197 coexisted with one or more NIFTP/cancer. Contrasting unifocal and multifocal settings, NIFTPs size was the only significantly different parameter. Preoperatively, NIFTP nodules mostly showed low-risk US characteristics, indeterminate cytology and a RAS-like molecular profile. Conclusion: NIFTPs often coexist with collateral thyroid tumours. However, no clinical-pathological differences can be observed between solitary and “multifocal” NIFTPs. Despite the well-established clinical indolence of NIFTP, a careful monitoring of the contralateral lobe should not be excluded.

Oral exfoliative cytology – A technical appraisal in oral diseases

Oral exfoliative cytology is one of the easy, simple, economical and non-cumbersome diagnostic adjunct. It involves examining the exfoliated buccal cells for alterations in cellular and nuclear features. It offers the advantage of being useful in less resource setting areas. Though associated with many false results, the newer technological advancements have proven its diagnostic efficiency. Oral exfoliative cytology can readily be used as adjunct to disease diagnosis, however, it cannot replace biopsy.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features and the risk of malignancy in thyroid cytology: Data from Singapore

Introduction: The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on the risk of malignancy (ROM) in fine-needle aspiration cytology (FNAC) per The Bethesda System for Reporting Thyroid Cytopathology has not been well reported in Singapore. Methods: We retrospectively identified 821 thyroid nodules with preoperative FNAC from 788 patients out of 1,279 consecutive thyroidectomies performed between January 2010 and August 2016 in a tertiary general hospital in Singapore. Possible cases of NIFTP were reviewed for reclassification and the impact of NIFTP on ROM was analysed. Results: The incidence of NIFTP was 1.2% (10 out of 821). If NIFTP is considered benign, ROM in Bethesda I through VI were 8.6%, 3.5%, 26.3%, 20.0%, 87.7%, 97.0% versus 8.6%, 4.2%, 28.1%, 26.7%, 89.2% and 100% if NIFTP is considered malignant. Eight patients with NIFTP had follow-up of 15 to 110 months. One had possible rib metastasis as evidenced by I131 uptake but remained free of structural or biochemical disease during a follow-up period of 110 months. None had lymph node metastasis at presentation, nor locoregional or distant recurrence. Conclusion: Classifying NIFTP as benign decreased ROM in Bethesda II through VI, but the benignity of NIFTP requires more prospective studies to ascertain. The impact of NIFTP on ROM in our institution also appears to be lower than that reported in the Western studies Keywords: Bethesda, cytology, NIFTP, risk of malignancy, TBSRTC, thyroid nodule

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features Is Not a Cytological Diagnosis, but It Influences Cytological Diagnosis Outcomes: A Systematic Review and Meta-Analysis

Background: A low-risk thyroid tumour, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced in 2016. NIFTP criteria require a thorough histological examination to rule out capsular and lymphovascular invasion, which denies the possibility of preoperative cytological diagnosis. Nevertheless, since the adoption of the new entity, the cytology of NIFTP has been a subject of interest. Objectives: The present systematic review and meta-analysis investigate the cytological diagnosis of NIFTP. Method: An online PubMed literature search was conducted between March 1, 2020, and June 30, 2020, for all original articles considering the cytology of histologically proven NIFTP. The studies including data on fine needle aspiration specimens classified by The Bethesda System for Reporting Thyroid Cytology (TBSRTC) categories, risk of malignancy (ROMs) in the TBSRTC categories, and cytomorphological features of NIFTP were included in the meta-analysis. Non-English studies and case reports were excluded. The data were tabulated and statistical analysis was performed with Open Meta-Analyst program. Results: Fifty-eight studies with a total of 2,553 NIFTP cases were included in the study. The pooled prevalence of NIFTP cases was calculated among 25,892 surgically resected cases from 20 studies and the results show that NIFTP consisted 4.4% (95% confidence interval [CI]: 3.5–5.4%) of all cases. Most of the NIFTP cases (79.0%) belonged to the intermediate categories of TBSRTC. The pooled distribution of NIFTP cases in each TBSRTC category was 1.3% (95% CI: 0.8–1.7%) in non-diagnostic (ND), 8.9% (95% CI: 6.9–10.8%) in benign, 29.2% (95% CI: 25.0–33.4%) in atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), 24.2% (95% CI: 19.6–28.9%) in follicular neoplasm (FN), 19.5% (95% CI: 16.1–22.9%) in suspicious for malignancy (SM), and 6.9% (95% CI: 5.2–8.7%) in malignant. Compared to pre-NIFTP era, the pooled risk differences of ROM were reduced by 2.4% in ND, 2.7% in benign, 8.2% in AUS/FLUS, 8.2% in FN, 7.3% in SM, and 1.1% in the malignant category. The cytomorphological features of NIFTP were similar to follicular variant of papillary thyroid carcinoma (FVPTC) but lesser to papillary thyroid carcinoma (PTC). Conclusions: Based on our results, NIFTP remains a histological diagnosis. Although cytomorphological features cannot be used in differentiating NIFTP from FVPTC, they may guide in separating NIFTP from PTC. Features such as papillae, microfollicles, giant cells, psammoma bodies, and the amount of papillary-like nuclear features should be taken into account when suspicious of NIFTP. NIFTP should not have papillae or psammoma bodies, and giant cells were rarely observed.

Immunohistochemistry Helps to Distinguish Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features/Noninvasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma with Other Follicular Thyroid Lesions

Background and Objectives: We aimed to assess the diagnostic value of various immunohistochemical (IHC) markers and panels for differentiation among benign follicular nodules (BFNs), noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), noninvasive encapsulated follicular variants of papillary thyroid carcinoma (NEFVPTCs), and infiltrative FVPTC (IFVPTC). Materials and Methods: Sixty-three cases were classified as BFNs, NIFTPs, NEFVPTCs, or IFVPTCs and were evaluated using the following markers: CK19, CD56, galectin-3, CITED1, HBME-1, VE1, and TROP-2. Results: The IHC results for NIFTP and NEFVPTC exhibited no statistically significant differences. In differentiating IFVPTCs from BFNs and NIFTPs/NEFVPTCs, galectin-3 and TROP-2 were the markers with the highest sensitivity plus high specificity, respectively. In various combinations, panel co-expression of two markers, including galectin-3 and/or HBME-1 and/or TROP-2, and the combination of galectin-3 and TROP-2 co-expression could achieve 100% in all aspects. In terms of discrimination of BFNs from NIFTP/NEFVPTC, CK19 was the single most sensitive marker (81.3%), while CD56 was the most specific (100%). The panel consisting of CK19 and/or HBME-1 exhibited the greatest sensitivity (96.9%), but the panel with CD56 and/or HBME-1 exhibited the greatest specificity (90.5%). Conclusions: Our results broaden the use of IHC markers for differential diagnoses among the four groups of follicular-based lesions. In addition, the similar IHC profiles of NIFTP and NEFVPTC also suggest the original criterion of <1% papillae within tumors, providing a reliable NIFTP diagnosis. Their close relationship may represent a spectrum of progressing neoplasia.