Diagnosis Of NIFTP Research Articles

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): what do we need to know?

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently defined thyroid nodule category characterized by follicular architecture with papillary nuclear features but lacking classical papillary carcinoma features like papillae or psammoma bodies. The diagnosis of NIFTP is based on histological examination and excludes cases with high-risk mutations like BRAFV600E. NIFTP carries a low risk of recurrence and distant metastasis, prompting a more conservative surgical approach compared to classical papillary thyroid carcinoma. The management of NIFTP typically involves lobectomy with postoperative monitoring of thyroglobulin levels and performing neck ultrasounds. While the identification of NIFTP represents a significant advancement in thyroid cancer diagnosis, challenges remain in refining preoperative diagnostic tools and establishing optimal long-term follow-up strategies. The objective of this review is to provide a comprehensive overview of NIFTP, including its histopathological characteristics, molecular profile, clinical presentation, diagnostic criteria, management strategies, and future research directions.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Prevalence, cyto-histo correlation, and molecular and ultrasonographic profile

Non-invasive follicular thyroid neoplasm with papillary like nuclear features (NIFTP) was introduced in 2017 WHO Classification of Endocrine Tumors. In this study, we aim to characterize the molecular and ultrasonographic profiles of NIFTP and evaluate the performance of fine needle aspiration (FNA) cytology. Consecutive thyroid resections at our institution between 2018 and 2022 were collected; 1282 thyroid resections were identified. NIFTP was diagnosed in 109 cases (prevalence: 8.5 %); 65 (60 %) were the targeted nodules with an average size of 2.5 cm. Among these 65 targeted, 27 had Afirma testing results, 44 had Thyroid Imaging Reporting and Data System (TIRADS) scores, and 53 had FNA results. Of the 27 cases with Afirma reports, 23 were labeled “suspicious”, including 5 with RAS-related mutations (risk of malignancy (ROM) 75 %) and 17 without a reportable genetic alternation (ROM 50 %). 60 % cases with TIRADS scores were classified as TIRADS 4, while 16 % were classified as TIRADS 5. The majority of the 53 FNA cases had a diagnosis of AUS/FLUS (53.7 %) or FN (31.5 %). One additional targeted nodule with a diagnosis of NIFTP had BRAFV600E mutation and was reclassified as papillary thyroid carcinoma. In summary, the majority of the targeted NIFTPs had “suspicious” Afirma testing results (85 %), TIRADS 4 scores (60 %) and either AUS/FLUS (53.7 %) or FN (31.5 %) FNA results. The sensitivity and specificity of cytology for diagnosing NIFTP were 90 % and 57 %, respectively, with a positive predictive value (PPV) of 16 % and negative predictive value of 98 %.

Reappraisal of BRAFK601E-positive thyroid tumors in the NIFTP era.

BRAFK601E is an uncommon mutation typically found in encapsulated follicular-patterned thyroid tumors. Previous studies on BRAFK601E-positive thyroid tumors were conducted before implementation of the non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP) diagnosis. This study aimed to characterize BRAFK601E-positive tumors and evaluate changes in diagnosis and management of these patients after introduction of NIFTP. We evaluated 25 thyroid tumors that were positive for BRAFK601E and diagnosed considering the NIFTP criteria. Clinicopathologic characteristics and recurrence rates of these tumors were compared to 29 BRAFK601E-positive tumors diagnosed prior to the acceptance of NIFTP diagnosis. RNA-seq analysis was performed on 10 BRAFK601E-positive tumors. In the current study, 72% of BRAFK601E-positive tumors were diagnosed as non-invasive tumors on resection, with NIFTP (48% of all tumors) being the most common diagnosis. BRAFK601E-positive tumors exhibited a RAS-like gene expression profile with BRAF-RAS score (BRS) and thyroid differentiation score (TDS) distinct from BRAFV600E-positive tumors (P<0.001). Since 2016, patients with BRAFK601E-positive tumors less frequently underwent total thyroidectomy (41% vs 100%, P<0.001) and received radioiodine (7% vs 75%, P<0.001). None of the tumors positive for an isolated BRAFK601E mutation from the current or 2016 studies showed recurrences on follow-up. Our study demonstrates that most BRAFK601E-positive tumors are low risk, RAS-like tumors, which were diagnosed as NIFTP in half of all study cases. Since 2016, patients with BRAFK601E-positive nodules receive less aggressive treatment. The risk of recurrence of BRAFK601E-positive tumors without other, high-risk features appears to be low, and lobectomy without radioiodine is likely sufficient treatment for these patients.

Maldi-ms imaging in niftp diagnosis: an alternative approach

Maldi-ms imaging in niftp diagnosis: an alternative approach

RAS-Mutant Follicular Thyroid Tumors: A Continuous Challenge for Pathologists.

The classification of thyroid nodules, particularly those with a follicular growth pattern, has significantly evolved. These tumors, enriched with RAS or RAS-like mutations, remain challenging for pathologists due to variables such as nuclear atypia, invasion, mitotic activity, and tumor necrosis. This review addresses the histological correlates of benign, low-risk, and malignant RAS-mutant thyroid tumors, as well as some difficult-to-classify follicular nodules with worrisome features. One prototypical RAS-mutant nodule is non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The assessment of nuclear characteristics in encapsulated/well-demarcated non-invasive RAS-mutant follicular-patterned tumors helps distinguish between follicular thyroid adenoma (FTA) and NIFTP. Despite this straightforward concept, questions about the degree of nuclear atypia necessary for the diagnosis of NIFTP are common in clinical practice. The nomenclature of follicular nodules lacking clear invasive features with increased mitotic activity, tumor necrosis, and/or high-risk mutations (e.g., TERT promoter or TP53) remains debated. Invasion, particularly angioinvasion, is the current hallmark of malignancy in RAS-mutant follicular-patterned neoplasms, with follicular thyroid carcinoma (FTC) as the model. Assessing the tumor interface is critical, though full capsule evaluation can be challenging. Multiple levels and NRASQ61R-specific immunohistochemistry can aid in identifying invasion. Controversies around vascular invasion persist, with ancillary stains like CD31, ERG, and CD61 aiding in its evaluation. Moreover, the review highlights that invasive encapsulated follicular variant papillary thyroid carcinoma (IEFVPTC) is closely associated with FTC, suggesting the need for better nomenclature. The concept of "high-grade" differentiated carcinomas, applicable to FTC or IEFVPTC with necrosis and/or high mitotic activity, is also discussed.

Seven years of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Rate of Acceptance and Variation of Diagnostic Approaches Across Different Continents.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in Mureș County, Romania: Incidence and impact of reclassification over a six-year period (2016-2021)

Abstract Objective: In 2016 a group of expert endocrine pathologists proposed a new terminology, NIFTP (Non-invasive follicular thyroid neoplasm with papillary-like nuclear features) for a histological subtype of thyroid carcinoma (encapsulated follicular variant of papillary thyroid carcinoma, non-invasive type). In this study, we aimed to assess on a retrospective basis the epidemiological trend and overall incidence of NIFTP in Mureș county, Romania, over a six-year period (2016-2021). Methods: All NIFTPs registered between 2016-2021 in Târgu-Mureș Pathology Departments were reevaluated. NIFTP’s incidence was calculated by dividing the number of NIFTPs with the number of papillary thyroid carcinomas (PTCs). Further on, we compared NIFTP’s incidence between 2016-2018 with NIFTP’s incidence between 2019-2021, as the diagnostic criteria of NIFTP were revised in 2018. Results: Forty-six cases of NIFTP were registered in our departments between 2016-2021, resulting in an overall NIFTP incidence of 17.9 % [CI (95%): 7.6-32.5] among the 257 PTCs. When we compared the NIFTP’ incidence between the two study periods (2016-2018 versus 2019-2021), our data revealed that the NIFTP’s overall incidence has dropped from 21.4 % [CI (95%): −14.5-60.1] to 15% [CI (95%): −8.2-43] in the second evaluated period (p=0.034). Conclusion: The overall NIFTP incidence was low in our departments between 2016-2021. Moreover, NIFTP’s incidence decreased after 2018, following revision of the diagnostic criteria. Our results highlight that very stringent morphologic criteria need to be apply when making a diagnosis of NIFTP, in order to avoid a misdiagnosis and/or an overtreatment of a tumor with indolent behavior.

Digital analyses of nuclear features can help discriminate among non-invasive follicular thyroid neoplasm with papillary-like nuclear features, papillary thyroid carcinoma follicular subtype, and follicular carcinoma in cytological specimens.

As it stands, the diagnosis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is primarily based on histological analysis. We hypothesised that computerised analysis of nuclear images of cytological specimens could be used to differentiate NIFTP from papillary thyroid carcinoma follicular subtype (PTCFS) and follicular carcinoma (FC), influencing patient management. We employed a retrospective analytical observational study based on nuclear morphometric variables of cytological material from thyroid nodules classified as PTCFS, NIFTP, or FC. Five cases of each entity were analysed. Cytological slides were photographed, and 1170 cells for each entity were analysed digitally. The captured images were evaluated (blindly) using the ImageJ software package. The morphometric evaluation included area, perimeter, width, height, and circularity. Numerical variables were expressed as mean, median, minimum, and maximum (min; max) values. Kruskal-Wallis and Dunn's tests were used with a 5% significance level. Regarding nuclear analysis, all variables differed among the three groups (p < 0.001). Given the interdependence among the variables, these data indicated that nuclear size was greatest in the NIFTP group, followed by FC and PTCFS. Our analysis of the digital images, with a focus on nuclear parameters, found significantly difference among cytological specimens from cases of NIFTP, PTCFS and FC. Thus, this tool has the potential to provide additional information that may help in the diagnosis of NIFTP, even during the preoperative period. Additional studies are needed to create protocols, evaluate the applicability of nuclear morphological and morphometric parameters-focusing on digital pathology-and create algorithms and tools to assist cytopathologists with their diagnostic routines.

Cytological Features of "Non-Invasive Follicular Tumour with Papillary like Nuclear Features" - A Single Institutional Experience in India.

The term noninvasive follicular tumor with papillary-like nuclear features (NIFTP) was introduced as a surrogate for noninvasive encapsulated follicular variant of papillary thyroid carcinoma with a defined set of histopathologic criteria. There are very few studies depicting the cytological cues for the diagnosis of NIFTP. The objective of the study was to determine the spectrum of cytological features in fine needle aspiration cytology (FNAC) smears of cases histopathologically diagnosed as NIFTP. This was a retrospective cross-sectional study conducted over a duration of four years between January 2017 and December 2020. All surgically resected cases (n-21), who met the diagnostic criteria of NIFTP on histopathology and who underwent preoperative FNAC were included and reviewed in the study. Out of a total of 21 cases, at FNAC, diagnosis of benign, suspicious for malignancy, follicular variant of papillary thyroid carcinoma, and classic papillary thyroid carcinoma (PTC) was rendered in 14 (66.6%), 2 (9.5%), 2 (9.5%), and 3 (14.28%), respectively. Scanty cellularity was noted in 12 (57.1%) cases. Papillae, sheets, and microfollicles were seen in 1 (4.7%), 10 (47.6%), and 13 (61.9%) cases, respectively. Nucleomegaly, nuclear membrane irregularities, nuclear crowding, and overlapping were seen in 7 (33.3%), 9 (42.8%), and 9 (42.8%), respectively. Nucleoli, nuclear grooving, and inclusions were seen in 3 (14.2%) 10 (47.6%), and 5 (23.8%) cases, respectively. At FNAC, NIFTP can be found in every category of The Bethesda System for Reporting Thyroid cytopathology (TBSRTC). Nuclear membrane irregularities, nuclear grooving, mild nuclear crowding, and overlapping were noted in a modest number of cases. However, the absence or rare occurrence of features such as papillae, inclusions, nucleoli, and metaplastic cytoplasm may help prevent an overdiagnosis of malignancy.

Is it Possible to Diagnose "Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features" Preoperatively?

There is no accepted consensus or algorithm for the preoperative diagnosis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in patients with thyroid nodules. In this study, we evaluated the importance of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in the differential diagnosis of NIFTP. Pathology preparations of 209 patients with a follicular variant of papillary thyroid carcinoma (FVPTC) diagnosed after thyroid surgery in a tertiary health center between January 2010 and January 2020 were re-evaluated. Patients were divided into NIFTP and encapsulated follicular variant papillary thyroid carcinoma (EFVPTC) to compare. Of the patients, 58 (27.7%) were NIFTP, and 151 (72.3%) were EFVPTC. There was no statistically significant difference in terms of age (p = 0.46), tumor size (p = 0.51), gender (p = 0.48), and surgical technique (p = 0.78) between the groups. The probability of the neutrophil-to-lymphocyte ratio (NLR) > 2 is more common in the EFVPTC group. It was statistically significant that the NIFTP group was 1.96 times more likely to have NLR > 2 (OR: 1.96, 95% CI: 1.06-3.63) (p < 0.05). However, there was no risk difference between the groups in terms of the platelet-to-lymphocyte ratio (PLR) (OR: 0.76, 95% CI: 0.41-1.43) (p > 0.05). The diagnosis of NIFTP should be kept in mind in the evaluation of patients whose thyroid fine-needle aspiration (FNA) biopsy results are in the intermediate group. NIFTP exhibits better prognostic findings than classic thyroid papillary cancer and EFVPTC. Therefore, preoperative diagnosis of NIFTP in line with laboratory, ultrasonography, and FNA findings will save the patient from unnecessary overtreatment.

PSAT241 Variation in the Diagnosis of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) in the United States

Abstract Background The North American Association of Central Cancer Registries (NAACCR) develops and promotes uniform data standards for cancer registries, such as uniform cancer coding, and is used by all central cancer registries in the United States (US) and Canada, including Surveillance, Epidemiology and End Results (SEER). Effective January 1, 2017, the NAACCR modified its coding scheme and noninvasive encapsulated follicular variant of papillary thyroid cancer (EFVPTC) was reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to reflect the indolent nature and very low risk of adverse outcomes of this thyroid tumor. The diagnostic use of NIFTP was anticipated to impact tens of thousands of patients in the US. Since NIFTP is no longer considered a cancer, as of January 1, 2021, it was no longer a reportable diagnosis in SEER. However, little is known about how the diagnosis of NIFTP was utilized across different regions and patient populations in the US when it was a reportable diagnosis. Methods Data was extracted from the US SEER-21 cancer registry (2000-2018). The study cohort comprised of individuals diagnosed with papillary or follicular thyroid cancer (2000-2018), or NIFTP (2017-2018). We examined the annual incidence of thyroid cancer by subtypes and NIFTP. Using data for 2018, we determined the rates of NIFTP for each of the 16 sites included in SEER-21. In addition, we compared the demographics of patients diagnosed with NIFTP to that of patients diagnosed with papillary and follicular thyroid cancer using Chi-square test. Results Between 2010 and 2018, we identified a total of 191,107 cases (182,893 PTC, 7,445 FTC, and 769 NIFTP). Incidence of FVPTC sharply declined from 2015 to 2018, with observed increases in NIFTP and encapsulated PTC/ invasive EFVPTC each accounting for 17% and 10% of the decline in FVPTC, respectively. High heterogeneity was observed in the regional incidence of NIFTP in 2018, with incidence rates ranging from 0.0% (Alaska) to 5.8% (Seattle-Puget Sound). Based on 2018 data, a diagnosis of NIFTP (2.2% of total thyroid cancer cases) was significantly associated with female sex (P=0.001), Black race (P&amp;lt;0.001), and non-Hispanic ethnicity (P&amp;lt;0.001) compared to diagnosis of papillary and follicular thyroid cancer. Conclusion There is marked variation in the use of the NIFTP diagnoses. The recent NAACCR coding change that resulted in NIFTP, a tumor with uncertain malignant potential and for which there is no long-term outcome data available, no longer being a reportable diagnosis will disproportionately affect women and Black patients, and patients who reside in regions with higher rates of NIFTP diagnoses. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Variation in the Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features.

Noninvasive encapsulated follicular variant of papillary thyroid cancer was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in January 2017. The impact of this nomenclature change at a population level remains unknown. Examine use of NIFTP across different US regions and populations. Descriptive epidemiology study using SEER-22 data (2000-2019). Individuals diagnosed with papillary or follicular thyroid cancer (2000-2019) or NIFTP (2017-2019). Annual incidence rates of thyroid cancer by subtype and NIFTP. Using 2018-2019 data, (1) rates of NIFTP at the 17 SEER-22 sites and (2) comparison of demographics for patients diagnosed with NIFTP vs papillary and follicular thyroid cancer. NIFTP comprised 2.2% and 2.6% of cases in 2018 and 2019, respectively. Between 2018 and 2019, large heterogeneity was observed in the regional use of NIFTP diagnosis, with site-specific incidence rates between 0.0% and 6.2% (median 2.8%, interquartile range 1.3-3.6%). A diagnosis of NIFTP (vs papillary and follicular thyroid cancer) in 2018 and 2019 was significantly associated with older age (P = 0.012 and P = 0.009, respectively), Black race (both Ps < 0.001), and non-Hispanic ethnicity (both Ps < 0.001). Marked variation exists in the use of the NIFTP diagnosis. The recent 2021 coding change that resulted in NIFTP, a tumor with uncertain malignant potential and for which there is no long-term outcome data available, no longer being a reportable diagnosis to SEER will disproportionately affect vulnerable patient groups such as older patients and Black patients, in addition to patients who reside in regions with higher rates of NIFTP diagnoses.

Non-invasive follicular neoplasm with papillary-like nuclear features: a challenging and infrequent entity in Argentina.

Non-invasive encapsulated follicular variant of papillary thyroid cancer was reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). These neoplasms have an extremely low malignant potential. The aim of this study was (1) to assess the prevalence of NIFTP in patients with papillary thyroid carcinoma, (2) to evaluate their outcomes, and (3) to determine their molecular profile. Multicenter, descriptive, retrospective study. Patients with papillary thyroid cancer diagnosed from January 2006 to December 2016 from 11 referral centers were included. Diagnosis of NIFTP was based on criteria described by Nikiforov et al. in 2018. At least two pathologists agreed on the diagnosis. Two thousand six hundred and seventy-seven papillary thyroid cancer patients were included; 456 (17%) of them were follicular variant papillary thyroid cancer, and 30 (1.12%) fulfilled diagnostic criteria for NIFTP. Each of the 30 included patients underwent a total thyroidectomy, and 50% were treated with radioiodine (median dose 100 mCi). After a median follow-up of 37 months, 84% of patients had an excellent response, 3% had an indeterminate response and data was missing in the remaining 13%. No metastatic lymph nodes, distant metastases or recurrences were found. RAS mutations were detected in 4 patients (13%). The prevalence of NIFTP in our series is amongst the lowest reported. Excellent outcomes of patients underscore their low malignant potential. Molecular findings differ from other series, probably related to environmental or ethnic features of our population and the meticulous criteria for diagnosing NIFTP.

Non-invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) Lowers the Risk of Malignancy in the Bethesda System for Reporting Thyroid Cytopathology Diagnostic Categories.

Background:The introduction of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has been shown to decrease the risk of malignancy (ROM) in The Bethesda System for Reporting Thyroid Cytopathology. This knowledge may alter the management of patients with thyroid nodules.Objectives:To correlate cytological diagnosis with histological diagnosis for establishing the ROM of all Bethesda system categories after the introduction of NIFTP.Methods:This was a retrospective cohort study. All consecutive fine-needle aspiration cytology (FNAC) specimens collected from January 1, 2013, to December 31, 2017, at King Abdullah Medical City, Jeddah, Saudi Arabia, were assessed, and patients who underwent surgical excision of thyroid nodules were further analyzed. The ROM and overall ROM for each Bethesda category were calculated with and without considering NIFTP as a malignant tumor.Results:Overall, 1066 FNAC specimens were collected, of which 281 had a surgical correlation. Our cases included 18 (6.4%) non-diagnostic (ND), 109 (38.8%) benign, 28 (9.9%) atypia/follicular lesion of undetermined significance (AUS/FLUS), 39 (13.8%) follicular neoplasm or suspicion for follicular neoplasm (FN/SFN), 20 (7.1%) suspicion for malignancy (SM), and 67 (23.8%) malignant (POM) cases. After considering NIFTP diagnosis on resection specimens, the ROM decreased as follows: ND, 38.8% to 27.7% (P = 0.2388); benign, 21.1% to 11.9% (P = 0.0343); AUS/FLUS, 50% to 39.2% (P = 0.2089); FN/SFN, 53.8% to 33.3% (P = 0.0336); SM, 85% to 75% (P = 0.2147); POM, 95.5% to 88% (P = 0.0582).Conclusion:The introduction of NIFTP would significantly decrease the ROM of thyroid FNAC in both benign and FN/SFN categories of the Bethesda system.

CD56 Expression in Papillary Thyroid Carcinoma Is Highly Dependent on the Histologic Subtype: A Potential Diagnostic Pitfall.

Loss of CD56 expression has been regarded as a diagnostic marker of papillary thyroid carcinoma (PTC). However, certain variants of PTC can aberrantly express CD56. Using a digital image analysis tool, we evaluated H-scores of CD56 immunostaining in 216 thyroid tumors. The H-score of the CD56 of all PTCs was lower than that of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (P<0.001). The H-scores of CD56 were lower in classic PTC, the infiltrative follicular variant, and the diffuse sclerosing variant than in other PTC variants (P<0.001), whereas the H-scores were higher in tall cell variant, Warthin-like variant, and cribriform-morular variant than in classic PTC (P<0.001). The optimal cutoff value of H-scores for the CD56 expression was 180 for differentiating the NIFTP from the follicular adenoma and 30 for the differential diagnosis of NIFTP and infiltrative follicular variant PTC. CD56 expression is predominantly lost in classic and infiltrative follicular variants of PTCs and more preserved in the other histologic subtypes of PTC and NIFTP. CD56 is particularly useful for differentiating PTC from follicular-pattern thyroid neoplasms, but the aberrant expression in uncommon variants of PTC could be a diagnostic pitfall.

What's in a Name? A Cost-Effectiveness Analysis of the Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features' Nomenclature Revision.

Background: The noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (eFVPTC) has been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reflect the indolent behavior and favorable prognosis of this type of tumor. This terminology change has also de-escalated its management approach from cancer treatment to a more conservative treatment strategy befitting a benign thyroid neoplasm. Objective: To characterize the reduced health care costs and improved quality of life (QOL) from management of NIFTP as a nonmalignant tumor compared with the previous management as eFVPTC. Methods: A cost-effectiveness analysis was performed by creating Markov models to simulate two management strategies for NIFTP: (i) de-escalated management of the tumor as NIFTP involving lobectomy with reduced follow-up, (ii) management of the tumor as eFVPTC involving completion thyroidectomy/radioactive iodine ablation for some patients, and follow-up recommended for carcinoma. The model was simulated for 5 and 20 years following diagnosis of NIFTP. Aggregate costs and quality-life years were measured. One-way sensitivity analysis was performed for all variables. Results: Over a five-year simulation period, de-escalated management of NIFTP had a total cost of $12,380.99 per patient while the more aggressive management of the tumor as eFVPTC had a total cost of $16,264.03 per patient (saving $3883.05 over five years). Management of NIFTP provided 5.00 quality-adjusted life years, whereas management as eFVPTC provided 4.97 quality-adjusted life years. Sensitivity analyses showed that management of NIFTP always resulted in lower costs and greater quality-adjusted life years (QALYs) over the sensitivity ranges for individual variables. De-escalated management for NIFTP is expected to produce ∼$6-42 million in cost savings over a five-year period for these patients, and incremental 54-370 QALYs of increased utility in the United States. Conclusion: The degree of cost savings and improved patient utility of de-escalated NIFTP management compared with traditional management was estimated to be $3883.05 and 0.03 QALYs per patient. We demonstrate that these findings persisted in sensitivity analysis to account for variability in recurrence rate, surveillance approaches, and other model inputs. These findings allow for greater understanding of the economic and QOL impact of the NIFTP reclassification.

What you see might not be what you get: Analysis of 15 prospective cases of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

IntroductionNoninvasive follicular thyroid neoplasm with papillary-like nuclear (NIFTP) is a new entity. No previous study reported prospective cases, outlining using many quantitative and qualitative variables.MethodsRetrospective analysis of all (15) prospective NIFTP cases diagnosed between 2017 and 2021 at our institution. Statistical quantitative analysis outlined demographic, history, ultrasound, histopathology and treatment characteristics. Qualitative analysis examined the cases, with details provided on three cases to highlight the different possible presentations and configurations.ResultsMean age was 41.5 ± 9.91 years, 73.3% were females, and mean BMI was 29.49 ± 5.74 kg/m2. About 87% patients were symptomatic; 86.6% had neck swelling. Ultrasound (US) showed multiple nodules in 71.4% of cases. Fine-needle aspiration cytology (FNAC) showed that follicular lesion of undetermined significance (42.8%) was most common, followed by benign nodule (21.3%). Using the Bethesda System for Reporting Thyroid Cytopathology, 7 cases were category III, 3 category IV, 3 category II, and 1 category I. 60% of patients underwent total thyroidectomy. All cases were diagnosed postoperatively, 2 patients had additional papillary microcarcinoma. In 3 cases, the NIFTP site in the histopathology of resected specimen was different than the US-recommended site of the FNAC.ConclusionWe found discrepancies in the site and diagnosis of the preoperative US recommendation for the FNAC vs the postoperative histopathology of the specimen. These suggest that NIFTP might be incidentally and postoperatively diagnosed, irrespective of US or FNAC findings, hence its ‘true’ incidence might remain underestimated. As NIFTP cases higher BMI, Future research could predict preoperative diagnosis of NIFTP and explore associations with BMI.

Trends in Diagnosis of Noninvasive Follicular Thyroid Neoplasm With Papillarylike Nuclear Features and Total Thyroidectomies for Patients With Papillary Thyroid Neoplasms

Increasing detection of early-stage papillary thyroid neoplasms without improvements in mortality has prompted development of strategies to prevent or mitigate overtreatment. To determine adoption rates of 2 recent strategies developed to limit overtreatment of low-risk thyroid cancers: (1) a new classification, noninvasive follicular thyroid neoplasm with papillarylike nuclear features (NIFTP), and (2) hemithyroidectomy for selected papillary thyroid carcinomas (PTCs) up to 4 cm in size. This is a cross-sectional analysis of 3368 pathology records of 2 cohorts of patients from 18 hospitals in 6 countries during 2 time periods (2015 and 2019). Participating hospitals were included from the US (n = 12), Canada (n = 2), Denmark (n = 1), South Korea (n = 1), South Africa (n = 1), and India (n = 1). The records of the first 100 patients per institution for each year who underwent thyroid-directed surgery (hemithyroidectomy, total thyroidectomy, or completion thyroidectomy) were reviewed. Frequency of diagnosis of NIFTP, PTCs, and thyroidectomies during the study period. Of the 790 papillary thyroid neoplasms captured in the 2019 cohort, 38 (4.8%) were diagnosed as NIFTP. Diagnosis of NIFTP was observed in the US, South Africa, and India. There was minimal difference in the total proportion of PTCs in the 2015 cohort compared with the 2019 cohort (778 [47.1%] vs 752 [44.5%]; difference, 2.6% [95% CI, -16.9% to 22.1%]). The proportion of PTCs eligible for hemithyroidectomy but treated with total thyroidectomy in the 2 cohorts demonstrated a decreasing trend from 2015 to 2019 (341 of 453 [75.3%] vs 253 of 434 [58.3%]; difference, 17.0% [95% CI, -1.2% to 35.2%]). Results of this cohort study showed that the 2 mitigation strategies for preventing overtreatment of early-stage thyroid cancer have had mixed success. The diagnosis of NIFTP has only been applied to a small proportion of thyroid neoplasms compared with expected rates. However, more patients eligible for hemithyroidectomy received it in 2019 compared with 2015, showing some success with this deescalation strategy.

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.