Papillary-like Nuclear Features Research Articles

Characteristics of PTEN Mutation in Thyroid Tumours: A Retrospective Chart Review

While some studies suggest that PTEN mutations correlate with a low-risk phenotype in pediatric thyroid nodules, the relationship between the mutation and malignancy in the adult populations is abstruse. This study investigated whether PTEN mutations result in thyroid malignancy, and whether these malignancies are aggressive. This multicenter study involved 316 patients who underwent preoperative molecular testing, and subsequent lobectomy or total thyroidectomy at two quaternary care hospitals. A four-year retrospective review was performed on the 16 charts of patients that opted for surgery following a positive PTEN mutation on molecular testing results from January 2018 to December 2021. Of the total 16 patients, 37.5% (n = 6) had malignant tumours, 18.75% (n = 3) had non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), and 43.75% (n = 7) had benign disease. Aggressive features were detected in 33.33% of the malignant tumours. Malignant tumours were found to have a statistically significant higher allele frequency (AF). The aggressive nodules were all poorly differentiated thyroid carcinomas (PDTCs) with copy number alterations (CNAs) and the highest AFs.

Transoral Thyroidectomy: Initial Results of the European TOETVA Study Group

BackgroundThe aim of this study was to evaluate a new surgical technique by the European Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) Study Group.MethodsThis study included 391 patients (47 [(12%]) male and 344 [(88%)] female) who had undergone endoscopic thyroid or parathyroid surgery via the vestibular approach between February 2016 and May 2022 at nine centers. The data were analyzed with regard to complications, surgery time and specimen retrieval.ResultsOverall, 376 (96.2%) TOETVA and 15 (3.8%) transoral endoscopic parathyroidectomy vestibular approach interventions were performed with an average surgery time of 145 (± 61.2) minutes and 509 nerves at risk. The specimens were retrieved via a transoral vestibular and retroauricular approach in 66 (16.9%) patients and via a transaxillary approach in 8 (2%). Benign histology including Grave’s disease was identified in 272 (69.6%) patients, 1 (0.3%) presented noninvasive follicular thyroid neoplasms with papillary-like nuclear features, and 103 (26.3%) showed differentiated thyroid carcinoma. Solitary parathyroid adenoma were removed in 15 (3.8%) patients. Conversion to open surgery was necessary in 13 (3.3%) and revision had to be performed in 2 (0.5%) patients. Transient recurrent laryngeal nerve palsy (RLNP) was present in 18 (4.6%) and permanent RLNP in 2 (0.5%) patients. Fifteen (3.8%) patients experienced transient hypoparathyroidism after thyroidectomy. No case of permanent hypoparathyroidism was observed. Postoperative surgical site infection occurred in 1 (0.3%) patient. Despite a higher rate of sensory and motor disorders and skin discoloration at discharge, permanent disorders were present in only 3 (0.8%) and 16 (4.1%) patients, respectively.ConclusionOur results show that transoral endoscopic surgery, performed by experienced endocrine surgeons, is a safe alternative to conventional thyroid surgery.

Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: Implications for molecular testing and surveillance.

Evidence guiding the management of cytologically indeterminate thyroid nodules with nondiagnostic (ND) or benign cytology on repeat fine-needle aspiration (FNA) is limited. This study evaluates the utility of molecular testing and estimates the risk of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and cancer among such nodules. This was a retrospective single-institution review of thyroid nodules from adults that were classified as atypia of undetermined significance (AUS) or follicular neoplasm (FN) on initial FNA and underwent repeat FNA for cytology and Afirma testing (June 2013-July 2021). The association between repeat FNA cytology and RNA yield for Afirma was determined. Histologic outcomes were integrated with Afirma results to define end points for each nodule. A total of 691 AUS and FN nodules underwent repeat FNA and Afirma testing. Diagnostic Afirma results were obtained in 98% of cases overall and in 91% of nodules with ND cytology on repeat FNA. Using combined molecular and histologic end points, the NIFTP and/or cancer prevalence for nodules with ND cytology on repeat FNA was 9% (95% confidence interval [CI], 0.042-0.182), falling between those nodules classified as benign (5%; 95% CI, 0.029-0.094) and those classified as AUS or FN (18%; 95% CI, 0.140-0.218) on repeat FNA, although not reaching statistical significance from either subgroup (p=.38 and .10, respectively). AUS and FN nodules that are ND on repeat FNA have low but nonnegligible risk of NIFTP and/or cancer and may benefit from molecular testing, given the low test failure rate in this subgroup. Conversely, AUS and FN nodules reclassified as benign on repeat FNA have a very low risk of NIFTP and/or cancer and are unlikely to benefit from molecular testing.

MicroRNA expression profiling of RAS-mutant thyroid tumors with follicular architecture: microRNA signatures to discriminate benign from malignant lesions

PurposeRAS mutations represent common driver alterations in thyroid cancer. They can be found in benign, low-risk and malignant thyroid tumors with follicular architecture, which are often diagnosed as indeterminate nodules on preoperative cytology. Therefore, the detection of RAS mutations in preoperative setting has a suboptimal predictive value for malignancy. In this study, we investigated differentially expressed microRNA (miRNA) in benign and malignant thyroid tumors with follicular architecture carrying mutations in RAS genes.MethodsTotal RNA was purified from 60 RAS-mutant follicular-patterned thyroid tumors, including follicular adenoma (FA), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), papillary and follicular thyroid carcinoma cases (PTC, FTC); 22 RAS-negative FAs were used as controls. The expression analysis of 798 miRNAs was performed by digital counting (nCounter nanoString platform).ResultsComparing RAS-mutant and RAS-negative FAs, 12 miRNAs showed significant deregulation, which was likely related to the oncogenic effects of RAS mutations. Twenty-two miRNAs were differentially expressed in RAS-mutant benign versus malignant tumors. Considering the tumor type, 24 miRNAs were deregulated in PTC, 19 in NIFTP, and seven in FTC and compared to FA group; among these, miR-146b-5p, miR-144-3p, and miR-451a showed consistent deregulation in all the comparisons with the highest fold change.ConclusionsThe miRNA expression analysis of follicular-patterned thyroid tumors demonstrated that RAS mutations influences miRNA profile in benign tumors. In addition, several miRNAs showed a histotype-specific deregulation and could discriminate between RAS-mutant benign and RAS-mutant malignant thyroid lesions, thus deserving further investigation as potential diagnostic markers.

Spatially Resolved Molecular Approaches for the Characterisation of Non-Invasive Follicular Tumours with Papillary-like Features (NIFTPs).

Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are low-risk thyroid lesions most often characterised by RAS-type mutations. The histological diagnosis may be challenging, and even immunohistochemistry and molecular approaches have not yet provided conclusive solutions. This study characterises a set of NIFTPs by Matrix-Assisted Laser Desorption/Ionisation (MALDI)-Mass Spectrometry Imaging (MSI) to highlight the proteomic signatures capable of overcoming histological challenges. Archived formalin-fixed paraffin-embedded samples from 10 NIFTPs (n = 6 RAS-mutated and n = 4 RAS-wild type) were trypsin-digested and analysed by MALDI-MSI, comparing their profiles to normal tissue and synchronous benign nodules. This allowed the definition of a four-peptide signature able to distinguish RAS-mutant from wild-type cases, the latter showing proteomic similarities to hyperplastic nodules. Moreover, among the differentially expressed signals, Peptidylprolyl Isomerase A (PPIA, 1505.8 m/z), which has already demonstrated a role in the development of cancer, was found overexpressed in NIFTP RAS-mutated nodules compared to wild-type lesions. These results underlined that high-throughput proteomic approaches may add a further level of biological comprehension for NIFTPs. In the future, thanks to the powerful single-cell detail achieved by new instruments, the complementary NGS-MALDI imaging sequence might be the correct methodological approach to confirm that the current NIFTP definition encompasses heterogeneous lesions that must be further characterised.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear feature: clinical, pathological, and molecular update 5 years after the nomenclature revision.

The term non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was proposed in 2016 and incorporated as a new entity in the World Health Organization (WHO) classification of tumours of endocrine organs in 2017. Since then, there has been debate regarding the histological criteria for the diagnosis, the need for molecular studies or the risk of lymph node metastasis or recurrence associated with this entity. Over the years, the concept of NIFTP evolved, now including both small (<1 cm) and large (>4 cm) tumours and oncocytic lesions. On the other hand, recent data on NIFTP in the setting of thyroid follicular nodular disease or frequent coexistence of malignant tumours raised concerns regarding the follow-up of these patients. Today, both pathologists and clinicians still face several challenges in the diagnosis, treatment, and follow-up of patients with NIFTP.

Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: What a Surgeon Should Know.

The inclusion of the less aggressive follicular form of papillary thyroid cancer (PTC) is associated with an increase in the incidence of the condition, with the follicular variant of PTC being the most common of all variants. The majority of individuals with the encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) are treated as though they have classic thyroid cancer, despite the availability of mounting evidence to contradict the aforementioned. According to numerous research, a certain type of noninvasive-EFVPTC (NI-EFVPTC) demonstrated poor histopathologic diagnostic reproducibility and has received aggressive treatment similar to that of a classical thyroid neoplasm. Therefore, to replace the term NI-EFVPC, a new nomenclature for these tumors, called "noninvasive follicular thyroid neoplasm with papillary-like nuclear characteristics" (NIFTP), was introduced in the year 2016. The present paper explores this recently introduced terminology, clinical, histologic, and molecular features, and diagnostic criteria.

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.

Behavior of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) During Initial Follow up

Behavior of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) During Initial Follow up

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Pitfalls of Cytological and Histopathologic Diagnosis

Classical papillary thyroid carcinoma (PTC) is the commonest primary thyroid neoplasm. Besides PTC, significant histological variants that differ from classical PTC in regard to the morphological, cytologic and histologic features are mentioned; among them is follicular variant papillary thyroid carcinoma (FVPTC). The update WHO classification and the update Bethesda system reclassified FVPTC introduced a new entity which is "non-invasive follicular thyroid neoplasm with papillary like nuclear features" (NIFTP) that is characterized by an indolent behavior with encapsulated noninvasive growth features. Recently this entity is considering one of an indeterminate cytological categories (category III-IV-V). Update studies are found a combination of triple diagnostic procedures included sonographical, cytologic and molecular investigations can be suspecting preoperative diagnosis. Methods: A total of 150 selected cases of solitary thyroid nodules (STNs) with preoperative FNAC have an indeterminate follicular patterned cytological lesions with their underlying thyroidectomies that were collected in a 5-year period included in this article. Results: Majority of our cases were females and suffering from neck swelling. Cytollogically all the enrolled cases were lying in the indeterminate categories and histologically they were encapsulated with variable sizes follicles, nuclear features, no vascular invasion, no psammoma bodies, no tumor necrosis or mitosis. Also, there is no any extra-thyroid invasion. Conclusion: The accurate diagnosis of this entity “”NIFTP” carries many congratulations in regard that is “not malignant” category among both update TBSRTC and the final histopathological examination of the excised thyroid tissue.

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.

Interpretation of low-risk neoplasms in the 5th edition of WHO classification of thyroid tumors

The fifth edition of World Health Organization (WHO) classification of thyroid tumors replaced the "borderline tumors" in the fourth edition with "low-risk tumors", including noninvasive follicular thyroid neoplasms with papillary-like nuclear features, uncertain malignant potential and hyalinizing trabecular tumors. All of them are thyroid tumors with follicular epithelial cell origin, capsule/clear boundary, no lymph node and distant metastasis (EX0, N0, M0). The spread probability of "low-risk tumor" is extremely low, and this new classification can protect the pathologists from medical litigation when encountering rare and special metastatic cases. Based on the interpretation of the thyroid tumor classification, this paper further discussed several low-risk tumors, which were not listed in the current WHO classification.

Coexisting Molecular Alterations Increase the Risk of Malignancy in Thyroid Nodules with Copy Number Alterations.

Molecular mutations and alterations play a role in thyroid tumorigenesis. Different alterations are associated with different clinical and pathological characteristics. Copy number alterations (CNAs) are known to be present in some thyroid tumors; however, their idiosyncratic clinicopathological implications are not yet well elucidated. A retrospective chart review was performed to identify patients with CNAs on pre-operative molecular testing results who subsequently underwent surgical treatment between January 2016 and April 2022 at McGill University teaching hospitals. Of the 316 patients with thyroid nodules who opted for molecular testing with ThyroSeqV3 followed by surgery, 67 (21.2%) nodules were positive for CNAs, including 23 Bethesda III, 31 Bethesda IV, 12 Bethesda V and 1 Bethesda VI nodules. On surgical pathology, 29.9% were benign and 70.1% were malignant or non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Among those that were malignant/NIFTP, 17.02% were considered to be aggressive cancers. The presence of other molecular alterations was found to be an independent predictor of malignancy in multivariate analysis (OR = 5.087, 95% C.I. = 1.12-23.04, p = 0.035). No unique factor was correlated with aggressiveness; however, CNA-positive thyroid nodules that were associated with high-risk mutations such as BRAF V600E, TP53, NTRK1/3 fusion, or PTEN mutation with high allele frequency (AF) ended up being aggressive cancers. Most of the CNA-positive thyroid nodules resulted in follicular patterned tumors in 41 (65.2%) cases and oncocytic tumors in 20 (29.9%) cases. This study demonstrates that 70.1% of surgically resected thyroid nodules with CNAs were malignant/NIFTP. Most CNA-positive thyroid nodules were either oncocytic patterned tumors or follicular patterned tumors. Furthermore, CNA-positive thyroid nodules were more likely to be malignant if they were associated with other molecular alterations or mutations.

Prognostic Indicators of EIF1AX-Mutated Thyroid Tumor Malignancy and Cancer Aggressiveness.

The risk of malignancy (ROM) of EIF1AX-mutated thyroid nodules has been theorized to be contingent on the position of the mutation within the gene and the presence of co-existing mutations. However, due to EIF1AX's low mutation frequency, sample sizes currently reported in the literature are too diminutive to appraise the clinical utility of molecular diagnostic testing. The objective of this study was to elucidate prognostic indicators of EIF1AX-mutated thyroid tumors and cancer aggressiveness by examining a large cohort of cytologically indeterminate thyroid nodules (CITNs) that underwent molecular testing and subsequent surgical resection. This is a multicenter study involving 764 subtotal and total thyroidectomy patients that underwent preoperative molecular testing at two quaternary care hospitals. A five-year retrospective review was performed on the 42 charts of patients that opted for surgery following a positive EIF1AX mutation on ThyroseqV3 results from January 2018 to May 2022. Patient demographics, cytopathology results, molecular testing results, and postoperative histopathology were reviewed. Of the 42 surgically resected nodules that harbored an EIF1AX mutation, 16 (38.1%) were benign, six (14.3%) were non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) or well-differentiated thyroid neoplasms of uncertain malignant potential (WDT-UMPs), and 20 (47.6%) were malignant. An isolated EIF1AX mutation conferred a ROM of 47.6%, whereas the ROM for nodules with at least one additional molecular alteration was 72.7%. The ROM increased to 100% for nodules with at least one additional molecular alteration and the A113_splice site mutation. Six malignant nodules were aggressive, with five having variegated components of poorly differentiated thyroid carcinoma (PDTC). EIF1AX-mutated thyroid nodules are more susceptible to malignancy in the presence of the A113_splice site mutation and when co-mutated with RAS and/or TP53. This deleterious amalgam is associated with aggressive disease and renders these nodules PDTC. A preoperative molecular test finding of an EIF1AX mutation can be a useful tool for thyroid specialists to optimize clinical management.

Real-World Performance of the Afirma Genomic Sequencing Classifier (GSC)-A Meta-analysis.

The Afirma® GSC aids in risk stratifying indeterminate thyroid nodule cytology (ITN). The 2018 GSC validation study (VS) reported a sensitivity (SN) of 91%, specificity (SP) of 68%, positive predictive value (PPV) of 47%, and negative predictive value (NPV) of 96%. Since then, 13 independent real-world (RW) postvalidation studies have been published. This study's objective is to compare the RW GSC performance to the VS metrics. Rules and assumptions applying to this analysis include: (1) At least 1 patient with molecular benign results must have surgery for that study to be included in SN, SP, and NPV analyses. (2) Molecular benign results without surgical histology are considered true negatives (TN) (as are molecular benign results with benign surgical histology). (3) Unoperated patients with suspicious results are either excluded from analysis (observed PPV [oPPV] and observed SP [oSP]) or assumed histology negatives (false positives; conservative PPV [cPPV] and conservative SP [cSP]) 4. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features is considered malignant. In RW studies, the GSC demonstrates a SN, oSP, oPPV, and NPV of 97%, 88%, 65%, 99% respectively, and conservative RW performance showed cSP of 80% and cPPV of 49%, all significantly higher than the VS except for SN and cPPV. There was also a higher benign call rate (BCR) of 67% in RW studies compared to 54% in the VS (P < 0.05). RW data for the Afirma GSC demonstrates significantly better oSP and oPPV performance than the VS, indicating an increased yield of cancers for resected GSC suspicious nodules. The higher BCR likely increases the overall rate of clinical observation in lieu of surgery.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy

Due to the extremely indolent behavior, a subset of noninvasive encapsulated follicular variant papillary thyroid carcinomas has been classified as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)" since 2016 and is no longer considered carcinoma. Since the introduction of this new terminology, changes and refinements have been made in diagnostic criteria. Initially, the incidence of NIFTP was estimated substantial. However, the reported incidence of NIFTP varies greatly among studies and regions, with higher incidence in North American and European countries than in Asian countries. Thus, the changes in the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) differ inevitably among regions. Because more conservative surgery is recommended for NIFTPs, distinguishing NIFTPs from papillary thyroid carcinomas in preoperative fine-needle aspiration cytology became one of the major concerns. This review will provide comprehensive overview of updates on diagnostic criteria, actual incidence and preoperative cytologic diagnoses of NIFTP, and its impact on the ROM in TBSRTC.

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.

The clinical significance of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) category 5 thyroid nodules: Not as risky as we think?

BackgroundAlthough the prevalence of thyroid nodules is high, few prove to be malignant. Based on sonographic features, the American College of Radiology Thyroid Imaging Reporting and Data System categorizes malignancy risk of thyroid nodules with associated management recommendations for each category level. Malignancy rates among nodules with a highly suspicious Thyroid Imaging Reporting and Data System category 5 warrant examination in the context of additional risk stratification tools, including cytopathology and molecular testing. MethodsAll patients who underwent fine-needle aspiration biopsy for Thyroid Imaging Reporting and Data System category 5 nodules from January 2018 to September 2021 in a large integrated academic health system were reviewed. Using the Bethesda System for Reporting Thyroid Cytopathology, categories V and VI were set as malignant. Molecular testing (ThyroSeq version 3; Rye Brook, NY) yielding ≥50% risk of malignancy was deemed positive and correlated with surgical pathology. ResultsA total of 496 Thyroid Imaging Reporting and Data System category 5 nodules were identified. On fine-needle aspiration cytopathology, 61 (12.3%) were malignant. The breakdown included Bethesda System for Reporting Thyroid Cytopathology I, 15 (3%); II, 362 (73%); III, 52 (10.5%); IV, 5 (1%); V, 6 (1.3%); and VI, 55 (11.1%). Of Bethesda System for Reporting Thyroid Cytopathology III/IV nodules with molecular testing (n = 53), 24.5% yielded positive results. In total, 42 (8.5%) nodules underwent surgical resection, most of which were Bethesda System for Reporting Thyroid Cytopathology VI (n = 26, 61.9%). Of excised nodules, 33 (78.6%) nodules were malignant, 6 (14.3%) benign, and 3 (7.1%) noninvasive follicular thyroid neoplasm with papillary-like nuclear features. All Thyroid Imaging Reporting and Data System category 5 nodules with malignant cytology (Bethesda System for Reporting Thyroid Cytopathology V/VI) that underwent surgery were malignant on histopathology. On average, the total Thyroid Imaging Reporting and Data System points were higher in malignant nodules compared with benign (9.3 vs 7.3; P = .015). Moreover, benign nodules more frequently received Thyroid Imaging Reporting and Data System points when the radiologist was unable to determine composition or echogenicity (33% vs 3% among malignant nodules; P = .01). ConclusionThyroid Imaging Reporting and Data System category 5 designation in thyroid nodules is associated with a lower risk of malignancy than previously reported. Benign and malignant nodules with Thyroid Imaging Reporting and Data System category 5 designation have discrepancies in certain Thyroid Imaging Reporting and Data System characteristics and individual points assigned, which may offer an opportunity for quality improvement and standardization measures in ultrasound reporting practices.

A Matched-Pair Analysis of Nuclear Morphologic Features Between Core Needle Biopsy and Surgical Specimen in Thyroid Tumors Using a Deep Learning Model.

Core needle biopsy (CNB) is a method that can be used as an alternative to fine-needle aspiration for the sampling of thyroid nodules to provide a preoperative diagnosis. Nuclear atypia is of paramount importance in diagnosing thyroid tumors. We aimed to identify the differences in nuclear morphologic features between CNB and surgical specimens. Quantitative image analysis was performed on whole slide images (WSI) of paired CNB and surgical specimens from 50 follicular cell-derived tumors including adenoma, non-invasive follicular thyroid neoplasm with papillary-like nuclear features, and carcinoma. The nuclear features of tumor cells were extracted from WSI using a pre-trained deep-learning model. In matched-pair analysis, the ratios (surgical specimens-to-CNB) of the mean nuclear diameters and the areas of the tumor cells were 1:0.75-0.85 and 1:0.54-0.73 according to the tumor types, respectively. The ratio of the nuclear optical density of tumor cells was 1.68-2.44 times higher in CNB specimens than it was in their corresponding surgical specimens. The significant nuclear size reduction and optical density increase in CNB were most prominent in papillary carcinoma cells. Normal follicular cells showed nuclear size reduction in CNB but no change in nuclear optical density between CNB and surgical specimens. Nuclear vacuolar artifacts mimicking nuclear pseudoinclusions were frequently seen in CNB regardless of the tumor types. In conclusion, tumor cells in CNB showed marked nuclear shrinkage, darker nuclear staining, and nuclear vacuolar changes. Awareness of the morphological differences according to the sampling types can facilitate correct diagnosis in thyroid histopathology.

The Significance of RAS-Like Mutations and MicroRNA Profiling in Predicting Malignancy in Thyroid Biopsy Specimens.

In cytologically indeterminate thyroid nodules undergoing molecular testing, estimated risk of malignancy is variable. Identification of a non-cancer-specific mutation (RAS-like) confirms a neoplastic process but does not differentiate between benign, malignant, and low-risk neoplasms. This study aims to retrospectively evaluate institutional experience of Interpace (ThyGeNEXT® and ThyraMIR®; Pittsburgh, PA) testing and to determine the rate of malignancy in resected nodules, stratified by mutational analysis and microRNA profile. Of 1917 fine need aspirations, 140 (7.3%) underwent Interpace testing: 47 (33.6%) were molecular-not-benign (harbored mutation, fusion, and/or positive miRNA) and 93 (66.4%) were molecular-benign (no mutations or fusions and negative microRNA). Surgery was spared in 79.6% of molecular-benign and 61.4% of all tested patients. Fifty-four (38.6%) underwent resection. Seventeen (89.5%) of the resected molecular-benign were benign and 2 were malignant. Thirteen (37.1%) of the resected molecular-not-benign were benign, 7 (20%) were noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and 15 (42.9%) were malignant (p < 0.05, negative predictive value (NPV) 89.4-95.6%, positive predictive value (PPV) 22.3-42.8%). Most molecular-not-benign (72.3%) had RAS-like mutation. Twenty-three were resected: 3 were malignant and 7 were NIFTP. Nodules with non-RAS-like mutations (BRAF V600E-like, others) were more likely to be malignant than RAS-like (H/N/KRAS, BRAF K601E) (p < 0.05, NPV 86.9-96.5%, PPV 100%). Most nodules had RAS-like mutations and most were benign or low-risk neoplasms (NIFTP). This study supports the role of histologic examination in the distinction of malignancy in RAS-like thyroid neoplasms and underscores the role of molecular testing in risk stratification, patient counseling, and operative management.