Noninvasive Follicular Neoplasm Research Articles

Study of non-invasive follicular thyroid neoplasm: A borderline entity

ABSTRACT Background: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a newly added entity in the fourth edition of the WHO Classification of Tumors of Endocrine Organs (2017). It is regarded as a neoplasm with very low malignant potential, thus affecting further treatment of the patients. Aims: To study the recently diagnosed entity, NIFTP, as not many cases have been reported of the same. Materials and Methods: A retrospective analysis of all thyroid neoplasms received in the Department of Pathology of our institute over two years was done. Out of the 188 cases that we reported, 38 were of non-invasive follicular neoplasms. Results: Thirty-two patients were female, whereas six patients were male. Thirty-five patients presented with solitary thyroid nodule and the others had an ill-defined thyroid swelling. Thirty-four patients had normal thyroid profile while two patients each presented with hypothyroidism and hyperthyroidism. Conclusion: It is crucial to carefully study the histopathological features of solitary thyroid swellings and correlate with clinical and radiological findings. The recently added diagnostic category of NIFTP helps clinicians prevent over-treatment of a group of low-risk thyroid tumors.

EphB3 protein is a potential ancillary diagnostic biomarker for thyroid cancers

ObjectiveTo investigate the expression of ephrin type B receptor 3 (EphB3) in thyroid tumors and its usage as an ancillary diagnostic biomarker for thyroid tumors. MethodsFormalin-fixed and paraffin-embedded (FFPE) tissue samples (78 cases) and FNAC samples (57 cases) were assessed with the EphB3 antibody using immunohistochemistry. PTC and other thyroid follicular tumors were compared regarding their EphB3 expression. Sanger sequencing was used to assess for the presence of a BRAF V600E mutation. ResultsEphB3 was positive in 81.8 % (27/33) of papillary thyroid carcinoma (PTC), 83.3 % (5/6) of medullary thyroid carcinoma (MTC), 25 % (1/4) of hyperplastic/adenomatoid nodule (HN), 14.3 % (1/7) of follicular adenoma (FA), and negative in follicular tumors of uncertain malignant potential (FT-UMP) (0/13), noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) (0/7), thyroid follicular carcinoma (TFC) (0/4), Hashimoto's thyroiditis (0/4), and normal thyroid follicular tissues (0/33). In cellular blocks, EphB3 was positive in 87.1 % (20/23) of PTC, 75 % (3/4) of MTC, 20 % (2/10) of HN, and negative in atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (0/20) and normal thyroid follicular cells (0/10). ConclusionEphB3 is expressed in the majority of PTC, but less so in benign follicular nodules. EphB3 expression in fine needle aspiration cytology (FNAC) specimens can be used as a diagnostic tool to differentiate thyroid cancer from other follicular lesions in its differential diagnosis, especially AUS/FLUS and PTC.

The Incidence Trend and Management of Thyroid Cancer-What Has Changed in the Past Years: Own Experience and Literature Review.

Because of ambiguous and widely debated observations concerning the incidence, trend, and management of TC, we performed this analysis. We drew attention to some events, such as "cancer screening activity", introduction of noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) to TC types, possibility of papillary thyroid microcarcinoma (PTMC) active surveillance (AS), occurrence of personalized medicine in TC management, and, finally, COVID-19 pandemic time. Because of the opinion that all changes have been made mostly by PTC, we compared it to the remaining types of TC in terms of incidence, clinical and pathological characteristics, and treatment. We analyzed patients treated in a single surgical center in eastern Europe (Poland). The prevalence of TC significantly increased from 5.15% in 2008 to 13.84% in 2015, and then significantly decreased to 1.33% in 2022 when the COVID-19 pandemic lasted (p < 0.0001). A similar trend was observed for PTC, when the incidence significantly increased to 13.99% in 2015 and then decreased to 1.38% in 2022 (p < 0.0001). At that time, the NIFTP category was introduced, and observation of PTMC began. The prevalence of FTC and MTC also increased until 2015 and then decreased. Significant differences in age, types of surgery, necessity of reoperation, and pTNM between PTCs and other types of TCs were observed. The average age was significantly lower in PTC patients than in patients with the remaining types of TC (p < 0.0001). Four milestones, including NIFTP introduction, the possibility of PTMC AS, personalized cancer medicine, and the COVID-19 pandemic, may have influenced the general statistics of TC.

THU678 Real-world Performance Of Afirma Genomic Sequencing Classifier (GSC) In A Community Healthcare Setting

Abstract Disclosure: V. Master: None. J. Syeda: None. S. Charatz: None. D. Reidy: None. K. Clary: None. Introduction: Indeterminate thyroid nodules pose a significant clinical challenge due to their potential risk of malignancy. The Afirma GSC has emerged as a valuable tool for the non-invasive management of these nodules. However, its real-world performance in community healthcare settings remains poorly understood. Aim: Comparison of GSC performance in a community healthcare setting to the validation study (VS) metrics. Method: A retrospective study was conducted in a community endocrine practice, where 91 Afirma GSC samples were obtained from patients who had either suspicious cytology or atypia of undermined significance (AUS) between 1/1/2021 and 12/31/2022. Ten samples were excluded due to insufficient material. Surgical pathology was used as the gold standard for diagnosis. Molecular benign results without surgical pathology were considered true negatives, and 2 unoperated patients with suspicious results were excluded from analysis. We calculated observed positive predictive value (oPPV) and observed specificity (oSP) to account for these exclusions. Non-invasive follicular neoplasm with papillary-like features is considered malignant. The prevalence of thyroid cancer in the study population was 19%. Results are compared to previously published VS of 191 samples. Result: Our study showed a higher accuracy of 89% of the Afirma GSC in our community healthcare setting, with a sensitivity (SN) of 93%, oSP of 88%, oPPV of 63%, and negative predictive value (NPV) of 98%. In comparison, the VS had a SN of 91%, SP of 68%, PPV of 47%, NPV of 96%, and accuracy of 74%. Additionally, our study showed a higher benign call rate (BCR) of 70% compared to 54% in the VS. Conclusion: Our study provides evidence of the real-world performance of the Afirma GSC and supports its use as a non-invasive tool for the management of indeterminate thyroid nodules. Better oSP and oPPV are suggestive of higher yield of cancers for resected nodules based on suspicious GSC.

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.

Down-regulation of miR-7-5p and miR-548ar-5p predicts malignancy in indeterminate thyroid nodules negative for BRAF and RAS mutations

PurposeThe value of molecular markers in refining preoperative risk assessment of indeterminate thyroid nodules is being widely investigated. MicroRNAs (miRNA) are emerging as promising biomarkers for diagnostic and prognostic purposes. The aim of this study is to identify miRNAs specifically deregulated in mutation-negative indeterminate thyroid nodules.MethodsNinety-eight nodules preoperatively diagnosed as TIR 3A or TIR 3B with available histological diagnosis of follicular adenoma (FA), noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP), and follicular variant papillary thyroid carcinoma (FV-PTC) have been retrospectively selected. Mutations in BRAF and RAS genes have been tested in all samples by real-time PCR; miRNAs were purified from cytology slides of 60 samples; expression analysis of 798 miRNAs was measured by the nCounter system.ResultsPoint mutations in BRAF and RAS genes were detected in 32 out of 98 nodules (32.7%), the majority of which in FV-PTCs. Differential expression of miRNA in wild-type nodules highlighted that two miRNAs, namely miR-7-5p and miR-548ar-5p, were downregulated in FV-PTCs compared to FAs. The combined expression of these miRNAs, tested by ROC analysis, showed an area under the curve of 0.79. Sensitivity and negative predictive value were high both in wild-type (93% and 92%, respectively) and in mutated nodules (94% and 85%, respectively).ConclusionThe analysis of miR-7-5p and miR-548ar-5p expression in indeterminate thyroid nodules demonstrated a promising value in ruling out malignancy.

Anxiety During the COVID-19 Pandemic: A Web-Based Survey of Thyroid Cancer Survivors

ObjectiveCancer patients and survivors may be disproportionately affected by COVID-19. We sought to determine the effects of the pandemic on thyroid cancer survivors’ health care interactions and quality of life. MethodsAn anonymous survey including questions about COVID-19 and the Patient-Reported Outcomes Measurement Information System profile (PROMIS-29, version 2.0) was hosted on the Thyroid Cancer Survivors’ Association, Inc website. PROMIS scores were compared to previously published data. Factors associated with greater anxiety were evaluated with univariable and multivariable logistic regression. ResultsFrom May 6, 2020, to October 8, 2020, 413 participants consented to take the survey; 378 (92%) met the inclusion criteria: diagnosed with thyroid cancer or noninvasive follicular neoplasm with papillary-like nuclear features, located within the United States, and completed all sections of the survey. The mean age was 53 years, 89% were women, and 74% had papillary thyroid cancer. Most respondents agreed/strongly agreed (83%) that their lives were very different during the COVID-19 pandemic, as were their interactions with doctors (79%). A minority (43%) were satisfied with the information from their doctor regarding COVID-19 changes. Compared to pre-COVID-19, PROMIS scores were higher for anxiety (57.8 vs 56.5; P < .05) and lower for the ability to participate in social activities (46.2 vs 48.1; P < .01), fatigue (55.8 vs 57.9; P < .01), and sleep disturbance (54.7 vs 56.1; P < .01). After adjusting for confounders, higher anxiety was associated with younger age (P < .01) and change in treatment plan (P = .04). ConclusionDuring the COVID-19 pandemic, thyroid cancer survivors reported increased anxiety compared to a pre-COVID cohort. To deliver comprehensive care, providers must better understand patient concerns and improve communication about potential changes to treatment plans.

Challenge in the Pathological Diagnosis of the Follicular- Patterned Thyroid Lesions.

Background:The follicular-patterned thyroid lesions (FPTLs) include hyperplastic nodules (HN), follicular adenoma (FA), non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP), follicular carcinoma (FC), and the follicular variant of papillary carcinoma (FVPTC). Sometimes the pathologists cannot accurately separate these lesions from each others on a histological basis. Aims: To evaluate the utility of immunohistochemistry in the diagnosis of FPTLs. Materials and methods:Immunohistochemical analysis, incorporating 83 cases of histologically confirmed FPTLs out of which 20 carcinomas, 51 benign FPTLs (38 HN and 13 FA), and 12NIFTP were separated from each others using four immunostains (HBME-1, CK19, Galectin-3, and CD56). Results: We found statistically significantly more frequent expression of HBME-1, CK19, Galectin-3 proteins in carcinomas as compared to benign FPTLs (p = <0.01). HBME-1 and Galectin-3 were the most sensitive markers for the diagnosis of malignant FPTLs (75%). Galectin-3 was the most specific marker for the diagnosis of carcinoma (90.3%). Conclusions:The histomorphological features remain the cornerstone of the diagnosis of FPTN. Although HBME-1, Galectin-3, and CK19 immunostains have some diagnostic value in the separation of malignant from benign FPTLs, they are variably expressed in the benign and malignant FPTLs. No single immunostain has sufficient sensitivity and specificity and therefore their diagnostic use is controversial. Future studies are mandated to find more reliable markers that can separate between benign and malignant FPTLs.

Total thyroidectomy can still remain the method of choice in some Bethesda III cases.

The latest WHO classification of tumours of endocrine organs defines new units of borderline thyroid tumours (BTT). The aim of our study was to evaluate ultrasonographic and cytological features, mutation profile and surgery treatment in rare thyroid tumours. An analysis of 8 BTT out of 487 patients, who underwent thyroid surgery between June 2016 and June 2020. The definitive diagnosis was made postoperatively by extensive histopathological examination. Molecular genetic analysis of genes associated with thyroid oncology (BRAF, HRAS, KRAS, NRAS, TERT, TP53, fused genes) were performed from one FNAB, and 7 formalin-fixed paraffin-embedded (FFPE) samples. BTT were found in a total of 8 patients (1.6%), with a predominance of men with respect to other operated patients. FNAB samples were classified in the Bethesda system as Bethesda I, Bethesda II and Bethesda III in one, four and three cases, respectively. Hemithyroidectomy and total thyroidectomy were performed equally in four patients. The histopathological diagnosis revealed non-invasive encapsulated follicular neoplasm with papillary-like nuclear features (NIFTP) in three patients, follicular tumour of uncertain malignant potential (FT-UMP) in three patients, well differentiated tumour of uncertain malignant potential (WDT-UMP) in one patient, and hyalinizing trabecular tumour (HTT) in one case. In NIFTP cases mutation in HRAS gene in one patient together with probable pathogenic variant in TP53 gene and in NRAS gene in two patients were detected. In HTT patient PAX8/GLIS3 fusion gene was detected. The surgical treatment of BTT is necessarily individual influenced by preoperative clinical, ultrasonographic, cytological and molecular genetic findings, and the presence of other comorbidities.

Molecular testing and thyroid nodule management in North America.

The incidence of thyroid cancer is rising for a variety of reasons. At the same time, the nomenclature revision of non-invasive encapsulated follicular-variant PTC to noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) has modified the incidence of thyroid cancer. Given that thyroid neoplasia is a molecular event, it is important for the thyroid physician to evaluate each patient systematically. Most thyroid cancers are sporadic; however, some are familial and may be associated with syndromes with genetic implications. Advances in radiologic imaging have made ultrasonography a near equivalent of gross examination. The American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) classifies nodules from TR1 to TR5 and is valuable in determining which patients should be guided toward fine-needle aspiration (FNA) sampling. While FNA procedures and processing may be varied, the key elements are cytologic diagnosis and collection of samples for potential molecular testing. The Bethesda System for Reporting Thyroid Cytology (BSRTC) is commonly used and categorizes each FNA specimen into one of six diagnoses. The indeterminate diagnoses with risk of malignancy (ROM) ranging from 10-75% comprise approximately 30% of thyroid FNA cases and for these, molecular testing is beneficial. In North America, the two most common molecular platforms are Veracyte Afirma GSC and ThyroSeq v3. Both panels cover an extensive array of genomic alterations associated with thyroid neoplasia and a negative result from either test effectively refines the ROM of an Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS) or Follicular Neoplasm/Suspicious for a Follicular Neoplasm (FN/SFN) diagnosis to 3-4%. Given that the refined ROMs are comparable to that of a Benign BSRTC diagnosis, these patients are recommended for observation of their nodules. However, differences exist in the implication of Afirma GSC-Suspicious and ThyroSeq v3-Positive molecular results with regard to the probability of cancer. For either test, the molecular test result should be integrated with other clinical parameters to determine if surgery is indicated and, if so, the extent of surgery.

Indeterminate thyroid nodules in the era of molecular genomics.

BackgroundIndeterminate thyroid nodules are diagnosed in up to 30% of fine‐needle aspirations and the risk of malignancy in these cases are highly variable. Consequently, managing these nodules has been a challenge. While a diagnostic thyroidectomy would help clarify the pathology, there is the risk of developing surgical‐related complications for a procedure that may not have been necessary and associated high costs. Genomic testing of indeterminate thyroid nodules may help better guide management.MethodsWe present an unbiased comprehensive review of available molecular testing for classifying indeterminate thyroid nodules, as well as their strengths and limitations, with the objective to allow practitioners to choose the best testing modality for their patients.ResultsMolecular testing of these nodules provided a platform to help distinguish benign versus malignant nodules, providing more confidence to rule in or rule out the likelihood of thyroid cancer in indeterminate nodules.ConclusionGenomic testing has evolved to more comprehensive panels to better stratify indeterminate nodules, including Hürthle cell neoplasms and noninvasive follicular neoplasm with papillary‐like nuclear features. Understanding the methodology of each available test improves patient care and reduces unnecessary costs.

Noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP): a 13-year retrospective review at Jordan University Hospital.

Noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) is the term to describe what was previously known as encapsulated follicular variant of papillary thyroid carcinoma. This new paradigm shift was agreed upon by experts in the field. The objective of this study is to evaluate cases previously diagnosed as follicular adenomas, follicular variant of papillary thyroid carcinoma and hyperplastic nodules to be reclassified as NIFTP according to the new criteria. Furthermore, the clinical follow-up of these NIFTP cases is evaluated. This retrospective study reviewed potential NIFTP cases over the last 13 years, at Jordan University Hospital. A total of 811 thyroid surgery reports were identified and revised to identify the potential NIFTP cases. The review yielded 173 cases identified as potential NIFTP cases. Further pathological slide review resulted in a revised diagnosis of 32 cases of NIFTP according to the new criteria. The NIFTP cases comprised 4% of the total number of thyroidectomy cases and 16.1% of the total pool of previously diagnosed papillary thyroid carcinoma cases at our institution. While 111 cases retained their original diagnosis. Follow-up showed that all patients are alive and well with no evidence of disease. Patients with NIFTP are not uncommon and the diagnosis is made only after a thorough evaluation of excision. Therefore, initial conservative management of solitary thyroid nodules suspicious for NIFTP in the form of lobectomy is recommended to avoid unnecessary total thyroidectomies. Our follow-up of NIFTP cases is similar to all previous reports.

Noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP): a new entity.

Since its first official definition in 2016, the new histo-pathological entity of noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) has attracted much interest among "thyroidologists" worldwide. This is a subset of encapsulated and noninvasive follicular variant papillary thyroid cancer, whose introduction had the intent of de-escalating treatment given its very low malignant potential, approaching to that of follicular adenomas. Many researchers focused on the possibility of preoperatively identifying NIFTP, and investigated their cyto-morphological and molecular characteristics; other ones explored histological and clinical-pathological NIFTP features. Although the majority of published studies confirmed that NIFTP are indolent lesions, some papers did question their low-risk nature. In this brief review, the main aspects of histology, cytology and molecular pathology of NIFTP are discussed based on the current literature.

Thyroid follicular cell tumors: cytohistological comparisons in the context of the new international classification

To carry out a correlation retrospective analysis of the histological and cytological findings of follicular cell neoplasms over a two-year period after the publication of the new WHO classification of thyroid tumors (2017), which identifies a category of follicular tumors of uncertain malignant potential (T-UMP). The investigators of the Clinic, National Medical Research Center for Endocrinology, Ministry of Health of Russia, made a cytohistological comparison of morphological findings, by using the material of surgically removed follicular cell neoplasms. The investigation showed the lack of unreasonably common usage of the histological classification category of T-UMP (3.08%). Non-invasive follicular neoplasm with papillary-like nuclei predominantly diagnosed in the T-UMP category was more frequently (83.3) assigned to Diagnostic Category IV of the 2017 Bethesda system for the cytological diagnosis of thyroid tumors. Cytology showed the highest (98.1%) sensitivity, including classic (97.8%), encapsulated (100%), and follicular (97.7%) options in diagnosing papillary cancer, being substantially inferior in diagnosing follicular and Hürthle cell neoplasms, in which diagnostic category IV category was more frequently established for adenomas (81.4%) and carcinomas (69.5%). The morphological differential diagnosis of follicular cell neoplasms seems to be a relevant problem.

Noninvasive follicular neoplasm with papillary like nuclear features: A comprehensive analysis with a diagnostic algorithm.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) lacks the carcinoma label, avoiding aggressive therapy, physiological, social and financial impact of cancer diagnosis. Unfortunately, the preoperative diagnosis is still a challenge. Varied incidence of NIFTP has been document with limited data on preoperative cytological, radiological characteristics and the impact on risk of malignancy in each category of the Bethesda system of reporting thyroid cytopathology. Retrospective analysis of 20 NIFTPs with an attempt to provide a preoperative diagnostic algorithm based on the cytological and ultrasound features along with incidence and implication on risk of malignancy in various Bethesda categories with its impact on patient management. Incidence of NIFTP in our study was higher in comparison to that documented from other Asian countries. TIRADS 3 was the most common sonographic diagnosis. NIFTP was commonly preceded by indeterminate or benign Bethesda category. Major impact of excluding NIFTP form malignant category was seen on Bethesda categories II and IV with 20% and 27% reduction in risk of malignancy, respectively. Retrospective analysis should not be confined only to follicular variant of papillary thyroid carcinoma but cases of follicular adenoma and adenomatous colloid nodule should always be included in review to ascertain the true incidence of NIFTP. NIFTPs are less likely to have malignant preoperative cytology. NIFTP shares major cytological and ultrasound features with follicular adenoma, adenomatous colloid nodule and minimally invasive follicular papillary carcinoma. When analyzed together, taking minor findings in consideration, can favor a diagnosis.

Digital Gene Expression Analysis on Cytology Smears Can Rule Out Malignancy in Follicular-Patterned Thyroid Tumors

Patients with indeterminate thyroid nodules (Bethesda III and IV) are often treated with diagnostic lobectomy, which in most cases represents an overtreatment. A reliable rule-out molecular test could spare patients unnecessary surgery. Stained smears of 88 indeterminate thyroid nodules with histologic diagnosis of follicular-patterned tumors were selected: 34 follicular adenomas (FAs), 34 follicular variant papillary thyroid carcinomas (FVPTCs), and 20 noninvasive follicular neoplasms with papillary-like nuclear features (NIFTPs). The expression level of 126 genes was measured by digital counting. Mutation testing was performed for the main gene mutations and fusions. Performance of gene expression and mutation tests was calculated by receiver operating characteristic analysis. The gene expression model showed an area under the curve (AUC) of 88%, with 91% negative predictive value in FAs and FVPTCs only. Part of NIFTPs was labeled as benign, and part was labeled as malignant; thus, the classifier performance worsened. Two FAs (5.9%), eight NIFTPs (40%), and 22 FVPTCs (64.7%) were mutation positive. Mutation testing AUC was 79% in FAs and FVPTCs, and decreased by including NIFTPs. This gene expression-based test was feasible in thyroid-stained smears, showed higher AUC than mutation test, and had a high negative predictive value-making it a good candidate as a rule-out test for indeterminate thyroid cytology. NIFTPs have a heterogeneous phenotype, and their preoperative diagnosis requires further investigation.

Non-invasive follicular thyroid neoplasm with papillary-like nuclearfeatures (NIFTP): a review and update.

The nomenclature "Non-invasive Follicular Neoplasm with Papillary-like Nuclear Features (NIFTP)" was introduced in 2016. While NIFTP differs from classic papillary thyroid carcinoma (PTC) in imaging, cytomorphology, histology, molecular profile, treatment, follow up, outcome, and behavior, it largely overlaps with follicular variant of PTC at imaging and cytomorphology. Herein, we review the literature for better understanding NIFTP, and its impact on patient care. The English literature was thoroughly evaluated with the key word of "Noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP)". NIFTP presents as a thyroid nodule. On imaging, it is a round-to-oval, well circumscribed mass with solid internal content. Aspirated material shows a microfollicular pattern with focal nuclear features of PTC mostly reported in categories 3-5 of the Bethesda System for Reporting Thyroid Cytology (TBRSTC). NIFTP has decreased risk of malignancy in TBRSTC categories 3-6. Histologic examination of NIFTP reveals an encapsulated neoplasm with follicular pattern and nuclear features of PTC with no capsular or vascular invasion. No papillary structure, atypia, or mitosis is present. In contrast to PTC, only 4% of NIFTP cases harbor a BRAF mutation. Because NIFTP carries an excellent prognosis and indolent behavior, the tumor behavior was changed from malignant to a neoplasm with tumor with extremely indolent behavior. The recommended treatment is lobectomy with no further ablation therapy. Until better understanding of NIFTP, patient's follow up should be occasionally performed by neck ultrasonography and serum thyroglobulin measurement. NIFTP carries an excellent prognosis. It is critical for both clinicians and patients to be aware of extremely indolent behavior of NIFTP in order to prevent unnecessary, aggressive treatment.

Histo-cyto correlation of NIFTP – a local experience

Background: Non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP) has a comparatively indolent course. Suspecting this entity on cytology helps prevent overtreatment. We perform histo-cytologic correlation of NIFTP cases over an 18 year period in a tertiary medical institution.

Outcome and molecular characteristics of non-invasive encapsulated follicular variant of papillary thyroid carcinoma with oncocytic features.

In 2016, non-invasive encapsulated follicular variant of papillary thyroid carcinoma (NI-EFVPTC) was renamed as noninvasive thyroid follicular neoplasm with papillary-like nuclear features (NIFTP). However, as the study cohort did not mention tumors with oncocytic features, such lesions are still labeled by some as FVPTC. It is therefore crucial to evaluate the outcome and molecular profile of oncocytic NI-EFVPTC. A multi-institutional clinico-pathologic review was conducted to select 61 patients having oncocytic NI-EFVPTC. A detailed molecular profile was carried out in 15 patients. Oncocytic NI-EFVPTCs predominantly affected women in their 50s. There was no distant metastasis, lymph node metastases, or structural recurrence in the entire cohort. Among patients with ≥5 years of FU, all 33 individuals did not recur with a median FU of 10.2 years. Oncocytic NI-EFVPTC commonly had RAS (33%) mutations, a high frequency of mitochondrial DNA mutations (67%) and multiple chromosomal gains/losses (53%). No fusion genes were detected. Oncocytic NI-EFVPTC, when stringently selected for, lacks metastasis at presentation and follows an extremely indolent clinical course, even when treated conservatively with lobectomy alone without RAI therapy. These tumors share a similar mutational profile as NIFTP, FVPTC, and follicular neoplasm and are predominantly RAS-related. Like Hurthle cell neoplasms, they harbor a high frequency of mitochondrial DNA mutations, which contribute to the oncocytic cytomorphology. However, they lack the widespread chromosomal alterations observed in Hurthle cell carcinoma. Consideration should be given to include oncocytic NI-EFVPTCs as NIFTP in order to avoid overtreatment of these highly indolent tumors.

Cytomorphologic Features of Non-Invasive Follicular Neoplasm with Papillary-like Nuclear Features

Cytomorphologic Features of Non-Invasive Follicular Neoplasm with Papillary-like Nuclear Features