Papillary-like Nuclear Features Research Articles

The expression of VISTA on CD4+ T cells associate with poor prognosis and immune status in non-small cell lung cancer patients.

V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a novel negative immune checkpoint considered to be relevant to immunotherapy resistance and a potential target for immunotherapy. In this study, we investigated the relevance of VISTA expression on CD4+ T cells and clinical prognosis in non-small cell lung cancer (NSCLC) patients. Tumor tissue samples from 140 NSCLC patients were organized into a tissue microarray. The prognostic value of CD4+ VISTA+ T cells was analyzed through immunohistochemistry and multicolor fluorescence immunostaining. Fresh tumor tissue samples from 33 NSCLC patients were collected and similarly analyzed to confirm the immune state of patients with VISTA expression on CD4+ T cells by flow cytometry. CD4+ VISTA+ T cells were significantly more infiltrated in tumor tissues. The expression of VISTA on CD4+ T cells was correlated with the reduced overall survival of patients with NSCLC and presented a high rate of lymphocyte metastasis. The expression of VISTA on CD4+ T cells in tumor tissue showed low secretion of cytokines including IFN-γ, IL-2, IL-4, IL-10, IL-17, and IL-12p70. The expression of VISTA on CD4+ T cells could regulate tumor immunity and serve as a prognostic indicator for survival outcomes.

TROP-2 and 5hmC expression in follicular-patterned thyroid neoplasm emphasizing tiny well-formed papillae

BackgroundFollicular-patterned thyroid neoplasms (FPTNs), characterized by predominantly follicular growth pattern, represent diverse pathological entities. We aimed to study the nuclear features and the immunoexpression of trophoblast cell-surface antigen 2 (TROP-2) and 5-hydroxymethylcytosine (5hmC) in FPTNs. DesignFPTNs were divided into 4 groups: I) noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), II) encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) with capsular invasion, III) infiltrative FVPTC, and IV) PTC with a predominantly follicular pattern and well-formed papillae (<1%). Nuclear characteristics were evaluated by image analysis. TROP-2 and 5hmC immunostains were analyzed correlating with histological features using QuPath. ResultsFrom the group I to II, III, and IV, there is a gradual increase in nuclear atypia in terms of the nuclear area, max caliper, perimeter, circularity, and hematoxylin OD means (corresponding to nuclear enlargement, membrane irregularity, and clearing). A similar trend is observed in the TROP-2 expression. 5hmC expression is highly preserved in groups I, II, and III in contrast to a significant loss in group IV. Group IV tumors show more frequent regional lymph node involvement and the highest BRAF V600E mutation rate. ConclusionAmong FPTNs, group IV tumors exhibit the most advanced nuclear atypia, highest TROP-2 expression, significant 5HMC expression loss, frequent regional lymph node involvement, and the highest BRAF V600E mutation rate. Our data further support that the presence of any true papillae should be an exclusion criterion for NIFTP. Therefore, well-formed papillae even if very minute (<1% of the tumor) should not be overlooked.

Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Tumour Entity with a Short History. A Review on Challenges in Our Microscopes, Molecular and Ultrasonographic Profile.

Since Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) was introduced as a new thyroid tumour entity, many studies, and meta-analyses on diagnosing NIFTP have been published. NIFTP-revised histopathological criteria emerged in 2018. NIFTP is defined as a histological entity and its diagnosis requires a careful histological examination. Its molecular profile is similar to follicular-like tumours. Ultrasound features are unable to differentiate NIFTP. NIFTP is not a cytological diagnosis, but it influences the risk of malignancy in several categories of The Bethesda System for Reporting Thyroid Cytopathology terminology.

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

Simple SummaryNon-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are follicular thyroid neoplasm with an indolent clinical behaviour. In this study, we evaluated a retrospective series of 451 NIFTPs, of which 197 (43.7%) presented in coexistence with collateral thyroid tumours. Unifocal and multifocal NIFTPs did not show peculiar ultrasound, cytological, molecular, and histo-pathological characteristics. Considering the high rate of coexisting carcinomas, NIFTP patients might benefit from monitoring of the contralateral lobe.Background: Non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were introduced in thyroid pathology in 2016. NIFTPs are a group of follicular neoplasm with an indolent behaviour. In this study, we gathered a large retrospective cohort of NIFTPs and compared those presenting as solitary lesions and NIFTPs found in multifocal setting. Methods: A retrospective search of NIFTPs was performed, and the clinico-pathological features were recorded. For a subgroup of patients, pre-surgical ultrasound (US) evaluation, cytological diagnosis, and molecular analysis were available. Results: We collected 451 NIFTPs; 254 (56.3%) were truly solitary tumours, while 197 coexisted with one or more NIFTP/cancer. Contrasting unifocal and multifocal settings, NIFTPs size was the only significantly different parameter. Preoperatively, NIFTP nodules mostly showed low-risk US characteristics, indeterminate cytology and a RAS-like molecular profile. Conclusion: NIFTPs often coexist with collateral thyroid tumours. However, no clinical-pathological differences can be observed between solitary and “multifocal” NIFTPs. Despite the well-established clinical indolence of NIFTP, a careful monitoring of the contralateral lobe should not be excluded.

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.

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.

Clinical and Sonographic Features of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: A Retrospective Study.

This study was designed to investigate the clinical and sonographic features of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) as compared with classical papillary thyroid carcinoma (cPTC), follicular adenoma (FA), and follicular thyroid carcinoma (FTC). A total of 178 patients were enrolled in this study. The clinical characteristics and sonographic features of thyroid nodules were compared between NIFTP and cPTC or FA/FTC. All nodules were reclassified according to the Thyroid Ultrasound Imaging Reporting and Data System and American Thyroid Association guidelines classification. The mean size of NIFTP was 29.91 ± 14.71 mm, which was larger than that of cPTC ( P = 0.000). Significant difference was found in lymph node metastases between NIFTP and cPTC ( P = 0.000). Most NIFTPs showed solid composition, hypoechoic echogenicity, smooth margin, wider than tall shape, none echogenic foci, absence of halo, and perinodular vascularity, which were similar with FA and FTC. Compared with NIFTP, hypoechoic and very hypoechoic, taller than wide, irregular margin, punctate echogenic foci, absence of halo, and low vascularity were more commonly observed in cPTC. There were statistical differences both in American College of Radiology Thyroid Ultrasound Imaging Reporting and Data System and in American Thyroid Association classification between NIFTP and cPTC ( P < 0.05), but there were no significant differences between NIFTP and FTC/FA ( P > 0.05). The ultrasonographic characteristics of NIFTP were obviously different from cPTC but overlapped with FTC and FA. Ultrasound could help increase preoperative attention of NIFTP in an appropriate clinical setting, which may lead to a more conservative treatment approach.

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.

Clinical outcomes of follicular tumor of uncertain malignant potential of the thyroid: real-world data.

Thyroid tumors arising from follicular cells can generally be divided into malignant and benign tumors. However, some cases are difficult to clearly diagnose whether they are benign or malignant. Therefore, in the most recent version of World Health Organization (WHO) classification, some borderline lesions such as follicular tumor of uncertain malignant potential (FT-UMP), well-differentiated tumor of uncertain malignant potential (WDT-UMP), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were proposed. In this study, we investigated the clinical aspects, including the prognosis, of FT-UMP patients. We investigated the clinical features of 339 patients with FT-UMP. On ultrasound, 68% of the tumors were diagnosed as intermediate, and only 5% of those tumors were diagnosed as malignant. On cytology, 40% of the tumors were diagnosed as follicular neoplasm, and only 1% of these were suspected to be or diagnosed as malignancy. The diagnosis was based on questionable capsular invasion for 332 patients, questionable vascular invasion for 2 patients, and both for 5 patients. Eighty-six percent of the tumors showed low cell proliferation activity. To date, five patients (1%) have shown distant recurrence during postoperative follow-up and underwent various treatments such as radioactive iodine therapy, orthopedic surgery, and denosumab injection. None of these patients have died due to thyroid carcinoma. Our findings suggest that FT-UMP is generally an indolent disease, but some patients show distant recurrence. Physicians should carefully follow patients, although it remains unknown how long they should be observed after surgery.

Differential diagnosis of follicular thyroid lesions and management of non-invasive follicular thyroid neoplasms with papillary-like nuclear features

Differential diagnosis of follicular thyroid lesions and management of non-invasive follicular thyroid neoplasms with papillary-like nuclear features

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

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

Lésions thyroïdiennes folliculaires encapsulées, classifications histologique et pTNM, examen extemporané et évaluation histopathologique

AbstractEncapsulated follicular-patterned thyroid tumors remain the daily challenge for pathologists, including experts. The differential diagnosis typically includes hyperplastic/adenomatous nodule, follicular adenoma, follicular carcinoma, follicular variant of papillary thyroid carcinoma (FVPTC), and non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The latter is a new terminology that was integrated into the WHO 2017 classification of endocrine tumors to replace the majority of non-invasive encapsulated FVPTC. Capsular and/or vascular invasion remains the main sign of malignancy. This invasion is, in the majority of cases, microscopic and necessitating an examination of the entire capsule. And for this reason, the frozen section is most often useless. The risk of recurrence and mortality correlates more with the importance of vascular invasion than with the size of the tumor and the management of these lesions must be discussed on a case-by-case basis and should not depend solely on the pTNM stage.

Do ACR TI-RADS scores demonstrate unique thyroid molecular profiles?

PurposeThe present study aimed to examine the molecular profiles of cytologically indeterminate thyroid nodules stratified by American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) categories and to determine whether certain ultrasonographic features display particular molecular alterations.MethodsA retrospective review was conducted of cases from January 1, 2016 to April 1, 2018. Cases with in-house ultrasonography, fine-needle aspiration Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnoses, molecular testing, and surgery were included. All cases were diagnosed as TBSRTC indeterminate categories. The ultrasound studies were retrospectively reviewed and assigned TI-RADS scores (TR1-TR5) by board-certified radiologists. The final diagnoses were determined based on the surgical resection pathology. Binary logistic regression analysis was used to study whether demographic characteristics, TI-RADS levels, and TBSRTC diagnoses were associated with ThyroSeq molecular results.ResultsEighty-one cases met the inclusion criteria. RAS mutations were the most common alteration across all TI-RADS categories (TR2 2/2; TR3 10/19, TR4 13/44, and TR5 8/16), and did not stratify with any particular TI-RADS category. Only TR4 and TR5 categories displayed more aggressive mutations such as BRAFV600E; and TERT. ThyroSeq results were positively correlated with thyroid malignancy when non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was categorized in the malignant category (odds ratio [OR], 6.859; P<0.01), but not when NIFTP was removed from the malignancy category. Echogenicity scores were found to be negatively correlated with ThyroSeq results in thyroid nodules (OR, 0.162; P<0.01).ConclusionHigher-risk molecular alterations tended to stratify with the higher TI-RADS categories.

Diagnostic significance of CyclinD1 and D2-40 expression for follicular neoplasm of the thyroid

ObjectivesTo evaluate the expression and differential diagnostic significance of CyclinD1 and D2–40 in follicular neoplasm (FN) and other thyroid adenomatoid lesions. MethodsA total of 144 cases of thyroid adenomatoid lesions were enrolled. Immunohistochemistry for CyclinD1 and D2–40 was performed. ResultsWe found two patterns of CyclinD1 expression: nuclear (N) and cytoplasmic (C). The expression of N-CyclinD1 / C-CyclinD1 in FN (77.4%, 48/62; 50.0%, 31/62) was much higher than that in multinodular goiters with dominant nodules (MNG-DN) (16.4%, 10/61; 4.9%, 3/61) (p < 0.05). In contrast, the expression of D2–40 in MNG-DN (82.0%,50/61) was much higher than that in FN (4.8%, 3/62) (p < 0.05). In addition, unique staining patterns were observed: CyclinD1 showed no immunostaining only in all 8 cases of oncocytic cell tumors (OCT); D2–40 staining showed the characteristic wide distribution of lymphatic vessels in all 8 cases of poorly differentiated thyroid carcinoma (PDTC). Finally, the expression of CyclinD1 and D2–40 did not differ among follicular thyroid adenoma and follicular thyroid carcinoma / noninvasive follicular thyroid neoplasm with papillary-like nuclear features (p > 0.05). ConclusionsCyclinD1 and D2–40 are helpful diagnostic markers of FN, which can assist to discern FN from MNG-DN / OCT / PDTC.

Three-dimensional telomere profiles in papillary thyroid cancer variants: A pilot study.

Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.

AACE2021-A-1098: Clinical and Pathological Characteristics of Thyroid Cancer in Adolescents and Young Adults (AYA): An Algerian Observation

We aim to describe clinical and pathological characteristics of thyroid cancer in an Algerian cohort of adolescents and adults patients. Medical records of patients followed in the endocrinology department of Constantine University Hospital during the period between July 2014 and December 2018 were retrospectively reviewed. Patients were subdivided into two age groups: < 30 (Group 1) and ≥ 40 years old (Group 2). Thyroid function, type of initial surgery, lymph node dissection, and histological findings were collected. 101 patients were included, the mean age was 31 (17- 40 years), 30.17% were aged <30 years and 85.1% were females. Diagnosis circumstances were multinodular goiter and unique thyroid nodule in 57.4% ,27.7% respectively and 12% had abnormal TSH at the moment of diagnosis. As the initial surgery, total thyroidectomy was done in 88.1% and lymph node dissection in 23.8% which was central in 13.9%, and central and lateral in 9.9%. 90.1% were papillary thyroid cancer, 7.9% (8 patients) were follicular carcinoma and 2 patients had Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Following the 8th AJCC classification,64% were T1, 12.9% T2, and 20.8% were T3 . Microcarcinoma represented 39.6% of cases, and 15.8% had lymph node involvement, while 1 patient had distance metastasis. Multifocality, bilaterality, vascular invasion, and capsular thyroid invasion were seen in 30.7%,15.8%,7.9%, and 17.8% respectively. As for risk stratification according to the American thyroid association (ATA) system, the initial risk was low, intermediate, and high in 41.6%,35.6%, and 10.9% respectively and data were insufficient for risk stratification in 11.9% of patients. 99% were stage I TNM and RAI therapy was done in 88.1% of patients. In analysis AYA patients aged >30 had more capsular invasion and lymph node involvement (p<0.05), and AYA patients with follicular thyroid carcinoma had more thyroid capsular invasion (p<0.05). These data give us a profile of AYA patients in the Algerian population. In our study, patients with follicular carcinoma had more capsular invasion and patients aged< 30 years had more capsular invasion and lymph node involvement.

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.

Thyroglobulin Levels in Patients who have Undergone Hemithyroidectomy for Differentiated Thyroid Cancer. An Assessment of Levels and Trends at a Tertiary Referral Centre.

Subramanian Kannan Serum thyroglobulin (Tg) and thyroglobulin antibody (TgAb) levels are used to monitor patients with differentiated thyroid cancer (DTC) after total thyroidectomy with or without radioiodine (RAI) ablation. However, they are also measured in patients who are treated with thyroid lobectomy (TL)/hemithyroidectomy (HT). Data on the levels of Tg and its trend in those undergoing TL/HT is sparse in India. We reviewed retrospective data of DTC patients who underwent TL/HT and were followed-up with postoperative Tg levels between 2015 and 2020. Out of 247 patients, 17 had undergone either TL or HT, which included papillary thyroid cancer ( n = 12), follicular thyroid cancer ( n = 4), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 1 patient. All patients with DTC had tumor size < 4 cm (T1/2, clinical N0, Mx). The median follow-up was 15 months (range, 1–125) and the median Tg level was 7.5 ng/mL (interquartile range [IQR]; 3.6, 7.5) and ranged from 0.9 to 36.7 ng/mL. The median thyroid-stimulating hormone (TSH) level was 2.03 IU/L (IQR; 1.21, 3.59) and it ranged from 0.05 to 8.54 IU/L. As of last follow-up, none of them underwent completion thyroidectomy; however, eight patients had a decline in Tg ranging from 8 to 64%, four patients had increase in Tg ranging from 14 to 145%, three patients had stable Tg, and one of them had an increase in TgAb titers. As per American Thyroid Association (ATA) response-to-treatment category, six patients had indeterminate response, five patients had biochemical incomplete response, four patients had excellent response, and two did not have follow-up Tg and TgAb levels. While absolute values of Tg were well below 30 ng/mL in almost all patients with HT/TL, the Tg trends were difficult to predict, and only 23% of patients were able to satisfy the criteria for “excellent response” on follow-up. We suggest keeping this factor in mind in follow-up and while counselling for HT in patients with low-risk DTC.

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.