Proteomics profile in encapsulated follicular patterned thyroid neoplasms.

Diagnosing encapsulated follicular-patterned thyroid tumors like Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma (IEFVPTC), Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP), and Well-Differentiated Tumor of Uncertain Malignant Potential (WDT-UMP) remains challenging due to their morphological and molecular similarities. This study aimed to investigate the protein distinctions among these three thyroid tumors and discover biological tumorigenesis through proteomic analysis. We employed total shotgun proteome analysis allowing to discover the quantitative expression of over 1398 proteins from 12 normal thyroid tissues, 13 IEFVPTC, 11 NIFTP, and 10 WDT-UMP. Principal component analysis revealed a distinct separation of IEFVPTC and normal tissue samples, distinguishing them from the low-risk tumor group (NIFTP and WDT-UMP). IEFVPTC exhibited the highest number of differentially expressed proteins (DEPs) compared to the other tumors. No discriminatory proteins between NIFTP and WDT-UMP were identified. Moreover, DEPs in IEFVPTC were significantly associated with thyroid tumor progression pathways. Certain hub genes linked to the response of immune checkpoint inhibitor therapy, revealing the potential predictor of prognosis. In conclusion, the proteomic profile of IEFVPTC differs from that of low-risk tumors. These findings may provide valuable insights into tumor biology and offer a basis for developing novel therapeutic strategies for follicular-patterned thyroid neoplasms.

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

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

Differentiating BRAF V600E- and RAS-like alterations in encapsulated follicular patterned tumors through histologic features: a validation study.

Differentiating BRAF V600E- and RAS-altered encapsulated follicular-patterned thyroid tumors based on morphology remains challenging. This study aimed to validate an 8-score scale nuclear scoring system and investigate the importance of nuclear pseudoinclusions (NPIs) in aiding this differentiation. A cohort of 44 encapsulated follicular-patterned tumors with varying degrees of nuclear atypia and confirmed BRAF V600E or RAS alterations was studied. Nuclear parameters (area, diameter, and optical density) were analyzed using a deep learning model. Twelve pathologists from eight Asian countries visually assessed 22 cases after excluding the cases with any papillae. Eight nuclear features were applied, yielding a semi-quantitative score from 0 to 24. A threshold score of 14 was used to distinguish between RAS- and BRAF V600E-altered tumors. BRAF V600E-altered tumors typically demonstrated higher nuclear scores and notable morphometric alterations. Specifically, the nuclear area and diameter were significantly larger, and nuclear optical density was much lower compared to RAS-altered tumors. Observer accuracy varied, with two pathologists correctly identifying genotype of all cases. Observers were categorized into proficiency groups, with the highest group maintaining consistent accuracy across both evaluation methods. The lower group showed a significant improvement in accuracy upon utilizing the 8-score scale nuclear scoring system, with notably increased sensitivity and negative predictive value in BRAF V600E tumor detection. BRAF V600E-altered tumors had higher median total nuclear scores. Detailed reevaluation revealed NPIs in all BRAF V600E-altered cases, but in only 2 of 14 RAS-altered cases. These results could significantly assist pathologists, particularly those not specializing in thyroid pathology, in making a more accurate diagnosis.

Diagnostic performances of the Afirma Gene Sequencing Classifier in comparison with the Gene Expression Classifier: A meta-analysis.

The Afirma microarray-based Gene Expression Classifier (GEC) with its high negative predictive value (NPV) and sensitivity has been used to rule out cancer from thyroid nodules with an indeterminate cytology but not to rule in cancer because of its low positive predictive value (PPV) and specificity. The Gene Sequencing Classifier (GSC) has been reported to improve on the weakness of GEC. In this study, a meta-analysis was performed to compare the clinical impact and diagnostic performance of GEC and GSC. Relevant data were searched in PubMed and Web of Science. Meta-analyses for proportion and dichotomous outcomes were performed to compare the benign call rates (BCRs), resection rates (RRs), risks of malignancy (ROMs), sensitivities, specificities, PPVs, and NPVs of GSC and GEC. Seven studies were included for the meta-analyses. Compared with GEC, GSC had a higher BCR (65.3% vs 43.8%; P < .001), a lower RR (26.8% vs 50.1%; P < .001), and a higher ROM (60.1% vs 37.6%; P < .001). The BCR of Hürthle cell-predominant nodules was significantly elevated (73.7% vs 21.4%; P < .001). In addition, the specificity (43.0% vs 25.1%; P = .003) and PPV (63.1% vs 41.6%; P = .004) of Afirma GSC were significantly improved while it still maintained a high sensitivity (94.3%) and a high NPV (90.0%). In conclusion, this study confirms and highlighted the clinical and diagnostic significance of GSC. With an increased BCR and improved diagnostic performance, GSC could reduce the rate of unnecessary surgical interventions and better tailor the clinical decisions of patients with indeterminate thyroid fine-needle aspiration results.

Risk factors for tumor recurrence and progression of spindle cell oncocytoma of the pituitary gland: a systematic review and pooled analysis.

INTRODUCTION: Spindle cell oncocytoma (SCO) is an extremely rare sellar neoplasm. No observational studies have been reported so far to investigate the prognostic factors of this tumor entity. This systematic review aimed to elucidate the risk factors for tumor recurrence/progression of SCO. METHODS: We searched for relevant articles in PubMed and Web of Science. Studies providing individual patient data with follow-up information of SCO cases were included. Pearson's Chi square and Fisher's exact test were used for categorical variables while t test or Mann-Whitney tests were applied for continuous variables, if applicable. We used the Cox regression model to assess the effects of suspected variables on progression-free survival (PFS). RESULTS: A total of 38 case reports and case series comprising of 67 SCOs were included for final analyses. Recurrent/progressive tumors were noted in 38.8% of cases. Among the clinicopathological factors, only the extent of surgery was a significant risk factor for tumor recurrence/progression. SCO patients with a subtotal resection had a significantly higher risk for tumor relapse in comparison with complete removal (HR 7.51; 95% CI 1.75-32.31; p = 0.007). CONCLUSION: Our study demonstrated the characteristic clinicopathological features of SCOs with a high recurrence/progression rate and outlined the predictor for tumor relapse. Failure to achieve gross total resection is the only risk factor for tumor recurrence/progression.

Impact of Molecular Testing on the Management of Indeterminate Thyroid Nodules Among Western and Asian Countries: a Systematic Review and Meta-analysis.

Molecular testing has a potential to improve the management of patients with indeterminate thyroid nodules considered for surgery. This study examined the influence of molecular tests on the treatment of indeterminate nodules, particularly the differences between Western and Asian countries. Electronic databases including PubMed and Web of Science were searched for relevant articles from 2010 to March 2019. We computed meta-analysis of proportion and their 95% confidence intervals (CIs) utilizing the random-effect model. We used independent samples t test to compare the resection rate (RR), rate of malignancy (ROM), rate of preoperative molecular testing (RMT), and rate of positive test (RP) between subgroups. We included a total of 34 studies with 7976 indeterminate nodules. The multigene panel testing methods were exclusively used in the USA. Compared with the non-molecular era, molecular testing was associated with a significantly increased ROM (47.9% versus 32.1%; p = 0.001). The ROM of indeterminate nodules in Asian institutes was significantly higher than that in Western countries (75.3% versus 36.6%; p < 0.001, respectively). Institutes employing single-gene tests achieved a higher ROM (59.8% versus 37.9%; p = 0.013). Molecular testing is a promising method to tailor the clinical management for indeterminate thyroid FNA. Certain differences in routine thyroid cytopathology practice among the West and the East are still present. The combination of molecular testing and active surveillance enhances the accuracy of case selection for surgery in Asian countries.

The diversities in thyroid cytopathology practices among Asian countries using the Bethesda system for reporting thyroid cytopathology.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been adopted and widely used among Asian countries. This study aims to investigate the application of TBSRTC in thyroid cytology practice among Asian countries. METHODS: We searched electronic databases including PubMed and Web of Science from 2010 to 2019. Meta-analysis of proportion and their 95% confidence intervals (CIs) were calculated using the random-effect model. Meta-regression and subgroup analysis were used to search for heterogeneity origins. RESULTS: We included 42 Asian studies with 84.953 fine-needle aspirations. Among six categories, benign was the most commonly diagnosed category. The resection rate (RR) and risk of malignancy (ROM) were highest in malignant and SM categories, and lowest among benign nodules. Thyroid cytology practice in Asia was characterized by a low RR and high ROM in patients with indeterminate thyroid nodules. There was a significant amount of heterogeneities of TBSRTC outputs (frequency, resection rate, and malignancy risk) among Asian countries. Meta-regression showed that the sources of heterogeneity might stem from the differences in study origin and the application of molecular testing. We highlighted the usefulness of preoperative molecular testing to select patients for surgery. CONCLUSIONS: Our study provided insight regarding thyroid cytology practice among Asian countries. Active surveillance is commonly used in Asian practice resulting in a low RR and high ROM for indeterminate nodules. There are still variations in general thyroid cytology practice in Asia. Future guidelines and consensus regarding the application of TBSRTC in thyroid cytology practice among Asian countries are required.