Diagnostic implication of thyroid spherules for cytological diagnosis of thyroid nodules.

OBJECTIVE: Thyroid fine-needle aspiration (FNA) is a principal diagnostic procedure for thyroid nodules. A specific cytomorphological structure, known as the thyroid spherule, is often seen in FNA specimens. The clinical significance of these spherules in terms of diagnosis and prevalence remains largely unexplored. METHODS: We performed a retrospective study on 310 thyroid FNA specimens and categorized them according to the Bethesda System for Reporting Thyroid Cytopathology. The presence, size and number of thyroid spherules in each specimen were examined and these data were subsequently correlated with the clinicopathological features. RESULTS: Thyroid spherules were almost exclusively detected in benign cases, comprising 7.6% of all benign diagnoses. The average diameter of spherules in benign cases was 84.9 µm. Benign cases and cases with atypia of undetermined significance cases primarily exhibited low cellularity, while follicular neoplasms and malignant cases typically showed moderate to high cellularity. In the subgroup of FNA cases with moderate to high cellularity, spherules were identified in 12 (20%) of 59 benign FNA cases. Within this group, the sensitivity and specificity of thyroid spherules for detecting benign FNA cases were 20% and 100%, respectively. CONCLUSIONS: Our results suggest that the presence of thyroid spherules in FNA specimens can serve as a highly specific marker for benign thyroid conditions. The prevalence of spherule detection is strongly influenced by the cellularity. In cases with moderate to high cellularity, the identification of spherules can assist the cytopathologists in diagnosing thyroid FNA cases as benign.

What's new in thyroid pathology 2024: updates from the new WHO classification and Bethesda system.

In line with the release of the 5th edition WHO Classification of Tumors of Endocrine Organs (2022) and the 3rd edition of the Bethesda System for Reporting Thyroid Cytopathology (2023), the field of thyroid pathology and cytopathology has witnessed key transformations. This digest brings to the fore the refined terminologies, newly introduced categories, and contentious methodological considerations pivotal to the updated classification.

Educational exchange in thyroid core needle biopsy diagnosis: enhancing pathological interpretation through guideline integration and peer learning.

Background: While fine needle aspiration cytology (FNAC) plays an essential role in the screening of thyroid nodules, core needle biopsy (CNB) acts as an alternative method to address FNAC limitations. However, diagnosing thyroid CNB samples can be challenging due to variations in background and levels of experience. Effective training is indispensable to mitigate this challenge. We aim to evaluate the impact of an educational program on improving the accuracy of CNB diagnostics. Methods: The 2-week observational program included a host mentor pathologist with extensive experience and a visiting pathologist. The CNB classification by The Practice Guidelines Committee of the Korean Thyroid Association was used for the report. Two rounds of reviewing the case were carried out, and the level of agreement between the reviewers was analyzed. Results: The first-round assessment showed a concordance between two pathologists for 247 thyroid CNB specimens by 84.2%, with a kappa coefficient of 0.74 (indicating substantial agreement). This finding was attributed to the discordance in the use of categories III and V. After peer learning, the two pathologists evaluated 30 new cases, which showed an overall improvement in the level of agreement. The percentage of agreement between pathologists on thyroid CNB diagnosis was 86.7%, as measured by kappa coefficient of 0.80. Conclusions: This educational program, consisting of guided mentorship and peer learning, can substantially enhance the diagnostic accuracy of thyroid CNB. It is useful in promoting consistent diagnostic standards and contributes to the ongoing development of global pathology practices.

A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules.

The 2023 Korean Thyroid Association (KTA) Management Guideline for Patients with Thyroid Nodules constitute an update of the 2016 KTA guideline for thyroid nodules and cancers that focuses specifically on nodules. The 2023 guideline aim to offer updated guidance based on new evidence that reflects the changes in clinical practice since the 2016 KTA guideline. To update the 2023 guideline, a comprehensive literature search was conducted from January 2022 to May 2022. The literature search included studies, reviews, and other evidence involving human subjects that were published in English in MEDLINE (PubMed), Embase, and other relevant databases. Additional significant clinical trials and research studies published up to April 2023 were also reviewed. The limitations of the current evidence are discussed, and suggestions for areas in need of further research are identified. The purpose of this review is to provide a summary of the 2023 KTA guideline for the management of thyroid nodules released in May 2023 and to give a balanced insight with comparison of recent guidelines from other societies.

Utilizing Immunoglobulin G4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis.

BACKGRUOUND: Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished. METHODS: This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm2 were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery. RESULTS: Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm2 was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT. CONCLUSION: This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.

Diagnostic utilities of washout CYFRA 21-1 combined with washout thyroglobulin for metastatic lymph nodes in thyroid cancer: a prospective study.

Cervical lymph node (LN) metastasis is common in differentiated thyroid cancer (DTC). This study evaluated the utility of the washout CYFRA 21-1 level, combined with the thyroglobulin (Tg) concentration, in terms of diagnosis of LN metastasis. We prospectively enrolled 53 patients who underwent thyroid surgery to treat DTC with lateral cervical LN metastases. Preoperative ultrasound guided needle localization was used to surgical sampling of specific LNs during the operation. The intraoperative washout Tg and CYFRA 21-1 levels were measured in such LNs. The Tg and CYFRA 21-1 levels differed significantly between metastatic and benign LNs. The cutoff values were 2.63 ng/mL for washout CYFRA 21-1 and 22.62 ng/mL for Tg. Combined use of the washout Tg and CYFRA 21-1 levels afforded the highest diagnostic accuracy (92.5%), better than that of individual markers. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) were 94.6%, 90.0%, 91.4%, 93.8%, respectively. The conjunction of the washout CYFRA21-1 and Tg levels enhances the diagnostic accuracy of LN metastasis in DTC patients. The washout CYFRA 21-1 level may be useful when malignancy is suspected, especially in cases where the cytology and washout Tg findings do not provide definitive results.

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.

PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma: A Multi-institutional Study.

Anti-PD immunotherapy is currently under investigation in anaplastic thyroid carcinoma (ATC). Tumor cell surface PD-L1 expression is considered predictive of therapeutic response. Although papillary thyroid carcinoma has been widely studied for PD-L1 expression, there are limited data on ATC. In this retrospective multi-institutional study involving 9 centers across Asia, 179 ATCs were assessed for PD-L1 expression using the SP263 (Ventana) clone. A tumor proportion score (TPS) ≥1% was required to consider a case PD-L1-positive. PD-L1 expression was compared with the histological patterns, the type of specimen (small or large), tumor molecular profile (BRAF V600E and TERT promoter mutation status), and patient outcome. PD-L1 expression in any co-existent differentiated thyroid carcinoma (DTC) was evaluated separately and compared with ATC. Most ATCs (73.2%) were PD-L1-positive. The median TPS among positive cases was 36% (IQR 11% to 75%; range 1% to 99%). A high expression (TPS ≥ 50%) was noted in 30.7%. PD-L1-negative cases were more likely to be small specimens (P=0.01). A negative result on small samples, hence, may not preclude expression elsewhere. ATCs having epithelioid and pleomorphic histological patterns were more likely to be PD-L1-positive with higher TPS than sarcomatoid (P<0.01). DTCs were more frequently negative and had lower TPS than ATC (P<0.01). Such PD-L1 conversion from DTC-negative to ATC-positive was documented in 71% of cases with co-existent DTC. BRAF V600E, but not TERT promoter mutations, correlated significantly with PD-L1-positivity rate (P=0.039), reinforcing the potential of combining anti-PD and anti-BRAF V600E drugs. PD-L1 expression, however, did not impact the patient outcome.

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.