Diagnostic conundrums of schwannomas: two cases highlighting morphological extremes and diagnostic challenges in biopsy specimens of soft tissue tumors

Schwannomas are benign, slow-growing peripheral nerve sheath tumors commonly occurring in the head, neck, and flexor regions of the extremities. Although most schwannomas are easily diagnosable, their variable morphology can occasionally create difficulty in diagnosis. Reporting pathologists should be aware that schwannomas can exhibit a broad spectrum of morphological patterns. Clinical and radiological examinations can show correlation and should be performed, in conjunction with ancillary tests, when appropriate. Furthermore, deferring a definitive diagnosis until excision may be necessary for small biopsy specimens and frozen sections. This report underscores these challenges through examination of two unique schwannoma cases, one predominantly cellular and the other myxoid, both of which posed significant challenges in histological interpretation.

The Asian Thyroid Working Group, from 2017 to 2023

The Asian Thyroid Working Group was founded in 2017 at the 12th Asia Oceania Thyroid Association (AOTA) Congress in Busan, Korea. This group activity aims to characterize Asian thyroid nodule practice and establish strict diagnostic criteria for thyroid carcinomas, a reporting system for thyroid fine needle aspiration cytology without the aid of gene panel tests, and new clinical guidelines appropriate to conservative Asian thyroid nodule practice based on scientific evidence obtained from Asian patient cohorts. Asian thyroid nodule practice is usually designed for patient-centered clinical practice, which is based on the Hippocratic Oath, “First do not harm patients,” and an oriental filial piety “Do not harm one’s own body because it is a precious gift from parents,” which is remote from defensive medical practice in the West where physicians, including pathologists, suffer from severe malpractice climate. Furthermore, Asian practice emphasizes the importance of resource management in navigating the overdiagnosis of low-risk thyroid carcinomas. This article summarizes the Asian Thyroid Working Group activities in the past 7 years, from 2017 to 2023, highlighting the diversity of thyroid nodule practice between Asia and the West and the background reasons why Asian clinicians and pathologists modified Western systems significantly.

Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy

As the application of core needle biopsy (CNB) in evaluating thyroid nodules rises in clinical practice, the 2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules have officially recognized its value for the first time. CNB procures tissue samples preserving both histologic structure and cytologic detail, thereby supplying substantial material for an accurate diagnosis and reducing the necessity for repeated biopsies or subsequent surgical interventions. The current review introduces the risk of malignancy within distinct diagnostic categories, emphasizing the implications of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on these malignancy risks. Prior research has indicated diagnostic challenges associated with follicular-patterned lesions, resulting in notable variation within indeterminate diagnostic categories. The utilization of mutation-specific immunostaining in CNB enhances the accuracy of lesion classification. This review underlines the essential role of a multidisciplinary approach in diagnosing follicular-patterned lesions and the potential of mutation-specific immunostaining to strengthen diagnostic consensus and inform patient management decisions.

Tumor Margin Infiltration in Soft Tissue Sarcomas: Prediction Using 3T MRI Texture Analysis

Purpose@#To determine the value of 3 Tesla (T) MRI texture analysis for predicting tumor margin infiltration in soft tissue sarcomas. @*Materials and Methods@#Thirty-one patients who underwent 3T MRI and had a pathologically confirmed diagnosis of soft tissue sarcoma were included in this study. Margin infiltration on pathology was used as the gold standard. Texture analysis of soft tissue sarcomas was performed on axial T1-weighted images (WI) and T2WI, fat-suppressed contrast-enhanced (CE) T1WI, diffusion-weighted images (DWI) with b-value of 800 s/mm², and apparent diffusion coefficient (ADC) was mapped. Quantitative parameters were compared between sarcomas with infiltrative margins and those with circumscribed margins. @*Results@#Among the 31 patients with soft tissue sarcomas, 23 showed tumor margin infiltration on pathology. There were significant differences in kurtosis with the spatial scaling factor (SSF) of 0 and 6 on T1WI, kurtosis (SSF, 0) on CE-T1WI, skewness (SSF, 0) on DWI, and skewness (SSF, 2, 4) on ADC between sarcomas with infiltrative margins and those with circumscribed margins (p ≤ 0.046). The area under the receiver operating characteristic curve based on MR texture features for identification of infiltrative tumor margins was 0.951 (p < 0.001). @*Conclusion@#MR texture analysis is reliable and accurate for the prediction of infiltrative margins of soft tissue sarcomas.

Diagnostic Performance of Thyroid Core Needle Biopsy Using the Revised Reporting System: Comparison with Fine Needle Aspiration Cytology

Background@#We aim to validate the diagnostic performance of thyroid core needle biopsy (CNB) for diagnosing malignancy in clinical settings to align with the changes made in recently updated thyroid CNB guidelines. @*Methods@#We retrospectively analyzed 1,381 thyroid CNB and 2,223 fine needle aspiration (FNA) samples. The FNA and CNB slides were interpreted according to the Bethesda System for Reporting Thyroid Cytopathology and updated practice guidelines for thyroid CNB, respectively. @*Results@#Compared to FNA, CNB showed lower rates of inconclusive results: categories I (2.8% vs. 11.2%) and III (1.2% vs. 6.2%), and higher rates of categories II (60.9% vs. 50.4%) and IV (17.5% vs. 2.0%). The upper and lower bounds of the risk of malignancy (ROM) for category IV of CNB were 43.2% and 26.6%, respectively. The CNB subcategory IVb with nuclear atypia had a higher ROM than the subcategory without nuclear atypia (40%–62% vs. 23%–36%). In histologically confirmed cases, there was no significant difference in the diagnostic performance between CNB and FNA for malignancy. However, neoplastic diseases were more frequently detected by CNB than by FNA (88.8% vs. 77.6%, P=0.046). In category IV, there was no difference in unnecessary surgery rate between CNB and FNA (4.7% vs. 6.9%, P=0.6361). @*Conclusion@#Thyroid CNB decreased the rate of inconclusive results and showed a higher category IV diagnostic rate than FNA. The revised guidelines for thyroid CNB proved to be an excellent reporting system for assessing thyroid nodules.

Benign versus Malignant Soft-Tissue Tumors: Differentiation with 3T Magnetic Resonance Image Textural Analysis Including Diffusion-Weighted Imaging

Purpose@#To investigate the value of MR textural analysis, including use of diffusionweighted imaging (DWI) to differentiate malignant from benign soft-tissue tumors on 3T MRI. @*Materials and Methods@#We enrolled 69 patients (25 men, 44 women, ages 18 to 84 years) with pathologically confirmed soft-tissue tumors (29 benign, 40 malignant) who underwent pre-treatment 3T-MRI. We calculated MR texture, including mean, standard deviation (SD), skewness, kurtosis, mean of positive pixels (MPP), and entropy, according to different spatial-scale factors (SSF, 0, 2, 4, 6) on axial T1-and T2-weighted images (T1WI, T2WI), contrast-enhanced T1WI (CE-T1WI), high b-value DWI (800 sec/mm2 ), and apparent diffusion coefficient (ADC) map. We used the Mann-Whitney U test, logistic regression, and area under the receiver operating characteristic curve (AUC) for statistical analysis. @*Results@#Malignant soft-tissue tumors had significantly lower mean values of DWI, ADC, T2WI and CE-T1WI, MPP of ADC, and CE-T1WI, but significantly higher kurtosis of DWI, T1WI, and CE-T1WI, and entropy of DWI, ADC, and T2WI than did benign tumors (P < 0.050). In multivariate logistic regression, the mean ADC value (SSF, 6) and kurtosis of CE-T1WI (SSF, 4) were independently associated with malignancy (P ≤ 0.009). A multivariate model of MR features worked well for diagnosis of malignant soft-tissue tumors (AUC, 0.909). @*Conclusion@#Accurate diagnosis could be obtained using MR textural analysis with DWI and CE-T1WI in differentiating benign from malignant soft-tissue tumors.

Clinical Outcome of Fine Needle Aspiration Cytology and Washout Thyroglobulin in Suspicious Lymph Nodes in Differentiated Thyroid Carcinoma: Discordant Results in Real-World Practice

Background and Objectives@#Fine needle aspiration cytology (FNAC) combined with washout thyroglobulin (Tg) measurement is the gold standard for the evaluation of metastatic lymph nodes (LNs) in thyroid cancer. However, few studies have assessed the clinical outcomes of discordant results between FNAC and washout Tg based on surgery status and follow-up imaging in real-world practice. @*Materials and Methods@#A total of 707 LNs in 512 patients who underwent FNAC and washout Tg measurements from 2015 to 2017 were analyzed. The final LN outcomes were confirmed through postoperative histology, or through metastatic FNAC findings combined with high washout Tg level, follow-up imaging studies, or repeat FNA, if LNs were not dissected. @*Results@#The cut-off values of washout Tg for indicating LN metastasis in preoperative and postoperative LNs were 9.6 ng/mL and 2.1 ng/mL. The diagnostic accuracy was improved by applying washout Tg according to surgery status and the results of discordant rate was reduced, Discordant between results of FNAC with washout Tg and final outcome were 9.2% (27/295) of preoperative LNs and 8.7% (36/412) of postoperative LNs. Due to inconclusive results, unnecessary neck dissection can occur in 13.9% (36/259 dissected cases). @*Conclusion@#To improve diagnostic accuracy, cut-off values of washout Tg should be applied depending on surgery status. New biomarkers in washout fluid is necessary to resolve discordant findings.

Clinicopathological Characteristics and Recurrence-Free Survival of Rare Variants of Papillary Thyroid Carcinomas in Korea: A Retrospective Study

Background@#We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. @*Methods@#We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. @*Results@#Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. @*Conclusion@#In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force

Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.

Benign versus Malignant Soft-Tissue Tumors: Differentiation with 3T Magnetic Resonance Image Textural Analysis Including Diffusion-Weighted Imaging

Purpose@#To investigate the value of MR textural analysis, including use of diffusionweighted imaging (DWI) to differentiate malignant from benign soft-tissue tumors on 3T MRI. @*Materials and Methods@#We enrolled 69 patients (25 men, 44 women, ages 18 to 84 years) with pathologically confirmed soft-tissue tumors (29 benign, 40 malignant) who underwent pre-treatment 3T-MRI. We calculated MR texture, including mean, standard deviation (SD), skewness, kurtosis, mean of positive pixels (MPP), and entropy, according to different spatial-scale factors (SSF, 0, 2, 4, 6) on axial T1-and T2-weighted images (T1WI, T2WI), contrast-enhanced T1WI (CE-T1WI), high b-value DWI (800 sec/mm2 ), and apparent diffusion coefficient (ADC) map. We used the Mann-Whitney U test, logistic regression, and area under the receiver operating characteristic curve (AUC) for statistical analysis. @*Results@#Malignant soft-tissue tumors had significantly lower mean values of DWI, ADC, T2WI and CE-T1WI, MPP of ADC, and CE-T1WI, but significantly higher kurtosis of DWI, T1WI, and CE-T1WI, and entropy of DWI, ADC, and T2WI than did benign tumors (P < 0.050). In multivariate logistic regression, the mean ADC value (SSF, 6) and kurtosis of CE-T1WI (SSF, 4) were independently associated with malignancy (P ≤ 0.009). A multivariate model of MR features worked well for diagnosis of malignant soft-tissue tumors (AUC, 0.909). @*Conclusion@#Accurate diagnosis could be obtained using MR textural analysis with DWI and CE-T1WI in differentiating benign from malignant soft-tissue tumors.

Clinical Outcome of Fine Needle Aspiration Cytology and Washout Thyroglobulin in Suspicious Lymph Nodes in Differentiated Thyroid Carcinoma: Discordant Results in Real-World Practice

Background and Objectives@#Fine needle aspiration cytology (FNAC) combined with washout thyroglobulin (Tg) measurement is the gold standard for the evaluation of metastatic lymph nodes (LNs) in thyroid cancer. However, few studies have assessed the clinical outcomes of discordant results between FNAC and washout Tg based on surgery status and follow-up imaging in real-world practice. @*Materials and Methods@#A total of 707 LNs in 512 patients who underwent FNAC and washout Tg measurements from 2015 to 2017 were analyzed. The final LN outcomes were confirmed through postoperative histology, or through metastatic FNAC findings combined with high washout Tg level, follow-up imaging studies, or repeat FNA, if LNs were not dissected. @*Results@#The cut-off values of washout Tg for indicating LN metastasis in preoperative and postoperative LNs were 9.6 ng/mL and 2.1 ng/mL. The diagnostic accuracy was improved by applying washout Tg according to surgery status and the results of discordant rate was reduced, Discordant between results of FNAC with washout Tg and final outcome were 9.2% (27/295) of preoperative LNs and 8.7% (36/412) of postoperative LNs. Due to inconclusive results, unnecessary neck dissection can occur in 13.9% (36/259 dissected cases). @*Conclusion@#To improve diagnostic accuracy, cut-off values of washout Tg should be applied depending on surgery status. New biomarkers in washout fluid is necessary to resolve discordant findings.

Clinicopathological Characteristics and Recurrence-Free Survival of Rare Variants of Papillary Thyroid Carcinomas in Korea: A Retrospective Study

Background@#We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. @*Methods@#We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. @*Results@#Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. @*Conclusion@#In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force

Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.

Molecular Correlates and Nuclear Features of Encapsulated Follicular-Patterned Thyroid Neoplasms

Background@#Assessing nuclear features is diagnostically challenging in the aspect of thyroid pathology. The aim of this study was to determine whether pathologists could distinguish BRAF-like and RAS-like nuclear features morphologically and identify morphological features to differentiate thyroid tumors with RAS-like mutations from encapsulated papillary thyroid carcinoma (PTC) with predominant follicular growth and BRAFV600E mutation. @*Methods@#Representative whole slide images of 16 encapsulated thyroid tumors with predominant follicular growth were reviewed by 12 thyroid pathologists using a web browser-based image viewer. Total nuclear score was calculated from semi-quantitatively scored eight nuclear features. The molecular profile of RAS and BRAF genes was determined by Sanger sequencing. @*Results@#Total nuclear score ranging 0 to 24 could differentiate BRAF-like tumors from RAS-like tumors with a cut-off value of score 14. The interobserver agreement was the highest for the assessment of nuclear pseudoinclusions (NPIs) but the lowest for nuclear elongation and sickle-shaped nuclei. NPIs were found in tumors with BRAFV600E mutation, but not in tumors with RAS-like mutations. Total nuclear scores were significantly higher for tumors with BRAFV600E than for those with RAS-like mutations (P<0.001). @*Conclusion@#Our results suggest that NPIs and high nuclear scores have diagnostic utility as rule-in markers for differentiating PTC with BRAFV600E mutation from benign or borderline follicular tumors with RAS-like mutations. Relaxation of rigid criteria for nuclear features resulted in an overdiagnosis of PTC. Immunostaining or molecular testing for BRAFV600E mutation is a useful adjunct for cases with high nuclear scores to identify true PTC.

Assessing the diagnostic performance of thyroid biopsy with recommendations for appropriate interpretation

Purpose@#The diagnostic performance of thyroid biopsy is influenced by several factors, including differences in the Bethesda categorization for malignancy, the inclusion or exclusion of non-diagnostic results, the definition used for the final diagnosis, and the definition of an inconclusive diagnosis. The purpose of this study was to provide an understanding of the factors influencing the diagnostic performance of thyroid biopsy. @*Methods@#We collected data retrospectively between January and December 2013 from a cohort of 6,762 thyroid nodules from 6,493 consecutive patients who underwent biopsy. In total, 4,822 nodules from 4,553 patients were included. We calculated the biopsy sensitivity according to the inclusion of different Bethesda categories in the numerator and the exclusion of non-diagnostic results, as well as the diagnostic accuracy according to different definitions of a benign diagnosis. We obtained the conclusive and inconclusive diagnosis rates. @*Results@#The sensitivity increased when more Bethesda categories were included in the numerator and when non-diagnostic results were excluded. When a benign thyroid nodule diagnosis was defined as benign findings on surgical resection, concordant benign results on at least two occasions, or an initial benign biopsy result and follow-up for more than 12 months, the accuracy was higher than when the diagnosis was based on surgical resection alone (68.7% vs. 91.1%). A higher conclusive diagnosis rate was obtained (78.3% vs. 72.8%, P<0.001) when Bethesda categories I and III were considered inconclusive. @*Conclusion@#Understanding the concepts presented herein is important in order to appropriately interpret the diagnostic performance of thyroid biopsy.

Recommendations for pathologic practice using digital pathology: consensus report of the Korean Society of Pathologists

Digital pathology (DP) using whole slide imaging (WSI) is becoming a fundamental issue in pathology with recent advances and the rapid development of associated technologies. However, the available evidence on its diagnostic uses and practical advice for pathologists on implementing DP remains insufficient, particularly in light of the exponential growth of this industry. To inform DP implementation in Korea, we developed relevant and timely recommendations. We first performed a literature review of DP guidelines, recommendations, and position papers from major countries, as well as a review of relevant studies validating WSI. Based on that information, we prepared a draft. After several revisions, we released this draft to the public and the members of the Korean Society of Pathologists through our homepage and held an open forum for interested parties. Through that process, this final manuscript has been prepared. This recommendation contains an overview describing the background, objectives, scope of application, and basic terminology; guidelines and considerations for the hardware and software used in DP systems and the validation required for DP implementation; conclusions; and references and appendices, including literature on DP from major countries and WSI validation studies.

Updates in the Pathologic Classification of Thyroid Neoplasms: A Review of the World Health Organization Classification

Advances in medical sciences and evidence-based medicine have led to momentous changes in classification and management of thyroid neoplasms. Much progress has been made toward avoiding overdiagnosis and overtreatment of thyroid cancers. The new 2017 World Health Organization (WHO) classification of thyroid neoplasms updated the diagnostic criteria and molecular and genetic characteristics reflecting the biology and behavior of the tumors, and newly introduced the category of borderline malignancy or uncertain malignant potential. Some neoplasms were subclassified, renamed, or redefined as a specific entity. This review introduces changes in the fourth edition WHO classification of thyroid tumors and updates the contemporary diagnosis and classification of thyroid tumors. We also discuss several challenges with the proposal of new diagnostic entities, since they have unique histopathologic and molecular features and clinical relevance.

Continuous quality improvement program and its results of Korean Society for Cytopathology

Since 1995, the Korean Society for Cytopathology has overseen the Continuous Quality Improvement program for cytopathology laboratories. The Committee of Quality Improvement has carried out an annual survey of cytology data for each laboratory and set standards for proficiency tests. Methods: Evaluations were conducted four times per year from 2008 to 2018 and comprised statistics regarding cytology diagnoses of previous years, proficiency tests using cytology slides provided by the committee, assessment of adequacy of gynecology (GYN) cytology slides, and submission of cytology slides for proficiency tests. Results: A total of 206 institutes participated in 2017, and the results were as follows. The number of cytology tests increased from year to year. The ratio of liquid-based cytology in GYN gradually decreased, as most of the GYN cytology had been performed at commercial laboratories. The distribution of GYN diagnoses demonstrated nearly 3.0% as atypical squamous cells. The rate for squamous cell carcinoma was less than 0.02%. The atypical squamous cell/squamous intraepithelial lesion ratio was about 3:1 and showed an upward trend. The major discordant rate of cytology-histology in GYN cytology was less than 1%. The proficiency test maintained a major discordant rate less than 2%. The rate of inappropriate specimens for GYN cytology slides gradually decreased. Conclusions: The Continuous Quality Improvement program should be included in quality assurance programs. Moreover, these data can contribute to development of national cancer examination guidelines and facilitate cancer prevention and treatment.

Introduction to digital pathology and computer-aided pathology

Digital pathology (DP) is no longer an unfamiliar term for pathologists, but it is still difficult for many pathologists to understand the engineering and mathematics concepts involved in DP. Computer-aided pathology (CAP) aids pathologists in diagnosis. However, some consider CAP a threat to the existence of pathologists and are skeptical of its clinical utility. Implementation of DP is very burdensome for pathologists because technical factors, impact on workflow, and information technology infrastructure must be considered. In this paper, various terms related to DP and computer-aided pathologic diagnosis are defined, current applications of DP are discussed, and various issues related to implementation of DP are outlined. The development of computer-aided pathologic diagnostic tools and their limitations are also discussed.

Highly prevalent BRAF V600E and low-frequency TERT promoter mutations underlie papillary thyroid carcinoma in Koreans

Background@#The presence of telomerase reverse transcriptase (TERT) promoter mutations have been associated with a poor prognosis in patients with papillary thyroid carcinomas (PTC). The frequency of TERT promoter mutations varies widely depending on the population and the nature of the study. @*Methods@#Data were prospectively collected in 724 consecutive patients who underwent thyroidectomy for PTC from 2018 to 2019. Molecular testing for BRAF V600E and TERT promoter mutations was performed in all cases. @*Results@#TERT promoter alterations in two hotspots (C228T and C250T) and C216T were found in 16 (2.2%) and 4 (0.6%) of all PTCs, respectively. The hotspot mutations were significantly associated with older age at diagnosis, larger tumor size, extrathyroidal extension, higher pathologic T category, lateral lymph node metastasis, and higher American Thyroid Association recurrence risk. The patients with C216T variant were younger and had a lower American Thyroid Association recurrence risk than those with hotspot mutations. Concurrent BRAF V600E was found in 19 of 20 cases with TERT promoter mutations. Of 518 microcarcinomas measuring ≤1.0 cm in size, hotspot mutations and C216T variants were detected in five (1.0%) and three (0.6%) cases, respectively. @*Conclusions@#Our study indicates a low frequency of TERT promoter mutations in Korean patients with PTC and supports previous findings that TERT promoter mutations are more common in older patients with unfavorable clinicopathologic features and BRAF V600E. TERT promoter mutations in patients with microcarcinoma are uncommon and may have a limited role in risk stratification. The C216T variant seems to have no clinicopathologic effect on PTC.