Virtual Remote Pathology Education in Support of Virtual Remote Gynecologic-Oncology Training: The Open Pathology Education Network Pilot Proof of Concept Experience.

CONTEXT.­: The subspecialty workforce in pathology globally is inadequate for the demands of many modern therapies. The Open Pathology Education Network (OPEN) was formed to augment the global pathology workforce. The International Gynecologic Cancer Society (IGCS) virtual gynecologic-oncology (gyn-onc) fellowship training identified needs for higher-level pathology support. OBJECTIVE.­: To report on an OPEN-IGCS pilot project to support gyn-onc and pathology education efforts in a developing country. DESIGN.­: Curriculum with learning objectives and content from open sources was assembled. Mentoring sessions included bidirectional case sharing. Trainees received sequential curricula assignments and had options for communication outside mentoring sessions. Pretest and posttest digital slide assessments were included. Mentors attended the gynecology tumor board, allowing for the assessment of quality and accuracy of pathology diagnosis for cases discussed. RESULTS.­: Learners completing the pretest and posttest showed substantial improvement, with 2 practicing pathologists improving their diagnostic scores from 60% to an average of 95%. A third trainee-level participant also improved, but to a lesser degree. Qualitative assessments included increased confidence in presentation and an increased ability to anticipate questions, raise issues of expanded differential diagnoses, and articulate appropriate workup. Observations of clinicians who participated also noted increased confidence in participating pathologists. Secondary value included establishing an expanded network of support in other subspecialties for participants. Pathologic issues at the tumor board decreased, from more than 50% in the first 3 months of study to 0% in the last 3 months of study. The curriculum was embedded into a self-paced learning portal at courses.open-pathology.org. CONCLUSIONS.­: The OPEN-IGCS collaboration model shows the potential to provide subspecialty pathology training remotely.

Evolving educational landscape in pathology: a comprehensive bibliometric and visual analysis including digital teaching and learning resources.

AIMS: Pathology education is a core component of medical training, and its literature is critical for refining educational modalities. We performed a cross-sectional bibliometric analysis to explore publications on pathology education, focusing on new medical education technologies. METHODS: The analysis identified 64 pathology journals and 53 keywords. Relevant articles were collected using a web application, PaperScraper, developed to accelerate literature search. Citation data were collected from multiple sources. Descriptive statistics, with time period analysis, were performed using Microsoft Excel and visualised with Flourish Studio. Two article groups were further investigated with a bibliometric software, VOSViewer, to establish co-authorship and keyword relationships. RESULTS: 8946 citations were retrieved from 905 selected articles. Most articles were published in the last decade (447, 49.4%). The top journals were Archives of Pathology & Laboratory Medicine (184), Human Pathology (122) and the American Journal of Clinical Pathology (117). The highest number of citations was found for Human Pathology (2120), followed by Archives of Pathology & Laboratory Medicine (2098) and American Journal of Clinical Pathology (1142). Authors with different backgrounds had the greatest number of articles and citations. 12 co-authorship, 3 keyword and 8 co-citation clusters were found for the social media/online resources group, 8 co-authorship, 4 keyword and 7 co-citation clusters for the digital pathology/virtual microscopy/mobile technologies group. CONCLUSIONS: The analysis revealed a significant increase in publications over time. The emergence of digital teaching and learning resources played a major role in this growth. Overall, these findings underscore the transformative potential of technology in pathology education.

Recommendations for Performance Evaluation of Machine Learning in Pathology: A Concept Paper From the College of American Pathologists.

CONTEXT.­: Machine learning applications in the pathology clinical domain are emerging rapidly. As decision support systems continue to mature, laboratories will increasingly need guidance to evaluate their performance in clinical practice. Currently there are no formal guidelines to assist pathology laboratories in verification and/or validation of such systems. These recommendations are being proposed for the evaluation of machine learning systems in the clinical practice of pathology. OBJECTIVE.­: To propose recommendations for performance evaluation of in vitro diagnostic tests on patient samples that incorporate machine learning as part of the preanalytical, analytical, or postanalytical phases of the laboratory workflow. Topics described include considerations for machine learning model evaluation including risk assessment, predeployment requirements, data sourcing and curation, verification and validation, change control management, human-computer interaction, practitioner training, and competency evaluation. DATA SOURCES.­: An expert panel performed a review of the literature, Clinical and Laboratory Standards Institute guidance, and laboratory and government regulatory frameworks. CONCLUSIONS.­: Review of the literature and existing documents enabled the development of proposed recommendations. This white paper pertains to performance evaluation of machine learning systems intended to be implemented for clinical patient testing. Further studies with real-world clinical data are encouraged to support these proposed recommendations. Performance evaluation of machine learning models is critical to verification and/or validation of in vitro diagnostic tests using machine learning intended for clinical practice.

Ought to The Changes Within the Immunophenotype of Solid Cell Nests (SCNs) and Follicular Cells in Hashimoto's Thyroiditis be Considered as Premalignant Lesions?

Background: Papillary thyroid carcinoma (PTC) is more frequently reported in patients with Hashimoto's thyroiditis (HT), which may be associated with the presence of solid cell nests (SCNs) and focal PTC-like nuclear alterations in the thyroid gland. The point of this consideration was to assess the morphological and immunohistochemical features of SCNs and follicular epithelial changes in Vietnamese patients with HT. Materials and Methods: Hematoxylin-eosin and immunohistochemistry were performed on 20 samples of HT patients who underwent thyroidectomy and were diagnosed with Hashimoto's thyroiditis at Military Medical Hospital 103 from 6/2018 to 6/2019. The expression of five markers (P63, Calcitonin, TTF1, CK19 and HBME-1) in SCNs and follicular epithelial changes were evaluated. Results: Ninety per cent of samples had SCNs with an average of 10 SCNs per section. Only type 1 and type 4 SCNs were presented (85% and 55%, respectively) and all SCNs were composed of main cells (p63-positive). Fifteen of the 18 cases having SCNs possessed nuclear features of PTC. C-cell hyperplasia was found in one case with 20 clusters. All SCNs showed strong staining with CK19 and weak staining with HBME-1. Follicular epithelial changes were Hürthle cell metaplasia, PTC-like nuclear alterations, atypical solid nodules, papillary and glomerular-like forms (40%, 100%, 25% and 50%, respectively). Follicular cells of glomerular-like forms (new alteration) especially were positive with CK19 (2+ ~ 3+), HBME-1 (1+) and TTF1, while the components in these follicles were negative with CK19, HBME-1 and TTF1. Among PTC-like nuclear alterations, all the atypical solid nodules related to HT showed markers related to PTC and without SCNs. Conclusions: Increasing the number of SCNs, as well as PTC-like nuclear alterations of main cells in SCNs and follicular epithelial changes were co-expressed CK19 and HBME-1. Therefore, the need for HT management should be considered.

Dedifferentiated Ovarian Carcinoma with ARID1A and ARID1B Mutations: A Clinicopathological Report and Literature Review.

Dedifferentiated carcinoma of the female genital tract is a relatively recently recognized aggressive tumor affecting predominantly perimenopausal and postmenopausal women. In addition to having an undifferentiated component, dedifferentiated carcinoma includes a juxtaposed endometrioid adenocarcinoma, FIGO grade 1 or 2. Molecular characterization of these tumors has been a subject of discussion in multiple recent articles. We present a case of dedifferentiated carcinoma of the ovary in a 70-year-old female demonstrating concurrent inactivation of ARID1A and ARID1B. To the best of our knowledge, this is the second clinical report demonstrating dedifferentiated carcinoma of the ovary with concurrent inactivation of ARID1A and ARID1B. ARID1A and ARID1B inactivation seems to represent an alternate mechanism of switch/sucrose nonfermentable complex inactivation in the development of dedifferentiated carcinoma. Additional studies are warranted to precisely understand the molecular mechanism of cellular dedifferentiation in the dedifferentiated endometrial/ovarian carcinomas, thus guiding the development of targeted therapy.

Primary Thyroid Mucoepidermoid Carcinoma (MEC) Is Clinically, Prognostically, and Molecularly Different from Sclerosing MEC with Eosinophilia: A Multicenter and Integrated Study.

Mucoepidermoid carcinoma (MEC) and sclerosing MEC with eosinophilia (SMECE) are rare primary thyroid carcinomas. In this study, we aimed to present our multicenter series of MEC and SMECE and integrated our data with published literature to further investigate the clinicopathological characteristics and prognoses of these tumors. We found 2 MECs and 4 SMECEs in our multicenter archives. We performed fluorescence in situ hybridization (FISH) to determine the MAML2 gene rearrangement. We screened for mutations in BRAF, TERT promoter, and RAS mutations using Sanger sequencing and digital polymerase chain reaction. Histopathologically, MECs and SMECEs were composed of two main cell types including epidermoid and mucin-secreting cells, arranged in cords, nests, and tubules. SMECEs were characterized by a densely sclerotic stroma with abundant eosinophils. We did not detect any MAML2 fusion in any of our cases. Two MEC cases harbored concomitant BRAF p.V600E and TERT C228T mutations. RAS mutations were absent in all cases. Concurrent foci of another thyroid malignancy were more commonly seen in MECs (p < 0.001), whereas SMECEs were associated with chronic lymphocytic thyroiditis (p < 0.001). MECs and SMECEs had equivalent recurrence-free survival (RFS) but MECs conferred significantly dismal disease-specific survival (DSS) as compared to SMECEs (p = 0.007). In conclusion, MECs and SMECEs not only shared some similarities but also demonstrated differences in clinicopathological characteristics, prognoses, and molecular profiles. SMECEs had a superior DSS in comparison to MECs, suggesting that they are low-grade cancers. This could help clinicians better evaluate patient outcomes and decide appropriate treatment plans.

Pathology Education Powered by Virtual and Digital Transformation: Now and the Future.

CONTEXT.­: Myriad forces are changing teaching and learning strategies throughout all stages and types of pathology education. Pathology educators and learners face the challenge of adapting to and adopting new methods and tools. The digital pathology transformation and the associated educational ecosystem are major factors in this setting of change. OBJECTIVE.­: To identify and collect resources, tools, and examples of educational innovations involving digital pathology that are valuable to pathology learners and teachers at each phase of professional development. DATA SOURCES.­: Sources were a literature review and the personal experience of authors and educators. CONCLUSIONS.­: High-quality digital pathology tools and resources have permeated all the major niches within anatomic pathology and are increasingly well applied to clinical pathology for learners at all levels. Coupled with other virtual tools, the training landscape in pathology is highly enriched and much more accessible than in the past. Digital pathology is well suited to the demands of peer-to-peer education, such as in the introduction of new testing, grading, or other standardized practices. We found that digital pathology was well adapted to apply our current understanding of optimal teaching strategies and was effective at the undergraduate, graduate, postgraduate, and peer-to-peer levels. We curated and tabulated many existing resources within some segments of pathology. We identified several best practices for each training or educational stage based on current materials and proposed high-priority areas for potential future development.

Clinicopathological significance of major fusion oncogenes in papillary thyroid carcinoma: An individual patient data meta-analysis.

INTRODUCTION: Fusion oncogenes (e.g., NTRK, RET, ALK, BRAF) are rare genetic events in papillary thyroid carcinoma (PTC). It is still unclear regarding the similarities and differences in clinicopathological manifestations and prognostic outcomes of these genetic alterations. This individual patient data (IPD) meta-analysis analyzed the clinicopathological significance and prognoses of different types of oncogenic fusions in PTC patients. METHODS: Categorical variables were compared by using Chi-square and Fisher's exact tests while Wilcoxon rank-sum and analysis of variance (ANOVA) tests were utilized for continuous covariates. Progression-free survival (PFS) and overall survival (OS) were computed using Kaplan-Meier analysis and log-rank test. RESULTS: We included 27 studies for meta-analyses. NTRK-, RET-, BRAF-, and ALK-rearranged PTCs had a unique demographic/clinicopathological profile but similar PFS and OS. NTRK1-positive PTCs demonstrated more aggressive clinical behaviors and shorter PFS in comparison to NTRK3-positive PTCs whereas RET rearrangement variants shared comparable clinicopathological backgrounds. CONCLUSION: This study provides new insights and facilitates our current understanding of clinicopathological features and survival outcomes of different fusion oncogenes in PTCs. It may help clinicians better counsel the patients and tailor appropriate treatment decisions.

Malignant transformation of mature cystic teratoma of the ovary.

Mature cystic teratoma is the most common ovarian germ cell neoplasm. Malignant transformation is a rare occurrence, accounting for 1.5%-2% of cases. Malignant changes can arise from any constituent tissue of a teratoma; however, squamous cell carcinoma is the most common histologic type seen, followed by adenocarcinoma and sarcoma respectively. Tumor marker concentration levels, age, and the tumor maximum diameter are predictive indicators for malignant transformation. Proper diagnosis includes recognizing the possibility of malignant transformation versus excluding other differential options, such as metastasis. Primary cytoreductive surgery, adjuvant chemotherapy, and radiotherapy are the current treatment methods. The aim of the review is to discuss the clinical and pathologic features of malignant transformation within mature cystic teratomas, while reviewing the reported malignant types, differential diagnoses, and treatment options. Data sources include review of pertinent peer-reviewed literature on malignant transformation of mature cystic teratoma and cases seen in authors' institutional practice. Mature cystic teratomas are a commonly encountered benign ovarian tumor. However, the possibility of malignant transformation should remain in consideration, especially with given clinical or pathologic features: increased patient age, tumor size, or tumor marker levels. Thorough sampling of solid tumor foci can help identify malignant components. Awareness and proper diagnosis, along with early detection and clinical management, shows improved patient outcomes.

Rules of engagement: Promoting academic-industry partnership in the era of digital pathology and artificial intelligence.

Academic industry partnership (AIP) represents an important alliance between academic researchers and industry that helps translate technology and complete the innovation cycle within academic health systems. Despite diverging missions and skillsets the culture for academia and industry is changing in response to the current digital era which is spawning greater collaboration between physicians and businesses in this marketplace. In the field of pathology, this is further driven by the fact that traditional funding sources cannot keep pace with the innovation needed in digital pathology and artificial intelligence. This concept article from the Digital Pathology Association (DPA) describes the rules of engagement for pathology innovators in academia and for their corporate partners to help establish best practices in this critical area. Stakeholders include pathologists, basic and translational researchers, university technology transfer and sponsored research offices, as well as industry relations officers. The article discusses the benefits and pitfalls of an AIP, reviews different partnership models, examines the role of pathologists in the innovation cycle, explains various agreements that may need to be signed, covers conflict of interest and intellectual property issues, and offers recommendations for ensuring successful partnerships.

The differences in distant metastatic patterns and their corresponding survival between thyroid cancer subtypes.

INTRODUCTION: This study aimed to systematically elucidate the metastatic patterns and their corresponding survival of each thyroid cancer subtype at time of diagnosis. METHODS: We accessed the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2018 to search for primary thyroid cancers with DM at presentation (M1). RESULTS: We included 2787 M1 thyroid cancers for statistical analyses and the incidence of DM at presentation was 2.4%. Lung was the most common metastatic site for anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), papillary thyroid carcinoma (PTC), and oncocytic (Hurthle) cell carcinoma (HCC) whereas bone is the favorable disseminated site of follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC). Patients with multi-organ metastases had the worst survival whereas bone metastases were associated with a favorable outcome (p < 0.001). CONCLUSION: There are significant differences in DM patterns of thyroid cancer subtypes and their corresponding survival.

Primary Versus Secondary Anaplastic Thyroid Carcinoma: Perspectives from Multi-institutional and Population-Level Data.

Primary (or de novo) anaplastic thyroid carcinoma (ATC) is ATC without pre-existing history of differentiated thyroid carcinoma (DTC) and no co-existing DTC foci at the time of diagnosis. Secondary ATC is diagnosed if the patient had a history of DTC or co-existing DTC components at time of diagnosis. This study aimed to investigate the incidence, clinical presentations, outcomes, and genetic backgrounds of primary versus secondary ATCs. We searched for ATCs in our institutional databases and the Surveillance, Epidemiology, and End Result (SEER) database. We also performed a systematic review and meta-analysis to analyze the genetic alterations of primary and secondary ATCs. From our multi-institutional database, 22 primary and 23 secondary ATCs were retrieved. We also identified 620 and 24 primary and secondary ATCs in the SEER database, respectively. Compared to primary ATCs, secondary ATCs were not statistically different in terms of demographic, clinical manifestations, and patient survival. The only clinical discrepancy between the two groups was a significantly larger tumor diameter of the primary ATCs. The prevalence of TERT promoter, PIK3CA, and TP53 mutations was comparable between the two subtypes. In comparison to primary ATCs, however, BRAF mutations were more prevalent (OR = 4.70; 95% CI = 2.84-7.78) whereas RAS mutations were less frequent (OR = 0.43; 95% CI = 0.21-0.85) in secondary tumors. In summary, our results indicated that de novo and secondary ATCs might share many potential developmental steps, but there are other factors that suggest distinct developmental pathways.

Recurrence risk of occult micrometastases and isolated tumor cells in early stage endometrial cancer: A case control study.

OBJECTIVES: To determine whether previously undetected occult micrometastasis (MM) or isolated tumor cells (ITC) is associated with increased recurrence odds in stage I-II endometrioid adenocarcinoma. METHODS: Women with recurrent stage I/II EC who had complete pelvic and para-aortic were identified as the outcome of interest. A case-control study was designed with the exposure defined as occult MM/ITC not seen on original nodal pathology. Controls were found by frequency-matching in a 1:2 case control ratio. Original nodal slides were re-reviewed, stained and tested with immunohistochemical to detect occult MM/ITC and the odds of associated recurrence was calculated. RESULTS: Of 153 included, 50 with and 103 without recurrence, there was no difference in age (p = 0.46), race (p = 0.24), stage (p = 0.75), FIGO grade (p = 0.64), lymphovascular space invasion (LVSI); p = 1.00, or GOG 99 high-intermediate risk (HIR) criteria (p = 0.35). A total of 18 ITC (11.8%) and 3 MM (2.0%) not previously identified were found in 19 patients. Finding occult MM/ITC was not associated with more lymph nodes (LN) removed (p = 0.67) or tumor grade (p = 0.48) but was significantly associated with stage (p < 0.01). LVSI (p = 0.09) and meeting high-intermediate risk criteria (p = 0.09), were closely associated but not statistically significant. Isolated ITC were not associated with increased odds for recurrence (OR 0.71, CL: 0.20 - 2.22, p = 0.57), recurrence free survival (RFS) (p = 0.85) or overall survival (OS) (p = 0.92). CONCLUSIONS: In early-stage EC, identification of occult MM or ITC is uncommon and associated with stage. The presence of ITC was not associated with increased odds of recurrence. Adjusting stage or treatment may avoided based on ITC alone. Isolated MM were rare in our population, and further investigation is warranted.

Malignant thyroid teratoma: an integrated analysis of case series/case reports.

Malignant thyroid teratoma (MTT) is a very rare thyroid malignancy. These neoplasms have been reported only in case reports and small-sized case series so far. In this study, we searched for MTTs in the Surveillance, Epidemiology, and End Result (SEER) program during 1975-2016. Subsequently, we incorporated the SEER data with published MTT cases in the literature to analyze the characteristics and prognostic factors of MTTs. Integrated data were analyzed using chi-square or Fisher's exact test for categorical covariates, and t-test or Mann-Whitney test for continuous variables. We included 28 studies with 36 MTT cases and found additional 8 cases from the SEER program for final analyses. Our results showed that MTT is typically seen in adult females. These neoplasms were associated with an aggressive clinical course with high rates of extrathyroidal extension (80%) and nodal involvement (62%). During follow-up, the development of recurrence and metastases were common (42% and 46%, respectively), and one-third of patients died at the last follow-up. Large tumor size (P = 0.022) and the presence of metastases during follow-up (P = 0.008) were associated with a higher mortality rate. In conclusion, our study demonstrated the characteristic features of MTT patients and outlined some parameters associated with a negative outcome which could help clinicians better predict the clinical course of these neoplasms.

Virtual Mega-Meetings: Here to Stay?

Among the paradigms changed by the COVID-19 pandemic is the traditional academic and educational conference. In the vein of turning lemons into lemonade, many organizations and individuals have discovered ways that this public health necessitated change can be transformed into a boon to both participants and organizations. However, the question of whether this shift becomes permanent, or a component of the future of academic and educational meetings remains to be seen, and likely will depend on the solution to some of the challenges that have not been sweetened by the shift. This editorial draws on experience with a limited scope of virtual meetings in two different disciplines to make the case that the Virtual Mega-Conference is likely to continue to be a part of life in the years ahead.

Flattening the World of Pathology Education and Training and Shortening the Curve of Pathology Learning.

OBJECTIVES: We review how the pandemic-related education disruption may interplay with pathology manpower worldwide and shifts in disease burden to identify workable solutions. METHODS: Literature related to pathology education, pathology services in low-resource settings, and application of digital tools to pathology education was reviewed for trends and training gaps. Publications covering pathology manpower and cancer incidence worldwide were also included to assess needs. RESULTS: Pandemic-related virtual teaching has produced abundant online training materials. Pathology learning resources in low- to middle-income countries remain considerably constrained and dampen pathology manpower growth to meet current needs. Projected increases in disease burden toward the developing world thus pose a major challenge. Digital pathology resources have expanded and are beginning to appear beyond the developed countries. CONCLUSIONS: This circumstance offers a unique opportunity to leverage digital teaching resources to enhance and equitize training internationally, potentially sufficient to meet the rising wave of noncommunicable diseases. We propose four next steps to take advantage of the current opportunity: curate and organize digital training materials, invest in the digital pathology infrastructure for education and clinical care, expand student exposure to pathology through virtual electives, and develop further competency-based certification pathways.

Clinicopathological Implications of RHOA Mutations in Angioimmunoblastic T-Cell Lymphoma: A Meta-analysis: RHOA mutations in AITL.

BACKGROUND: Studies have recently shown that RHOA mutations play a crucial role in angioimmunoblastic T-cell lymphoma (AITL) pathogenesis. We aimed to pool data from these studies to provide a comparison of clinicopathological features between the RHOA mutant and RHOA wild-type groups in the AITL population. METHODS: We searched PubMed and Web of Science for the keywords "RHOA AND lymphoma" and selected only studies reporting the clinical significance of RHOA mutations in AITL. We calculated the odds ratios (OR) or the mean difference with 95% CI using a random effect model. RESULTS: Our pooled results showed a significant association between RHOA mutations and a T-follicular helper cell (TFH) phenotype, especially CD10 (OR, 5.16; 95% CI, 2.32-11.46), IDH2 mutations (OR, 10.70; 95% CI, 4.22-27.15), and TET2 mutations (OR, 7.03; 95% CI, 2.14-23.12). Although DNMT3A together with TET2 and IDH2 mutations are epigenetic gene alterations, we found an insignificant association between RHOA and DNMT3A mutations (OR, 1.72; 95% CI, 0.73-4.05). No significant associations of RHOA mutations with other clinicopathological features and overall survival were found. CONCLUSIONS: RHOA mutations are strongly correlated with a T-follicular helper cell phenotype and epigenetic mutations such as TET2 and IDH2. Further studies with large AITL samples should be conducted to validate the relationship of TET2, DNMT3A, and RHOA co-mutations.

Pushed Across the Digital Divide: COVID-19 Accelerated Pathology Training onto a New Digital Learning Curve.

Bringing digital teaching materials into residency training programs has seen slow adoption, expected for many new technologies. The COVID-19 pandemic dramatically shifted the paradigm for many resident teaching modalities as institutions instituted social distancing to prevent spread of the novel coronavirus. The impact of this shift on pathology trainee education has not been well studied. We conducted an online survey of pathology trainees, program directors, and faculty to assess pre- and post-COVID-19 use of, and response to, various digital pathology modalities. Responses were solicited through both social media and directed appeals. A total of 261 respondents (112 faculty, 52 program directors, and 97 trainees) reported a dramatic and significant increase in the use of digital pathology-related education tools. A significant majority of faculty and program directors agreed that this shift had adversely affected the quality (59% and 62%, respectively) and effectiveness (66%) of their teaching. This perception was similar among learners relative to the impact on quality (59%) and effectiveness (64%) of learning. Most respondents (70%-92%) anticipate that their use of digital pathology education tools will increase or remain the same post-COVID. The global COVID-19 pandemic created a unique opportunity and challenge for pathology training programs. Digital pathology resources were accordingly readily adopted to continue supporting educational activities. The learning curve and utilization of this technology was perceived to impair the quality and effectiveness of teaching and learning. Since the use of digital tools appears poised to continue to grow post-COVID19, challenges due to impaired quality and effectiveness will need to be addressed.

The Use of the Bethesda System for Reporting Thyroid Cytopathology in Pediatric Thyroid Nodules: A Meta-Analysis.

Background: Little is known about the application of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) in pediatric thyroid nodules. This meta-analysis was aimed to investigate the use of TBSRTC in the pediatric population. Methods: Relevant articles were searched in PubMed and Web of Science. Meta-analysis of proportion and its 95% confidence interval (CI) were computed utilizing the random-effect model. We used subgroup analyses and meta-regression to explore the sources of heterogeneities. Egger's regression test and funnel plot visualization were used to examine publication bias. Results: We included 17 articles comprising of 3687 pediatric thyroid nodules for meta-analyses. TBSRTC outputs including frequency and risk of malignancy (ROM) for the majority of categories were not statistically different from recently published meta-analysis of 145,066 thyroid nodules in adult patients. The resection rate (RR) in the pediatric group was significantly higher in most of the categories compared with published adult data: benign, 23.2% [CI = 18.6-27.9] vs. 13.0% [CI = 9.5-16.5]; atypia of undetermined significance/follicular lesion of undetermined significance, 62.6% [CI = 50.3-74.9] vs. 36.2% [CI = 29.9-42.5]; follicular neoplasm/suspicious for follicular neoplasm, 84.3% [CI = 75.2-93.4] vs. 60.5% [CI = 54.5-66.5]; and suspicious for malignancy, 93.8% [CI = 90.1-97.6] vs. 69.7% [CI = 64.0-75.5]. Conclusion: TBSRTC is a valuable tool to make clinical decisions for pediatric patients with thyroid nodules. Pediatric patients with benign and indeterminate thyroid nodules had a higher RR than adult counterpart, but ROM of these categories in adults and children was not statistically different suggesting a potential risk of overtreatment in pediatric patients. Determining the best treatment guidelines and additional tools for risk stratification must be a top priority to precisely identify the target patient groups for surgical intervention.