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Introduction: Distant metastasis (DM) is not a frequent event in differentiated thyroid carcinoma (DTC) but has an adverse impact on mortality of patients with DTC. In the current study, we aimed to conduct a comprehensive systematic review and meta-analysis to investigate the risk factors for DM in DTCs and for each histological subtype.Methods: Five electronic databases were searched from inception to December 2016 for relevant articles. Pooled odd ratios and 95% confidence interval were calculated using random-effect model.Results: Thirty-four articles with 73,219 patients were included for meta-analyses. In DTCs, male gender, age ≥45 years, tumor size ≥4 cm, multifocality, vascular invasion (VI), extrathyroidal extension (ETE), lymph node metastasis (LNM), and lateral LNM were demonstrated to be associated with significant risks for DM. In addition, several clinicopathological factors such as age ≥45 years, VI, ETE, and LNM were shown to be significant risk factors for DM in both PTC and FTC subgroups.Conclusion: Our study demonstrated the promising value of several clinicopathological factors such as male gender, older age, VI, ETE, and LNM in predicting DM in PTCs and FTCs. Our study affirms the value of the selected clinicopathological factors for tumor risk stratification and assessment of patients’ prognosis. [ABSTRACT FROM AUTHOR]

The clinical significance of telomerase reverse transcriptase ( TERT) promoter mutation in glioma remains unclear. The aim of our meta-analysis is to investigate the prognostic impact TERT promoter mutation in glioma patients and its interaction with other molecular markers, particularly Isocitrate Dehydrogenase (IDH) mutation from aggregate level data. Relevant articles were searched in four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library. Pooled HRs were calculated using random effect model weighted by inverse variance method. From 1010 studies, we finally included 28 studies with 11519 patients for meta-analyses. TERT mutation is significantly associated with compromised overall survival (OS) (HR = 1.38; 95% CI = 1.15–1.67) and progression-free survival (PFS) (HR = 1.31; 95% CI = 1.06–1.63) in glioma patients. In studying its reaction with IDH , TERT promoter mutation was associated with reduced OS in both IDH -mutant ( IDH- mut) and IDH -wild type ( IDH- wt) glioblastomas but shown to have inverse effects on IDH- mut and IDH- wt grade II/III tumors. Our analysis categorized WHO grade II/III glioma patients into four distinct survival subgroups with descending survival as follow: TERT- mut/ IDH- mut ≫ TERT- wt/ IDH- mut ≫ TERT- wt/ IDH- wt ≫ TERT- mut/ IDH- wt. Prognostic value of TERT promoter mutations in gliomas is dependent on tumor grade and the IDH mutational status. With the same tumor grade in WHO grade II and III tumors and the same IDH mutation status, TERT-mut is a prognostic factor. [ABSTRACT FROM AUTHOR]

Introduction The use of molecular markers, especially BRAF and TERT promoter mutations, for risk stratification in papillary thyroid carcinoma ( PTC) is subject to continuing debate. In this study, we aimed to investigate the clinicopathological implication of each genotype when combining BRAF and TERT promoter mutations in PTCs. Methods We searched four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library for relevant studies. Pooled estimates of odds ratios and corresponding 95% confidence intervals were calculated using random-effect model. Results From 111 results, we finally included 11 studies with 3911 PTC patients for meta-analyses. Our results demonstrated that PTCs with concurrent BRAF and TERT promoter mutations were associated with increased tumour aggressiveness in comparison with PTCs harbouring BRAF or TERT promoter mutation alone. The combination of BRAF and TERT promoter mutations could classify PTCs into four distinct risk groups with decreasing aggressiveness as follows: coexisting BRAF and TERT > TERT alone= BRAF alone > no mutations. Conclusion The risk stratification of PTC based on these four genotypes can help improve the clinical management of PTCs by identifying the group of PTCs with the highest aggressiveness. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Context.--Despite great interest in using whole slide imaging (WSI) in pathology practice and education, few pathology journals have published WSI pertinent to articles within their pages or as supplemental materials. Objective.--To evaluate whether there is measurable added educational value of including WSI in publications. Design.--Thirty-seven participants, 16 (43.3%), 15 (40.5%), and 6 (16.2%) junior pathology residents (postgraduate year 1-2), senior pathology residents (postgraduate year 3-4), and board-certified pathologists, respectively, read a sequence of 10 journal articles on a wide range of pathology topics. A randomized subgroup also reviewed the WSI published with the articles. Both groups completed a survey tool assessing recall of text-based content and of image-based material pertinent to the diseases but not present in the fixed published images. Results.--The group examining WSI had higher performance scores in 72% of image-based questions (36 of 50 questions) as compared with the non-WSI group. As an internal study control, the WSI group had higher performance scores in only 40% of text-based questions (6 of 15 questions). The WSI group had significantly better performance than the non-WSI group for image-based questions compared with text-based questions (P, .05, Fisher exact test). Conclusion.--Our study provides supporting evidence that WSI offers enhanced value to the learner beyond the text and fixed images selected by the author. We strongly encourage more journals to incorporate WSI into their publications. [ABSTRACT FROM AUTHOR]

Context.—: For equitable global health care, the United Nations has outlined Sustainable Development Goals for health in low-income and middle-income countries (LMICs) with the goal of reaching universal health care by 2030. Currently, 47% of the global population lacks access to basic diagnostics for many common diseases. The need for diagnostic access has never been more critical owing to the dramatic rise of noncommunicable diseases in LMICS. In a recent analysis, The Lancet Commission on Diagnostics estimated that 1.1 million deaths occurring on an annual basis could be avoided if the diagnostic gap were reduced to 10% for only 6 priority conditions., Objective.—: To provide a nonexhaustive summary of the progress made to overcome the barriers to adequate access and explore the potential solutions needed to achieve global diagnostic equity., Data Sources.—: Several experts in global pathology were interviewed in addition to pathologists working in low-resource settings outside of the United States. Published literature on the topic of global pathology work was analyzed and summarized to provide a cohesive snapshot of the status of global pathology., Conclusions.—: Working to increase access to diagnostics in low-resource settings will save millions of lives. The solution to the current inadequate availability of global pathology services will require a global commitment from the entire pathology and laboratory medicine community, government support, and collaboration between the public-private sectors to achieve equitable health care., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Context.—: Generative artificial intelligence (AI) technologies are rapidly transforming numerous fields, including pathology, and hold significant potential to revolutionize educational approaches., Objective.—: To explore the application of generative AI, particularly large language models and multimodal tools, for enhancing pathology education. We describe their potential to create personalized learning experiences, streamline content development, expand access to educational resources, and support both learners and educators throughout the training and practice continuum., Data Sources.—: We draw on insights from existing literature on AI in education and the collective expertise of the coauthors within this rapidly evolving field. Case studies highlight practical applications of large language models, demonstrating both the potential benefits and unique challenges associated with implementing these technologies in pathology education., Conclusions.—: Generative AI presents a powerful tool kit for enriching pathology education, offering opportunities for greater engagement, accessibility, and personalization. Careful consideration of ethical implications, potential risks, and appropriate mitigation strategies is essential for the responsible and effective integration of these technologies. Future success lies in fostering collaborative development between AI experts and medical educators, prioritizing ongoing human oversight and transparency to ensure that generative AI augments, rather than supplants, the vital role of educators in pathology training and practice., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Sickle cell disease patients have routinely been excluded from liver transplant donation due to patients historically manifesting liver disease themselves. Marginal donors have become increasingly more welcome given organ shortage. Our institution performed a liver transplant in a recipient with cholangiocarcinoma using a sickle cell disease donor liver. Postoperatively, patient progressed well and is now cancer free. Pathology indicated sickle cells, and hemosiderin present at time of transplant had largely resolved by repeat biopsy on postoperative day 5. We conclude that sickle cell disease patients should be considered as donors for liver transplant in the appropriate setting., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2023 College of American Pathologists.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Endocrinology and Metabolism.)

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., (© 2022 Japan Society of Obstetrics and Gynecology.)

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., (© 2022 Published by Elsevier Inc. on behalf of Association of Pathology Chairs.)

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., (© 2022 Wiley Periodicals LLC.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Author Jackson reports the following disclosures: Consulting: Clovis, LEAP, Cordgenics, Agenus, GSK/Tesaro; Research Funding: Lilly, Genentech, Clovis].

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.

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., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Liron Pantanowitz is a consultant for Hamamatsu., (© The Author(s) 2021.)

Background: Crizotinib has been approved for the treatment of non-small-cell lung cancer (NSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion. This drug has also been granted breakthrough designation for NSCLCs with MET exon 14 alterations., Objective: This systematic review and meta-analysis aimed to investigate the efficacy and safety of crizotinib in patients with these diseases., Methods: We searched PubMed and Web of Science for relevant studies. Meta-analysis of proportions was conducted to calculate the pooled rate of complete response, partial response, stable disease, progressive disease, disease control rate (DCR), objective response rate (ORR), and drug adverse effects (AEs) of crizotinib in NSCLCs with ROS1 rearrangement or MET alterations., Results: A total of 20 studies were included for meta-analysis. Among patients with ROS1-positive NSCLC, crizotinib exhibited a pooled DCR of 93.2% (95% confidence interval [CI] 90.8-95.5) and a pooled ORR of 77.4% (95% CI 72.8-82.1). The median progression-free survival (PFS) and overall survival (OS) of patients in this group was 14.5 and 32.6 months, respectively. For NSCLC with MET alterations, crizotinib was associated with a lower efficacy (DCR 78.9% [95% CI 70.3-87.4] and ORR 40.6% [95% CI 28.3-53.0]). The median PFS was 5.2 months, and median OS was 12.7 months. The most common drug AEs were vision impairment (43.7%), edema (42.9%), and fatigue (40.1%)., Conclusion: Our study highlighted and confirmed the efficacy of crizotinib in patients with NSCLC with ROS1 or MET genetic alterations. Crizotinib had remarkable effects on advanced NSCLC with ROS1 fusion, as previously reported. However, the role of this targeted therapy in MET-altered NSCLC remains investigational.

Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of histologic classification. BRAF mutation, especially BRAF V600E, is common in a subset of gliomas and may represent a potential prognostic marker. The aim of our study is to investigate the potential use of BRAF mutations on prognosis of glioma patients. Four electronic databases were searched for potential articles, including PubMed, Scopus, ISI Web of Science, and Virtual Health Library (VHL). Data of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were directly obtained from original papers or indirectly estimated from Kaplan Meier curve (KMC). A random effect model weighted by inverse variance method was used to calculate the pooled HR. From 705 articles, we finally included 11 articles with 1308 glioma patients for the final analysis. The overall estimates showed that BRAF V600E was associated with an improved overall survival (OS) in glioma patients (HR = 0.60; 95% CI = 0.44-0.80). Results for progression-free survival (PFS), however, were not statistically significant (HR = 1.39; 95% CI = 0.82-2.34). In subgroup analyses, BRAF V600E showed its effect in improving survival in pediatric and young adult gliomas (under 35 years) but did not have prognostic value in old adult. Additionally, BRAF V600E was only associated with a favorable prognosis in lower grade glioma. Our meta-analysis provides evidence that BRAF mutation has a favorable prognostic impact in gliomas and its prognostic value might be dependent on patient age and tumor grade. This mutation can be used as a prognostic factor in glioma but additional studies are required to clarify its prognostic value taking into account other confounding factors.

Background: Adequacy assessment for fine-needle aspiration procedures is a standard of care in large medical centers. Although the benefits of this approach include higher adequacy rates with fewer passes, it costs cytopathologist time and affects other clinical responsibilities. The objective of the current study was to evaluate the use of mobile video streaming (FaceTime) technology with the help of smartphone adapters attached to microscopes for remote adequacy assessment of cytologic samples., Methods: The study consisted of 2 phases: Phase 1 was a retrospective assessment of 25 samples by a primary pathologist with simultaneous streaming to a second pathologist using a smartphone (iPhone/iPad) FaceTime connection. Data on the adequacy of each sample and preliminary diagnoses were recorded. In phase 2, live cases were assessed prospectively by an onsite primary pathologist and by a remote pathologist using an iPhone/iPad-FaceTime connection. The testing phase involved prospective assessment of additional samples with a resident or cytotechnologist as the slide driver., Results: In phase 1, retrospective evaluation of 25 samples yielded considerable agreement (22 of 25 samples; 88%) between onsite and remote adequacy assessments. Three samples (12%) yielded results that did not agree, including 2 samples that were read as adequate in the onsite evaluation that were assessed as indeterminate using FaceTime. In phase 2 and in the testing phase, 14 samples exhibited considerable agreement on both adequacy and preliminary diagnosis (6 samples in phase 2 and 8 samples in the testing phase) and are currently available for reporting. Problems encountered include software version standardization, camera alignment, and (rarely) comprehension of the audio stream., Conclusions: The current data indicate that iPhone/iPad FaceTime technology can be used to perform remote adequacy assessments of fine-needle aspirations and can help save valuable time for pathologists., (© 2015 American Cancer Society.)

This article presents an overview of the curriculum deemed essential for trainees in pathology, with mapping to the Milestones competency statements. The means by which these competencies desired for pathology graduates, and ultimately practitioners, can best be achieved is discussed. The value of case (problem)-based learning in this realm, in particular the kind of integrative experience associated with hands-on projects, to both cement knowledge gained in the lecture hall or online and to expand competency is emphasized., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This article presents an overview of the curriculum deemed essential for trainees in pathology, with mapping to the Milestones competency statements. The means by which these competencies desired for pathology graduates, and ultimately practitioners, can best be achieved is discussed. The value of case (problem)-based learning in this realm, in particular the kind of integrative experience associated with hands-on projects, to both cement knowledge gained in the lecture hall or online and to expand competency is emphasized., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Human melanoma contains multipotent stem cells that express the neural crest stem cell marker CD271. CD271-expressing melanoma cells in murine xenografts give rise to metastatic tumor. However, a comprehensive clinical investigation of its role in different stages of melanomagenesis has not been well studied. We studied CD271 expression with immunohistochemistry in 11 cases of banal melanocytic nevus, 9 cases of primary cutaneous melanoma, 10 cases of primary mucosal melanoma, 5 cases of metastatic melanoma in regional lymph nodes, and 11 cases of metastatic melanoma in the brain. In addition, 9 cases of metastatic, high-grade adenocarcinomas from breast and lung to the brain were studied as controls. The staining was scored based on the number of positive cells and analyzed by student t-test. All banal melanocytic nevi showed negative to equivocal staining. Primary cutaneous melanomas showed variable patterns, mucosal melanomas were mostly negative, and metastases to lymph nodes ranged from negative to moderate positivity. In contrast, all 11 cases of metastatic melanoma to the brain showed moderate (4 cases) to strong positivity (7 cases). Metastases from lung and breast origin were used as controls and showed negative to weakly positive staining in all but one case. Statistically, CD271 has significantly increased expression in metastatic melanoma to the brain when compared to the other groups studied (P < 0.05). The findings suggest that CD271 expression is specifically increased in metastatic melanoma to the brain. Further prospective study for the role of CD271 in prediction of melanoma brain metastasis as well as prognosis assessment will be of great clinical significance.

Surgical pathologists use a variety of phrases to communicate varying degrees of diagnostic certainty which have the potential to be interpreted differently than intended. This study sought to: (1) assess the setting, varieties and frequency of use of phrases of diagnostic uncertainty in the diagnostic line of surgical pathology reports, (2) evaluate use of uncertainty expressions by experience and gender, (3) determine how these phrases are interpreted by clinicians and pathologists, and (4) assess solutions to this communication problem. We evaluated 1500 surgical pathology reports to determine frequency of use of uncertainty terms, identified those most commonly used, and looked for variations in usage rates on the basis of case type, experience and gender. We surveyed 76 physicians at tumor boards who were asked to assign a percentage of certainty to diagnoses containing expressions of uncertainty. We found expressions of uncertainty in 35% of diagnostic reports, with no statistically significant difference in usage based on age or gender. We found wide variation in the percentage of certainty clinicians assigned to the phrases studied. We conclude that non-standardized language used in the communication of diagnostic uncertainty is a significant source of miscommunication, both amongst pathologists and between pathologists and clinicians., (Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.)

We recently reported three cases of metastatic melanoma that does not express S100, HMB45, Melan A and Tyrosinase. A concurrent cutaneous scalp primary melanoma was identified later in one of the cases, which showed strong expression of these markers. The difference in immunophenotype between the primary melanoma and its metastasis in the parotid gland in this case raised the question of the biological significance of the expression of these markers and metastatic potential. To address this question, we utilized microarray comparative genomic hybridization (aCGH) to compare the cytogenetic features between the primary and metastatic melanoma. We observed chromosomal gains including 6p, entire chromosome 7, and 8q11.1-q24.3 in both primary and metastatic tumors. However, the metastatic lesion showed unique additional copy of chromosomal 7q, and loss of chromosome 9p24.3-q13 and chromosome 4, which included Melan A encoding gene region in 9p24.1. The above findings suggest the unique cytogenetic changes in the parotid lesion are most likely related to the metastatic behavior, as well as responsible for loss of multiple melanocytic marker expression in the metastatic melanoma for this case.

Metastatic malignant melanoma has a wide spectrum of histopathologic patterns and often lacks melanin pigment. Without a known primary tumor, the diagnosis of metastatic malignant melanoma relies on a combination of morphology and immunohistochemical profile. Infrequently, commonly used markers for melanoma (S100, HMB45, Melan-A and Tyrosinase A) are negative. These cases pose critical diagnostic challenges. Recent studies show that Microphthalmia Transcription Factor (MITF) has high sensitivity (88-100%) and specificity for metastatic melanoma. We are reporting here three cases of high grade tumors that were studied by a comprehensive immunohistochemical panel including cytokeratins, S100, HMB-45, Melan A, Tyrosinase, and MITF. All three tumors were also analyzed for the presence of BRAF mutations. All three metastatic tumors were negative for S100, Melan A, HMB-45 and Tyrosinase but positive for MITF. Subsequent to the diagnoses, previously existing or concurrent primary melanomas were identified in 2 of the 3 cases. Interestingly, S100, Melan A, and HMB-45 were positive in the primary tumors. No BRAF (V600E) mutations were identified in the three metastatic melanomas and CD 117 (c-kit) was positive in one of the cases. In summary, our experience shows that MITF can be a valuable adjunct in the diagnosis of metastatic tumors that are suspicious for melanoma but negative for other melanoma markers.

Pathology reports represent a rich data source for cancer registries. The College of American Pathologists (CAP) Cancer Checklists present pathology reports in synoptic form and allow registries to be updated electronically. To assess the challenge of employing the CAP Cancer Checklists in pathology laboratories and transmitting that information to cancer registries, we conducted a pilot project: the Reporting Pathology Protocols project (RPP2). The RPP2 project was a multi-year, "proof of concept" demonstration that assessed pathology report-generated data for 3 CAP Cancer Checklists (breast, prostate, and melanoma) in several different cancer registry-pathology laboratory combinations in 3 states. Collaborating pathology laboratories and state cancer registries in California, Maine, and Pennsylvania identified key questions (queries) to address in the course of the project, developed and tested standardized HL7 messaging specifications to link senders and recipients, and then assessed the actual process results using either parallel reporting or retrospective-prospective cases for each tumor type. Successful electronic transfer and capture of pertinent data elements for numerous examples of each tumor type was accomplished in each participating cancer registry/reporting laboratory/information system combination. We noted shortcomings in the electronically encoded CAP Checklists as opposed to text-based reports, particularly for breast cancers. We uncovered opportunities to improve Checklists and the information systems that incorporate them. Workflow, productivity, and timeliness of reporting are areas where electronically encoded reports may enhance cancer registry processes. The accuracy and completeness of electronically encoded data appears largely comparable to text-based data, but subject to the degree of synchrony between the formats of text-based and electronic reports.