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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

Potential response to curcumin in infantile hemangioendothelioma of the liver.

A case of life-threatening infantile hemangioendothelioma of the liver in a 6-month-old infant treated successfully with the dietary supplement curcumin is reported, with 6-year follow-up. Implications for pathogenesis based on sites of action of curcumin are considered.

The combined positive impact of Lean methodology and Ventana Symphony autostainer on histology lab workflow.

BACKGROUND: Histologic samples all funnel through the H&E microtomy staining area. Here manual processes intersect with semi-automated processes creating a bottleneck. We compare alternate work processes in anatomic pathology primarily in the H&E staining work cell. METHODS: We established a baseline measure of H&E process impact on personnel, information management and sample flow from historical workload and production data and direct observation. We compared this to performance after implementing initial Lean process modifications, including workstation reorganization, equipment relocation and workflow levelling, and the Ventana Symphony stainer to assess the impact on productivity in the H&E staining work cell. RESULTS: Average time from gross station to assembled case decreased by 2.9 hours (12%). Total process turnaround time (TAT) exclusive of processor schedule changes decreased 48 minutes/case (4%). Mean quarterly productivity increased 8.5% with the new methods. Process redesign reduced the number of manual steps from 219 to 182, a 17% reduction. Specimen travel distance was reduced from 773 ft/case to 395 ft/case (49%) overall, and from 92 to 53 ft/case in the H&E cell (42% improvement). CONCLUSIONS: Implementation of Lean methods in the H&E work cell of histology can result in improved productivity, improved through-put and case availability parameters including TAT.

Rare Jejunal Diverticular Bleeding.

Severe gastrointestinal bleeding (GIB) secondary to jejunal diverticulosis (JD) is very rare. Delay in establishing a diagnosis is common and GIB from JD is associated with significant morbidity and mortality. We report an illustrative case diagnosed by push enteroscopy and managed with surgery.

Educational Value of Digital Whole Slides Accompanying Published Online Pathology Journal Articles: A Multi-Institutional Study.

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.

Performance validation in anatomic pathology: successful integration of a new classification system into the practice setting using the updated lung non-small cell carcinoma recommendations.

CONTEXT: The new, international, multidisciplinary classification of lung adenocarcinoma, from the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society, presents a paradigm shift for diagnostic pathologists. OBJECTIVE: To validate our ability to apply the recommendations in reporting on non-small cell lung cancer cases. DESIGN: A test based on the new non-small cell lung cancer classification was administered to 16 pathology faculty members, senior residents, and fellows before and after major educational interventions, which included circulation of articles, electronic presentations, and live presentations by a well-known lung pathologist. Surgical and cytologic (including cell-block material) reports of lung malignancies for representative periods before and after the educational interventions were reviewed for compliance with the new guidelines. Cases were scored on a 3-point scale, with 1 indicating incorrect terminology and/or highly inappropriate stain use, 2 indicating correct diagnostic terminology with suboptimal stain use, and 3 indicating appropriate diagnosis and stain use. The actual error type was also evaluated. RESULTS: The average score on initial testing was 55%, increasing to 88% following the educational interventions (60% improvement). Of the 54 reports evaluated before intervention, participants scored 3 out of 3 points on 15 cases (28%), 2 of 3 on 31 cases (57%), and 1 of 3 on 8 cases (15%). Incorrect use of stains was noted in 23 of 54 cases (43%), incorrect terminology in 15 of 54 cases (28%), and inappropriate use of tissue, precluding possible molecular testing, in 4 out of 54 cases (7%). Of the 55 cases after intervention, participants scored 3 out of 3 points on 46 cases (84%), 2 of 3 on 8 cases (15%), and 1 of 3 on 1 case (2%). Incorrect use of stains was identified in 9 of 55 cases (16% of total reports), and inappropriate use of tissue, precluding possible molecular testing, was found in 1 of the 55 cases (2%). CONCLUSIONS: The study results demonstrated marked improvement in the pathologists' understanding and application of the new non-small cell lung cancer classification recommendations, which was sufficient to validate our use of the system in routine practice. The results also affirm the value of intensive education on, and validation of, pathologists' use of a classification or diagnostic algorithm.

Communicating diagnostic uncertainty in surgical pathology reports: disparities between sender and receiver.

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.

Progress toward improved leadership and management training in pathology.

CONTEXT: Competency gaps in leadership and laboratory management skills continue to exist between what training programs deliver and what recent graduates and future employers expect. A number of recent surveys substantiate this. Interest in delivering content in these areas is challenged by time constraints, the presence of knowledgeable faculty role models, and the necessary importance placed on diagnostic skills development, which overshadows any priority trainees have toward developing these skills. OBJECTIVE: To describe the problem, the near-future horizon, the current solutions, and the recommendations for improving resident training in laboratory management. DATA SOURCES: The demands of new health care delivery models and the value being placed on these skills by the Pathology Milestones and Next Accreditation System initiative of the Accreditation Council for Graduate Medical Education for training programs emphasizes their importance. This initiative includes 6 milestone competencies in laboratory management. Organizations like the American Society for Clinical Pathology, the American Pathology Foundation, the College of American Pathologists, and the Association of Pathology Chairs Program Directors Section recognize these competencies and are working to create new tools for training programs to deploy. CONCLUSIONS: It is our recommendation that (1) every training program develop a formal educational strategy for management training, (2) greater opportunity and visibility be afforded for peer-reviewed publications on management topics in mainstream pathology literature, and (3) pathology milestones-oriented tools be developed to assist program directors and their trainees in developing this necessary knowledge and skills.

Melanotic Xp11 translocation renal cancer: report of a case with a unique intratumoral sarcoid-like reaction.

BACKGROUND: Melanotic Xp11 translocation renal cancer is a rare tumor belonging to the family of microphthalmia-associated transcription factor (MiTF)/transcription factor E (TFE) neoplasms. This tumor family also includes alveolar soft part sarcoma, perivascular epithelioid cell neoplasms, Xp11 translocation renal cell carcinoma, and melanoma. To date, six confirmed melanotic Xp11 translocation cancers (five renal, one ovarian) have been reported in the literature. CASE REPORT: Here, we report the clinical, histologic, immunohistochemical, and molecular features of a unique melanotic Xp11 translocation renal cancer arising in a 34-year-old African-American female. Histologically, the tumor was composed of epithelioid tumor cells arranged in a nested pattern. The cells had clear to eosinophilic granular cytoplasm, vesicular nuclear chromatin, and prominent nucleoli. Multifocal intracytoplasmic deposits of granular brown melanin pigment were identified and confirmed by Fontana-Masson stain. An unusual histologic feature, not previously reported in melanotic Xp11 translocation renal cancer, was a sarcoid-like granulomatous reaction consisting of tight epithelioid granulomas with lymphocytic cuffing, numerous giant cells, and calcifications. Nuclear transcription factor E3 expression was identified by immunohistochemistry and TFE3 rearrangement was confirmed by fluorescence in situ hybridization. Additional immunohistochemical findings included immunoreactivity for HMB45, cathepsin K, and progesterone receptor; negative staining was seen with actin, desmin, cytokeratins, epithelial membrane antigen, CD10, vimentin, and PAX-8. The patient is currently free of disease, two years following initial clinicoradiologic presentation and twenty-two months following partial nephrectomy without additional therapy. CONCLUSION: This report further expands the spectrum of morphologic and clinical findings previously described in melanotic Xp11 translocation renal cancer, a distinctive tumor showing overlapping features between Xp11 translocation renal cell carcinoma, melanoma, and perivascular epithelioid cell neoplasms. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7225796341180634.