Is Social Media Here to Stay?: Survey Results Indicate Increasing Pathologist Interest and Engagement Over Time.

CONTEXT.­: Social media has become widely adopted by pathologists and other physicians for professional purposes. While engagement has likely increased over time, there remain few concrete data regarding attitudes toward its use. OBJECTIVE.­: To assess pathologists' use of and attitudes toward social media over time. DESIGN.­: We created a survey regarding personal and professional use of social media and circulated it via multiple channels in December 2017 and again in February 2022. Results of the 2 surveys were compared for statistically significant differences. RESULTS.­: The 2017 survey was completed by 97 participants, and the 2022 survey by 305 participants. Respondents were predominantly female and academics, included pathologists in all age categories and all time-in-practice length. In both surveys, Twitter (now X) was the most popular platform for professional use and Facebook was the most popular for personal use. Professional barriers to social media use remained consistent between the 2 surveys, including the amount of time required. Education was seen as the main benefit of social media use in both surveys, while other benefits such as networking and increasing professional visibility were endorsed significantly less often in the second survey. While the second survey received more than 3 times as many responses as the first, several aspects of social media use (mainly demographics) remained similar during the timeframe, while other aspects (such as usage and perceived values) decreased. CONCLUSIONS.­: Pathologists continue to find social media valuable. Barriers remain, though overall pathologists of all ages and practice settings appear receptive to using social media to further educational and other opportunities.

How do cytopathologists learn fine needle aspiration techniques? An international survey.

INTRODUCTION: Fine needle aspiration cytology (FNAC) is a widely accepted diagnostic technique, but performance varies according to expertise. Little is known about variation in FNAC training practices worldwide. We surveyed pathologists using social media networks to determine FNAC training practices internationally. DESIGN: Pathologists were surveyed on questions related to FNAC simulation training using direct messaging on the Twitter and WhatsApp platforms. Survey responses over a period of 2 weeks were collected. RESULTS: In total, 149 pathologists participated (96.1% response rate). The respondents came from 24 countries and 87 institutions. The majority of the pathologists (63.8%) performed FNAC directly on patients for the first time. Only 36.2% of them had simulation instruction during their training. It was performed on food items such as fruit (64.8%), surgical specimens (37.0%), autopsies (13.0%) and others (9.3%), including commercially available phantom simulators for ultrasound-guided FNAC (US-FNAC) (two pathologists). DISCUSSION: Most pathologists did not receive formal training in a simulated environment, and of the pathologists who had simulation instruction, food items were commonly used for education. A few participants used a commercial US-FNAC simulator, but since most pathologists perform FNAC by palpation, this method of simulation training is not applicable to many practices. Social media is an effective and efficient way to perform survey research, yielding a very high response rate.

Virtual Pathology Elective, Real Education: The PathElective.com Experience as a Model for Novel Pathology Pedagogy and a Primer for Curricular Evolution.

CONTEXT.­: PathElective.com was created in response to the pandemic's restrictions on interactions with trainees, and since has been incorporated into many training programs worldwide, serving as a unique means of delivering high-quality pathology and laboratory medical education at multiple levels of training. OBJECTIVE.­: To analyze student usage, performance, and satisfaction to provide insight into the effectiveness of virtual education to guide curricular evolution. DESIGN.­: Squarespace (Squarespace, Inc) was used for website development and to collect website analytics. Students were assessed before and after course participation using a dual-form crossover quiz design. Quiz data were anonymous and analyzed with a paired t test to account for varying student background. A novel analysis was performed aimed at examining the attrition rate of students across multiple modules. RESULTS.­: Over the study period (May 1, 2020 to October 31, 2021), PathElective.com received 577 483 page views, 126 180 visits, 59 928 unique visitors, and 10 278 registered users who earned 15 305 certificates. A total of 7338 premodule and postmodule quiz pairs were analyzed. The overall average increase in score was 13.83% (P = .02). All but 5 of the 56 courses experienced a statistically significant increase in score. All courses received median scores of Very Satisfied/Satisfied in all 6 assessment domains. Aggregate attrition data revealed a unique, negative polynomial relationship (R2 = 0.656). CONCLUSIONS.­: PathElective.com is a free, effective means of enhancing anatomic/clinical pathology training in medical education. These analyses offer a unique perspective on the online user experience and could guide the development of future online medical education resources.

Top Ten Oncocytic Head and Neck Lesions to Contemplate.

BACKGROUND: Oncocytes are a component of many metaplastic and neoplastic lesions throughout the head and neck area, primarily originating in salivary/seromucinous glands and the thyroid gland. In addition, other lesions can contain cells that mimic oncocytes (pseudo-oncocytes); these can be of epithelial or non-epithelial origin. METHODS: Review article. RESULTS: Oncocytic metaplasia is common in seromucinous glands throughout the upper aerodigestive tract, most notable in the oral cavity, nasopharynx and larynx. The main oncocytic salivary gland neoplasms are Warthin tumor and oncocytoma. Infarction of Warthin tumor may lead to recognition difficulties. Oncocytic subtypes of mucoepidermoid carcinoma and intraductal carcinoma have morphologic and immunohistochemical features that allow distinction from major oncocytic entities. Oncocytic thyroid tumors include adenoma, carcinoma (follicular, papillary and medullary), along with poorly differentiated tumors. Oncocytic papillary sinonasal and middle ear tumors must be distinguished from low grade adenocarcinomas. Pseudo-oncocytic entities include paraganglioma, Langerhans cell histiocytosis, giant cell tumor, rhabdomyoma, and metastatic tumors. CONCLUSIONS: Correct diagnosis of oncocytic head and neck lesions requires a knowledge of the spectrum of possible entities, their characteristic sites of occurrence, architecture, histomorphology, and immunohistochemistry. Oncocytic subtypes of several newly described entities are now recognized. Both epithelial and non-epithelial mimics of oncocytes exist. The molecular features of oncocytic tumors can be helpful in their diagnosis and understanding their pathogenesis.

Retracted: Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats With Reflux Esophagitis.

This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study. Reference: Jia-Yuan Zhuang, Zhi-Yao Chen, Tao Zhang, Du-Peng Tang, Xiao-Yin Jiang, Ze-Hao Zhuang. Effects of Different Ratio of n-6/n-3 Polyunsaturated Fatty Acids on the PI3K/Akt Pathway in Rats with Reflux Esophagitis. Med Sci Monit, 2017; 23: 542-547. DOI: 10.12659/MSM.898131.

Roles of lncRNAs in pancreatic ductal adenocarcinoma: Diagnosis, treatment, and the development of drug resistance.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. DATA SOURCES: We carried out a systematic review on lncRNAs-based research in the context of pancreatic cancer and presented an overview of the updated information regarding the molecular mechanisms underlying lncRNAs-modulated pancreatic cancer progression and drug resistance, together with their potential value in diagnosis, prognosis, and treatment of PDAC. Literature mining was performed in PubMed with the following keywords: long non-coding RNA, pancreatic ductal adenocarcinoma, pancreatic cancer up to January 2022. Publications relevant to the roles of lncRNAs in diagnosis, prognosis, drug resistance, and therapy of PDAC were collected and systematically reviewed. RESULTS: LncRNAs, such as HOTAIR, HOTTIP, and PVT1, play essential roles in regulating pancreatic cancer cell proliferation, invasion, migration, and drug resistance, thus may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. They participate in tumorigenesis mainly by targeting miRNAs, interacting with signaling molecules, and involving in the epithelial-mesenchymal transition process. CONCLUSIONS: The functional lncRNAs play essential roles in pancreatic cancer cell proliferation, invasion, migration, and drug resistance and have potential values in diagnosis, prognostic prediction, and treatment of PDAC.

Pathologist-performed ultrasound-guided fine needle aspiration biopsies of extrathyroidal sites: An observational study.

BACKGROUND: Pathologist-performed ultrasound-guided fine needle aspiration (USFNA) biopsies have become an increasingly important component of the interventional cytopathologist's toolbox. However, its application varies between institutions, and there is limited literature describing its performance characteristics when utilized in extrathyroidal sites. Here we review our institutional experience within our pathologist-run FNA clinic. METHODS: A retrospective review was conducted of pathologist-performed USFNAs of extrathyroidal sites over a 9-year period. Data collected included lesion site, size, patient age, patient gender, diagnostic category, and corresponding results from surgical resection when available. The diagnosis on surgical resection was considered the gold standard for determining discordance rates. RESULTS: A total of 143 pathologist-performed USFNAs of extrathyroidal lesions were performed from October 2011 to October 2020. These encompassed a wide range of sites, with most biopsies from the head and neck. The mean recorded size was 2.2 cm, with a range of 0.6-6 cm. Larger lesions (over 2 cm) were more likely to be noted in challenging locations, demonstrate difficult features, or be cystic. Most (n = 133) biopsies were sufficient for diagnosis, with a non-diagnostic rate of 7% (n = 10). Accuracy when compared to subsequent surgical resection was high, with sensitivity of 89%, specificity of 93%, positive predictive value of 94%, and negative predictive value of 87%. CONCLUSION: Our experience supports that pathologist-performed USFNA of extrathyroidal lesions-even those with challenging features-can result in excellent diagnostic yield and accuracy. The addition of USFNA to the interventional cytopathologists' repertoire can be a valuable tool to enhance patient care.

Remission of progressive metastatic castration-resistant prostate cancer during abiraterone therapy following unilateral adrenalectomy for a functioning adrenal adenoma.

Despite advances and introduction of new therapies in the last decade, metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. The development of androgen axis-targeted therapies such as abiraterone acetate, enzalutamide and darolutamide can prolong survival in mCPRC; however, resistance remains a barrier to prolonged response, necessitating exploration into resistance mechanisms and locoregional therapies. Here, we describe a patient with mCRPC that was progressing on abiraterone acetate. He was also found to have primary hyperaldosteronism from a functional adrenal adenoma, and thus he had a partial adrenalectomy to remove this tumour. Pathology confirmed an aldosterone-producing adrenal adenoma. After his adrenalectomy, he had a sharp decline in both his PSA (prostate specific antigen) and testosterone levels, and he enjoyed a year-long period of remission after his adrenalectomy. We propose several explanations for his response, the most likely being that his adenoma was producing both aldosterone and androgens. This is a unique case of mCRPC responding to partial adrenalectomy from a functional adrenal adenoma, and it raises insights that warrant further investigation into underlying mechanisms of resistance to androgen-targeted therapies.

Juxtametallic Bipolar Bone Radiofrequency Ablation: Thermal Monitoring in an Ex-Vivo Model with Specimen MRI and Histopathologic Correlation.

PURPOSE: To measure the ablation zone temperature and nontarget tissue temperature during radiofrequency (RF) ablation in bone containing metal instrumentation versus no metal instrumentation (control group). MATERIALS AND METHODS: Ex vivo experiments were performed on 15 swine vertebrae (control, n = 5; titanium screw, n = 5; stainless steel screw, n = 5). Screws and RF ablation probe were inserted identically under fluoroscopy. During RF ablation (3 W, 5 minutes), temperature was measured 10 mm from RF ablation centerpoint and in muscle contacting the screw. Magnetic resonance (MR) imaging, gross pathologic, and histopathologic analyses were performed on 1 specimen from each group. RESULTS: Ablation zone temperatures at 2.5 and 5 minutes increased by 12.2 °C ± 2.6 °C and 21.5 °C ± 2.1 °C (control); 11.0 °C ± 4.1 °C and 20.0 °C ± 2.9 °C (juxta-titanium screw), and 10.0 °C ± 3.4 °C and 17.2 °C ± 3.5 °C (juxta-stainless steel) screw; differences among groups did not reach significance by analysis of variance (P = .87). Mixed-effects linear regression revealed a statistically significant increase in temperature over time in all 3 groups (4.2 °C/min ± 0.4 °C/min, P < .001). Compared with the control, there was no significant difference in the temperature change over time for titanium (-0.3 °C/min ± 0.5 °C/min, P = .53) or steel groups (-0.4 °C/min ± 0.5 °C/min, P = .38). The mean screw temperature at the final time point did not show a statistically significant change compared with baseline in either the titanium group (-1.2 °C ± 2.3 °C, P = .50) or steel group (2.6 °C ± 2.9 °C, P = .11). MR imaging and pathologic analyses revealed homogeneous ablation without sparing of the peri-hardware zones. CONCLUSIONS: Adjacent metallic instrumentation did not affect the rate of or absolute increase in temperature in the ablation zone, did not create peri-metallic ablation inhomogeneities, and did not result in significant nontarget heating of muscle tissue in contact with the metal instrumentation.

Crystals and crystalloids in cytopathology: Incidence and importance.

Many crystals and crystal-like structures may be encountered in cytopathology practice and can represent both beautiful novelties and diagnostic aids. The authors present an organ-specific review of the published literature on crystals combined with personal experiences. The purpose is not only to serve as a reference guide by highlighting the clinical and morphologic features of crystals, crystalloids, and crystal-like structures but also to review their significance and to offer reporting strategies in cases that bear management implications.

Pathologist-performed ultrasound-guided fine-needle aspirations of the thyroid: A single institution observational study.

BACKGROUND: Ultrasound-guided fine-needle aspiration biopsies (USFNAs) are increasingly performed by pathologists. This study was designed to assess the diagnostic yield and characterization of thyroid nodules biopsied at a teaching hospital setting in which both attending physicians and trainees are involved in the performance of USFNAs. METHODS: A retrospective study of pathologist-performed USFNAs of thyroid cases was performed over a period of 9 years at a tertiary medical center. Data collected included patient characteristics and The Bethesda System diagnostic categories. RESULTS: Over the study period, 1531 USFNAs of thyroid nodules were performed in the pathology-based clinic, with 1209 lesions in females and 322 in males. Ninety-three percent of samples were sufficient for diagnosis (n = 1420). The majority of nodules biopsied were benign (65.4%, n = 1002). Overall, 3.1% of nodules biopsied were diagnostic of malignancy (n = 47). The number of USFNAs over the years showed a rapid increase initially, with a coronavirus disease 2019-related decrease in 2020. CONCLUSIONS: The authors report their experience with thyroid USFNA over nearly a decade. The most common diagnosis was benign and the second most common was Bethesda category III. Lesions that were diagnostic of malignancy were relatively uncommon. Over the study period, the results showed that at a large tertiary care center in which USFNAs were performed by trainees as well as attending physicians, the diagnostic yield was good with a majority of thyroid nodules biopsied associated with a definitive diagnosis.

Pathology Engagement in Global Health: Survey Data of Global Pathology Interest and Barriers.

CONTEXT.­: Although pathology is essential to almost every practice in medicine, laboratory medicine professionals do not routinely volunteer in global health practice. OBJECTIVE.­: To gather information about the experience and interest levels of the pathology community in global health work. DESIGN.­: Data were analyzed from an 8-question, online, anonymous survey directed toward anyone working in the field of pathology and laboratory medicine. The survey collected data from respondents on their interest level in participating in global health pathology, potential barriers to participation, and the types of volunteer opportunities that would be of interest. RESULTS.­: A total of 267 people participated in the survey, of whom 142 (53%) were American citizens. One hundred seventy (64%) indicated that they had never volunteered in a low-resource setting. The majority of respondents (237; 89%) indicated interest in global pathology opportunities. More than half of the 267 respondents indicated interest in short-term trips (136; 51%), digital education opportunities (138; 52%), and reviewing slides/cases digitally (160; 60%). Lack of time to travel and lack of financial support were the 2 most cited reasons for lack of participation. One hundred nine respondents (41%) indicated that they were "willing and able, but do not know where to start." CONCLUSIONS.­: Our data demonstrate that laboratory medicine professionals are highly interested in global pathology efforts, but factors such as lack of time, lack of funding, and lack of knowledge of potential volunteer opportunities are barriers to participation. A significant number of respondents were willing and able to participate, indicating that pathology and laboratory medicine professionals may be an untapped resource for global health volunteers.

COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study.

BACKGROUND: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). METHODS: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. RESULTS: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). CONCLUSIONS: The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.

Teaching interventional cytopathology.

Interventional cytopathology is a unique area of pathology, where cytopathologists play a primary role in obtaining fine needle aspiration biopsies and/or making determinations through rapid on-site evaluations to guide sample procurement in real-time. Unsurprisingly, experience and skill are directly related to success in these endeavors, and both can be fostered with formal instruction. There is a wealth of resources available to aid in teaching interventional cytopathology, including instructional videos, courses, and model phantoms which can help to build familiarity and confidence. These tools can provide a basic framework upon which skills can be developed through in-person guidance, real-time feedback and practice. This article reviews the tools available to enhance training, details the authors' institutional experience in teaching interventional cytopathology at a tertiary care center, and provides recommendations and pearls for success in this endeavor.

Performance of repeat cytology with reflex ThyroSeq genomic classifier for indeterminant thyroid cytology.

BACKGROUND: The American Thyroid Association recommends either repeat fine-needle aspiration biopsy (FNAB) or molecular testing (eg, ThyroSeq) of Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS]) nodules to provide further risk stratification. How a testing algorithm that uses ancillary molecular tests performs as a reflex test for repeat sampling of indeterminant nodules remains unclear. METHODS: Thyroid FNABs performed over a 24-month period that received a diagnosis of AUS/FLUS and underwent subsequent FNAB were analyzed. RESULTS: In total, 187 patients were identified who received an FNAB diagnosis of AUS/FLUS and had repeat sampling. Of these patients, 64% received a subsequent indeterminant diagnosis on repeat biopsy: 7 (3.7%) repeat biopsies were diagnosed as nondiagnostic/unsatisfactory, 104 (55.6%) were diagnosed as AUS/FLUS, and 8 (4.3%) were diagnosed as follicular neoplasm/suspicious for follicular neoplasm. Of the repeat biopsied nodules, 63% underwent subsequent testing with ThyroSeq version 3. The diagnostic performance was calculated using only surgically confirmed nodules (sensitivity, 100%; specificity, 30%; positive predictive value, 41%; negative predictive value, 100%) and by assigning nonresected nodules with negative ThyroSeq or benign cytology results as benign (sensitivity, 100%; specificity, 88%; positive predictive value, 41%; negative predictive value, 100%). CONCLUSIONS: In the majority of patients, repeat FNAB for AUS/FLUS did not preclude subsequent molecular ancillary testing because of the high rate of indeterminant results on repeat biopsy. The diagnostic performance of the testing algorithm reported here was very similar to other reports using either repeat biopsy or molecular testing alone. Ultimately, the algorithm of performing molecular testing on repeat indeterminant nodules increased the number of biopsies performed and lengthened the time to definitive risk stratification without a disproportionate decrease in the use of molecular testing or an appreciable improvement in diagnostic performance.

Pre-existing Castration-resistant Prostate Cancer-like Cells in Primary Prostate Cancer Promote Resistance to Hormonal Therapy.

BACKGROUND: Hormonal therapy targeting the androgen receptor inhibits prostate cancer (PCa), but the tumor eventually recurs as castration-resistant prostate cancer (CRPC). OBJECTIVE: To understand the mechanisms by which subclones within early PCa develop into CRPC. DESIGN, SETTING, AND PARTICIPANTS: We isolated epithelial cells from fresh human PCa cases, including primary adenocarcinoma, locally recurrent CRPC, and metastatic CRPC, and utilized single-cell RNA sequencing to identify subpopulations destined to become either CRPC-adeno or small cell neuroendocrine carcinoma (SCNC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We revealed dynamic transcriptional reprogramming that promotes disease progression among 23226 epithelial cells using single-cell RNA sequencing, and validated subset-specific progression using immunohistochemistry and large cohorts of publically available genomic data. RESULTS AND LIMITATIONS: We identified a small fraction of highly plastic CRPC-like cells in hormone-naïve early PCa and demonstrated its correlation with biochemical recurrence and distant metastasis, independent of clinical characteristics. We show that progression toward castration resistance was initiated from subtype-specific lineage plasticity and clonal expansion of pre-existing neuroendocrine and CRPC-like cells in early PCa. CONCLUSIONS: CRPC-like cells are present early in the development of PCa and are not exclusively the result of acquired evolutionary selection during androgen deprivation therapy. The lethal CRPC and SCNC phenotypes should be targeted earlier in the disease course of patients with PCa. PATIENT SUMMARY: Here, we report the presence of pre-existing castration-resistant prostate cancer (CRPC)-like cells in primary prostate cancer, which represents a novel castration-resistant mechanism different from the adaptation mechanism after androgen deprivation therapy (ADT). Patients whose tumors harbor increased pre-existing neuroendocrine and CRPC-like cells may become rapidly resistant to ADT and may require aggressive early intervention.

A multiple instance learning approach for detecting COVID-19 in peripheral blood smears.

A wide variety of diseases are commonly diagnosed via the visual examination of cell morphology within a peripheral blood smear. For certain diseases, such as COVID-19, morphological impact across the multitude of blood cell types is still poorly understood. In this paper, we present a multiple instance learning-based approach to aggregate high-resolution morphological information across many blood cells and cell types to automatically diagnose disease at a per-patient level. We integrated image and diagnostic information from across 236 patients to demonstrate not only that there is a significant link between blood and a patient's COVID-19 infection status, but also that novel machine learning approaches offer a powerful and scalable means to analyze peripheral blood smears. Our results both backup and enhance hematological findings relating blood cell morphology to COVID-19, and offer a high diagnostic efficacy; with a 79% accuracy and a ROC-AUC of 0.90.

Excellence Available Everywhere: The Virtual Pathology Grand Rounds Experience.

OBJECTIVES: The goal is to describe the use of a virtual platform in the delivery of Virtual Pathology Grand Rounds (VPGR) and discuss the overall experience from the perspective of hosts, speakers, and participants. METHODS: Zoom was a natural choice for an online format because virtual platforms had been increasingly used to conduct meetings and medical education. VPGR hosted 14 speakers on a variety of topics, including subspecialty anatomic pathology material, digital pathology, molecular pathology, and medical education. RESULTS: There were 221 registrants and 114 participants for the first lecture, reaching a maximum of 1,268 registrants for the 12th lecture and the maximum limit of 300 participants during 3 lectures. Speakers stated that VPGR conveniently provided career-building opportunities through partnerships with host universities and remote attendance. Participants identified a lack of interpersonal communication and technical challenges as downsides. CONCLUSIONS: VPGR serves as strong proof of concept for the feasibility and demand for high-quality, remote academic pathology talks.