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Objectives We sought to assess the expression of human leukocyte antigen (HLA) proteins and β2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC). Methods A total of 953 CRC cases were evaluated by immunohistochemistry for HLA class I, HLA class II, and B2M. The expression level of these biomarkers was correlated with clinicopathologic information, BRAF V600E and mismatch repair (MMR) proteins, and the quantitated expression levels of immune cells (CD8 and CD163) and immune regulatory proteins (FoxP3, programmed cell death 1 ligand 1 [PD-L1], and LAG3). Results We found that B2M-low tumors were statistically correlated with aggressive histologic features, including higher stage, higher grade, extramural venous invasion, perineural invasion, and distant metastasis. Expression of B2M was positively correlated (R 2 = 0.3) and significantly associated with MMR-deficient tumors (P <.001); B2M-low tumors were also associated with an "immune cold"' microenvironment, including a reduced number of immune cells (CD8 and CD163), reduced expression of immune regulatory proteins by immune cells (PD-L1, FoxP3, and LAG3), and reduced tumor cell expression of PD-L1. These B2M-low tumors correlated with lower disease-specific survival (P =.018), a finding that maintained significance only for the proficient MMR cohort (P =.037). Conclusions Our findings suggest that B2M expression may support predictive models for both outcome and checkpoint inhibitor therapy treatment response for colorectal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effectiveness of ChatGPT 4 in generating multiple-choice questions (MCQs) with explanations for pathology board examinations, specifically for digestive system pathology. Methods The customized ChatGPT 4 model was developed for MCQ and explanation generation. Expert pathologists evaluated content accuracy and relevance. These MCQs were then administered to pathology residents, followed by an analysis focusing on question difficulty, accuracy, item discrimination, and internal consistency. Results The customized ChatGPT 4 generated 80 MCQs covering various gastrointestinal and hepatobiliary topics. While the MCQs demonstrated moderate to high agreement in evaluation parameters such as content accuracy, clinical relevance, and overall quality, there were issues in cognitive level and distractor quality. The explanations were generally acceptable. Involving 9 residents with a median experience of 1 year, the average score was 57.4 (71.8%). Pairwise comparisons revealed a significant difference in performance between each year group (P <.01). The test analysis showed moderate difficulty, effective item discrimination (index = 0.15), and good internal consistency (Cronbach's α = 0.74). Conclusions ChatGPT 4 demonstrated significant potential as a supplementary educational tool in medical education, especially in generating MCQs with explanations similar to those seen in board examinations. While artificial intelligence–generated content was of high quality, it necessitated refinement and expert review. [ABSTRACT FROM AUTHOR]

Objectives To perform a systematic review of published academic literature related to lost, mislabeled, and mishandled surgical and clinical pathology specimens during the preanalytical stage. Methods The authors used Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines to search PubMed, MEDLINE, Web of Science, and Scopus for relevant articles published from January 1, 1990, to May 1, 2023. Results The authors screened 1313 articles and identified 44 peer-reviewed, English-language articles published between 1990 and 2021 for inclusion in the final systematic review. Most articles (n = 36) reported results from US-based facilities. Articles primarily focused on general clinical and general surgical pathology. Analysis of the articles revealed that articles reported a range of methodological approaches, including incident reports, implementation analyses, case studies, and commentary recommendations. Most articles focused on mislabeling errors (61.3%) and missing or lost specimens (18.2%), while several articles combined specimen errors (20.5%). Several implementation studies (22.7%) reported using multiple interventions to mitigate errors. Implementation efforts reported between 70% and 100% reduction in pathology errors. Conclusions The review highlights the limited research on the topic, with an average of 2 articles per year discussing lost, mislabeled, or mishandled specimens. Intervention studies addressed The Joint Commission's patient safety goals for laboratory practice. More research is needed about error incidents and reporting in non-Western countries to gain a more global perspective on the topic. [ABSTRACT FROM AUTHOR]

Objectives Severe macrovesicular steatosis in donor livers is associated with primary graft dysfunction. The Banff Working Group on Liver Allograft Pathology has proposed recommendations for steatosis assessment of donor liver biopsy specimens with a consensus for defining "large droplet fat" (LDF) and a 3-step algorithmic approach. Methods We retrieved slides and initial pathology reports from potential liver donor biopsy specimens from 2010 to 2021. Following the Banff approach, we reevaluated LDF steatosis and employed a computer-assisted manual quantification protocol and artificial intelligence (AI) model for analysis. Results In a total of 113 slides from 88 donors, no to mild (<33%) macrovesicular steatosis was reported in 88.5% (100/113) of slides; 8.8% (10/113) was reported as at least moderate steatosis (≥33%) initially. Subsequent pathology evaluation, following the Banff recommendation, revealed that all slides had LDF below 33%, a finding confirmed through computer-assisted manual quantification and an AI model. Correlation coefficients between pathologist and computer-assisted manual quantification, between computer-assisted manual quantification and the AI model, and between the AI model and pathologist were 0.94, 0.88, and 0.81, respectively (P <.0001 for all). Conclusions The 3-step approach proposed by the Banff Working Group on Liver Allograft Pathology may be followed when evaluating steatosis in donor livers. The AI model can provide a rapid and objective assessment of liver steatosis. [ABSTRACT FROM AUTHOR]

Objectives Traditional histopathology is a time-intensive and labor-intensive process involving tissue formalin fixation, paraffin embedding, and microtoming into thin sections for H&E staining. Frozen section analysis is a modality used during surgery to quickly evaluate tissue, but it has limitations, such as the size and number of the specimens that can be analyzed as well as difficulties with fatty and bony tissues. Our objective was to investigate the performance of nonlinear microscopy, a fluorescence microscopy technique, for the rapid examination of resected lung tumors. Methods In this proof-of-principle study, nonlinear microscopy imaging of resected lung tissue was performed on a total of 73 tissue specimens collected from 13 patients who underwent lobectomy, segmentectomy, or wedge resection for pulmonary nodules. Results Two pathologists reviewed the digital nonlinear microscopy images in comparison to the corresponding histopathologic H&E slides from a variety of pulmonary pathologies. Conclusions This study demonstrated that nonlinear microscopy readily replicates traditional H&E staining for both lung tumors and nonneoplastic pulmonary structures. Nonlinear microscopy provides many advantages over frozen section analysis and is an optical imaging platform that has the potential to augment rapid pathologic evaluation of resected tissues in the age of digital pathology. [ABSTRACT FROM AUTHOR]

Objectives Few cytologically indeterminate thyroid fine-needle aspirations (FNAs) harbor BRAF V600E. Here, we assess interobserver agreement for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III (atypia of undetermined significance [AUS]) FNAs harboring BRAF V600E and contrast their features with those harboring non- BRAF V600E alterations, with attention to cytopathology experience. Methods Seven reviewers evaluated 5 AUS thyroid FNAs harboring BRAF V600E. To blind reviewers, cases were intermixed with 19 FNAs falling within other TBSRTC categories and in which genetic alterations other than BRAF V600E had been identified (24 FNAs total). Interobserver agreement against both "index" and most popular ("mode") diagnoses was calculated. Four additional BRAF V600E cases were independently reviewed. Results Reviewers included 3 trainees and 3 American Board of Pathology (board)–certified cytopathologists. Board-certified cytopathologists, whose experience ranged from 2 to more than 15 subspecialty practice years, had known AUS rates. BRAF V600E was identified in 5 of 260 (2%) AUS FNAs. Interobserver agreement was higher among cytopathologists with more experience. Mode diagnosis differed from index diagnosis in 6 of 11 cases harboring RAS-like alterations; mode diagnosis was AUS in 4 of 5 BRAF V600E FNAs. Conclusions Atypia of undetermined significance of thyroid FNAs harboring BRAF V600E is uncommon yet relatively reproducible, particularly among pathologists with experience. It is advisable to sequence BRAF across V600 in such cases. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the accuracy of ChatGPT and Bard in answering pathology examination questions requiring image interpretation. Methods The study evaluated ChatGPT-4 and Bard's performance using 86 multiple-choice questions, with 17 (19.8%) focusing on general pathology and 69 (80.2%) on systemic pathology. Of these, 62 (72.1%) included microscopic images, and 57 (66.3%) were first-order questions focusing on diagnosing the disease. The authors presented these artificial intelligence (AI) tools with questions, both with and without clinical contexts, and assessed their answers against a reference standard set by pathologists. Results ChatGPT-4 achieved a 100% (n = 86) accuracy rate in questions with clinical context, surpassing Bard's 87.2% (n = 75). Without context, the accuracy of both AI tools declined significantly, with ChatGPT-4 at 52.3% (n = 45) and Bard at 38.4% (n = 33). ChatGPT-4 consistently outperformed Bard across various categories, particularly in systemic pathology and first-order questions. A notable issue identified was Bard's tendency to "hallucinate" or provide plausible but incorrect answers, especially without clinical context. Conclusions This study demonstrated the potential of ChatGPT and Bard in pathology education, stressing the importance of clinical context for accurate AI interpretations of pathology images. It underlined the need for careful AI integration in medical education. [ABSTRACT FROM AUTHOR]

Objectives ChatGPT (OpenAI, San Francisco, CA) has shown impressive results across various medical examinations, but its performance in kidney pathology is not yet established. This study evaluated proficiencies of GPT-4 Vision (GPT-4V), an updated version of the platform with the ability to analyze images, on kidney pathology questions and compared its responses with those of nephrology trainees. Methods Thirty-nine questions (19 text-based questions and 20 with various kidney biopsy images) designed specifically for the training of nephrology fellows were employed. Results GPT-4V displayed comparable accuracy rates in the first and second runs (67% and 72%, respectively, P  =  .50). The aggregated accuracy, however—particularly, the consistent accuracy—of GPT-4V was lower than that of trainees (72% and 67% vs 79%). Both GPT-4V and trainees displayed comparable accuracy in responding to image-based and text-only questions (55% vs 79% and 81% vs 78%, P  =  .11 and P  =  .67, respectively). The consistent accuracy in image-based, directly asked questions for GPT-4V was 29%, much lower than its 88% consistency on text-only, directly asked questions (P  =  .02). In contrast, trainees maintained similar accuracy in directly asked image-based and text-based questions (80% vs 77%, P  =  .65). Although the aggregated accuracy for correctly interpreting images was 69%, the consistent accuracy across both runs was only 39%. The accuracy of GPT-4V in answering questions with correct image interpretation was significantly higher than for questions with incorrect image interpretation (100% vs 0% and 100% vs 33% for the first and second runs, P  =  .001 and P  =  .02, respectively). Conclusions The performance of GPT-4V in handling kidney pathology questions, especially those including images, is limited. There is a notable need for enhancement in GPT-4V proficiency in interpreting images. [ABSTRACT FROM AUTHOR]

Objectives Gender equity studies have shown that women are underrepresented in journal editor in chief positions, which confer major professional opportunities and influence. We sought to systematically investigate editor in chief gender and journal attributes within pathology. Methods We constructed a journal data set using the Scimago Journal & Country Rank and Clarivate Journal Citation Reports databases. We also included official journals of the major medical societies for the 12 pathology subspecialties recognized by the Association of American Medical Colleges. The final data set included 126 journals. We obtained editor in chief gender, impact factor, publication model (ie, hybrid access vs open access), year of founding, and geographic location for all included pathology journals. Results Women made up only 18% of the 141 total editor in chief positions. This inequity was present irrespective of all pathology journal variables studied. Among 10 journals with 2 editor in chief positions, 5 had only men and 5 had 1 man and 1 woman. All 3 journals with 3 editor in chief positions had 2 men and 1 woman. Conclusions Women are significantly underrepresented among editor in chiefs across pathology journals. Journals and affiliated members should advocate for diversity among these influential positions, given their impact on research, science, and medicine. [ABSTRACT FROM AUTHOR]

Objectives To characterize the role of pathology explanation clinics (PECs) in prostate cancer care and determine their impact on patients, urologic oncologists, and quality of care. Methods Semistructured interviews with 10 patients with newly diagnosed prostate cancer were conducted before and after a PEC pilot and at the 1- and 6-month follow-up visits. Information about participants' cancer knowledge and anxiety were collected quantitatively. Documented pathologist communications and proper review of outside biopsy slides were collected. Semistructured interviews were also completed with participating urologic oncologists following the pilot. Results Pathology explanation clinics improved participants' understanding of their diagnosis, cognitively and emotionally supporting them first in their urologic oncology visit and later in making an informed treatment decision. Mean knowledge scores were high, and a minority of participants had prostate cancer anxiety. Urologic oncologists noted improved understanding and reduced anxiety among participants, enabling nuanced conversations about prognosis and management during the visit. By ensuring review of outside biopsy slides and communication of clinically significant or unexpected diagnoses, PECs supported high-quality care and patient safety. Conclusions In this small pilot, PECs positively affected patients with prostate cancer, their clinicians, and the overall care system. Additional studies in larger populations and diverse settings will be useful. [ABSTRACT FROM AUTHOR]

Objectives Informal payments (IPs) are unofficial cash or in-kind payments for goods or services that should be covered by the health care system. They are a common but regressive method of financing health care in low- and lower-middle-income countries (LMICs). This study aims to characterize the prevalence and impact of IPs on pathology and laboratory medicine (PALM) services. Methods From September 2021 to September 2022, PALM staff were surveyed about the frequency, determinants, and impacts of IPs in their respective workplaces. Results In total, 268 responses were received, and 46.6% (125/268) reported experience with IPs. These 125 participants were more likely to work in the public sector and in LMICs. Approximately 65% reported accepting IPs to perform tests or release results. Obtaining faster results was the most commonly perceived reason for patients offering IPs. Overall, participants reported that IPs had more negative than positive impacts on their workplace. Conclusions This represents a first step in characterizing IPs within PALM and how this practice may affect access to these services in LMICs. Specifically, the fact that faster turnaround time was the most frequently perceived reason for offering IPs uncovers a potential barrier to improving PALM capacity in these regions. [ABSTRACT FROM AUTHOR]

Objectives Pathologists interpreting kidney allograft biopsies using the Banff system usually start by recording component scores (eg, i, t, cg) using histopathologic criteria committed to memory. Component scores are then melded into diagnoses using the same manual/mental processes. This approach to complex Banff rules during routine sign-out produces a lack of fidelity and needs improvement. Methods We constructed a web-based "smart template" (software-assisted sign-out) system that uniquely starts with upstream Banff-defined additional diagnostic parameters (eg, infection) and histopathologic criteria (eg, percent interstitial inflammation) collectively referred to as feeder data that is then translated into component scores and integrated into final diagnoses using software-encoded decision trees. Results Software-assisted sign-out enables pathologists to (1) accurately and uniformly apply Banff rules, thereby eliminating human inconsistencies (present in 25% of the cohort); (2) document areas of improvement; (3) show improved correlation with function; (4) examine t-Distributed Stochastic Neighbor Embedding clustering for diagnosis stratification; and (5) ready upstream incorporation of artificial intelligence–assisted scoring of biopsies. Conclusions Compared with the legacy approach, software-assisted sign-out improves Banff accuracy and fidelity, more closely correlates with kidney function, is practical for routine clinical work and translational research studies, facilitates downstream integration with nonpathology data, and readies biopsy scoring for artificial intelligence algorithms. [ABSTRACT FROM AUTHOR]

Objectives The high incidence of prostate cancer causes prostatic samples to significantly affect pathology laboratories workflow and turnaround times (TATs). Whole-slide imaging (WSI) and artificial intelligence (AI) have both gained approval for primary diagnosis in prostate pathology, providing physicians with novel tools for their daily routine. Methods A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was carried out in electronic databases to gather the available evidence on the application of AI-based algorithms to prostate cancer. Results Of 6290 articles, 80 were included, mostly (59%) dealing with biopsy specimens. Glass slides were digitized to WSI in most studies (89%), roughly two-thirds of which (66%) exploited convolutional neural networks for computational analysis. The algorithms achieved good to excellent results about cancer detection and grading, along with significantly reduced TATs. Furthermore, several studies showed a relevant correlation between AI-identified histologic features and prognostic predictive variables such as biochemical recurrence, extraprostatic extension, perineural invasion, and disease-free survival. Conclusions The published evidence suggests that AI can be reliably used for prostate cancer detection and grading, assisting pathologists in the time-consuming screening of slides. Further technologic improvement would help widening AI's adoption in prostate pathology, as well as expanding its prognostic predictive potential. [ABSTRACT FROM AUTHOR]

Objectives We conducted the first Irish national study assessing the value of multidisciplinary team meeting review in pathology practice and its impact on error detection before treatment. Methods Public and private pathology laboratories across Ireland capture their quality activities using standardized codes and submit their data to a centralized database (National Quality Assurance Intelligence System) overseen by the National Histopathology Quality Improvement (NHQI) program. A total of 1,437,746 histopathology and cytopathology cases submitted to the NHQI program over a 60-month period (January 2017 to December 2021) were included in this study. Cases were analyzed with respect to multidisciplinary team meeting peer review and the presence of a revised report (amended or corrected report), a surrogate marker for error detection before treatment. Results Across all cases assessed, 13.74% (197,587) underwent multidisciplinary team meeting discussion. Cases discussed at review had a statistically significantly higher rate of revised reports (1.25% [2470]) than cases not discussed at review (0.16% [1959]) (Pearson χ2, 6619.26; P  < .0001; odds ratio, 8.00 [95% CI, 7.54-8.49]). Overall, multidisciplinary team meeting review made it 8 times more likely to detect an error before treatment. Cancer resections had the highest rate of review at 55.29% (46,806), reflecting the prioritization of oncology case discussion at review meetings. Conclusions The multidisciplinary team meeting review process plays a valuable role in pathology error detection. A pathologist's participation in the review process comes with a clinically significant workload that needs to be recognized for future workforce planning. This study highlighted the positive role pathologists play in enhancing patient safety. [ABSTRACT FROM AUTHOR]

ObjectivesThe aim of this study is to evaluate the effectiveness of a CRISPR-based human and bacterial ribosomal RNA (rRNA) depletion kit (JUMPCODE Genomics) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shotgun metagenomic sequencing in weakly positive respiratory samples.MethodsShotgun metagenomics was performed on 40 respiratory specimens collected from solid organ transplant patients and deceased intensive care unit patients at UCLA Medical Center in late 2020 to early 2021. Human and bacterial rRNA depletion was performed on remnant library pools prior to sequencing by Illumina MiSeq. Data quality was analyzed using Geneious Prime, whereas the identification of SARS-CoV-2 variants and lineages was determined by Pangolin.ResultsThe average genome coverage of the rRNA-depleted respiratory specimens increased from 72.55% to 93.71% in overall samples and from 29.3% to 83.3% in 15 samples that failed to achieve sufficient genome coverage using the standard method. Moreover, rRNA depletion enhanced genome coverage to over 85% in 11 (73.3%) of 15 low viral load samples with cycle threshold values up to 35, resulting in the identification of genotypes.ConclusionThe CRISPR-based human and bacterial rRNA depletion enhanced the sensitivity of SARS-CoV-2 shotgun metagenomic sequencing, especially in low viral load samples.

Objectives The appendix, although considered a vestigial organ, is of considerable clinical importance because acute appendicitis is a common medical problem. There are also other disease processes involving the appendix. The appendix is among the first specimens that the pathologist (and surgeon) cuts one's teeth on. Thus, there may be a tendency to underestimate the clinically and prognostically significant appendiceal pathologies. Methods We provide a vade mecum of the pathologic features of a wide range of nonneoplastic appendiceal pathologies, with an emphasis on developing a practical approach to grossing, microscopy, and reporting—all with clinical and therapeutic implications. Much of this is based on literature on MEDLINE with reference to years 2008 to 2023, as well as on personal experiences and interpretations. Results The appendix can harbor a myriad of nonneoplastic pathologies, including infections, inflammations of varying etiologies (including interval appendectomy), endometriosis, diverticulosis, and so on. Chronic appendicitis, Crohn disease, and clinical audit are recurring themes while COVID-19 is a new entity. Conclusions Most importantly, all pathologists should appreciate that the appendix is not as "routine" a specimen as one would want to believe. [ABSTRACT FROM AUTHOR]

Objectives Afirma has recently introduced its Xpression Atlas (XA) as an adjunct to its Genomic Sequencing Classifier (GSC) for risk stratification of cytologically indeterminate thyroid nodules. We evaluated the performance of Afirma XA and associated pathologic findings for Afirma GSC suspicious nodules. Methods Intradepartmental records of thyroid fine-needle aspirations (FNAs) from January 2021 to December 2022 were identified and reviewed for patient and nodule characteristics, FNA findings, molecular test results, and final surgical pathology, if available. Results Material for Afirma GSC testing was collected in 624 thyroid FNAs, and 148 (24%) were classified as cytologically indeterminate. Afirma GSC testing was successful in 132 (89%) of those cases, of which 35 (27%) were Afirma GSC suspicious. Afirma XA testing was positive in 11 cases (11/35 [31%]). Eight (73%) patients underwent surgery that revealed 7 patients with papillary thyroid carcinoma and 1 patient with noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (risk of malignancy: 100% [8/8]). Among the 24 patients with negative Afirma XA results, 19 (79%) underwent surgery, revealing 5 patients with malignancy and 3 patients with NIFTP (risk of malignancy: 42% [8/19]). Overall, the risk of malignancy for Afirma GSC suspicious nodules was 59% (16/27). Conclusions Afirma XA improved risk stratification of thyroid disease with a high risk of malignancy in Afirma GSC suspicious nodules. A negative Afirma XA result, however, should not be used as a rule-out test. [ABSTRACT FROM AUTHOR]

Objectives We aimed to investigate the clinicopathologic features of and genetic changes in Sturge-Weber syndrome (SWS) in patients with refractory epilepsy. Methods Clinical data were retrospectively analyzed. H&E and immunohistochemistry were performed to assess pathologic changes. Targeted amplicon sequencing was applied to investigate the somatic GNAQ (c.548G>A) mutation. The potential predictors of seizure outcomes were estimated by univariate and multivariate statistical analyses. Results Forty-eight patients with SWS and refractory epilepsy were enrolled. According to the imaging data and pathologic examination, ipsilateral hippocampal sclerosis (HS), calcification of leptomeningeal arteries, and focal cortical dysplasia were found in 14 (29.2%), 31 (64.6%), and 37 (77.1%) patients, respectively. A high frequency of GNAQ alteration was detected in both cerebral cortex (57.7%) and ipsilateral hippocampus (50.0%) from patients with SWS. During follow-up, 43 of 48 patients (85.4%) had achieved seizure control (Engel class I). Statistically, HS signs on imaging were found to be independent predictors of unfavorable seizure outcomes (P =.015). Conclusions Calcification of leptomeningeal arteries, focal cortical dysplasia, and GNAQ alteration are common features in SWS pathology. Patients with refractory epilepsy caused by SWS can achieve satisfactory seizure control after surgery, but seizure control was compromised in patients with comorbid HS. [ABSTRACT FROM AUTHOR]

Objectives ChatGPT is an artificial intelligence chatbot developed by OpenAI. Its extensive knowledge and unique interactive capabilities enable its use in various innovative ways in the medical field, such as writing clinical notes and simplifying radiology reports. Through this study, we aimed to analyze the pathology knowledge of ChatGPT to advocate its role in transforming pathology education. Methods The American Society for Clinical Pathology Resident Question Bank 2022 was used to test ChatGPT, version 4. Practice tests were created in each subcategory and answered based on the input that ChatGPT provided. Questions that required interpretation of images were excluded. We analyzed ChatGPT performance and compared it with average peer performance. Results The overall performance of ChatGPT was 56.98%, lower than that of the average peer performance of 62.81%. ChatGPT performed better on clinical pathology (60.42%) than on anatomic pathology (54.94%). Furthermore, its performance was better on easy questions (68.47%) than on intermediate (52.88%) and difficult questions (37.21%). Conclusions ChatGPT has the potential to be a valuable resource in pathology education if trained on a larger, specialized medical data set. Those relying on it (in its current form) solely for the purpose of pathology training should be cautious. [ABSTRACT FROM AUTHOR]

Objectives To measure rates of potentially inappropriate pathology testing in the hospital setting. Methods Retrospective cross-sectional study in hospital setting from July 2021 to December 2021. We examined 3 potentially inappropriate uses: overordering, selection errors, and unnecessary repeat testing. Overordering included vitamin D and lipids (rarely required in acute hospital care). Selection error was the ratio of iron studies to standalone ferritin requests. Unnecessary repeats included any repeat vitamin D, lipids, iron, or ferritin in an episode of care or C-reactive protein (CRP) repeated within 3 days and N-terminal pro–brain natriuretic peptide (NT-proBNP) within 7 days and repeated previously abnormal CRP and NT-proBNP tests. Costs of inappropriate tests were estimated using the Australian Medicare Benefits Schedules. Results Among 55,904 test requests, 15% (n = 8120) were potentially inappropriate. Vitamin D was frequently ordered (n = 4498), as were lipids (n = 2872). Ratio of iron studies to standalone ferritin was 36. Of 19,233 repeat CRPs, 36% (n = 6947) were within 3 days and 62% (n = 179) of repeat NT-proBNPs were within 7 days of the first test. For initially abnormal tests, 89% of CRPs and 97% of NT-proBNPs remained abnormal. Inappropriate test costs accounted for 12% to 30% of costs. Conclusions Frequent potential inappropriate use and selection of pathology tests was observed in South Australian hospitals. [ABSTRACT FROM AUTHOR]

Objectives Aneurysmal dermatofibroma (ADF) and hemosiderotic dermatofibroma (HDF) are rare variants of dermatofibroma (DF) characterized by distinct histologic features. While HDF is traditionally considered a precursor to ADF, supporting evidence is limited, and the etiology remains unclear. A retrospective analysis of 2128 DF cases (2016-2019) was conducted to investigate the clinicopathologic characteristics of ADF, HDF, and other DFs. Methods Histopathologically diagnosed DF cases were examined for ADF and HDF. Univariate analyses were performed to compare clinicopathologic features. Results Among the cases, 168 (7.9%) were ADF and 29 (1.4%) were HDF. Aneurysmal dermatofibroma and HDF shared several common characteristics, including lower occurrence in females, larger size, and increased cellularity (all P <.0001). Notably, 29% of ADFs lacked hemosiderin deposition. Aneurysmal dermatofibroma primarily manifested on exposed areas (face and forearm, both P <.001). In contrast, 41% of HDFs occurred on the lower leg (P =.018), and all lower leg HDFs exhibited signs of venous stasis, distinguishing them from other HDFs (P <.0001). Conclusions Our findings indicate a potential close relationship between ADF and HDF. Contrary to conventional beliefs, we also presented the possibility of ADF progressing into HDFs. Physical trauma may induce ADF, and HDFs may emerge from ADFs in conjunction with venous stasis in the lower extremities. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the gender composition of departmental chairs and program leadership of Accreditation Council for Graduate Medical Education–accredited pathology residencies and American Board of Pathology–certified subspecialty fellowships across the United States. Methods In this cross-sectional analysis, we examined the gender of individuals holding leadership positions in academic pathology in the United States. Using publicly available online data, 2 authors independently coded perceived gender (ie, man/woman/other) with 100% concordance. Results In 144 pathology residency programs, more women hold residency program director positions (52.1% [75/144]). Among 11 pathology subspecialties, women overall hold fewer fellowship program director positions (45.0% [212/471]). Among the residency-associated pathology department chair positions identified, women hold fewer positions (31.8% [42/132]). There is some geographic variation in pathology leadership gender composition when stratified using US Census regions. Conclusions Women in academic pathology departments are well represented in residency and overall fellowship program leadership but are underrepresented in department chair and certain pathology subspecialty leadership positions. The disproportionate number of women in department chair positions is observed across medical specialties, highlighting the need for improved gender equity among high-level academic medicine positions. [ABSTRACT FROM AUTHOR]

Objectives To determine the extent and distribution of laboratory workforce shortages within the nation's medical laboratories. Methods The Vacancy Survey was conducted through collaboration between the American Society for Clinical Pathology (ASCP) Institute for Science, Technology and Public Policy in Washington, DC, and the Evaluation, Measurement, and Assessment Department and ASCP Board of Certification in Chicago, IL. Data were collected through an internet survey distributed to individuals who were able to report on staffing and certifications for their laboratories. Results Results of the ASCP 2022 Vacancy Survey show increased overall vacancy rates for laboratory positions in all departments compared with 2020. Overall retirement rates for laboratory professionals increased across most departments. Conclusions Current Vacancy Survey data show continued increases in the numbers of laboratory vacancies and retirements as well as changes in certification requirements, with trends amplified during the pandemic continuing into the present. Qualitative analysis results showed that there is an urgent need to focus not only on recruitment but—equally important—on retention of laboratory professionals. [ABSTRACT FROM AUTHOR]

Objectives Microvascular invasion (MVI) has previously been reported to be related to cancer prognosis; however, its significance in patients with dual-phenotype hepatocellular carcinoma (DPHCC) remains uncharacterized. We studied the role of MVI in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of HCC. Methods Patients with DPHCC (n = 84) who had undergone surgical interventions at the 900th Hospital of the Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between MVI and patient survival. Results Our results indicated that MVI was related to poor survival. According to the univariate analysis, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, the expression of cytokeratin 19 (CK19), and serum levels of both ɑ-fetoprotein (AFP) and cancer antigen-199 showed a strong correlation with overall survival. Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Tumor size; the number of tumor lesions; differentiation; peripheral hepatic fibrosis; liver capsule invasion; and expression of CK19, vascular endothelial growth factor, CK7, and mucin 1 showed a correlation with MVI, per the outcomes of χ2 tests. Conclusions Microvascular invasion may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival. [ABSTRACT FROM AUTHOR]

ObjectivesDespite multiple trials demonstrating that procalcitonin (PCT) is an effective tool for antibiotic stewardship, inconsistent application in real-world settings continues to fuel controversy regarding its clinical utility. We sought to determine rates of concordance between PCT results and antibiotic prescribing in hospitalized patients.MethodsWe performed a retrospective review of all inpatient encounters at an academic tertiary care health system with a PCT result between February 2017 and October 2019. Concordant prescribing was defined as starting or continuing antibiotics following an elevated PCT (>0.5 ng/mL) finding and withholding or stopping antibiotics following a low PCT (< 0.1 ng/mL) finding.ResultsAntibiotic prescribing decisions were discordant from the PCT level in 32.5% of our sample. Among patients not receiving antibiotics at the time of testing, 25.9% (430 of 1,662) were prescribed antibiotics despite a low PCT result. Among patients already receiving antibiotics, treatment was continued despite a low PCT level in 80.4% (728 of 906) of cases. Enhanced decision support tools introduced during the study period had no impact on PCT use for antibiotic decisions.ConclusionsOverall concordance between PCT results and antibiotic use is relatively low in a real-world setting. The potential value of PCT for antibiotic stewardship may not be fully realized.

Objectives To assess if the distribution of villous intraepithelial lymphocytes (IELs) in a pediatric cohort with Marsh I histopathology is specific to celiac disease (CeD). Methods Multicenter, retrospective case-control study between January 2001 and December 2019 in children (<18 years) with and without CeD with intraepithelial lymphocytosis and normal villous architecture. Pathology specimens were reviewed by 2 study pathologists who were blinded to the final diagnosis. Morphologic features (villous height to crypt depth ratio [Vh:Cd]) and IELs in the villous tip, top, or bottom half of the villus were quantified. Results Of the 97 children with Marsh I histopathology identified during the study period, 63 were excluded due to an insufficient number of well-oriented villous-crypt complexes or a Vh:Cd less than 2. Villous IELs were measured in 34 cases (14 CeD, 20 non-CeD controls). There was no difference between the non-CeD and CeD groups in the mean IELs at the villous tip (14.0 ± 7.1 vs 11.7 ± 6.0, P =.31), top (46.4 ± 18.4 vs 38.3 ± 10.8, P =.11), or bottom (29.8 ± 16.8 vs 28.5 ± 12.8, P =.80) half of each villus, respectively. Conclusions The distribution of IELs in Marsh I lesions is not specific for CeD. [ABSTRACT FROM AUTHOR]

Objectives Adult T-cell leukemia/lymphoma (ATLL) is a rare aggressive T-cell leukemia/lymphoma associated with human T lymphotropic virus type 1 infection. The patients might present with skin rash before, at, or after the diagnosis. The dermatopathologic finding might be diagnostically very challenging. Methods We retrospectively identified 110 patients with ATLL at a single institution in a 19-year period, with 19 patients having skin biopsies. Clinical, dermatopathologic, immunophenotypic, and molecular findings were studied. Results The cohort included 13 skin-first (5 acute, 5 lymphomatous, 2 chronic, 1 smoldering), 6 skin-second (4 acute, 1 lymphomatous, 1 smoldering), and 91 patients without skin biopsy. Some nonphotoprotected areas of body such as the forearm and lower lip were also seen. Skin manifestations included papular (5), erythroderma (1), nodulotumoral (3), plaques (1), patches (1), and a combination of skin rashes (2). Histopathologic findings included large pleomorphic cells, angiocentrism, epidermal infiltration with large Pautrier-like microabscesses, and folliculotropism. Fifteen (78.9%) cases showed CD4+/CD7–/CD25+. Next-generation sequencing study was conducted on 5 patients using either blood or bone marrow samples, revealing multiple genetic mutations across multiple signaling pathways. Conclusions Pleomorphic large, atypical cells with CD4+/CD25+/CD7– immunophenotype from a non–"bathing trunk" location, especially in a patient from endemic regions, raise suspicion for ATLL. T-cell receptor gene rearrangement is almost always positive, and the neoplasm usually demonstrates multiple mutations by next-generation sequencing study. [ABSTRACT FROM AUTHOR]

Objectives To assess the utility and performance of the large language model ChatGPT 4.0 regarding accuracy, completeness, and its potential as a time-saving tool for pathologists and laboratory directors. Methods A deidentified database of questions previously sent to pathology residents from health care providers was used as a source of general knowledge–type pathology questions. These questions were submitted to the large language model and the responses graded by subject matter experts in different pathology subspecialties. The grading criteria assessed accuracy, completeness, and the potential time savings for helping the pathologist craft the response. Results Overall, respondents thought that most of the answers would take less than 5 minutes of additional work to be used (85%). Accuracy and completeness for the 61 questions was high, with 98% of responses being at least "completely or mostly accurate" and 82% of responses "containing all relevant information." Of the respondents, 97% stated that the response would have "zero or near-zero potential for medical harm," and all thought the tool had potential to save time in constructing answers to health care providers' queries. Performance was similar in both Anatomic Pathology (AP) and Clinical Pathology (CP), with the only exception being some relevant information was excluded in 46% of AP answers vs only 10% in CP (P <.01). Conclusions ChatGPT version 4.0 gave responses that were predominantly accurate and complete for general knowledge–type pathology questions. With further research and when reviewed by a pathologist or laboratorian, this could facilitate its use as a pathologist's aid in answering questions from health care providers. [ABSTRACT FROM AUTHOR]

Objectives Pathology services are limited across most of sub-Saharan Africa. We sought to ascertain the availability of anatomic and clinical pathology services and diagnostic resources in Zambia. Methods Two individual surveys—one for anatomic pathology and one for clinical pathology/laboratory medicine—were developed by subject matter experts. These surveys were administered to individuals involved in pathology and laboratory medicine diagnostic services at hospitals and laboratories across Zambia from May to October 2022 using the American Society for Clinical Pathology email listserv. Results A total of 20 responses were received from 17 unique laboratories—8 sites provide anatomic pathology (AP) services, 12 provide clinical pathology (CP) services, and 3 perform both AP and CP services. Anatomic pathology services are variable and generally limited to a few of the responding laboratories, as only 1 laboratory performs immunohistochemical staining on surgical pathology specimens, and only 2 perform general histochemical stains. Conversely, certain microbiology testing (eg, for HIV) is more widely available. Conclusions This study of 17 unique laboratories represents the most complete analysis of pathology capabilities in Zambia. Despite initiatives to improve pathology services, both personnel and infrastructure challenges remain. Given a population of approximately 20 million, expansion of anatomic pathology in Zambia must be prioritized. [ABSTRACT FROM AUTHOR]

Objectives Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC. Methods A cohort of 134 patients with PC was studied for PD-L1 immunohistochemistry. The PD-L1 expression was evaluated using a combined proportion score with a cutoff of 1 or higher to define positivity. The results were correlated with various clinicopathologic parameters. Results Overall, 77 (57%) patients had positive PD-L1 expression. Significantly high PD-L1 expression was observed in high-grade tumors (P =.006). We found that 37% of human papillomavirus (HPV)–associated subtypes and 73% of other histotype tumors expressed PD-L1, while 63% of HPV-associated tumors and 27% of other histotype tumors did not (odds ratio, 1.35; P =.002 when compared for HPV-associated groups vs all others). Similarly, PD-L1–positive tumors had a 3.61-times higher chance of being node positive than PD-L1–negative tumors (P =.0009). In addition, PD-L1 high–positive tumors had a 5-times higher chance of being p16ink4a negative than PD-L1 low–positive tumors (P =.004). The PD-L1–positive tumors had a lower overall survival and cancer-specific survival than PD-L1–negative tumors. Conclusions Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1–based immunotherapeutics in PC. [ABSTRACT FROM AUTHOR]

Objectives To quantitatively measure liver biopsy adequacy requirements and the effect of a teaching intervention that uses a virtual biopsy platform. Methods A library of virtual liver biopsies was created using digital whole-slide, trichrome-stained tissue sections from liver resection material and QuPath image analysis software. Blinded participants staged fibrosis on the virtual biopsies before and after a teaching intervention. Results This platform both modeled adequacy requirements for cirrhosis diagnosis on biopsy material and measured the effect of a teaching intervention on participant performance. Using this platform, diagnostic accuracy for cirrhosis could be modeled according to the function y = λ(1 ‒ e ‒x/ γ). The platform demonstrated that the relationship between biopsy size and diagnostic accuracy was statistically significant and that biopsies smaller than 6 mm long and 0.8 mm wide were insufficient to diagnosis cirrhosis. The platform also measured improvement in fibrosis staging accuracy among participants following a teaching intervention. Conclusions These results provide proof of concept for a virtual biopsy method by which outstanding questions in anatomic pathology can be addressed quantitatively using open source software. Future work is needed to validate these findings in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives Multinucleated tumor cells (MTCs) in clear cell renal cell carcinoma (ccRCC) are not well understood. Methods Our study included ccRCC cases in a single institution between 2010 and 2019. We classified MTC as MTC with degenerative atypia (MTCD), MTC with no anaplasia (MTCNA), and MTC with anaplasia (MTCA). Clinicopathologic characteristics and outcomes were compared between MTC groups. Results In all, 92 of 256 people (36%) with ccRCC had MTC. People with ccRCC with MTCD and those with ccRCC but no MTC had similar clinicopathologic characteristics and outcomes. Also, MTCNA and MTCA were associated with larger tumor size, advanced pathologic tumor stage, higher World Health Organization/International Society of Urologic Pathologists nuclear grade, and higher metastatic potential (P  < .001 for each parameter). Overall, MTCA was associated with an increased rate of recurrence (P =.004), higher metastatic potential (P  < .001), and shorter time to metastasis (P =.033), regardless of tumor stage. Univariate Cox regression revealed MTCNA as a significant predictor of metastasis at 5 years (hazard ratio [HR], 4.171; 95% CI, 1.934-8.998); moreover, MTCA was a significant predictor of recurrence (HR, 5.723; 95% CI, 2.495-13.124), metastasis (HR, 12.024; 5.966-24.232), and death (HR, 5.661; 95% CI, 2.688-11.924) at 5 years. Conclusions Although MTCD may not be relevant in tumor grading, MTCNA and MTCA are associated with adverse outcomes. [ABSTRACT FROM AUTHOR]

Objectives Health care systems worldwide are facing a shortage in the pathology workforce that could negatively affect health care services, particularly oncology. To address this potential shortfall, the pathology community must identify the reasons why graduating students are not choosing pathology as a specialty. Methods We analyzed 226 free-text essay responses submitted by nonpathology residents at a teaching hospital. We used a general inductive approach and quantitative analysis to identify the barriers that prevent medical college graduates from choosing pathology as a specialty. Results Residents at our institution view pathology similar to residents from other countries, with the main obstacles to choosing pathology as a specialty being a perception that it lacks practical application to patient care or provides "no real help" and has a lack of patient interaction. In Russia specifically, there is a focus on the perceived negative aspects of autopsy as a barrier to selecting pathology. Less significant factors that may be based more on stereotypes than reality include the expectation that the work is not engaging, the emotional burden, and the occupational risks. Conclusions For medical students who place less importance on patient interaction, addressing these secondary factors could help select potential pathologists during students' undergraduate years. [ABSTRACT FROM AUTHOR]

Objectives Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is historically associated with Helicobacter pylori (HP) infections in more than 80% of patients. However, the incidence of HP-negative MALT lymphoma has been increasing. The clinicopathologic features have not been well studied, and optimal management strategies remain unclear. Methods The pathology database was searched for primary gastric MALT lymphomas diagnosed from 2000 to 2017. The clinical data and the slides were reviewed. The cases were divided for analysis into those with a background of chronic gastritis with HP, chronic gastritis without HP, and without either a background of chronic gastritis or HP. Results Of 70 gastric MALT lymphoma cases identified, 26 (37% of total) had chronic gastritis and were positive for HP histologically (n = 23) or were HP positive by additional laboratory testing (n = 3). The remaining 44 (63% of total) cases were HP negative by histology. Within the HP-negative cases, 5 (11% of HP-negative cases) showed histologic gastritis while 39 (89% of HP-negative cases) did not have sufficient evidence of gastritis through review of slides (n = 18) or based on available pathology reports (n = 21). The HP-negative cases without gastritis had higher propensities to show a mass lesion on endoscopy compared with HP-positive cases (37.5% vs 11.1%, P =.02) at the initial diagnosis. The immunophenotype and rate of positive B-cell gene rearrangement were not significantly different between the 2 groups. While all HP-positive patients received antibiotics for HP eradication, treatment in the HP-negative group varied among antibiotics, radiation, rituximab, or chemotherapy. Among HP-negative patients with available follow-up, 13 (39%) showed disease recurrence, similar to the recurrence rate in HP-positive patients; however, no individual from either group has died of the disease thus far. Conclusions The incidence of HP-negative MALT lymphoma is increasing, and in our practice, it is currently more common than HP-associated MALT lymphomas. The pathophysiology of HP-negative MALT lymphoma without chronic gastritis remains unclear. Follow-up data in our study suggest that the prognosis of these cases is excellent despite varied management modalities. [ABSTRACT FROM AUTHOR]

ObjectivesThis study aimed to assess whether the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Epsilon variant (B.1.429/427) is more virulent, leading to more hospitalization and more severe disease requiring intensive care unit (ICU) admission.MethodsSARS-CoV-2 genomic surveillance was performed on respiratory samples from 231 unique patients, collected at a single large health system in Southern California between November 2020 and March 2021 during the winter surge.ResultsThe frequencies of the Epsilon variant among outpatients, hospitalized patients, and ICU patients were indifferent.ConclusionsOur study suggests that the Epsilon variant is not associated with increased hospitalization and ICU admission.

ObjectivesThe analytical sensitivity of high-sensitivity cardiac troponin T (hsTnT) assays has enabled rapid myocardial infarction rule-out algorithms for emergency department (ED) presentations. Few studies have analyzed the real-world impact of hsTnT algorithms on outcomes and operations.MethodsComparison of ED length of stay (LOS) and 30-day outcomes (return to ED, inpatient admission, and mortality) for patients presenting with chest pain during 2 separate 208-day periods using a 0/1-hour hsTnT-enabled algorithm or fourth-generation TnT.ResultsDischarge, 30-day readmission, and 30-day mortality rates were not significantly different with fourth-generation TnT vs hsTnT. Thirty-day return rates were significantly decreased with hsTnT (17.4% vs 14.9%; P

ObjectivesSmall-volume biopsy-fine-needle aspiration biopsy (FNAB) with or without core biopsy-is in increasing use in diagnosis and management of lymphoma patients. Our objective was to survey the current practice in small-volume biopsy diagnosis of lymphoma, focusing on the interaction among hematopathologists and cytopathologists and the integration of FNAB, core biopsy, and flow cytometry studies at sign-out.MethodsThis study used a cross-sectional survey design employing the RedCap database distributed via nine pathology professional society email listservs. The survey consisted of 25 multiple-choice questions and several free text fields. In total, 128 pathologists participated.ResultsMost respondents indicated that FNAB specimens in which lymphoma is a diagnostic consideration (FNAB-L) are seen daily or weekly (68/116; 58.6%). However, most institutions have separate hematopathology and cytopathology services (72/116; 62.1%) with inconsistent communication. When communication occurred, respondents were frequently inclined to reconsider their original diagnoses. Barriers identified included lack of communication, inadequate access to diagnostic studies, no formal subspecialty training, and various opinions regarding FNAB in diagnosing lymphoma.ConclusionsThis survey showed that FNAB-L specimens are common, with a lack of uniformity in how complementary fine-needle aspiration and core biopsy specimens or flow immunophenotyping results are shared across hematopathology and cytopathology services.

ObjectivesCefiderocol is a novel siderophore cephalosporin with in vitro activity against multidrug-resistant (MDR), gram-negative bacteria and intrinsic structural stability to all classes of carbapenemases. We sought to identify gene variants that could affect the mechanism of action (MOA) of cefiderocol.MethodsWe report a case of bacteremia in a liver transplant candidate with a strain of carbapenem-resistant Escherichia coli that was found to be resistant to cefiderocol despite no prior treatment with this antimicrobial agent. Using whole-genome sequencing, we characterized the genomic content of this E coli isolate and assessed for genetic variants between related strains that were found to be cefiderocol susceptible.ResultsWe identified several variants in genes with the potential to affect the mechanism of action of cefiderocol.ConclusionsThe cefiderocol resistance in the E coli isolate identified in this study is likely due to mutations in the cirA gene, an iron transporter gene.

Objectives This article aims to establish the relationship between pathologic diagnosis and the rate of success in cancer next-generation sequencing testing. Methods Clinical next-generation sequencing results performed for solid tumors were reviewed. The rate of success was analyzed in the context of tumor type and accompanying variables. Results Out of 683 total specimens, 533 (78.0%) underwent successful sequencing. The rate of success was 91.8% for ovarian carcinomas, 87.5% for lung non–small cell carcinomas, 82.0% for colorectal adenocarcinomas, 78.3% for melanomas, 75.9% for breast carcinomas, and 64.7% for pancreatic adenocarcinomas. For specimens that successfully underwent sequencing, pancreatic adenocarcinomas had the lowest median tumor proportion and somatic RAS and TP53 mutation allele fractions compared with other tumor types. Cytology specimens had a 33.3% success rate for pancreatic adenocarcinomas (5 of 15) and a 93.3% success rate for lung carcinomas (14 of 15). Compared with tissue from primary sites, tissue from metastatic sites showed a higher success rate for pancreatic adenocarcinomas and lower success rates for colorectal adenocarcinomas and melanomas. Conclusions The success rate of cancer next-generation sequencing testing is dependent on pathologic diagnosis, tissue site, and diagnostic procedure. Understanding which specimens are at higher risk for failing molecular testing may help pathologists and clinical care teams optimize tissue acquisition and usage for patient care. [ABSTRACT FROM AUTHOR]

Objectives The practicing pathologist is challenged by the ever-increasing diagnostic complexity of myeloid neoplasms. This guide is intended to provide a general roadmap from initial case detection, often triggered by complete blood count results with subsequent blood smear review, to final diagnosis. Methods The integration of hematologic, morphologic, immunophenotypic, and genetic features into routine practice is standard of care. The requirement for molecular genetic testing has increased along with the complexity of test types, the utility of different testing modalities in identifying key gene mutations, and the sensitivity and turnaround time for various assays. Results Classification systems for myeloid neoplasms have evolved to achieve the goal of providing a pathology diagnosis that enhances patient care, outcome prediction, and treatment options for individual patients and is formulated, endorsed, and adopted by hematologists/oncologists. Conclusions This guide provides diagnostic strategies for all myeloid neoplasm subtypes. Special considerations are provided for each category of testing and neoplasm category, along with classification information, genetic testing requirements, interpretation information, and case reporting recommendations based on the experience of 11 Bone Marrow Pathology Group members. [ABSTRACT FROM AUTHOR]

Objectives The histopathologic diagnosis of colorectal sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) is of low consistency among pathologists. This study aimed to develop and validate a deep learning (DL)–based logical anthropomorphic pathology diagnostic system (LA-SSLD) for the differential diagnosis of colorectal SSL and HP. Methods The diagnosis framework of the LA-SSLD system was constructed according to the current guidelines and consisted of 4 DL models. Deep convolutional neural network (DCNN) 1 was the mucosal layer segmentation model, DCNN 2 was the muscularis mucosa segmentation model, DCNN 3 was the glandular lumen segmentation model, and DCNN 4 was the glandular lumen classification (aberrant or regular) model. A total of 175 HP and 127 SSL sections were collected from Renmin Hospital of Wuhan University during November 2016 to November 2022. The performance of the LA-SSLD system was compared to 11 pathologists with different qualifications through the human-machine contest. Results The Dice scores of DCNNs 1, 2, and 3 were 93.66%, 58.38%, and 74.04%, respectively. The accuracy of DCNN 4 was 92.72%. In the human-machine contest, the accuracy, sensitivity, and specificity of the LA-SSLD system were 85.71%, 86.36%, and 85.00%, respectively. In comparison with experts (pathologist D: accuracy 83.33%, sensitivity 90.91%, specificity 75.00%; pathologist E: accuracy 85.71%, sensitivity 90.91%, specificity 80.00%), LA-SSLD achieved expert-level accuracy and outperformed all the senior and junior pathologists. Conclusions This study proposed a logical anthropomorphic diagnostic system for the differential diagnosis of colorectal SSL and HP. The diagnostic performance of the system is comparable to that of experts and has the potential to become a powerful diagnostic tool for SSL in the future. It is worth mentioning that a logical anthropomorphic system can achieve expert-level accuracy with fewer samples, providing potential ideas for the development of other artificial intelligence models. [ABSTRACT FROM AUTHOR]

ObjectivesAngioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma derived from T-follicular helper cells. For pathologists, diagnosing AITL may be challenging due to its wide clinical and histopathologic spectrum, which can mimic a variety of reactive and neoplastic processes.MethodsWe summarize and discuss the clinicopathologic features of AITL, emphasizing diagnostic tools available to the practicing pathologist. Common diagnostic dilemmas are discussed.ResultsAITL exhibits various histologic patterns and is often associated with a prominent microenvironment that can obscure the neoplastic cells. Atypical B-cell proliferations, which can take a number of forms, are common in AITL, and clonal B-cell expansion can be seen. The atypical B cells can closely resemble Hodgkin/Reed-Sternberg cells, leading to misdiagnosis as classic Hodgkin lymphoma. Molecular studies have revealed recurrent genetic alterations, which can aid in differential diagnosis, particularly in problematic cases.ConclusionsGiven the complex diagnostic challenges in AITL, an integrated approach, incorporating clinical, morphologic, immunophenotypic, and molecular findings, is helpful to reach an accurate diagnosis.

ObjectivesThe Lower Anogenital Squamous Terminology (LAST) recommendations classify human papillomavirus-associated squamous lesions into low- and high-grade squamous intraepithelial lesions (LSILs/HSILs). Our study aimed to assess interobserver agreement among 6 experienced pathologists in assigning 40 anal lesions previously diagnosed as anal intraepithelial neoplasia 2 (AIN 2) to either HSIL or non-HSIL categories.MethodsAgreement based on photomicrographs of H&E alone or H&E plus p16 immunohistochemistry was calculated using κ coefficients.ResultsAgreement was fair based on H&E alone (κ = 0.42; 95% confidence interval [CI], 0.34-0.52). Adding p16 improved agreement to moderate (κ = 0.55; 95% CI, 0.54-0.62). On final diagnosis, 21 cases (53%) had unanimous diagnoses, and 19 (47%) were divided. When designating p16 results as positive or negative, agreement was excellent (κ = 0.92; 95% CI, 0.83-0.95). Among variables (staining location, extent, and intensity), staining of the basal/parabasal layers was a consistent feature in cases with consensus for positive results (20/20). Of the 67 H&E diagnoses with conflicting p16 results, participants modified 32 (48%), downgrading 23 HSILs and upgrading 9 non-HSILs.ConclusionsAlthough p16 increased interobserver agreement, disagreement remained considerable regarding intermediate lesions. p16 expression, particularly if negative, can reduce unwarranted HSIL diagnoses and unnecessary treatment.

ObjectivesSerologic testing for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in potential donors of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) may not be performed until after blood donation. A hospital-based recruitment program for CCP may be an efficient way to identify potential donors prospectively.MethodsPatients who recovered from known or suspected COVID-19 were identified and recruited through medical record searches and public appeals in March and April 2020. Participants were screened with a modified donor history questionnaire and, if eligible, were asked for consent and tested for SARS-CoV-2 antibodies (IgG and IgM). Participants positive for SARS-CoV-2 IgG were referred for CCP collection.ResultsOf 179 patients screened, 128 completed serologic testing and 89 were referred for CCP donation. IgG antibodies to SARS-CoV-2 were detected in 23 of 51 participants with suspected COVID-19 and 66 of 77 participants with self-reported COVID-19 confirmed by polymerase chain reaction (PCR). The anti-SARS-CoV-2 IgG level met the US Food and Drug Administration criteria for "high-titer" CCP in 39% of participants confirmed by PCR, as measured by the Ortho VITROS IgG assay. A wide range of SARS-CoV-2 IgG levels were observed.ConclusionsA hospital-based CCP donor recruitment program can prospectively identify potential CCP donors. Variability in SARS-CoV-2 IgG levels has implications for the selection of CCP units for transfusion.

ObjectivesThe inconclusive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) result causes confusion and delay for infection prevention precautions and patient management. We aimed to develop a quantitative algorithm to assess and interpret these inconclusive results.MethodsWe created a score-based algorithm by combining laboratory, clinical, and epidemiologic data to evaluate 69 cases with inconclusive coronavirus disease 2019 (COVID-19) PCR results from the Centers for Disease Control and Prevention (CDC) assay (18 cases) and the TaqPath assay (51 cases).ResultsWe determined 5 (28%) of 18 (CDC assay) and 20 (39%) of 51 (TaqPath assay) cases to be false positive. Lowering the cycle threshold cutoff from 40 to 37 in the TaqPath assay resulted in a dramatic reduction of the false-positive rate to 14%. We also showed testing of asymptomatic individuals is associated with a significantly higher probability of having a false-positive result.ConclusionsA substantial percentage of inconclusive SARS-CoV-2 PCR results can be false positive, especially among asymptomatic patients. The quantitative algorithm we created was shown to be effective and could provide a useful tool for clinicians and hospital epidemiologists to interpret inconclusive COVID-19 PCR results and provide clinical guidance when additional PCR or antibody test results are available.

Objectives Almost half of all patients diagnosed with uveal melanoma will die of metastatic disease. This has been attributed to early seeding of micrometastases. We investigate the presence, density, organ involvement, and characteristics of micrometastases of uveal melanoma in tissue obtained at autopsy of patients with and without coexisting macrometastases. Methods Patients diagnosed with primary uveal melanoma at a national referral center between 1960 and 2020 (n = 4,282) were cross-referenced with autopsy registers at nearby hospitals. Eleven patients were included. Formalin-fixed, paraffin-embedded tissue samples obtained during autopsy were examined with routine histology, immunohistochemistry, and immunomagnetic separation. Results Micrometastases were detected in 5 of 5 patients with and in 5 of 6 patients without coexisting macrometastases. Micrometastases were identified in several sites, including lungs, kidneys, myocardium, and bone marrow. Their highest density per mm2 of tissue was seen in the liver. Of 11 examined patients, 2 had at least 1 BAP-1–positive metastasis. All micrometastases had immune cell infiltrates and no or very low proliferative activity. Conclusions We demonstrate multiorgan involvement of apparently dormant micrometastases in patients with uveal melanoma. This suggests that micrometastases are present in nearly all patients diagnosed with primary uveal melanoma, regardless of coexisting macrometastases. [ABSTRACT FROM AUTHOR]

Objectives Amyloid light chain (AL)-κ and AL-λ share common histopathologic changes; however, the potential difference in clinical manifestations, histologic findings, and clinical significance between the 2 subtypes remain unclear. Methods In a retrospective study, 94 kidney biopsies for AL amyloidosis were evaluated using the composite scarring injury score (CSIS) and amyloid score (AS). Results were then compared between AL-κ and AL-λ. Results Comparing AS and CSIS between AL-κ and AL-λ, the AS was significantly higher in AL-κ than in AL-λ, with 2 components of AS (capillary wall and vascular amyloid) scoring higher in AL-κ than in AL-λ, while mesangial and interstitial ASs were similar in the 2 cohorts. In addition, the proportion of periodic acid–Schiff strong-staining amyloid in AL-κ was markedly higher than in AL-λ. There was no significant difference in CSIS and its components between the 2 subtypes of AL amyloidosis. Conclusions Overall, AL-κ presents with higher serum creatinine and a higher AS score than AL-λ at biopsy, which may indicate a worse prognosis and be an important reference for clinical management. [ABSTRACT FROM AUTHOR]

Objectives This study compares the effectiveness of an interactive e-learning module with a traditional text-based method for teaching peripheral blood smear analysis. Methods Pathology trainees at Accreditation Council for Graduate Medical Education residency programs were asked to participate. Participants completed a multiple-choice test on peripheral blood smear findings. Trainees were randomized into completing an e-learning module or a PDF reading exercise with the same educational content. Respondents rated their experience and completed a postintervention test composed of the same questions. Results In total, 28 participants completed the study; 21 improved their score in the posttest (mean, 21.6 correct answers) compared with the pretest (19.8; P <.001). This improvement was seen in both the PDF (n = 19) and interactive (n = 9) groups, with no difference in performance between the 2 groups. Trainees with less clinical hematopathology experience showed a trend of having the largest performance improvement. Most participants completed the exercise within 1 hour, rated the exercise as easy to navigate, were engaged, and reported learning new information about peripheral blood smear analysis. All participants indicated that they would likely complete a similar exercise in the future. Conclusions This study suggests that e-learning is an effective tool for hematopathology education and equivalent to traditional narrative-based methods. This module could easily be incorporated into a curriculum. [ABSTRACT FROM AUTHOR]

Objectives To determine the prognostic significance of the maximum allowable percentage of Gleason pattern 4 (GP4) at prostate biopsy compared with adverse pathology observed at radical prostatectomy (RP) to expand active surveillance eligibility among a cohort with intermediate risk of prostate cancer. Methods A retrospective study of patients with grade group (GG) 1 or 2 prostate cancer on prostate biopsy with subsequent RP was performed at our institution. A Fisher exact test was used to understand the relationship among GP4 subgroups (0%, ≤5%, 6%-10%, and 11%-49%) assigned at biopsy and adverse pathologic findings at RP. Additional analyses comparing the GP4 ≤5% cohort's prebiopsy prostate-specific antigen (PSA) level and GP4 length with adverse pathology at RP were also performed. Results No statistically significant difference in adverse pathology at RP was observed between the active surveillance–eligible control (GP4 0%) and the GP4 ≤5% subgroup. In total, 68.9% of the GP4 ≤5% cohort showed favorable pathologic outcomes. A separate analysis of the GP4 ≤5% subgroup revealed that neither prebiopsy serum PSA levels nor GP4 length showed statistical correlation with adverse pathology at RP. Conclusions Active surveillance may be a reasonable option for management of patients in the GP4 ≤5% group until long-term follow-up data become available. [ABSTRACT FROM AUTHOR]

Objectives"Assurance behaviors," a type of defensive medicine, involve physicians' utilization of additional patient services to avoid adverse legal outcomes. We aim to compare the use of clinical behaviors (such as ordering additional tests, services, and consultations) due to malpractice concerns with the same behaviors due to patient safety concerns.MethodsA national sample of dermatopathologists (n = 160) completed an online survey.ResultsParticipants reported using one or more of five clinical behaviors due to concerns about medical malpractice (95%) and patient safety (99%). Self-reported use of clinical behaviors due to malpractice concerns and patient safety concerns was compared, including ordering additional immunohistochemistry/molecular tests (71% vs 90%, respectively, P < .0001), recommending additional surgical sampling (78% vs 91%, P < .0001), requesting additional slides (81% vs 95%, P < .0001), obtaining second reviews (78% vs 91%, P < .0001), and adding caveats into reports regarding lesion difficulty (85% vs 89%, P > .05).ConclusionsDermatopathologists use many clinical behaviors both as assurance behaviors and due to patient safety concerns, with a higher proportion reporting patient safety concerns as a motivation for specific behaviors.