Archives of pathology & laboratory medicine最新文献

Context.—: Clinical laboratories are increasingly implementing pharmacogenomic (PGx) testing. Although PGx is similar to genetic testing for other indications, there are unique aspects that laboratories should consider.

Objective.—: To aid clinical laboratories that are implementing clinical PGx testing by describing characteristics of PGx test design and validation, as well as approaches to reporting. Resources that are useful for clinical laboratories performing PGx testing will be highlighted.

Design.—: The College of American Pathologists formed a workgroup composed of laboratorians with expertise in clinical PGx testing. The workgroup included representatives from the Association for Molecular Pathology and the American College of Medical Genetics and Genomics. The workgroup reviewed pertinent literature, as well as experience from proficiency testing and from members' laboratories.

Results.—: The workgroup recommends that laboratories implementing PGx consider the following concepts: testing platform, test design (ie, selection of pharmacogenes and variants/alleles), use of reference materials during test development and as controls during clinical runs, star allele and standard nomenclature systems, translations from genotype to predicted phenotype, and considerations for result reporting including making medication recommendations. The workgroup provides considerations when using report vendors, emphasizing the clinical laboratory's role and responsibility when implementing such reporting tools from vendors.

Conclusions.—: Clinical laboratories should be familiar with the fundamentals of PGx, ensure that PGx testing meets the applicable regulatory requirements for all aspects of the clinical laboratory testing process, and follow recommendations for standardization of nomenclature and reporting.

Context.—: Succinate dehydrogenase-deficient renal cell carcinoma (RCC) is a newly classified subtype of RCC in the World Health Organization classification of urinary and male genital tumours. However, systemic reports on this tumor are limited.

Objective.—: To give new insights into the clinicopathologic and molecular features of succinate dehydrogenase complex iron sulfur subunit B (SDHB)-deficient RCC.

Design.—: Data from 5 SDHB-deficient RCC patients diagnosed at our hospital between 2016 and 2022 were collected and studied through light microscopy, immunohistochemistry (IHC), ultrastructural analysis, and Sanger sequencing.

Results.—: The median age of patients was 34 years; 2 were male and 3 female. Grossly, the tumors were well defined, with an average diameter of 7 cm. Histologically, the cells were arranged in diverse patterns: solid, nested, glandular, or tubular with scattered cysts containing eosinophilic, wispy, or bubbly appearances. One patient's tumor exhibited an obvious papillary structure with focal aggregation of foam cells, and 3 tumors displayed focal micropapillary structures. Two patients presented with high-grade International Society of Urologic Pathology 3 nuclei. The tumor cells in all cases lacked SDHB expression by IHC stain. In addition, the average value of the combined positive score of programmed death ligand-1 (PD-L1, SP263) in all patients was 18. Electron microscopy revealed significant mitochondrial abnormalities. Genetic testing confirmed SDHB germline mutations in all tumors. One patient's tumor presented a novel, previously unreported mutation: c.697_700del in exon 7. Follow-up revealed metastasis in 1 patient, leading to mortality.

Conclusions.—: Our findings broaden the morphologic spectrum and highlight a new point mutation in the SDHB gene, providing a genetic change spectrum for this tumor entity.

Context.—: The Nottingham grading system, developed by Elston and Ellis, is the recommended method for grading invasive breast carcinoma. A previous study demonstrated the mean concordance for 35 breast pathologists in classifying 58 images as glandular (acinar)/tubule formation (G/TF) based on the World Health Organization definition was only 64%.

Objective.—: To determine if an expanded description of G/TF according to the original definition and current use of the Nottingham grading system would improve recognition of G/TF among breast pathologists and pathologists in training.

Design.—: Fifty-eight images with one structure circled were classified as G/TF or non-G/TF by Dr Ian Ellis. Images were sent as a PowerPoint (Microsoft) file to the breast pathologists who participated in the original study and to 21 trainees. Participants were asked to classify the structures based on the expanded description and were also provided with the 58 images from the first study with annotation.

Results.—: Among the participating 28 of the original 35 breast pathologists, the mean concordance increased from 64% (range, 40%-97%) to 94% (range, 86%-100%). Trainees had a mean concordance of 90% (range, 52%-100%).

Conclusions.—: The expanded description assisted in the recognition of G/TF for both breast pathologists and trainees. The most important impact on grading will likely be for carcinomas with complex cribriform patterns or micropapillary patterns with "inverted tubules." Participants endorsed that the expanded description of G/TF and the annotated images would be helpful reference material for pathologists.

Context.—: On May 14, 2024, the US Food and Drug Administration (FDA) approved self-collected vaginal samples for human papillomavirus (HPV) testing, expanding cervical cancer screening access.

Objective.—: To evaluate the feasibility and acceptability of HPV self-collection through community outreach programs targeting underscreened populations in Oregon.

Design.—: From October 2024 to June 2025, women aged 25 to 65 years were recruited through local organizations. Following instruction by pathologists, participants completed self-collection by using Copan swabs, which were transferred to ThinPrep media for high-risk HPV testing using the Cobas 8800 system. Postcollection surveys assessed user experience.

Results.—: Among 156 participants (mean age, 47.1 years), 87 (55.8%) identified as Hispanic and 69 (44.2%) as non-Hispanic. Racial groups included Hispanic White (87; 55.8%), Asian (33; 21.1%), Black (16; 10.3%), non-Hispanic White (14; 9.0%), Pacific Islander (2; 1.3%), and nondisclosed (4; 2.5%). All tests were valid; 10 participants (6.4%) were HPV-positive, including 1 with HPV-18 and 9 with non-16/18 types. Follow-up cytology showed 1 case of atypical squamous cells of undetermined significance and 2 negative results; the remainder are pending follow-up. Of 129 survey respondents, 8 (6.2%) had received the HPV vaccine. Overall, 117 (90.7%) found the self-collection kit easy to use, 114 (88.4%) would recommend it, and 91 (70.6%) were likely to choose self-collection over clinician-collected samples for future testing. Common feedback included convenience, comfort, and privacy.

Conclusions.—: HPV self-collection is a practical, user-friendly, and accessible screening option. Pathologist-led outreach may help close screening gaps. This study represents the first academic center-led implementation of FDA-approved self-collection in US community settings.

Context.—: Before adopting a new hematology analyzer in clinical laboratories, evaluating its platelet counting performance is critical.

Objectives.—: To assess the analytical performance of impedance (PLT-I), hybrid (PLT-H), and optical (PLT-O) platelet counts on the novel Mindray BC-7800 (BC-7800) and to compare platelet parameters obtained from the BC-7800 and Sysmex XN-3000 (XN-3000), including PLT-I, PLT-O, and PLT-F (optical fluorescent platelet count using oxazine dye), against the international reference method (IRM) in specimens with platelet interferences.

Design.—: Analytical parameters of the BC-7800, including limit of blank, linearity, reproducibility, and carryover, were evaluated. Interference testing included 126 specimens with red blood cell (RBC) microcytosis and 21 specimens from patients with blasts. Diagnostic performance against the IRM was assessed at platelet transfusion thresholds of 10 × 103/µL and 20 × 103/µL.

Results.—: The BC-7800 met acceptable criteria for most basic parameters, except within-run precision for PLT-I and PLT-H in some thrombocytopenic specimens. In RBC microcytosis, all methods showed strong correlations with the IRM, though PLT-I exhibited proportional bias. In leukemia specimens, PLT-O from the BC-7800 and PLT-F from the XN-3000 showed the strongest agreement with the IRM, while PLT-H and PLT-O from the XN-3000 exhibited systematic bias. Specificity and positive predictive value were excellent across all methods. Sensitivity, negative predictive value, and accuracy were highest for PLT-O from the BC-7800 and PLT-F.

Conclusions.—: The BC-7800 demonstrated reliable platelet analysis, particularly with PLT-O in thrombocytopenic and interference-prone specimens. PLT-H and optical fluorescent platelet methods showed strong reliability in specimens with RBC microcytosis, while PLT-O from the BC-7800 and PLT-F offered the highest accuracy for guiding platelet transfusion decisions.

Context.—: Despite studies indicating its importance to pathology practice, there is a perception that pathologists are poorly trained in management and business operational (MBO) skills. The College of American Pathologists charges its Practice Management Committee (PMC) with providing MBO intelligence. PMC activities included the online course "Pathology Business Fundamentals" (PBF) and a series of roundtable webinars.

Objective.—: To determine the degree to which the PMC meets its charge of providing MBO education.

Design.—: We conducted evaluation surveys following the PBF course and roundtables. From these surveys we selected several outcome metrics to evaluate our objective.

Results.—: Six hundred fifty individuals attended the PBF course, 186 (29%) of whom completed course evaluation surveys. On a scale of 1 to 5 (5 = highest score), the mean aggregate score for "overall value" was 4.64. On a scale of 1 to 5 (5 = very likely), the mean aggregate score for our outcome metric, "intent to apply" was 4.54. Of 1539 individuals who had access to post-roundtable evaluation questionnaires, 378 (25%) completed evaluations; of these, 233 (62%) indicated that the PMC is their "primary source" for MBO. Of the 132 individuals who completed a second year-end roundtable evaluation survey, 98 (74%) agreed that the sessions were "one of the best sources available for support/guidance related to practice management."

Conclusions.—: To our knowledge, this is the first study evaluating MBO education effectiveness for postgraduate pathologists and laboratory professionals. Based on evaluation survey data, the PMC appears to achieve its mission of providing adequate laboratory and pathology MBO information.

Context.—: Despite studies indicating its importance to pathology practice, there is a perception that pathologists are poorly trained in management and business operational (MBO) skills. The College of American Pathologists charges its Practice Management Committee (PMC) with providing MBO intelligence. PMC activities included the online course "Pathology Business Fundamentals" (PBF) and a series of roundtable webinars.

Objective.—: To determine the degree to which the PMC meets its charge of providing MBO education.

Design.—: We conducted evaluation surveys following the PBF course and roundtables. From these surveys we selected several outcome metrics to evaluate our objective.

Results.—: Six hundred fifty individuals attended the PBF course, 186 (29%) of whom completed course evaluation surveys. On a scale of 1 to 5 (5 = highest score), the mean aggregate score for "overall value" was 4.64. On a scale of 1 to 5 (5 = very likely), the mean aggregate score for our outcome metric, "intent to apply" was 4.54. Of 1539 individuals who had access to post-roundtable evaluation questionnaires, 378 (25%) completed evaluations; of these, 233 (62%) indicated that the PMC is their "primary source" for MBO. Of the 132 individuals who completed a second year-end roundtable evaluation survey, 98 (74%) agreed that the sessions were "one of the best sources available for support/guidance related to practice management."

Conclusions.—: To our knowledge, this is the first study evaluating MBO education effectiveness for postgraduate pathologists and laboratory professionals. Based on evaluation survey data, the PMC appears to achieve its mission of providing adequate laboratory and pathology MBO information.

Context.—: The latest WHO (World Health Organization) Classification of Bone and Soft Tissue Tumours (5th edition) has recently defined undifferentiated round cell sarcomas (URCSs) with EWSR1/FUS::NFATC2 (EWS RNA binding protein 1 or FUS RNA binding protein fused with nuclear factor of activated T cells 2) fusions. Given the rarity of this fusion, cytologic findings remain unreported, and information regarding clinical presentation, biological behavior, diagnostic markers, and molecular characteristics is scarce.

Objective.—: To provide a review of the clinicopathologic, molecular, and prognostic features of URCSs with EWSR1/FUS::NFATC2 fusions. Classic histopathologic findings, uncommon variations, and diagnostic pitfalls are addressed, along with the utility of recently developed immunohistochemical and molecular markers.

Data sources.—: Bringing together our institutional expertise and a thorough evaluation of the literature, this review captures key findings and trends through an extensive PubMed search. By integrating our own practical insights with evidence-based data, we offer a well-rounded perspective that sheds light on both foundational concepts and new advancements in the field.

Conclusions.—: This review underscores the importance of integrating clinicopathologic features and immunohistochemical results with EWSR1/FUS testing to effectively identify sarcomas with rare gene fusions via next-generation sequencing, which carry prognostic significance. Additionally, URCS-harboring EWSR/FUS::NFATC2 fusions exhibit notable differences from Ewing sarcoma and other URCSs, including a limited response to neoadjuvant chemotherapy; unique morphologic characteristics; and distinct genomic, transcriptomic, and epigenetic (methylation) profiles. Given the potential differences in biological behavior, accurate subclassification of EWSR1/FUS fusion variants is essential.

Context.—: Core needle biopsies (CNBs) are among the most common biopsy procedures, yielding long, thin deformation-prone cores. Core deformation results in both distorted histologic features and tortuosity (ie, deviation from the ideal straight path) along the length of the core. Tortuosity creates challenges in slide preparation and downstream pathologist assessment (eg, absent diagnostically relevant tissue after sectioning), indicating a clinical need for its minimization. Despite this need, there is no standard protocol for reporting CNB tortuosity.

Objectives.—: To (1) establish an actionable protocol for scoring CNB tortuosity, (2) build BiopTort, a software tool assigning CNB images interpretable, tiered scores consistent with the protocol, and (3) investigate our protocol and BiopTort's impact on interpathologist concordance and scoring time.

Design.—: Using a held-out CNB data set (N = 167), 3 pathologists assessed tortuosity in 3 sequential stages: (1) Baseline: a 3-tier scale based on prior experience, (2) Protocol: rescored with our 4-tier Tortuosity Scoring Protocol, (3) BiopTort-Aided: rescored with the protocol alongside BiopTort. Interrater concordance for each stage, using the Fleiss κ, was recorded.

Results.—: Fleiss κ was 0.19, 0.40, and 0.63, and average time per slide was 8.0, 24.2, and 13.3 seconds for stages 1 to 3, respectively. BiopTort was statistically noninferior to human interrater pairwise concordance.

Conclusions.—: These results suggest our protocol lessens interpathologist variability, with BiopTort further reducing variability and scoring protocol employment time cost. When deployed in CNB quality control workflows, our computer-aided protocol appears well situated to facilitate standardized, efficient, and actionable reporting of CNB tortuosity. BiopTort is open-source (http://bioptort.com).

Context.—: The identification of adipose tissue in endometrial biopsy or curettage specimens is an important yet rare histologic finding that may suggest uterine perforation, warranting careful pathologic evaluation to distinguish it from histologic mimickers.

Objective.—: To assess the presence of adipose tissue in endometrial samples and evaluate its diagnostic challenges and clinical implications.

Design.—: A retrospective cohort study was performed on cases from an 8-year period in which adipose tissue was identified in endometrial biopsy or curettage specimens. Hematoxylin-eosin-stained sections were reviewed, and relevant clinical data, including postoperative outcomes, were analyzed.

Results.—: Twenty-three patients were included (mean age ± standard deviation, 60.6 ± 13.3 years); 18 of 23 patients (78.3%) underwent curettage. Endometrial polyp was the most common concurrent diagnosis (8 of 23; 34.8%). Uterine perforation was clinically identified intraoperatively in 6 cases (6 of 23; 26.1%), all managed without complications. Most samples (16 of 23; 69.6%) contained a small amount of adipose tissue (1%-25%). Common risk factors included fibroids (5 of 23; 21.74%); cervical stenosis, polyps, intrauterine synechiae (4 of 23; 17.39% each); and history of prior cesarean delivery (10 of 23; 43.48%). The mean interval to notify clinicians of the adipose finding was 2.79 ± 1.65 days. One patient developed a postoperative abscess, successfully treated with antibiotics. No significant associations were found between risk factors or adipose proportion and intraoperative detection or postoperative complications (all P ≥ .05).

Conclusions.—: While adipose tissue in endometrial specimens may indicate uterine perforation, it was not associated with significant adverse outcomes in this cohort. Pathologists must remain vigilant, as benign mimics such as pseudolipomatosis or lipomatous tumors should be excluded during evaluation.