Archives of pathology & laboratory medicine最新文献

Context.—: Aided by tissue microarray (TMA) technology, several RNA-correlated immunohistochemistry-based algorithms have been developed for cell-of-origin (COO) prediction in diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS). However, there is currently no empirical evidence to guide the optimal application of these algorithms to whole tissue sections (WTSs).

Objective.—: To assess the impact of various scoring methods on the accuracy and reproducibility of the popular Hans algorithm.

Design.—: We compared 3 different WTS-based scoring methods, designated as global, selective, and hotspot scoring, to a matched TMA evaluation and gold standard RNA analysis (Lymph2Cx; germinal center B cell n = 64; activated B cell/unclassified n = 68) using a representative series of 132 excisional biopsies of de novo DLBCL-NOS. Positivity scores (10% increments) were submitted by 3 expert lymphoma pathologists, with 30% or more defining positivity.

Results.—: Sixty-eight of the 132 cases of DLBCL-NOS (52%) exhibited variation in Hans immunohistochemistry marker phenotype as a consequence of scoring method and/or interscorer discordance. Although this led to changes in Hans COO assignment in 27 of 132 cases (20%), none of the WTS-based scoring methods were statistically inferior to one another in terms of raw accuracy. Hotspot scoring yielded the lowest proportion of borderline scores (20%-40% range) for BCL6 transcription repressor (BCL6) and IRF4 transcription factor (MUM1) but negatively impacted the balance between sensitivity and specificity for these markers. Selective scoring was associated with significantly worse interscorer concordance compared to TMA evaluation, which it was designed to replicate.

Conclusions.—: Overall, our data favor the use of global scoring for its noninferior accuracy, solid interscorer concordance, nonnegative influence on individual Hans markers, and current widespread use.

Context.—: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by proliferation of the granulocytic cell line. The incidence of CML in Kenya is estimated at near 2000 cases annually. The disorder is associated with a poor prognosis without treatment. Tyrosine kinase inhibitors are approved for treatment in adults and children with confirmed disease. Diagnostic testing for CML in the public setting in Kenya is limited and not covered by the Kenyan National Health Insurance Fund.

Objective.—: To establish a clinical fluorescence in situ hybridization assay for the diagnosis of CML in the Academic Model Providing Access to Healthcare (AMPATH) Reference Laboratory in Eldoret, Kenya.

Design.—: Peripheral blood and bone marrow smears were split between the AMPATH Reference Laboratory and the Indiana University Cytogenetics Laboratory for concordance studies.

Results.—: Seventeen specimens from patients with a provisional diagnosis of CML were studied by fluorescence in situ hybridization in both the AMPATH and Indiana University Cytogenetics laboratories. The analysis for 1 specimen could not be completed by both laboratories, and the results for 1 other specimen were discordant. The interpretations of 15 of 16 specimens (93.7%) were concordant. Normal specimens were also studied to establish the normal range for the assay.

Conclusions.—: We report the establishment of diagnostic testing for CML in the AMPATH Reference Laboratory and the Moi Teaching and Referral Hospital in Eldoret, Kenya.

Context.—: Placental pathology reports may contain terminology that obstetric providers do not feel comfortable discussing with their patients.

Objective.—: To determine if lay language comments appended to the placental pathology report increase provider comfort and understanding of the report.

Design.—: We drafted a priori lay language comments explaining the major pathologic findings in the placenta. To test the acceptability and value of the comments, we designed an anonymous and randomized provider survey aimed to assess understanding of the terminology in the pathology report and comfort with explaining the report to their patients. Survey respondents were randomly assigned to receive 2 hypothetical placental pathology reports, one with and one without lay language comments. Respondents were asked to rate their understanding and comfort level explaining the report to their patients on a scale of 1 to 4. Within-provider differences in understanding and comfort by report type and pathology type were assessed by using repeated measures analysis of variance.

Results.—: Thirty-one providers responded to the survey. Providers reported greater complete understanding of the report when reading the report with lay language comments as compared to the report without the comments (mean comfort of 3.5 for lay language versus 2.97 for original report, P < .001), as well as greater comfort with the report (mean comfort of 3.29 for lay language versus 2.81 for original report, P = .002). There was no difference in provider understanding or comfort by the pathology findings represented (P = .66).

Conclusions.—: Our survey results indicate that the inclusion of lay language comments in the placental pathology report can improve provider understanding of the placental findings and therefore improve their comfort when discussing the findings with a patient and considering future treatment options.

Context.—: High-grade astrocytoma with piloid features (HGAP) is a newly recognized glioma defined by its methylation profile. Understanding of its clinical, histologic, and molecular characteristics continues to evolve.

Objective.—: To review the HGAP literature, emphasizing updates in our understanding of the entity since its codification in the 2021 World Health Organization (WHO) Blue Book. Additionally, to present a case series illustrating a single institutional experience with HGAP.

Data sources.—: The English-language HGAP literature from 2018 to 2024 was reviewed. Four cases of HGAP were reviewed, along with relevant medical records.

Conclusions.—: HGAP is an important consideration in the differential diagnosis of isocitrate dehydrogenase-wild-type gliomas and is more frequently encountered in adults. A handful of studies published following the entity's codification in the 2021 WHO Blue Book have refined our understanding of its clinical, histologic, and hallmark molecular characteristics. The most substantial updates include the description of 3 provisional subtypes, further characterization of an association with neurofibromatosis 1 syndrome, identification of new rare molecular alterations, and documentation of a unique case of possible transformation of pilocytic astrocytoma into HGAP. Clues to the diagnosis of HGAP include histologic infiltrating glioma with moderate pleomorphism, posterior fossa location, CDKN2A/B (cyclin dependent kinase inhibitor 2A/B) deletion, MAPK (mitogen-activated protein kinase) pathway alterations, ATRX (alpha thalassemia/mental retardation syndrome X-linked) loss, and association with neurofibromatosis 1 syndrome in some cases; these findings should prompt further molecular testing, including genome-wide DNA methylation analysis, which is currently essential for diagnosis.

Context.—: Complex surgical specimens are associated with complex Current Procedural Terminology (CPT) coding.

Objective.—: To assess and optimize the accuracy of CPT coding of complex genitourinary specimens at our institution.

Design.—: Baseline CPT codes for nephrectomy and cystectomy surgical pathology specimens were examined during a 3-month period. Pathology reports were reviewed for accurate CPT coding, and commensurate tests of change were implemented. Post-test-of-change data were re-collected, analyzed, and compared to the baseline data.

Results.—: Baseline data consisted of 71 genitourinary specimens (April to June 2021) and demonstrated undercoding in 46% (n = 33 of 71) of specimens, mostly in specimens with 2 or more billable organs. From findings in baseline data, we implemented test-of-change efforts consisting of awareness, education, and increased documentation and communication between all involved parties. Marked improvement was noted in the coding accuracy of specimens with 2 billable organs (pretest: n = 4 of 21, 19%; posttest: n = 14 of 21, 67%) and 3 or more billable organs (pretest: n = 0 of 16, 0%; posttest: n = 7 of 12, 58%) (P value = .002). Problematic areas included nephrectomy specimens resected with adrenal glands (pretest: n = 2 of 12, 17%; posttest: n = 12 of 14, 86%) and ureters for urothelial carcinoma (pretest: n = 0 of 10, 0%; posttest: n = 3 of 6, 50%), as well as regional lymph nodes commingled with resection specimens (pretest: n = 0 of 11, 0%; posttest: n = 7 of 9, 78%).

Conclusions.—: A comprehensive approach involving all stakeholders is necessary for CPT coding of complex surgical specimens. Documentation and familiarity with coding rules, specifically bundling and unbundling, as well as clinical indications for resection, are important factors in optimizing CPT coding.

Context.—: Generative artificial intelligence (AI) has emerged as a transformative force in various fields, including anatomic pathology, where it offers the potential to significantly enhance diagnostic accuracy, workflow efficiency, and research capabilities.

Objective.—: To explore the applications, benefits, and challenges of generative AI in anatomic pathology, with a focus on its impact on diagnostic processes, workflow efficiency, education, and research.

Data sources.—: A comprehensive review of current literature and recent advancements in the application of generative AI within anatomic pathology, categorized into unimodal and multimodal applications, and evaluated for clinical utility, ethical considerations, and future potential.

Conclusions.—: Generative AI demonstrates significant promise in various domains of anatomic pathology, including diagnostic accuracy enhanced through AI-driven image analysis, virtual staining, and synthetic data generation; workflow efficiency, with potential for improvement by automating routine tasks, quality control, and reflex testing; education and research, facilitated by AI-generated educational content, synthetic histology images, and advanced data analysis methods; and clinical integration, with preliminary surveys indicating cautious optimism for nondiagnostic AI tasks and growing engagement in academic settings. Ethical and practical challenges require being addressed by rigorous validation, prompt engineering, federated learning, and synthetic data generation to help ensure trustworthy, reliable, and unbiased AI applications. Generative AI can potentially revolutionize anatomic pathology, enhancing diagnostic accuracy, improving workflow efficiency, and advancing education and research. Successful integration into clinical practice will require continued interdisciplinary collaboration, careful validation, and adherence to ethical standards to ensure the benefits of AI are realized while maintaining the highest standards of patient care.

Context.—:

Objective.—: To report the isolation and significance of C kroppenstedtii, features of patients with GLM, pathologic findings and mechanism, bacteriologic workup, and optimal treatment.

Design.—: Analysis of the cases with C kroppenstedtii at The University of Texas MD Anderson Cancer Center from 2016 to March 2024 for mechanistic insights.

Results.—: During a period of 8 years, isolates of C kroppenstedtii were obtained from 10 women and 7 men. All of the women, with an average age of 34 years (range, 18-61 years), presented with chronic or subacute mastitis, and were subsequently diagnosed with GLM. The men, with an average age of 66 years, had neoplastic diagnoses with the bacterium being commensal in 6 cases. Thus, C kroppenstedtii shows a predilection to infect the female breast (P < .001). Predisposing risks for GLM included childbirth in 8 women and nipple inversion in 2 women. Histopathology revealed xanthogranulomatous inflammation and Gram-positive bacilli within fat droplets or extracellularly. From GLM aspirates or tissue, the liquid culture media and/or anaerobic incubation yielded 9 of 10 isolates. Up to 14 tested strains were susceptible to vancomycin, linezolid, rifampin, and gentamicin. Nine women received extensive antimicrobial therapy.

Conclusions.—:

Context.—: The College of American Pathologists Hematology and Clinical Microscopy Committee implemented a hemoglobinopathy proficiency testing and education program to monitor and assess the performance of participating laboratories.

Objective.—: To evaluate the performance of clinical laboratories for hemoglobinopathy proficiency testing from 2005 to 2023.

Design.—: The hemoglobinopathy challenges are composed of clinical case summaries and electrophoretic and chromatographic gel and tracing images. The participants are asked to determine (1) what hemoglobin chain is affected and (2) the hemoglobinopathy diagnosis.

Results.—: A total of 365 to 676 laboratories were enrolled in the proficiency testing program each year. Overall, the error rates for determination of the affected globin chain and a hemoglobinopathy diagnosis ranged from 0.6% to 56.5% and 0.5% to 86.5%, respectively. Twenty-three of 66 surveyed hemoglobinopathies (34.8%) had an error rate exceeding the consensus threshold of 20%. The globin gene detection error rate of the compound hemoglobinopathies was significantly higher when compared with just the α (P = .01) and β (P = .003) gene disorders. However, the error rate for the overall compound α/β-globin interpretation, although high at 23%, was not statistically significant when compared with just the α- or β-globin chain disorders. In repeat testing of the variants, there was no consistent improvement in performance.

Conclusions.—: The program participants demonstrated variable performance with one-third of the surveys exceeding the 20% error rate. The error rate for compound hemoglobinopathies was even higher. Our data illustrate a critical need for continuing educational efforts with an algorithmic approach to hemoglobin disorders.

Context.—: The co-occurrence of plasma cell neoplasm (PCN) and lymphoplasmacytic lymphoma (LPL) is rare, and their clonal relationship remains unclear.

Objective.—: To evaluate the clinicopathologic characteristics of concomitant LPL/PCN.

Design.—: Retrospectively analyzed clinical and laboratory data of 14 cases.

Results.—: Three patients initially presented with immunoglobulin (Ig) M paraprotein, 1 with IgG paraprotein, and 10 had simultaneous diagnoses of PCN and LPL. In 13 cases, flow cytometry detected both LPL and PCN in marrow biopsies. Furthermore, immunohistochemistry highlighted the 2 neoplastic populations, demonstrating an increased proportion of plasma cells and their expression of cyclin D1, CD56, and/or a non-IgM isotype restriction. All cases exhibited discordant heavy-chain isotypes between LPL and PCN. Thirteen of the 14 cases (92.9%) had concordant light-chain restrictions between the 2 neoplasms, and the remaining case (7.1%) showed discordant light-chain restrictions. Of the 12 patients with follow-up, 5 were treated with myeloma regimens, 2 with LPL regimens, 3 with combined therapy, and 2 with observation alone. Follow-up ranged from 2 to 146 months (median, 12.5 months). One patient died of PCN progression, one died of comorbidity, and 10 patients were alive with or without disease. Survival analysis showed no significant difference from the control.

Conclusions.—: The discordant heavy-chain isotype restrictions between PCN and LPL suggest biclonal B-cell neoplasms, which is supported by PCN's phenotypic distinction, such as the expression of cyclin D1 and/or CD56. However, our series exhibited a tendency toward concordant light-chain restrictions between the 2 neoplasms, raising the possibility that PCN may evolve from LPL through class switching.

Context.—: All member boards of the American Board of Medical Specialties have continuing certification (ie, maintenance of certification) programs. The efficacy of these programs has been questioned and, therefore, warrants study.

Objective.—: To determine if the American Board of Pathology CertLink program, as structured, is associated with an improvement in the performance of participants on the assessment of content that was previously missed (ie, inaccurately answered).

Design.—: We reviewed the performance of American Board of Pathology CertLink participants from January 2022 through December 2023 on the readministration of the content from 110 036 multiple-choice items that were previously missed by the participants in a program with enhanced learning strategies and incentives.

Results.—: The correct response rate upon the assessment of readministered content that was previously missed increased from 0% to 62.2% (68 394 of 110 036), which exceeds that which would be achieved by guessing (P < .001).

Conclusions.—: The American Board of Pathology CertLink program, which incentivizes learning and was constructed from adult learning principles and modern educational precepts to improve knowledge retention, interrupt forgetting, and introduce practice-relevant content, is associated with an improvement in the performance of diplomates on continuing certification knowledge assessments.