American journal of clinical pathology最新文献

Objective: Differentiating between the repertoire of immunoglobulin rearrangements is important in guiding diagnoses and management of B-cell lymphoma processes. A subset of these disease entities, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), can show distinct genomic profiles with a shared cell of origin. In this report, we describe a rare case in which differentiating between the immunoglobulin family of rearrangements (IGH, IGK, IGL) with optical genome mapping (OGM) helped revise the clinical suspicion of CLL.

Methods: We present a 50-year-old woman with a lymphoproliferative disorder. Her clinical laboratory genetics workup included chromosomal banding analysis, fluorescence in situ hybridization, next-generation sequencing, and OGM. Optical genome mapping was performed on the bone marrow specimen, starting with the ultra-high molecular weight DNA mapped on the Saphyr system. Structural variants with OGM were detected using rare variant analysis set to default parameters.

Results: In 2021, flow cytometry performed on the peripheral blood detected a monotypic CD5+/CD23+ B-cell population. A subsequent bone marrow in 2024 detected similar findings by flow with κ light chain restriction. Chromosomal banding analysis found a translocation between the long arms of chromosomes 11 and 22. Optical genome mapping demonstrated that this translocation involved the CCND1 locus juxtaposed to the regulatory immunoglobulin λ (IGL) gene cluster.

Conclusions: We present a case of CD5+/CD10- small B-cell lymphoma that immunophenotypically resembled CLL but showed positive immunostaining for cyclin D1. The combination of the clinicopathologic findings and the CCND1 translocation involving IGL, detected by OGM, supported a revised diagnosis of MCL.

Objective: Research on CD9 expression has been extensive in B lymphoblastic leukemia, with fewer studies focusing on acute myeloid leukemia (AML). We investigated the usefulness of CD9 in differentiating normal from abnormal myeloid progenitors, as well as expression in normal cell types and in AML.

Methods: Flow cytometry was used to assess the level of CD9 expression on normal and leukemic myeloid blasts and other normal bone marrow populations. Geometric mean fluorescence intensity levels and expression patterns were compared among cell types and AML subtypes.

Results: In normal subsets (n = 69), the level of CD9 expression was lowest in mature B cells, myeloid blasts, promyelocytes, and neutrophils, with intermediate expression in monocytes and highest in hematogones (stages 1 and 2). Committed myeloid progenitors (CMPs) had lower expression than hematopoietic stem cells (HSCs). CD9 typically has higher expression in AML (n = 58) compared to normal myeloid blasts and promyelocytes, and it is differentially expressed in AML, with the highest expression in PML::RARA AML.

Conclusions: Aberrant CD9 expression can be useful differentiating normal from abnormal myeloid progenitors, with the highest level of expression in AML with PML::RARA in our cohort. There was differential expression between HSCs and CMPs in the small numbers studied. Normal mature B cells can be used as an internal negative control in most cases.

Objective: We sought to investigate the frequency of diagnostic changes in hematopathology cases referred to the University of Michigan during a 3-year period and explore which parameters contribute to diagnostic change.

Methods: Pathology reports from hematology patients who came to the University of Michigan for a second opinion from 2017 to 2019 were reviewed. Diagnostic discrepancies were classified into major or minor. Specimen type, hematopathology board certification and practice time of the outside pathologists, referring practice type, and whether the second review was done at the referring institution were recorded too. Agreement in diagnosis by the above-listed specimen characteristics was analyzed.

Results: A total of 2786 cases were reviewed (2016 bone marrow and 770 tissue specimens). Disagreements in diagnosis were found in 263 cases (9.4% of total cases), and 163 (5.9%) were major disagreements. Among the major disagreements, 119 (73%) were in bone marrow specimens and 44 (27%) in tissue specimens. Among bone marrows, the most common revisions were myeloid neoplasm reclassifications (35.3%), whereas lymphoma subtype revisions comprised 70.4% of all changes in tissues. Univariate analysis showed that major disagreement rates were significantly higher in cases signed out by pathologists without hematopathology certification, those practicing for more than 10 years, and in cases from nonacademic institutions. When analyzing bone marrows and tissues separately, these differences remained significant only for bone marrows.

Conclusions: Second review of pathology material serves as an important quality assurance and patient safety measure. Lack of hematopathology training of the referring pathologists may contribute to the rate of diagnostic discrepancy.

Objective: We sought to determine the extent and distribution of workforce shortages within US medical laboratories.

Methods: The survey was conducted through collaboration between the American Society for Clinical Pathology's (ASCP's) Institute for Science, Technology and Policy in Washington, DC, and the Evaluation, Measurement and Assessment Department and ASCP Board of Certification in Chicago, Illinois. Data were collected using an internet survey distributed to individuals in a position to report on staffing and certifications for their laboratories.

Results: Findings from the ASCP 2024 Vacancy Survey indicate that although vacancy rates have declined compared with 2022, they remain elevated relative to those observed before the COVID-19 pandemic. Retirement rates continue to rise, with 10 of the 17 laboratory departments surveyed reporting increases. Among surveyed laboratory departments, the most frequently cited concern regarding artificial intelligence was the challenge of adapting to emerging technologies. Despite this sentiment, the perceived potential of artificial intelligence to transform laboratory operations remains a major source of enthusiasm.

Conclusions: Current vacancy survey data suggest continued challenges in recruitment of laboratory professionals. Qualitative analysis results show that there is an urgent need for advocacy for laboratory professionals, increased credentialing of laboratory professionals, and an increase in the number of laboratory education and training programs.

Objective: Atypical ductal hyperplasia (ADH) shares histologic features with low-grade ductal carcinoma in situ (DCIS). "ADH bordering on DCIS" represents a diagnostic gray zone with variable interobserver agreement, complicating clinical management.

Methods: We retrospectively analyzed 54 cases of ADH bordering on DCIS between 2010 and 2023. Each case underwent independent histologic review by multiple breast pathologists from different institutions. Histologic features, radiologic findings, clinical follow-up data, and interobserver agreement were analyzed.

Results: While pathologists showed moderate to substantial agreement on individual histologic features, agreement in distinguishing ADH from DCIS was poor (κ = 0.16). Lesion extent (47.7%) was the most frequently cited diagnostic factor, followed by nuclear features (24.9%) and duct involvement (18.5%). Among biopsy cases, those with carcinoma (DCIS or invasive) on subsequent excision (n = 22) were compared to those without (n = 16). Nuclear size more than 2-fold of background epithelial cells (P = .02), spindle-shaped nuclei (P = .006), and necrosis (P = .048) were significantly associated with carcinoma on excision. The presence of any 1 feature had 36.4% sensitivity and 72.2% specificity.

Conclusions: Breast pathologists demonstrated substantial agreement on individual histologic features but poor agreement on final diagnoses, likely due to differences in weighting histologic parameters. While lesion extent was frequently cited, it did not significantly differ between cases with and without carcinoma on excision. Instead, nuclear enlargement, necrosis, and spindle-shaped nuclei were significantly associated with carcinoma in subsequent excision. We propose that biopsy cases exhibiting a nuclear size more than 2-fold of background epithelial cells, necrosis, or spindle-shaped nuclei should be suggestive of DCIS.

Objective: The role of NPM1 immunostaining as a surrogate marker for acute myeloid leukemia (AML) with nucleophosmin (NPM1) mutation (AML-NPM1) in leukemia cutis has not been investigated.

Methods: NPM1 immunostaining was performed using a polyclonal antibody on leukemia cutis diagnosed in 2017-2024 of 15 patients with and 15 without the NPM1 mutation. Targeted next-generation sequencing assays were performed on the initial bone marrow biopsy specimens.

Results: There were 18 skin biopsy specimens from 15 patients (11 men, 4 women, 33-90 years, median: 66 years) with AML-NPM1. Thirteen (87%) patients had multiple lesions, often on the trunk and extremities. There were 8 and 10 skin biopsies done concurrently and after the bone marrow AML diagnosis, respectively. The time interval between AML-NPM1 diagnosis and leukemia cutis was 0 to 38 months (median, 1 month). NPM1 immunostaining was positive in 18 of 18 skin biopsy specimens of patients with AML-NPM1 with a leukemic infiltrate. NPM1 immunostaining was negative in 15 of 15 leukemia cutis specimens of patients with AML who had other molecular alterations not involving NPM1. The sensitivity and specificity of NPM1 immunostaining in detecting cutaneous AML-NPM1 infiltrate are 100% and 100%, respectively.

Conclusions: Although limited in number, our study shows that NPM1 immunostaining is sensitive and specific in detecting AML-NPM1-mutated cells in skin.

Objective: To develop an automated detection tool for Helicobacter pylori (HP) microorganisms (HPOrg) and intestinal metaplasia (IM) identification on gastric biopsy specimens on hematoxylin and eosin (H&E) whole-slide images (WSIs), incorporating background histopathologic features.

Methods: A total of 180 H&E gastric biopsy WSIs, archived at the Department of Anatomical Pathology, Singapore General Hospital, were used to train, validate, and test (60:20:20) a decision support tool. Eighty WSIs displayed non-HP inflammation; 100 were annotated for HP-associated gastritis, HPOrg, and IM. A 2-stage model was employed-a Vision Transformer-based model filtered artifacts after stain normalization, and then a Graph Attention Network component aggregated patch-level features, giving a prediction for each of 6 tissue sections within each WSI, with a majority vote determining the final WSI prediction.

Results: A total of 776 636 patches were used for training/validation and testing. The optimized model showed HPOrg classification (precision: 0.604, F1-score: 0.617, and top 10 micro F1-score: 0.714) and IM classification (precision: 0.905, F1-score: 0.861, and top 10 micro F1-score: 1.0). The macro average F1-score was 0.739, section-level precision was 0.981, and the F1-score was 0.945. The WSI-level precision achieved was 1.0, with a F1-score of 0.96.

Conclusions: We demonstrate a 2-stage model to detect HP and IM in gastric biopsy specimens, considering background inflammation, which more closely reflects real-world clinical diagnosis.

Objective: In this study, we compared the workflow of the Genius Digital Diagnostics System (Hologic, Inc) with our current workflow based on the ThinPrep Imaging System (Hologic, Inc) to assess potential efficiencies associated with digitalization of Papanicolaou screening.

Methods: Each step of the current workflow (glass slide movement and slide review) and the experimental workflow were documented. Substantial workflow efficiencies were associated with the reduction of glass slide movement observed with the experimental workflow of the Genius system compared with the ThinPrep system.

Results: The ThinPrep-based workflow required more than 5 hours of hands-on time at specific synchronized times throughout the day, whereas the hands-on time of the experimental Genius Digital Diagnostics System was just over an hour and allowed glass movement at flexible times. In addition to these workflow efficiencies, the Genius Digital Diagnostics System resulted in much shorter review times (70.1 seconds) than the ThinPrep Imaging system (138.0 seconds) while maintaining similar agreement to the sign-out diagnosis.

Conclusions: This study demonstrated that implementing a Genius Dx-based workflow may result in substantial efficiency gains, which can mitigate workforce shortages and improve turnaround time without compromising screening accuracy.

Objective: Large language models (LLMs) can process text for various applications, including surgical pathology reports, but studies primarily focus on English. Their performance has not been systematically studied for a low-resource language. To analyze the performance of various LLMs, 759 Turkish pathology reports from 5 different procedures were selected.

Methods: We used 10 examples from every procedure to optimize prompts for OpenAI's GPT-3.5 Turbo, GPT-4o mini, and GPT-4o. The rest was used to test generalizability.

Results: The GPT-4o model performed superior in processing Turkish reports (12%-25% over GPT-3.5 Turbo, 3%-16% over GPT-4o mini). English-translated versions of the reports have been demonstrated to enhance accuracy, especially for GPT-3.5 Turbo and GPT-4o mini. GPT4-o showed comparable results for Turkish and English. A 12% to 22% performance gap was observed between GPT-4o and GPT-3.5 Turbo for English-translated reports. Domain-related tips in prompts increased accuracy. Results of larger test sets were parallel for all models with the validation set. The GPT-4o model yielded the most accurate results, while the GPT-4o mini model demonstrated intermediate performance. The GPT-3.5 Turbo model exhibited the least accuracy.

Conclusions: To our knowledge, for the first time in the literature, we have demonstrated the performance of GPT models in Turkish surgical pathology reports, and results indicate that data extracted by GPT-4o are almost ready for direct application.

Objective: Underfilled blood tubes (short draws) are often collected from children or those with poor venous access. In a pilot study, we investigated which tests among a large acute care panel could be reported on short draws.

Methods: Blood was drawn in BD vacutainers (short draw: 1 mL [33%-56% fill volume] vs complete draw: 1.8-3 mL [100% fill volume]) from 12 volunteers for 3 coagulation tests, 36 chemistry tests, and the complete blood count (CBC) with differential. Tests that were strong candidates for reporting did not have statistically significant biases between short and complete draws, whereas potential candidates had statistically significant biases that were small (<25% of total allowable error and less than desirable bias from biological variation). Biases that increased or decreased across concentration ranges invalidated reporting candidacy.

Results: Two coagulation tests, 14 chemistry tests, and 15 CBC components were strong candidates for reporting. There were 9 chemistry tests and 2 CBC components that were potential candidates for reporting.

Conclusions: Underfilled blood tubes, or short draws, may be valid collections for several coagulation, chemistry, and hematology tests-which may prevent additional unnecessary phlebotomy. Laboratories should perform their own studies to determine if short draws are acceptable for limited testing using their tube and instrument types.