American journal of clinical pathology最新文献

Objective: Endoscopic ultrasound (EUS)-guided, fine-needle core biopsy (FNB), and through-the-needle microforceps biopsy (TTNB) are latest tools for evaluating pancreatic lesions. We aim to provide subspecialty surgical pathologists' experience with EUS-FNB/TTNB in diagnosing pancreatic lesions at a large academic center.

Methods: A 3-year review identified 101 EUS pancreatic specimens submitted for surgical pathology: 87 biopsy specimens (FNB = 58, TTNB = 29) and 14 fine-needle aspirations (FNAs). Diagnoses were compared with cytology and resection specimens when available.

Results: Of the 101 cases, 10 had previous EUS-FNA cytology with inconclusive diagnoses. Rebiopsy with EUS-FNB/TTNB provided definitive diagnoses in 9 cases. Thirty-five cases (18 cystic and 17 solid lesions) had concurrent surgical pathology and cytology specimens. The diagnostic yield of EUS-FNB/TTNB biopsy specimens (69%) was significantly higher than that of cytology specimens (26%, P = .0017), as was the diagnostic accuracy (P = .0012). This diagnostic advantage was statistically significant in cystic lesions (FNB/TTNB [83.3%] vs cytology [16.7%] for achieving a specific diagnosis, P = .0002) but not in solid lesions (61.5% vs 46.2%, P = .6951). Only in 1 case did cytology (adenocarcinoma) provide a more definitive diagnosis than surgical pathology (high-grade dysplasia cannot exclude adenocarcinoma).

Conclusions: The EUS-FNB/TTNB methods complement EUS-FNA cytology in diagnosing pancreatic lesions, and they often outperforms concurrent cytology specimens, particularly in cystic lesions.

Objective: According to the American Joint Committee on Cancer (AJCC) 8th edition, tumor depth of invasion is one of the essential parameters required for the staging of oral cavity squamous cell carcinoma (OSCC). We conducted this study to overview our diagnostic challenges and share our institutional experiences related to the measurement of depth of invasion.

Methods: We selected 90 OSCC cases between 2017 and 2023. The depth of invasion and tumor thickness were remeasured in each case, and the tumor stage was assigned according to the AJCC 8th edition criteria.

Results: We found that 84 of 90 (93.3%) had the same tumor stage, whether defined by tumor thickness or depth of invasion. Overall, the difference between tumor thickness and depth of invasion ranged from 0 to 3 mm. In only 6 of the 90 (6.7%) cases was the tumor stage changed based on tumor thickness. Of these 6 cases, 4 were upgraded from T1 to T2, while the remaining 2 were upgraded from T2 to T3.

Conclusions: We observed that in 93.3% of our OSCC cases, tumor stage remained the same with either depth of invasion or tumor thickness, while 6.7% were upstaged based on tumor thickness. Based on the study observations, tumor thickness appears to be more straightforward to measure than depth of invasion. In contrast, depth of invasion measurement requires certain prerequisites and can pose diagnostic challenges. Additional studies with larger cohorts are needed to compare tumor thickness with depth of invasion findings.

Objective: Fine-needle aspiration (FNA) is the gold standard for evaluating thyroid nodules. However, the patient's clinical condition rarely demands an immediate, definitive diagnosis or additional ancillary studies. This study evaluates the utility of thyroid core needle biopsies (CNBs) as an adjunct to FNA, particularly when ancillary studies are not feasible on cytologic material.

Methods: The electronic pathology database at a large academic institution was searched for cases of thyroid FNA with concurrent CNB (2000-2024). In total, 140 cases were included, and data on patient demographics, nodule characteristics, diagnoses from cytology and CNB, ancillary studies, and surgical pathology diagnosis were recorded.

Results: A definitive diagnosis was made on 98 (70%) cases of CNB concurrent with FNA. Core needle biopsies provided a definitive diagnosis in 16 (64%) FNA category I cases of The Bethesda System for Reporting Thyroid Cytopathology. Fifty-four (38.5%) CNBs were benign, and 43 (30.7%) CNBs were malignant, including 23 (16.4%) primary thyroid carcinomas, 9 (6.4%) lymphomas, 6 (4.2%) secondary carcinomas, and 5 (3.5%) other malignancies. Nine CNB cases were diagnosed as indeterminate, including 5 atypical cases and 4 suspicious for malignancy. Ancillary studies, including immunostains (49), molecular testing (19), PD-L1 (3), and fluorescence in situ hybridization (2), were performed in 73 (52%) CNBs, and histology diagnoses were in agreement in 39 (79.6%) of 49 cases. Eleven (7.8%) CNBs were nondiagnostic. Minor complications (small hematomas) occurred in 3 (2%) cases.

Conclusions: Concurrent FNA and CNB can be valuable, potentially reducing the surgery rate. Core needle biopsy is particularly useful for repeatedly nondiagnostic FNA, atypical cells, or when tissue is needed for diagnostic, prognostic, or molecular profiling of malignancies such as anaplastic thyroid carcinoma.

Objective: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described autoinflammatory syndrome caused by pathogenic variants in UBA1. However, there is a dearth of widely available UBA1 testing aside from large, expensive sequencing studies. Thus, we sought to rapidly develop, validate, and clinically deploy a cost-effective assay for detecting the most common UBA1 variants.

Methods: We developed, validated, and implemented a single base extension mass spectrometry assay for detecting pathogenic UBA1 variants at the c.121, c.122, and c.118-1 positions in patients with suspected VEXAS syndrome. Assay performance characteristics were assessed using peripheral blood and bone marrow samples from patients with (n = 8) and without (n = 36) VEXAS.

Results: The assay demonstrated a lower limit of detection (LOD) of 10% variant allele fraction for each mutation. The analytical accuracy, sensitivity, and specificity were each demonstrated to be 100% at the LOD, with excellent intra- and interrun reproducibility. Based on literature review of reported UBA1 variants associated with VEXAS, to date, this assay detects the most prevalent variants, with a clinical sensitivity of 97% or more.

Conclusions: A cost-effective, mass spectrometry-based assay with high analytical and clinical performance can feasibly be implemented in hospital laboratories for diagnosis of VEXAS syndrome.

Objective: The practice of surgical neuropathology incorporates molecular results into diagnoses that already integrate histologic, radiologic, and clinical findings. Many surgical pathologists evaluate central nervous system (CNS) tumors without neuropathology board certification.

Methods: This review describes key preanalytical, analytical, and postanalytical considerations for molecular testing and provides context for these considerations using frequently encountered CNS tumors. An overview of common molecular modalities, including limitations, is given, and pitfalls in interpretation are addressed.

Conclusions: In summary, this review offers a practical reference for the diagnosis of CNS specimens in a general surgical pathology practice.

Systemic mastocytosis with an associated myeloid neoplasm (SM-AMN) represents a diagnostic challenge. The first section of the XVI European Bone Marrow Working Group Workshop, held in Barcelona, Spain, in 2023, focused on such cases. Three main lessons were learned from the workshop. First, both the SM and the AMN components can mask each other. Second, because of their overlapping clinical and laboratory findings, it is usually impossible to recognize advanced systemic mastocytosis within an SM-AMN. In other words, unless the International Consensus Classification "C" findings were clearly caused by the SM, for purposes of classification, the SM component was regarded as not advanced. The distinction between indolent and smoldering SM was impossible, but the presence of mast cell leukemia as the SM component is usually recognizable and should be reported. Finally, the presence of myeloid gene mutations (other than KIT) were strongly associated with SM-AMN. These variations include SRFS2-p95, biallelic (double) TET2 or a TET2 mutation combined with an SRSF2 variation to identify chronic myelomonocytic leukemia associated with SM. Additional diagnostic issues included disease progression in the SM or the AMN component, the distinction between SM-AMN and acute myeloid leukemia with partial mast cell differentiation (aka, myelomastocytic leukemia), and rare types of disease proliferations occurring in SM-AMN.

Objective: We evaluated the clinical performance of Roche Digital Pathology Dx, a whole slide imaging (WSI) system, in 2 studies according to US Food and Drug Administration (FDA) and Digital Pathology Association criteria.

Methods: Precision was measured by pathologists identifying 23 histopathology features; accuracy was assessed by comparing diagnoses from 2047 clinical cases with those from manual microscopy, with exploratory analyses including subgroup-specific diagnostic discrepancy rates.

Results: Both studies met all predetermined primary endpoints. Precision between systems/sites was 89.3%; between days, 90.3%; and between readers, 90.1% (lower bound of 95% CI for each, ≥85%). The difference in accuracy between digital reads (DRs) and manual microscopy reads (MRs) vs reference sign-out diagnosis (SD), DRs - MRs, was -0.61% (lower bound of 95% CI, -1.59%), which was greater than the lower bound acceptance criterion (-4%). Mean case reading times were similar: 2.33 minutes (DRs) and 2.34 minutes (MRs). Review of breast, lung, bladder, kidney, and stomach case diagnoses did not identify DR modality-specific root causes for major diagnostic disagreements. Higher than expected disagreements in both modalities were traced to COVID-19 pandemic-related resource constraints, leading to challenging case adjudications and higher disagreement rates for longer SDs. Direct DR/MR adjudication supported this hypothesis, resulting in an intermodality disagreement rate of 4.77%; using SD as a "tiebreaker" reduced the overall DR disagreement rate to 2.97%.

Conclusions: Roche Digital Pathology Dx is noninferior to manual microscopy for primary diagnosis in surgical pathology, with performance results similar to 5 distinct FDA-cleared WSI systems using different scanners.

Objective: Due to low malaria prevalence, implementation of the only US Food and Drug Administration (FDA)-cleared rapid malaria diagnostic, BinaxNOW Malaria, in US clinical laboratories is challenging due to limited clinical specimens for test verification. We describe the initial BinaxNOW evaluation at an academic medical center and its verification across a large health care network with site-based microbiology laboratories, using well-characterized, previously tested blood samples.

Methods: For the initial evaluation, we compared the BinaxNOW Malaria to blood smear examination in 294 whole-blood specimens at the primary evaluation site. For subsequent site-based verification, each site tested 10 previously malaria antigen-positive and 10 previously malaria antigen-negative whole-blood specimens. Positive percent agreement (PPA), negative percent agreement (NPA), concordance, and reproducibility were calculated.

Results: For the initial evaluation, the BinaxNOW Malaria correctly identified Plasmodium species in 100% of specimens positive for Plasmodium falciparum with 96% identified to the species level. Overall BinaxNOW Malaria test sensitivity and specificity were 100%. For the subsequent site-based verification, PPA, NPA, concordance, and reproducibility were 100%.

Conclusions: The approach described provides proof of concept for BinaxNOW Malaria test verification in areas with low malaria prevalence using archived well-characterized blood samples. With this strategy, rapid malaria antigen testing could be expanded, improving diagnostic capabilities across the United States.

Objective: Panfungal sequencing (PFS) using formalin-fixed, paraffin-embedded (FFPE) tissue aids genus-level or species-level identification in suspected invasive fungal infections. Given the limited availability of PFS and potential risk of environmental contamination, defining histopathologic features predictive of clinically interpretable results is important.

Methods: We evaluated FFPE tissue samples submitted for PFS over a 5-year period. Histopathologic data were extracted from pathology reports; in-house cases were re-reviewed, and the burden of fungal elements was assessed using Grocott methenamine silver stain. Any available fungal culture data were also obtained for in-house cases.

Results: Of 153 cases with fungal elements reported by histopathology, 54% were positive by PFS. Of 97 cases without histologic evidence of fungal elements, only 9% were positive by PFS, and all were considered potential environmental contaminants. Culture results were available for only 9 of 461 (2%) cases, and all cultures were concordant with the PFS results. When the pathologist proposed 1 or more specific organisms based on histologic appearance alone, PFS was discrepant in 37% of cases. Of those discrepant diagnoses, and if we designate the PFS result as the true diagnosis, then 53% of misclassifications had the potential for administration of suboptimal antifungal therapy. There was no correlation between the relative abundance of fungal elements in tissue sections and detection of fungal organisms by PFS.

Conclusions: Panfungal sequencing can provide genus-level and species-level identification in the setting of visible fungal elements in FFPE tissue. It is a valuable diagnostic tool, particularly when fungal infections are clinically suspected but fungal cultures were not performed.

Objective: Somatic hypermutation at immunoglobulin heavy chain variable (IGHV) genes, an established prognostic and predictive biomarker for chronic lymphocytic leukemia (CLL), is assessed by gene sequencing. We developed a single methylation-specific droplet digital polymerase chain reaction (methyl-ddPCR) to predict IGHV status in patients with CLL.

Methods: The CLL methylation array and IGHV data from the International Cancer Genome Consortium (ICGC) were used for biomarker discovery. Top-ranked candidate regions were manually screened for PCR primer and probe binding sites. A single methyl-ddPCR was evaluated on an internal cohort of CLLs with mutated (M), unmutated (U), and inconclusive IGHV results originally determined by next-generation sequencing (NGS).

Results: Analysis of ICGC data identified array probe cg23844018 as a candidate for the PCR. The corresponding CpG site showed high methylation levels in U-CLL and lower levels in M-CLL. On the internal cohort, a single optimal cutoff correctly classified 104 of 115 U- and M-CLLs (90.4%; area under the curve = 0.96). The PCR data correlated with some prognostic fluorescence in situ hybridization and CLL subset groupings. Limited analysis suggests that the PCR may be able to stratify some patients with CLL who have inconclusive results on IGHV NGS testing.

Conclusions: The methyl-ddPCR showed high concordance with CLL IGHV status in an internal cohort.