American journal of clinical pathology最新文献

Objective: Prior studies have reported the loss of α-smooth muscle actin (α-SMA) immunoreactivity in the inner circular layer of the muscularis propria in small bowel motility disorder cases, but this remains controversial with conflicting data. In this study, we aimed to characterize α-SMA immunoreactivity in the muscularis propria of the small intestine-specifically, jejunum-in patients with and without small bowel motility disorder.

Methods: A total of 28 transmural proximal jejunum biopsy specimens from adult patients with clinical impression of upper gastrointestinal dysmotility disorder and 64 control tissues were evaluated. The controls were full-thickness, longitudinal tissue sections from segmental resections performed due to gunshot wounds, multivisceral transplant donation, and tumors. Immunostaining for α-SMA was performed with appropriate controls to confirm the presence of immunoreactivity in the circular and longitudinal muscle layers of the muscularis propria in each sample and recorded as retained or diminished.

Results: In the small bowel motility disorder and control cases, 42.9% (12/28) and 70.3% (49/64) of the cases showed no or minimal α-SMA immunoreactivity in the inner circular layer with peripheral accentuation, respectively.

Conclusions: Loss or diminished α-SMA immunoreactivity in the inner circular layer of the muscularis propria occurs with a similar frequency in cases with and without small bowel motility disorder and does not correlate with impairment of function.

Objective: Neurogenic differentiation factor 1 (NeuroD1) is a known marker of a subtype of small cell lung carcinoma (SCLC). In this study, we aim to assess whether there is an association between NeuroD1 with Merkel cell polyomavirus (MCPyV) status, keratin 20, thyroid transcription factor 1 (TTF1), and overall survival (OS) in 125 Merkel cell carcinomas (MCCs).

Methods: NeuroD1-positive MCC tumors were characterized by immunohistochemical stains and an external RNA sequencing data set.

Results: NeuroD1 positivity (10%-100%) was seen in 29 (23%) of 125 cases, with 60 (48%) of 126 and 113 (94%) of 120 tumors MCPyV positive and keratin 20 positive, respectively. Focal TTF1 expression was seen in 9 (7.5%) of 120 tumors. NeuroD1 expression was seen more frequently in MCPyV-negative than MCPyV-positive MCCs (P = .0002) and more frequently in keratin 20-negative tumors vs keratin 20-positive ones (P < .0001). Increased NEUROD1 expression in MCPyV-negative MCC (P < .005) was confirmed in an external RNA sequencing data set (GSE235092). Univariate analyses showed NeuroD1 positivity and MCPyV-negative status correlated with worse OS (P = .024 and P = .0076, respectively); however, only MCPyV status remained significant in multivariate analyses (P = .033).

Conclusions: NeuroD1-positive MCCs are significantly correlated with MCPyV-negative, keratin 20-negative expression, and focal TTF1 expression. NeuroD1 expression can pose a potential diagnostic pitfall in the distinction of MCC from SCLC, especially in a setting of a limited immunohistochemical panel.

Objective: Drug interference with pretransfusion testing in patients with multiple myeloma (MM) treated with daratumumab (DARA) is well recognized. Current guidelines recommend that these patients should have a red blood cell (RBC) phenotype or genotype before DARA initiation; however, there are no other standards for pretransfusion testing. While prior publications report mitigation strategies and low RBC alloimmunization risk, they do not propose a cost-effective strategy for pretransfusion testing. This study aims to assess the RBC alloimmunization risk in patients treated with DARA and propose a cost-effective algorithm for pretransfusion testing.

Methods: This is a retrospective study of patients treated with DARA and receiving RBC transfusions over 9.4 years (October 1, 2015, to January 30, 2025). Demographic data; a complete serologic profile, including blood typing, antibody screen (Ab screen), and antibody identification (Ab ID); RBC phenotype/genotype; and crossmatch data were collected for each patient. The clinically significant antibody formation incidence was recorded pre- and post-DARA and compared with a control group, with statistical significance defined as P < .05. The mitigation strategy initially used for pretransfusion testing and its optimized version are described along with their cost.

Results: Of the 850 patients with MM on DARA therapy who were identified, 172 (20%) received at least 1 RBC transfusion. Ab screens were performed on all patients pre- and post-DARA therapy. Following drug administration, all patients showed a panagglutinin, and no patients formed new clinically significant alloantibodies. The turnaround time (TAT) and cost significantly decreased when the pretransfusion strategy with optimizing pretransfusion strategy.

Conclusions: This is the most extensive study on patients treated with DARA and transfused, demonstrating no increased alloimmunization risk. DARA-related transfusion interference may be successfully mitigated by the novel strategy proposed here.

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: 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: 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.