American journal of clinical pathology最新文献

Objectives: To investigate the correlation between the extent of (percentage of tumor cells) immunohistochemistry (IHC) staining and final human epidermal growth factor receptor 2 (HER2)-positive result in fluorescence in situ hybridization (FISH) groups 2 to 4 with equivocal (2+) IHC requiring second, blinded FISH evaluation.

Methods: Breast cancer cases submitted for HER2 FISH testing with group 2 to 4 results were included.

Results: Of the 2548 cases with HER2 FISH groups 2 to 4 that had HER2 IHC performed, 1104 (43.3%) (76/182 [41.8%] of group 2, 94/161 [58.4%] of group 3, 934/2205 [42.4%] of group 4) had equivocal (2+) IHC. After second blinded, IHC-guided recounts, 217 of 1104 (19.7%) (17/76 [22.4%], 75/94 [79.8%], 125/934 [13.4%] of FISH groups 2, 3, 4 with IHC 2+, respectively) had final HER2-positive status. Only 13 of 217 (6%) of the cases with HER2-positive status had more than 50% circumferential staining of the tumor targeted for rescoring.

Conclusions: In over 90% of HER2 FISH group 2 to 4 breast cancers with equivocal (2+) IHC followed by targeted, blinded second FISH evaluation and final HER2-positive result, the amplified population of tumor cells was limited (<50%). Current guidelines recommend cancers having 10% to 50% of the subpopulation with amplified cells classified as having genetic heterogeneity (GH), which have a poor response to targeted therapies. Identifying these tumors as having GH and/or repeat testing may be recommended.

Objectives: Acute myeloid leukemia (AML) with mast cell (MC) differentiation was recently described as an aggressive subgroup of AML cases. The objectives of this study were to assess the flow cytometric immunophenotypic features of AML-MC cases.

Methods: We characterized the immunophenotypic features of 21 AML-MC cases by flow cytometry and compared them to 20 reactive/regenerating bone marrow specimens.

Results: The number of MCs detected by flow cytometry in AML-MC cases ranged from 0.4% to 21.1%, with a median of 3.5%, significantly higher than that of normal/reactive bone marrow (BM) (median, 0.01%; range, 0.000%-0.396%; P < .0001). Immunophenotypically, MCs in AML-MC cases demonstrated immaturity, differing from MCs in normal/reactive BMs, including dimmer CD45 (100% vs 0%), lower side scatter (100% vs 0%), more frequent CD34 (81% vs 20%), and CD123 (100% vs 10%) positivity, and more frequent uniform/increased CD38 expression (95% vs 20%) (all P ≤ .0001). CD2 (0/5) and CD25 (2/6, 1 uniform and 1 partial) were assessed in a subset of cases. The myeloblasts in AML-MC were typically CD34+CD117+HLA-DR+ with unusually frequent expression of CD56 (57%, all partial) and CD25 (63%, mostly partial), increased CD117 (62%), and decreased CD38 (86%). The MC percentage determined by flow cytometry correlated well with MCs detected by tryptase immunohistochemistry (r = 0.76, P < .001).

Conclusions: The MCs in AML-MC cases are characterized by dim CD45, low side scatter, CD34 and CD123 positivity, and uniform and increased CD38 expression. Flow cytometry is an excellent tool for identifying AML-MC cases.

Objectives: The blasts in most cases of chronic myeloid leukemia blast phase (CML-BP) have a myeloid or precursor-B immunophenotype, with only a small subset having T-cell or natural killer-cell lineage. Patients with CML-BP having early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) are extremely rare.

Methods: We report the clinicopathologic, immunophenotypic, and molecular genetic features and outcome of 3 patients with CML-BP who had ETP-ALL, with a review of the literature.

Results: Only patient 1 had a history of chronic myeloid leukemia chronic phase. Fluorescence in situ hybridization revealed BCR::ABL1 rearrangement in cells with round nuclei (blasts) and cells with segmented nuclei (neutrophils) in cases 2 and 3, supporting a diagnosis of CML-BP rather than de novo Ph+ ETP-ALL. The blasts were positive for cytoplasmic CD3, CD7, CD33, and CD117; were negative for CD1a and CD8; and had dim CD5 expression in 2 cases. Next-generation sequencing showed a TET2 mutation in case 1 and BCOR, RUNX1, and STAG2 mutations in case 3. All patients received chemotherapy and tyrosine kinase inhibitors. Patients 2 and 3 died 33 days and 39 days, respectively, after diagnosis. Patient 1 received stem cell transplantation and was alive 14 months after blast phase.

Conclusions: Patients with CML-BP may have ETP-ALL. These patients usually have an aggressive clinical course, requiring intensive therapy, and may benefit from stem cell transplantation.

Objectives: ROS-1 immunohistochemistry (IHC) is a common method for screening ROS1 fusion in the clinical management of non-small cell lung cancer. The interpretation criteria for ROS-1 SP384 IHC, however, remain unestablished.

Methods: Sixty-five non-small cell lung cancer cases underwent AmoyDx ROS1 fusion real-time polymerase chain reaction (PCR) study and ROS-1 SP384 IHC tests, which were retrieved for analysis. ROS-1 IHC tests were interpreted based on the established classifiers as well as the presence of diffuse homogeneous immunoreactivity. The diagnostic accuracies of these ROS-1 IHC interpretation methods were evaluated by comparing them with the ROS1 real-time PCR results.

Results: Previous ROS-1 IHC classifiers demonstrated high sensitivity for positive ROS1 real-time PCR results (100%), but they showed low specificities (25%-50%) and overall accuracies (58%-72%). In contrast, the diffuse homogeneous ROS-1 immunoreactivity predicted positive ROS1 real-time PCR results with much higher specificity (94%) and overall accuracy (95%), albeit with a slightly lower sensitivity (97%). Some cases that showed discrepancy between diffuse homogeneous ROS-1 immunoreactivity and real-time PCR results involved rare ROS1::LDLR fusion and suboptimal IHC staining.

Conclusions: A 3-tier reporting system for ROS-1 SP384 IHC testing combining previous interpretation criteria and diffuse and homogeneous immunoreactivity may better predict ROS1 fusion status without decreasing specificity.

Objectives: Laboratory testing, crucial for medical diagnosis, has 3 phases: preanalytical, analytical, and postanalytical. This study set out to demonstrate whether automating tube labeling through artificial intelligence (AI) support enhances efficiency, reduces errors, and improves outpatient phlebotomy services.

Methods: The NESLI tube-labeling robot (Labenko Informatics), which uses AI models for tube selection and handling, was used for the experiments. The study evaluated the NESLI robot's operational performance, including labelling time, technical problems, tube handling success, and critical stock alerts. The robot's label readability was also tested on various laboratory devices. This research will contribute to the field's understanding of the potential impact of automated tube-labeling systems on laboratory processes in the preanalytical phase.

Results: NESLI demonstrated high performance in labeling processes, achieving a success rate of 99.2% in labeling parameters and a success rate of 100% in other areas. For nonlabeling parameters, the average labeling time per tube was measured at 8.96 seconds, with a 100% success rate in tube handling and critical stock warnings. Technical issues were promptly resolved, affirming the NESLI robot's effectiveness and reliability in automating the tube-labeling processes.

Conclusions: Robotic systems using AI, such as NESLI, have the potential to increase process efficiency and reduce errors in the preanalytical phase of laboratory testing. Integration of such systems into comprehensive information systems is crucial for optimizing phlebotomy services and ensuring timely and accurate diagnostics.

Objectives: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). Its most common immunophenotype is CD4+/CD7-/CD25+, although unusual immunophenotypes can occur and may lead to misdiagnosis.

Methods: The immunophenotypes, cytogenetics, molecular features, clinical presentations, treatment, and prognosis of 131 patients with ATLL were retrospectively studied in a large tertiary medical center in the United States.

Results: All cases showed loss of CD7 expression. While 82.4% of cases demonstrated CD4+, 17.6% exhibited unusual phenotypes, including CD4+/CD8+ (6.9%), CD4-/CD8- (2.3%), CD5- (3.1%), CD2-, and CD3-. The most common cytogenetics abnormalities included polysomy 3 (34.6%), translocation 1 (23.1%), and abnormalities found on chromosome 11 (30.8%) and chromosome 14 (26.9%). The common gene mutations identified by the next-generation sequencing study were TP53 (16.7%), TBL1XR1 (16.7%), EP300 (14.3%), and NOTCH1 (14.3%). TBL1XR1 mutation is associated with genetic instabilities. There was no significant difference between the clinical presentations of these 2 groups.

Conclusions: Adult T-cell leukemia/lymphoma exhibits versatile immunophenotypic, cytogenetic, and molecular features. Simultaneous involvement of blood, lymph nodes, and other organs, along with hypercalcemia in a patient from an endemic area, necessitates HTLV-1 testing to avoid underdiagnosis of this dismal disease that might need aggressive chemotherapy followed by bone marrow transplant.

Objectives: Nodular regenerative hyperplasia (NRH) is a rare vascular disorder of the liver. Clinically, patients present with portal hypertension with or without a cholestatic pattern of injury. Histologically, the liver parenchyma is composed of small nodules of hypertrophic hepatocytes surrounded by atrophic hepatocytes without significant fibrosis. Nodular regenerative hyperplasia is a difficult diagnosis on biopsy specimens, but biopsy remains the gold standard for diagnosis. In this retrospective review, cytokeratin 7 (CK7) immunohistochemistry (IHC) was used to aid in the diagnosis and further characterization of NRH and NRH-like changes.

Methods: The H&E-stained slides, reticulin, and CK IHC were reviewed for 22 cases. The percentage of hepatocytes staining for CK7 (0%-100%), the location of staining (centrilobular hepatic progenitor cells vs periportal/bile ductular reaction), and the pattern of staining distribution (patchy or diffuse) were recorded for comparison.

Results: Of the 22 cases, 9 were CK7 positive. Cases of NRH, however, expressed various degrees of CK7 positivity in centrilobular hepatic progenitor cells, unlike NRH-like changes, which were either CK7 negative or CK7 positive in periportal hepatocytes or in areas of bile ductular reaction.

Conclusions: In cases with the appropriate clinical history and histology, CK7 immunohistochemistry can be performed to distinguish nodular regenerative hyperplasia (primary) and NRH-like changes (secondary). In difficult cases, CK7 positivity in centrilobular hepatic progenitor cells can help confirm the diagnosis of NRH. These data support NRH as a true entity with a distinct pathophysiology from NRH-like changes.

Objectives: This review summarizes the current and potential uses of artificial intelligence (AI) in the current state of clinical microbiology with a focus on replacement of labor-intensive tasks.

Methods: A search was conducted on PubMed using the key terms clinical microbiology and artificial intelligence. Studies were reviewed for relevance to clinical microbiology, current diagnostic techniques, and potential advantages of AI in routine microbiology workflows.

Results: Numerous studies highlight potential labor, as well as diagnostic accuracy, benefits to the implementation of AI for slide-based and macroscopic digital image analyses. These range from Gram stain interpretation to categorization and quantitation of culture growth.

Conclusions: Artificial intelligence applications in clinical microbiology significantly enhance diagnostic accuracy and efficiency, offering promising solutions to labor-intensive tasks and staffing shortages. More research efforts and US Food and Drug Administration clearance are still required to fully incorporate these AI applications into routine clinical laboratory practices.