Clinics in Laboratory Medicine

No abstract text is available yet for this article.

The advent of high-dimensional single-cell technologies has enabled detection of cellular heterogeneity and functional diversity of immune cells during health and disease conditions. Because of its multiplexing capabilities and limited compensation requirements, mass cytometry or cytometry by time of flight (CyTOF) has played a superior role in immune monitoring compared with flow cytometry. Further, it has higher throughput and lower cost compared with other single-cell techniques. Several published articles have utilized CyTOF to identify cellular phenotypes and features associated with disease outcomes...

In this review, the authors discuss the fundamental principles of machine learning. They explore recent studies and approaches in implementing machine learning into flow cytometry workflows. These applications are promising but not without their shortcomings. Explainability may be the biggest barrier to adoption, as they contain "black boxes" in which a complex network of mathematical processes learns features of data that are not translatable into real language. The authors discuss the current limitations of machine learning models and the possibility that, without a multiinstitutional development process, these applications could have poor generalizability...

Primary immunodeficiencies were initially identified on the basis of recurrent, severe or unusual infections. Subsequently, it was noted that these diseases can also manifest with autoimmunity, autoinflammation, allergy, lymphoproliferation and malignancy, hence a conceptual change and their renaming as inborn errors of immunity. Ongoing advances in flow cytometry provide the opportunity to expand or modify the utility and scope of existing laboratory tests in this field to mirror this conceptual change. Here we have used the B cell subset, variably known as CD21low B cells, age-associated B cells and T-bet+ B cells, as an example to demonstrate this possibility...

Flow cytometry analysis has stood the test of time as a powerful tool in the assessment of hematologic neoplasms. The role of flow cytometry has expanded to evaluate various nonhematologic neoplasms encountered in body cavity malignant effusions, lymph nodes, and other body sites. This review explores the use of routine antibody panels as well as specially designed multicolor antibody panels that have been investigated by different groups and reported in the literature for evaluating nonhematologic neoplasms...

Clinical flow cytometry tests for inherited and acquired platelet disorders are useful diagnostic tools but are not widely available. Flow cytometric methods are available to detect inherited glycoprotein deficiencies, granule release (secretion defects), drug-induced thrombocytopenias, presence of antiplatelet antibodies, and pharmacodynamic inhibition by antiplatelet agents. New tests take advantage of advanced multicolor cytometers and allow identification of novel platelet subsets by high-dimensional immunophenotyping...

Classic Hodgkin lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and T cell/histiocyte-rich large B cell lymphoma form a unique set of lymphomas with similar morphologic growth patterns (occasional neoplastic cells within a prominent cellular cell background) that are pathobiologically related. Distinguishing these entities has been historically difficult by flow cytometry; however, our laboratory has developed antibody-fluorochrome combinations capable of immunophenotyping these lymphomas. Additionally, characterization of the background reactive lymphocytes can aid in narrowing the differential diagnosis...

The utility of flow cytometry analysis in the evaluation of chronic myeloid neoplasms, such as myelodysplastic neoplasms and chronic myeloproliferative neoplasms, continues to be emphasized and explored. Recently flow cytometry analysis has been also proven to be able to distinguish persistent clonal hematopoiesis from measurable residual disease in patients with acute myeloid leukemia (AML), a finding with potential critical treatment impact in the management of patients with AML.

This review discusses recent updates in the diagnosis of acute leukemias of ambiguous lineage and emphasizes the necessary elements for proper flow cytometric evaluation of these cases. The current emphasis of the classification system is toward interpreting the marker expression in light of the intensity of lineage markers and avoiding a diagnosis of mixed phenotype acute leukemia based solely on immunophenotyping without considering underlying genetic findings. Novel entities including mixed phenotype acute leukemia with ZNF384 rearrangements and acute leukemias of ambiguous lineage with BCL11B rearrangements seem to show characteristic flow cytometric immunophenotypes discussed here...

Although final classification of acute myeloid leukemia (AML) integrates morphologic, cytogenetic, and molecular data, flow cytometry remains an essential component of modern AML diagnostics. Here, we review the current role of flow cytometry in the classification, prognostication, and monitoring of AML. We cover immunophenotypic features of key genetically defined AML subtypes and their effects on biological and clinical behaviors, review clinically tractable strategies to differentiate leukemias with ambiguous immunophenotypes more accurately and discuss key principles of standardization for measurable residual disease monitoring...

Flow cytometry plays a critical role in the diagnosis, prognostication, therapy response evaluation, and clinical management of plasma cell neoplasms. The review summarizes how flow cytometry is used in the initial evaluation to distinguish primary and secondary clonal plasma cell populations from each other and from reactive plasma cells. We further illustrate the kinds of prognostic information the assessment can provide at diagnosis and disease follow-up of primary plasma cell neoplasms. Technical requirements for MRD assays and their use in therapy efficacy assessment and clinical decision-making in multi-myeloma are discussed...

Flow cytometry (FC) is a well-established method important in the diagnosis and subclassification of lymphoma. In this article, the role of FC in lymphoma prognostication will be explored, and the clinical role for FC minimal/measurable residual disease testing as a monitoring tool for mature lymphoma will be introduced. Potential pitfalls of monitoring for residual/recurrent disease following immunotherapy will be presented.

Multiparametric flow cytometry assays are long recognized as an essential diagnostic test for leukemias and lymphomas. Lacking Food and Drug Administration-approved standardized tests, these assays remain laboratory developed tests. The recently published guidelines, CLSI H62, are the most detailed and up-to-date instructions for designing and validating clinical flow cytometry assays. This review provides a historical background for the current situation, summarizes key points from the CLSI guidelines, and lists practical points for assay development gained from personal experience...

Flow cytometry enables multiparametric characterization of hematopoietic cell immunophenotype. Deviations from normal immunophenotypic patterns comprise a cardinal feature of many hematopoietic neoplasms, underscoring the ongoing essentiality of flow cytometry as a diagnostic tool. However, understanding of aberrant hematopoiesis requires an equal understanding of normal hematopoiesis as a comparator. In this review, we outline key features of healthy adult hematopoiesis and lineage specification as illuminated by flow cytometry and provide diagrams illustrating what a diagnostician may observe in flow cytometric plots...

No abstract text is available yet for this article.

Predictive biomarker testing on metastatic breast cancer is essential for determining patient eligibility for targeted therapeutics. The National Comprehensive Cancer Network currently recommends assessment of specific biomarkers on metastatic tumor subtypes, including hormone receptors, HER2, and BRCA1/2 mutations, on all newly metastatic breast cancers subtypes; programmed death-ligand 1 on metastatic triple-negative carcinomas; and PIK3CA mutation status on estrogen receptor-positive carcinomas. In select circumstances mismatch repair protein deficiency and/or microsatellite insufficiency, tumor mutation burden, and NTRK translocation status are also testing options...

This review summarizes current knowledge on several novel and emerging renal entities, including eosinophilic solid and cystic renal cell carcinoma (RCC), RCC with fibromyomatous stroma, anaplastic lymphoma kinase-rearranged RCC, low-grade oncocytic renal tumor, eosinophilic vacuolated tumor, thyroidlike follicular RCC, and biphasic hyalinizing psammomatous RCC. Their clinical features, gross and microscopic morphology, immunohistochemistry, and molecular and genetic features are described. The diagnosis of most of them rests on recognizing their morphologic features using immunohistochemistry...

This article focuses on the recent advances in ovarian sex cord-stromal tumors, predominantly in the setting of their molecular underpinnings. The integration of genetic information with morphologic and immunohistochemical findings in this rare subset of tumors is of clinical significance from refining the diagnostic and prognostic stratifications to genetic counseling.

Metaplastic breast carcinoma (MpBC) is a heterogeneous group of tumors that clinically could be divided into low risk and high risk. It is important to recognize the different types of MpBC, as the high-risk subtypes have worse clinical outcomes than triple-negative breast cancer. It is important for the pathologist to be aware of the MpBC entities and use the proposed algorithms (morphology and immunohistochemistry) to assist in rendering the final diagnosis. Few pitfalls are discussed, including misinterpretation of immunohistochemistry and certain histomorphologies, particularly spindle lesions associated with complex sclerosing lesions...

Invasive fungal infections are increasing worldwide due to factors such as climate change and immunomodulating therapies. Unfortunately, the detection of these infections is limited due to the low sensitivity and long periods required for laboratory testing. Point-of-care testing could lead to more rapid diagnosis of these often devasting infections. However, there are currently no true point-of-care tests on the market for the detection of fungi. In this article, the current state of fungal antigen and molecular testing is reviewed, with commentary on the potential for development and use in the point-of-care setting...