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Analysis: Principles Of Instrumentation

Key Points Many analytic determinations made in clinical laboratories are based on measurements of radiant energy that is absorbed or transmitted. The devices used to measure absorbed or transmitted light energy are photometers and spectrophotometers. The basic components of spectrophotometers include a radiant energy source, wavelength selector, cuvette holder, photodetector, signal processors, and readout devices. A reflectometer is used to measure analytes by measuring the quantity…

Preanalysis

Key Points Errors and variables in the preanalysis stage can affect test results. Patient variables include physical activity, diet, age, sex, circadian variations, posture, stress, obesity, smoking, and medication. Strict adherence to proper technique and site selection can minimize collection variables such as hemolysis, hemoconcentration, clots, and other causes for sample rejection or erroneous results. Blood collection containers are color coded based on additive or preservative,…

Optimizing Laboratory Workflow and Performance

Key Points An effective testing process requires integration of preanalytic, analytic, and postanalytic steps. An understanding of workflow is a fundamental prerequisite to any performance optimization strategy. A variety of techniques should be used to collect workflow data. These include sample and test mapping, tube analysis, workstation analysis, staff interviews, and task (process) mapping. Though technology is a critical component of every laboratory, it is only…

General Concepts and Administrative Issues

Key Points Effective laboratory management requires leaders to provide direction and managers to get things done. Strategic planning, marketing, human resource management, financial management, and quality management are all key elements of a laboratory organization. Most laboratory errors occur in the preanalytic and postanalytic stages. Six Sigma and Lean Six Sigma are quality management tools that can be used to reduce laboratory errors and increase productivity.…

Molecular Hematopathology

▪ Introduction Molecular investigation of the hematopoietic neoplasms has contributed significantly to our understanding of the “genetic basis” of cancer, and progress in this dynamic field continues unabated. Accordingly, new knowledge concerning recurrent genetic abnormalities in myeloid and lymphoid cancers continues to be integrated within the most recent World Health Organization (WHO) classification of the hematopoietic and lymphoid tumors. This chapter summarizes key technical considerations, essential…

Flow Cytometric Principles in Hematopathology

■ Introduction The importance of immunophenotyping in diagnostic hematopathology was first emphasized by the Revised European-American Lymphoma classification, and more recently by the 2001, 2008, and 2016 World Health Organization (WHO) classifications of hematolymphoid neoplasms. In these classifications, nearly all myeloid and lymphoid malignancies are defined, at least in part, by the antigenic features of the neoplastic cells. Flow cytometry (FC) is an immunophenotyping technique in…

Disorders of the Spleen

▪ Introduction The spleen is a secondary lymphoid organ that functions in the development of the immune response and in blood filtration. In the spleen, blood-borne antigens are presented to lymphocytes and macrophages to facilitate antibody development and cytotoxic immune responses. In addition, senescent red blood cells and blood-borne foreign substances are introduced to and removed by macrophages. Finally, the spleen also serves as a reservoir…

Multiple Myeloma and Other Plasma Cell Neoplasms

■ Introduction Monoclonal expansion of plasma cells and their precursors gives rise to a spectrum of plasma cell neoplasms ranging from indolent to aggressive. These include monoclonal gammopathy of undetermined significance (MGUS; 67%), multiple myeloma (14%), solitary plasmacytoma of bone or extraosseous tissue (3%), primary amyloidosis (AA; 9%) and immunoglobulin (Ig) chain deposition diseases (>1%), POEMS (polyneuropathy, organomegaly, endocrinopathy, M component, and skin changes) syndrome, and…

Mastocytosis

▪ Introduction Mast cells (MCs) were initially recognized in 1878 by Paul Ehrlich, a Nobel laureate in immunology. They are unique inflammatory mediator cells that contain distinctive metachromatic and electron-dense cytoplasmic granules. MCs derive from bone marrow pluripotent hematopoietic progenitors. The committed bone marrow MC progenitors are first released into the bloodstream, then they transmigrate and subsequently mature in various organs under the influence of a…

Disorders of Histiocytes

▪ Derivation of Histiocytes The term histiocyte has come to encompass two cell lines, the monocyte-macrophages and the specialized antigen-presenting dendritic cells (DCs). Although a long-held belief that myeloid-derived monocytes were the immediate precursors of all macrophages and dendritic cells, the understanding of the mononuclear phagocytic system (MPS), which includes DC, monocytes, and macrophages, is undergoing continual refinement, including the nomenclature, cellular origin, and overlapping functional…

Myelodysplastic Syndromes

Overview The myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis. Clinically, this ineffective hematopoiesis manifests as progressive bone marrow failure with cytopenias and a variable probability of progression to acute myeloid leukemia (AML). Pathologically, MDSs are usually characterized by dysplastic morphologic features in one or more of the three hematopoietic lineages, with or without an accompanying increase…

Myeloproliferative and “Overlap” Myelodysplastic/Myeloproliferative Neoplasms

▪ Introduction Myeloproliferative neoplasms (MPNs), formerly referred to as myeloproliferative disorders, are a group of clonal multipotential hematopoietic stem cell diseases, proliferative in nature. MPNs are frequently associated with hypercellular bone marrow and with an elevation of one or more cell types in the blood with no ineffective hematopoiesis. These neoplasms are insidious in onset, chronic in course, but have variable tendency to terminate in marrow…

Acute Undifferentiated Leukemia and Mixed-Phenotype Acute Leukemias

■ Introduction Acute leukemias of ambiguous lineage may be divided into acute undifferentiated leukemia (AUL) and mixed-phenotype acute leukemias (MPALs). AULs are leukemias with very primitive phenotypes that lack definitive lineage-specific antigens. MPAL encompasses rare blastic hematopoietic cell neoplasms that express a mixture of myeloid and lymphoid (B- or T-lineage) antigens. Alternative names for these leukemias include hybrid acute leukemias, acute leukemias of indeterminate lineage, and…

Precursor Lymphoid Neoplasms

▪ Introduction Acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) constitute a biologic continuum of neoplastic lymphoid disorders characterized by the proliferation of immature (blast) cells of B-cell or T-cell lineage. For clinical purposes, an arbitrary cutoff has been used for many years to separate lymphoblastic leukemias and lymphomas. Cases with tissue involvement and less than 25% replacement of the marrow cellularity by lymphoid blasts have…

Acute Myeloid Leukemia

■ Introduction and Classification Expanding knowledge of acute myeloid leukemia (AML) over the past four decades has resulted in major advances in the understanding and classification of this disease. AML is known to represent a number of distinct but related diseases, some of which require unique therapeutic approaches. The 2016 World Health Organization (WHO) classification integrates blast morphology and immunophenotype with cytogenetics and molecular studies to…

Mature T-Cell and Natural Killer–Cell Leukemias

■ Introduction The mature T-cell and natural killer (NK)-cell leukemias form a heterogeneous group of diseases with diverse etiologies and markedly varied clinical behavior. When applied to T cells, the term mature or peripheral is often used to describe nonblastic T-cell neoplasms marked by their resemblance to post-thymic T lymphocytes and characterized by the absence of terminal deoxynucleotidyl transferase (TdT) expression and usually by the presence…

B-Cell Leukemias of Mature Lymphocytes

▪ Introduction The leukemias of mature B cells are a limited set of diseases in which blood and bone marrow are the primary sites of involvement. Although any lymphoproliferative disorder can eventually enter a leukemic phase, this chapter is limited to B-cell chronic lymphocytic leukemia (CLL), B-cell prolymphocytic leukemia (PLL), hairy cell leukemia (HCL), and HCL variant (HCLv). Burkitt lymphoma, which may present as leukemia, and…

Hodgkin Lymphoma

▪ Introduction In this chapter we review the definition and current classification of Hodgkin lymphoma (HL), describe the histologic and immunohistochemical features, and discuss the differential diagnosis of this intriguing disease. HL has some unusual clinical, morphologic, and biological features that set it apart from most other malignant neoplasms. Histologically it is characterized by a small minority of neoplastic cells, termed Hodgkin and Reed-Sternberg (H/RS) cells…

Immunodeficiency-Related Lymphoproliferative Disorders

■ Introduction Lymphoproliferative disorders are innately disorders of the immune system, and the immunodeficiency-related lymphoproliferative disorders are of particular interest because they offer a paradigm for studying the relationships between the immune system and the evolution of neoplastic disease. Although the various entities offer a complicated spectrum of lymphoid proliferations with heterogeneous morphologies, there are similarities across varying immunodeficiency backgrounds. They have a number of features…

Peripheral T-Cell Lymphomas

■ Introduction Peripheral T-cell lymphomas (PTCLs) are much less common than B-cell lymphomas, and they constitute approximately 10% of non-Hodgkin lymphomas (NHLs) in the United States and Europe. Derived from post-thymic T cells, PTCLs generally arise in lymphoid tissues ”peripheral” to the thymus, such as the lymph nodes, spleen, gastrointestinal tract, and skin. PTCLs have a mature T-cell phenotype and occur most frequently in adults. Because…