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Molecular Genetics and Cell Biology for Hematopathology

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Practical Lymph Node and Bone Marrow Pathology

Part of the book series: Practical Anatomic Pathology ((PAP))

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Abstract

Molecular genetic tests provide objective evidence for a final diagnosis and refined classification in hematopathology. In this chapter, the principles of genetic and molecular tests, including chromosome analysis (conventional karyotyping), fluorescence in situ hybridization (FISH), microarray, polymerase chain reaction (PCR)-based tests, next-generation sequencing (NGS)-based clonality tests and cancer mutation profiling, are outlined to help understand their application in clinical practice. The test methods frequently used to assess bone marrow and lymph node samples are compared in detail for their advantages and disadvantages, to help pathologists make better decision in choosing the most appropriate test to facilitate pathologic diagnosis. The concept of a clonal process is introduced, followed by discussions on the relationship between a clonal process and a neoplasm and the tests used in detecting clonality, clonal diversity, and clonal evolution. The approaches to identify clonal B-cell or T-cell population based on the immunoglobulin or T-cell receptor gene rearrangement are described with focus on their indications, value in facilitating lymphoma diagnosis, and the pitfalls in result interpretation. Detection of chromosome rearrangements and fusion genes is frequently used to confirm a diagnosis and monitor treatment response. Different methods are explained for their utility in identifying commonly seen translocations including BCR-ABL1, PML-RARA, IGH/BCL2, CCND1/IGH, and other less well-defined, not disease-specific chromosome rearrangements. The application of PCR-based methods, Sanger sequencing, and pyrosequencing in identifying mutations is elaborated with a special focus on how to choose these methods for different diagnostic indications in a cost-effective way. Questions about the benefit of performing clonality test by NGS and the indications of NGS-based mutation profiling for hematopoietic and lymphoid disorders are answered. In the second part of the chapter, five cases are presented to illustrate how an appropriate molecular genetic test is used to facilitate the final diagnosis of each case. The tests used in these five cases include the conventional karyotyping to detect complicated translocations, a FISH test needed for the final diagnosis of a B-cell lymphoma, the clonality tests to facilitate a diagnosis of a T-cell lymphoma, and the NGS-based mutation profiling to identify a germline mutation that would likely be missed without the novel technology.

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  1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Linsheng Zhang

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  1. Department of Pathology, Duke University School of Medicine and Duke Health System, Durham, NC, USA

    Endi Wang

  2. Department of Pathology, Duke University School of Medicine and Duke Health System, Durham, NC, USA

    Anand Shreeram Lagoo

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Zhang, L. (2020). Molecular Genetics and Cell Biology for Hematopathology. In: Wang, E., Lagoo, A.S. (eds) Practical Lymph Node and Bone Marrow Pathology. Practical Anatomic Pathology. Springer, Cham. https://doi.org/10.1007/978-3-030-32189-5_2

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  • DOI: https://doi.org/10.1007/978-3-030-32189-5_2

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  • Online ISBN: 978-3-030-32189-5

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