In this chapter, Manier et al. describe the 'driver' gene alterations involved in the development and progression of multiple myeloma (MM) and discuss the therapeutic implications of a comprehensive understanding of the genomic complexity of MM. Summary points The pathologic diagnosis of multiple myeloma (MM) and other plasma cell proliferative disorders (PCPD) is made on the bone marrow aspirate and biopsy specimen. The goal of the pathologic examination of the bone marrow is to: (a) quantify bone marrow plasma cells (PC); (b) establish PC clonality; (c) distinguish MM from lymphoplasmacytic lymphoma (LPL) and other B-cell lymphomas with plasmacytic differentiation; (d) analyze prognostic factors; (e) detect amyloid deposits; and (f) detect other potential pathologic processes. The standard of care for PC quantification is still morphologic assessment of the bone marrow aspirate and biopsy. Clonality of PCs is inferred by showing of monotypic immunoglobulin light chain expression (kappa or lambda) and/or abnormal patterns of antigen expression. Bone marrow examination helps differentiate LPL from MM. In MM, a monomorphic PC population is usually pure without associated lymphoid component, whereas in LPL small lymphocytes and plasmacytoid lymphocytes typically predominate. The most important laboratory prognostic factors are proliferation rate of neoplastic plasma cells and cytogenetic findings. Amyloid accumulation in extracellular space leads to multiple organ dysfunction; amyloid deposits can be detected in the tissue biopsy using Congo Red stain under polarized light. There is a wide range of pathologic processes that can accompany PCPDs. The most common ones are large granular lymphocyte proliferations and therapy-related myeloid neoplasms. Jevremovic D & Morice W. In: Multiple Myeloma . Edited by Gertz MA & Rajkumar SV. Springer New York, 2014. doi:10.1007/978-1-4614-8520-9_3

Diagnostic criteria and classification of lymphoblastic leukemias The diagnosis of the precursor lymphoid neoplasms, acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL), is based on a combination of morphology and immunophenotyping.

In contrast, the p190 isoform occurs in about 50% of BCR-ABL -positive ALL but is rare in CML including lymphoid BP. 

Pax-5 (PAX5) is required for B-lymphoid lineage commitment and maturation. 61 The PAX5 genetic alterations observed in ALL include deletions, sequence mutations and chromosomal rearrangements encoding PAX5 chimeric gene fusions 6, 62, 63, 64 that result in loss of PAX5 function (and for gene fusions, a dominant negative effect) and an arrest in lymphoid maturation that contributes to the block in B-cell maturation that is characteristic of B-ALL. 65 The DNA-binding transcription factor Ikaros (IKZF1, also known as IKAROS) is required for the development of all lymphoid lineages.