Multiple myeloma from the pathologist's perspective

Abstract

Multiple myeloma (MM) is one of the most common hematological neoplasms and accounts for approximately 1% of human cancers. Description of current diagnostics and classification of MM and related plasma cell neoplasms from the pathology viewpoint. Current knowledge regarding pathology and genetics of MM is summarized and tissue-based diagnostics following international consensus classifications and the current S3 guideline are described. MM and related neoplasms are composed of malignant plasma cells that secrete amonoclonal immunoglobulin, which is an important parameter of disease activity. MM shows amultistage development. Almost all cases are preceded by aclinically inapparent precursor lesion, monoclonal gammopathy of undetermined significance (MGUS), which can progress to smoldering myeloma with ahigher tumor burden, but absence of organ damage. Systemic MM needs to be discerned from the localized forms, solitary osseous and primary extramedullary plasmacytoma. MM is genetically very heterogeneous and can be broadly subdivided into two cytogenetic groups, cases with primary IGH translocations and cases with hyperdiploidy. Intratumoral genetic heterogeneity is frequently pronounced and correlates with the size of focal lesions in imaging. Diagnosis of plasma cell neoplasms is done according to the criteria of the International Myeloma Working Group (IWMG) and requires interdisciplinary evaluation of clinical, serological, pathological and radiological features. In addition to clinical parameters, molecular markers, especially cytogenetic aberrations, are of great prognostic relevance.