Plasma cell myeloma: role of histopathology, immunophenotyping, and genetic testing

Abstract

Myeloma is a malignant neoplasm of plasma cells with complex pathogenesis. Diagnosis and risk stratification require the integration of histology, radiology, serology, and genetic data. Bone marrow biopsies are essential for myeloma diagnosis by providing material for histologic and cytologic assessment as well as immunophenotypic and genetic studies. Flow cytometry and genetic studies are, in particular, becoming increasingly important for diagnosis, risk stratification, and assessment of treatment response. Myeloma has traditionally been characterized by recurrent cytogenetic abnormalities that can be divided into two subtypes: hyperdiploid, characterized by trisomies, and non-hyperdiploid, characterized by translocations involving chromosome 14. These abnormalities are thought to be primary events, initiating a premalignant state, which progresses to myeloma through the acquisition of secondary mutations. The emergence of next-generation sequencing has led to the discovery of numerous mutations and gene fusions that comprise the heterogenous genomic landscape of myeloma. As the underlying pathogenesis of myeloma continues to be delineated, possible therapeutic targets have also emerged. Herein, we describe the importance of histology, immunophenotype, and mutational analysis in the assessment of myeloma.

Keywords: Cytogenetics; Flow cytometry; Fluorescence in situ hybridization; Myeloma; Next-generation sequencing; Plasma cell.