Which molecular and genetic findings are characteristic of plasma cell lesions?

Updated: Oct 14, 2019
  • Author: Lesley Elizabeth Fox, MD; Chief Editor: Francis H Gannon, MD  more...
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At the time of isotype switching, complex genetic events occur which transform normal plasma cells into a malignant population of plasma cells, with clonally rearranged heavy and light chain genes and immunoglobulin heavy chain variable (IgH-V) gene somatic hypermutation. [1, 5] Numeric and structural abnormalities are seen, and plasma cell myeloma can be divided into two groups based on cytogenetic and molecular findings, as follows: (1) a nonhyperdiploid karyotype with a high incidence of recurrent immunoglobulin heavy chain (IgH) translocations and/or abnormalities of chromosome 13 and (2) a hyperdiploid karyotype with multiple associated trisomies (chromosomes 3, 5, 7, 9, 11, 15, 19, 21) but with a low incidence of IgH translocations or chromosome 13 abnormalities. [1, 3, 5]

Routine cytogenetic studies detect a limited portion of the underlying chromosomal abnormalities commonly seen in plasma cell myeloma, and fluorescence in situ hybridization (FISH) (or other molecular methods) should be combined with conventional cytogenetics to detect cryptic translocations that are known to occur in plasma cell myeloma. [1, 5]

A working model of multistep development has been proposed for plasma cell neoplasms, suggesting a portion of monoclonal gammopathy of undetermined significance (MGUS) progresses to asymptomatic (smoldering) plasma cell myeloma, and a portion of these cases will then progress onto symptomatic plasma cell myeloma, with or without evidence of disease progression (plasma cell leukemia and/or extramedullary disease). [3]

A study estimated the impact of prior knowledge of monoclonal gammopathy of uncertain significance (MGUS) diagnosis and comorbidities on multiple myeloma (MM) survival. The study found that patients with MM with prior knowledge of MGUS had better MM survival, suggesting that earlier treatment of MM leads to better survival. [13, 14]

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