Molecular Pathology of Plasma Cell Neoplasms

Abstract

The plasma cell neoplasms are a heterogeneous category of disorders that are defined by a combination of clinical, pathologic, and radiologic criteria and range from the very indolent (monoclonal gammopathy of undetermined significance (MGUS)) to clinically aggressive, overt malignancies (such as plasma cell leukemia). The majority of the molecular pathology literature in plasma cell neoplasms has focused on plasma cell myeloma (PCM). However, the molecular abnormalities identified in PCM are not unique to this disorder, and may also be found in other plasma cell neoplasms, such as plasma cell leukemia or solitary plasmacytomas. For this reason, molecular studies do not assist in the classification of plasma cell neoplasms. Once a diagnosis of PCM is ascertained, however, molecular studies may be very helpful in assessing a patient’s prognosis. Several molecular abnormalities have been shown to be of prognostic significance in patients treated with standard chemotherapy, or with high dose chemotherapy and single or tandem bone marrow (BM) transplants. Through an assessment for the molecular abnormalities described in this chapter, patients with PCM may be divided into those with “high-risk” or “standard-risk” disease, and risk-stratified treatment regimens may therefore be possible. It must be kept in mind, however, that therapeutic regimens for patients with PCM continue to evolve, with the introduction of immunomodulatory agents, such as thalidomide and its derivatives and other novel agents such as bortezomib. Whether the molecular abnormalities described below maintain their prognostic significance in the face of these new therapeutic options remains to be determined.