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Plasma cell dyscrasias (PCDs)

Spectrum of progressively more severe monoclonal gammopathies characterized by the expansion of a population of monoclonal bone-marrow plasma cells that produce monoclonal immunoglobulins.

Spectrum of progressively more severe monoclonal gammopathies characterized by the expansion of a population of monoclonal bone-marrow plasma cells that produce monoclonal immunoglobulins.

  • Monoclonal gammopathies: Group of related disorders characterized by a clone of plasma cells or lymphocytes with the capacity to secrete a homogeneous immunoglobulin or its components, which may be recognized as a peak on serum or urine protein electrophoresis.

Pathophysiology

Most plasma cell dyscrasias (PCDs) develop after affinity maturation has occurred in the germinal center, as the gene sequence of most myeloma cells are hypermutated, exhibit phenotypic features similar to those of long-lived PCs, and are usually distributed in multiple compartments of the bone marrow.

nrdp201746-f1
The development of multiple myeloma is a multistep process, which starts with precursor disease states, such as monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM). Although MGUS, SMM and multiple myeloma are clinically well defined, many biological similarities between these disease states have been found. Multiple myeloma can progress to bone marrow-independent diseases, such as extramedullary myeloma and plasma cell leukaemia. Primary genetic events in the development of MGUS, SMM and multiple myeloma include chromosomal translocations involving the immunoglobulin heavy-chain genes (IGH) and aneuploidy (with hyperdiploidy as the most frequent entity). The number of secondary genetic alterations increases from MGUS to SMM and then to multiple myeloma. | Kumar, S. K., Rajkumar, V., Kyle, R. A., van Duin, M., Sonneveld, P., Mateos, M.-V., … Anderson, K. C. (2017). Multiple myeloma. Nature Reviews Disease Primers, 3, 17046. Retrieved from https://doi.org/10.1038/nrdp.2017.46
Diagnostic Criteria for Plasma Cell Dyscrasias | Michels, T. C., & Petersen, K. E. (2017). Multiple Myeloma: Diagnosis and Treatment. American family physician, 95(6), 373–383.

Diagnosis

Since both PC and lymphoproliferative disorders can produce M proteins, making the distinction between which type of disorder is responsible for the M protein is critically important and flow cytometry can assist in this process. Diseases of PCs include MGUS, multiple myeloma, and PC leukemia.

Standard workup:

  • Total serum protein
  • Serum and urine protein electrophoresis
  • Immunofixation in serum and urine
  • Detection of serum free light chains (sFLC)
  • Additional parameters: Complete blood count, serum creatinine, electrolytes (including calcium), lactate dehydrogenase, and β2 microglobulin

Bone marrow biopsy:

In a patient with suspected multiple myeloma, a bone marrow biopsy is normally obtained.

Multiparametric flow cytometry (MFC):

In clinical flow cytometry, cell populations are considered as abnormal if they have an atypical differentiation patterns, increased or decreased expression of normal antigens, asynchronous maturational patterns, or the expression of aberrant antigens.
  • Discrimination of normal plasma and myeloma cells from other leukocytes: CD38, CD138, CD45, CD19, CD56, and cytoplasmic immunoglobulin light chains in combination with light scatter.
Algorithm for the initial evaluation and management of a patient with multiple myeloma. (CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; MGUS = monoclonal gammopathy of undetermined significance; MRI = magnetic resonance imaging; PET/CT = positron emission tomography/computed tomography; POEMS = polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes.) | Munshi NC, Jagannath S. Plasma cell neoplasms. In: Hoffman R, Benz EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J, eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, Pa: Saunders/Elsevier; 2013:1308–1337. | Bianchi G, Anderson KC. Understanding biology to tackle the disease: multiple myeloma from bench to bedside, and back. CA Cancer J Clin. 2014;64(6):422–444. | Röllig C, Knop S, Bornhäuser M. Multiple myeloma. Lancet. 2015;385(9983):2197–2208. | Kumar SK, Callander NS. National Comprehensive Cancer Network Guideline: Multiple Myeloma, Version 3.2017. http://www.nccn.org/professionals/physician_gls/PDF/myeloma.pdf (login required). Accessed December 26, 2016. | Nicolaides AN, Fareed J, Kakkar AK, et al. Prevention and treatment of venous thromboembolism–International Consensus Statement. Int Angiol. 2013;32(2):111–260.

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