Plasma Cell Neoplasms

Plasma cell neoplasms are diseases resulting from the excessive clonal proliferation of plasma cells – or myeloma cells – in the bones and soft tissues of the body. Plasma cell neoplasms can be benign, but can also lead to malignant diseases including multiple myeloma (MM), where myeloma cells build up in the bone marrow to form tumors, preventing the production of healthy blood cells.1 MM accounts for 10% of hematological malignancies worldwide, with an incidence rate of 160,000 cases resulting in 106,000 deaths per year.2

Other plasma cell neoplasm disorders include:3

  • Monoclonal gammopathy of undetermined significance (MGUS)
  • Idiopathic Bence Jones proteinuria
  • Monoclonal gammopathy of renal significance (MGRS)
  • POEMS syndrome
  • AL amyloidosis, light and heavy chain deposition disease
  • Solitary plasmacytoma

Multiple myeloma formation

MM disrupts the homeostasis in bone formation and resorption, and is characterized by anemia, bone destruction, renal insufficiency or hypercalcemia. The disease begins as premalignant monoclonal gammopathy of undetermined significance (MGUS), before progressing to a smoldering, asymptomatic myeloma, and finally becoming overt myeloma in 1-2% of patients per year.4 MM can then result in bone marrow infiltration and osteolytic bone lesions.5

Figure 1. Example micrograph of a multiple myeloma.

Diagnosis and treatment assessment

The major challenge of diagnosing plasma cell neoplasms is the need to distinguish between patients with benign forms and those with premalignant conditions that may become more progressive diseases. Plasma cell neoplasms are characterized by the excess production of clonal plasma cells, excess monoclonal M spike proteins and beta-2-microglobulin (>5.5 mg/L at stage III), or free light chains in urine or serum (typically >30 g/L of IgG or >25 g/L of IgA or >1 g/24 h of urine light chain), as well as evidence of organ or tissue damage.6 Patients with MGUS or asymptomatic smoldering myeloma usually do not require treatment and are monitored for disease progression. Risk factors that predict this include abnormal serum free light chain ratios, non-IgG MGUS, and high M protein serum levels (>1.5 g/dL).7

Cell Markers

Abnormal populations of plasma cells are identified with bright expression of CD38 and CD138. Overexpression of CD56, CD28, CD33 and/or CD117, and progressively lowered or lack of CD27, CD19 and/or CD45 expression, help to distinguish malignant from benign plasma cells.

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  1. PDQ® Adult Treatment Editorial Board. PDQ Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment. Bethesda, MD: National Cancer Institute. Updated 03/12/2021. Available at: Accessed 06/12/2021. [PMID: 26389437]
  2. Ludwig, H., Novis Durie., et al. (2020). Multiple Myeloma Incidence and Mortality Around the Globe; Interrelations Between Health Access and Quality, Economic Resources, and Patient Empowerment. The Oncologist, 25(9): e1406-e1413
  3. Wahed, A., Quesada, A., & Dasgupta, A. (2020). Monoclonal gammopathies and their detection. In Hematology and Coagulation (2nd ed): 113-126. Academic Press.
  4. Fairfield H., Falank C., et al. (2016). Multiple myeloma in the marrow: pathogenesis and treatments. Annals of the New York Academy of Sciences. 1364:32-51. doi: 10.1111/nyas.13038. PMID: 27002787; PMCID: PMC4806534.
  5. Hameed, A., Brady, J. J., Dowling, P., Clynes, M., & O'Gorman, P. (2014). Bone disease in multiple myeloma: pathophysiology and management. Cancer growth and metastasis, 7:33–42.
  6. PDQ Adult Treatment Editorial Board. (2021). Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Health Professional Version. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US). Retrieved 1 November 2021, from!po=0.641026.
  7. Kumar S., Kimlinger T., & Morice W. (2010). Immunophenotyping in multiple myeloma and related plasma cell disorders. Best Practice & Research Clinical Haematology. 23(3): 433-51. doi: 10.1016/j.beha.2010.09.002. PMID: 21112041; PMCID: PMC3005703.
  8. Based on

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