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plasma cell myeloma


Tuesday 30 September 2003

plasma cell myeloma, multiple myeloma

Definition: Multiple myeloma (MM) is a malignancy of clonal bone marrow plasma cells characterized by a high genomic instability increasing with disease progression.

MM is characterized by neoplastic proliferation of plasma cells involving more than 10% of the bone marrow.

Multiple myeloma is a plasma cell malignancy characterized by complex heterogeneous cytogenetic abnormalities.

Digital slides

- UI:755 - Multiple myeloma
- UPD:9668 : Atypical myeloma cells in bone marrow. (ICSFramework)
- HPC:282 (Atypical myeloma cells in bone marrow)

Case studies

- UPMC:599


- plasma cell myeloma with numerous cytoplasmic granules

- myeloma cells in bone marrow cytology

- Dutcher Bodies (nuclear pseudo-inclusions) in plasma cell myeloma

- plasma cell myeloma


In the United States, about four people per 100,000 are diagnosed with MM each year. This condition is slightly more common among men than women, and almost twice as common among blacks as among whites. The average age at diagnosis is 65 to 70 years.

Bone marrow examination

In most individuals with MM, a bone marrow aspiration and biopsy (a collection of a small sample of bone marrow for laboratory analysis, usually taken from the hip) shows that plasma cells comprise an abnormally high percentage of bone marrow cells (more than 10 percent).

It may be necessary to collect samples from different areas because MM can affect the marrow of some bones but not others.

MM is characterized by an increased number of bone marrow plasma cells.

Plasma cells show low proliferative activity, as measured by using the labeling index. This index is a reliable parameter for the diagnosis of MM. High values are strongly correlated with progression of the disease.

Obtain bone marrow aspirate and biopsy samples from patients with MM to calculate the percentage of plasma cells in the aspirate (reference range, up to 3%) and to look for sheets or clusters of plasma cells in the biopsy specimen.

Bone marrow biopsy

Bone marrow biopsy enables a more accurate evaluation of malignancies than does bone marrow aspiration.

Bone marrow aspirate demonstrating plasma cells of multiple myeloma. Blue cytoplasm, eccentric nucleus, and perinuclear pale zone (or halo) can be noted. Bone marrow biopsy demonstrates sheets of malignant plasma cells in multiple myeloma.

Plasma cells are 2-3 times larger than typical lymphocytes; they have eccentric nuclei that are smooth (round or oval) in contour with clumped chromatin and have a perinuclear halo or pale zone (see the image below). The cytoplasm is basophilic.

Many MM cells have characteristic, but not diagnostic, cytoplasmic inclusions, usually containing immunoglobulin. The variants include Mott cells, Russell bodies, grape cells, and morula cells. Bone marrow examination reveals plasma cell infiltration, often in sheets or clumps.

This infiltration is different from the lymphoplasmacytic infiltration observed in patients with Waldenstrom macroglobulinemia.

Analysis of bone biopsy specimens may reveal plasmacytic, mixed cellular, or plasmablastic histologic findings. With the plasmacytic type, median survival is approximately 39.7 months. With the mixed cellular type, survival is 16.1 months, and with the plasmablastic type, survival is 9.8 months.

Plasma cell labeling index

The plasma cell labeling index (PCLI) determines how rapidly the abnormal plasma cells are growing and dividing. Patients in whom the labeling index is low tend to have slower disease progression than those with high values. This test is also useful for distinguishing MM from related conditions that generally have a better prognosis.

A normal plasma cell labeling index suggests that MM is less likely, while an elevated index suggests that multiple myeloma is more likely.

Although this test is not readily available in many centers, PLCI is a reliable marker of high risk disease. Thus, if it is available, it is recommended to help differentiate between high risk and standard risk MM.

Criteria for diagnosis

The diagnosis of multiple myeloma requires the following:

- A bone marrow aspirate or biopsy showing that at least 10 percent of the cells are plasma cells or the presence of a plasma cell tumor (called a plasmacytoma)
- M protein in the blood or urine
- Evidence of damage to the body as a result of the plasma cell growth, such as destructive bone lesions, kidney failure, anemia, or high calcium in the blood.


The simplest measure of prognosis in MM is based on blood levels of two markers: beta-2-microglobulin and albumin. In general, higher levels of beta-2-microglobulin and lower levels of albumin are associated with a poorer prognosis.

This staging system is referred to as the International Staging System, or ISS.

The Durie-Salmon staging system is an older system that divides patients into three stages: Stages I, II, and III, corresponding to low, intermediate, and high cell mass, depending upon the severity of anemia, calcium level, kidney function, presence or absence of bone lesions, and the quantity of abnormal proteins. This staging system is best used as a measure of the overall amounts of malignant plasma cells present in the patient, and is less useful as a measure of prognosis.

Standard versus high-risk MM

Approximately 25 percent of people with MM have high-risk disease. This type of MM is aggressive and may shorten survival.

As such, patients with high risk disease are treated with more aggressive therapy.

Tests performed to distinguish between high and standard risk MM include studies looking for chromosomal abnormalities and the plasma cell labeling index (PLCI).


The 5-year relative survival rate for MM is around 35%. Survival is higher in younger people and lower in the elderly.

With the plasmacytic type, median survival is approximately 39.7 months. With the mixed cellular type, survival is 16.1 months, and with the plasmablastic type, survival is 9.8 months.


- Usual expression: CD79a, VS38c, CD138, CD38
- CD19-
- Aberrant expression: CD56+ (67-79%), CD117, CD20, CD52, CD10, CyD1.

Molecular forms

- TP53 deletion-associated multiple myeloma (28664940)

CGH (Genome-wide DNA profiling)

- losses

  • 1p losses
  • 13q losses
  • 17p losses
  • 14q losses

- gains

  • 1q gains (88%)
  • 8q gains
  • 18q gains
  • 7q gains
  • 20q gains

- regional amplifications


Cytogenetic analysis of the bone marrow may contribute significant prognostic information in multiple myeloma. Although not as well defined as in other hematologic malignancies, such as acute leukemia, risk-adapted therapy based on cytogenetic abnormalities is at the forefront of myeloma research.

The most significant cytogenetic abnormality appears to be deletion of 17p13. This abnormality is associated with shorter survival, more extramedullary disease, and hypercalcemia. This locus is the site of the TP53 tumor suppressor gene.

Chromosome 1 abnormalities and c-myc defects are also significant prognostic factors in multiple myeloma.

- translocations

- hyperdiploidy (hyperdiploid myeloma)


Increasing evidence suggests that the bone marrow microenvironment of tumor cells plays a pivotal role in the pathogenesis of myelomas.

The malignant cells of MM, plasma cells, and plasmacytoid lymphocytes are the most mature cells of B-lymphocytes. B-cell maturation is associated with a programmed rearrangement of DNA sequences in the process of encoding the structure of mature immunoglobulins. It is characterized by overproduction of monoclonal immunoglobulin G (IgG), immunoglobulin A (IgA), and/or light chains, which may be identified with serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP).

The role of cytokines in the pathogenesis of MM is an important area of research. Interleukin (IL)–6 is also an important factor promoting the in vitro growth of myeloma cells. Other cytokines are tumor necrosis factor and IL-1b.

The pathophysiologic basis for the clinical sequelae of MM involves the skeletal, hematologic, renal, and nervous systems, as well as general processes.



- Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer. 2007 Aug;7(8):585-98. PMID: 17646864

- Fabris S, Todoerti K, Mosca L, Agnelli L, Intini D, Lionetti M, Guerneri S, Lambertenghi-Deliliers G, Bertoni F, Neri A. Molecular and transcriptional characterization of the novel 17p11.2-p12 amplicon in multiple myeloma. Genes Chromosomes Cancer. 2007 Sep 6; PMID: 17823926

- Lombardi L, Poretti G, Mattioli M, Fabris S, Agnelli L, Bicciato S, Kwee I, Rinaldi A, Ronchetti D, Verdelli D, Lambertenghi-Deliliers G, Bertoni F, Neri A. Molecular characterization of human multiple myeloma cell lines by integrative genomics: insights into the biology of the disease. Genes Chromosomes Cancer. 2007 Mar;46(3):226-38. PMID: 17171682

- Chng WJ, Ketterling RP, Fonseca R. Analysis of genetic abnormalities provides insights into genetic evolution of hyperdiploid myeloma. Genes Chromosomes Cancer. 2006 Dec;45(12):1111-20. PMID: 16955468

- Claudio JO, Stewart AK. Advances in myeloma genetics and prospects for pharmacogenomic testing in multiple myeloma. Am J Pharmacogenomics. 2005;5(1):35-43. PMID: 15727487