Plasma Cell Myeloma Variants

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Primary Author(s)*

  • Fariborz Rashid-Kolvear, PhD, FACMG, FCCMG

Cancer Category/Type

In 2017 WHO Classification, plasma cell myeloma (PCM) variants are classified under the categories of Mature B cell Neoplasm/Plasma cell neoplasms (PCN)[1]

Cancer Sub-Classification / Subtype [1]

1 - Smoldering (asymptomatic) plasma cell myeloma (SPCM)

2 - Non-secretory myeloma

3 - Plasma cell leukemia (PCL)

Definition / Description of Disease

1- Smoldering (asymptomatic) plasma cell myeloma (SPCM):

Both criteria must be met [2]:

- Serum monoclonal protein (IgG or IgA) ≥ 30g/L or urinary monoclonal protein ≥ 500mg per 24h and/or clonal bone marrow plasma cells 10-60%

- Absence of myeloma-defining events or amyloidosis

2 - Non-secretory myeloma:

- Absence of an M protein by serum and urine immunofixation electrophoresis

- 85% of cases have M protein evaluated by IHC (producer myeloma)

- 15% of cases have no cytoplasmic Ig synthesis (non-producer myeloma)

3 - Plasma cell leukemia:

Neoplastic plasma cells in the blood is greater than 20% of the total leukocytes or the absolute plasma cell count exceeds 2 × 109/L.

Primary PCL: present at the time of initial diagnosis (~60% to 70%)

Secondary PCL: evolving during the course of disease in a patient with previously diagnosed myeloma

Synonyms / Terminology

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Epidemiology / Prevalence

1- Smoldering (asymptomatic) plasma cell myeloma (SPCM):

About 8% to 14% of patients with PCM are asymptomatic at the time of diagnosis

2 - Non-secretory myeloma:

Approximately 1% of PCMs

3 - Plasma cell leukemia:

Primary PCL is found in approximately 2% to 4% of cases of myeloma

Secondary PCL is a leukemic transformation that occurs in approximately 1% of previously diagnosed PCM

Clinical Features

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Sites of Involvement

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Morphologic Features

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Immunophenotype

Refer to Plasma cell myeloma page.

Finding Marker
Positive (universal) EXAMPLE CD1
Positive (subset) EXAMPLE CD2
Negative (universal) EXAMPLE CD3
Negative (subset) EXAMPLE CD4

Chromosomal Rearrangements (Gene Fusions)

Adapted from

Chromosomal Rearrangement Pathogenic Derivative Prevalence
Cyclin D translocation
t(6;14)(p25;q32) CCND3 2%
t(11;14)(q13;q32) CCND1 16%
t(12;14)(p13;q32) CCND2 <1%
NSD2 (MMSET) translocation
t(4;14)(p16;q32) NSD2 and FGFR3 15%
MAF translocation
t(8;14)(q24;q32) MAFA 1%
t(14;16)(q32;q23) MAF 5%
t(14;20)(q32;q11) MAFB 2%
Chromosome 1 abnormalities
Loss of 1p

Characteristic Chromosomal Aberrations / Patterns

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Genomic Gain/Loss/LOH

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Chromosome Number Gain/Loss/Amp/LOH Region
EXAMPLE 8 EXAMPLE Gain EXAMPLE chr8:0-1000000
EXAMPLE 7 EXAMPLE Loss EXAMPLE chr7:0-1000000

Gene Mutations (SNV/INDEL)

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Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
EXAMPLE TP53 EXAMPLE R273H EXAMPLE Tumor Suppressor EXAMPLE LOF EXAMPLE 20%

Other Mutations

Type Gene/Region/Other
Concomitant Mutations EXAMPLE IDH1 R123H
Secondary Mutations EXAMPLE Trisomy 7
Mutually Exclusive EXAMPLE EGFR Amplification

Epigenomics (Methylation)

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Genes and Main Pathways Involved

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Diagnostic Testing Methods

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Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

Table from S. Vincent Rajkumar [3]

Chromsome abnormalities Smoldering plasma cell myeloma
Trisomies Intermediate‐risk of progression, median TTP* of 3 y
t(11;14) (q13;q32) Standard‐risk of progression, median TTP of 5 y
t(6;14) (p21;q32) Standard‐risk of progression, median TTP of 5 y
t(4;14) (p16;q32) High‐risk of progression, median TTP of 2 y
t(14;16) (q32;q23) Standard‐risk of progression, median TTP of 5 y
t(14;20) (q32;q11) Standard‐risk of progression, median TTP of 5 y
Gain(1q21) High‐risk of progression, median TTP of 2 y
Del(17p) High‐risk of progression, median TTP of 2 y
Trisomies plus any one of the IgH translocations Standard‐risk of progression, median TTP of 5 y
Isolated monosomy 13, or isolated monosomy 14 Standard‐risk of progression, median TTP of 5 y
Normal Low‐risk of progression, median TTP of 7–10 y

* TTP: Time To Progression

Familial Forms

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Other Information

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Links

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References

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  1. 1.0 1.1 Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p249-250
  2. Sv, Rajkumar; et al. (2014). "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma". PMID 25439696.
  3. Sv, Rajkumar (2020). "Multiple myeloma: 2020 update on diagnosis, risk-stratification and management". PMID 32212178 Check |pmid= value (help).

EXAMPLE Book

  1. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.

Notes

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