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Malignant Plasma Cell Neoplasm

Posted on January 21 2014

Malignant Plasma Cell Neoplasm
Case Study

NCCN clinical practice guidelines recommend prognostic genetic evaluation for newly diagnosed plasma cell myelomas to include karyotyping and FISH for del 13q, del 17p13/ p53, t (4:14)/ FGFR / IGH, t(11;14)/ BCL1/IGH, and t (14;16)/ IGH/ MAF. In this regard, FISH testing is significantly more sensitive than conventional cytogenetics, as is demonstrated by the current case. Prognostically unfavorable abnormalities include del 13q, del 17p13, t (4:14), t(14;16), and hypodiploidy. Prognostically favorable abnormalities include BCL1/ t(11;14) and hyperdiploidy.




An 85-year-old female with monoclonal paraproteinemia (IgG 5 g/dL) underwent bone marrow biopsy.


Decalcified core biopsy
Demonstrates cellularity averaging 75% with a patchy distribution of expansive, sheet like islands of atypical plasma cells. Between these islands are zones of normal appearing trilineage hematopoiesis containing myeloid, erythroid and megakaryocytic elements in normal relative numbers. Paraffin immunohistochemical stains highlight expansive, sheet like islands of atypical plasma cells, CD138+ CD56-, comprising roughly 45% of cellularity in core biopsy.

Aspirate smears
Show a variable distribution of plasma cells, averaging 29%.

Fig.1 CD138+ plasma cells

Special Studies

Flow Cytometry
Bone marrow aspirate flow cytometry: reveals an 8.7% aberrant, monoclonal plasma cell population, CD45+, CD19-, CD20-, CD33-, CD38+ (bright), CD56-, CD117+ (dim), CD138+, cIg lambda+

Fig 2. Backgating on strongly CD38+ events
highlights plasma cells (blue) on SS Log and CD45

Fig 3. Backgating on CD138+ events highlights
cytoplasmic lambda light-chain restricted plasma cells (red).


Indicated: 46,XX[20], normal female karyotype

Studies revealed:

Hyperdiploidy in 5% of cells with 4 copies of loci on chromosomes 5, 9, 15, 13 and 17

t(11;14) with extra copies of BCL1 and IGH in 11.5% of cells

Extra copies of FGFR3, IGH, and MAF in 11-12% of cells

No rearrangements between IGH/MAF or FGFR3/IGH

Fig 4. Tetrasomy 5, 9 and 5 with 4 copies each signal
Fig 5 Tetrasomy 17 with 4 copies of the p53 locus
Fig 6.BCL1/IGH rearrangement with two fusion signals (yellow) and duplicate copies of each of the CCND1 and IgH signals (red and green)

Differential Diagnosis

The current case is CD56 negative, but is clearly malignant based on morphologic and clinical criteria.


Roughly 75% of plasma cell myelomas demonstrate aberrant, strong expression of CD56, which supports a diagnosis of malignancy. In contrast, weak-intensity paraffin-based CD56 staining can be seen in benign plasma cell expansions and should not be over interpreted as evidence for plasma cell malignancy.

Flow cytometry is a useful method for plasma cell phenotyping, especially assessing surface CD56 staining and cytoplasmic light chain restriction. Flow cytometry typically underrepresents plasma cell number and must be correlated with morphologic plasma cell enumeration. Aberrant plasma cell staining for CD117, CD20, or CD33 can be useful in follow-up disease monitoring, but is not prognostically significant.


Badros A, (2010). In the Age of Novel Therapies, What Defines High-Risk Multiple Myeloma? J Natl Compr Canc Netw; 8:S-28-S-34.