Plasma cell myeloma

Definition

A multifocal bone marrow based plasma cell neoplasm characterised by a serum monoclonal protein (M-component) and skeletal destruction. There is a spectrum from localised indolent disease to aggressively disseminated infiltration of multiple organs and plasma cell leukaemia.

Synonyms

Epidemiology

Plasma cell myeloma represents 15% of all haematological malignancies. It is predominantly a disease of the elderly.

Clinical features

The most common sites of bone involvement are the vertebrae, ribs, skull, pelvis, femur, clavicles and scapulae. Bone destruction results in bone pain, pathological fractures, hypercalcaemia and anaemia. There may be renal failure due to tubular damage by light chain proteinuria. Recurrent infections result from depressed normal immunoglobulin synthesis. 99% of patients show an M-component in serum or urine.

Variants

Histopathology

The bone marrow shows an excess of plasma cells, frequently in large nodules or sheets, displacing normal marrow elements. Although in many cases typical plasma cells are easily recognised, the morphology may make this very difficult:

Diagnostic criteria

For the diagnosis of plasma cell myeloma, one major and one minor criteria or three minor criteria are required a symptomatic patient

Immunohistochemistry

cytoplasmic Ig

positive (most often IgG, occasionally IgA, rarely IgD, IgE or IgM). 15% express light chain only.

 

surface Ig

negative

CD5

negative

CD10

usually negative

CD19†

most negative

CD20

most negative, 12/668: CD20 positive myelomas also tend to be positive for Pax-57

CD22

-

CD38

most positive5

CD45

var

CD56 / CD58

usually positive, negative in PCL

CD79a

most positive

CD117

43/8512

CD138

most positive4

cyclin D1

25%3

VS38c

most positive

   

†: fresh frozen tissue only

CD56 may be useful in differentiating myeloma from MGUS and polyclonal plasmacytosis:

CD 56 in plasma cell proliferations

 

polyclonal plasmacytosis smear

1/510

 

polyclonal plasmacytosis biopsy

1/510, 0/8811

MGUS smear

0/1610

MGUS biopsy

0/1610, 3/4611

myeloma smear

11/1410

myeloma biopsy

12/1310, 107/15011

Amyloidosis

0/311

Plasmacytoid NHL

0/6511

   

†A case was considered to be CD56+ if > 50% of the CD138+ plasma cells showed expression of CD56 at a level comparable to that of the osteoblast layer (used as an internal positive control).11

The expression of CD56 by myeloma cells may inhibit osteoid production: both myeloma cells and osteoblasts express CD56 and the inhibition may be mediated by homophilic binding.11.

There is increasing evidence that neoplastic plasma cells express various haemopoietic and non-haemopoietic antigens. Since this issue could raise problems in diagnostic histopathology, Petruch et al investigated 51 cases of multiple myeloma (plasmacytoma) systematically with a broad panel of antibodies applicable on paraffin-embedded and mildly decalcified tissue. In approximately 90% of the cases the neoplastic plasma cells reacted with at least one antibody detecting haemopoietic antigens:

MB2

75%

DF-T1/CD 43

59%

UCHL1/CD 45RO

47%

Ki-B3

41%

anti-LCA/CD 45

40%

L26/CD 20

26%

4KB5/CD 45RA

18%

Ber H2/CD 30

10%

Leu-7/CD 57

8%

neutrophil elastase

4%

Dako-M1/CD 15

2%

KP1/CD 68

2%

glycoprotein IIIa

2%

 

In approximately 70% of the cases the cells reacted with antibodies against non-haemopoietic antigens:

epithelial membrane antigen

65% - 85%2 (mainly membrane)

BMA120

53%

vimentin

44%

pan-cytokeratin/KL1

8%

carcino-embryonic antigen

6%

HMB45

6%

Lack of awareness of the frequent expression of both haemopoietic and non- haemopoietic antigens by neoplastic plasma cells could lead to mis-diagnosis of plasmacytomas as malignant lymphomas or even as carcinomas or sarcomas.

Parathyroid hormone related protein may be produced by myelomas and contribute to osteolysis and hypercalcaemia. The use of mercury-based fixation and decalcification procedures may prevent immunostaining for PTHrP in bone marrow specimens; detection of PTHrP mRNA may therefore be more sensitive1.

Differential diagnosis

 

CD19

CD20

CD22

CD38

CD45

EMA

PCA-1

lymphoplasmacytoid lymphoma

+

+

+

-

+

-

-

diffuse large B cell lymphoma

+

+

+

-

+

-

-

plasmacytoma

-

-

-

+

var

+

+

Prognosis

References

World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

Petruch, U. R., Horny, H. P., Kaiserling, E. Frequent expression of haemopoietic and non-haemopoietic antigens by neoplastic plasma cells: an immunohistochemical study using formalin- fixed, paraffin-embedded tissue. Histopathology 1992;20:35-40.

1 Zeimer H et al. Assessment of cellular expression of parathyroid hormone-related protein mRNA and protein in multiple myeloma. J Pathol 2000;192:336-341.

2 ten Berge, R. L., Snijdewint, F. G., von Mensdorff-Pouilly, S. MUC1 (EMA) is preferentially expressed by ALK positive anaplastic large cell lymphoma, in the normally glycosylated or only partly hypoglycosylated form. J Clin Pathol 2001;54:933-939.

3 Swerdlow, S. H., Williams, M. E. From centrocytic to mantle cell lymphoma: a clinicopathologic and molecular review of 3 decades. Human Pathol 2002;33;7-20.

4 Costes V, Magen V, Legouffe E et al. The Mi15 monoclonal antibody (anti-syndecan-1) is a reliable marker for quantifying plasma cells in paraffin-embedded bone marrow biopsy specimens. Human Pathology 1999;30:1405-11.

5 Vallario A, Chilosi M, Adami F et al. Human myeloma cells express the CD38 ligand CD31. British Journal of Haematology 1999;105:441-4.

6 Pillai, G., K. Lwin, et al. (2002). "Malignant plasmacytosis mimicking erythrophagocytosis." Histopathology 41(5): 468-70.

7 Lin, P., M. Mahdavy, et al. (2004). "Expression of PAX5 in CD20-positive multiple myeloma assessed by immunohistochemistry and oligonucleotide microarray." Mod Pathol 17(10): 1217-22.

8 Robillard, N., H. Avet-Loiseau, et al. (2003). "CD20 is associated with a small mature plasma cell morphology and t(11;14) in multiple myeloma." Blood 102(3): 1070-1. FULL TEXT

9 Garcia-Sanz, R., A. Orfao, et al. (1999). "Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics." Blood 93(3): 1032-7.

10 Martin, P., A. Santon, et al. (2004). "Neural cell adhesion molecule expression in plasma cells in bone marrow biopsies and aspirates allows discrimination between multiple myeloma, monoclonal gammopathy of uncertain significance and polyclonal plasmacytosis." Histopathology 44(4): 375-80.

11 Ely, S. A. and D. M. Knowles (2002). "Expression of CD56/neural cell adhesion molecule correlates with the presence of lytic bone lesions in multiple myeloma and distinguishes myeloma from monoclonal gammopathy of undetermined significance and lymphomas with plasmacytoid differentiation." Am J Pathol 160(4): 1293-9. FULL TEXT

12 Pruneri G, Ponzoni M, Ferreri AJ, et al. The prevalence and clinical implications of c-kit expression in plasma cell myeloma. Histopathology 2006; 48:529-35

This page last revised 3.5.2006.

©SMUHT/PW Bishop