Cytogenetics of extramedullary manifestations in multiple myeloma

Abstract

SummaryExtramedullary disease in patients with multiple myeloma is a rare event, occurring mostly in advanced disease or relapse. Outcome is poor and prognostic factors predicting the development of extramedullary disease have not been defined. We investigated cytogenetic alterations of myeloma cells in different extramedullary manifestations by adapting the fluorescence in situ hybridization (FISH) technique in combination with cytoplasmic immunoglobulin staining to study the cytogenetics of plasma cell tumours on paraffin embedded material. Thirty six patients were investigated: 19 with extramedullary disease, 11 with skeletal extramedullary disease and six with solitary extramedullary plasmacytoma. The first two groups showed the following results: del(17p13) 32% vs. 27%, del(13q14) 35% vs. 27%, MYC-overrepresentation 28% vs. 18% and t(4;14) 37% vs. 18%. We detected an overall higher incidence of del(17p13) in both groups compared to data from bone marrow samples of multiple myeloma reported to date (range 7-16%). The solitary extramedullary plasmacytomas presented overall less cytogenetic aberrations than the other groups. Most important, three patients with extramedullary disease and one with skeletal extramedullary disease presented different FISH findings in the extramedullary tumour compared to their bone marrow plasma cells. del(17p13), occurring additional in three of four cases, seems a strong marker for extramedullary progression of myeloma.

Impact of extramedullary plasmacytomas on outcomes according to treatment approach in newly diagnosed symptomatic multiple myeloma

“…In contrast, Billecke et al reported that patients with MM and extramedullary involvement presenting different FISH findings in the EMPs compared to their bone marrow plasma cells. In their study, del(17p13) seems a strong marker for extramedullary progression [21]. Bone marrow genetic abnormalities are not associated with extramedullary spread per se, which also suggests that microenvironmental interactions appear to be important.…”

How I treat extramedullary myeloma

“…6 High LDH levels, anemia, thrombocytopenia, nonsecretory MM, and highrisk cytogenetic features are more frequent in patients with de novo EMM than in patients with classic MM. 16,21,22 Interestingly, the combination of high LDH level and high-risk cytogenetic features, parameters found to be more frequent in EMM, has been described to be associated with an ultrahigh risk of early progression or disease-related death in MM patients. 23 Moreover, the frequency of high-risk gene expression profiles (MAF and PR) is found to be higher in EMM patients.…”

From carcinoma through lymphoma to myeloma: a gastric mass diagnostic rollercoaster ride

“…Among others, the two distinct cytogenetic aberrations del(17p13) and del(13q14) seem to occur more commonly in EMD when compared with MM with sole manifestation in bone marrow and have been suggested as markers for progression to EMD 7–10. EMD seems an advanced, cytologically distinct and more aggressive form of MM 7. Our case emphasises to actively consider MM and EMD in patients with known monoclonal gammopathy of unknown significance (MGUS) encountering a new medical problem, irrespective of the clinical presentation.…”