Cytogenetics of extramedullary manifestations in multiple myeloma.

Extramedullary 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.

Similar incidences of TP53 deletions in extramedullary organ infiltrations, soft tissue and osteolyses of patients with multiple myeloma.

BACKGROUND: Extramedullary (EM) organ impairment in patients with multiple myeloma (MM) is a rare event, occurring mostly during disease relapse after high-dose chemotherapy with autologous or allogeneic stem cell transplantation. This manifestation is commonly associated with an unfavourable outcome. Previous studies suggested a correlation between the clinical course of patients with MM and EM and the cytogenetic findings, e.g. deletion of TP53 on 17p13. MATERIALS AND METHODS: We investigated patients with these rare plasma cell organ infiltrations (n=17) as well as bone lesions or soft tissue lesions, known to be a common clinical feature of MM (n=14), using a newly established method of fluorescence in situ hybridization in combination with cytoplasmic immunoglobulin staining (cIg-FISH) on paraffin-embedded sections and a specific probe for TP53 on 17p13. RESULTS AND CONCLUSION: The incidence of del(17)(p13) was similar in both groups but overall it was higher when compared to published data obtained from bone marrow samples and material originating from osteolyses. Further investigations on a larger patient cohort are needed in order to confirm these findings.