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We aimed to establish the role of hyperattenuating medullary abnormalities detected by whole-body non-enhanced low-dose multidetector CT (WBLD-MDCT) in multiple myeloma (MM) patients referred for primary evaluation. 50 consecutive patients with untreated Stage I (n(I) = 11), Stage II (n(II) = 10) and Stage III (n(III) = 29) MM underwent WBLD-MDCT for staging. The number and size of osteolysis, as well as haematologic parameters including paraprotein and beta2-microglobulin levels, were assessed and related to the number, size and density of medullary abnormalities assumed to represent myeloma involvement. Bone marrow abnormalities were found in 2/11 (18%) Stage I, 6/10 (60%) Stage II and 20/29 (69%) Stage III myeloma patients, and did not parallel the incidence of osteolysis. Patients with medullary lesions had higher levels of immunoglobulin A (median, 4730 mg dl(-1) vs 1520 mg dl(-1)), light-chain proteinuria (median, 690 mg dl(-1) vs 214 mg dl(-1)) and IgG paraprotein (median, 3270 mg dl(-1) vs 2610 mg dl(-1)) compared with patients without medullary lesions. In patients with medullary abnormalities, levels of serum beta2-microglobulin were significantly higher than in patients without detectable marrow infiltrates (median, 4.3 mg dl(-1) vs 2.4 mg dl(-1); p = 0.0015). In conclusion, medullary abnormalities visualized by WBLD-MDCT are encountered in all stages of myeloma, including cases without osteolysis. They are associated with significantly elevated serum levels of paraprotein (reflecting tumour mass) and beta2-microglobulin, a prospective prognostic marker for myeloma. The nature and possible prognostic significance of medullary abnormalities detected by WBLD-MDCT therefore warrants further investigation.