Hyperlipidemic myeloma: review of 53 cases

Abstract

Hyperlipidemic myeloma is a rare and poorly understood variant of multiple myeloma. We report the case of a 53-year-old woman with hyperlipidemic myeloma, skin xanthomas and hyperviscosity syndrome who underwent allogeneic bone marrow transplantation. A comprehensive literature search identified 52 additional cases with plasma cell disease and hyperlipidemia. A detailed analysis revealed several characteristics of these patients as compared to multiple myeloma with normal lipid status: (1) IgA paraprotein was present in the majority (53% vs. 21% in classical multiple myeloma). (2) Skin xanthomas, especially in the palmar creases, elbows, and knees were common (70%). (3) Hyperviscosity syndrome occurred more often (26% vs. 2-6%). While conventional lipid-lowering therapy had only marginal effects, successful anti-myeloma therapy also reduced hyperlipidemia. Analyses of the mechanisms leading to hyperlipidemia documented complexes of paraprotein and lipoprotein in 75% of the 32 cases tested, suggesting an inhibitory role of the paraprotein on lipid degradation. In conclusion, the clinical characteristics, the therapeutic options, and the pathophysiologic mechanisms of hyperlipidemic myeloma are comprehensively reported using the available data from all 53 published cases in the literature.

Pathogenesis and treatment of xanthomatosis associated with monoclonal gammopathy

“…In HX and NX, an interaction between the MIg and lipoprotein has been more or less well documented in 16 and 9 cases, respectively. 3,21 In HX, this interaction may alter the lipoprotein linkage to its receptor leading to hyperlipidemia, 55 whereas in NX the interaction seems to result in enhanced lipid accumulation in the macrophages. 6 Few data are available for NXG, but an interaction between the MIg and a lipoprotein and activation of circulating monocytes has been described in 1 case each.…”

“…Touton cells were found in 2 patients. Of the 15 treated patients, 3 treatment was reported as effective in 53% (8 of 15) of the patients who received standarddose chemotherapy using alkylating agents and steroids (n ϭ 6) or adriamycin and steroids (n ϭ 1). In addition, 1 patient was treated by high-dose therapy and autotransplant, which produced both hematologic and cutaneous complete remission; at myeloma (and hyperlipemia) relapse, he received an allogeneic transplant, but there is no information about subsequent progression of the xanthomatous lesions.…”

“…We reviewed 216 well-described cases of xanthomatosis associated with MIg in the literature, including 37 cases of HX, 3 63 of NX, 6,9-30 and 116 of NXG 4,8,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] (Tables 3 and 4). The main patient characteristics are listed in Tables 3 and 4.…”

“…Xanthoma lesions in HX and NX are similar (yellow maculae or papules, although NX lesions are usually diffuse and plane), whereas HX lesions are more polymorphic and can include tuberous, tendinous, palmar, or eruptive xanthoma. 3 In contrast, NXG lesions are firm papules, nodules, or plaques, the color of which varies from violaceous to red-orange or yellow. 4 HX and NX are characterized by foam cell infiltration in the skin, whereas NXG is featured by the association of necrobiosis, giant cells (Touton type), asteroid bodies, cholesterol clefts, and foam cells.…”

“…However, the antilipoprotein activity of MIg has been documented in some patients with HX and NX, and this points toward a cause-and-effect link between the 2 disorders. 3,6,7 The physiopathology of NXG remains much less well understood than the 2 other forms. 8 Therapeutic options for patients with xanthoma lesions and associated MIg, which depend on the demonstration of a relationship between the 2 disorders, are currently poorly defined.…”