Unusual morphological cryoglobulin manifestations on blood and bone marrow smears.

Case report A 66-year-old female presented with a 3 years history of multiple ulcerations on the lower extremities of both legs. The diagnosis of necrotic angiodermitis had been previously proposed. The skin lesions were numerous (6 on right side and 7 on left side), purpuric, evolutive and painful, with width ranging from 0.5 to 4.5 centimeters. No adenopathy, neither liver or spleen enlargement was found. Deep vein thrombosis was ruled out by ultrasonography. At admission, blood cell count anomalies were observed (Table 1), in particular high platelet count (945×10/L). The blood cell analyzer (Bayer Advia 120, Tarrytown, NY, USA) indicated a high percentage of large platelets, red blood cell fragments and ghosts. The blood smear showed a peculiar aspect of poïkilocytosis, with multiple loss of red blood cell periphery (bite cell, Figure 1). Staining the blood film with phloxine B revealed micro-aggregates of pink amorpheous particles between red cells (Figure 2) suggesting the presence of cryoglobulin precipitates. No basophilic inclusion body in the neutrophils was observed. A serum prepared from whole blood at 37°C demonstrated protein precipitation while cooling to room temperature. The protein was identified as a mixed cryoglobulin (type 2, IgG+IgM), with a monoclonal component IgM Kappa. The clotting screen and the thrombophilic explorations were normal (proteins C and S, antithrombin 3, Leiden factor), apart an anticardiolipn IgG. A cold agglutinin was excluded. Skin biopsy demonstrated capillaries thrombosis. A bone marrow aspiration was performed showing 22% lympho-plasmocytes and 3% plasma cells. Extracellular deposits were observed again. Moreover, one part of the plasma cells contained dust -like cytoplasmic inclusions (Figure 3) and some of the macrophages had phagocytized amorpheous particles (Figure 4). Diseases often associated with cryoglobulins were unsuccessfully investigated (lymphoma, multiple myeloma, systemic lupus erythematosus, carcinoma, glomerulonephritis, chronic hepatitis...). In the absence of any apparent relevant disease, the significance of the cryoglobulinemia remains currently unclear. An autoimmune disease is still questionable.