A 66-year-old man presented with a 5-year history of lower-limb livedo reticularis. Complete blood count demonstrated: hemoglobin, 108 g/L; leukocytes, 9.46 × 109/L; and platelets, 393 × 109/L; increased large unstained cells were noted on automated differential. His plasma showed gel-like precipitation (panel A). His blood smear showed visible fine-grained agglutinates compared with control (panel B). Wright-Giemsa staining (panels C, D, F, G) demonstrated multiple extracellular cylindrical crystals (panel C; original magnification ×1000) that partially resolved with warming to 37°C for 30 minutes (panel D; original magnification ×1000). Variable sizes of cylindrical and irregular crystals were observed by phase-contrast microscopy after lysing red blood cells (RBCs) (panel E; original magnification ×400). However, when the patient’s sample was delivered at 37°C and tested immediately, only scattered amorphous particles were observed (panel F; original magnification ×1000), which aggregated at room temperature after 30 minutes and induced RBC morphologic changes mimicking schistocytes and helmet cells (panel G; original magnification ×1000) without actual hemolysis (indirect bilirubin, 3.3 μmol/L; lactate dehydrogenase, 382 U/L). Cryoglobulin testing showed monoclonal immunoglobulin G λ (13091.5 mg/L). Bone marrow examination revealed 15.5% myeloma cells, and multiple myeloma with type 1 cryoglobulinemia was diagnosed.

Cryoglobulin crystallization with clear morphology is a rare phenomenon with different structures. This case illustrates how cryoglobulin transforms from cylindrical to amorphous in shape, and induces RBC morphologic changes on a peripheral smear.

A 66-year-old man presented with a 5-year history of lower-limb livedo reticularis. Complete blood count demonstrated: hemoglobin, 108 g/L; leukocytes, 9.46 × 109/L; and platelets, 393 × 109/L; increased large unstained cells were noted on automated differential. His plasma showed gel-like precipitation (panel A). His blood smear showed visible fine-grained agglutinates compared with control (panel B). Wright-Giemsa staining (panels C, D, F, G) demonstrated multiple extracellular cylindrical crystals (panel C; original magnification ×1000) that partially resolved with warming to 37°C for 30 minutes (panel D; original magnification ×1000). Variable sizes of cylindrical and irregular crystals were observed by phase-contrast microscopy after lysing red blood cells (RBCs) (panel E; original magnification ×400). However, when the patient’s sample was delivered at 37°C and tested immediately, only scattered amorphous particles were observed (panel F; original magnification ×1000), which aggregated at room temperature after 30 minutes and induced RBC morphologic changes mimicking schistocytes and helmet cells (panel G; original magnification ×1000) without actual hemolysis (indirect bilirubin, 3.3 μmol/L; lactate dehydrogenase, 382 U/L). Cryoglobulin testing showed monoclonal immunoglobulin G λ (13091.5 mg/L). Bone marrow examination revealed 15.5% myeloma cells, and multiple myeloma with type 1 cryoglobulinemia was diagnosed.

Cryoglobulin crystallization with clear morphology is a rare phenomenon with different structures. This case illustrates how cryoglobulin transforms from cylindrical to amorphous in shape, and induces RBC morphologic changes on a peripheral smear.

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