title: Fatal Cryocrystalglobulinemia With Intravascular and Renal Tubular Crystalline Deposits.
abstract: Cryocrystalglobulinemia is a rare variant of cryoglobulinemia in which monoclonal immunoglobulins self-assemble into crystalline arrays. We report a case of a 53-year-old man who presented with systemic thrombotic microangiopathy causing multiorgan failure, including decreased kidney, lung, and gastrointestinal function; skin necrosis; and mental status changes. Skin and kidney biopsy specimens showed intravascular thrombi, along with intravascular, intratubular, and periglomerular crystalline deposits. Typical morphologic features of cryoglobulinemia, such as a leukocytoclastic vasculitis and pseudothrombi, were absent. Spindled crystals precipitated in the cryoglobulin assay, and immunofixation showed them to be composed of monoclonal immunoglobulin G κ light chains. Ultrastructural analysis demonstrated deposits to have an array-like substructure. The patient was successfully treated with a combination of plasmapheresis, steroids, and bortezomib, but experienced a relapse and died 12 months after his initial diagnosis. Cryocrystalglobulinemia causes significant morbidity and mortality and should be classified as a monoclonal gammopathy of renal significance when it occurs in patients not meeting diagnostic criteria for multiple myeloma.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Ann Arbor, MI.
authors.forename: Paul A
authors.initials: PA
authors.lastname: DeLyria
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Avedschmidt
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI.
authors.forename: Chisa
authors.initials: C
authors.lastname: Yamada
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI. Electronic address: efarkash@med.umich.edu.
authors.forename: Evan A
authors.initials: EA
authors.lastname: Farkash
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000069286:Bortezomib / Q000627:therapeutic use; D003449:Cryoglobulinemia / Q000150:complications / Q000473:pathology* / Q000628:therapy; D003450:Cryoglobulins; D003460:Crystallization; D017809:Fatal Outcome; D005921:Glomerulonephritis / Q000150:complications / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007145:Immunoglobulin kappa-Chains; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000150:complications / Q000473:pathology* / Q000628:therapy; D010956:Plasmapheresis; D057049:Thrombotic Microangiopathies / Q000150:complications / Q000473:pathology* / Q000628:therapy
chemical_list: D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents; D003450:Cryoglobulins; D007145:Immunoglobulin kappa-Chains; D000069286:Bortezomib
keywords: Cryocrystalglobulinemia; MGUS; bortezomib; cryoglobulin; crystalglobulinemia; kidney biopsy; monoclonal gammopathy; purpura; renal cortical necrosis; thrombotic microangiopathy