Atypical Crystal Morphology in Crystal-Storing Histocytosis in Multiple Myeloma

Abstract

Crystal-storing histiocytosis with massive accumulation of particulate immunoglobulin fragments is a rare phenomenon accompanying multiple myeloma and B-cell dyscrasias. The pathogenesis is not fully understood. A 68-year-old female was hospitalized for pyelonephritis, possible pancreatitis, anemia, and 20-pound weight loss. Abnormal blood work included elevated serum IgG kappa (4,129 mg/dL) on SPEP. A final diagnosis of stage II kappa-restricted IgG multiple myeloma was made. Bone marrow aspirate smears, touch prep, clot sections, and core biopsy showed atypical clusters and sheets of a CD138-positive plasmacellular infiltrate comprising 65% of the marrow cellularity with numerous multinucleated forms. The infiltrate was kappa light chain restricted by ISH and IHC. Approximately 35% of the marrow space was replaced by crystalline deposits that was faintly positive for CD68 and CD163 and contained iron on the Prussian blue stain. Crystalline deposits were negative for CD20, CD138, kappa, and lambda, using immunohistochemical PAS, Congo red, and thioflavin T. Immunofluorescence on Pronase kappa- and lambda-digested paraffin sections was negative. Electron microscopy (EM) revealed two distinct types of intra- and extracellular crystalline deposits. These varied in size and shape; one was electron dense rectangular and, less commonly, rhomboidal. The other was delicate, less electron dense, and fibrillary. Molecular genetic studies results revealed an abnormal FISH panel with aneuploidy (gain of chromosomes 9, 13, and 17) and loss of chromosome 15 and IgH/14q. Although the ultrastructure of crystalline inclusions in plasma cell neoplasms has been previously described, to the best of our knowledge, this is the first report of such inclusions with two distinct ultrastructural features.