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A7246 - The Analyses of Immunoglobulin Crystal Formation at Lung in Crystal Storing Histiosytosis and Crystalglobulinemia Syndrome
Author Block: N. Kokuho, Y. Terasaki, K. Yusuke, S. Kunugi, M. Terasaki, Y. Takada, A. Gemma, A. Shimizu; Nippon Medical School, Tokyo, Japan.
RATIONALE: In cases of abnormal plasma cell proliferative diseases, the findings of immunoglobulin (Ig) crystal deposition inside and/or outside of the cells are reported as rare conditions such as crystal storing histiocytosis (CSH) and crystalglobulinemia syndrome (CGS), however the mechanism of crystallization is poorly understood. We experienced a case of lung lesion with CSH combined with pulmonary MALT lymphoma and a case of lung lesion with CGS associated with multiple myeloma (MM) (monoclonal IgG lambda type exhibiting). In recent years, the usefulness of analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS) using the samples from laser microdissected paraffin tissue has attracted attention because the precise component of protein can be identified by it in addition to paraffin tissue analyses with immunohistochemistry or in situ hybridization.METHODS: We analyzed the crystals and plasma cells in each two different conditions by electron microscopy and LC-MS/MS using the samples from laser microdissection to elucidate the mechanism of the crystal formations. As negative controls, five cases of MM (monoclonal IgG lambda type exhibiting) without crystallization were performed LC-MS/MS analyses of plasma cells in bone marrow.RESULTS: In CGS case, the crystals, which were 100 μm less in length, were present mainly outside of the cells such as in the alveolar space and renal tubular cavities, and were not found inside or outside of plasma cells in bone marrow. On the other hand, in CSH case, the crystals, which were 10 μm less in length, were present only inside of histiocytes and plasma cells. In the analyses with LC-MS/MS of CGS case using the samples from laser microdissection, the low-frequency spectra of Ig lambda-2-constant region was detected from plasma cells in bone marrow and the high-frequency spectra of same region was detected from the lung crystals. On the other hand, in case of the CSH, the low-frequency spectra of Ig kappa-constant region was detected from plasma cells around the lung lesion of MALT lymphoma, however, the high-frequency spectra of the Ig kappa-variable region was detected from the crystals. In five negative control cases, only the low-frequency Ig lambda-like polypeptides were detected from the bone marrow plasma cells in all cases.CONCLUSIONS: Thus the different the crystal localization at a cellular level and different predominant components of the Ig light chain between crystals and plasma cells in each two different conditions (CSH and CGS) suggested the different mechanisms of the crystal formation of them.