TY - JOUR
T1 - Immunoglobulin derived depositions in the nervous system
T2 - Novel mass spectrometry application for protein characterization in formalin-fixed tissues
AU - Rodriguez, Fausto J.
AU - Gamez, Jeffrey D.
AU - Vrana, Julie A.
AU - Theis, Jason D.
AU - Giannini, Caterina
AU - Scheithauer, Bernd W.
AU - Parisi, Joseph E.
AU - Lucchinetti, Claudia F.
AU - Pendlebury, William W.
AU - Bergen, H. Robert
AU - Dogan, Ahmet
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/10
Y1 - 2008/10
N2 - Proteinaceous deposits are occasionally encountered in surgically obtained biopsies of the nervous system. Some of these are amyloidomas, although the precise nature of other cases remains uncertain. We studied 13 cases of proteinaceous aggregates in clinical specimens of the nervous system. Proteins contained within laser microdissected areas of interest were identified from tryptic peptide sequences by liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). Immunohistochemical studies for immunoglobulin heavy and light chains and amyloidogenic proteins were performed in all cases. Histologically, the cases were classified into three groups: 'proteinaceous deposit not otherwise specified' (PDNOS) (n=6), amyloidoma (n=5), or 'intracellular crystals' (n=2). LC-MS/MS demonstrated the presence of λ, but not κ, light chain as well as serum amyloid P in all amyloidomas. λ-Light-chain immunostaining was noted in amyloid (n=5), although demonstrable monotypic lymphoplasmacytic cells were seen in only one case. Conversely, in PDNOS κ, but not λ, was evident in five cases, both light chains being present in a single case. In three cases of PDNOS, a low-grade B-cell lymphoma consistent with marginal zone lymphoma was present in the brain specimen (n=2) or spleen (n=1). Lastly, in the 'intracellular crystals' group, the crystals were present within CD68+ macrophages in one case wherein κ-light chain was found by LC-MS/MS only; the pathology was consistent with crystal-storing histiocytosis. In the second case, the crystals contained immunoglobulin G within CD138+ plasma cells. Our results show that proteinaceous deposits in the nervous system contain immunoglobulin components and LC-MS/MS accurately identifies the content of these deposits in clinical biopsy specimens. LC-MS/MS represents a novel application for characterization of these deposits and is of diagnostic utility in addition to standard immunohistochemical analyses.
AB - Proteinaceous deposits are occasionally encountered in surgically obtained biopsies of the nervous system. Some of these are amyloidomas, although the precise nature of other cases remains uncertain. We studied 13 cases of proteinaceous aggregates in clinical specimens of the nervous system. Proteins contained within laser microdissected areas of interest were identified from tryptic peptide sequences by liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). Immunohistochemical studies for immunoglobulin heavy and light chains and amyloidogenic proteins were performed in all cases. Histologically, the cases were classified into three groups: 'proteinaceous deposit not otherwise specified' (PDNOS) (n=6), amyloidoma (n=5), or 'intracellular crystals' (n=2). LC-MS/MS demonstrated the presence of λ, but not κ, light chain as well as serum amyloid P in all amyloidomas. λ-Light-chain immunostaining was noted in amyloid (n=5), although demonstrable monotypic lymphoplasmacytic cells were seen in only one case. Conversely, in PDNOS κ, but not λ, was evident in five cases, both light chains being present in a single case. In three cases of PDNOS, a low-grade B-cell lymphoma consistent with marginal zone lymphoma was present in the brain specimen (n=2) or spleen (n=1). Lastly, in the 'intracellular crystals' group, the crystals were present within CD68+ macrophages in one case wherein κ-light chain was found by LC-MS/MS only; the pathology was consistent with crystal-storing histiocytosis. In the second case, the crystals contained immunoglobulin G within CD138+ plasma cells. Our results show that proteinaceous deposits in the nervous system contain immunoglobulin components and LC-MS/MS accurately identifies the content of these deposits in clinical biopsy specimens. LC-MS/MS represents a novel application for characterization of these deposits and is of diagnostic utility in addition to standard immunohistochemical analyses.
KW - Amyloid
KW - Crystal-storing histiocytosis
KW - Immunoglobulin
KW - Lymphoma
KW - Mass spectrometry
KW - Nervous system
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U2 - 10.1038/labinvest.2008.72
DO - 10.1038/labinvest.2008.72
M3 - Article
C2 - 18711355
AN - SCOPUS:52649137511
SN - 0023-6837
VL - 88
SP - 1024
EP - 1037
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 10
ER -