Immunoglobulin derived depositions in the nervous system: novel mass spectrometry application for protein characterization in formalin-fixed tissues.
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 lambda, but not kappa, light chain as well as serum amyloid P in all amyloidomas. lambda-Light-chain immunostaining was noted in amyloid (n=5), although demonstrable monotypic lymphoplasmacytic cells were seen in only one case. Conversely, in PDNOS kappa, but not lambda, 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 kappa-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.
Rodriguez
Fausto J
FJ
Department of Laboratory Medicine and Pathology, Research Center, Mayo Clinic, Rochester, MN 55905, USA. rodriguez.fausto@mayo.edu
Gamez
Jeffrey D
JD
Vrana
Julie A
JA
Theis
Jason D
JD
Giannini
Caterina
C
Scheithauer
Bernd W
BW
Parisi
Joseph E
JE
Lucchinetti
Claudia F
CF
Pendlebury
William W
WW
Bergen
H Robert
HR
Dogan
Ahmet
A
D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D005260:Female; D015614:Histiocytosis / Q000473:pathology; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000032:analysis; D008223:Lymphoma / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D010525:Peripheral Nerves / Q000473:pathology*; D012189:Retrospective Studies; D000683:Serum Amyloid P-Component / Q000032:analysis; D021241:Spectrometry, Mass, Electrospray Ionization; D013116:Spinal Cord / Q000473:pathology*
D007146:Immunoglobulin lambda-Chains; D009419:Nerve Tissue Proteins; D000683:Serum Amyloid P-Component