1. ¹Department of Laboratory Medicine and Pathology, Research Center, Mayo Clinic, Rochester, MN, USA
2. ²Department of Neurology, Research Center, Mayo Clinic, Rochester, MN, USA
3. ³Department of Pathology, University of Vermont College of Medicine, Burlington, VT, USA
4. ⁴Department of Proteomics, Research Center, Mayo Clinic, Rochester, MN, USA

Correspondence: Dr FJ Rodriguez, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Mayo Clinic, Rochester, MN 55905, USA. E-mail: rodriguez.fausto@mayo.edu

Received 30 January 2008; Revised 4 May 2008; Accepted 5 May 2008; Published online 18 August 2008.

Abstract

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 , but not , light chain as well as serum amyloid P in all amyloidomas. -Light-chain immunostaining was noted in amyloid (n=5), although demonstrable monotypic lymphoplasmacytic cells were seen in only one case. Conversely, in PDNOS , but not , 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 -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.