Brain Pathology Case of the Month - December 2005




Monoclonal Ig deposition diseases (MIDD) are defined by tissue deposits of monotypic Ig heavy or light chains, the major cause being a clonal expansion of Ig-secreting plasma cells. The most common form of MIDD is light chain-derived amyloidosis (AL), characterized by Congo red staining of the deposits and green birefringence under polarization microscopy caused by the -pleated sheet arrangement of amyloid protein. Electron microscopy visualizes nonbranching fibrils with an accompanying pentagonal glycoprotein (P component). Immunohistochemically, the deposits stain monotypically for or chains, the latter predominating (Gallo 1986). In contrast, the less frequently recognized LCDD and the combined light and heavy chain deposition diseases (LHCDD) are characterized by deposits of non-fibrillary, amorphous material without -pleated sheet configuration, which makes them Congo-red-negative. Amyloid P or apolipoprotein E is not detectable. In LCDD, deposits are overrepresented compared to ones (Buxbaum 1999).

The mechanisms leading to light-chain aggregation to either amyloid or non-fibrillary structures are not fully understood. The observation of both amyloid and light-chain deposits in the same patient suggests that the aggregation pathway is strongly affected by environmental conditions in addition to sequence properties (Davis 2002). LCDD usually involves the kidneys, but frequently also the liver, heart and nerves and occasionally the joints. Thus, the clinical picture comprises nephrotic syndrome, renal failure, congestive heart failure and, less frequently, liver-related coagulopathy, arthropathy and peripheral neuropathy (Buxbaum 1999, 2000). Plasma cell dyscrasia with monoclonal gammopathy is present in the majority of cases. Though a systemic manifestation was not found in our patient, it cannot be ruled out, since monoclonal light chains may only be detectable intermittently and at low concentrations in serum and/or urine. Moreover, up to 30% of the LCDD patients do not have a demonstrable lymphoplasmacytic disease (Buxbaum 1999).

This is the first published report on LCDD exclusively confined to the brain. The reason for this unusual LCDD site remains unclear, and it is likewise unknown why the disease is restricted to the brain. The most probable explanation is that LCDD originated from the low-grade cerebral lymphoma diagnosed 3 months earlier. PCNSL is a rare entity which accounts for maximal 2% of primary brain tumors with the low-grade subtype comprising approximately 20% in recent publications (Paulus 1999). The ability to produce Ig light chains which aggregate as amyloid has been demonstrated in a few cases (Laeng 1998, Ellie 1989). Conversely, occasional deposits of amyloid-like, Congo-red-negative material in areas surrounding primary CNS lymphoma (PCNSL) were described by Jellinger et al. (Jellinger 1975). In other respects light chain deposits were found in the choroid plexus and pituitary gland of two patients with plasmacytoma and systemic LCDD pituitary gland as well as in the choriocapillaris and the Bruch's membrane of another patient, attributed to plasmacytoma and systemic LCDD (Russell 1976, Daicker 1995). However, the first report does not state whether the deposits were found in the neurohypophysis.

In our patient, the low-grade lymphoplasmacytic cerebral B-cell lymphoma probably led to the production of light chains which did not aggregate as amyloid but formed light chain deposits. According to this hypothesis, LCDD of the CNS is a neoplasm of an Ig light chain-producing B-cell clone capable of terminal differentiation.


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Contributed by L. Fischer MD, A. Korfel MD, G. Stoltenburg-Didinger MD, C. Ransco MD, E. Thiel MD

International Society of Neuropathology