Amyloidomas of the nervous system: a monoclonal B-cell disorder with monotypic amyloid light chain lambda amyloid production.

BACKGROUND: Amyloidomas or localized tumor-like amyloid deposits rarely affect the nervous system. To the authors' knowledge, no comprehensive studies on central and peripheral nervous system amyloidomas have been published. The amyloid subtype of amyloidomas of the nervous system only recently was characterized and almost invariably was found to be of amyloid light chain (AL) lambda type. The nature of the plasma cell population responsible for AL amyloid production has not been investigated further.

METHODS: The current analysis included the clinical findings, neuroimaging characteristics, and pathology of seven amyloidomas (four cerebral and three involving peripheral nerves). All were subjected to histochemical staining (Congo red, thioflavine S) and to immunohistochemical study using primary antibodies detecting serum amyloid component P, serum amyloid protein A (SAA), transthyretin, beta2 microglobulin (beta2m), and free immunoglobulin (Ig) light chain. For the detection of mRNA of light chain Ig, fluorescein-conjugated kappa and lambda mRNA oligonucleotide probes were used. For the assessment of B-cell clonality, polymerase chain reaction (PCR) was applied on extracted DNA from two cases using VH FRIII and JH primers. Two cases were assessed ultrastructurally.

RESULTS: All amyloidomas were organ restricted and unrelated to systemic amyloidosis. The clinical symptoms of the cerebral lesions were nonspecific, whereas neurologic deficits were noted in the distribution of the involved peripheral nerves. Cerebral deposits, either solitary or multiple, were associated spatially with the choroid plexus and secondarily extended into white matter. All peripheral nerve amyloidomas involved the gasserian ganglion of the trigeminal nerve. Imaging by computed tomography and magnetic resonance imaging scans revealed hyperdense and contrast-enhancing mass lesions unassociated with significant edema. Immunohistochemically, the amyloid was present in the interstitium and within the walls of the intralesional vessels, was invariably of AL lambda subtype, and was negative for free Ig kappa light chains, SAA, transthyretin, and beta2m. Plasma cells along the perivascular sheaths and occasionally squeezed between amyloid masses showed no cytologic atypia. In situ hybridization for Ig light chain mRNA reflected a massive preponderance of lambda-producing cells. PCR revealed monoclonal rearrangement of the heavy chain Ig gene.

CONCLUSIONS: The results of the current study provide strong support for the concept that amyloidomas of the nervous system are neoplasms of an AL lambda-producing B-cell clone capable of terminal differentiation. Nevertheless, all seven patients lacked clinical evidence of an aggressive or systemic lymphoplasmacytic neoplasm. Unlike plasmacytomas, the relatively indolent course of most nervous system amyloidomas is reminiscent of the similarly indolent biologic behavior of extranodal, low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.