Localized AL amyloidosis: a suicidal neoplasm?

Abstract

Although AL amyloidosis usually is a systemic disease, strictly localized AL deposits are not exceptionally rare. Such case reports form a considerable body of published articles. Although both AL amyloidosis types are formed from an N-terminal segment of a monoclonal immunoglobulin light chain, a typical localized AL amyloid differs from the systemic counterpart by the morphological appearance of the amyloid, and presence of clonal plasma cells and of giant cells. In this article it is pointed out that localized AL amyloidosis ('amyloidoma') represents a true plasma cell neoplasm and not a pseudotumor. The pathogenesis of localized AL amyloidosis may differ from that of the systemic type, a suggestion underlined by the fact that localized AL amyloidosis of kappa type is as common as that of lambda origin, in contrast to the systemic form where lambda chains constitute the overwhelming majority of cases. It is suggested that oligomeric assemblies of the produced immunoglobulin light chain are toxic to plasma cells, which in this way commit suicide.

Figure 1.

Localized AL amyloidosis in a breast. The localized nature and occurrence of microcalcifications (arrows) constitute a risk of misdiagnosis of mammary carcinoma.

Figure 2.

Typical appearance of localized AL amyloidosis with discrete amyloid formation and multiple giant cells. Note the concentric appearance of some amyloid particles (arrows).

Figure 3.

‘Amyloidoma' immunolabeled with the immunoglobulin light chain lambda-specific monoclonal antibody pwlam (73). Amyloid and a majority of plasma cells (PC) are strongly labeled. Note the giant cells (GC) between plasma cells and amyloid. The hypothesis is that plasma cells are synthesizing an amyloidogenic Ig light chain, which is modified by giant cells to amyloid fibrils.

Figure 4.

Amyloid adjacent to giant cells (GC). An organization of amyloid fibrils is apparent when in contact with giant cells. This organization is interpreted as assemblage of protein, probably after some modification, into fibrils on or at the surface of the cells. Congo red stained section in polarized light with crossed polars.

Figure 5.

Suggested events in localized AL amyloidosis. A plasma cell clone develops at one site. The cells express amyloidogenic Ig light chains and, in addition, an unknown factor that attracts macrophages and cause them to fuse into giant cells. Ig light chains are modified by giant cells and aggregate into bundles of amyloid fibrils at the surface of these cells. In addition, smaller aggregates of Ig light chains are toxic to plasma cells, an event controlling the plasma cell clone.