Upsala Journal of Medical Sciences. 2012; 117: 244–250 REVIEW ARTICLE Localized AL amyloidosis: A suicidal neoplasm? PER WESTERMARK Department of Immunology, Genetics and Pathology, Uppsala University, SE 751 85 Uppsala, Sweden 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. Key words: Amyloid, immunoglobulin light chain, ﬁbrils, giant cells, plasmacytoma, neoplasm Introduction The amyloidoses constitute a large and heterogeneous group of protein misfolding disorders in which pro- teins adopt a high degree of beta-sheet structure, allowing molecules to bind to each other in long, cross-beta-sheet ﬁbrils. In this form the protein is comparatively resistant to degradation, explaining why the amyloid masses may increase as long as the protein substrate is present. The mechanisms behind the ﬁbril formations are still insufﬁciently understood, but it is generally accepted that generation of amyloid from a protein includes three phases. The ﬁrst phase is nucleation, at which misfolded molecules assemble to form a nucleus, resembling the process of crysta- llization (1). This nucleus can catalyze an amyloid- prone misfolding of other molecules, which adopt b-structure and form rapidly growing ﬁbrils. This second elongation phase proceeds until a steady state (third phase) has been obtained. A particularly favor- able milieu is consequently formed where there is a high concentration of substrate. This mini-review deals with the nature of one localized form of amyloidosis that clinically often presents as a malignant tumor but that is often regarded as a pseudotumor or tumor-like nodule (2,3). One of the main messages in this communica- tion is that it is a manifestation of a real neoplasm. AL amyloidosis Amyloidosis can either be systemic or localized. In systemic forms, the precursor of the ﬁbril protein is expressed at one site, e.g. liver or bone-marrow, released to blood plasma in soluble form, distributed via the circulation, and ﬁnally deposited as amyloid ﬁbrils in different organs by yet unknown mecha- nisms. In human, 15 different proteins have been shown to be able to cause systemic amyloidosis, although most forms are very rare (4). One of the least uncommon is AL amyloidosis where the ﬁbril protein is derived from monoclonal immunoglobulin (Ig) light chains. The primary cause of this form of Correspondence: Per Westermark, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden. E-mail: Per.Westermark@igp.uu.se (Received 25 November 2011; accepted 23 December 2011) ISSN 0300-9734 print/ISSN 2000-1967 online 2012 Informa Healthcare DOI: 10.3109/03009734.2012.654861