248 P. Westermark Plasma cells Macrophages Unknown factor Ig light chains Fusion Toxic aggregates Giant cell 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. formation of localized AL amyloidosis has been outlined in Figure 5. Another interesting aspect of localized AL amyloid is the sparse occurrence of plasma cells in the lesions. In fact, the number of plasma cells is sometimes so low that the clonality can be difﬁcult to demonstrate. The lesion has therefore been suggested to represent a ‘burnt-out’ plasmacytoma (9,69). In many other amyloid diseases, e.g. Alzheimer’s disease or type 2 diabetes, there is increasing evidence that amyloid protein aggregation involves genesis of smaller aggre- gates (oligomers, protoﬁbrils) that exert a toxic effect on nearby cells and generate apoptosis (reviewed in (70,71)). In addition, such a mechanism is believed to explain the rapid effect on myocardial dysfunction after successful treatment of a plasma cell clone in systemic AL amyloidosis (72). If generation of toxic oligomers is true also with the formation of localized AL amyloid, this may lead to apoptosis of plasma cells in an ‘amyloidoma’. This event may then be regarded as a suicide of tumor plasma cells creating a self-limiting neoplasm. Acknowledgements Thanks to Gunilla T. Westermark for help with ﬁgures. Supported by the Swedish Research Council. Declaration of interest: The author reports no conﬂicts of interest. The author alone is responsible for the content and writing of the paper. References 1. Jarrett JT, Lansbury PT. Seeding "one-dimensional crystalli- zation" of amyloid: a pathogenic mechanism in Alzheimer’s disease and scrapie? Cell. 1993;73:1055–8. 2. Bhagwandeen BS, Taylor S. Primary localized amyloidosis of the bladder with a monoclonal plasma cell inﬁltrate. Patho- logy. 1988;20:67–9. 3. Monge M, Chauveau D, Cordonnier C, Noël LH, Presne C, Makdassi R, et al. Localized amyloidosis of the genitourinary tract: report of 5 new cases and review of the literature. Medicine (Baltimore). 2011;90:212–22. 4. Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G, Saraiva MJ, et al. Amyloid ﬁbril protein nomenclature: 2010 recommendations of the nomenclature committee of the International Society of Amyloidosis. Amyloid. 2010;17: 101–4. 5. Solomon A, Frangione B, Franklin EC. Bence Jones proteins and light chains of immunoglobulins. Preferential association of the V–VI subgroup of human light chains with amyloidosis AL(l). J Clin Invest. 1982;70:453–60. 6. Stevens FJ. Protein structure, stability, and conformational disease: human antibody light chains 1999. Springﬁeld, VA: National Technical Information Service, U.S. Department of Commerce; 1999. 7. Isobe T, Osserman EF. Patterns of amyloidosis and their association with plasma-cell dyscrasia, monoclonal immuno- globulins and Bence-Jones proteins. N Engl J Med. 1974;290: 473–7. 8. Bellotti V, Mangione P, Merlini G. Review: immunoglobulin light chain amyloidosis—the archetype of structural and path- ogenic variability. J Struct Biol. 2000;130:280–9. 9. Glenner GG. Amyloid deposits and amyloidosis. The b-ﬁbrilloses. N Engl J Med. 1980;302:1283–92; 1333–43. 10. Tveteraas T, Sletten K, Westermark P. The amino acid sequence of a carbohydrate-containing immunoglobulin-