amyloid is consequently a clonal expansion of one plasma cell expressing one light chain, usually in excess. The plasma cell clone is spread in the bone- marrow, either as a malignant tumor (myeloma) or as apparently benign cells. The Ig light chain circulates in blood plasma before it aggregates into amyloid ﬁbrils in virtually all organs outside the brain by so far unknown mechanisms. Systemic AL amyloidosis is usually lethal. Although many of the subclasses of Ig light chains are represented in amyloid only, not all light chains are amyloidogenic. There is strong evidence that this restriction depends on the variability in the amino acid sequences, and certain variable subgroups and amino acid substitutions are particularly important (5,6). AL protein of lambda type is 2–3 times more common than of kappa type (7,8). The major part of amyloid AL protein lacks a portion of the constant region (9-12), although a minor component always is the complete Ig light chain (13). Whether or not this truncation is pathogenically important or occurs after ﬁbrillogenesis is not clear. Localized AL amyloidosis Amyloid localized to one tissue, where multiple deposits appear, is very common, particularly in association with aging. Examples are amyloid in the brain in Alzheimer’s disease and in islets of Langerhans in type 2 diabetes (14). In contrast local- ized AL amyloidosis usually appears as one, often tumor-like lesion, although multiple nodules may occur. The symptoms may vary depending on loca- tion of the lesion, but, initially, malignant tumors are often suspected, particularly when the nodules are present in the breast, lung, or urinary tract (3,15,16). Calciﬁcations are common (17), and in the case of breast nodules mammographic appearance may include microcalciﬁcations, increasing the suspicion of malignancy (Figure 1) (18,19). A monoclonal component in plasma is usually absent (20). Treat- ment of choice seems to be local resections endo- scopically, although radical excision has been performed successfully, e.g. for respiratory lesions (3,21). Local resections often have to be repeated (22). The long-term prognosis is usually favorable, although deaths due to severe hemorrhages or other complications have been described (20,21). While a monoclonal gammopathy of unknown signiﬁcance (MGUS) may develop to systemic amyloidosis or myeloma (23) this does not seem to happen with a localized plasma cell clone associated with localized amyloidosis, which almost never progresses to a systemic disease (20,24,25). Localized AL amyloidosis: A suicidal neoplasm? 245 A A A Figure 1. Localized AL amyloidosis in a breast. The localized nature and occurrence of microcalciﬁcations (arrows) constitute a risk of misdiagnosis of mammary carcinoma. Appearance of localized AL amyloid Usually, amyloid deposits are observed in a strictly limited but not encapsulated area. Involvement of vessel walls is common but does only occur very close to the main deposit. Like systemic AL amyloidosis, afﬁnity for Congo red is variable between patients but always present, as is the concomitant green birefrin- gence in polarized light. Unlike deposits in most cases of systemic amyloidosis, crystal-like structures with Maltese cross appearance are as common as areas with concentric ring structures (Figure 2). These formations usually have stronger afﬁnity for Congo red and a brighter green birefringence. Typically, scattered and small groups of plasma cells occur in the amyloid deposits. Localized AL amyloid can occur at virtually any site of the body, including the brain (26). Most common sites are eyelids, larynx, bronchi, skin, and urinary tract. Biochemical nature of localized AL amyloid An immunoglobulin light chain nature of localized nodular pulmonary amyloid was indicated by peptide mapping and immunodiffusion soon after the mono- clonal light chain origin of primary systemic amyloid- osis had been demonstrated (27). Later, amino acid sequence analyses proved the monoclonal immuno- globulin light chain nature in a number of cases (28-35). AL kappa is as common as AL lambda (Solomon A., personal communication). On very rare occasions, a heavy chain fragment has been demonstrated (36). As in systemic AL amyloidosis, most of the amyloid protein is not full-length light chain molecules, and a varying part of the constant