How to distinguish multiple myeloma and amyloidosis

Multiple myeloma is a malignant plasma cell tumor, which ranks second in terms of prevalence among the hematologic malignancies. Diagnostic criteria includes occurrence of a monoclonal component detectable on serum and/or urine electrophoresis, light chain restricted bone marrow plasmacytosis, and the demonstration of related organ or tissue impairment shown by increased calcium, renal failure, anemia, and bone lesions. The staging procedure, whereby demonstration of skeletal sparing or at most a solitary osteolytic lesion allowed a multiple myeloma patient to be defined as stage I and, conversely, the occurrence of multiple osteolytic lesions was sufficient by itself to assign a patient to stage III. This staging system has been extensively used for approximately 30 years for its prognostic implications and as a reliable tool of patient stratification in clinical trial research. Recently, in step with the introduction of more accurate and advanced imaging techniques, an updated anatomic and functional Durie and Salmon ‘‘plus’’ staging system has been established, which allows a better classification of patients with early stage multiple myeloma, who can more easily be differentiated from those with monoclonal gammopathy of undetermined significance or smoldering myeloma; a better discrimination among patients with stage II or stage III multiple myeloma, based on the occurrence of more than 20 focal lesions and/or extra-medullary disease

At least twenty-three different unrelated proteins exhibit amyloidogenic properties, in that their low molecular weight subunits may become amyloid fibers and undergo extra-cellular deposition in localized or systemic fashion, eventually resulting in functional impairment of the affected organ(s) . Localized amyloidosis involves more frequently single districts, for example, larynx, ureter, skin, eyelid, and cardiac atria, and is characterized by the occurrence of foci of monoclonal plasma cells that synthesize amyloidogenic light chains. It is conceivable that giant cells are able to misfold these chains to AL amyloid fibrils. Systemic amyloidosis, on the other hand, is structurally heterogeneous and includes three main types: 1. AL amyloidosis, formed by lambda and less often kappa light chains, produced in the course of a usually indolent monoclonal B cell expansion; 2. AA amyloidosis, whose precursor is the acute phase protein SAA, synthesized in excess by the liver following chronic inflammatory and infectious conditions; 3. ATTR amyloidosis that results from a point mutation of the precursor protein transthyretin secreted by the liver, a carrier of retinol-binding protein and thyroxine in the blood and a ‘‘negative’’ acute phase protein. By definition, systemic amyloidosis can virtually affect many organs and tissues, and most frequently kidneys, liver, heart, lungs, nerves, and spleen.

Dammacco, Franco, et al. Clinical and Experimental Medicine 15.1 (2015):1-18.

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