Amyloidosis

Morie Gertz, Steven R. Zeldenrust

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Amyloidosis is defined by its tinctorial properties. Deposits seen in tissues that bind Congo red and demonstrate green birefringence when viewed under polarized light is the sine qua non. Amyloid deposits are extracellular and amorphous when seen with a light microscope. They are pinkish-appearing when stained with hematoxylin and eosin. By electron microscopy, amyloid deposits are rigid, nonbranching fibrils of indefinite length and a width of approximately 9.5 nm [1]. Amyloid deposits can be purified because they are insoluble in saline and represent the residue after repeated homogenizations in water [2]. Historically, amyloidosis was classified as familial when seen with an autosomal dominant inheritance pattern [3]. Amyloidosis was defined as secondary when it occurred in the presence of a longstanding inflammatory process bronchiectasis, osteomyelitis, tuberculosis, leprosy, inflammatory bowel disease, or abscess. All unknown forms of amyloidosis were referred to as primary amyloidosis. With the advent of modern biochemical techniques, amyloidosis can be classified based on the subunit protein comprising the amyloid fibril. An abbreviated nomenclature for amyloidosis is given in Table 22.1 [4]. Forms other than immunoglobulin light chain amyloidosis are unlikely to be encountered by a practicing oncologist. All forms of AL are composed of immunoglobulin light chains or heavy chains or fragments thereof. Experimentally, it is possible to digest immunoglobulin light chains in vitro and have them form amyloid fibrils [5]. Most light chain amyloid fibrils are composed of a fragment of the immunoglobulin light or heavy chain and have a molecular weight of approximately 12 kDa. The clinical characteristics of light and heavy chain amyloidosis are not distinct, and the determination can be made by mass spectroscopy. Light chains from the urine of patients with amyloidosis can produce amyloid deposits in mice when injected [6]. It is, therefore, assumed that certain Bence Jones proteins have an amyloidogenic predisposition. This suggests they are more prone to misfolding into the beta-pleated sheet configuration. Additional evidence of the amyloidogenicity of light chains is derived from the fact that in multiple myeloma and MGUS, κ light chains account for two-thirds of the immunoglobulin proteins; but in light chain amyloidosis, λ light chains represent three-quarters of the deposits seen [7] (Fig. 22.1). Moreover, the λ<Subscript>VI</Subscript> subclass of light chain amyloidosis is virtually always associated with AL [8]. Patients with amyloidosis may be classified into those with and those without multiple myeloma. It appears that the percentage of plasma cells has an impact on outcome [9]. However, only the rare patient actually develops lytic bone disease, cast nephropathy, or cytopenias related to marrow infiltration. If a patient does not present with multiple myeloma at the time of diagnosis, the likelihood of overt myeloma developing during the course of the disease is <1 % [10]. Amyloidosis has an incidence of 8 per million per year with a median age of approximately 67. The ratio of patients seen with multiple myeloma to amyloidosis is approximately 5:1. The median number of plasma cells seen at the time of diagnosis ranges from 5 to 7 % [11]. Generally, in amyloidosis, the cells are nonproliferative, fail to carry the genetic abnormalities typically seen in multiple myeloma, and have a very small percent in S phase.

Original languageEnglish (US)
Title of host publicationMultiple Myeloma
Subtitle of host publicationDiagnosis and Treatment
PublisherSpringer New York
Pages265-282
Number of pages18
ISBN (Electronic)9781461485209
ISBN (Print)9781461485193
DOIs
StatePublished - Jan 1 2014

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Gertz, M., & Zeldenrust, S. R. (2014). Amyloidosis. In Multiple Myeloma: Diagnosis and Treatment (pp. 265-282). Springer New York. https://doi.org/10.1007/978-1-4614-8520-9_22