Amyloidosis

Amyloidosis

Introduction:

Amyloidosis is the name for a group of rare, serious conditions caused by a build-up of amyloid in organs and tissues throughout the body. Amyloid is an abnormal insoluble protein that is produced in the bone marrow and can be deposited in any tissue or organ. The build-up of the amyloid proteins (deposits) can make it difficult for the organs and tissues to work properly.

The word “amylon” was first used in 1834 by the German botanist Matthias Schleiden to describe the waxy starch in plants. Rudolph Virchow then coined the word “amyloid” in 1854 to describe tissue deposits that stained like cellulose when exposed to iodine. Pathologists now know that amyloid, using the Congo red stain introduced in the 1920s, looks pink with normal lighting and demonstrates apple-green birefringence under polarized light. The various types of amyloid are indistinguishable using light microscopy. It is therefore essential for the pathologist to perform additional studies to definitively identify the type of protein involved since the prognosis and treatment of amyloidosis can vary widely depending on the protein responsible.

Amyloidosis

Amyloidosis, Node, Congo Red

Apple-green birefringence under polarized light. Positive lambda light chain stain in a glomerulus.

Amyloidosis can affect different organs in different people, and there are different types of amyloid. Amyloidosis frequently affects the heart, kidneys, liver, spleen, nervous system and digestive tract. Without treatment, severe amyloidosis can lead to life-threatening organ failure. There’s no cure for amyloidosis, but treatments can help to manage the symptoms and limit the production of amyloid protein.

Primary (AL) Amyloidosis:

The most common type of amyloidosis results when light chains are produced in excess by clonal or frankly malignant plasma cells. It occurs in 10-15% of patients with full-blown multiple myeloma but can also be seen when the affected patient has less than 10% bone marrow plasma cells, the quantity typically required to make a diagnosis of myeloma. Light-chain amyloidosis may also arise in association with non-Hodgkin’s lymphoma and Waldenström’s macroglobulinemia. It is a relatively rare disease with an incidence of 5.1-12.8 per million person-years and only 1,275-3,200 new cases being diagnosed in the United States annually. The male-to-female ratio is 3:2. Although healthy individuals have a preponderance of kappa free light chains (K/λ) = 2:1), the reverse is true in most patients with primary amyloidosis, as excess lambda light chains have a greater propensity to be amyloidogenic.

References:

Baker KR, Rice L. The amyloidoses: clinical features, diagnosis and treatment. Methodist Debakey Cardiovasc J. 2012;8(3):3–7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487569/

Guidelines on the diagnosis and investigation of AL amyloidosis – Gillmore – 2015 – British Journal of Haematology – Wiley Online Library https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.13156

Amyloidosis – Symptoms and causes https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20353178

Kyle RA. Amyloidosis: a convoluted story. Br J Haematol. 2001 Sep;114(3):529–38.

Lachmann HJ, Booth DR, Booth SE, Bybee A, Gilbertson JA, Gillmore JD, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002 Jun 6;346(23):1786–91.

Comenzo RL. How I treat amyloidosis. Blood. 2009 Oct 8;114(15):3147–57.

Falk RH, Comenzo RL, Skinner M. The systemic amyloidosis. N Engl J Med. 1997 Sep 25;337(13):898–909.

Dubrey SW, Cha K, Andersen J, Chamarthi B, Reisinger J, Skinner M, et al. The clinical feature of immunoglobulin light-chain (AL) amyloidosis with heart involvement. QJM. 1998 Feb;91(2):141–57.

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