Kidney non-tumor - Amyloidosis

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Kidney non-tumor

Associated with systemic conditions

Amyloidosis

Reviewers: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 10 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
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● Group of conditions with extracellular deposition of fibrillar proteins having an anti-parallel, beta-pleated sheet tertiary structure, leading to Congo Red staining and apple-green birefringence under polarized light
● Amyloid is composed of a fibrillary protein (types described below) and non-fibrillary glycoproteins (amyloid P component also called serum amyloid P [SAP], glycosaminoglycans and apolipoprotein E)
● Serum amyloid P may contribute to stability of amyloid deposits; radioactive iodine-labeled SAP is used in nuclear medicine studies to assess amyloid deposition
● Irrespective of molecular composition, amyloid always has the same characteristic histologic and ultrastructural appearance
● Amyloid is resistant to digestion, accumulates within tissue, interferes with function and destroys vital organs

Clinical features
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● Renal amyloidosis causes 5% of adult cases of nephrotic syndrome
● Suggestive of renal amyloidosis (Chinese study): middle-age, nephrotic syndrome, weight loss, organ enlargement, monoclonal light chains in serum or urine (Clin Lab 2011;57:947)
● Systemic or localized
● Duodenal biopsy is sensitive for diagnosing amyloidosis in chronic kidney disease patients, and highly correlates with renal amyloidosi (Clin Nephrol 2012;77:114)
● Can determine specific type based on immunohistochemistry / immunofluoresence; also laser microdissection and mass spectrometry (Kidney Int 2012;82:226)

AL type:
● Also called primary amyloidosis
● Most common cause of renal amyloidosis in US
● Due to plasma cell dyscrasias with systemic deposition of amyloid and mild increase in bone marrow plasma cells that are monoclonal
● 20% have myeloma or other lymphoproliferative disorders
● Deposits are more likely lambda (75%) light chains or fragments than kappa type, often from amino-terminal fragment of variable region of light chain
● Either vascular-limited or diffuse patterns (Nephrol Dial Transplant 2012;27:1097)
● 40% develop nephrotic syndrome
● Urinary exosomes may be useful to identify patients with AL amyloidosis (PLoS One 2012;7:e38061)
● Poor prognosis (Intern Med 2011;50:2511); patients may develop acute leukemia after alkylating agents, secondary malignancies after autologous transplantation

AA type:
● Also called secondary amyloidosis
● Associated with chronic inflammatory conditions such as osteomyelitis, bronchiectasis, decubitus ulcers, Crohn’s disease, rheumatoid arthritis, tuberculosis (Swiss Med Wkly 2012 May 31;142:w13580)
● Main amyloid component is protein A, derived from proteolytic cleavage of serum amyloid A protein, an acute phase reactant
● 90% have renal insufficiency or nephrotic syndrome at diagnosis
● Renal function is associated with amount of amyloid deposition (Rheumatol Int 2011 Sep 27 [Epub ahead of print])>
● Treatment: treat the underlying inflammatory condition

Beta 2 microglobulin type:
● Associated with long-term hemodialysis or peritoneal dialysis; also renal failure between treatments; increases with duration of dialysis
● Amyloid protein composed of intact and modified beta 2 microglobulin, an integral part of HLA class I antigen complex, that is usually eliminated by the kidney
● Amyloid deposits occur in blood vessel walls, perineural and periarterial tissue, bone, joint, skin, subcutaneous tissue, heart, GI and lungs
● May cause carpal tunnel syndrome, joint disease and bone cysts

ATTR type:
● Amyloid fibrils consist of transthyretin (Clin J Am Soc Nephrol 2012;7:1337)
● Associated with familial amyloidosis

Familial Mediterranean fever:
● Autosomal recessive, deposits consist of AA amyloid (Yonsei Med J 2012;53:454)

AH type:
● Due to heavy chains
● Very rare (predominantly lambda)

Case reports
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● 57 year old man with amyloid fibrils 3x usual size (Hum Pathol 1990;21:868)
● 59 year old man with IgM heavy chain amyloidosis (Am J Surg Pathol 2003;27:541)
● Patient developing lambda light chain deposition disease (treated with autologous peripheral blood stem cell transplant) and later IgG heavy chain amyloidosis (Am J Surg Pathol 2003;27:1477)
● Bilateral buttock tumors of beta 2 microglobulin after long term hemodialysis (Arch Pathol Lab Med 1994;118:651)
● AA-amyloid like deposits but fibrils twice the usual size (Arch Pathol Lab Med 1992;116:261)

Gross images
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Pale amyloid deposits in enlarged kidney

Micro description
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● Salmon orange amorphous, fluffy, extracellular deposits in mesangium and subendothelium that obliterate glomeruli
● Also deposits in blood vessel walls, interstitium and around tubules
● Also mast cells that lead to interstitial fibrosis in AA type (Mod Pathol 2000;13:1020 (mast cells and interstitial fibrosis))
● Proposed histopathologic classification system: Arch Pathol Lab Med 2010;134:532
● 10% of AL patients lack glomerular deposits
● Glomerular cell proliferations are uncommon

Micro images
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Various images


Patient with Amyloid AA due to hidradenitis suppurativa (H&E, PAS, Congo Red)

Patient with familial Mediterranean fever


Congo Red and amyloid immunostains

Interstitial mast cells accumulate around amyloid deposits

Virtual slides
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Amyloidosis

Positive stains
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● Congo Red: causes apple-green birefringence on polarization microscopy; staining lost in AA amyloidosis if pretreated with potassium permanganate
● Silver stain: may show spiking along glomerular capillary loops
● PAS: weak staining
● Thioflavine T: fluoresces; may be positive for anti-AA antibodies, light chain restriction

Electron microscopy description
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● 7.5-10 nm in diameter fibrils with randomly dispersed, non-branching arrangement in mesangium and subendothelium

Electron microscopy images
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10 nm haphazard fibrils

Mast cell (MC) within extracellular matrix of renal interstitial containing collagen fibers (C) and amyloid fibrils (A); inset-mast cells stained with anti-chymase

Differential diagnosis
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● Fibrillary glomerulonephritis: fibrils are 15-30 nm, negative amyloid stains
● Diabetic glomerulosclerosis: no deposits, intense silver staining
● Immunotactoid glomerulonephritis: microtubules, 20–50nm

End of Kidney non-tumor > Associated with systemic conditions > Amyloidosis

Ref Updated: 7/17/12

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