Department of Pathology, University of Oklahoma Health Sciences Center

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Answer: (A) The followings are true-

• Can be demonstrated by immunohistochemistry for P-component.

• Usually associated with relative preservation of large myelinated axons.

• The salient ultrastructural feature is straight, unbranched fibrils that are 7-10 nm in width.

Discussion: 

• Diagnosis: Amyloid polyneuropathy.

• Pathology of the case: The semithin section is stained by osmium tetraoxide to highlight the myelinated fibers and counterstained by toulidine blue. There is severe lost of myelinated fibers (Þ). An irregular island of amorphous material (Þ). This type of deposition is suggestive of amyloid deposition until proved otherwise. Although there are severe loss of axons, the large and myelinated fibers are relatively preserved; this is a property of amyloid neuropathy. 

• P-component: For investigating purpose, a Congo red stain should be performed. Immunohistochemical detection of amyloid could be facilitated by antisera against lambda and kappa light chain,  transthyretin, and also P-component which is a protein that is almost always associated with amyloid deposition. These special features are useful to distinguish amyloid from immunoglobulin deposition disease (IDD). Congo red and other stains are negative in IDD. This distinction is important since IDD may response to treatment. The P-component also helps to distinguish geniue amyloid deposition from non-specific immunoglobulin depositions.

• Straight filaments: Electron microscopy is also useful because of the unique morphologic features of amyloid. Amyloid occurs as straight, unbranched fibrils that are 7-10 nm in width. [Click here to see electron micrograph of amyloid in this case]

• Paired helical filaments: They are found in neuofibrillary tangles in neurodegenerative diseases such as Alzheimer's disease.

• Amyloid polyneuropathy: The term amyloid was first coined by Vichow to reflect the morphologic and staining characteristics that are suggestive of starch or cellulose material. When amyloid is stained with Congo red, it gives a orange-red color on bright field microscopy and a apple-green birefrigence under polarized light; the later feature is best appreciated with torsion free objectives. Under electron microscopy, amyloid fibris appear as straight, unbranched fibrils that are 7-10 nm in width. Amyloidosis falls into a category of diseases featured by conformational change in protein structure. Molecules that are involved in this category involves immunoglobulin light chains, serum amyloid protien A, b₂-microglobulin, apoprotein A1, cystatin C, lysosome, prion proteins and transthyretin. Abnormal conformational changes of these molecules give rise to amyloid deposition in different organs. There are at least three varieties of hereditary amyloid neuropathy and they are all uncommon. Amyloid peripheral neuropathy associated with transthyretin is the most common, amyloid peripheral neuropathy associated with gelsolin and Apo A1 are far less common. [Click here to see a case of amyloid neuropathy]

Comment: KarMing-Fung@ouhsc.edu