Page 103 - Textbook of Pathology, 6th Edition

the vessel walls at the synovium, joints, tendon sheaths and 3. Endocrine amyloidosis (Hormone precursors). Some 87
subchondral bones. However, systemic distribution has also endocrine lesions are associated with microscopic deposits
been observed in these cases showing bulky visceral deposits of amyloid. The examples are as follows:
of amyloid. i) Medullary carcinoma of the thyroid (from procalcitonin
i.e. ACal).
4. Heredofamilial Amyloidosis ii) Islet cell tumour of the pancreas (from islet amyloid CHAPTER 4
A few rare examples of genetically-determined amyloidosis polypeptide i.e. AIAPP or Amylin).
having familial occurrence and seen in certain geographic iii) Type 2 diabetes mellitus (from pro-insulin, i.e. AIns).
regions have been described. These are as under: iv) Pituitary amyloid (from prolactin i.e. APro).
i) Hereditary polyneuropathic (ATTR) amyloidosis. This v) Isolated atrial amyloid deposits (from atrial natriuretic
is an autosomal dominant disorder in which amyloid is factor i.e. AANF).
deposited in the peripheral and autonomic nerves resulting vi) Familial corneal amyloidosis (from lactoferrin i.e. ALac).
in muscular weakness, pain and paraesthesia, or may have
cardiomyopathy. This type of amyloid is derived from 4. Localised tumour forming amyloid (AL). Sometimes,
transthyretin (ATTR) with single amino acid substitution in isolated tumour like formation of amyloid deposits are seen
the structure of TTR; about 60 types of such mutations have e.g. in lungs, larynx, skin, urinary bladder, tongue, eye,
been described. Though hereditary, the condition appears isolated atrial amyloid. In most of these cases, the amyloid
well past middle life. type is AL.
ii) Amyloid in familial Mediterranean fever (AA). This is STAINING CHARACTERISTICS OF AMYLOID
an autosomal recessive disease and is seen in the Immunopathology Including Amyloidosis
Mediterranean region (i.e. people residing in the countries 1. STAIN ON GROSS. The oldest method since the time of
surrounding the Mediterranean sea e.g. Sephardic Jews, Virchow for demonstrating amyloid on cut surface of a gross
Armenians, Arabs and Turks). The condition is characterised specimen, or on the frozen/paraffin section is iodine stain.
by periodic attacks of fever and polyserositis i.e. Lugol’s iodine imparts mahogany brown colour to the amyloid-
inflammatory involvement of the pleura, peritoneum, and containing area which on addition of dilute sulfuric acid turns
synovium causing pain in the chest, abdomen and joints blue. This starch-like property of amyloid is due to AP
respectively. Amyloidosis occurring in these cases is AA component, a glycoprotein, present in all forms of amyloid.
type, suggesting relationship to secondary amyloidosis due Various stains and techniques employed to distinguish
to chronic inflammation. The distribution of this form of and confirm amyloid deposits in sections are as given in
heredofamilial amyloidosis is similar to that of secondary Table 4.12.
amyloidosis. 2. H & E. Amyloid by light microscopy with haematoxylin
iii) Rare hereditary forms. Heredofamilial mutations of and eosin staining appears as extracellular, homogeneous,
several normal proteins have been reported e.g. apolipo- structureless and eosinophilic hyaline material, especially in
protein I (AApoAI), gelsolin (AGel), lysozyme (ALys), relation to blood vessels. However, if the deposits are small,
fibrinogen α-chain (AFib), cystatin C (ACys) and amyloid of they are difficult to detect by routine H and E stains. Besides,
familial dementia etc. These types may also result in systemic a few other hyaline deposits may also take pink colour (page
amyloidosis. 35).
3. METACHROMATIC STAINS (ROSANILINE DYES).
B. LOCALISED AMYLOIDOSIS
Amyloid has the property of metachromasia i.e. the dye
1. Senile cardiac amyloidosis (ATTR). Senile cardiac amy- reacts with amyloid and undergoes a colour change.
loidosis is seen in 50% of people above the age of 70 years.
The deposits are seen in the heart and aorta. The type of
amyloid in these cases is ATTR but without any change in  TABLE 4.12: Staining Characteristics of Amyloid.
the protein structure of TTR. Stain Appearance
2. Senile cerebral amyloidosis (Aβ β ββ β, APrP). Senile cerebral 1. H & E Pink, hyaline, homogeneous
amyloidosis is heterogeneous group of amyloid deposition 2. Methyl violet/Crystal violet Metachromasia: rose-pink
of varying etiologies that includes sporadic, familial, 3. Congo red Light microscopy: pink-red
hereditary and infectious. Some of the important diseases Polarising light: red-green
associated with cerebral amyloidosis and the corresponding birefringence
amyloid proteins are: Alzheimer’s disease (Aβ), Down’s 4. Thioflavin-T/Thioflavin-S Ultraviolet light: fluorescence
syndrome (Aβ) and transmissible spongiform encephalo- 5. Immunohistochemistry Immunoreactivity: Positive
pathies (APrP) such as in Creutzfeldt-Jakob disease, fatal (antibody against fibril protein)
familial insomnia, mad cow disease, kuru. 6. Non-specific stains:
In Alzheimer’s disease, deposit of amyloid is seen as i) Standard toluidine blue Orthochromatic blue,
Congophilic angiopathy (amyloid material in the walls of polarising ME dark red
cerebral blood vessels), neurofibrillary tangles and in senile ii) Alcian blue Blue-green
plaques. iii) PAS Pink