Amyloidosis is a condition associated with a number of inherited and inflammatory disorders in which extracellular deposits of fibrillar proteins are responsible for tissue damange and functional compromise. (Robbins Basic Pathology, 9th Edition) The following slideshow deals with the classification of Amyloidosis:

1. CLASSIFICATION OF AMYLOIDOSIS
ABHINEET DEY
Department of Pathology
Gauhati Medical College & Hospital

2. According to a combined biochemical-clinical classification,
Amyloid may be
 Systemic (generalized), involving several organ systems,
 Localized, when deposits are limited to a single organ, such
heart.
As should become evident, several different biochemical forms
of amyloid are encompassed by such segregation.

3. Clinicopathologic Category Associated Diseases Major Fibril Protein
Chemically Related Precursor
Protein
Systemic (Generalized) Amyloidosis
Immunocyte dyscrasias with
amyloidosis (primary
amyloidosis)
Multiple myeloma and other
monoclonal B-cell proliferations AL
Immunoglobulin light chains,
chiefly λ type
Reactive systemic amyloidosis
(secondary amyloidosis)
Chronic inflammatory conditions
AA SAA
Hemodialysis-associated
amyloidosis Chronic renal failure Aβ2m β2-microglobulin
Hereditary amyloidosis
Familial Mediterranean fever AA SAA
Familial amyloidotic
neuropathies (several types) ATTR Transthyretin
Systemic senile amyloidosis ATTR Transthyretin
Localized Amyloidosis
Senile cerebral Alzheimer disease Aβ APP
Endocrine
Medullary carcinoma of
thyroid — A Cal Calcitonin
Islet of Langerhans Type II diabetes AIAPP Islet amyloid peptide
Isolated atrial amyloidosis — AANF Atrial natriuretic factor
Prion diseases Various prion diseases of the
CNS
Misfolded prion protein (PrPSC) Normal prion protein PrP

4. SYSTEMIC (GENERALISED)
On clinical grounds, the systemic, or generalized, pattern is
again sub classified into some groups. These are as follows:

5. PRIMARY AMYLOIDOSIS
 Plasma Cell Disorder associated with Amyloidosis.
 Amyloid in this category is usually systemic in distribution and is of
the AL type. This is the most common form of amyloidosis.
 This disorder is caused by clonal proliferation of plasma cells that
synthesise Ig.
 About 30% cases of AL Amyloid have some form of plasma cell
dyscrasias, most commonly multiple myeloma.
 The remaining 70% cases do not have evident B Cell proliferative
disorder.

6. REACTIVE SYSTEMIC AMYLOIDOSIS
SECONDARY AMYLOIDOSIS
 The fibril protein contains AA Amyloids.
 It occurs typically as a complication chronic infection, non
infectious chronic inflammatory conditions.

7. HEREDOFAMILIAL AMYLOIDOSIS
 This constitutes a separate, albeit heterogeneous group, with
several distinctive patterns of organ involvement.
 Most of them are rare and occur in limited geographical
area.
 These are as under:
1. Hereditary Poly-Neuropathy Amyloidosis
2. Amyloid in Familial Mediterranean Fever
3. Rare Hereditary Form

8. LOCALISED AMYLOIDOSIS
 Amyloid deposition are limited to a single organ or tissue
without involvement of any other site in the body.
 The deposits may produce detectable nodular masses, most
often encounter in lung, larynx, skin, tongue and urinary
bladder.

9. LOCALISED AMYLOIDOSIS may be described
under the following headings:
1. Endocrine Amyloidosis
Microscopic deposits may be found in certain endocrine tumours
such as:
• Medullary Carcinoma of the thyroid gland
• Islet Tumour of the pancreas
• Undifferentiated Carcinoma of the stomach.
2. Senile Cardiac Amyloidosis
3. Senile Cerebral Amyloidosis
4. Localised Tumour forming Amyloid

10. Morphological features of
amyloidosis of organs

11. AMYLOIDOSIS OF KIDNEY
 It is most common and most serious because of its ill effect
on renal functions.
 The deposits in the kidney are found in most cases of
secondary amyloidosis and in about one third of cases of
primary amyloidosis.

12. AMYLOIDOSIS OF KIDNEY (contd.)
GROSSLY
 The kidney may be of normal size and colour.
 In advanced cases they may be shrunken because of
ischemia caused by vascular narrowing induced by
deposition of amyloid.
HISTOLOGICALLY
 The amyloid is deposited primarily in the glomeruli but the
interstitial peritubular tissues, arteries and arterioles are also
affected.
 The glomerular architecture is almost totally obliterated by
the massive accumulation of amyloid.

13. AMYLOIDOSIS OF KIDNEY (contd.)
The glomerular architecture is almost totally
obliterated by the massive accumulation of amyloid.

14. AMYLOIDOSIS OF SPLEEN
 Amyloidosis of Spleen may be not apparent grossly or may
cause moderate to marked splenomegaly.
 Amyloid deposition in the spleen may have on of the
following two pattern:
1. Sago Spleen: The deposits are largely limited to splenic follicle
producing tapioca-like granules.
2. Lardaceous Spleen: Amyloid involves the wall of splenic sinuses
and connective tissue in red pulp. Fusion of the early deposits
gives rise to large, map like areas of amyloidosis.

15. AMYLOIDOSIS OF SPLEEN (Contd.)
Spleen showing amyloid deposition in blood
vessels.

16. AMYLOIDOSIS OF LIVER
GROSSLY
 The liver is often enlarged, pale, waxy and firm.
HISTOLOGICALLY
 The amyloid initially appears in the Space of Disse.
 Later as the deposit increases, they compress the chords of
hepatocytes.

17. PROGNOSIS
 The prognosis of patient with generalised amyloidosis is
generally poor.
 Primary amyloidosis, if left untreated, is rapidly progressive
and fatal.
 For secondary amyloidosis, control of inflammation is the
main step of treatment.

18. THANK YOU
d!