40. AMYLOIDOSIS.ppt

amyloidosis

1. AMYLOIDOSIS
Dept of Pathology
JNMC

2. Learning Objective
•At the end of the lecture the learner should be
able to:-
1.Define and classify amyloidosis
2.Describe the physical and chemical nature of
amyloidosis
3. Describe the etiopathogenesis and morphology of
amyloidosis

3. Amyloidosis
•amylum = starch; amyloid = starchlike
•abnormal proteinaceous substance deposited
between cells in many tissues and organs
•intercellular pink translucent material
•variety of clinical disorders

4. •A. = not a single chemical entity
•two major and several minor biochemical forms
•several pathogeneticallydifferent mechanisms
•unique tertiary structure -ß-pleated sheet
conformation
•responsible for staining properties and for
resistance to enzymes

5. Chemical nature of amyloid
•two types-
•immunoglobulin light chains -AL (amyloid
light chain)-in B-cell disorders
•nonimmunoglobulinprotein -AA (amyloid
associated)-in chronic inflammations

6. Classification of amyloidosis
•SYSTEMIC-kidneys, liver, spleen, adrenals,
lymph nodes
•LOCALIZED-various organs

9. Systemic amyloidosis
1.PRIMARY -IMMUNOCYTE DYSCRASIAS
deposition of AL-A., produced by aberrant clones of B-
cells -most frequent form. in multiple myeloma
monoclonal proliferation (neoplasm) of plasma cells -
monoclonal gammopathy
multiple osteolyticlesions of the bones
in addition to monoclonal Ig-production of isolated
kappa or lambda light chain (Bence-Jones protein)
only 6-15% of patients with MM develop amyloidosis

10. 2. SECONDARY AMYLOIDOSIS
•reactive AA amyloid-protracted breakdown of
cells, usually in chronic inflammatory disorders
•TBC, osteomyelitis, bronchiectasis
•RA, connective tissue disorders, ulcerative
colitis, tumors (Hodgkin's ML)

11. Localized amyloidosis
•heterogenous group
•nodular deposits -lungs, larynx, skin, urinary
bladder, tongue -infiltration of B-cells -probably
well differentiated plasmacytoma
•special forms:
•AE -endocrine tumors (medullary ca of thyroid)
•AS -senile amyloid (brain, heart)

12. Staining of amyloid
Gross reactions
Virchow I. -staining by Lugol'ssol.
Virchow II. -reaction with H
2
SO
4
Microscopy
Hematoxylinand Eosin (HE) staining results in amorphous
eosinophilicappearancewhen viewed on light
microscopy.
metachromasia(cresylviolet, gentian violet)
Congo red -green birefringence
monoclonal antibodies against different types of amyloid-
more precise classification

13. Congo red staining of a cardiac biopsy specimen
containing amyloid, viewed under polarized light

14. Involvement of organs
Kidneys
most common, most serious
glomeruli, vessels, peritubularstroma
nephroticsyndrome
Spleen
two types -follicular (sago) and diffuse (lardaceous) spleen

15. Liver
weight up to 9kg!
space of Disse-atrophy of hepatocytes
Heart
AS-amyloid-left atrium (ANF granules)
AA -in systemic involvement -firm, wax-like

16. Amorphous eosinophilic interstitial amyloid
observed on renal biopsy

17. CARDIAC AMYLOID

18. Liver amyloid

19. Clinical symptomatology
•incidental finding at autopsy
•severe clinical symptoms -renal malfunctions,
hepatosplenomegaly, heart involvement
•Dx.: needle biopsy of lesion; in systemic -
biopsy of rectal or oral mucosa

20. SUMMARY
Can affect any organ system , classify
Hematoxylinand Eosin (HE) and Congo stain only
tells you these are amyloidfibrils
Need to immunostainto determine subtype

21. References
•Harsh Mohan . Textbook of Pathology, 6
th
Ed.
2010
•Robbins and Cotran. Pathologic Basis of
Disease

22. THANK YOU