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  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 pathogenetically different 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 • nonimmunoglobulin protein - AA (amyloid associated) - in chronic inflammations
  6. Classification of amyloidosis • SYSTEMIC - kidneys, liver, spleen, adrenals, lymph nodes • LOCALIZED - various organs
  7. 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 osteolytic lesions 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
  8. 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)
  9. 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)
  10. Staining of amyloid Gross reactions  Virchow I. - staining by Lugol's sol.  Virchow II. - reaction with H2SO4 Microscopy  Hematoxylin and Eosin (HE) staining results in amorphous eosinophilic appearance when viewed on light microscopy.  metachromasia (cresyl violet, gentian violet)  Congo red - green birefringence  monoclonal antibodies against different types of amyloid - more precise classification
  11. Congo red staining of a cardiac biopsy specimen containing amyloid, viewed under polarized light
  12. Involvement of organs Kidneys  most common, most serious  glomeruli, vessels, peritubular stroma  nephrotic syndrome Spleen  two types - follicular (sago) and diffuse (lardaceous) spleen
  13. 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
  14. Amorphous eosinophilic interstitial amyloid observed on renal biopsy
  16. Liver amyloid
  17. 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
  18. SUMMARY  Can affect any organ system , classify  Hematoxylin and Eosin (HE) and Congo stain only tells you these are amyloid fibrils  Need to immunostain to determine subtype
  19. References • Harsh Mohan . Textbook of Pathology, 6th Ed. 2010 • Robbins and Cotran. Pathologic Basis of Disease