5 immunology-csbrp
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5 immunology-csbrp
- 2. Gist - AMYLOID • It’s only a manifestation of different diseases • it’s an abnormal protein • It’s deposited Extracellularly • It’s bland and Non-reactive • Enzyme resistant • Affects all tissues • It causes organ failure by pressure atrophy APR-2015-CSBRP
- 3. Gist - AMYLOID Two processes are associated with such deposition • Prolonged inflammation • Excessive immunoglobulin synthesis APR-2015-CSBRP
- 4. Amyloid Amyloid is a pathologic proteinaceous substance, deposited between cells in various tissues and organs of the body in a wide variety of clinical settings. APR-2015-CSBRP
- 5. AmyloidAmyloid With the light microscope and standard tissue stains, amyloid appears as • An amorphous, eosinophilic, hyaline like, extracellular substance APR-2015-CSBRP
- 6. DD Hyaline & Amyloid FeatureFeature HyalineHyaline AmyloidAmyloid Location Both extra & intracellular Extracellular Nature Protein / others Protein Inflammation Inflammatory reaction No inflammation Etiology Variety of agents Immunological H&E Eosinophilic Eosinophilic Congo red Negative Positive CR+Polarizer No change Apple green EM variety of morphology Nonbranching fibrils APR-2015-CSBRP
- 7. Amyloid • Is not a single protein • Chemically different proteins with identical staining properties APR-2015-CSBRP
- 8. Amyloid – Physical nature By electron microscopy:By electron microscopy: (It’s common to all amyloid proteins(It’s common to all amyloid proteins)) • Non-branching fibrils • Diameter of 7.5-10 nm • cross-β-pleated sheet conformation This β-pleated nature is responsible for its special staining character APR-2015-CSBRP
- 9. Amyloid – Physical nature APR-2015-CSBRP
- 10. The Nature of Amyloid Ultrastructure Structure of an amyloid fibril APR-2015-CSBRP
- 11. Amyloid – Chemical nature Mainly composed of: 1. Fibrillary protein - 95% 2. P-component - 5% 3. Glycoprotein - a fraction APR-2015-CSBRP
- 12. gist - The Nature of Amyloid • Physical Nature: • Electron microscopy: Amyloid material contains two components. (1) Rigid nonbranching fibrils* (7.5 to 10 nm): Constitute the major component (about 90%) (2) Pentagonal rod shaped sub-unit (P components): Forms 10% of amyloid tissue and is a glycoprotein (variable PAS positive staining). • X-ray diffraction analysis: Characteristic β-pleated configuration* in both major subtypes of amyloid. • Chemical nature: • Peptide mapping analysis of the sequence of amino acids: Of the 15 biochemically distinct forms identified, 3 are major chemical types of amyloid: (1) Amyloid of light chain origin (AL) from plasma cells, (2) Unique nonimmunoglobulin protein synthesized in the liver (AA), (3) Aβ amyloid in cerebral lesion of Alzheimer disease APR-2015-CSBRP
- 13. Classification Amyloid may be:Amyloid may be: Systemic (generalized), involving several organ systems, or Localized, when deposits are limited to a single organ, such as the Heart, Skin et.c. APR-2015-CSBRP
- 14. Localized Amyloid Deposits Endocrine associated: • Amyloid deposits in the stroma of medullary thyroid carcinoma, a C- cell tumor; amyloid is derived from a polypeptide hormone calcitonin. • Amyloid deposits in the stroma of islet cell tumors, particularly those producing insulin (amyloid is produced by proteolysis of insulin or its prohormone). Senile amyloidosis: • Deposits are common in the aged (seventies and eighties); found in heart (atria affected more frequently than ventricles) and brain (as senile plaques). • The plaques found in Alzheimers disease is derived from β-amyloid protein (Aβ), derived from a glycoprotein called amyloid precursor protein (APP). Other localized deposits: Microscopic deposits to nodular masses in sites such as lung, larynx, skin, bladder, and tongue. Consist of AL protein in most cases. APR-2015-CSBRP
- 15. 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 Aβ2 m 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 APR-2015-CSBRP
- 16. Classification of Systemic AmyloidosisClassification of Systemic Amyloidosis on clinical groundson clinical grounds • Primary amyloidosis, when associated with some immunocyte dyscrasia, or • Secondary amyloidosis, when it occurs as a complication of an underlying chronic inflammatory or tissue destructive process. • Hereditary or familial amyloidosis constitutes a separate, albeit heterogeneous group, with several distinctive patterns of organ involvement. • Hemodialysis associated Amyloidosis • Localized amyloidosis - (A). Endocrine associated, (B). Senile, and (C). Others APR-2015-CSBRP
- 17. Immunocyte Dyscrasias with Amyloidosis (Primary Amyloidosis) • Most common form of amyloidosis • many of these patients have some form of plasma cell dyscrasia / B-cell dyscrasia • Amyloid has AL composition APR-2015-CSBRP
- 18. Reactive Systemic Amyloidosis • Secondary to an inflammatory condition • Protracted breakdown of cells • Composed of AA protein Chronic osteomyelitis Rheumatoid arthritis Bronchiectasis Connective tissue disease Tuberculosis RCC Leprosy Hodgkin’s disease APR-2015-CSBRP
- 19. Patients on long-term hemodialysis for renal failure High β2-microglobulin in the serum Amyloid deposits in the synovium, joints, and tendon sheaths Hemodialysis-Associated Amyloidosis APR-2015-CSBRP
- 20. • Many familial forms of amyloidosis • Confined to limited geographic areas • The most common is familial Mediterranean fever • Others - familial amyloidotic polyneuropathies Heredofamilial Amyloidosis APR-2015-CSBRP
- 21. Microscopic localized deposits of amyloid in endocrine tumors, Eg: Medullary carcinoma of the thyroid gland, Islet tumors of the pancreas Pheochromocytomas and Undifferentiated carcinomas of the stomach Amyloid derived from hormones or unique proteins Endocrine Amyloid APR-2015-CSBRP
- 22. Several well-documented forms of amyloid deposition occur with aging Senile systemic amyloidosis - systemic deposition of amyloid in elderly patients called senile cardiac amyloidosis Amyloid of Aging APR-2015-CSBRP
- 23. Amyloid – Chemical nature Fibrillary component: 15 bio-chemically distinct forms have been identified Three are most common: (1) AL (amyloid light chain) immunoglobulin light chains (2) AA (amyloid-associated) nonimmunoglobulin protein synthesized by the liver and (3) Aβ amyloid is found in Alzheimer disease APR-2015-CSBRP
- 24. Proposed Scheme of Pathogenesis of Two Major Forms of Amyloid Fibrils APR-2015-CSBRP
- 25. Pathogenesis of Amyloidosis • Amyloid fibrils (AL protein or AA protein) formed in vivo from a variety of polypeptide fragments, derived either from immunoglobulin of plasma cell origin or from other protein (SAA) of hepatocytic origin. • Amyloidogenic proteins (Immunoglobulin light chains or SAA) present in the blood is deposited in various sites following limited proteolysis by the action of monocyte-derived enzymes. • Thus, mononuclear phagocyte system may play a role by taking up immunoglobulins, Ag-Ab complexes, or other proteins and produce necessary polypeptides for formation of amyloid fibrils. APR-2015-CSBRP
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- 28. The “Beta-Sheet”, rigid folding pattern APR-2015-CSBRP
- 30. Specific Organ Involvement in Amyloid Disease • Kidney • Liver • Spleen • Heart • Lymph nodes • Adrenal • Thyroid • Pituitary • Gastrointestinal tract • Respiratory tract APR-2015-CSBRP
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- 34. Bilateral periorbital ecchymosis (raccoon eyes) and mild proptosis. Another example of "raccoon eyes" which is a clinical sign of a base of skull fracture. APR-2015-CSBRP
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- 36. Kidney in Amyloidosis Gross: The organ is usually enlarged and pale but a small scarred kidney results in long standing cases due to secondary ischemic changes. Micro: Amyloid is deposited primarily in the glomeruli. Mesengial deposition and the deposits along basement membrane cause capillary narrowing and distortion of glomerular tuft. The arterioles, and interstitial tissue between the tubules are also affected. APR-2015-CSBRP
- 37. Kidney in Amyloidosis Clinical impact: Renal involvement in amyloidosis is most common and result is nephrotic syndrome, often as the presenting feature. It is the most serious manifestation and major cause of death. APR-2015-CSBRP
- 38. Renal biopsy in AL amyloidosis Staining with anti-K light chain Abs APR-2015-CSBRP
- 39. Renal biopsy in secondary AA amyloidosis Glomerulus is strongly positive for AA protein APR-2015-CSBRP
- 40. Liver in Amyloidosis Gross: Liver is enlarged, heavy, pale, and firm. Micro: Amyloid is deposited in the space of Disse between the endothelium and the liver cells, and progressively encroaches on adjacent hepatocytes and sinusoids. The liver cells undergo atrophy. Vascular involvement and Kupffer cell depositions are frequent. Clinical impact: Liver function is preserved in the presence of marked involvement. APR-2015-CSBRP
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- 43. Spleen in Amyloidosis Gross: Spleen is enlarged and firm. Focal distribution is common. The cut surface shows numerous translucent nodules distributed throughout the red pulp (characteristic appearance, called ‘sago spleen’). A diffuse type is also recognized. Micro: In localized type amyloid is laid down in the walls of the arterioles in the white pulp and subsequently replaces the malpighian bodies. In diffuse type, amyloid is laid down in the walls of the sinuses and tends to spare the follicles. Fusion of early deposits lead to large map-like areas of amyloidosis (lardaceous spleen).APR-2015-CSBRP
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- 48. Lardaceous spleen • fat from the abdomen of a pig, especially as prepared for use in cooking APR-2015-CSBRP
- 49. Lardaceous spleen • fat from the abdomen of a pig, especially as prepared for use in cooking APR-2015-CSBRP
- 50. Heart in Amyloidosis Cardiac involvement is the major manifestation of primary amyloidosis. It occurs in multiple myeloma and usually in elderly people. Gross: Heart is enlarged, rigid, and firm. Micro: Begin with focal subendocardial deposition. In due course widespread deposition of amyloid in the walls of blood vessels and in the interstitial tissue surrounding and replacing muscle fibers. Clinical impact: Cardiomegaly with intractable heart failure. Heart block and arrhythmia due to involvement of conduction system are common. Condition mimicking constrictive pericarditis due to rigidity of the muscle. APR-2015-CSBRP
- 52. Congo Red Staining of Liver in Amyloidosis APR-2015-CSBRP
- 54. Immunocyte-derived Systemic Amyloidosis • Found in with 5 to 15% multiple myeloma patients and in patients with B-cell dyscrasias (monoclonal B-cell proliferations). • Amyloid is systemic indistribution (AL type) and derived from Ig light chains (chiefly λ type). • An excess of corresponding light chain is usually present in the blood and secreted in urine as Bence-Jones protein Organ involvement and its effect: • Kidney involvement is a major feature and usual cause of death. • Myocardium : refractory heart failure. • Tongue: enlargement interferes with speech. • Esophagus: dysphagia. • Intestine: lesions lead to obstruction, bleeding, and perforation. • Skin: deposits cause purpura. • Nerve: peripheral neuropathy. • The liver, spleen, lungs, and endocrine organs are affected less frequently. APR-2015-CSBRP
- 56. Diagnosis of Amyloid Disease in Life • Amyloid may be demonstrated in biopsy material obtained from liver, spleen, kidney, intestine, and bone marrow. Most common site of biopsy is kidney, when renal manfestations are present. • Tissue involved by amyloidosis has a tendency to bleed when subjected to trauma. Biopsy of gingiva and rectal mucosa has advantage over other sites in that, and should hemorrhage occur, it can readily be controlled. • Fine needle aspiration biopsy of the abdominal fat is also an easily followed and extemely useful procedure for detection of systemic amyloidosis. • Appearance in routine stains: With light microscope and standard tissue stains, amyloid appears as an amorphous, eosinophilic, hyaline, extracellular substance. • Appearance by special stain (Congo red): Amyloid stains an orange red color under ordinary light but when the stained slide is viewed in a polarizing microscope, a characteristic green birefringence is imparted. • Other investigations: In immunocyte-associated amyloidosis, serum and urine protein electrophoresis, and immunoelectrophoresis. Bone marrow aspiration for plasmacytosis. APR-2015-CSBRP
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- 61. Amyloid - Apple green birefringence under polarized light APR-2015-CSBRP
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- 63. Demonstration of Amyloid Stain Result Technique Lugol’s Iodine Mahagany brown – Blue On Fresh tissue Methyl violet Pink to Red Metachromasia Thiflavine-T Bright red fluorescence Fluorescent technique Thioflavine-S Bright red fluorescence Fluorescent technique Alcian blue Green Chemical Silver impregnantion Black Impregnation Congo red Red Beta-pleated nature CR + Polarization Apple green birefringens Polarization Sirius red Green Polarization APR-2015-CSBRP
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Notas del editor
- Figure 6-53 Structure of an amyloid fibril, depicting the β-pleated sheet structure and binding sites for the Congo red dye, which is used for diagnosis of amyloidosis. (Modified from Glenner GG: Amyloid deposit and amyloidosis. The β-fibrilloses. N Engl J Med 52:148, 1980. By permission of The New England Journal of Medicine.)
- Figure 6-53 Structure of an amyloid fibril, depicting the β-pleated sheet structure and binding sites for the Congo red dye, which is used for diagnosis of amyloidosis. (Modified from Glenner GG: Amyloid deposit and amyloidosis. The β-fibrilloses. N Engl J Med 52:148, 1980. By permission of The New England Journal of Medicine.)
- *responsible for unique staining and biological properties (e. g., orange red staining under ordinary light and apple green birefringence while examined under polarized light after Congo red staining).
- On clinical grounds, the systemic, or generalized, pattern is subclassified into primary amyloidosis, when associated with some immunocyte dyscrasia, or secondary amyloidosis, when it occurs as a complication of an underlying chronic inflammatory or tissue destructive process. Hereditary or familial amyloidosis constitutes a separate, albeit heterogeneous group, with several distinctive patterns of organ involvement. Immunocyte Dyscrasias with Amyloidosis (Primary Amyloidosis). Hemodialysis associated Amyloidosis Localized amyloidosis - (A). Endocrine associated, (B). Senile, and (C). Others
- Immunocyte Dyscrasias with Amyloidosis (Primary Amyloidosis). Amyloid in this category is usually systemic in distribution and is of the AL type. With approximately 1275 to 3200 new cases every year in the United States, this is the most common form of amyloidosis. In many of these cases, the patients have some form of plasma cell dyscrasia. Best defined is the occurrence of systemic amyloidosis in 5% to 15% of patients with multiple myeloma, a plasma-cell tumor characterized by multiple osteolytic lesions throughout the skeletal system ( Chapter 14 ). The malignant B cells characteristically synthesize abnormal amounts of a single specific immunoglobulin (monoclonal gammopathy), producing an M (myeloma) protein spike on serum electrophoresis. In addition to the synthesis of whole immunoglobulin molecules, only the light chains (referred to as Bence Jones protein) of either the λ or the κ variety may be elaborated and found in the serum. By virtue of the small molecular size of the Bence Jones protein, it is frequently excreted in the urine. The amyloid deposits contain the same light chain protein. Almost all the patients with myeloma who develop amyloidosis have Bence Jones proteins in the serum or urine, or both, but a great majority of myeloma patients who have free light chains do not develop amyloidosis. Clearly, therefore, the presence of Bence Jones proteins, although necessary, is by itself not enough to produce amyloidosis. We discuss later the other factors, such as the type of light chain produced (amyloidogenic potential) and the subsequent handling (possibly degradation) that may have a bearing on whether Bence Jones proteins are deposited as amyloid. The great majority of patients with AL amyloid do not have classic multiple myeloma or any other overt B-cell neoplasm; such cases have been traditionally classified as primary amyloidosis because their clinical features derive from the effects of amyloid deposition without any other associated disease. In virtually all such cases, however, monoclonal immunoglobulins or free light chains, or both, can be found in the serum or urine. Most of these patients also have a modest increase in the number of plasma cells in the bone marrow, which presumably secrete the precursors of AL protein. Clearly, these patients have an underlying B-cell dyscrasia in which production of an abnormal protein, rather than production of tumor masses, is the predominant manifestation. Recent studies have revealed chromosomal translocations in many of these patients, suggesting the presence of neoplastic clones.[171] Whether most of these clones would evolve into myeloma if the patients lived long enough can only be a matter for speculation.
- Reactive Systemic Amyloidosis. The amyloid deposits in this pattern are systemic in distribution and are composed of AA protein. This category was previously referred to as secondary amyloidosis because it is secondary to an associated inflammatory condition. The feature common to most of the conditions associated with reactive systemic amyloidosis is protracted breakdown of cells resulting from a wide variety of infectious and noninfectious chronic inflammatory conditions. At one time, tuberculosis, bronchiectasis, and chronic osteomyelitis were the most important underlying conditions, but with the advent of effective antimicrobial chemotherapy, the importance of these conditions has diminished. More commonly now, reactive systemic amyloidosis complicates rheumatoid arthritis, other connective tissue disorders such as ankylosing spondylitis, and inflammatory bowel disease, particularly Crohn disease and ulcerative colitis. Among these, the most frequent associated condition is rheumatoid arthritis. Amyloidosis is reported to occur in approximately 3% of patients with rheumatoid arthritis and is clinically significant in one half of those affected. Heroine abusers who inject the drug subcutaneously also have a high occurrence rate of generalized AA amyloidosis. The chronic skin infections associated with "skin-popping" of narcotics seem to be responsible for amyloidosis in this group of patients. Reactive systemic amyloidosis may also occur in association with non-immunocyte-derived tumors, the two most common being renal cell carcinoma and Hodgkin disease.
- Hemodialysis-Associated Amyloidosis. Patients on long-term hemodialysis for renal failure develop amyloidosis owing to deposition of β2-microglobulin. This protein is present in high concentrations in the serum of patients with renal disease and is retained in circulation because it cannot be filtered through the cuprophane dialysis membranes. In some series, as many as 60% to 80% of the patients on long-term dialysis developed amyloid deposits in the synovium, joints, and tendon sheaths.
- Heredofamilial Amyloidosis. A variety of familial forms of amyloidosis have been described. Most of them are rare and occur in limited geographic areas. The most common and best studied is an autosomal recessive condition called familial Mediterranean fever.[172] This is a febrile disorder of unknown cause characterized by attacks of fever accompanied by inflammation of serosal surfaces, including peritoneum, pleura, and synovial membrane. This disorder is encountered largely in individuals of Armenian, Sephardic Jewish, and Arabic origins. It is associated with widespread tissue involvement indistinguishable from reactive systemic amyloidosis. The amyloid fibril proteins are made up of AA proteins, suggesting that this form of amyloidosis is related to the recurrent bouts of inflammation that characterize this disease. The gene for familial Mediterranean fever has been cloned, and its product is called pyrin (for its relation to fever). Although its exact function is not known, it has been suggested that pyrin is responsible for regulating acute inflammation, presumably by inhibiting the function of neutrophils.[173] The relationship of this mutation to the disease is not understood. In contrast to familial Mediterranean fever, a group of autosomal dominant familial disorders is characterized by deposition of amyloid predominantly in the nerves—peripheral and autonomic. These familial amyloidotic polyneuropathies have been described in different parts of the world. As mentioned previously, in all of these genetic disorders, the fibrils are made up of mutant transthyretins (ATTR).
- Endocrine Amyloid. Microscopic deposits of localized amyloid may be found in certain endocrine tumors, such as medullary carcinoma of the thyroid gland, islet tumors of the pancreas, pheochromocytomas, and undifferentiated carcinomas of the stomach, and in the islets of Langerhans in patients with type II diabetes mellitus. In these settings, the amyloidogenic proteins seem to be derived either from polypeptide hormones (e.g., medullary carcinoma) or from unique proteins (e.g., islet amyloid polypeptide).
- Amyloid of Aging. Several well-documented forms of amyloid deposition occur with aging.[174] Senile systemic amyloidosis refers to the systemic deposition of amyloid in elderly patients (usually in their seventies and eighties). Because of the dominant involvement and related dysfunction of the heart, this form was previously called senile cardiac amyloidosis. Those who are symptomatic present with a restrictive cardiomyopathy and arrhythmias. The amyloid in this form is composed of the normal TTR molecule. In addition to the sporadic senile systemic amyloidosis, another form, affecting predominantly the heart, that results from the deposition of a mutant form of TTR has also been recognized. Approximately 4% of the black population in the United States is a carrier of the mutant allele, and cardiomyopathy has been identified in both homozygous and heterozygous patients. The precise prevalance of patients with this mutation who develop clinically manifest cardiac disease is not known.
- Figure 6-53 Structure of an amyloid fibril, depicting the β-pleated sheet structure and binding sites for the Congo red dye, which is used for diagnosis of amyloidosis. (Modified from Glenner GG: Amyloid deposit and amyloidosis. The β-fibrilloses. N Engl J Med 52:148, 1980. By permission of The New England Journal of Medicine.)
- Direct dermal infiltration can produce subcutaneous nodules and plaques. Classically described as smooth, waxy, yellowish lesions, these are uncommon and more often appear hemorrhagic. They are generally found on flexor surfaces, the face, and the buccal mucosa (Fig. 2). Cutaneous nodules can be demonstrated to follow the path of blood vessels within the skin [2]. Direct skin infiltration with amyloid can produce the appearance of scleroderma on the face, hands, and feet. Rarely, infiltrative nodular lesions may coalesce to form gross distortion and enlargement or tumefaction
- Purpura, petechiae, and ecchymoses occur commonly in the skin and mucous membranes. They are due to intracutaneous hemorrhage, the result of amyloid infiltrating and weakening blood-vessel walls. These lesions may occur spontaneously and are particularly common in skin folds such as the eyelids, axillae, umbilicus, and anogenital area. Periorbital purpura may arise after coughing, sneezing, performing proctoscopy, or the valsalva maneuver --------------------------- Direct dermal infiltration can produce subcutaneous nodules and plaques. Classically described as smooth, waxy, yellowish lesions, these are uncommon and more often appear hemorrhagic. They are generally found on flexor surfaces, the face, and the buccal mucosa (Fig. 2). Cutaneous nodules can be demonstrated to follow the path of blood vessels within the skin [2]. Direct skin infiltration with amyloid can produce the appearance of scleroderma on the face, hands, and feet. Rarely, infiltrative nodular lesions may coalesce to form gross distortion and enlargement or tumefaction
- Raccoon Eyes: A I5-month-old girl was admitted to hospital with the complaints of bruising around the eyes for 10 days. She had one month history of abdominal pain and accompanied by fever and vomiting for one week. Physical examination demonstrated pallor, periorbital ecchymoses (raccoon eyes) and bilaterally mild proptosis (Fig. 1). She also had a left sided abdominal mass, which was 5 × 8 cm in diameter. The laboratory investigation revealed hemoglobin level 6g/dL, white cell count 10,000/mm3 and platelet count 34,000/mm3. Urinary vanillymandelic acid level was high. Bilateral bone marrow aspiration revealed infiltration with neuroblasts. Abdominal CT showed a left supra-renal mass (5 × 7 cm in diameter), which was diagnosed as a neuroblastoma on histopathologic examination. The metastatic involvement of the periorbital tissues. has been described and the resultant proptosis and orbital ecchymosis has been given the tag of ‘raccoon eyes’. Orbital metastases can be found in up to 20% of children with stage IV neuroblastoma. The raccoon eyes appearance associated with neuroblastoma is probably related to obstruction of the palpebral vessels by tumor tissue in and around the orbis. There are a multitude of differential diagnoses for the presentation of periorbital edema and ecchymosis, e.g., child abuse or trauma, infection of the soft tissues associated with a spreading dental infection and an allergic reaction. Other systemic causes to be considered include myxoedema, other neoplasias such as lymphoma or haematological coagulopathies such as haemophilia.
- Notice the large hyaline masses arranged diagonally across the screen. The upper left and the lower right areas of the field are occupied by normal white pulp. Amyloidosis of the spleen is seen in two forms - the sago spleen in which amyloid depositis are limited to the follicles, and the lardaceous spleen in which amyloid is deposited in the walls of the splenic sinusoids and spares the follicles. It is not clear which form is seen in this picture.
- Notice the large hyaline masses arranged diagonally across the screen. The upper left and the lower right areas of the field are occupied by normal white pulp. Amyloidosis of the spleen is seen in two forms - the sago spleen in which amyloid depositis are limited to the follicles, and the lardaceous spleen in which amyloid is deposited in the walls of the splenic sinusoids and spares the follicles. It is not clear which form is seen in this picture.
- (A) The amyloid appears pink and is localized to the perifollicular zone. (B) The identical area exhibits green birefringence in polarized light. Amyloid is indicated by arrows.
- Lugol’s Iodine: Mahagany brown, and treatment with 10% H2SO4 turns blue. 1% aqueous Methyl violet (5minutes) and differentiated with 1% acetic acid – Oink to red Sirius red: similar to congo red. It’s an alternative. Toludene blue: Dark red polariazation. Thioflavine-T&S: bright red fluorescenece Alcian blue: green. Cong red: red with polarized light, apple green birefringence.
- Amyloidosis, Lymphnode, Lugol's Reaction: left: Positive Lugol reaction in node with amyloidosis. right: Negative Lugol reaction in normal myometrium. A slice of the affected node (left) was treated for less than a minute in Lugol's solution. At right is a piece of normal myometrium treated similarly. The amyloid in the node reacts so strongly, it is almost black.