Hemolytic Anemia Overview

Hemolytic Anemia

• A condition where red blood cells (RBCs) are destroyed faster than they can be produced.
• Associated with Type II hypersensitivity (antibody-mediated hypersensitivity).
• Microscopy shows a "chewed-up" appearance of RBCs, with fragmented or abnormally shaped cells like schistocytes (fragmented RBCs) and spherocytes (spherical RBCs).
• These features are hallmarks of hemolysis.

Key Features of Hemolytic Anemia

• Chewed-Up Appearance of Red Cells:
  • RBCs are prematurely destroyed due to factors like autoimmune processes, mechanical damage, or abnormal red cell membranes.
• Odd-Shaped and Fragmented Cells:
  • Red blood cells are damaged while traveling through the blood vessels or attacked by the immune system.
  • This is a critical diagnostic feature in conditions like microangiopathic hemolytic anemia, where RBCs are sheared.
• Target Cells:
  • Red blood cells with a bullseye appearance.
  • Can be seen in various conditions like hemolytic anemias, liver disease, or certain hemoglobinopathies.
• Presence of Reticulocytes:
  • Immature red blood cells released from the bone marrow.
  • The percentage of reticulocytes usually increases to compensate for the rapid destruction of red cells in hemolytic anemia

Hashimoto's Thyroiditis

• Associated with Type IV hypersensitivity (delayed-type hypersensitivity) and involves a combination of cell-mediated immunity and autoantibody production (Type II hypersensitivity may also contribute).
• Microscopic Features:
  • Lymphoid Aggregates: Dense clusters of lymphocytes (both B-cells and T-cells) infiltrate the thyroid gland. These aggregates often form germinal centers, where B-cells mature and differentiate.
  • Destruction of Follicular Cells: Thyroid follicular cells are destroyed and replaced by inflammatory cells. Some areas may show atrophic follicles with pink-staining colloid.
  • Hurthle Cell Metaplasia: Thyroid follicular cells transform into Hurthle cells (enlarged cells with abundant, eosinophilic cytoplasm) due to chronic injury and inflammation.
  • Fibrosis: Fibrosis replaces the normal thyroid architecture, giving a lobulated appearance. This contributes to the thyroid gland's firmness on palpation.
  • Atrophic Follicles: The normal glandular tissue is significantly reduced or absent in areas of advanced disease.
  • Chronic Inflammatory Infiltrate: Hashimoto's thyroiditis is characterized by the infiltration of lymphocytes, plasma cells, and other immune cells. These inflammatory cells lead to destruction of the normal thyroid architecture.
  • Lymphoid Germinal Centers: Active germinal centers are a hallmark of Hashimoto's thyroiditis. These centers form within the thyroid tissue itself, where B-cells proliferate and mature, indicating an autoimmune process.
  • Destruction of the Gland: Extensive damage to thyroid follicles is observed, leading to a decrease in functional thyroid tissue over time.
  • Hurthle Cells: In areas attempting regeneration, Hurthle cells appear. These are large, eosinophilic cells with abundant, granular cytoplasm. They result from follicular cell transformation due to chronic inflammation

Skin with Amyloidosis

• Amyloidosis is a condition characterized by the extracellular deposition of misfolded proteins, forming insoluble fibrils known as amyloid.
• These deposits disrupt normal tissue architecture and function.
• Congo Red Staining:
  • Congo red is a special stain used to detect amyloid.
  • The dye binds specifically to the β-pleated sheet structure of amyloid fibrils. Microscopy shows the deposits as homogenous pink to orange-red material.
  • Under polarized light, amyloid deposits show an apple-green birefringence - a hallmark of amyloidosis.

Vascular Amyloid Deposits

• Within the dermis, amyloid accumulates primarily in the walls of blood vessels.
• This deposition weakens the vessel walls and may impair normal blood flow.

Kaposi's Sarcoma

• A vascular tumor arising from endothelial cells, associated with Human Herpesvirus-8 (HHV-8) infection.
• Commonly affects the skin, but can involve mucous membranes, lymph nodes, and visceral organs.
• Microscopic Features:
  • Malignant Endothelial Cells: observation of spindle-shaped and distorted-looking endothelial cells, sometimes resembling fibroblasts in appearance.
  • Irregular Vascular Structures: Endothelial cells form irregular vascular structures, a hallmark of Kaposi's sarcoma.
  • Diagnostic Clues: Atypical features such as nuclear pleomorphism, hyperchromasia, and abnormal mitoses are observed.
  • Extravasated Red Blood Cells: Red blood cells are present outside of blood vessels in the connective tissue, due to leakage from the abnormal vascular channels.
  • Hemosiderin Deposits: Evidence of prior RBC degradation within the background connective tissue, or histiocytes.
  • Inflammatory Infiltrate: Mixed inflammatory cells like lymphocytes, plasma cells, and macrophages are often present.
  • Characteristic Vascular Slits: Irregular, slit-like spaces filled with red blood cells are a key diagnostic feature, reflecting abnormal angiogenesis driven by malignant endothelial cells.
  • Malignant Cells Lining Abnormal Vascular Spaces: Malignant cells line the abnormal blood vessels.

Histological features of Kaposi's Sarcoma

• Spindle Cells: Malignant endothelial cells
• Slit-like vascular spaces: Poorly formed vascular channels containing RBC's
• Hemosiderin deposits: Evidence of prior RBC degradation
• Inflammatory infiltrate: Lymphocytes, plasma cells, and macrophages are commonly present
• HHV-8 positivity: Confirmatory with immunohistochemical staining.