Plasma Cell Dyscrasias Overview

Plasma Cell Dyscrasias

• Disorders marked by proliferation of a single plasma cell clone producing a monoclonal immunoglobulin, also known as paraprotein.
• Commonly observed in older adults.
• Screening methods include serum protein electrophoresis (M spike indicates monoclonal Ig overproduction), serum immunofixation, and serum free light chain assay.
• Urine protein electrophoresis and immunofixation are necessary for confirming urine involvement; urine dipstick only detects albumin.
• Bone marrow biopsy is crucial for diagnostic confirmation.
• Peripheral blood smear may reveal rouleaux formation, where red blood cells appear stacked like poker chips.

Multiple Myeloma

• Characterized by the overproduction of IgG (most prevalent), followed by IgA and Ig light chains.
• Clinical features encapsulated by the acronym CRAB:
  • Calcium elevation due to increased cytokine secretion (e.g., IL-1, TNF-α, RANK-L) from malignant plasma cells, stimulating osteoclast activity.
  • Renal insufficiency.
  • Anemia.
  • Bone lytic lesions, often described as "punched out" on X-ray, frequently causing back pain.
• Complications include heightened infection risk and primary amyloidosis (AL).
• Diagnosis involves urinalysis identifying Ig light chains (Bence Jones proteinuria) using θ urine dipstick.
• Bone marrow biopsy findings include:
  • More than 10% monoclonal plasma cells featuring clock-face chromatin.
  • Intracytoplasmic inclusions containing immunoglobulin.

Waldenström Macroglobulinemia

• Defined by overproduction of IgM, leading to macroglobulinemia as IgM is the largest immunoglobulin.
• Clinical manifestations include:
  • Anemia.
  • Constitutional symptoms ("B" symptoms).
  • Lymphadenopathy.
  • Hepatosplenomegaly.
  • Hyperviscosity causing symptoms like headache, bleeding, blurry vision, and ataxia.
  • Peripheral neuropathy.
• Diagnosis through fundoscopy reveals dilated, segmented, and tortuous retinal veins, resembling sausage links.
• Bone marrow biopsy characteristics:
  • More than 10% monoclonal B lymphocytes.
  • Features of plasma cells (lymphoplasmacytic lymphoma).
  • Intranuclear pseudoinclusions containing IgM.

Monoclonal Gammopathy of Undetermined Significance

• Characterized by the overproduction of any immunoglobulin type, typically indicated by the presence of an M spike.

Plasma Cell Dyscrasias

• Disorders result from the proliferation of a single plasma cell clone producing monoclonal immunoglobulin (paraprotein).
• Primarily affects older adults.
• Screening involves:
  • Serum protein electrophoresis (identifies M spike for monoclonal Ig overproduction).
  • Serum immunofixation and serum free light chain assay.
  • Urine protein electrophoresis and immunofixation used to confirm urinary involvement (urine dipstick is insufficient as it only detects albumin).
• Bone marrow biopsy is necessary for diagnostic confirmation.
• Peripheral blood smear may exhibit rouleaux formation, resembling stacked poker chips.

Multiple Myeloma

• Characterized by the overproduction of IgG (most common), followed by IgA and Ig light chains.
• Clinical features summarized as CRAB:
  • Calcium elevation (hypercalcemia) due to cytokine secretion by malignant plasma cells, promoting osteoclast activity.
  • Renal insufficiency resulting from hypercalcemia and potential nephrotoxic effects.
  • Anemia linked to bone marrow infiltration.
  • Bone lytic lesions appearing “punched out” on x-ray, leading to back pain.
• Complications include increased risk of infections and primary amyloidosis (AL type).
• Diagnosis methods:
  • Urinalysis reveals Ig light chains (Bence Jones proteinuria) using urine dipstick.
  • Bone marrow biopsy shows:
    • Over 10% monoclonal plasma cells with clock-face chromatin.
    • Intracytoplasmic inclusions containing immunoglobulin.

Waldenström Macroglobulinemia

• Characterized by the overproduction of IgM, the largest immunoglobulin, leading to macroglobulinemia.
• Clinical features include:
  • Anemia and constitutional ("B") signs/symptoms (fever, weight loss, night sweats).
  • Lymphadenopathy and hepatosplenomegaly.
  • Hyperviscosity syndrome resulting in headaches, bleeding, blurry vision, and ataxia.
  • Peripheral neuropathy due to IgM levels.
• Diagnosis methods:
  • Fundoscopy may reveal dilated, segmented, and tortuous retinal veins with a sausage link appearance.
  • Bone marrow biopsy shows:
    • Over 10% monoclonal B lymphocytes.
    • Plasma cell features indicating lymphoplasmacytic lymphoma.
    • Intranuclear pseudoinclusions containing IgM.

Monoclonal Gammopathy of Undetermined Significance (MGUS)

• Represents overproduction of any immunoglobulin type.
• Often identified by the presence of an M spike in serum protein electrophoresis.

Plasma Cell Dyscrasias

• Characterized by the proliferation of a single plasma cell clone resulting in the overproduction of monoclonal immunoglobulin (paraprotein).
• Commonly affects older adults.
• Screening methods include serum protein electrophoresis (M spike indicates monoclonal Ig), serum immunofixation, and serum free light chain assay.
• To confirm urinary involvement, use urine protein electrophoresis and immunofixation as urine dipstick primarily detects albumin.
• Diagnostic confirmation requires a bone marrow biopsy.
• Peripheral blood smear may reveal rouleaux formation, where RBCs stack like poker chips.

Multiple Myeloma

• Most frequently associated with the overproduction of IgG, followed by IgA and Ig light chains.

Clinical Features (CRAB):

• Hypercalcemia due to increased cytokine secretion (e.g., IL-1, TNF-a, RANK-L) promoting osteoclast activity.
• Renal insufficiency as a complication.
• Anemia common in presentation.
• Bone lytic lesions appear "punched out" on X-ray, often causing back pain.

Complications:

• Increased risk of infections.
• Primary amyloidosis (AL) may occur.

Diagnosis:

• Urinalysis reveals Ig light chains (Bence Jones proteinuria) and results from urine dipstick.
• Bone marrow biopsy shows >10% monoclonal plasma cells, characterized by clock-face chromatin and intracytoplasmic Ig inclusions.

Waldenström Macroglobulinemia

• Characterized by an overproduction of IgM, the largest immunoglobulin, leading to macroglobulinemia.

Clinical Features:

• Anemia is commonly observed.
• Common "B" signs and symptoms include fatigue and unintentional weight loss.
• Lymphadenopathy (swollen lymph nodes) is frequent.
• Hepatosplenomegaly (enlargement of liver and spleen) may occur.
• Hyperviscosity symptoms include headaches, bleeding, blurry vision, and ataxia (loss of full control of bodily movements).
• Peripheral neuropathy may develop.

Diagnosis:

• Fundoscopy typically shows dilated, segmented, and tortuous retinal veins, resembling a "sausage link" appearance.
• Bone marrow biopsy reveals >10% monoclonal B lymphocytes with plasma cell features indicative of lymphoplasmacytic lymphoma and intranuclear pseudoinclusions containing IgM.

Monoclonal Gammopathy of Undetermined Significance

• Involves overproduction of any type of immunoglobulin, identifiable by the presence of an M spike.

Plasma Cell Dyscrasias

• Characterized by proliferation of a single plasma cell clone, resulting in overproduction of a monoclonal immunoglobulin (paraprotein).
• Primarily affects older adults.
• Diagnostic tools include serum protein electrophoresis (M spike indicates monoclonal immunoglobulin), serum immunofixation, and serum free light chain assay.
• Urine protein electrophoresis and immunofixation required to assess urinary involvement; urine dipstick detects only albumin.
• Bone marrow biopsy is crucial for diagnostic confirmation.
• Peripheral blood smear may reveal rouleaux formation, where red blood cells stack like poker chips.

Multiple Myeloma

• Most commonly involves overproduction of IgG, followed by IgA and Ig light chains.
• Clinical features encapsulated by CRAB:
  • Hypercalcemia caused by cytokine secretion (IL-1, TNF-α, RANK-L) from malignant plasma cells, enhancing osteoclast activity.
  • Renal insufficiency due to deposition of light chains.
  • Anemia leading to fatigue and complications.
  • Bone lytic lesions visible as "punched-out" areas on X-ray, often causing back pain.
• Complications include increased risk of infections and primary amyloidosis (AL type).
• Diagnostic criteria include:
  • Urinalysis revealing Bence Jones proteinuria (Ig light chains).
  • Bone marrow biopsy showing over 10% monoclonal plasma cells with clock-face chromatin and intracytoplasmic Ig inclusions.

Waldenström Macroglobulinemia

• Features overproduction of IgM, the largest immunoglobulin, causing macroglobulinemia.
• Clinical symptoms include:
  • Anemia and constitutional ("B") signs such as fever, night sweats, and weight loss.
  • Lymphadenopathy and hepatosplenomegaly.
  • Hyperviscosity symptoms like headache, bleeding, blurred vision, and ataxia.
  • Peripheral neuropathy.
• Diagnosis involves:
  • Fundoscopy revealing dilated, segmented, and tortuous retinal veins (sausage link appearance).
  • Bone marrow biopsy indicating more than 10% monoclonal B lymphocytes, plasma cell features, and intranuclear pseudoinclusions containing IgM.

Monoclonal Gammopathy of Undetermined Significance

• Involves the overproduction of any type of immunoglobulin, identifiable through the presence of an M spike.

Plasma Cell Dyscrasias

• Characterized by proliferation of a single plasma cell clone leading to monoclonal immunoglobulin overproduction (paraprotein).
• Typically affects older adults.
• Screening performed with serum protein electrophoresis, where M spike indicates monoclonal Ig overproduction.
• Additional tests include serum immunofixation and serum free light chain assay.
• Urine protein electrophoresis and immunofixation confirm urinary involvement; urine dipstick detects only albumin.
• Diagnosis confirmed through bone marrow biopsy.
• Peripheral blood smear may show rouleaux formation, indicating stacked red blood cells.

Multiple Myeloma

• Most common type overproduces IgG, followed by IgA and light chains.

Clinical Features (CRAB)

• Hypercalcemia due to increased cytokine secretion (IL-1, TNF-a, RANK-L) by malignant plasma cells, enhancing osteoclast activity.
• Renal insufficiency connected to high levels of paraprotein.
• Anemia resulting from decreased erythrocyte production.
• Bone lytic lesions observed as "punched out" areas on X-rays, commonly causing back pain.

Complications

• Increased susceptibility to infections due to immune system compromise.
• Possible development of primary amyloidosis (AL type).

Diagnosis

• Urinalysis detects immunoglobulin light chains, termed Bence Jones proteinuria, via urine dipstick.
• Bone marrow biopsy reveals more than 10% monoclonal plasma cells with clock-face chromatin and intracytoplasmic inclusions containing Ig.

Waldenström Macroglobulinemia

• Characterized by overproduction of IgM, the largest immunoglobulin, resulting in macroglobulinemia.

Clinical Features

• Anemia presents with fatigue and weakness.
• Constitutional symptoms include fever, night sweats, and weight loss.
• Lymphadenopathy and hepatosplenomegaly are common findings.
• Hyperviscosity leads to headaches, bleeding, visual disturbances, and ataxia.
• Peripheral neuropathy may occur, affecting sensation and motor function.

Diagnosis

• Fundoscopy shows dilated, segmented, and tortuous retinal veins, resembling sausage links.
• Bone marrow biopsy indicates over 10% monoclonal B lymphocytes with plasma cell features, consistent with lymphoplasmacytic lymphoma, and intranuclear pseudoinclusions containing IgM.

Monoclonal Gammopathy of Undetermined Significance (MGUS)

• Defined by overproduction of any immunoglobulin type, indicated by the presence of an M spike.

Plasma Cell Dyscrasias

• A group of disorders caused by the proliferation of a single plasma cell clone.
• Typically involves the overproduction of monoclonal immunoglobulin (paraprotein).
• Commonly observed in older adults.
• Screening tests include serum protein electrophoresis (detects M spike), serum immunofixation, and serum free light chain assay.
• Confirmation of urinary involvement requires urine protein electrophoresis and immunofixation; urine dipstick can only detect albumin.
• Diagnostic confirmation is achieved through bone marrow biopsy.
• Peripheral blood smear may reveal rouleaux formation, where RBCs appear stacked like poker chips.

Multiple Myeloma

• Characterized by excessive production of IgG (most common), followed by IgA and Ig light chains.
• Clinical features represented by the acronym CRAB:
  • Calcium elevated (hypercalcemia) due to cytokine secretion from malignant plasma cells, leading to increased osteoclast activity.
  • Renal insufficiency as a consequence of heavy protein loads.
  • Anemia resulting from bone marrow infiltration.
  • Bone lytic lesions, identifiable as "punched-out" areas on X-ray, often causing back pain.
• Complications include increased susceptibility to infections and primary amyloidosis (AL).
• Diagnosis involves:
  • Urinalysis: Shows presence of Ig light chains (Bence Jones protein).
  • Bone Marrow Biopsy: Must show over 10% monoclonal plasma cells with clock-face chromatin and intracytoplasmic inclusions containing Ig.

Waldenström Macroglobulinemia

• Involves overproduction of IgM, noted for being the largest immunoglobulin, leading to macroglobulinemia.
• Clinical features include:
  • Anemia and constitutional symptoms (B symptoms like fever, night sweats).
  • Lymphadenopathy and hepatosplenomegaly.
  • Symptoms related to hyperviscosity, such as headaches, bleeding, blurry vision, and ataxia.
  • Peripheral neuropathy.
• Diagnosis includes:
  • Fundoscopy: Observes dilated, segmented, and tortuous retinal veins, noted for appearing like "sausage links."
  • Bone Marrow Biopsy: Must show greater than 10% monoclonal B lymphocytes with plasma cell characteristics (lymphoplasmacytic lymphoma) and intranuclear pseudoinclusions containing IgM.

Monoclonal Gammopathy of Undetermined Significance

• Involves the overproduction of any type of immunoglobulin, characterized by an identified M spike.