Plasma Cell Dyscrasias Overview

Plasma Cell Dyscrasias

• Characterized by proliferation of a single plasma cell clone producing monoclonal immunoglobulin (paraprotein).
• Usually occurs in older adults.
• Screening methods include serum protein electrophoresis (detects M spike indicating monoclonal Ig), serum immunofixation, and serum free light chain assay.
• Urine protein electrophoresis and immunofixation assess urinary involvement; urine dipstick only detects albumin.
• Diagnostic confirmation is performed through a bone marrow biopsy.
• Peripheral blood smear may reveal rouleaux formation, which looks like stacked red blood cells.

Multiple Myeloma

• Commonly shows overproduction of IgG, followed by IgA and light chains.
• Clinical features (CRAB):
  • Hypercalcemia resulting from increased cytokine secretion (e.g., IL-1, TNF-α, RANK-L) by malignant plasma cells stimulates osteoclast activity.
  • Renal insufficiency caused by light chain cast nephropathy.
  • Anemia due to bone marrow infiltration.
  • Bone lytic lesions appear as "punched out" holes on X-ray, often leading to back pain.
• Complications:
  • Increased risk of infections due to immune suppression.
  • Primary amyloidosis (AL) related to excess light chain production.
• Diagnosis:
  • Urinalysis reveals Bence Jones proteinuria, which indicates Ig light chains.
  • Bone marrow biopsy shows over 10% monoclonal plasma cells with clock-face chromatin and intracytoplasmic inclusions containing Ig.

Waldenström Macroglobulinemia

• Characterized by the overproduction of IgM, the largest immunoglobulin, leading to macroglobulinemia.
• Clinical features:
  • Anemia resulting from marrow infiltration.
  • Constitutional symptoms, such as fatigue and weight loss.
  • Lymphadenopathy and hepatosplenomegaly.
  • Hyperviscosity symptoms, including headache, bleeding tendencies, blurry vision, and ataxia.
  • Peripheral neuropathy due to IgM effects on nerve tissue.
• Diagnosis:
  • Fundoscopic examination may show dilated, segmented, and tortuous retinal veins, described as a "sausage link" appearance.
  • Bone marrow biopsy reveals over 10% monoclonal B lymphocytes, plasma cell features consistent with lymphoplasmacytic lymphoma, and intranuclear pseudoinclusions containing IgM.

Monoclonal Gammopathy of Undetermined Significance

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

Plasma Cell Dyscrasias

• Disorders arise from the proliferation of a single plasma cell clone that overproduces a monoclonal immunoglobulin, referred to as paraprotein.
• Primarily observed in older adults, with screening methods including:
  • Serum protein electrophoresis (M spike indicates monoclonal Ig overproduction)
  • Serum immunofixation
  • Serum free light chain assay
• Urinary involvement is confirmed through urine protein electrophoresis and immunofixation, as urine dipstick only detects albumin.
• Diagnosis is confirmed via bone marrow biopsy.
• Peripheral blood smear may show rouleaux formation, resembling RBCs stacked like poker chips.

Multiple Myeloma

• Characterized by overproduction of immunoglobulins, predominantly IgG, followed by IgA and light chains.

Clinical Features (CRAB)

• Calcium elevation (hypercalcemia) caused by cytokine secretion (e.g., IL-1, TNF-a, RANK-L) increasing osteoclast activity.
• Renal insufficiency due to plasma cell malignancy.
• Anemia resulting from bone marrow infiltration.
• Bone lytic lesions visible on x-ray as “punched out” areas, often leading to back pain.

Complications

• Increased risk of infections and the development of primary amyloidosis (AL type).

Diagnosis

• Urinalysis revealing Ig light chains and Bence Jones proteinuria detected with urine dipstick.

Bone Marrow Biopsy

• Presence of more than 10% monoclonal plasma cells with clock-face chromatin.
• Intracytoplasmic inclusions containing immunoglobulin.

Waldenström Macroglobulinemia

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

Clinical Features

• Symptoms include anemia, constitutional symptoms (B symptoms), lymphadenopathy, and hepatosplenomegaly.
• Hyperviscosity symptoms such as headache, bleeding, blurry vision, and ataxia.
• Presence of peripheral neuropathy as a common feature.

Diagnosis

• Fundoscopy reveals dilated, segmented, and tortuous retinal veins with a sausage link appearance.

Bone Marrow Biopsy

• More than 10% monoclonal B lymphocytes with plasma cell characteristics indicative of lymphoplasmacytic lymphoma.
• Intranuclear pseudoinclusions containing IgM.

Monoclonal Gammopathy of Undetermined Significance (MGUS)

• Involves the overproduction of various immunoglobulin types, identifiable by the presence of an M spike.

Plasma Cell Dyscrasias

• Characterized by the proliferation of a single plasma cell clone producing monoclonal immunoglobulin (paraprotein).
• Commonly affects older adults and usually detected via serum protein electrophoresis.
• M spike indicates overproduction of monoclonal immunoglobulin.
• Diagnosis confirmed through serum immunofixation, serum free light chain assay, and bone marrow biopsy.
• Urine protein electrophoresis required for urinary involvement confirmation; urine dipstick only identifies albumin.
• Peripheral blood smear may show rouleaux formation, where RBCs stack like poker chips.

Multiple Myeloma

• Most frequent variant involves overproduction of IgG, followed by IgA and immunoglobulin light chains.
• Clinical features summarized as CRAB:
  • Hypercalcemia due to cytokine secretion (IL-1, TNF-a, RANK-L) by malignant plasma cells, leading to increased osteoclast activity.
  • Renal insufficiency resulting from increased calcium and light chains.
  • Anemia due to bone marrow infiltration and reduced red blood cell production.
  • Bone lytic lesions appear on X-ray as "punched out" areas, often causing back pain.
• Complications include increased risk of infections and primary amyloidosis (AL type).
• Diagnosis involves:
  • Urinalysis showing Bence Jones proteinuria indicative of Ig light chains.
  • Bone marrow biopsy revealing more than 10% monoclonal plasma cells with clock-face chromatin and intracytoplasmic inclusions.

Waldenström Macroglobulinemia

• Characterized by overproduction of IgM, the largest immunoglobulin, leading to macroglobulinemia.
• Clinical features include:
  • Anemia and constitutional ("B") signs/symptoms such as fever and night sweats.
  • Lymphadenopathy and hepatosplenomegaly due to lymphoproliferation.
  • Hyperviscosity symptoms, including headache, bleeding tendencies, blurry vision, and ataxia.
  • Peripheral neuropathy related to IgM excess.
• Diagnosis confirmed by:
  • Fundoscopy, revealing dilated, segmented, tortuous retinal veins with a "sausage link" appearance.
  • Bone marrow biopsy showing over 10% monoclonal B lymphocytes, plasma cell features, and intranuclear pseudoinclusions of IgM.

Monoclonal Gammopathy of Undetermined Significance (MGUS)

• Involves the overproduction of any type of immunoglobulin, usually identified by the presence of an M spike.
• Typically asymptomatic and requires monitoring for progression to more serious conditions.

Plasma Cell Dyscrasias

• Disorders involve proliferation of a single plasma cell clone with excess monoclonal immunoglobulin (paraprotein).
• Typically affects older adults, often identified through specific screening tests.
• Screening methods include serum protein electrophoresis (M spike indicates monoclonal Ig), serum immunofixation, and serum free light chain assay.
• Confirm urinary involvement with urine protein electrophoresis and immunofixation; urine dipstick detects only albumin.
• Diagnostic confirmation typically achieved via bone marrow biopsy.
• Peripheral blood smear may exhibit rouleaux formation, indicated by RBCs stacked like poker chips.

Multiple Myeloma

• Characterized by overproduction of IgG (most common), followed by IgA and Ig light chains.

Clinical Features (CRAB)

• Hypercalcemia: Caused by increased cytokine secretion (e.g., IL-1, TNF-a, RANK-L) from malignant plasma cells leading to osteoclast activity.
• Renal Insufficiency: A significant complication affecting kidney function.
• Anemia: Common in patients due to bone marrow infiltration.
• Bone Lytic Lesions: "Punched out" appearance on X-ray, often associated with back pain.

Complications

• Elevated infection risk due to immune system compromise.
• Potential for primary amyloidosis (AL).

Diagnosis

• Urinalysis: Reveals Bence Jones proteinuria from Ig light chains.
• Bone Marrow Biopsy: Shows:
  • Over 10% monoclonal plasma cells with clock-face chromatin.
  • Intracytoplasmic inclusions containing immunoglobulin.

Waldenström Macroglobulinemia

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

Clinical Features

• Anemia: Commonly observed and related to bone marrow suppression.
• Constitutional Symptoms: Includes fever, weight loss, and night sweats (B symptoms).
• Lymphadenopathy and Hepatosplenomegaly: Enlargement of lymph nodes and spleen.
• Hyperviscosity Symptoms: Manifestations include headache, bleeding tendencies, blurry vision, and ataxia.
• Peripheral Neuropathy: Nerve damage symptoms related to IgM levels.

Diagnosis

• Fundoscopy: Demonstrates dilated, segmented, tortuous retinal veins with a "sausage link" appearance.
• Bone Marrow Biopsy: Displays:
  • Over 10% monoclonal B lymphocytes.
  • Characteristics of lymphoplasmacytic lymphoma.
  • Intranuclear pseudoinclusions containing IgM.

Monoclonal Gammopathy of Undetermined Significance

• Defined by overproduction of any immunoglobulin type, typically detected through M spike on electrophoresis.

Plasma Cell Dyscrasias

• Characterized by proliferation of a single plasma cell clone that overproduces monoclonal immunoglobulin (paraprotein).
• Commonly seen in older adults.
• Diagnostic screening includes serum protein electrophoresis (M spike indicates monoclonal Ig overproduction), serum immunofixation, and serum free light chain assay.
• Urine assessments require urine protein electrophoresis and immunofixation for confirmation, as urine dipstick only detects albumin.
• Diagnostic confirmation is obtained through bone marrow biopsy.
• Peripheral blood smear may show rouleaux formation, resembling stacked poker chips.

Multiple Myeloma

• Involves overproduction of IgG (most common), followed by IgA and Ig 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 as a consequence of light chain deposition or obstructive nephropathy.
• Anemia stemming from ineffective erythropoiesis and bone marrow infiltration.
• Bone lytic lesions, visible as "punched out" areas on X-ray, often leading to back pain.

Complications

• Higher risk of infections due to immune compromise.
• Primary amyloidosis (AL) may develop, resulting from light chain deposition.

Diagnosis

• Urinalysis shows Bence Jones proteinuria, indicative of Ig light chains.

Bone Marrow Biopsy

• Presence of over 10% monoclonal plasma cells with clock-face chromatin patterns.
• Intracytoplasmic inclusions containing immunoglobulin found.

Waldenström Macroglobulinemia

• Associated with overproduction of IgM, the largest immunoglobulin, resulting in macroglobulinemia.

Clinical Features

• Symptoms of anemia and generalized constitutional symptoms (e.g., fatigue, weight loss).
• Lymphadenopathy and hepatosplenomegaly due to lymphocytic infiltration.
• Hyperviscosity syndrome, leading to headaches, bleeding tendencies, blurred vision, and ataxia.
• Peripheral neuropathy may occur as a result of IgM accumulation.

Diagnosis

• Fundoscopy reveals dilated, segmented, and tortuous retinal veins, described as a "sausage link appearance."

Bone Marrow Biopsy

• More than 10% of monoclonal B lymphocytes with plasma cell features indicative of lymphoplasmacytic lymphoma.
• Intranuclear pseudoinclusions containing IgM may be noted.

Monoclonal Gammopathy of Undetermined Significance

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

Plasma Cell Dyscrasias

• Disorders feature proliferation of a single plasma cell clone producing a monoclonal immunoglobulin, known as paraprotein.
• Primarily observed in older adults.
• Diagnostic screening includes serum protein electrophoresis, revealing an M spike indicative of monoclonal Ig overproduction.
• Serum immunofixation and serum free light chain assay are also utilized.
• Urine tests like protein electrophoresis and immunofixation are necessary to detect urinary involvement; urine dipstick is insufficient as it only detects albumin.
• Bone marrow biopsy is crucial for diagnostic confirmation.
• Peripheral blood smear may show rouleaux formation, where red blood cells stack resembling poker chips.

Multiple Myeloma

• Characterized by overproduction of immunoglobulins, predominantly IgG, followed by IgA and Ig light chains.
• Clinical features summarized as CRAB:
  • Calcium elevation (hypercalcemia) due to increased osteoclast activity from cytokines (e.g., IL-1, TNF-α, RANK-L).
  • Renal insufficiency caused by the accumulation of malignant plasma cells.
  • Anemia linked to diminished erythropoiesis.
  • Bone lytic lesions that appear 'punched out' on x-ray, often causing back pain.
• Complications include a heightened risk of infections and 1° amyloidosis (AL type).
• Diagnosis involves:
  • Urinalysis indicating Bence Jones proteinuria (presence of Ig light chains).
  • Bone marrow biopsy revealing over 10% monoclonal plasma cells exhibiting clock-face chromatin and cytoplasmic inclusions containing immunoglobulin.

Waldenström Macroglobulinemia

• Defined by the overproduction of IgM, the largest immunoglobulin, causing macroglobulinemia.
• Clinical features include:
  • Anemia and constitutional ‘B’ symptoms (fever, night sweats, weight loss).
  • Lymphadenopathy and hepatosplenomegaly.
  • Hyperviscosity symptoms, such as headaches, bleeding, visual disturbances, and ataxia.
  • Peripheral neuropathy may occur.
• Diagnosis includes:
  • Fundoscopy revealing dilated, segmented, and tortuous retinal veins, also referred to as a sausage link appearance.
  • Bone marrow biopsy identifies more than 10% monoclonal B lymphocytes with plasma cell characteristics, including intranuclear pseudoinclusions containing IgM.

Monoclonal Gammopathy of Undetermined Significance

• Characterized by the overproduction of various immunoglobulin types, indicated by the presence of an M spike.