19. Plasma Cell Dyscrasia SLG 2025

What characterizes plasma cell dyscrasias

Production of monoclonal immunoglobulin molecules.

What is the clinical spectrum of plasma cell disorders

Ranges from indolent to life-threatening.

What diseases are included under plasma cell dyscrasias

Multiple myeloma, smoldering MM, MGUS, and amyloidosis.

What do all antibodies consist of

Two identical light chains and two identical heavy chains.

What regions are found in both light and heavy chains

Variable (V) and constant (C) regions.

What part of the antibody binds the antigen

Variable region.

What part of the antibody binds Fc receptors on cells

Constant region (Fc fragment).

What are Fab and Fc fragments derived from

Cleavage of the antibody molecule.

What does the Fab fragment contain

Variable region plus part of the constant region.

What does the Fc fragment contain

Only constant region.

Can light chains be secreted independently

Yes.

What are free light chains in the urine called

Bence-Jones proteins.

Which antibody is most abundant in serum

IgG.

Which antibody crosses the placenta

IgG.

Which antibody is found on mucosal surfaces and secretions

IgA.

Which antibody is passed via breast milk

IgA.

Which antibody is the earliest produced in infection

IgM.

What is IgM also called

Macroglobulin.

Why is antibody structure reviewed in this SLG

To understand abnormal monoclonal protein secretion in plasma cell dyscrasias.

What is MGUS

A premalignant clonal plasma cell condition.

How is MGUS typically found

Incidentally on routine labs (e.g., protein gap).

What is the clinical workup for MGUS

Review of systems, exclusion of CRAB criteria, monitor for progression.

Does MGUS always progress to malignancy

No.

What is the most important plasma cell malignancy

Multiple Myeloma.

Who is most commonly affected by Multiple Myeloma

Older adults.

Which racial group is disproportionately affected by MM

Black Americans.

What are hallmark symptoms of MM

Bone pain, fatigue, malaise.

What does CRAB stand for in MM diagnosis

Calcium elevation, Renal dysfunction, Anemia, Bone disease.

What type of bone disease is seen in MM

Lytic or osteopenic lesions.

What is Waldenström’s Macroglobulinemia

A rare lymphoplasmacytoid lymphoma.

What is the characteristic monoclonal protein in Waldenström’s

IgM.

What symptoms result from hyperviscosity in Waldenström’s

Headache, visual changes, retinal hemorrhages, altered mental status, stroke.

What other features may be seen in Waldenström’s

Renal disease, neuropathy, Raynaud’s, autoimmune cytopenias.

How is Waldenström’s treated

Based on symptoms — observation, chemotherapy, or plasmapheresis.

What causes AL amyloidosis

Malignant plasma cells producing unstable free light chains (κ or λ).

What happens to light chains in AL amyloidosis

They misfold into amyloid fibrils that deposit in organs.

What organs are affected in AL amyloidosis

Heart, kidneys, liver, CNS.

What can AL amyloidosis arise from

MGUS.

What percentage of hematologic malignancies does Waldenström Macroglobulinemia account for

1–2%.

How does Waldenström Macroglobulinemia usually present

Older adults with fatigue and malaise, progressing to symptoms of marrow infiltration and excess IgM.

What lab findings support Waldenström Macroglobulinemia

Cytopenias on CBC, monoclonal IgM on SPEP, >10% lymphoplasmacytic clone on marrow biopsy.

How is Waldenström Macroglobulinemia treated

Based on symptoms; may observe, use chemotherapy, or plasmapheresis.

What syndrome is associated with Waldenström’s and elevated IgM

Hyperviscosity Syndrome.

What are symptoms of hyperviscosity syndrome

Headache, blurred vision, retinal hemorrhages, altered mental status, stroke.

What antibody is associated with peripheral neuropathy in Waldenström’s

Myelin-associated globulin antibodies.

What type of autoimmune hemolytic anemia is seen in Waldenström’s

Cold agglutinin disease.

What is MGUS

Premalignant clonal plasma cell or lymphoplasmacytic disorder.

How common is MGUS in adults over 50

Up to 3%.

How is MGUS often discovered

Incidentally, e.g., via protein gap on routine chemistry.

Does MGUS always progress

No, it may remain stable or progress to SMM, MM, or amyloidosis.

What is the significance of SPEP

Separates serum proteins to detect M-protein.

What is the role of serum immunofixation

Identifies the specific immunoglobulin class of M protein.

Where do immunoglobulins migrate on SPEP

Usually the gamma region, sometimes the beta region.

What does a positive serum free light chain assay indicate

Increased free κ or λ chains in plasma cell disorders.

What are organs affected by AL Amyloidosis

Heart, kidney, liver, nervous system, GI tract, skin, soft tissue.

What causes amyloid fibril formation in AL amyloidosis

Unstable light chains secreted by plasma cells.

What is a hallmark of AL amyloidosis diagnosis delay

43% diagnosed over a year after symptom onset.

Why is AL amyloidosis often misdiagnosed

It mimics other diseases and lacks a typical presentation.

What percentage of AL amyloidosis patients have elevated serum free light chains

95%.

How many Americans live with multiple myeloma

About 45,000.

Who has the highest risk of multiple myeloma

African Americans (2–3x higher than white Americans).

What is the gender ratio for MM incidence

1.4:1, more common in males.

What is the median age at MM diagnosis

69 years.

What immunoglobulin is most commonly secreted in MM

IgG.

What is the second most common immunoglobulin in MM

IgA.

What protein is found in the urine of patients with light chain MM

Bence-Jones protein.

What causes renal dysfunction in MM

Cast nephropathy from filtered light chains.

What does rouleaux formation on smear suggest

High serum proteins from MM.

What is the role of skeletal surveys in MM

Identify lytic bone lesions.

What CRAB feature corresponds to calcium >11.5 mg/dL

Hypercalcemia.

What creatinine level defines renal dysfunction in CRAB criteria

2 mg/dL.

What defines anemia in MM

Hemoglobin <10 g/dL or 2 g below normal.

What are lytic bone lesions a sign of

Active multiple myeloma.

What is the disease course of MM

Chronic, relapsing and remitting.

What does initial MM workup include

H&P, CBC, renal and liver function, SPEP, SIFE, light chains, skeletal survey, marrow biopsy.

What drug class is bortezomib

Proteasome inhibitor.

What drugs are commonly used in initial MM therapy

Bortezomib, dexamethasone, cyclophosphamide, lenalidomide.

What is the goal of MM maintenance therapy

Prolong remission and delay relapse.

What are common adjuncts in MM therapy

Bisphosphonates, antivirals, anticoagulation, IVIG, vaccines.

What regimen is used for high-risk MM patients

Melphalan + prednisone + bortezomib or IMiD.

What is the disease progression pathway from MGUS to MM?

MGUS → Smoldering Multiple Myeloma → Multiple Myeloma.

What conditions can IgM MGUS progress to?

Waldenstrom Macroglobulinemia and Light Chain Amyloidosis.

When might MGUS require therapy despite being asymptomatic?

When it causes symptoms like neuropathy.

What is the second most common hematologic malignancy in the U.S.?

Multiple Myeloma.

What are possible presenting symptoms of multiple myeloma besides fatigue?

Hip or bone pain (especially chronic, such as for 5 months)

What lab findings may suggest MM before SPEP?

Anemia, thrombocytopenia, neutropenia, elevated creatinine, and elevated calcium

What is the significance of a normal MCV in MM workup?

It suggests normocytic anemia, which is common in MM

What type of monoclonal protein is most commonly seen in MM?

IgG

What does a skeletal survey showing lytic lesions suggest?

Bone involvement in multiple myeloma

What does a bone marrow biopsy with 42% plasma cells indicate?

Confirms clonal plasma cell proliferation, diagnostic for MM

What cytogenetic finding is associated with poor prognosis in MM?

del(17p)