Clinical Hematology Series

Multiple Myeloma

From pathogenesis to diagnosis — the plasma-cell clone, CRAB, and the diagnostic triad.

15 slides·English·2026
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Title slide with a detailed illustration of a single cell showing a rounded nucleus containing multiple clumped chromatin masses arranged in a radial pattern.
01 / 15

Multiple Myeloma: From Pathogenesis to Diagnosis

A Clinical & Pathophysiological Review

Source: [Medical Institutio… (text cut off at slide edge)

Clinical case slide with a narrative paragraph on the left and a Lab Results panel plus an Investigative Clue callout on the right, including a serum protein electrophoresis tracing with a tall spike.
02 / 15

The Case Presentation

A 60-year-old gentleman presents with new exertional fatigue. He has no significant past medical history.

Lab Results

TestValueInterpretation
Hemoglobin10.6 g/dLLow – Anemia
Creatinine1.8 mg/dLHigh – Renal Insufficiency
Calcium11.2 mg/dLHigh – Hypercalcemia
Total Protein11 g/dLHigh — vs. Albumin 3.1 g/dL (Low)

Investigative Clue (Clinical Blue)

Serum protein electrophoresis demonstrates a monoclonal IgA protein of 60 g/dL.

Labeled illustration of a plasma cell showing an eccentric nucleus with clockface chromatin, a perinuclear halo (Golgi apparatus), oval basophilic cytoplasm, and secreted antibodies.
03 / 15

The Cell of Origin: The Plasma Cell

Plasma cells are the terminal differentiation of B-cells, primarily responsible for humoral immunity. They normally reside in the bone marrow (3–5%) and secrete polyclonal antibodies (IgG, IgM, IgA, IgD, IgE).

Labeled cell features:

  • Eccentric nucleus
  • Clockface chromatin pattern
  • Perinuclear halo (Golgi apparatus)
  • Oval shape with deeply basophilic cytoplasm
  • Antibody (secreted)
Two-panel comparison of bone marrow: a normal polyclonal response with varied plasma cells secreting multi-colored antibodies versus a monoclonal malignancy with many identical clones secreting a single antibody type.
04 / 15

Pathogenesis: The Clonal Proliferation

Normal Response (Polyclonal)

Different plasma cells secrete a variety of immunoglobulins to fight infection.

Malignancy (Monoclonal)

A single malignant clone replicates uncontrollably. The clone secretes a single, identical immunoglobulin known as the Paraprotein or M-Protein.

Serum protein electrophoresis graph plotting absorbance (protein concentration) against migration distance, overlaying a normal serum tracing and a myeloma serum tracing that shows a tall narrow M-spike in the gamma region.
05 / 15

Detecting the Clone: Serum Protein Electrophoresis (SPEP)

Graph axes: Absorbance (Protein Concentration) on the vertical axis versus Migration Distance on the horizontal axis.

Two tracings are overlaid: Normal Serum (blue) and Myeloma Serum (red).

Peaks labeled along the migration axis, from left to right: Albumin, Alpha-1, Alpha-2, Beta, Gamma. The Myeloma Serum shows a tall, narrow M-Spike (Paraprotein) at the far right.

Proteins are separated by charge. In Myeloma, the monoclonal protein accumulates in the gamma region, creating a tall, narrow spike.

Legend: Blue: Normal Serum, Red: Myeloma S… (text cut off at slide edge)

Diagram of an antibody in Y-shape with labeled Heavy Chain and Light Chain regions, alongside explanatory text and a Case Insight callout box.
06 / 15

Decoding the M-Spike

The spike represents the physical quantity of the monoclonal protein. It is identified by its Heavy Chain and Light Chain.

  • Common: IgG or IgA
  • Rare: IgD or IgE
  • Very Rare: IgM (Suggests Waldenström's)

Antibody structure labels: Heavy Chain, Light Chain.

Case Insight

Our patient has an IgA spike of 60 g/L—indicating a massive tumor burden.

Ascending three-step staircase diagram showing progression from MGUS to Smoldering Myeloma to Multiple Myeloma with increasing tumor burden, plus a CRAB Criteria key box.
07 / 15

The Spectrum: From MGUS to Symptomatic Myeloma

A three-step progression of increasing tumor burden:

MGUS

  • M-spike < 3 g/dL.
  • < 10% Plasma cells.
  • Asymptomatic.
  • Management: Observe.

Smoldering Myeloma

  • M-spike ≥ 3 g/dL OR ≥ 10% Plasma cells.
  • Asymptomatic.
  • Management: Observe.

Multiple Myeloma

  • M-spike ≥ 3 g/dL OR ≥ 10% Plasma cells.
  • + SYMPTOMS (CRAB criteria).
  • Management: Treat.

CRAB Criteria

  • C → hyperCalcemia
  • R → Renal insufficiency
  • A → Anemia
  • B → Bone disease

Source: Adapted from Kumar & Law, AccessMedicine, McGraw… (text cut off at slide edge)

Central circular CRAB Criteria hub with four surrounding icons and labels for Hypercalcemia, Renal Insufficiency, Anemia, and Bone Disease.
08 / 15

Clinical Manifestations: The CRAB Criteria

Symptomatic Myeloma is defined by end-organ damage.

  • C – Hypercalcemia
  • R – Renal Insufficiency
  • A – Anemia
  • B – Bone Disease

These four pillars explain the constellation of symptoms in our patient case.

Lateral skull X-ray showing multiple punched-out lytic lesions on the left, with a Consequences bullet list on the right.
09 / 15

Bone Destruction & Hypercalcemia

Myeloma cells disrupt bone remodeling by increasing Osteoclast activity (bone eating) and decreasing Osteoblast activity (bone building).

Consequences:

  • Diffuse osteopenia
  • Lytic Lesions ("Punched-out" appearance)
  • Pathological fractures
  • Hypercalcemia (leached from destroyed bone)

Figure X. Lateral skull X-ray demonstrating multiple "punched-out" lytic lesions characteristic of myeloma.

Diagram of a nephron labeling glomerulus, proximal and distal convoluted tubules, loop of Henle, and collecting duct, with a magnified inset showing an obstructing cast in a tubule.
10 / 15

Renal Insufficiency: The Mechanism of Injury

Primary Cause: Cast Nephropathy

Light chains bind with proteins in the tubules to form insoluble casts, obstructing flow.

Contributing Factors:

  • Hypercalcemia
  • Hyperviscosity
  • NSAID use

Nephron diagram labels: Glomerulus, Proximal Convoluted Tubule, Distal Convoluted Tubule, Loop of Henle, Collecting Duct.

Inset label: Cast Nephropathy (Bence Jones Proteins + Tamm–Horsfall Proteins).

Blood smear illustration showing red blood cells stacked in chains (rouleaux formation) with a single white blood cell, alongside explanatory text.
11 / 15

Anemia & Immunodeficiency

Normocytic Anemia: Caused by marrow infiltration (cancer cells crowding out RBC precursors) and renal failure (low EPO).

Infection: Patients are immunodeficient because the clonal antibodies are ineffective, and normal immunoglobulins are suppressed.

Blood smear label: Rouleaux Formation.

High protein levels reduce charge repulsion, causing RBCs to stack.

Two-column slide: an MRI of the spine showing a paraspinal mass causing cord compression, and an illustration comparing a healthy nerve with a damaged nerve.
12 / 15

Neurological Complications

Spinal Cord Compression

Caused by paraspinal masses or vertebral body collapse. A medical emergency.

MRI label: Paraspinal Mass / Compression.

Peripheral Neuropathy

Direct damage to nerves by monoclonal proteins, or a side effect of chemotherapy.

Illustration labels: Healthy Nerve; Damaged Nerve (Protein Deposits & Chemo Effect).

Two-column comparison table of Multiple Myeloma versus Waldenström's, with a fundus photograph showing engorged retinal veins.
13 / 15

Differential Diagnosis: Waldenström's Macroglobulinemia

Multiple MyelomaWaldenström's
IgG or IgAIgM (Pentameric – Large Molecule)
Lytic Bone Lesions presentHyperviscosity Syndrome
Organomegaly (Spleen/Liver)
NO Lytic Bone Lesions

Fundus image: Retinal Vein Engorgement ('Sausage Link' effect due to hyperviscosity).

Diagnostic criteria checklist with three checked items and a Patient's Verdict box, beside a bone marrow smear showing plasma cells.
14 / 15

Confirming the Diagnosis: The Triad

Diagnostic Criteria (Must have all three):

  • Monoclonal Protein: M-Spike > 3 g/dL (or Bence Jones protein in urine)
  • Bone Marrow Clones: Biopsy showing >10% CD138+ Plasma Cells
  • End Organ Damage: Presence of CRAB features

The Patient's Verdict

  • M-Spike 60g/L [Check]
  • Anemia + Renal + Hypercalcemia [Check]

Diagnosis: Symptomatic Multiple Myeloma requiring treatment.

Summary slide with four bulleted points on demographics, incidence, etiology, and key takeaway, beside an illustration of clustered plasma cells.
15 / 15

Summary & Epidemiology

  • Demographics: Median age at diagnosis 65–70 years. Slight male predominance.
  • Incidence: Represents 1% of all malignancies and 10% of hematologic malignancies.
  • Etiology: Generally unknown; links to radiation, benzene, and chronic antigen stimulation.
  • Key Takeaway: Recognize the progression from asymptomatic MGUS to the toxic, end-organ effects of Symptomatic Myeloma (CRAB).

Source: American Society of Hematology. Kyle RA, et al. Mayo Clin Proc. 2003;78:21-33.