Week 9: Plasma Cell Dyscrasia

What are Plasma Cells?

Plasma cells are differentiated B lymphocytes that produce and secrete large amounts of antibodies, playing a crucial role in the immune response.

• aka the end stage of b cells that make antigens

What are Osteoblast?

Cells responsible in utilizing calcium in the blood to form new bones

What are Osteoclast?

Cells that break down the bone and release calcium in the blood

What is an immunoglobulin?

A monoclonal antibody produced by a plasma cell.
Made up by 1 light chain and 1 heavy chain

How many types of heavy chains are there?
What are their designated names?

There are 5 types: γ, α, μ, δ, ε
aka IgG, IgA, IgM, IgD, IgE

How many types of light chains are there?

2 types: k, λ

What is Monoclonal gammopathy?

Any abnormal production of identical antibodies

What is Plasmacytoma?

Extramedullary proliferation of plasma CW

What is Plasma Cell Neoplasms?

A neoplastic proliferation of abnormal plasma cells resulting in wa ack amount of Ig or Ig fragments
* aka unbalanced production of light / heavy chains

Where does most Plasma Cell Neoplasm occurs?

Bone Marrow

What does seg rate test for in the blood?

Roule in the blood / stacking of RBC in the blood

Why does the RBC start stacking when there’s an increase of immungloblin?

The positive charge attaches the antibodies to the RBC and keeps them close together —> results in roule rbc stacks

• think of a child holding both parent together despite them hating each other

What is Monoclonal Gammopathy of Undetermined Significance? (MGUS)

Proliferation of plasma cells, specifically serum M protein

• No CRAB

• No evidence of other B-cell disorder

What is CRAB?

C: HyperCalcemia

R: Renal insufficiency

A: Anemia

B: Bone lytic lesion

What is Plasma Cell Myeloma? Aka multiple myeloma

A BM based plasma cell neoplasm via serum monoclonal protein and skeletal destruction with osteolytic lesions

• TLDR: 1 malignant cells = TOO MANY MALIGNANT CELLS

What is the morphology characteristic of plasma cell / multiple myeloma?

PB: Roule

Bone Marrow: Plasma cells

What is the site of involvement for multiple myeloma?

The most active hematopoiesis aka the long bones :^]

What is the pathogenesis of PCM?

• Expanding Plasma cell mass

• Overproduction of Ig

• Production of osteoclast-activating factor & cytokines

• Hypercalcemia

What is the Expanding Plasma of PCM?

Abnormal marrow plasmablasts undergo continual clonal proliferation

• aka invades and stretches the cortex of the bone thus compressing adjacent neurological structure

• produces IL-6 that induces proliferation of plasma cells and osteocytes cells (breaking bone)

What are the effects of overproduction of Ig in PCM?

1) Monoclonal gammopathy

2) Hyperviscocity

3) ↓ Production of normal Ig

4) Bence-Jones Protein

5) Amyloidosis

6) Autoimmune occurrence

7) Bleeding disorders and cryoglobulins

8 ) Cryoglobulinemia

What is Monoclonal gammopathy?

Inappropriate production of abnormally large amount of useless, identical Ig, usually IgG, followed by IgA, excess of free light chains or free heavy chains

What happens when hyperviscocity occurs in the blood?

Excess Ig alters physicals characteristic of blood and increase blood viscosity —> higher resistance to flow —> lower flow to smaller blood vessels (cause clumping) —> heart ends up over worked to try and make up for the lack of blood flow

What happens when theres a decrease of production of normal Ig?

Normal function of B-Lymphocytes & plasma cells are suppressed thus leading to infection and possible death

What is Bence-Jones protein?

A protein detected mostly in the urine due to the light chain being excessively produced and filtered by the kidney

• Over worked kidneys = renal problems

What is Amyloidosis?

Fibrous extracellular protein, specifically light chain, accumulates in the organ —> leads to loss of function of said organ and can lead to death / heart failure

What happens during Autoimmune Phenomena?

Ig start targeting the host own cells —> autoimmune hemolytic anemia (AIHA)

What are the bleeding disorders and cryoglobulins involvived in PCM?

Antibodies targeting clotting factors = bleeding issues

Cryoglobulins —> Ig that precipitates on exposure to cold thus causing pain in extremities

What is cryoglobulinemia?

When your blood clots at lower temperature

What is the issue of osteoclast-activating factors/cytokines pathogenesis in PCM?

• More production of osteoclast (bone resorption) vs osteoblast (bone formation)

• Hypercalcemia due to increased bone turnover

• Increased stimulation of osteoclast —> results in increased bone destruction

What is the effect of hypercalcemia?

Free calcium in the blood alters the motility in the intestine, muscle weakness, formation of kidney stones / failure

What is Renal Insufficiency?

Excretion of monoclonal Ig obstructs / dmgs the nephrons in the kidney tissues

How does PCM cause anemia?

Due to direct marrow infiltration & replacement —> results in cell line being repressed

What are the 2 different Diagnostic Criteria of PCM? (MM)

Systemic plasma cell myeloma & Asymptomatic (smoldering) myeloma

What are the diagnostic criteria of the systemic plasma cell myeloma?

• M-protein in serum / urine

• CRAB present

• BM clonal plasma cells / plasmacytoma

What is the diagnostic criteria of the asymptomatic plasma cell myeloma?

• M-Protein in serum at myeloma lvl

• >10% plasma cells in BM

• NO CRAB

What is the lab diagnosis of PCM?

• Presence of rouleaux

• Increase seg-rate (ESR)

• increase CRP (activity of IL-6 aka oestoclast)

• Radiology

What is the blood morphology in PCM?

Rouleaux formation

Leukoerythroblastosis

• nRBC

Plasma cells in 15% of cases

What is the BM morphology in PCM?

Plasmacytosis

What is the immunophenotyping of PCM?

CD79a, CD38, CD138

What is the prognosis of PCM?

• Usually incurable but can reduce the M-spike, prolong survival rate & improve quality of life in patient w/ the disease

• Infection is the major cause of death

What is Asymptomatic (smoldering) PC myeloma?

• Inactive PCM —> no clinical symptoms

• M Protein >3 g/dL

• BM plasmacytosis 10-30%

• NO CRAB

TLDR: starting stages of PCM but not quite there yet

What is Non-secretory Myeloma?

Plasma cells synthesize Ig but do not secret Ig

• however they are still positive for monoclonal cytoplasmic Ig —> they just dont secrete them at all so theyre in the cytoplasm just not in the blood :(

What is Plasma Cell Leukemia?

When high lvl of plasma cells are circulating in the PB (not just BM) and even in extramedullary tissues

• >5-20% or 0.5-2×10^9/ L plasma cells of PB differential

What is Plasmacytoma?

Localized growth tumors

What are the 2 types of plasmacytoma?

1) Solitary plasmacytoma of bone

2) Extraosseous (extramedullary) plasmacytoma

What is the solitary plasmacytoma of bone?

Localized bone tumor with no other bone lesions (usually inside the body)

• no clinical features of PCM + no BM plasmacytosis except for the pt of lesion

What is extraosseous plasmacyotma?

Localized growth at extramedullary sites (outside the body)

What is Primary Amyoloidosis?

Fibrous light chain that deposit itself into the organ and results in progressive loss of function within said organ

• Goes from primary amyloid fibrils (made from Ig Light chains) to b-pleated sheets (secondary structure) and deposits itself into the organs

What is monoclonal light and heavy chain deposition disease?

Secretion of abnormal light and/or heavy chain which deposit in tissues causing organ dysfunction but do not form amyloid b-pleated sheets

• unlike primary amyolodiosis

What does POEMS stand for?

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes

What is Waldenstrom Macroglobumiemia?

B-cell disorder characterized by an overproduction of IgM by leukemic plasmacytoid cells —> results in hyperviscosity, hypercellular bone marrow etc

• its pretty much the same as other plasma neoplasm just done by IgM instead

What is the clinical findings of Waldenstorm Macroglobumiemia?

• Hyperviscosity

• Congestive heart failure

• Cryoglobulinemic purapura (extensive bruising)

What is Heavy Chain Disease?

A disorder where plasma cells lost their ability to synthesize light chain components