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Life Protection > Histopathology of myeloma > Flashcards

Histopathology of myeloma Flashcards

1
Q

What is a plasma cell myeloma?

A

malignant tumour arising from plasma cells in BM
made up on monoclonal plasma cells

one of the most common haematological cancers
incidence: 10/100,000
median age @ Dx is 68yo

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2
Q

What is a plasma cell?

A

formed after B cell activation when it fully differentiates
Plasma cells are the final stage of B cell differentiation
(however, not all B cells will differentiate into plasma cells)

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3
Q

How are plasma cells formed?

A

B cell exposed to specific Ag
Clonal activation of B cell mediates transdifferentiation into plasma cell
Somatic hypermutation of plasma cell aids generating a highly specific binding site @ the F-Ab
Secreted Ig molecules released in mass (kg) by plasma cells

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4
Q

What is meant by a polyclonal immune response generated against one pathogen?

A

One pathogen is made up of a number of Ag
But one single B cell/plasma cell can only generate Ig specific to one of these Ag epitopes
Therefore, for that one pathogen there must be multiple clones of B cells produced (each targeting a distinct Ag epitope on that pathogen)
This ensures an efficiency immune response and elimination

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5
Q

Which clinical and radiological features may raise suspicion of myeloma?

A
  • bony pain
  • anaemia
  • recurrent infections
  • renal impairment
  • hypercalcaemia
  • raised ESR
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6
Q

What further testing is used in the Dx of myeloma (additional to clinical and radiological features)

A

serum/urine electrophoresis

bone marrow biopsy (aspirate and trephine)

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7
Q

How can identification of Ig markers (class and light chain type) be important in Dx of myeloma?

A

important in distinguishing malignancy from a reactive condition of BM

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8
Q

How does ‘cellular pathology’ inform Dx of myeloma?

A
  • BM infiltration by (dysplastic) plasma cells
  • Abnormal if plasma cells make up >30% of the BM cellularity (normally it would only be 2-3%)
  • Dx made in conjunction with other clinical evidence
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9
Q

Are dysplastic plasma cells always present in the BM biopsy in myeloma?

A

No
plasma cell abundance may be elevated (>30%) but cells may not be dysplastic
Infiltration itself is a warning sign that this may soon occur though
(hence why Dx is not based solely on BM trephine)

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10
Q

What 3 blood cell lineages are present in a normal BM aspirate?

A
  • RBC
  • WBC
  • Megakaryocyte
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11
Q

How do megakaryocytes become platelets?

A

cytoplasmic blebs present in megakaryocyte are released and become platelets/thrombocytes

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12
Q

How does the cellularity in BM change with a reactive condition?

A

There may be slight elevations in plasma cells
but abundance would not exceed 30%
unlike myeloma

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13
Q

How is cellularity in BM related to age?

A

Low cellularity associated with older age

Cellularity = 100 - age (yr)

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14
Q

What do plasma cells look like with H&E stain?

A

contains eccentric nucleus (not centrally placed)
this produces a ‘clock face’ caused by chromatin condensation
Also may be able to observe a perinuclear blob, where there is a slightly paler patch of cytosol surrounding the nucleus

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15
Q

What is the normal ratio of kappa: lambda light chains present in healthy individuals (in BM)?

A

2-3 kappa: 1 lambda

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16
Q

How do light chains look in a slide section following staining?

A

plasma cells producing monoclonal light chain will stain brown
Nuclei from normal cells stain as blue/purple

17
Q

What is light chain restriction?

A

in myeloma, neoplastic plasma cells will preferentially one type of light chain over the other
this skews the ratio between normal and abnormal ratios
This would not occur in reactive conditions and can be a strong indicator of a malignant neoplasm

18
Q

When looking at kappa and lambda light chains, why is a neoplastic rather than inflammatory process?

A

neoplastic plasma cells are making only one type of light chain

in reactive processes, a large number of Ig are secreted from multiple cells and would have included both lambda and kappa

neoplasms are clonal, that is they are derived from a single mutated parent cell

19
Q

What are the major criteria used for Dx of myeloma?

A
  • marrow plasmacytosis >30% (normal is 2-3% max)
  • plasmacytoma (biopsy)
  • M-component
    serum: IgG most common then IgA
    urine: Bence-Jones protein (1g/24hr)
20
Q

Which genetic markers may be investigated in plasma cells in myeloma?

A

CD56

Cyclin D1

21
Q

What are the minor criteria used for Dx of myeloma?

A
  • marrow plasmacytosis (10-30%)
  • M-component present but less than above
  • lytic bone lesions
  • reduced normal Ig (< 50% of normal)
22
Q

What are the main mechanisms by which myeloma affects patient health?

A
  • lytic lesions: impaired bone health
  • pancytopenia: caused by replacement of BM
  • paraprotein: secretory product of neoplastic plasma cells
23
Q

What is the pathogenesis of lytic lesions in myeloma? What are the consequences?

A

Appears as punched out appearance on X ray films. ‘pepper pot’ appearance when multiple lytic lesions on skull

inflammatory cytokines (IL-1B and IL-6) stimulate osteoclast activity (and inhibit osteoblast)

Promotes bone resorption, release Ca2+ (hypercalcaemia) and bone thinning

causes pain, pathological #, vertebral collapse and wedge fractures

24
Q

Where are osteoclasts derived from?

A

derived from BM monocytes

these proliferate and fuse to form MULTINUCLEATE OSTEOCLASTS

25
Q

Where are osteoblasts derived from?

A

derived from periosteum or BM stromal cells

26
Q

What signals released by osteoclasts trigger concomitant bone deposition by osteoblasts in physiology?

A

Ca2+

TGF (act on osteoblasts to promote bone deposition)

27
Q

What is pancytopenia?

A

comprises:

  • resultant immunosuppression
  • thrombocytopenia
  • anaemia
28
Q

How does paraprotein/mutated Ig mediate damage in myeloma?

A

M-component = monoclonal gamma globulin
Bence-Jones proteins in urine (75% of cases)
High [bence-jones] can mediate precipitation in renal tubules -> ATN -> AKI

29
Q

How does renal impairment in myeloma result in an acutely unwell patient?

A

hypercalcaemia -> dehydration (osmotic pressure differences)
Acute RF
Amyloid AL (deposits)
hyperviscosity syndromes (caused by paraprotein which makes blood sticky, increased ESR)

30
Q

What are the 4 main mechanisms by which renal failure occurs in myeloma?

A
  • Bence-Jones proteins: filtered through glomerulus and form protein casts in DCT causing AKI/ATN
  • free light chains can cause amyloid (AL) deposits (nephrotic syndrome)
  • hypercalcaemia (dehydration)
  • NSAIDs taken for bony pain
31
Q

What are the complications of myeloma protein/amyloid in kidneys?

A

can cause sloughing of tissue
formation of granulomas
Functional deficit to GFR etc

32
Q

What is amyloid?

A
  • any protein that has abnormally folded into a beta-pleated sheet
  • makes protein very insoluble
  • Body not able to break down amyloid
  • amyloid deposits in the extracellular spaces -> cell necrosis
33
Q

What are common sites of amyloid deposit?

A

heart
blood vessels
functional deficits: ischaemia ?

34
Q

What is amyloidosis?

A

group of conditions where there is excess deposition of amyloid tissues
body has no inflammatory/reactive response to amyloid

35
Q

What are the 4 main types of amyloid protein?

A

Amyloid AA
precursor: serum amyloid A

Amyloid A beta

precursor: amyloid precursor protein
e. g. tau protein in Alzheimer’s

Amyloid AL
Precursor: Ig light chain
most common type, seen in myeloma (caused by light chain fragments)

Amyloid ATTR
precursor: transthyretin
more commonly seen in inherited/genetic conditions. Driven by constitutive amyloid expression

36
Q

What is systemic amyloidosis?

A

generalised deposition of amyloid in multiple organs

leads to gradual organ failure
often undiagnosed until patients are really unwell (when organ damage starts)
most important organs affected: kidney, heart, GI tract,

37
Q

What are the most common types of amyloidosis?

A 
Amyloid AA (complication of chronic inflammation)
Amyloid AL (poor prognosis, observed in plasma cell disorders e.g. MGUS)
38
Q

What kind of staining can be used to visualise amyloid?

A

H&E: difficult to see, nodular deposition of pink amorphous material observed

Congo red: salmon pink coloured deposits of amyloid

Can take Congo red stained section and POLARISE under UV to observe amyloid as apple green bifringence

Polarised congo red (apple green staining) is a diagnostic marker of myeloma

39
Q

What is the prognosis of myeloma generally?

A

poor

Life Protection (30 decks)

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