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Clinical Pathology > Lymphoma and myeloma > Flashcards

Lymphoma and myeloma Flashcards

1
Q

Is B-cell differentiation Ag dependent or independent?

A

Independent

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2
Q

Where does B-cell differentiation take place?

A

Bone marrow

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3
Q

What is the antigen-dependent stage of b-cell differentiation?

A

Mature naïve B-cells develop into proliferating blast cells after encounter with antigen and can either apoptose, differentiate into a short-lived plasma cell or enter the germinal centre (GC)

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4
Q

What is direct activation of naive B cells?

A

By antigens - cells will either apoptose, differentiate into short-lived plasma cells producing IgM - no memory or migrate into a germinal centre.

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5
Q

What is a germinal centre?

A

Formed from 3-10 naïve B-cells and eventually contains 10,000-15,000 B-cells.

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6
Q

Where do somatic hypermutation and class switching take place?

A

Germinal centre

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7
Q

What is the process by which naive B-cell blasts become either plasma or memory B cells?

A
  1. proliferation
  2. immunoglobulin somatic hypermutation
  3. class switch
  4. selection and differentiation
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8
Q

What happens during proliferation?

A

Following antigen stimulation, B-cells differentiate into centroblasts which accumulate in the dark zone of the GC; these are highly proliferative with a cell cycle that is completed within 6-12 hours. Within centroblasts, the anti-apoptopic genes eg: BCL-2 are downregulated and proapoptopic molecules eg: CD95 therefore only cells which generate highly specific receptors to the antigen in the GC will survive.

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9
Q

What happens to centroblasts to increase intraclonal diversity?

A

Somatic hypermutation of the Ig V-region.

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10
Q

What do centroblasts mature to?

A

Non-proliferating centrocytes

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11
Q

Where are centrocytes found?

A

In the light zone of the GC

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12
Q

What occurs in centrocytes?

A

Class switching - alters the Ig constant regions to IgG, IgA or IgE

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13
Q

What happens if a centrocytes Ig gene mutation results in a low affinity Ab for the given Ag?

A

Undergoes apoptosis

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14
Q

What happens if the Ig gene mutation results in increased affinity?

A

They can bind the antigen which up to now has been trapped by complelment receptors on follicular dendritic cells.

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15
Q

What do the centrocytes do with antigen once they have bound it?

A

Process the antigen, present it to T-cells which express CD40 ligand; this binds to the B-cell CD40 and rescues it from apoptosis.

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16
Q

What is required for B-cell differentiation post-GC?

A

Inactivation of BCL6

17
Q

What is one of the inactivation mechanisms of BCL6? (i.e. the one mentioned in the lecture)

A

The CD40-CD40ligand interaction stimulates centrocyte expression of IRF4 which represses BCL6

18
Q

What is protein electrophoresis?

A
  • The laboratory technique whereby serum is placed in a gel and exposed to an electric current
  • Five major fractions are normally identified: Serum albumin, Alpha-1 globulins, Alpha-2 globulins, Beta blogulins, Gamma globulins
19
Q

What is immunofixation?

A
  • Enables the detection and identification of monoclonal immunoglobulins
  • Performed when “M-spike” seen on electrophoresis
  • Serum or urine is placed on a gel and electric current is applied to separate the proteins
  • Anti-immunoglobulin antisera is added to each migration lane
  • If the immunoglobulin is present, a complex precipitated
20
Q

What is myeloma?

A

An incurable malignant disorder of clonal plasma cells

21
Q

What is the epidemiology of myeloma?

A
  • Annual incidence of 60-70 per million in the UK
  • Median age at presentation = 70 years
  • Higher incidence in Afro-Caribbean ethnic groups compared with Caucasians
22
Q

What is myeloma preceded by?

A

Monoclonal gammopathy of undetermined significance

23
Q

What are the diagnostic criteria for myeloma?

A

Clonal BM plasma cells >10% or biopsy-proven bony or extramedullary plasmacytoma AND any one or more of: CRAB features or MDEs

24
Q

What are CRAB features?

A 
C = Calcium (elevated)
R = Renal failure 
A = Anemia
B = Bone lesions.
25
Q

What are MDEs?

A

Myeloma defining events.

26
Q

What are the three myeloma defining events?

A
  • > 60% clonal plasma cells on BM biopsy
  • SFLC ratio >100mg/L provided the absolute level of the involved LC is >100mg/L
  • > 1 focal lesion on MRI measuring >5mm
27
Q

What is the effect of myeloma on the kidney?

A
  • 20-25% of patients have renal insufficiency at diagnosis - 50% have renal insufficiency at some point during their disease course
  • 50% will have persistent renal impairment despite therapy
  • 2-12% will require RRT
28
Q

How is AKI with suspected myeloma managed?

A
  • Medical emergency
  • Blood film
  • Electrophoresis
  • Immunofixation
  • Bone marrow biopsy with flow cytometry
  • STEROIDS
  • Dialysis
29
Q

What is the risk of pogression from MGUS to myeloma?

A

1% per year

30
Q

What is AL amyloidosis?

A

Amyloid light chain (AL) amyloidosis - Light chain fragments misfold and self-aggregate to form beta-pleated fibrils

31
Q

What are the features of AL amyloidosis?

A
  • Nephrotic-range proteinuria: Mainly albumin. Small monoclonal light chain component
  • Cardiac and liver involvement in 30%
  • Peripheral neuropathy in 10%
  • ESRF in 40%
32
Q

What is follicular lymphoma?

A
  • Neoplastic disorder of lymphoid tissue
  • Type of non-Hodgkin lymphoma characterised by slowly enlarging lymph nodes
  • Accounts for approximately 15% of all non-Hodgkin lymphoma diagnoses
  • Incidence rises with age
  • M=F
33
Q

What is the acquired chromosomal abnormality in the majority of cases of follicular lymphoma?

A

Translocation - t(14:18)

34
Q

What is the consequence of the t(14:18) translocation?

A

Brings the BCL2 proto-oncogene under the influence of the immunoglobulin heavy-chain gene, leading to over-expression of the BCL2 protein.

35
Q

What is the survival rate of follicular lymphoma?

A

Median survival 8-10 years

Five-year overall survival 72-77%

36
Q

What is the follicular international prognostic index (FLIPI)?

A
  • age >60 years
  • Ann Arbor stage III or IV
  • LDH above the limit of normal at diagnosis
  • Hb

Clinical Pathology (65 decks)

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