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Clinical Pathology > Myeloma and lymphoma > Flashcards

Myeloma and lymphoma Flashcards

1
Q

where does the first stage of B cell differentiation take place

A

bone marrow.

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2
Q

what happens to B cells in the first stage of differentiation.

A

pro B cells form naïve B cells.
gain surface immunoglobulins
each B cell is committed to a single light chain (kappa or lambda)

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3
Q

what are 2 light chains in B cell called

A

kappa and lambda.

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4
Q

the first stage of B cell differentiation is also known as

A

antigen independent stage.

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5
Q

where does the second stage of B cell differentiation take place.

A

inside the lymph organs- lymph nodes

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6
Q

what is the second stage of B cell differentiation also known as

A

antigen dependent stage.

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7
Q

what happens in the second stage of cell differentiation

A

Mature naïve B cells develop into proliferating blast cells after encountering an antigen or T cell activation, and here they apoptose, become short-lived plasma cells or enter the germinal centre.

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8
Q

where does somatic hypermutation and heavy class switching occur

A

germinal centre in response to antigen presentation.

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9
Q

The process by which naïve B-cell blasts become either plasma or memory B-cells involve four steps which are

A 
proliferation
immunoglobulin somatic hypermutation and class switching, selection and differentiation.
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10
Q

what protein is needed to form plasma blasts

A

NF-kB

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11
Q

what B cells which undergo somatic hypermutations are known as

A

centrocytes/ centroblasts.

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12
Q

define somatic hypermutation

A

A process by which the Mature B cells undergo mutation making them more or less specific to the antigen which they were presented with.
If the mutation is not favourable the cell will undergo apoptosis.

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13
Q

what molecule are immunoglobulins made up of

A

glycoprotein.

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14
Q

immunoglobulins are composed of how many polypeptide chains

A

two “light chains” and two “heavy chains”

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15
Q

what tip of bond holds the light and heavy chains of an immunoglobulin together

A

covalent disulphide bonds

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16
Q

what are the 5 main types of heavy chains

A

IgG, IgM, IgA, IgD, IgE-

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17
Q

define protein electrophoresis

A

laboratory technique whereby serum is placed in a gel and exposed to an electric current

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18
Q

what 5 major fractions are shown on a normal antibody electrophorus

A 
Serum albumin
Alpha-1 globulins
Alpha-2 globulins
Beta glogulins
Gamma globulins- flat hump, with no peaks as all the immunoglobulin’s are produced in equal amounts.
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19
Q

When is immunofixation used

A

after the protein electrophoresis comes back with a M peak.

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20
Q

what does a immunofixation show

A

Enables the detection and identification of monoclonal immunoglobulins

21
Q

define myeloma

A

incurable malignancy of plasma cells.

22
Q

what form do all myelomas originate at

A

MGUS- monoclonal gammopathy of uncertain significance- abnormal spike on protein electrophoresis up asymptomatic.

23
Q

what organ is commonly affected in myeloma

A

kidney

MGRS- monoclonal gammopathy of renal significance- so has renal dysfunction

24
Q

define solitary plasmacytoma

A

group of plasma cells deposit e.g. in femur., not much myeloma in the bone marrow.

25
Q

what is the name given to the worst form of myeloma

A

plasma cell leukaemia- full-blown myeloma with severe symptoms

26
Q

what is the diagnostic criteria for myeloma.

A

Clonal BM plasma cells >10%( more than 10% neoplastic plasma cells in bone marrow) or biopsy-proven bony or extramedullary plasmacytoma AND any one or more of:
CRAB features
MDEs

27
Q

what are CRAB features

A

– C- hypercalcemia (177 micrimol/L.

– A- anaemia Hb

28
Q

what are the myeloma defining events.

A

– > 60% clonal plasma cells on BM biopsy
– SFLC (serum free light chain) ratio >100mg/L provided the absolute level of the involved LC is >100mg/L
– Light chains clog up the kidney.
– >1 focal lesion on MRI measuring >5mm

29
Q

how is initial management of acute kidney injury with suspected myeloma carried out.
(what investigations need to be carried out)

A
  • Blood film
  • Electrophoresis
  • Immunofixation
  • Bone marrow biopsy with
  • flow cytometry
  • start on steroids- even before diagnosis.
30
Q

what intensive therapy is provided for patients with myeloma

A

VCD-chemotherpay (given in 4 cyclic whilst you harvest patient stem cell)
GCSF- injections which helps spill stem cells form the bone marrow in t peripheral blood.
Melphalan-big chemotherapy dose resulting in neutropenia, reduced RBC and platelets and then they patient is regiven their stem cells to help them recover.

31
Q

what is the function of treatment with GCSF

A

spill stem cells form the bone marrow in t peripheral blood.

32
Q

what are the negative consequences of melphalan chemotherapy

A

neutropenia, reduced RBC and platelets

33
Q

newer drugs from the treatment of myeoma

A

Daratumumab (antiCD138)
Carfilzomib (proteosome inhibitor)
Ixazomib (proteosome inhibitor)

34
Q

what is the non-intensive therapy that is used to treat myeloma

A
  • CDTa- given initially (a= attenuated)= attenuated chemotherapy.
  • VCD- given next in small dose= aim of treatment is to prevent complications such as bone injury not cure.
  • RD (oral chemotherapy)= given after CDTa and VCD until disease progression.
35
Q

In what groups of people are non-invasive treatment for myeloma typically provided

A

elderly, immunocompromised.

36
Q

what is the initial treatment given all all patients who have suspected myeloma even if it hasn’t yet been confirmed

A

steroids

37
Q

what are patients in remission treated with

A

oral chemotherapy- RD

38
Q

what is the future of treatment of monoclonal antibodies

A

Targeted therapies
Individualised therapy
monoclonal antibodies

39
Q

what condition is commonly associated with myeloma

A

AL amyloidosis

40
Q

define AL amyloidosis

A

Amyloid light chain amyloidosis.
Neoplastic plasma cells secrete abnormal proteins which misfold and then accumulate in organs causing them to enlarge.
Light chain fragments misfold and self-aggregate to form beta-pleated fibrils

41
Q

what are the complications of AL amyloidosis

A 
Nephrotic-range proteinuria:
Mainly albumin
Small monoclonal light chain component
Cardiac and liver involvement in 30%
Peripheral neuropathy in 10%
end stage renal failure
42
Q

how does follicular lymphoma commonly present

A

painful lump in eck

43
Q

define follicular lymphoma

A

neoplastic disorder of lymphoid tissue.

44
Q

how do you acquire follicular lymphoma

A

chromosomal translocation – t(14;18) – which brings the bcl2 protooncogene under the influence of the immunoglobulin heavy-chain gene leading to over-expression of the bcl-2 protein.

45
Q

if follicular lymphoma equally present in both genders

A

yes

46
Q

Follicular International Prognostic Index (FLIPI) can be used to prognosticate lymphoma:

A
  • age >60 years
  • LDH above the limit of normal at diagnosis.
  • Hb
47
Q

is follicular lymphoma a hodgkin or non hodgkin lymphoma

A

non- hodgkin lymphoma

48
Q

In AL amyloidosis the light chains misfiled into what.

A

Light chain fragments misfold and self-aggregate to form beta-pleated fibrils

Clinical Pathology (45 decks)

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