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MBD And M&I Sem 4 > Introduction to Lymphoid Malignancies > Flashcards

Introduction to Lymphoid Malignancies Flashcards

1
Q

For the following conditions, list the corresponding normal cells:

  • Acute Lymphoblastic Leukaemia (ALL)
  • T-ALL
  • Lymphoma
  • T-cell Lymphoma
  • Chronic Lymphocytic Leukaemia (CLL)
  • Myeloma
A

Acute Lymphoblastic Leukaemia (ALL): B-cell precursors in the bone marrow.

T-ALL: T-cell precursors in the bone marrow or thymus.

Lymphoma: B-cells in secondary lymphoid organs.

T-cell Lymphoma: T-cells in the secondary lymphoid organs.

Chronic Lymphocytic Leukaemia (CLL): Mature circulating B-cells.

Myeloma: Ig-secreting plasma cells in the bone marrow.

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2
Q

Describe the presentation and epidemiology of ALL.

A

PRESENTATION:

  • usually non-specific symptoms of bone marrow suppression
  • symptoms of organ infiltration more often in advanced disease

EPIDEMIOLOGY:

  • commonest leukaemia in children <10 years old
  • but majority of patients are >40 years old
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3
Q

What are some different ways to investigate and diagnose ALL.

A

Bone marrow morphology:
- Infiltration by undifferentiated blast cells

Immunophenotyping:

  • B-cell surface markers (or T markers for T-ALL)
  • Light chain restriction

TdT positive:

  • At the join, some nucleotides randomly removed by exonuclease
  • Some nucleotides randomly added by terminal deoxynucleotidyl transferase (TdT)

Cytogenetics

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4
Q

What is the treatment of ALL?

A

Chemotherapy:

  • Induction
  • Intensification
  • CNS directed chemotherapy
  • Maintenance
  • Radiotherapy to CNS (much less common now)
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5
Q

What is the prognosis of ALL?

A

Children have a >90% cure rate.

Adults have much lower survival, because

  • different cell of origin
  • different oncogene mutations
  • older patients do not tolerate intensive treatment
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6
Q

Describe the presentation and epidemiology of Hodgkin’s Lymphoma.

A

PRESENTATION: enlarged lymph node(s)

EPIDEMIOLOGY:

  • peak incidence in young adults
  • possible association with Epstein Barr Virus (EBV) aka Human Herpes Virus 4 (HHV4)
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7
Q

Describe the histopathology of Hodgkin’s Lymphoma.

A

It is a clonal B-cell malignancy that develops within the lymphatic system.
The malignant Reed-Sternberg cell typically has a bi-lobed nucleus that gives an owl’s eyes appearance.

You would diagnose it via an excisional lymph node biopsy.
It spreads in an orderly fashion to adjacent nodes.

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8
Q

Describe the treatment and prognosis of Hodgkin’s lymphoma.

A

TREATMENT:
- chemotherapy +/- radiotherapy

PROGNOSIS:
- 5 year survival, ~50-90% depending on age, stage and histology (Especially good results in young adults)

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9
Q

Describe Non-Hodgkin’s Lymphomas.

A

Because there are so many of them, they are categorized into low grade, intermediate grade and high grade.

These include T-cell lymphomas and EBV (HHV4) driven lymphomas.
Normally, people can carry the EBV virus without it affecting them as the immune system keeps it at bay. it only manages to have an effect on immuno-suppressed patients.

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10
Q

What is the relation between chromosome translocations and lymphomas?

A

Many lymphomas carry chromosome translocations involving the Ig heavy chain or light chain loci.

Ig genes are highly expressed in B-cells.
Each Ig gene has a powerful tissue specific enhancer near to the constant (C) segment.
Its normal role is activating the promoter of the rearranged segment.

In lymphomas, we get these translocations (as expected) but they don’t happen as they should.

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11
Q

What is the most common chromosome translocation in lymphomas?

A

Most cases of follicular lymphoma carry t(14;18)(q32;q31).

This juxtaposes the BCL-2 gene on chromosome 18 with the IgH locus on chromosome 14.
This causes the overexpression of the BCL-2 protein.

BCL-2 is an apoptosis inhibitor.

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12
Q

What is another chromosome translocation that high-grade lymphomas can carry?

A

Some cases of high grade lymphoma carry t(18;14)(q24;q32).

This juxtaposes the MYC gene on chromosome 18 with the IgH locus on chromosome 14.
MYC is a powerful oncogene.

We can also get MYC or BCL-2 translocations to one of the Ig light chain loci.

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13
Q

Describe the presentation and histology of a Non-Hodgkin’s Lymphoma (NHL).

A

PRESENTATION:
enlarged lymph node(s)

HISTOLOGY:

  • normal tissue architecture partially preserved
  • normal cell of origin recognisable
  • used to name lymphoma- follicular lymphoma, mantle cell lymphoma etc.
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14
Q

How would you diagnose low grade NHL?

A
  • Histology
  • Immunocytochemistry
  • Cytogenetics
  • Light chain restriction
  • PCR
    (looking for clonal Ig gene rearrangement)
    (looking for chromosome translocations e.g. t(14;18) Ig : BCL-2)
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15
Q

Describe the treatment anf prognosis of low grade NHL.

A 
TREATMENT:
- Chemotherapy
- Glucocorticoids (e.g. prednisolone)
- Radiotherapy
- Monoclonal Ab therapy
(Rituximab (anti-CD20))

PROGNOSIS:

  • Relatively indolent (slow growing)
  • Respond well to therapy
  • But hard to cure
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16
Q

Describe the presentation and histology of high grade NHL.

A

PRESENTATION:
enlarged lymph node(s)

HISTOLOGY:

  • Loss of normal tissue architecture
  • Normal cell of origin hard to determine
17
Q

How would you diagnose high grade NHL?

A

(similar to low grade)

  • Histology
  • Immunocytochemistry
  • Cytogenetics
  • Light chain restriction
  • PCR
    (for clonal Ig gene rearrangement)
    (for chromosome translocations)
18
Q

How would you treat high grade NHL?

A

(similar to low grade)

  • Chemotherapy
  • Glucocorticoids
  • Radiotherapy
  • Monoclonal Ab therapy
  • Rituximab- anti CD20
19
Q

What is the prognosis of high grade NHL?

A

It’s variable depending on type, stage and other factors.

Overall, long term survival is ~65%.

20
Q

Describe T-cell Lymphomas.

A

They’re rare. It’s usually the CD4 cells that are affected.

It often presents with skin infiltration, e.g.:

  • Sezary Syndrome
  • Mycosis Fungoides
21
Q

Describe Acute T-cell Leukaemia/Lymphoma.

A

It’s found in Japan, Caribbean and UK citizens of Caribbean origin.

It’s associated with the retrovirus HTLV-1 (human T-cell leukaemia/lymphoma virus 1) infection.

22
Q

Describe Epstein Barr Virus (EBV) Driven Lymphomas.

A

EBV or Human Herpes Virus 4 (HHV4) directly transforms B-lymphocytes in culture. This is due to the viral oncogene LMP-1.

Over half of all normal individuals carry latent EBV infection.
However, they do not develop lymphomas due to effective immune surveillance by cytotoxic T-cells.

However, in highly immunosuppressed individuals:

  • the endogenous latent EBV may transform B-cells
  • they are no longer eliminated by cytotoxic T-cells
  • the patient develops high grade lymphoma
23
Q

Who typically gets EBV Driven Lymphomas?

A

transplant patients on cyclosporine.

  • the lymphoma usually regresses on withdrawal of immunosuppression
  • but the patient may lose the graft

AIDS patientS
- although, the lymphoma may regress on successful HAARTH (highly active antiretroviral therapy)

24
Q

Describe the presentation of Chronic Lymphocytic Leukamia (CLL.)

A

It is spotted most often as incidental finding on FBC.

- Get persistent infection(s) 
due to immunosuppression.
- Low IgG, and suppression of normal B cells.
- Lymph node enlargement
- Symptoms of bone marrow suppression
25
Q

Describe the epidemiology and diagnosis of CLL.

A

EPIDEMIOLOGY:
85% of cases are >50 years old

DIAGNOSIS:

  • FBC: Lymphocytosis
  • Immunophenotyping
  • Cell surface markers
  • Light chain restriction
  • Cytogenetics
26
Q

Describe the three aspects of myeloma that give rise to its different clinical features.

A
  1. Suppression of normal bone marrow, blood cell and immune cell function
  2. Bone resorption and release of calcium
  3. Pathological effects of the paraprotein –(single monoclonal Ig in the serum- high levels – malignancy))
27
Q

Describe blood cell/immune suppression in myelomas.

A

It can lead to:

  • Anaemia
  • Recurrent infections
  • Bleeding tendency
28
Q

Describe bone resorption in myelomas.

A
  • Myeloma cells produce cytokines (esp. IL-6), which stimulate bone marrow stromal cells to release the cytokine RANKL
  • RANKL activates osteoclasts

Leads to:

  • Lytic lesions of bone
  • Bone pain
  • Fractures
  • Calcium released from bone causes hypercalcaemia
    (this leads to multiple symptoms including mental disturbance)
29
Q

Describe the effects of paraprotein in myelomas.

A
  • Precipitates of paraprotein in kidney tubules cause renal failure
  • It’s deposited as amyloid in many tissues

2% of cases develop hyperviscosity syndrome

  • Increased viscosity of blood leading to
  • Stroke
  • Heart failure
30
Q

How would you diagnose myeloma?

A
  • Serum electrophoresis to look for paraprotein
  • Urine electrophoresis (to look for Bence-Jones protein, which represents free monoclonal light chains)
  • Increased plasma cells in bone marrow
  • ESR (very high due to rouleaux formation)
  • Radiological investigation of skeleton for lytic lesions
31
Q

Describe the treatment of myelomas.

A

CHEMOTHERAPY (not curative):

  • Cytotoxic drugs
  • Glucocorticoids
  • Thalidomide analogues
  • Bortezomib

ALLOGENIC BONE MARROW TRANSPLANT:
- Only available for a small number of younger patients (<45yo, not too ill)
- Need to find an HLA (MHC) - matched donor
But potentially curative

MBD And M&I Sem 4 (62 decks)

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