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Clinical Pathology > 20. Intro to Lymphoid Malignancies > Flashcards

20. Intro to Lymphoid Malignancies Flashcards

1
Q

What is the difference between a lymphoma and leukaemia?

A
  • Lymphoma – cancer in the lymph/ nodes etc. ~ ‘lump’

- Leukaemia – cancer in the blood/bone marrow

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2
Q

Describe the lymphocyte development in the bone marrow.

A
  1. Haematopoietic stem cell (HSC) -> common myeloid progenitor (CMP) ~ neutrophils, red cells, platelets etc.
  2. HSC -> Common lymphoid progenitor (CLP) -> T-cell precursors (Pre-T)
  3. HSC-> CLP -> B-cell precursors (Pre-B) -> immature B-cell
    - From Pre-B to Imm-B = immunoglobulin gene rearrangement
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3
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
  • ALL: B-cell precursos in the bone marrow
  • T-ALL: T-cell precursors in teh bone marrow or thymus
  • Lymphoma: B-cells in secondary lymphoid organs
  • T-cell lymphoma: T-cells in the secondary lymphoid organs.
  • CLL: Mature circulating B-cells
  • Myeloma: Ig-secreing plasma cells in the bone marrow
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4
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 <10yo
  • But majority of patients >40 yo
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5
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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6
Q

What is treatment of ALL?

A

Chemotherapy

  • Induction
  • Intensification
  • CNS directed chemotherapy
  • Maintenance
  • (Radiotherapy to CNS)
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7
Q

What is the prognosis of ALL?

A

Children >90% cure

Adults much lower survival, because

  • Different cell of origin
  • Different oncogene mutations
  • Older patients do not tolerate intensive treatment
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8
Q

Describe the presentation and epidemiology of Hogkin’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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9
Q

Describe the histopathology of Hogkin’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 spread in an orderly fashion to adjacent nodes
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10
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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11
Q

Describe non-hodgkin’s lymphomas.

A

• Can be divided into 4 categories

  • Low grade
  • High grade
  • T-cell lymphomas
  • EBV (HHV4) driven lymphomas in immunosuppressed patients
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12
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
  • In lymphomas, we get these translocations (as expected) but they don’t happen as they should,
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13
Q

What is the most common chromosomes 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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14
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 of BCL-2 translocations to one of the Ig light chain loci

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15
Q

Describe the presentation and histology of a low grade non-Hogkin’s lymphoma (NHL)

A

Presentation- enlarged lymph node(s)

Histology

  • Normal tissue architecture partially preserved
  • Normal cell of origin recognisable
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16
Q

How would you diagnose low grade NHL?

A
  • Histology
  • Immunocytochemistry
  • Cytogenetics
  • Light chain restriction
  • PCR:
    • For clonal Ig gene rearrangement
    • For chromosome translocations e.g. t(14;18) Ig : Bcl-2
17
Q

Describe the treatment and prognosis of low grade NHL

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

Prognosis

  • Relatively indolent (slowly growing)
  • Respond well to therapy
  • But hard to cure
18
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
19
Q

How would you diagonse high grade NHL?

A 
(similar to low grade)
•Histology
•Immunocytochemistry
•Cytogenetics
•Light chain restriction
• PCR
- For clonal Ig gene rearrangement
- For chromosome translocations
20
Q

How would you treat high grade NHL?

A
  • Chemotherapy
  • Glucocorticoids
  • Radiotherapy
  • Monoclonal Ab therapy
  • Rituximab- anti CD20
21
Q

What is the prognosis of high grade NHL?

A
  • Variable depending on type, stage and other factors

- Overall long term survival ~65%

22
Q

Describe T-cell lymphomas

A
  • Rare
  • Usually CD4 cells
  • Often present with skin infiltration e.g. Sezary syndrome and Mycosis Fungoides
23
Q

Describe acute T-cell leukaemia/lymphoma

A
  • Found in Japan, Caribbean and UK citizens of Caribbean origin
  • Associated with retrovirus HTLV-1 (human T-cell leukaemia/lymphoma virus 1) infection
24
Q

Describe EBV driven lymphomas

A

•Epstein Barr Virus
•EBV or Human Herpes Virus 4 (HHV4) directly transforms B-lymphocytes in culture
Due to viral oncogene LMP-1

  • Over half of all normal individuals carry latent EBV infection
  • 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
  • No longer eliminated by cytotoxic T-cells
  • Develop high grade lymphoma
25
Q

Who typically gets EBV driven lymphomas?

A

•Transplant patients on cyclosporine

  • Lymphoma usually regresses on withdrawal of immunosuppression
  • But patient may lose the graft

•AIDS patients
- Lymphoma may regress on successful HAART (highly active antiretroviral therapy)

26
Q

Describe the presentation of chronic lymphocytic leukaemia (CLL)

A

•Most often as incidental finding on fbc
•Persistent infection(s)
- due to immunosuppression
- Low IgG, suppression of normal •B cells
•Lymph node enlargement
•Symptoms of bone marrow suppression

27
Q

Describe the epidemiology and diagnosis of CLL

A

Epidemiology
•85% of cases >50yo

Diagnosis
•FBC: Lymphocytosis
•Immunophenotyping
   - Cell surface markers
   - Light chain restriction
•Cytogenetics
28
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))

29
Q

Describe blood cell/immune suppression in myelomas

A
  • Anaemia
  • Recurrent infections
  • Bleeding tendency
30
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
  • Which activates osteoclasts

• Leads:

  • Lytic lesions of bone
  • Bone pain
  • Fractures

•Calcium released from bone causes hypercalcaemia ~ Multiple symptoms including mental disturbance

31
Q

Describe the effects of paraprotein in myelomas

A
  • Precipitates in kidney tubules cause renal failure
  • Deposited as amyloid in many tissues

•2% of cases develop hyperviscosity syndrome

  • Increased viscosity of blood leading to
  • Stroke
  • Heart failure
32
Q

How would you diagnose myeloma?

A

•Serum electrophoresis for paraprotein
•Urine electrophoresis
-Bence-Jones protein 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

33
Q

Describe the treatment of myelomas

A

•Chemotherapy (not curative)

  • Cytotoxic drugs
  • Glucocorticoids
  • Thalidomide analogues
  • Bortezomib

• Allogeneic 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
34
Q

Describe the Ig gene PCR electrophoresis.

A
  • Normally would get a smear because so much variation in the B-cells and so you will not have a single band produced.
  • If clonal B-cell = fixed band. ~ Position of the band will tell you the type of translocation that has occurred

Clinical Pathology (62 decks)

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