Cancers of the Immune System L16-17

Question 1

What are lymphoid neoplasms?

Answer 1

Clonal expansions of lymphoid cells resulting from acquired genetic changes leading to abnormal proliferation / survival / differentiation and a selective advantage in a given microenvironment.

Question 2

List the symptoms/signs on persons with lymphoid neoplasms.

Answer 2

• Lump / lymphadenopathy
• Organ specific symptoms – extranodal lymphoma / compression / destruction (eg fractures)
• Fatigue, sweats, weight loss, breathlessness, fever, itch
• Bone marrow infiltration: – infection, anaemia, bleeding / bruising
• Autoimmune phenomena: – anaemia, bleeding / bruising

Question 3

List the risk factors for developing a lymphoid neoplasm.

Answer 3

Chance consequence of normal lymphocyte physiology (B-cell)

Viruses:

• EBV
• HTLV-1
• HHV-8

Immunodeficiency:

• genetic instability
• viral susceptibility
• immune dysregulation

Chronic immune stimulation: - autoimmune diseases

• chronic Helicobacter pylori gastritis
• coeliac disease (gluten sensitivity)

Mutagenic agents:

• radiotherapy
• chemotherapy
• pesticides

Question 4

How many types of lymphoid neoplasms have been scientifically recognised?

Answer 4

> 65.

Question 5

Oncogenic lesions in DNA are an inevitable consequence of the genetic ___1___ and mutation process of B-cell development and differentiation

B-cell ___2___ retain properties of their distinct normal cell counterparts.

B-cell ___2___ depend upon transcription factors required for their normal cell counterparts. Altered interactions between these transcription factors lead to ___3___ in differentiation.

Many B-cell ___4___ require antigen receptor signalling, either through cognate antigen or otherwise.

Answer 5

1. Recombination
2. Neoplasms
3. Blocks
4. Lymphomas

Question 6

WHICH CANCER?

• Many B-cell neoplasms retain surface BCR expression despite frequent IG-associated translocations and potential for destructive SHM.
• SHM profile of many B-cell neoplasms suggests antigen-mediated selection for functional BCR (non-random concentration of replacement mutations in CDRs vs FRs).
• Some B-cell neoplasms (eg. CLL, MCL) express closely homologous “stereotyped” BCRs (same V/D/J segments, similar CDR3 sequences, same heavy-light chain pairings) suggesting recognition of common antigens.
• Some B-cell neoplasms (eg. CLL, MALT lymphoma) express BCRs with autoantigen recognition.

Answer 6

B-cell lymphoma.

Question 7

WHICH CANCER?

• Indolent lymphoma
• Arises from acquired MALT in the context of infection or chronic inflammation

- Eg.	Helicobacter pylori gastritis (stomach)
Sjogren syndrome (salivary gland)
Autoimmune thyroiditis (thyroid gland)
Borrelia Burgdorferi infection (skin)
Chlamydia psittaci infection (orbit)

• Can treat using antibiotics

Answer 7

MALT Lymphoma.