Hodgkins Lymphoma Flashcards
What is Lymphoma?
class of haematological malignancy involving white blood cells. Form solid tumours in lymphatics and reticuloendothelial system. rarely found in peripheral blood
What are Hodgkin Lymphomas?
Lymphoma of B-cell origin.
Comprise a range of sub-types.
Responsible for ~15% of all lymphoma cases.
~2000 cases per year in UK
What common feature do all Hodgkin Lymphomas have?
Reed-Sternberg cells.
Reed-Sternberg cells.
Derived from B-lymphocytes.
Large cells (~50 microns). , x5 larger than normal
Bi-lobed/ multinucleated cells.
Identifying Reed-Sternberg cells.
Slightly unique clusters of differentiation, so can use immunochemistry to find cells. Much quicker
CD30 and 15 positive.
Do not express antibody.
Rare, two or three in a tissue sample is clinical significant
Where do RS Cells originate?
RS Cells originate from the germinal centres of lymphatic tissue.
Mutations of RS cells
Evidence of having undergone VDJ recombination and somatic hypermutation.
Hypersomatic mutations are believed to cripple the ability of the RS cells to express typical lymphocyte genes.
RS cells however develop hyperactive proinflammatory cascades:
NF-kB and Jak/STAT.
Lymphatic microenvironment may play a role in suppressing apoptosis in these cells!
Clinical Presentation of HL x4
Lymphadenopathy.
Night sweats.
Weight loss.
Symptoms brought about by localised infiltration of tumour
Epidemiology of HL
Accounts for approx. 1 per 200 of all cancer diagnoses in UK.
> 1600 cases per annum.
3rd most common cancer in people 15-29 years old.
> Has bimodal age distribution.
What is the geographical variation in incidence of HL?
Rare in East Asia but common in West Asia.
Aetiology of HL.
Epstein-Barr virus infection.
EBV DNA found in ~90% of HD cases.
> rates vary!
> All cases of HD in HIV patients are EBV positive.
Which EBV specific genes are strongly associated with malignancy? x3
LMP1
LMP2a
EBNA1
Investigation of HL; Specific tests
Lymph node biopsy.
Immunohistochemistry.
Investigation of HL; Non-specific tests.
Full blood count.
Serum lactate dehydrogenase.
Liver function tests.
Lactate Dehydrogenase.
Enzyme used in the reversible conversion of lactate to pyruvate.
Found in trace amounts in health in the blood.
Lactate dehydrogenase is useful as a non-specific tumour marker.
What is the Warburg Effect?
Cancer cells will preferentially convert glucose into lactic acid.
(Anaerobic respiration)
Possible explanations for Warburg Effect? x4
Low oxygen environments in tumours?
Mitochondria defects?
Mitochondria deliberately disabled?
Glycolysis provides more essential intermediaries?
Classification of HD
According to the WHO five types of HD exist.
All, but Nodular lymphocyte predominant, are variants of classical HD and are treated in the same manner.
Nodular Sclerosis Classical HD
Approximately 60-80% of HD falls into this group.
Malignant cells are found in nodules within the affected lymph node.
Recruitment of fibroblasts in lymph nodes. Produces collagen. Replaces cells but performs no functions
Nodular Sclerosis Classical HD histology
Pink cuts through cells is scar tissue
Mixed cellularity classical HD
Accounts for 15-30% of HD.
Most common form in patients with HIV.
R-S cells are found in affected lymph nodes surrounded by varied cell background.
Histology of Mixed cellularity classical HD
Characteristic inflammatory background round tumour