Pathology - WBCs Flashcards
Characteristic features of Haematopoetic Stem Cells include:
Pluripotency
Capacity for self-renewal
Besides congenital immunodeficiency diseases, lymphopenia is associated with which diseases/states?
HIV Viral infections Glucocorticoid or cytotoxic therapy Autoimmune disorders Malnutrition
What is the most common cause of agranulocytosis?
Drug toxicity.
Alkylating agents and anti metabolites are often at fault.
Monocytosis is associated with which conditions?
Chronic infections; TB, SBE, Malaria
Collagen vascular diseases; SLE
IBD
Eosinophilia is associated with which conditions?
Allergies, parasitic infections, drug reactions, lymphomas, vasculitides.
Follicular hyperplasia is characterised by what histological appearance?
Prominent large germinal centres (secondary follicles) surrounded by a rim of resting naive B cells (the mantle zone)
Where do B cells reside in lymph nodes?
B-cells aggregate in follicles in the outer cortex.
What are primary and secondary follicles?
What is a germinal centre?
In unstimulated lymph nodes, B-cells form primary follicles, composed of follicular dendritic cells.
After antigenic challenge they form secondary follicles and express IgG and IgM.
A germinal centre is the pale staining centre of a secondary follicles which contains proliferating B cells and follicular dentritic cells.
What is the importance of the germinal centre in a lymph node?
Germinal centres are greatly enlarged in secondary antibody responses and are regarded as important sites of B-cell maturation and generation of B-cell memory.
What causes follicular hyperplasia?
Inflammatory processes that activate B-cells:
RA
Toxoplasmosis
Early HIV infection
What is the mantle zone?
Simply a rim of resting, naive, B-cells
Acute viral infections cause what type of lymph node reaction?
Paracortical hyperplasia:
Large T cell partially efface B-cell follicles.
What are the 3 broad categories of white cell neoplasm?
Lymphoid: B, T, NK cells neoplasms
Myeloid: AMLs, Myelodysplasias, chronic myeloproliferative disorders.
Histiocytoses: Macrophage or dendritic neoplasms.
Which 3 viruses are associated with white cell malignancies?
Human T Cell Leukaemia Virus 1:
Associated with adult T cell leukaemia
Ebstein Barr Virus:
Subset of Burkitt’s. 30-40% of HL. B-cell lymphomas and NK lymphomas.
Human Herpes Virus-8:
Large B-cell lymphomas.
H. pylori is associated with what malignancy?
Coeliac’s is associated with what malignancy?
Gastric B-cell lymphoma.
Intestinal T-cell lymphoma.
How can we distinguish lymphoid reactivity versus malignancy?
Reactive lymphocytosis is polyclonal, lymphoid neoplasms are monoclonal.
ALL are neoplasms of what cell type?
Immature precursor B (85%) or precursor T lymphoblasts.
Pre-T ALL tends to occur in which population?
Adolescent boys as thymic lymphoma (50-70% of cases)
Are single gene mutations sufficient to cause ALL?
Explain.
No. Additional, complementary mutations, which typically increase survival or proliferation are necessary to convert a pre-leukaemic clone to full blown malignancy.
Peak incidence for B cell ALL?
Peak incidence for T cell ALL?
3 years
Adolescence
Both occur less frequently in adults.
Pathognomonic features of CLL/SLL?
Proliferation centres (clusters of mitotically active cells).
Smudge cells are often present but not pathognomonic.
Prognosis of ALL?
With aggressive chemo: 95% of children achieve remission, 75-85% are cured.
Age less than 2 or greater than 10 or t9:22 chromosome are poor prognostic features.
Prognosis of CLL?
Variable: median survival is 4-6 years. May be up to 10.
With transformation: 1 year.
What is Richter syndrome?
Transformation of CLL to diffuse Large B-cell Lymphoma. Occurs in 5-10% of CLL cf prolymphocytic transformation in 15-30%. Bad news.
Centrocytes and centroblasts are features of which type of lymphoma?
Follicular lymphoma.
Which 2 chromosomal rearrangements are common in DLBCL?
- 30% have translocations involving the BCL6 locus, a growth regulator and silencer of p53.
- 1-20% have t(14:18) which leads to over expression of anti-apoptotic BCL2.
Despite being histologically identical, what are the 3 types of Burkitt’s lymphoma?
African (endemic)
Sporadic
HIV associated
With which WBC neoplasm is “starry sky” appearance associated with?
Burkitt’s lymphoma.
Apoptotic cells ingested by scattered macrophages produce this appearance.
Burkitt’s lymphoma is associated with which translocation?
c-MYC (chromosome 8) translocation.
Increases c-MYC expression, may suppress p53
What are Bence Jones Proteins?
Free L chains (small enough) arising from neoplastic cells that end up in the urine.
As opposed to NHL ( which occurs in extra nodal sites and spreads unpredictably), Hodgkin’s lymphoma…
Arises in a single node or chain and spreads in a predictable way to anatomically contiguous lymphoid tissue.
HL is characterised by what histological feature?
Reed-Sternberg cells in a background of reactive, non-neoplastic inflammation.
(RS cells can occur with EBV, NHL)
RS cells of HL fail to express what?
Most B-cell specific genes, including Ig
What are Auer rods?
Red-staining, per oxidase positive, needle-like structures present on myeloblasts.
What is the most common pathogenetic feature of myeloproliferative disorders?
Mutated, constitutively active tyrosine kinases.
CML is distinguished from other MPDs by what?
The presence of a chimeric, constitutively active BCR-ABL tyrosine kinase.
CML is associated with which chromosomal abnormality?
In more than 90% of CML, the BCR-ABL fusion gene is generated t(9;22).
Termed the Philadelphia chromosome.
CML is curable with?
CML is treatable with?
Allogenic BMT during the stable period.
Imatinib sustains haematolic remissions in 90% of patients.
What mutation underlies PCV and ET?
Activating mutations in the JAK2 tyrosine kinase pathway.
What is the most common cause of death in multiple myeloma?
Infection by pyogenic organisms.
