Haematology: Haem malignancies, proliferative and dysplastic blood disorders (From Module 2 exam) Flashcards
Mainly SAQ revision
What disease does this blood film suggest?
- ALL
- Could also possibly be AML M0-1
What disease does the following immunophenotype suggest? Sig+, CD5+, Cyclin D1+, CD20+, CD10-, CD23-, BCL6-, MUM1-
- Mantle cell lymphoma
- (abnormal CD5 and Cyclin D1 expression)
What disease does this blood film suggest?
CLL
- Lymphocytosis
- Smear cells
What is the treatment for APML (Acute promyelocytic leukemia)?
-ATRA and arsenic
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-ATRA is All trans retinoic acid
What is the main genetic cause of Burkitt lymphoma?
-Lost regulation of c-myc
Outline clinical presentation of MDS (Myelodysplastic syndrome)
- Signs of bone marrow failure
- fatigue, infections, easy bruising
- Bone marrow hypercellular
- Cytopenia (a dysplastic change of a particular lineage causes the cytopenia of that lineage, i.e anaemia in erythroid dysplasia)
What disease does the following immunophenotype suggest? CD45+, CD13+, CD33+, CD117+, CD34+, HLA-DR+, CD19-, Tdt-
- AML M0/M1/M2
- CD34+, HLA-DR+, (Both markers of immaturity)
-What viruses can cause infectious mononucleosis?
EBV and CMV
What disease does this blood film show?
CML, in chronic phase
Myelocytes and basophils can be present
Outline the pathophysiology of CML
- Translocation occurs between chromosome 9 and 22, forming BCR-ABL1 fusion gene
- BCR-ABL1 molecule is a constitutively active tyrosine kinase
- Causes downstream activation of oncogenes, such as JAK, PI3K and RAS
- Leading to increased proliferation, survival and clonal expansion of cells with the initial t(9;22) mutation.
Outline the clinical presentation of Adult T-cell laeukaemia/lymphoma (ATL)
- Human T-cell lymphotrophic virus 1 (HTLV-1)
- Hypercalcaemia (Stones, bones, groans etc.)
- Skin rash
- Other things pertaining to ALL or NHL
How does Multiple myeloma lead to bone weakness?
- Multilpe myeloma (MM) cells overproduce RANK ligand
- Leads to activation of osteoclasts
- Imbalance of osteoblast/osteoclast activity leads to osteolytic lesions and bone weakness
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- Osteoprotegerin (OPG, regulator of normal bone formation) is downregulated (MM endocytosis)
- MM cels produce Dkk-1 which inhibit osteoblasts
- produces sclerostin, which inhibits osteoblasts
Case: A 51 year old woman was admitted to hospital showing: Asthenia(weakness), anorexia, weight loss. No significant findings on physical examination. Haemoglobin 83, WBC 6.5, platelets: 245. ESR 138 (high). IgA 14.1(high). Creatine 290 (high). See serum protein electrophoresis. CD38+, CD56+. What is the most likely diagnosis?
Multiple myeloma
Outline the causes of Marginal zone lymphoma
- Hep C
- H pylori
- Autoimmune causes
What disease does the following immunophenotype suggest? CD30+, CD15+, CD79a-, SmIg-, CD45-, CD34-, Tdt-
Hodgkin lymphoma
(CD30+, CD15+)
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You see CD30+ and CD15+, you know its hodgkins lymphome
What disease oes this immunophenotype suggest?CD45-, no SCC, CD19-, CD33+, CD7-, CD13+
-AML M0-M1
What disease does this blood film suggest?
Multiple myeloma
-Characteristic, pushed off to one side, extended cytoplasm
What are the viruses that can contribute to lymphoma?
EBV (Burkitt, Hodgkin)
HIV (Hodgkin, High grade B-cell lymphoma)
HTLV-1 (ATLL)
Hep C (Marginal zone lymphoma)
Human Herpes Virus (HHV8)
Hep B
What are the most common cytogenetic abnormalities associated with ALL?
- High hyperdiploidy (good prognosis)
- t(12;21)/ETV6-RUNX1 (Childhood, Good prognosis)
- t(9;22)/BCR-ABL1/Ph (older adults, bad prognosis)
- T-ALL: t(10;14)
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- 11q23 rearrangements/KMT2A (infants, bad prognosis)
- t(1;19)/TCF-PBX1
What is the mechanism of action of Imatinib?
- Imatinib is a tyrosine kinase inhibitor
- It binds to the ATP binding site of BCR-ABL1, preventing ATP from binding and donating it’s phosphate.
- Therefore no activation of oncogenic proteins
What disease does this blood film suggest?
Mantle cell lymphoma
-Characteristic morphology?
Outline the main subtypes of myelodysplastic syndrome
- So it’s classified into these 5 subtypes though a condition can belong to more than one I suppose
- Single lineage dysplasia
- Erythroid dysplasia
- Granulocytic dysplasia
- Megakaryocytic dysplasia
- Multiple lineage dysplasia
- Adult
- Childhood
- Ring Sideroblasts (Single lineage erythroid dysplasia)
- 5q deletion
- Excess blasts
- Excess blasts type 1 (5-9% blasts)
- Excess blasts type 2 (10-19% blasts)
What genes are involved in multiple myeloma?
- IGH gene can be fused with:
- Cyclin D1
- MMSET gene
- Maf
- All leading to overproduction of Ig
Describe the myeloid maturation sequence
Myeloblast,
Promyelocyte,
Myelocyte,
Metamyelocyte,
Band,
granulocyte (e.g Neutrophil)
What blood parameters are associated with CML?
- High white cell count
- Anaemia (Sometimes)
- platelets can be either high or low (Mostly high)
- Basophiliia
What disease does this immunophenotype suggest? CD8-, CD4+, CD7-, CD3+, CD25+, CD5+, CD19-, CD34-, Tdt-
- Adult T-cell leukaemia/lymphoma (ATLL)
- CD25+
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CD25+: ATLL
Describe the typical blood film of multiple myeloma
- Plasma cells (lymphocytes with extended cytoplasm, usually shifted in one direction.
- Granulation with pale are of ‘golgi zone’
- Roleaux formation
Case: See blood film. Immunophenotype: CD19+, CD5+, CD79b+/-, CD20+, CD2+/-, CD22+. What is the most likely diagnosis?
- CLL
- Smear cells, lymphocytosis
- CD5+, CD79b+,
What are the nucleated cells here?
Nucleated red cells/erythroblasts
What is the main clinical presentation of CML?
- Weight loss,
- Low grade fever
- Abdominal enlargement
What is the characteristic feature of multiple myeloma in a bone marrow aspirate?
>10% plasma cells
outline the pathophysiology of AML M2
- RUNX1-RUNX1T fusion causes the ineffectiveness of CBFalpha
- This leads to decreased differentation and maturation
What disease does the following immunophenotype suggest? CD45+, CD34+, Tdt+, CD20-, CD22-, CD10-, CD19-, CD7+, CD3+, CD2+, CD13-, CD33-, cytoplasmic m-.
T-ALL (T acute lymphoblastic leukaemia)
(CD7 is a t cell thing)
What disease does the following immunophenotype suggest? CD19+, CD20+, CD22+, CD79a+, CD79b+, BCL6+, CD10+(/-), Tdt-, Sig+, CD5-, CD23-, MUM1-, Monoclonal mature IgM (based on kappa:Lambda)
- Burkitt lymphoma.
- Monoclonal mature IgM (kappa 75% of cases/lambda 25% of cases)
- BCL6+ (maintains cells at germinal centre stage of development)
What disease does this lymph node histology suggest?
- ATLL
- Large T lymphocytes
- Reactive cell population (most likely eosinophils)
What are the most common cytogenetic abnormalities associated with MDS
- Del(11q) or –Y (Very good prognosis)
- Normal karyotype or del(5q) (Good prognosis)
- Del(7q) or double independent clones (intermediate)
- Inv(3) or double including -7 or 1del(7q) (Poor prognosis)
- Complex: >3 abnormalities (Very poor prognosis)
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This is really fringe knowledge you probably dont need to know for path. Just understand that particular cytogenetic abnormalities are associated with/ cause MDS
Case: 66 year old woman, 2 week history of fatigue and pallor. Full blood count showing pancytopenia: Hb 98, WBC 4, platelets 16. No family history. No hepatomegaly or lymphadenopathy. Abdominal CT, mild splenomegaly. Blood film, immature granulocytes, occasional circulating blasts, with granules. Flow cytometry: High FSC, low SCC, cCD79, MPO-, HLA-DR+, CD34+, CD19+, CD20(mostly -), CD10+, CD38-, CD19+, CD45+/-, Tdt+, CD33-, CD13 (mostly-). What is the most likely diagnosis?
- CLL, B-lineage.
- granules rule out MDS
Case: See blood film: Immunophenotype: high FCC, moderate SCC. CD19+, CD5-, CD79b+, CD20+, CD2+/-, CD22+, CD23-, CD10+, monoclonal Ig (Lambda:kappa). t(14;18). What is the most likely diagnosis?
Follicular lymphoma
(Coffee bean/ butt cells)
Herpes zoster can increase incidence of:
-CLL or Hodgkin lymphoma
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Don’t ask me how, something to do with constantly stimulating the immune cells to proliferate
The white cell shown is:
A normal large granular lymphocyte.
What is the normal range of haemoglobin?
- Male: 130-180 g/L
- Female: 115-165 g/L
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Major Key Alert
What disease does the following lymph node histology suggest?
- Hodgkin lymphoma
- Sclerosis
- Reed-sternberg cells
What disease does the following immunophenotype suggest? CD45+, CD34+, Tdt+, CD20+, CD22+, CD10(+/-), CD19+, CD7-, CD3-, CD13-, CD33-, cytoplasmic m+.
B-ALL, specifically PreB-ALL
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One of these markers make it a ‘PreB-ALL’ rather than a regular B-ALL but this is beyond path.
What disease does this blood film suggest?
- ATLL
- Pleomorphism. Flower cell morphology
How does multiple myeloma cause kidney failure?
Excess Ig (normally IgG) leads to precipitation of light chains in the renal tubules of the kidney
What haematologial malignancy is Coxiella Burnetti linked to?
Diffuse large B-cell lymphoma (Non-Hodgkin)
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no idea how or why really other than the whole ‘infection causes chronic stimulation and proliferation of immune cells leading to malignancy of those cells’ principle.
What disease does this blood film suggest
- Large cell lymphoma
- large and pleomorphic cell
What disease does this immunophenotype suggest? Large FCC, large SCC, CD117-, CD3-, CD34-, HLA-DR-, CD13+, CD33+, CD45+, CD14-
CML
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Myeloid cells are CD13+, CD33+
What disease does this blood film suggest?
- Burkitt lymphoma
- mature blasts, with no granules (lymphoid cells)
- Characteristic prominent vacuolation
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This vacuolation is pathognomonic of Burkitt’s Lymphoma