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Module 2 exam Flashcards

Mainly SAQ revision

1
Q

What disease does this blood film suggest?

A
  • ALL
  • Could also possibly be AML M0-1
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2
Q

What disease does the following immunophenotype suggest? Sig+, CD5+, Cyclin D1+, CD20+, CD10-, CD23-, BCL6-, MUM1-

A
  • Mantle cell lymphoma
  • (Aberrant CD5 and Cyclin D1 expression)
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3
Q

What disease does this blood film suggest?

A

CLL

  • Lymphocytosis
  • Smear cells
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4
Q

What is the treatment for APML?

A

ATRA and arsenic

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5
Q

What is the main genetic cause of Burkitt lymphoma?

A

-Lost regulation of c-myc

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6
Q

Outline clinical presentation of MDS

A
  • 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)
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7
Q

What disease does the following immunophenotype suggest? CD45+, CD13+, CD33+, CD117+, CD34+, HLA-DR+, CD19-, Tdt-

A
  • AML M0/M1/M2
  • CD34+, HLA-DR+, (Both markers of immaturity)
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8
Q

-What viruses can cause infectious mononucleosis?

A

EBV and CMV

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9
Q

What disease does this blood film show?

A

CML, in chronic phase

Myelocytes and basophils can be prewent

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10
Q

Outline the pathophysiology of CML

A
  • 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.
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11
Q

Outline the clinical presentation of Adult T-cell laeukaemia/lymphoma (ATL)

A
  • Human T-cell lymphotrophic virus 1 (HTLV-1)
  • Hypercalcaemia
  • Skin rash
  • Other things pertaining to ALL or NHL
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12
Q

How does Multiple myeloma lead to bone weakness?

A
  • Multilpe myeloma (MM) cells overproduce RANK ligand
  • Osteoprotegerin (OPG) is downregulated (MM endocytosis)
  • Leads to activation of osteoclasts
  • MM cels produce Dkk-1 which inhibit osteoblasts
  • produces sclerostin, which inhibits osteoblasts
  • Imbalance of osteoblast/osteoclast activity leads to osteolytic lesions and bone weakness
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13
Q

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?

A

Multiple myeloma

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14
Q

Outline the causes of Marginal zone lymphoma

A
  • Hep C
  • H pylori
  • Autoimmune causes
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15
Q

What disease does the following immunophenotype suggest? CD30+, CD15+, CD79a-, SmIg-, CD45-, CD34-, Tdt-

A

Hodgkin lymphoma

(CD30+, CD15+)

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16
Q

What disease oes this immunophenotype suggest?CD45-, no SCC, CD19-, CD33+, CD7-, CD13+

A

-AML M0-M1

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17
Q

What disease does this blood film suggest?

A

Multiple myeloma

-Characteristic, pushed off to one side, extended cytoplasm

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18
Q

What are the viruses that can contribute to lymphoma?

A

EBV (Burkitt, Hodgkin)

HIV (Hodgkin, High grade B-cell lymphoma)

HTLV-1 (ATLL)

Hep C (Marginal zone lymphoma)

Human Herpes Virus (HHV8)

Hep B

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19
Q

What are the most common cytogenetic abnormalities associated with ALL?

A
  • High hyperdiploidy (good prognosis)
  • t(12;21)/ETV6-RUNX1 (Childhood, Good prognosis)
  • t(9;22)/BCR-ABL1/Ph (older adults, bad prognosis)
  • 11q23 rearrangements/KMT2A (infants, bad prognosis)
  • t(1;19)/TCF-PBX1
  • T-ALL: t(10;14)
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20
Q

What is the mechanism of action of Imatinib?

A
  • 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
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21
Q

What disease does this blood film suggest?

A

Mantle cell lymphoma

-Characteristic morphology?

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22
Q

Outline the main subtypes of myelodysplastic syndrome

A
  • 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)
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23
Q

What genes are involved in multiple myeloma?

A
  • IGH gene can be fused with:
  • Cyclin D1
  • MMSET gene
  • Maf
  • All leading to overproduction of Ig? (I think lol)
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24
Q

Describe the myeloid maturation sequence

A

Myeloblast,

Promyelocyte,

Myelocyte,

Metamyelocyte,

Band,

granulocyte (e.g Neutrophil)

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25
What blood parameters are associated with CML?
- High white cell count - Anaemia (Sometimes) - platelets can be either high or low (Mostly high) - Basophiliia
26
What disease does this immunophenotype suggest? CD8-, CD4+, CD7-, CD3+, CD25+, CD5+, CD19-, CD34-, Tdt-
- Adult T-cell leukaemia/lymphoma (ATLL) - CD25+
27
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
28
Case: See blood film. Immunophenotype: CD19+, CD5+, CD79b+/-, CD20+, CD2+/-, CD22+. What is the most likely diagnosis?
- CLL - Smear cells, lymphocytosis - CD5+, CD79b+,
29
What are the nucleated cells here?
Nucleated red cells/erythroblasts
30
What is the main clinical presentation of CML?
-weight loss, low grade fever and abdominal enlargement
31
What is the characteristic feature of multiple myeloma in a bone marrow aspirate?
\>10% plasma cells
32
outline the pathophysiology of AML M2
RUNX1-RUNX1T fusion causes the ineffectiveness of CBFalpha This leads to decreased differentation and maturation
33
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)
34
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)
35
What disease does this lymph node histology suggest?
- ATLL - Large T lymphocytes - Reactive cell population (most likely eosinophils)
36
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)
37
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
38
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
39
Herpes zoster can increase incidence of:
-CLL or Hodgkin lymphoma
40
The white cell shown is:
A normal large granular lymphocyte.
41
What is the normal range of haemoglobin?
- Male: 130-180 g/L - Female: 115-165 g/L
42
What disease does the following lymph node histology suggest?
- Hodgkin lymphoma - Sclerosis - Reed-sternberg cells
43
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
44
What disease does this blood film suggest?
- ATLL - Pleomorphism. Flower cell morphology
45
How does multiple myeloma cause kidney failure?
Excess Ig (normally IgG) leads to precipitation of light chains in the renal tubules of the kidney
46
What haematologial malignancy is Coxiella Burnetti linked to?
Diffuse large B-cell lymphoma (Non-Hodgkin)
47
What disease does this blood film suggest
- Large cell lymphoma - large and pleomorphic cell
48
What disease does this immunophenotype suggest? Large FCC, large SCC, CD117-, CD3-, CD34-, HLA-DR-, CD13+, CD33+, CD45+, CD14-
CML
49
What disease does this blood film suggest?
- Burkitt lymphoma - mature blasts, with no granules (lymphoid cells) - Characteristic prominent vacuolation
50
Outline presentation of MALT lymphoma
- Extranodal sites - Caused by infection (H. Pylori) or autoimmune causes (Coeliacs) - Immunophenotype: SIg+, CD20+, CD5-, CD10-, CD23+/-, BCL6-, MUM1+/- - Cytogenetics: t(11;18). Activation of NFkB pathway.
51
Hypogranular neutrophil, blast cell, stomatocytes. Most likely diagnosis?
MDS
52
This white cell shows what?
Toxic granulation and vacuolisation.
53
What disease does the following immunophenotype suggest? CD7-, CD13-, CD19-, CD33+, HLA-DR-, CD117+, CD15-, CD34+
- AML M3 (APML) - Could also be AML M0, M1, M2
54
What is the typical presentation of multiple myeloma?
- Back pain - Fatigue, pallor (anaemia) - Infections (eg pneumonia) - Signs of acute renal failure (polydipsia)
55
What disease does the following immunophenotype suggest? CD11c+, CD103+
Hairy cell leukaemia (A type of CLL)
56
The white cell shown is:
An eosinophil
57
What are the clinical signs and symptoms of CLL?
- Lymphadenopathy - features of anaemia (fatigue, pallor) - Bruising/purpura from thrombocytopenia - rarely hepatosplenomegaly - Features of immune suppression (Infection)
58
What is the normal range of red cell count?
- Male: 4.5-6.5 1012/L - Female: 3.8-4.8 1012/L
59
What haematological malignancy can coeliacs lead to?
-(non-hodgkin), of M.A.L.T lymphoma,
60
What are the most common cytogenetic abnormalities associated with CLL?
- Del(6q) - Trisomy 12 - Del(13q)/miR-15a - Del(13q)/retinoblastoma gene - Del(17p)/TP53 loss - Del(11q)/ATM
61
What disease does this blood film show?
CML (Left shift) Myelocyte \> promyelocyte \> metamyelocyte \> Band forms
62
What kind of white cell is this?
Atypical lymphocyte - Minimal chromatin condensation, lots of cytoplasm - Large cell with no granulation
63
Describe the typical laboratory findings of Hodgkin lymphoma
- Normochromic, normocytic anaemia (without later bone marrow involvement) - neutrophilia (1/3 of patients) - ESR raised, CRP raised. - Raised serum LDH
64
What disease is associated with a bone marrow trephine biopsy showing a marked increase in marrow lymphocytes, a nodular pattern of lymphoid accumulation and interstitial infiltration?
CLL
65
What disease does this blood film suggest?
- MDS - White cells showing psudeo-pelger cells, agranular myelocytes an neutrophils - Red cells are usually macrocytic but can be hypochromic. - Granulocytes reduced in number and show lack of granulation - Pelger abnormality (single or bilobed nucleus) - Platelets unusual (usually reduced)
66
Case: A 38 year old woman of Caribbean origin. Rash of several years duration. Family history of ‘leukaemia’. Shortly before she had developed marked cervical lymphadenopathy and hypercalcaemia. Her skin showed plaque-like infiltrates. Flow cytometry: High SCC, CD2+, CD5+, CD7-, CD4+, CD8+, CD25+, CD71. She had also recently broken her clavicle
ATLL 'Contagious leukaemia'
67
What is the most prominent cytogenetic abnormality associated with Burkitt lymphoma?
- t(8;14) C-MYC and IgH locus (90%) - Other translocations of chromosome 8
68
What disease does this blood film suggest?
- MDS - Mononuclear megakaryocyte - Red cells are usually macrocytic but can be hypochromic. - Granulocytes reduced in number and show lack of granulation - Pelger abnormality (single or bilobed nucleus) - Platelets unusual (usually reduced)
69
What is the main translocation associated with Burkitt lymphoma?
t(8;14) MYC and IgH locus (90%) | (Or others involving chromosome 8)
70
What disease does this blood film suggest?
- One of the myelodysplastic syndromes - Hypogranular neutrophil - blast cell - stomatocytes
71
Outline the clinical presentation of Burkitt lymphoma
- Painless lymphadenopathy, normally on jaw or abdomen - History of Epstein Barr virus - Can affect abdominal organs (Sporadic Burkitt lymphoma) - Signs of pancytopenia in advanced disease
72
What disease does this blood film suggest?
- Follicular lymphoma - Cleft/coffee bean/butt cells pathognomonic
73
What are the main cytogenetic abnormalities associated with multiple myeloma?
- Del(13q) - mutations of telomere end of chromosome 14q32 (location of heavy chains, IgH) - eg. t(4;14) IGH-MMSET1
74
Describe the typical blood count of a patient with CLL
- Lymphocytosis - Anaemia - Thrombocytopenia
75
What disease is the following karyotype associated with? 46, XX, inv(16)(p13q22)
AML M4
76
What are the main sub-types of CLL?
- CLL - Prolymphocytic leukaemia (PLL) - Hairy cell leukaemia (HCL) - Plasma cell leukaemia - T cell: - Large granular lymphocytic leukaemia - T-PLL - ATLL (Can be classed as a type of CLL or lymphoma)
77
What is the normal range of white cell count?
3.6-11.0 109/L
78
What is the clinical presentation of CML (symptoms and signs)?
- Fatigue - Night sweats - Malaise and weight loss - Left upper quadrant pain - Splenomegaly - Less common (in advanced diseas) - Bone pain - Lymphadenopathy - Skin infiltration - Extra medullary mass
79
What is the major complication of CLL?
- Autoimmune haemolytic anaemia: shown by spherocytes and polychromasia - Direct antiglobulin test would be positive
80
What bacteria can contribute to the development of lymphoma?
Helicobacter pylori (MALT lymphoma) Campylobacter jejuni Mycobacterium tuberculosis Borrelia burdorferi Chlamydophila psittaci
81
Outline the treatment for ATLL
Interferon and zidovudine. It’s as good as chemotherapy
82
What is the normal range of platelet count?
140-400 109/L
83
Outline the clinical presentation of Hodkin lymphoma
- Painless lymphadenopathy, more often localised to a single nodal site - Splenomegaly - History of Epstein Barr virus or HIV-1 - Consitutional symptoms in widespread disease: weight loss, night sweats, weight loss, etc.
84
What disease does the following lymph node histology suggest?
- Hodgkin lymphoma - Sclerosis - Reed-sternberg cells
85
Which is the most common haematological malignancy in children?
ALL
86
What are the genes most commonly involved in CLL?
- P53 (bad prognosis) - Retinoblastoma gene (bad prognosis) - MiR15a - ATM gene - Loss of P53/del(17p) (bad prognosis)
87
A child with mediastinal mass. Most likely diagnosis?
-T-ALL | (thymus enlargement)
88
What disease does this blood film suggest?
- MDS - Monocytoid cells and an agranular neutrophil - Red cells are usually macrocytic but can be hypochromic. - Granulocytes reduced in number and show lack of granulation - Pelger abnormality (single or bilobed nucleus) - Platelets unusual (usually reduced)
89
What is the main cytogenetic abnormality associated with follicular lymphoma?
t(14;18) involving BCL-2 gene (Causing abberrant expression)
90
What disease does this lymph node histology suggest?
- Mantle cell lymphoma - Characteristic deformed pattern of small lymphocytes with angular nuclei - Expression of cyclin D1 can also show up - Located in mantle zone
91
What disease does the following immunophenotype suggest? CD45+, CD34-, CD2-, CD13+, CD33+, CD117+, CD235a/Glycophorin+, CD19-
- AML M6 acute erythroid leukaemia - CD235a/Glycophorin (erythroid marker)
92
In what disease may CAR-T cell therapy be effective?
-B-ALL(Specific for CD19)
93
Describe the typical blood count of a non-Hodgkin lymphoma
-In advanced disease there may be anaemia, neutropenia or thrombocytopenia
94
Describe the pathophysiology of APML
- PML-RARA fusion protein binds NCoR-HD complex - This leads to inhibition of transcription and in turn a block in cell differentiation - Retinoic acid is unable to exert it’s effect of continuing transcription
95
Describe how t(12;21) leads to ALL
- RUNX1 encodes CBFalpha, which binds to HAT (Activating transcription) - In ETV6-RUNX1 fusion, the protein cannot bind to HAT. - Therefore transcription is not activated
96
What disease does this immunophenotype suggest? CD45-, no SCC, CD10 (mostly+), CD19+, CD34(mostly+), CD5-, HLA-DR(+/-)
B-ALL
97
What disease does this blood film suggest?
AML -M2. 1 Aur rod present
98
Outline the symptoms of acute lymphoblastic/Myeloid leukaemia.
Fever, sweats, weight loss - Caused by Bone marrow failure: - tiredness, bruising and bleeding, infections/sepsis - Caused by tissue infiltration - Pulmonary infiltrates -\> Shortness of breath, hepatomegaly, splenomegaly, gum hypertrophy -
99
What disease does the following immunophenotype suggest? CD13+, CD33+, CD117+, CD7-, CD2- CD34-, CD41+, CD42+, CD61+.
- AML M7. Acute myeloid megakaryoblastic leukaemia - CD41+, CD42+, CD61+ are platelet antigens.
100
Describe the typical node biopsy of Hodgkin lymphoma
- Sclerosis - Reed-Sternberg cells/Owl cells
101
What disease does this lymph node histology (with BCL-6 staining) suggest?
- Follicular lymphoma - Germinal centre cell origin - BCL-6 stain +ve - Also BCL-2 stain +ve in follicles - Also diffusely CD10 +ve
102
What disease does the following immunophenotype suggest? CD19-, CD20- CD34-, Tdt- CD38+, CD138+, SIg-, CD7-, CD3-
- Multiple myeloma - CD38, CD138 classic plasma cell markers - MM cells don’t have SIg
103
What is the difference between MGUS, smouldering myeloma and multiple myeloma?
- MGUS: - Monoclonal serum protein: \<30g/L - BM plasma cells: \<10% of BM cells - Multiple Myeloma - Monoclonal serum protein: \>/=30g/L - BM plasma cells: \>10% of BM cells - Smouldering myeloma: - Is just asymptomatic multiple myeloma
104
What disease does this blood film suggest?
- CLL - Lymphocytosis, smear cells, thrombocytopenia
105
What disease does the following immunophenotype suggest? CD45+, CD34+, Tdt+, CD20+, CD22+, CD10+, CD19+, CD7-, CD3-, CD13-, CD33-, cytoplasmic m-
B-ALL
106
What are the lab findings associated with multiple myeloma?
- Calcium raised - Renal impairment (raised creatinine) - Anaemia (reduced Hb) - Bone lesions (osteolytic) on x-ray - monoclonal protein \>/=30mg/L - Abnormal immunoglobulins on electrophoresis (Monoclonal gammopathy). Excessive amounts of gammaglobulin - increased serum immunoglobulin-free light chains - Increased ESR
107
What disease does this blood film suggest?
ALL -Could also possibly be AML M0-1
108
What disease does the following immunophenotype suggest? CD13+, CD33+, CD117+, CD15+, CD11c+, CD14+, CD64+, CD34-, CD19-, CD22-, Tdt-
- AML M5 acute myeloid monocytic leukaemia - CD15, CD11c, CD14, CD64 are monocyte markers
109
What is the main cytogenetic abnormality associated with Mantle Cell lymphoma?
t(11;14), Cyclin D1 overexpression (also TP53 mutation)
110
What is the typical immunophenotype of AML?
CD13+, CD33+, CD117+, -CD 34+ (if immature cells)
111
What disease does the following immunophenotype suggest? CD45+, CD34+, Tdt+, CD20+, CD22+, CD10-, CD19+, CD7-, CD3-, CD13-, CD33-, cytoplasmic m-
B-ALL, specifically ProB-ALL
112
What disease does this lymph node histology (with cyclin D1 stain) suggest?
- Mantle cell lymphoma - expression of cyclin D1 - Located in mantle zone - Characteristic deformed pattern of small lymphocytes with angular nuclei
113
Outline the treatment of Multiple myeloma
- Steroids - Alkylating agents (melphalan) - Adds alkyl group to guanine residues, blocks replication, causes lymphopenia. - Proteosome inhibitors - proteosome required for protein degredation into oligopeptides/amino acids. - Blocking proteasome leads to decreased amino acids in cell, leading to decreased protein synthesis - Effective in MM as there is lots of protein production - Monoclonal Abs (daratumumab: anti CD38 antibody) - Immunomodulatory drugs (IMIDS)
114
What disease does the following immunophenotype suggest? CD34-, Tdt-, CD19+, CD20+,CD23+, CD5+, CD13-, CD33-, CD7-, CD10-, CD79b-, light chain restriction (large disparity between Lambda:kappa)
CLL -Not to be confused with mantle cell lymphoma (CD23-, Cyclin D1+)
115
What is the typical immunophenotype of AML M0?
CD13+, CD33+, CD117+, CD34+, HLA-DR+, CD7-, CD19-
116
What complications can arise from TKI therapy?
- Renal impairment - Nausea and vomiting - Pancytopenia - Pleural effusion (From dasatinib)
117
What is the main translocation associated with CML?
t(9;22)/BCR-ABL1/Philadelphia chromosome
118
What diseases are caused by Epstein-Barr Virus?
- Burkitt’s lymphoma - Hodgkin lymphoma
119
Presentation of tonsillar enlargement and cervical lymphadenopathy. Atypical lymphocytes and atypical mononuclear cells on blood film. Most likely diagnosis?
infectious mononucleosis.
120
What disease does this blood film suggest?
Multiple myeloma - Plasma cell. Paler area is golgi zone. - Roleux formation
121
Describe the typical blood count of a patient with ALL
- Anaemia - Thrombocytopenia - Neutropenia
122
What disease does this immunophenotype suggest? SIg+, CD20+, CD5-, CD10+, CD23+/-, BCL6+, MUM1-
- Follicular lymphoma (NHL) - CD10+ main give away
123
What disease does this lymph node histology suggest?
- Burkitt lymphoma - Germinal centre cell - ‘starry sky appearance’
124
What disease does this immunophenotype suggest? CD45+, some SCC, Tdt-, MPO+, CD13+, CD33+, CD117+, CD34-, HLA-DR-, CD2(+/-)
- APML - Suggested by abberant T-cell marker expression

Module 2 (4 decks)

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