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Module 2 > Module 2 ICA original order > Flashcards

Module 2 ICA original order Flashcards

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1
Q

What is the typical immunophenotype of AML?

A

CD13+, CD33+, CD117+, -CD 34+ (if immature cells)

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2
Q

What is the typical immunophenotype of AML M0?

A

CD13+, CD33+, CD117+, CD34+, HLA-DR+, CD7-, CD19-

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3
Q

The white cell shown is:

A

A normal large granular lymphocyte.

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4
Q

What disease does the following immunophenotype suggest? CD13+, CD33+, CD117+, CD7-, CD2- CD34-, CD41+, CD42+, CD61+.

A
  • AML M7. Acute myeloid megakaryoblastic leukaemia
  • CD41+, CD42+, CD61+ are platelet antigens.
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5
Q

What is the normal range of haemoglobin?

A
  • Male: 130-180 g/L
  • Female: 115-165 g/L
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6
Q

Describe the myeloid maturation sequence

A

Myeloblast, Promyelocyte, Myelocyte, Metamyelocyte, Band, granulocyte (e.g Neutrophil)

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7
Q

What is the normal range of white cell count?

A

3.6-11.0 109/L

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8
Q

What is the normal range of platelet count?

A

140-400 109/L

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9
Q

What is the normal range of red cell count?

A
  • Male: 4.5-6.5 1012/L
  • Female: 3.8-4.8 1012/L
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10
Q

What disease does the following immunophenotype suggest? CD13+, CD33+, CD117+, CD15+, CD11c+, CD14+, CD64+, CD34-, CD19-, CD22-, Tdt-

A
  • AML M5 acute myeloid monocytic leukaemia
  • CD15, CD11c, CD14, CD64 are monocyte markers
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11
Q

What disease does the following immunophenotype suggest? CD45+, CD34-, CD2-, CD13+, CD33+, CD117+, CD235a/Glycophorin+, CD19-

A
  • AML M6 acute erythroid leukaemia
  • CD235a/Glycophorin (erythroid marker)
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12
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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13
Q

What disease does the following immunophenotype suggest? CD7-, CD13-, CD19-, CD33+, HLA-DR-, CD117+, CD15-, CD34+

A
  • AML M3 (APML)
  • Could also be AML M0, M1, M2
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14
Q

Outline the symptoms of acute lymphoblastic/Myeloid leukaemia.

A

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

-

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15
Q

What diseases are caused by Epstein-Barr Virus?

A
  • Burkitt’s lymphoma
  • Hodgkin lymphoma
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16
Q

What haematological malignancy can coeliacs lead to?

A

-(non-hodgkin), of M.A.L.T lymphoma,

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17
Q

What haematologial malignancy is Coxiella Burnetti linked to?

A

Diffuse large B-cell lymphoma (Non-Hodgkin)

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18
Q

What are the viruses that can contribute to lymphoma?

A

EBV (Burkitt, Hodgkin)

HHV8 (ATLL)

Hep C (Marginal zone lymphoma)

HIV (Hodgkin, High grade B-cell lymphoma)

Hep B

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19
Q

What bacteria can contribute to the development of lymphoma?

A

Helicobacter pylori (MALT lymphoma)

Campylobacter jejuni

Mycobacterium tuberculosis

Borrelia burdorferi

Chlamydophila psittaci

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20
Q

What is the main translocation associated with Burkitt lymphoma?

A

t(8;14) MYC and IgH locus (90%)

(Or others involving chromosome 8)

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21
Q

What is the main translocation associated with CML?

A

t(9;22)/BCR-ABL1/Philadelphia chromosome

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22
Q

The white cell shown is:

A

An eosinophil

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23
Q

This white cell shows what?

A

Toxic granulation and vacuolisation.

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24
Q

What kind of white cell is this?

A

Atypical lymphocyte

  • Minimal chromatin condensation, lots of cytoplasm
  • Large cell with no granulation
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25
What disease does this blood film suggest?
- CLL - Lymphocytosis, smear cells, thrombocytopenia
26
What are the nucleated cells here?
Nucleated red cells/erythroblasts
27
What disease does this blood film suggest?
Multiple myeloma - Plasma cell. Paler area is golgi zone. - Roleux formation
28
What disease does this blood film suggest?
- One of the myelodysplastic syndromes - Hypogranular neutrophil - blast cell - stomatocytes
29
What disease does this blood film suggest?
AML -M2. 1 Aur rod present
30
What disease does this blood film suggest
- Large cell lymphoma - large and pleomorphic cell
31
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.
32
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
33
What blood parameters are associated with CML?
- High white cell count - Anaemia (Sometimes) - platelets can be either high or low (Mostly high) - Basophiliia
34
What disease does this blood film show?
CML, in chronic phase Myelocytes and basophils can be prewent
35
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
36
What complications can arise from TKI therapy?
- Renal impairment - Nausea and vomiting - Pancytopenia - Pleural effusion (From dasatinib)
37
What disease does this blood film show?
CML (Left shift) Myelocyte \> promyelocyte \> metamyelocyte \> Band forms
38
What disease does the following immunophenotype suggest? CD45+, CD34+, Tdt+, CD20+, CD22+, CD10+, CD19+, CD7-, CD3-, CD13-, CD33-, cytoplasmic m-
B-ALL
39
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
40
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
41
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)
42
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
43
What disease does this blood film suggest?
- ALL - Could also possibly be AML M0-1
44
What disease does this blood film suggest?
ALL -Could also possibly be AML M0-1
45
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) - 11q23 rearrangements/KMT2A (infants, bad prognosis) - t(1;19)/TCF-PBX1 - T-ALL: t(10;14)
46
Describe the typical blood count of a patient with ALL
- Anaemia - Thrombocytopenia - Neutropenia
47
Which is the most common haematological malignancy in children?
ALL
48
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)
49
Describe the typical blood count of a patient with CLL
- Lymphocytosis - Anaemia - Thrombocytopenia
50
What disease does this blood film suggest?
CLL - Lymphocytosis - Smear cells
51
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
52
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
53
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+)
54
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)
55
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)
56
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
57
What is the typical presentation of multiple myeloma?
- Back pain - Fatigue, pallor (anaemia) - Infections (eg pneumonia) - Signs of acute renal failure (polydipsia)
58
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
59
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
60
What disease does this blood film suggest?
Multiple myeloma -Characteristic, pushed off to one side, extended cytoplasm
61
What is the characteristic feature of multiple myeloma in a bone marrow aspirate?
\>10% plasma cells
62
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
63
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
64
How does Multiple myeloma lead to bone weakness?
- 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
65
What genes are involved in multiple myeloma?
- IGH gene can be fused with: - Cyclin D1 - MMSET gene - Maf - All leading to overproduction of Ig? (I think lol)
66
How does multiple myeloma cause kidney failure?
Excess Ig (normally IgG) leads to precipitation of light chains in the renal tubules of the kidney
67
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)
68
Outline clinical presentation of MDS
- 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)
69
Outline the main subtypes of myelodysplastic syndrome
- 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)
70
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)
71
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)
72
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)
73
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)
74
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.
75
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
76
Describe the typical node biopsy of Hodgkin lymphoma
- Sclerosis - Reed-Sternberg cells/Owl cells
77
What disease does the following immunophenotype suggest? CD30+, CD15+, CD79a-, SmIg-, CD45-, CD34-, Tdt-
Hodgkin lymphoma | (CD30+, CD15+)
78
What disease does the following lymph node histology suggest?
- Hodgkin lymphoma - Sclerosis - Reed-sternberg cells
79
What disease does the following lymph node histology suggest?
- Hodgkin lymphoma - Sclerosis - Reed-sternberg cells
80
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
81
Describe the typical blood count of a non-Hodgkin lymphoma
-In advanced disease there may be anaemia, neutropenia or thrombocytopenia
82
What disease does this blood film suggest?
- Burkitt lymphoma - mature blasts, with no granules (lymphoid cells) - Characteristic prominent vacuolation
83
What disease does this lymph node histology suggest?
- Burkitt lymphoma - Germinal centre cell - ‘starry sky appearance’
84
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
85
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)
86
What is the main genetic cause of Burkitt lymphoma?
-Lost regulation of c-myc
87
What disease does the following immunophenotype suggest? CD11c+, CD103+
Hairy cell leukaemia (A type of CLL)
88
What disease does this blood film suggest?
- Follicular lymphoma - Cleft/coffee bean/butt cells pathognomonic
89
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
90
What is the main cytogenetic abnormality associated with follicular lymphoma?
t(14;18) involving BCL-2 gene (Causing abberrant expression)
91
What disease does this immunophenotype suggest? SIg+, CD20+, CD5-, CD10+, CD23+/-, BCL6+, MUM1-
- Follicular lymphoma (NHL) - CD10+ main give away
92
What disease does this blood film suggest?
Mantle cell lymphoma -Characteristic morphology?
93
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
94
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
95
What is the main cytogenetic abnormality associated with Mantle Cell lymphoma?
t(11;14), Cyclin D1 overexpression (also TP53 mutation)
96
What disease does the following immunophenotype suggest? Sig+, CD5+, Cyclin D1+, CD20+, CD10-, CD23-, BCL6-, MUM1-
- Mantle cell lymphoma - (Aberrant CD5 and Cyclin D1 expression)
97
Outline the clinical presentation of Adult T-cell laeukaemia/lymphoma (ATL)
- Human T-cell lymphotrophic virus 1 (HTLV-1) - Hypercalcaemia - Skin rash - Other things pertaining to ALL or NHL
98
What disease does this blood film suggest?
- ATLL - Pleomorphism. Flower cell morphology
99
What disease does this lymph node histology suggest?
- ATLL - Large T lymphocytes - Reactive cell population (most likely eosinophils)
100
What disease does this immunophenotype suggest? CD8-, CD4+, CD7-, CD3+, CD25+, CD5+, CD19-, CD34-, Tdt-
- Adult T-cell leukaemia/lymphoma (ATLL) - CD25+
101
Outline the treatment for ATLL
Interferon and zidovudine. It’s as good as chemotherapy
102
Outline the causes of Marginal zone lymphoma
- Hep C - H pylori - Autoimmune causes
103
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.
104
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
105
What disease does this immunophenotype suggest? CD45-, no SCC, CD10 (mostly+), CD19+, CD34(mostly+), CD5-, HLA-DR(+/-)
B-ALL
106
What disease oes this immunophenotype suggest?CD45-, no SCC, CD19-, CD33+, CD7-, CD13+
-AML M0-M1
107
What disease does this immunophenotype suggest? Large FCC, large SCC, CD117-, CD3-, CD34-, HLA-DR-, CD13+, CD33+, CD45+, CD14-
CML
108
What disease is the following karyotype associated with? 46, XX, inv(16)(p13q22)
AML M4
109
Case: See blood film. Immunophenotype: CD19+, CD5+, CD79b+/-, CD20+, CD2+/-, CD22+. What is the most likely diagnosis?
- CLL - Smear cells, lymphocytosis - CD5+, CD79b+,
110
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
111
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
112
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'
113
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
114
What is the major complication of CLL?
- Autoimmune haemolytic anaemia: shown by spherocytes and polychromasia - Direct antiglobulin test would be positive
115
What is the main clinical presentation of CML?
-weight loss, low grade fever and abdominal enlargement
116
Herpes zoster can increase incidence of:
-CLL or Hodgkin lymphoma
117
A child with mediastinal mass. Most likely diagnosis?
-T-ALL | (thymus enlargement)
118
Hypogranular neutrophil, blast cell, stomatocytes. Most likely diagnosis?
MDS
119
-What viruses can cause infectious mononucleosis?
EBV and CMV
120
Presentation of tonsillar enlargement and cervical lymphadenopathy. Atypical lymphocytes and atypical mononuclear cells on blood film. Most likely diagnosis?
infectious mononucleosis.

Module 2 (4 decks)

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