Malignancy Flashcards by Kerry Hendrie

Outline the kinetics/processes that occur in normal haemopoiesis

Self-renewal
Proliferation
Differentiation (lineage commitment)
Maturation
Apoptosis

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What happens in malignant haemopoiesis?

Increased numbers of dysfunctional cells, due to one or more of
 increased proliferation
 lack of differentiation
 lack of maturation
 lack of apoptosis

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How does acute leukaemia affect normal haemopoeitic processes? What do the cells look like?

Proliferation of abnormal progenitors with block in differentiation/ maturation, therefore abnormal looking cells

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How do chronic myeloproliferative disorders affect normal haemopoeitic processes? What do the cells look like?

Proliferation of abnormal progenitors with NO block in differentiation/ maturation, therefore normal looking cells

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What causes haematological malignancies?

Genetic, epigenetic and environmental interactions causing the expression of driver mutations (chromosome change) which pass onto daughter cells

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Driver mutations select clones. Normal haemopoeisis is monoclonal/ polyclonal.

Polyclonal - involves input from different populations of cells

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Driver mutations select clones. Malignant transformation is monoclonal/ polyclonal.

Monoclonal - involves input from a single clone

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How are types of haematological malignancies classified?

Lineage (myeloid/lymphoid)
Developmental stage (precursor/lymphocyte/plasma)
Anatomical site involved (blood, lymph node))

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Leukaemias involve the blood, whereas lymphomas involve the lymph node. What is the exception to this?

Chronic lymphocytic leukaemia involves the blood and the lymph nodes

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What type of leukaemias and lymphomas are histologically and clinically more aggressive?

Acute leukaemias

High grade lymphomas

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List histological features of aggression

Large cells
High nuclear-cytoplasmic ratio
Prominent nucleoli
Rapid proliferation

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State the main feature of clinical aggression

Rapid progression of symptoms

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What is the main difference between acute and chronic leukaemia?

Acute leukaemia shows failure of normal bone marrow function

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List the main haematological malignancies

Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
Lymphoma (Hodgkins or Non-Hodgkins)
Myeloma

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What is acute leukaemia?

Rapidly progressive clonal malignancy of marrow/blood with cell maturation defects

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State the histological findings of acute leukaemia on blood film or bone marrow aspirate

Excess of blasts (>20%) in peripheral blood or marrow

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What may the blood results show in an acute leukaemia?

Reduced or loss of normal haemopoietic reserve

Anaemia, thrombocytopaenia, neutropaenia

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State the two types of acute leukaemia

Acute myeloid leukaemia (plasma cells in marrow)

Acute lymphoblastic leukaemia (lymphoid precursors)

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Which haematological malignancy is more common in the elderly?

Acute myeloid leukaemia (over 60s)

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Which haematological malignancy is the most common childhood cancer?

Acute lymphoblastic leukaemia, a malignant disease of lymphocytes

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Give two distinct clinical features of AML subgroups

DIC

Gum infiltration

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List some clinical features of acute lymphoblastic leukaemia

Anaemia
Infection
Bleeding
CNS involvement
Bone pain

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List investigations for acute leukaemia

Blood count
Blood film (abnormal blasts)
Coagulation screen
Bone marrow aspirate
Immunophenotyping

What is the diagnostic feature of AML seen on blood film?

Auer rods (elongated needles seen in the cytoplasm of myeloid leukemic blasts)

What investigation for acute leukaemia is diagnostic of the particular subtype?

Immunophenotyping

How is acute leukaemia treated?

Curative chemotherapy (AML more intensive) Stem cell transplantation Targeted treatments

What are the problematic consequences of bone marrow suppression treatment for leukaemia?

Anaemia Neutropenia (infections) Thrombocytopenia (bleeding)

What type of infection is most common in bone marrow suppression treatment for leukaemia? How is it treated?

Gram negative bacterium related sepsis | Broad spectrum antibiotics as soon as fever

If an infection is resistant to antibiotics, what type of infection in leukaemia should be suspected?

Fungal infection

What is the prognosis like in acute leukaemia?

Man go into remission but later relapse

List early side effects of chemotherapy

``` Nausea, vomiting Hair loss Liver, renal dysfunction Tumour lysis syndrome Infection ```

List late side effects of chemotherapy

Infertility | Cardiomyopathy with anthracyclines

List some causes of lymphadenopathy and give examples

Lymphoma (Hodgkin's disease) Infection (viral e.g. glandular fever, bacterial e.g. TB) Metastatic cancer (breast, lung, ovarian) Connective tissue disease (sarcoidosis, SLE)

What is the classic presentation of Hodgkin's lymphoma?

Drinking alcohol causes painful lymph nodes, especially in chest

List symptoms to ask about if a patient complains of lymphadenopathy

``` Night sweats Weight loss Itch without rash Alcohol-induced pain Fatigue ```

What are the two main types of lymphadenopathy it is important to differentiate between?

Regional lymphadenopathy | Generalised lymphadenopathy

Describe the nature of viral lymphadenopathy, commenting on tenderness, consistency, surface appearance, skin inflammation and tethering

``` Tenderness: yes Consistency: hard Surface: smooth Skin inflammation: no Tethering: no ```

Describe the nature of bacterial lymphadenopathy, commenting on tenderness, consistency, surface appearance, skin inflammation and tethering

``` Tenderness: yes Consistency: hard Surface: smooth Skin inflammation: yes Tethering: maybe ```

Describe the nature of lymphoma, commenting on tenderness, consistency, surface appearance, skin inflammation and tethering

``` Tenderness: no Consistency: soft Surface: smooth Skin inflammation: no Tethering: no ```

Describe the nature of metastatic lymph nodes, commenting on tenderness, consistency, surface appearance, skin inflammation and tethering

``` Tenderness: no Consistency: hard Surface: irregular Skin inflammation: no Tethering: yes ```

What sampling/biopsy methods are used for lymph nodes?

Core biopsy | FNA aspirate is usually not enough

Lymphoma can be diagnosed by CT. True/ False?

False | Looks very similar to metastatic malignancy

List the methods used to assess lymph node pathology

``` Histology (architecture) Immunohistochemistry of solid node Immunophenotyping of blood or marrow Cytogenic analysis (G banding, FISH) Molecular analysis ```

What histological pattern is characteristic of Hodgkin's lymphoma?

Nodular sclerosing

What is the difference between immunohistochemistry and immunophenotyping?

Immunohistochemistry looks at pattern of proteins on surface of lymphoma cells from a solid sample whereas immunophenotyping uses a liquid phase

What is the purpose of cytogenic analysis?

Looks for specific patterns of chromosome abnormality in certain lymphomas

What is the purpose of molecular analysis?

Looks at patterns of gene expression, and which are switched on or off

Describe the immunohistochemistry of Hodgkin's lymphoma

CD30 Reed Sternberg cells Look like boobs Few tumour cells

Describe the immunohistochemistry of non-Hodgkin's lymphoma

CD20 cells | Many tumour cells

List types of lymphoma

Hodgkin's lymphoma T cell Non-Hodgkin's lymphoma B cell Non-Hodgkin's lymphoma Burkitt's lymphoma (B cell cancer, very aggressive) Mantle cell lymphoma (abnormal B cells) Marginal zone NHL (B cells in wrong place)

Chronic lymphocytic leukaemia typically presents asymptomatically. True/False? What are the signs/symptoms to look out for?

True | Lymphadenopathy, splenomegaly (in 50% of cases), and shortness of breath and fatigue

What is the characteristic histopathological sign of CLL?

Smudge or smear cells

List causes of lymphocytosis

Viral infection Pertussis Childhood response to infection Chronic lymphocytic leukaemia

What is a diagnostic test to differentiate between NHL and HL ?

Node biopsy

How is lymphoma staged?

Using CT and PET scan: 1: one lymph node group 2: two lymph node groups on same side of diaphragm 3: two or more above or below the diaphragm 4: infiltration of other organs