Case 14- Leukaemia Flashcards Preview

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Flashcards in Case 14- Leukaemia Deck (74):
1

Clonal disease

Derived from single cell in marrow (leukemia) or lymphoid tissue (lymphoma) which has undergone genetic alteration

2

Aetiology of Haematological Malignancy

Inherited/genetic alterations e.g Downs Syndrome

Environmental factors e.g
Chemicals (Benzene in AML)
Drugs ( previous chemotherapy increased AML)
Radiation
Infections - Viral : EBV and Burkitts lymphoma
Bacterial: Helicobacter pylori causes gastric MALT lymphoma

3

Control of haematopoeisis by GF

Growth factors binds to its corresponding receptor. The receptor dimerises. Binding activates JAK/STAT and PI3K (anti-apoptotic) pathways
Leads to increased transcription of particular genes. The genes that are involved in proliferation and differentiation of cells. E2F is a transcription factor needed for cell from G1 to S phase. Inhibited by Rb gene. Activated by p53.
(p53->pRB->E2F)
AKT--protein kinase that suppresses apoptosis

4

M phase

Mitosis- cell physically divides

5

Interphase

Chromosome duplicate and cell growth occurs prior to cell division

3 stages
G1, S, G2 and G0

6

G0

Cells rest prior to division

7

G1

Cell begin to commit to replication
First checkpoint occurs. If successful, cell enters S phase

8

S phase

DNA content doubles and chromosomes replicate

9

G2

Cell organelles copied and cytoplasm volume increases
Another checkpoint at G2 to ensure DNA replication has been satisfactory

10

Checkpoints

Control cell cycle
Act as brakes to co-ordinate the divisions
Check integrity of DNA--if DNA requires repair. Cell cycle progression is delayed

11

Cycling and Cdk

Two major classes of molecules controlling checkpoints

12

p53

If p53 senses DNA damage
Prevents activation of Cyclins required for movement through checkpoint
Cell cycle progression is delayed if DNA requires repair
If cannot be repaired, cell undergoes apoptosis

13

Follicular lymphoma

t(14;18)
Translocation of BCL2 gene to Ig heavy chain locus
Leads to over-expression of BCL2
BCL2 is anti-apoptotic
Results in decreased apoptosis and accumulation of malignant cells due to failure of apoptosis

14

Mechanism of apoptosis

Results from action of intracellular proteases called caspases

15

Role of BAX protein in apoptosis

p53 up regulates BAX--increases cytochrome C release
BCL2 protects cell from apoptosis
Ratio of BAX:BCL2 determines cell susceptibility to apoptosis
BAX increases permeability of mitochondrial membrane and cytochrome C release

16

Genes involved in development of cancer

Oncogenes--arise from mutation of proto-oncogene such as myc

Tumor suppressor gene such as pRB and p53

17

Epigenetic alterations

DNA methylation or deactylation of histones suppresses gene transcription

18

Fusion protein

From joining of two genes that originally coded for separate proteins
Fusion gene undergoes gene transcription and a fusion protein is formed (BCL-ABL in CML)

19

Aberrant expression of normal protein

Dysregulation results in expression of abnormal protein

BCL2 in follicular lymphoma
C-myc in Burkitts lymphoma

20

Acute leukaemia

Proliferation of cells at early stage of development
Rapid proliferation and lack of maturation--increased blasts

((Proliferation with arrest of differentiation))

21

Chronic leukaemia

Cells are able to mature
Full spectrum of maturation
Lose normal function
Accumulate due to failure of apoptosis mechanism
Increases WCC

((Proliferation with differentiation))

22

Acute vs Chronic leukaemia

ACUTE
Rapid onset
Death within weeks or months
Continued expansion of leukaemic clones without maturation or dying
Requires high dose chemotherapy

CHRONIC
Slow onset
Death in months to years
Expansion of leukaemic cells that retain their capacity to differentiate
May not require treatment

23

Chronic lymphoid leukaemia

Chronic lymphocytic leukaemia
Hairy cell leukaemia
Hodgkin Lymphoma
Non-Hodgkin Lymphoma

24

Myeloproliferative Neoplasm

Chronic myeloid leukaemia
Polycythemia Vera
Essential thrombocytosis
Primary myelofibrosis

25

WHO classification

Morphology
Immunophenotyping
Cytogenetics or karyotyping
Molecular studies--FISH, PCR

26

Immunophenotyping

Flow cytometry -- Identifying cell surface markers expressed on cell surface e.g CD13

27

Clinical effects of leukaemia

BONE MARROW failure
Bleeding --low platelets (thrombocytopenia) with or without DIC...granulocytes release pro-coagulants

Infections-- neutropenia

Anaemia (fatigue or pallor) --decreased red cell production


OTHER ORGANS
Bone pain
Gum hypertrophy
Lymphadenopathy
HSM

28

Spleen congenital abnormalities

Accessory spleens OR splenunculi
Congenital asplenia OR polysplenia

29

Hypersplenism

Association between a peripheral blood pancytopaenia and splenic enlargement
Hypersplenism occurs when there's a hyperactive spleen which results in premature removal of blood cells

30

Primary hypersplenism

Idiopathic
Marked and massive splenimegaly
Pancytopaenia
Tx: Splenectomy

31

Secondary hypersplenism

Congestion
Infection
Immune disorders
RBC abnormalities
Primary or metastatic neoplasms
Storage disorders
Amyloidosis

32

Congestive splenomegaly

Persistent elevation of splenic venous blood pressure

33

Splenomegaly

PreHepatic-- thrombosis of portal vein or splenic vein

Hepatic -- cirrhosis

Post hepatic-- raised pressure in IVC

34

Hypersplenism cause

INFECTION
Systemic infection
Bacterial infection
Viral
Malarial
Granulomatous inflammation

IMMUNE DISORDERS
Fetty's syndrome -- Rheumatoid arthritis and splenomegaly
Systemic Lupus Erythmatous

Red Blood Cell Abnormalities
Sickle cell anaemia--become stuck in spleen
Hereditary spherocytosis

Storage disorders
Niemann pick disease
Gaucher's disease
Mucopolysaccharidoses

Neoplasms

35

Non-neoplastic lymphadenopathy

Reactive hyperplasia
Lymphadenitis

36

Specific infective disorders

Granulomatous lymphadenitis
Necrotizing lymphadenitis
Follicular hyperplasia
Paracortical hyperplasia

37

Granulomatous lymphadenitis (infection)

Mtb

Toxoplasmosis
Histologival triad-- Follicular hyperplasia
Adjacent granulomas
Marginal zone B cell hyperplasia

38

Necrotizing lymphadenitis

Caused by infectious agents which lead to necrosis

Lymphogranuloma venereum
Sexually transmitted chlamydial disease
Stellate abscesses with lymph nodes surrounded by palisaded hostiocytes

39

Cat scratch disease

Bite or scratch from an infected cat
Caused by Bartonella henselae
Stellate abscesses within lymph nodes surrounded by palisaded histiocytes

40

Follicular hyperplasia

Syphillis
Occurs in any stage of acquired or congenital syphillis
Marked follicular hyperplasia
Many plasma cells in interfollicular areas

41

Paracortical hyperplasia

Infectious mononucleosis
Due to EBV

42

Specific non-infective disorders

Granulomatous lymphadenitis
Necrotizing lymphadenitis
Follicular hyperplasia
Sinus histiocytosis
Paracortical hyperplasia

43

Granulomatous lymphadenitis (non infection)

Sarcoidosis
Crohn's disease
Reaction to tumor antigen
Foreign body reaction

44

Necrotizing lymphadenitis

Kikuchi's disease

Systemic Lupus Erythematosus

45

Sinus Histiocytes

Lymph node sinuses are greatly distended by large histiocytic cells
Mixed with lymphocytes and plasma cells

46

Paracortical hyperplasia

Dermatopathic lymphadenopathy
From eczema or psoriasis
Cutaneous T cell lymphoma

47

Lymphoma

Are malignant neoplasms which arises from the cells of the immune system

Can be Hodgkin or Non-Hodgkin lymphoma

48

Hodgkin lymphoma

Painless lymphadenopathy

Presents with large neoplastic cells set in a background (Reed Sternberg cells) of reactive cells
RS cells- large cell, bilobed or two nuclei, prominent nucleolus

49

Non-Hodgkin lymphoma

Arise from B or T lymphocytes
Group includes Burkitt lymphoma

50

Hodgkin lymphoma

Reed Steenberg cells
In variable background of reactive cells (lymphocytes, plasma cells, histiocytes)

51

Reed Sternberg cells

Large cell with a large multilobated or bilobed (mirror image) nucleus
Very large eosinophilic nucleolus
Acidophilic cytoplasm

52

Classification of HL

Nodular lymphocyte predominant HL

Classical HL :
lymphocyte rich
Nodular sclerosing
Mixed cellularity
Lymphocyte depleted

53

(Nodular) lymphocyte predominant HL

Prognosis is very good
May transform into high grade diffuse large B cell lymphoma

Features
Nodular pattern
Neoplastic cells appear as popcorn variants, typical RS cells are rare.

54

Lymphocyte Rich HL

Predominantly early stage disease
Prognosis less favorable

55

Nodular sclerosing

Most common
Mediastinal involvement is common
Lacunae variants of Reed Sternberg cell are numerous, typically RS is rare
LN divided into nodules by broad bands of fibrous tissue
Nodular pattern of collagen

56

Mixed cellularity

Mummified cell- dense chromatin
Reactive component of lymphocytes, plasma cells

57

Lymphocyte depleted

Reduced number of lymphocyte
Atypical RS cells
Bizarre morphology

HISTOLOGY
Decrease in lymphocyte
Fibrosis
Increased number of RS cells


Prognosis poor

58

Non-Hodgkin lymphoma
Risk factors

Viruses- EBV, HTLV1, HHV8, HIV
Immunodeficiency: primary-- X linked immunodeficiency
Secondary-- AIDS, transplantation

59

Mature B cell neoplasm

Follicular lymphoma
Diffuse large B cell lymphoma
Burkitt lymphoma

60

Follicular lymphoma

Painless lymphadenopathy
Resembles normal follicular B cells
Indolent

t(14;18)
IgH on chr 14 and BCL-2 on chr 18
Oncogene is BCL 2

61

Diffuse large Bcell lymphoma

HIV
High grade lymphoma

62

Burkitt's lymphoma

t(8;14)
t(2;8) and t(8;22)
EBV association
Endemic-- jaw mass
Sporadic--abdominal mass
Immunodeficiency form

63

Mature T and NK neoplasms

Anaplastic large cell lymphoma
t( 2;5)

64

Human herpes viruses

HSV 1 and HSV 2
Varicella Zoster (3)
Epstein Barr Virus(4)
Cytomegalovirus (5)
HHV6 and 7
HHV8

65

Human herpes viruses

dsDNA
Large and enveloped

66

Pattern of herpes disease

Primary infection->latency->reactivation

67

Herpes simplex 1 and 2

Skin or mucous membranes

HSV 1- Oral infections or lesions
HSV 2- genital infection

68

Transmission

Virus is shed from lesions
Direct contact, kissing, genital contact

69

Clinical features of HSV 1&2

Primary
Recurrent (reactivation)
Lesions occur at site of inoculation

70

Conditions of HSV 1 and 2

Gingivo-stomatitis
Eczema herpeticum--super infection of atopic eczema or of abraded skin

71

HSV and the eye

Conjunctivitis
Keratitis - dendritic ulcer

72

Latency of HSV 1&2

Oro-facial-- trigeminal ganglion
Genital-- sacral ganglia

Reaction provoked by
Sunlight
Stress
Febrile illness
Menstruation
Immuno-suppresion

Reactivation --lytic phase

Lesions
Cold sores
Recurrent genital herpes
Recurrent keratitis

73

Neonatal HSV infection

Maternal genital herpes
Worse if mother does not have preformed antibodies

74

Encephalitis

Out of the blue, healthy individuals