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PATHOLOGY > phil -ve myeloproliferative disorders > Flashcards

phil -ve myeloproliferative disorders Flashcards

1
Q

what are myeloid cells

A

things from bone marrow – granulocytes, monocytes and RBC

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2
Q

what is polycythaemia

A

raised Hb concentration and haematocrit %

can be
* relative - lack of plasma = non-malignant
* true - excess erythrocytes

true can be
* secondary - non-malignant
* primary - myeloproliferative neoplasm

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3
Q

what are the myeloproliferative neoplasms

A

Ph (Philadelphia Chromosome)negative
* Polycythaemia vera (PV)
* Essential Thrombocythaemia (ET)
* Primary Myelofibrosis (PMF)

Ph positive
* Chronic myeloid leukaemia (CML)

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4
Q

how can you differentiate true or relative polycythaemia

A

dilution – label RBC with chromium and albumin with iodine

True – is where RBC is raised

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5
Q

causes of pseudopolycythaemia

A

alcohol
obesity
drugs

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6
Q

causes of secondary polycythaemia

A

high eyrthropoeitin levels,
expect normal feedback mechanism so when oxygen normalises EPO drops back to normal

appropriately high EPO:
* hugh altitude
* hypoxic lung disease
* cyanotic heart disease
* high affinity Hb - sickling, failure to release Ox

inappropriately high EPO:
* renal disease - cysts, tumours, inflammation - meduloblastomas
* uterine myoma
* other tumours - liver lung

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7
Q

cause of primary polycythaemia

A

low EPO
disease involving bone marrow – blood cells growing autonomously even though low EPO

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8
Q

what are the myeloid haematological malignancies

A

Acute myeloid leukaemia (blasts >20%
Myelodysplasia (blasts 5-19%)
Myeloproliferative disorders
* Essential thrombocythaemia (megakaryocyte)
* Polycythemia vera (erythroid)
* Primary myeofibrosis
* Chronic myeloid leukaemia

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9
Q

what are the lymphoid haematological malignancies

A

Precursor cell malignancy
* Acute lymphoblastic leukaemia (B & T)

Mature cell malignancy
* Chronic Lymphocytic leukaemia
* Multiple myeloma
* Lymphoma (Hodgkin & Non Hodgkin)

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10
Q

depict normal haematopoiesis

A
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11
Q

difference between myeloproliferative neoplasm and acute leukaemia

A

Myeloproliferative – extra proliferation but no impairment of diff
Acute leukaemia –more proliferation and no diff

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12
Q

what is CML an excess of

A

myeloid granulocytic and neutrophils

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13
Q

what processes are mutated in blood cancer

A

cellular proliferation
cellular differentiation
apoptosis in lymphoid malignancies -> prolongue cell survival

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14
Q

mutations involved in blood cancers

A

DNA point mutations
Chromosomal translocations
* Creation of novel Fusion gene (myeloid malignancies)
* Disruption of proto-oncogene (over expressed)

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15
Q

how are tyrosine kinases involved in myeloproloferative disorders

A

normally they:
* transmit growth signals from surface receptors to nucleus
* activated by transfer phos gps to self and downstream protein
* are held tightly in inactive state
* promote cell growth - dont block maturation

activating TK mutations ->
* expansion - increase in mature cells ie
* polycythaemia/essential thrombocytopenia/CML

JAK2 – linked kinase on EPO receptor. When receptor gets EPO = dimerase = change structure = phosphorylate kinase = pass phosphate downstream = cellular proliferation

Excess prolif due to kinase mutations

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16
Q

JAK2 mutation

A

Acquired point mutation in JAK2 – recurring single nucleotide mutation at V617F – seen in all cases of polycythaemia vera because of somatic cancer causing mutation

Occurs in ET a megakaryocyte precurser at lower freq -> essential thrombocytopenia.

Can develop malignant haemopoietic cell in myelofibrosis

If mutation there then it is true polycythaemia

17
Q

diagnosis of myeloproliferative disorders (Ph negative)

A

based on:
* clinical features
* splenomegaly/hepatomegaly

FBC +- bone marrow biopsy
EPO llevels
mutation testing - phenotype linked to acquired mutation

18
Q

epi of polycythaemia vera

A

> male
age 60yrs

19
Q

polycythaemia vera dx

A

can be incidental dx on FBC
sx
* blood hyperviscoity -> headache, light headedness, TIA, stroke, visual disturbances, fatigue, dyspnoea
* increased histamine release -> aquagenic pruritus, peptic ulceration

Test for JAK2 V617F mutation

20
Q

Rx of polycythaemia vera

A

Aim to reduce HCT : target HCT <45%
* venesection
* Cytoreductive therapy hydroxycarbamide – chemo like agents that stop cell division – if cant cope with venesection (ie older pt)

Aim to reduce risks of thrombosis
* Control HCT
* Keep platelets below 400x109/l

21
Q

what is essential thrombocytopenia

A

Chronic MPN mainly involving megakaryocytic/platelet lineage
Sustained thrombocytosis >600x109/L

22
Q

epidemiology of essential thrombocytopenia

A

bimodal - 30yrs, 55yrs
in younger gp- females more
in older gp - genders equal

23
Q

clinical presentation of essential thrombocytopenia

A

Incidental finding on FBC (50% cases) – plts >600
Thrombosis: arterial or venous – hypercoaguability
* CVA, gangrene, TIA
* DVT or PE

Bleeding: mucous membrane and cutaneous – plts might not function properly so = plt bleeding (mucous rather than deep bleeds)

Headaches, dizziness visual disturbances
Splenomegaly (modest)

24
Q

Rx for essential thrombocythaemia

A

aspirin - prevent thrombosis and strokes
Hydroxycarbamide: antimetabolite. Suppression of other cells as well. Brings plts down to normal
Anagrelide: specific inhibition of platelet formation, side effects include palpitations and flushing

25
Q

Px of essential thrombocythaemia

A

normal life span if prevent stroke etc
Leukaemic transformation in about 5% after >10 years. Increasing numbers of cell division – chance of survival advantage to subclone
Myelofibrosis also uncommon, unless there is fibrosis at the beginning

26
Q

what is primary myelofibrosis

A

A clonal myeloproliferative disease associated with reactive bone marrow fibrosis

Abnormal clone of haemopoeisis of blood cell production in bone marrow – associated with clone – abnormality is expansion of clone which will pridyce fibroblast growth stimulating factor – fibroblast respond to this and proliferate = lay down collagen

extramedullary haematopoiesis

27
Q

epidemiology of primary myelofibrosis

A

m=f
present in 7th decade
Other MPDs (ET & PV) may as terminal phase transform to PMF

28
Q

clinical presentation and dx of primary myelofibrosis

A

incidental finding
cytopenia - thrombocytopenia/anaemia
thrombocytosis
can have massive splenomegaly - Budd-Chiari syndrome
hepatomegaly
hypermetabolic state
* wht loss
* fatigue and dyspnoea
* night sweats
* hyperuricaemia

Haemopoesis cant function because fibrosed bone marrow. Haemopoeisis moves to other organs – make blood cells in liver – liver expanded with extramedullary out of the bone marrow haematopoeisis
can get haematopoietic deposits in brain and meninges

29
Q

blood film for primry myelofibrosis

A

Leucoerythroblastic picture
Tear drop poikilocytes
Giant platelets
Circulating megakaryocytes

30
Q

DNA in primary myelofibrosis

A

JAK2 or CALR mutation

31
Q

bone marrow in primary myelofibrosis

A

‘Dry tap’
Trephine – core of bone marrow find collagen:
* Increased reticulin or collagen fibrosis
* Prominent megakaryocyte hyperplasia and clustering with abnormalities
* New bone formation

32
Q

px of primary myelofibrosis

A

Median 3-5 years but very variable
Bad prognostic signs:
* Severe anaemia <100g/L
* Thrombocytopenia <100x109/l
* Massive splenomegaly

Prognostic scoring system (DIPPS)
* Score 0 – median survival 15years
* Score 4-6– median survival 1.3 years

33
Q

primary myelofibrosis rx

A

Supportive: RBC and platelet transfusion often ineffective because of splenomegaly (consumes cells)
Cytoreductive therapy: hydroxycarbamide (for thrombocytosis, may worsen anaemia)
Ruxolotinib: JAK2 inhibitor (high prognostic score cases)
Allogeneic SCT (potentially curative reserved for high risk eligible cases) - massive treatment mortality
Splenectomy for symptomatic relief: hazardous and often followed by worsening of condition – can make it better or worse

PATHOLOGY (94 decks)

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