REVIEW BLOCK CASES - Chronic lymphocytic leukaemia, Myelofibrosis, Chronic myeloid leukaemia, Acute myeloid (myelomonocytic) leukaemia

Question 1

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Answer 1

He has a lymphocytosis with smear cells Likely that this patient may have a chronic lymphocytic leukaemia Along with the fact he is presenting in an older age group and the cytopenias can due due to CLL association with autoimmune cytopenias ie AIHA or ITP

Question 2

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Answer 2

Immunophentoyping of the peripheral blood - could identify any cell surface antigens to identify the exact cell type in the blood - ie the type of lymphocyte

Question 3

What does immunophenotyping allow us to?

Answer 3

Immunophenotyping by flow cytometry allows us to identify proteins present on the surface of the cells using monoclonal antibdies tagged with fluorescent markers These proteins are identified using the ‘cluster of differentiation’ or CD nomenclature. Different CD molecules are expressed on different cell types and at different stages of differentiation.

Question 4

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Answer 4

Tells us he has a monolconal B cell proliferation - as only the Kappa chains expressed this shows how it is monoclonal,not polyclonal The diagnosis is CLL Film is made by spreading the drop of blood across a slide and CLL cells are fragile and some can burst during this process. These appear as smeared cells.

Question 5

Q What do you predict the lymph nodes on the neck would feel like? a craggy and fixed to skin b smooth and tender c smooth and non tender

Answer 5

C -Smooth and non tender In lymphoid malignancies the nodes are usually non tender, not tethered and smooth. Craggy and fixed nodes are usually a feature of metastatic carcinoma (cells that are not normally found in a lymph node)

Question 6

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Answer 6

Due to the raised bilirubin and decreased haptoglobins (if Hb present in blood, it binds it and therefore decreases its own concentration in blood) - likely to be a haemolytic anaemia Option C COnfirmed by a direct antiglobulin test - Otpion E

Question 7

Haptoglobins are not a reliable distinguisher between intra- and extravascular haemolysis What does chronic lymphoctic leukaemia have an association with?

Answer 7

It has an association with autoimmune cytopenias

Question 8

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Answer 8

B - Leucoerythroblastic change means red and white cell precursors in the bloodstream We have come across this before - leuco =white cell, erythro=red cell, -blastic= immature So if we see immature white and red cells in the blood we call it leucoerythroblastic

Question 9

Blood film is very helpful in this case and provides a lot of useful information Look at the red cells - they do not all have the normal round shape some look like teardrops so we call them teardrop poikilocytes What are teardrop poikoilocytes often seen in? Why would there be splenomegaly?

Answer 9

These are often seen in myelofibrosis - often a sign that the cells are being squeezed out of the fibrosed bone marrow Splenogmegaly is very common in all the myeloproliferative disorders In this case it is due to the excess need for extramedullary haematopoiesis

Question 10

What test(s) would you do now to establish the diagnosis? a bone marrow aspirate and trephine b reticulocyte count c bone marrow cytogenetics d Jak 2 kinase mutation analysis of peripheral blood e peripheral blood immunophenotyping

Answer 10

a) bone marrow aspirate and trepine d) Jak 2 kinase mutation analysis of peripheral blood

Question 11

H and E shows increased cellularity and notably there is an increase in megakaryocytes that are abnormal (the big cells with large cytoplasm that make platelets) seen to make almost a long line across the middle of the slide. Reticulin stains the supporting fibres in the marrow as black and shows a marked increase in these black fibres in this patient’s marrow. This is known as reticulin fibrosis. Q Why could the doctor not get a bone marrow aspirate? Q What is the diagnosis?

Answer 11

The DRY TAP was because of the extensive reticulin fibres preventing the cells from coming away when suction was applied Diagnosis is myelofibrosis

Question 12

What serves as a JAK1and2 inhibitor recently licensed for use in myelofibroiss?

Answer 12

Rutoxlitinib

Question 13

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Answer 13

There is an extensive leucocytosis due to the myeloid lineage - neutrophilia and not the lympoid lineage

Question 14

Q Do you think the leucocytosis is reactive or a primary marrow problem? Q What might be the causes of the visual disturbance?

Answer 14

Most likely a primary problem The cause of the visual disturbance may be due to the hyperviscoisty of the blood The sticky myeloid cells are causing the blood to be very sluggish hence the much distended veins in this patient

Question 15

Q what test would you now do to establish the diagnosis? A Peripheral blood/Marrow cytogenetics B Retinal biopsy C Splenic biopsy D Peripheral blood immunophenotyping E Peripheral Blood Jak2 mutation analysis Q What would you expect to find?

Answer 15

Can see on the film that the myeloid cells are mature so no need for peripheral blood immunophenotyping to distinguish between lymphoid and myeloid lineage Would do a peripheral blood/marrow cytogenetics here Would expect to find the philadelphia chromsome on cytogenetics showing CML

Question 16

Q What is the diagnosis? Q What is the molecular basis for the diagnosis? Q What is the treatment?

Answer 16

The diagnosis is chronic myeloid leukaemia The molecular basis is that there has been a reciprocal transloaction between chromsome 9 and 22 (22 brings the bcl gene and 9 brings the abl gene) resulting in a BCR-ABL complex which has tryosine kinase activity resulting in uncontrolled proliferation Treatment would be with the tyrosine kinase inhibitor imatinib

Question 17

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Answer 17

These cells almost resemble monocyte cells

Question 18

What further test(s) would help confirm the diagnosis a Coombs’ test (direct antiglobulin test) b Reticulocyte count c Bone Marrow aspirate D Bone marrow immunophenotyping E Bone marrow cytogenetics F Liver biopsy

Answer 18

Bone marrow aspirate Bone marrow immunophenoyping Bone marrow cytogenetics

Question 19

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Answer 19

This tells us the cells are of a myeloid lineage Likely she has a subtype of acute myelomonocytic leukaemia - causes poliferation of myeloblasts and monoblasts

Question 20

Q What is the basis of the pathophysiology of this disease? A Block in maturation causing a build up of precursors B Block in cell death resulting in an in an accumulation in mature forms C Increased proliferation of stem cells resulting in production of mature progeny

Answer 20

There is a block in maturation causing build up of precursors

Question 21

The blasts have monocytic differentiation.The CD20 expression is aberrant and can be off putting (malignant cells expressing a protein their normal counterparts wouldn’t normally) How does the lineage of the abnormal cells explain the clinical presentation with abdominal pain, hepatomegaly and gum swelling?

Answer 21

Monocytes enter tissues to become tissue macrophages. Malignant monoblasts retain this tendency and can therefore enter other sites (gums a classic presentation but also lymph nodes, liver, spleen and CNS. Abdominal pain likely due to rapid enlargement of of abdominal nodes possibly with local pressure effects. Rapidity of leukaemia onset in this case explains why not anaemic I suspect. Usual presentation is pancytopenia