Haematological (lymphatic and bone marrow, erythropoiesis)

Question 1

A 25 year old patient presents with persistent non-productive cough, temperature >38 and lymphadenopathy:

After examination and history, what are the first two investigations?

Answer 1

FBC - check for raised WCC

CXR - check for any signs of respiratory disease

Question 2

When is lymphadenopathy clinically relevant?

Answer 2

In an adult:
>1cm that isn’t related to local infection

Or >1.5cm if it is at level 2 (The tonsillar lymph node, normally bigger)

Or Any size node with persistent associated head/neck symptoms

In a child: >2cm (90% of children have irrelevant lymphadenopathy if examined)

Question 3

What investigations should be done for a suspected malignant lymph node of the neck?

Answer 3

1. Refer to ENT for full head and neck examination (inc fibreoptic endoscopy) at neck lump clinic
2. USS Imaging
3. CT, MRI or PET
4. Fine needle aspiration biopsy (cytology)
5. Core biopsy (histopathology)

Question 4

How is malignant lymphadenopathy (Hodgkin’s and non-Hodgkin’s) clinically staged?

Answer 4

Stage 1 = only one group of nodes affected e.g. submental

Stage 2 = 2 or more groups affected but restricted to one side of the diaphragm

Stage 3 = Lymphadenopathy is present above and below the diaphragm

Stage 4 = Spread beyond nodes to organs (spleen, bone, marrow, lungs, liver)

Beside the stage, a letter is given:
A - no systemic symptoms present (asymptomatic)
B - systemic symptoms present (weight loss, fever and night sweats)

e.g. a patient with cervical lymphadenopathy and night sweats would be stage 1B

Question 5

What is the Ann-arbor system?

Answer 5

Another name for the staging system of lymphoma.

Remember: the most important anatomical division in staging is the diaphragm, it decides between stage 2 and stage 3

Question 6

How do we diagnose Hodgkin’s lymphoma?

Answer 6

1. Bloods:
   WBC Increase
   Blood film (for RS cells)
   Lactic acidosis dehydrogenase (increases with high cell turnover)
   Eosinophil Increase
   ESR Increase (lots of inflammatory processes occurring in lymph nodes)
   Hb (falling means poor prognosis)
2. Lymph node core biopsy - for reed-sternburg cells (their presence confirms the diagnosis),
   We will also see lots of inflammatory infiltrative cells in the lymph node.
3. CT-thorax/abdomen/pelvis and bone scan - We will want to then use CT to stage the lymphoma (stages 2-3) and a bone scan to stage the lymphoma (stage 4)
4. LFTs - check for liver involvement

Question 7

How can we distinguish Hodgkin’s and non-Hodgkin’s lymphoma on a biopsy?

Answer 7

There are inflammatory infiltrative cells in a Hodgkin’s lymphoma biopsy.

There are no inflammatory infiltrative cells in a non-Hodgkin’s lymph node biopsy

Question 8

What are the four classifications of Hodgkin’s lymphoma?

Answer 8

Types are on a scale of increasing Reed-sternburg cell number, they progress from 1 up to 4:

1. Lymphocyte-predominant type (mostly Lymphocytes, only a few Reed-Sternburg cells)
   - 70% of cases
2. Nodular sclerosis (Bands of collagen where the increasing number of RS cells are held)
   - 20/25% of cases
3. Mixed cellularity (so many RS cells that they equal the lymphocytes)
   - 5% of cases
4. Lymphocyte depletion (less than 10% of lymphocytes present) - the worst prognosis

Question 9

Which type of Hodgkin’s lymphoma has a bad prognosis?

Answer 9

Lymphocyte depleted - when lymphocyte numbers are below 1% of their normal concentration

Question 10

How do you diagnose multiple myeloma?

Answer 10

1. Bone pain/back pain presentation in old people
2. Check blood film for rouleaux formation (red cells on each other) and subsequent raised ESR
3. Serum or urine electrophoresis monoclonal band protein band (antibodies)
4. Marrow biopsy - increased plasma cell number
5. Bone lesions on X-ray chest, spine, pelvis
6. Evidence of end organ damage;
   - serum Hypercalcemia (crystalline bone)
   - anaemia (bone marrow)
   - renal insufficiency

Question 11

How do we diagnose acute myeloid leukaemia?

Answer 11

1. Blood film potentially showing increased monoblast numbers
2. Bone marrow biopsy - shows proliferation of myeloblasts and Auer Rods (crystals of coalesced granules) within monoblasts

Question 12

How do we diagnose acute lymphoblastic leukaemia?

Answer 12

1. Blood film - characteristic blast cells seen

2. Marrow biopsy - characteristic blast cells

Question 13

How do you diagnose chronic myeloid leukaemia?

Answer 13

Blood or bone marrow cytogenetic analysis for the Philadelphia chromosome

Question 14

What are Bence-Joyce proteins?

Answer 14

Bence-Joyce proteins are monoclonal globulins (from antibodies) detected in urine, that suggests multiple myeloma.

Present in 60% of patients with multiple myeloma.

Question 15

How do you assess size of a red blood cell when looking at a blood film?

Answer 15

An RBC should be the size of a lymphocyte nucleus (T/B cells)

Question 16

How do you assess chromicity (hypo/hyper/normo-chromic) on a blood film?

Answer 16

If the area of central pallor on an RBC is less than 33% of the total diameter, the RBC is normal.

Question 17

How do you diagnose iron deficiency anaemia?

Answer 17

Gold standard - give iron supplement (ferrous fumerate tablets or sodium feredetate liquid)and check for improvement

Ferritin - can be checked but levels are low in infancy and adolescence, and falsely high in infection and long term inflammatory disorders (acute phase reactant)

Question 18

Which investigations should be carried out first in any suspected haemolytic anaemia?

Answer 18

Essential:

1. FBC and reticulocyte count
2. Blood film (shape may be cause)
3. Bilirubin level (increases in haemolysis)
4. Lactate dehydrogenase (LDH) level (increases in haemolysis)

• for ALL kinds of haemolytic anaemia

Question 19

Which test is for diagnosis of immune haemolytic anaemia?

Answer 19

Coomb’s test, aka direct antiglobulin test (DAT)

Question 20

Which test is diagnostic of hereditary spherocytosis?

Answer 20

EMA binding test

Eosin maleimide binding test, binds band 3 proteins that are present in RBCs in hereditary spherocytosis

Question 21

Which test is diagnostic of GLP-6 deficiency haemolytic anaemia?

Answer 21

GLP-6 dehydrogenase level

Question 22

In the investigation of anemia, what does the reticulocyte level indicate?

Answer 22

Reticulocytes are the compensatory mechanism for anemia, released in response to low RBC levels.

Anemia + Low reticulocyte level = Anemia due to low production rate e.g. leukaemia

Anemia + high reticulocyte level = Anemia due to haemolysis or