Haematological Malignancies

Question 1

What are the differentials for lymphadanopathy?

Answer 1

• Infective: Viral, TB, HIV, bacterial
• Inflammatory Sarcoidosis
• Malignant: Lymphoma / mets from other cancers e.g. gastric (virchow’s node)
• Reaction to drugs (allergy e.g. to beta lactam abx)
• Autoimmune e.g. Lupus

Question 2

What does enlarged Virchow’s node suggest (AKA Troisier’s sign)?

Answer 2

A malignancy, commonly gastric, also kidney or ovarian/testicular

(supraclavicular nodes could also indicate lung cancer)

Question 3

What are the “B” symptoms for lymphoma?

Answer 3

Night sweats, fever, weight loss

Question 4

What is the staging of lymphoma?

Answer 4

1. Stage 1: single lymph node affected
2. Stage 2: 2+ lymph nodes affected above diaphragm
3. Stage 3: lymph nodes above AND nodes below diaphragm
4. Stage 4: Organ involvement (with or without lymph nodes)

Question 5

What scan is used to stage lymphoma and why?

Answer 5

PET scan, needs to assess if nodes are affected above or below diaphragm.

Question 6

What are the 2 most common types of Non-Hodkin’s lymphoma?

Answer 6

1. Diffuse Large B Cell (high grade)
   
   • aggressive but responds well to aggressive treatment
   • 60 years
   • cureable
2. Follicular (indolent)
   
   • slow onset
   • often watched rather than treated
   • Good response to treatment but no cure

Question 7

When does lymphadenopathy become clinically relevant?

Answer 7

• Adult > 1cm (or 1.5cm at level II)
• Paediatric > 2cm
• Any node with associated head neck symptoms that is persistent

Question 8

Name some common bacterial causes of lymphadenopathy

Answer 8

• Strep - group A
• Staph A
• Strep pneumoniae
• Anaerobes
  
  • fusobacterium (teeth)
• TB

Immunocompromised:

• Bartonella (cat scratch disease)
• Toxoplasmosis = parasitic (rare)

Question 9

Name some common viral causes of lymphadenopathy

Answer 9

• Adenovirus
• Rhinovirus
• Coxsackie virus A + B
• EBV → glandular fever includes tender, enlarged lymphnodes

Question 10

How can you tell the difference between an inflammatory and a malignant lymphadenopathy?

Answer 10

Inflammatory:

• Post-infection (symptomatic)
• Should decrease in size over time, or fluctuate in size

Malignant:

• Not necessarily post-infection
• Increases in size over time; progressive enlargements
• May have associated head and neck symptoms
  
  • e.g. dysphagia, hoarse voice
• Often painless (pain = sign of inflammation)

Question 11

What shape should a lymph node be?

Answer 11

Rugby ball shaped!

Football shape = baaad

Question 12

What is TB?

Answer 12

• Infection with organism Mycobacterium tuberculosis.
• TB is more common in
  
  • developing countries
  • immunocompromised people e.g. HIV patients
  • malnourished
  • IV drug users
• It is droplet spread - usually needs sustained close contact with an infectious case
• Starts in the alveoli, can become dormant in the lymphatic system and reactivate later at a time of immunocompromise

Question 13

What are the symptoms of TB?

Answer 13

Symptoms - 90% present with pulmonary symptoms only:

• Cough +/- haemoptasis
• Shortness of breath

Constitutional symptoms include:

• Fever + chills
• Night sweats
• Lymphadenopathy
• Fatigue
• Weight Loss / loss of appetite

Question 14

Malignant nodes are 1 of 2 types of cancer

Answer 14

1. Lymphoma
   
   • Hodgkins
   • Non-Hodgkins
2. Metastatic
   
   • Majority from head/neck primary
   • Supraclavicular fossa nodes (Virchow’s) are 2º to lung / GI tract

Question 15

How do you clinically discern between a lymphoma and metastatic lymph node

Answer 15

Lymphomas: smooth, firm lumps, can present with B symptoms

Mets: Harder, irregular, skin can be stuck to them - fixed

Question 16

How do you assess a neck lump?

Answer 16

1. Size – width / height / depth
2. Location – can help narrow the differential – anterior triangle / posterior triangle / mid-line
3. Shape – well defined?
4. Consistency – smooth / rubbery / hard / nodular / irregular
5. Fluctuance – if fluctuant, this suggests it is a fluid-filled lesion – cyst
6. Trans-illumination – suggests mass is fluid-filled – e.g. cystic hygroma
7. Pulsatility – suggests vascular origin – e.g. carotid body tumour/aneurysm
8. Temperature – increased warmth may suggest inflammatory / infective cause
9. Overlying skin changes – erythema / ulceration / punctum
10. Relation to underlying/overlying tissue – tethering/mobility (ask to turn head)
11. Auscultation – to assess for bruits – e.g. carotid artery aneurysm

Question 17

Name the lymph nodes of the head and neck

Answer 17

Question 18

What investigations should you do on finding a suspected lymphoma?

Answer 18

1. Core biopsy* (w US guidance)
2. [USS - excellent for characterising benign nodes]
3. Full body CT scan w contrast / MRI for staging
4. PET for lymphoma staging (above / below diaphragm)

*fine needle aspiration is not helpful in lymphoma as sample too small

Question 19

What does this x-ray show? What are your differentials?

Answer 19

Bilateral Mediastnal Lympadenopathy

• Sarcoid Lymphoma
• Glandular fever
• Disseminated Malignancy
• Tuberculosis
• Lung cancer

Question 20

What are lymphomas?

Answer 20

• Lymphomas are malignancies that involve the lymphocytes.
• Lymphocytes are present in the
  
  • circulation
  • bone marrow
  • lymph nodes
  • other organs that form the reticulo-endothelial system:
    
    • liver
    • spleen
• Characteristically, lymphomas are solid tumours involving the lymph nodes and when there is involvement of other organs it is referred to as extra-nodal involvement:
  
  • skin
  • brain
  • bowels
  • bone
• Lymphomas are closely related to lymphoid leukaemias, which originate in the marrow and therefore typically involves circulating lymphocytes.

Question 21

What are the subtypes of malignant lymphomas?

Answer 21

1. Hodgkins (malignancy of the young, peak incidence 15-30, 2nd peak over 50, 80% are cured)
   
   • characterised by the presence of Reid Sternberg cells
2. Non-hodgkins
   
   • High grade (fast growing, symptomatic but curable)
     
     • Diffuse Large B-cell
     • Burkitt lymphomas
   • Indolent (slow, growing, may not require treatement for long periods of time - watchful waiting, responds to chemo but never cured)
     
     • Follicular lumphomas

Question 22

What are the risk factors for developing lymphoma?

Answer 22

1. FH
2. Immunocompromise
   
   1. HIV
   2. Iatrogenic e.g. methotrexate
3. EBV infection (more likely to have B symptoms)

Question 23

Which cells derive from myeloid precursors and which from lymphoid?

Answer 23

Question 24

What is the classification of leukemias?

Answer 24

1. Firstly categorised as
   
   1. Acute (ends in “-blastic”) or
   2. Chronic (begins with “chronic”)
2. Then catergorised as
   
   1. Myeloid
   2. Lymphocytic

Question 25

What is the most common malignancy of childhood?

Answer 25

acute lymphoblastic leukaemia (ALL)

Question 26

What is the first abnormality noted in leukemia?

What investigations are essential?

Answer 26

Raised white cell count

1. Blood film
2. Bone Marrow aspirate

Question 27

What symptoms might an acute leukemia present with?

Answer 27

Symptoms are usually indicative of bone marrow failure, and include the following:

1. Anaemia – generally feeling tired, SOB on exercise, weakness
2. Bleeding and bruising – as a result of thrombocytopaenia
3. Infection – as a result of leukopaenia
4. Bone pain – as a result of bone marrow infiltration

Question 28

Why does the bone marrow fail in actue leukemia?

Answer 28

• Crowding of the bone marrow by such immature cells renders the marrow unable to produce healthy blood cells.
• The patient may therefore become anaemic and/or thrombocytopenic.

Question 29

What are the differentials for easy bruising, and purpura

Answer 29

• In elderly, not always associated with underlying pathology, result of aging
• In young:
  
  • TTP - thrombotic thrombocytopenic purpura
  • HUS - haemolytic uraemic syndrome
  • Infections: such as meningococcal sepsis
  • Haematological malignancies: such as leukaemias

Question 30

What is TTP?

Answer 30

Thrombotic thrombocytopenic purpura

• a type of Thrombotic microangiopathy (TMA)
• blood disorder that results in blood clots forming in small blood vessels throughout the body
  
  • As platelets are used up in the formation of thrombi → low platelet count, low red blood cells due to their breakdown
  • Red blood cells passing the microscopic clots are subjected to shear stress, which damages their membranes, leading to rupture of red blood cells within blood vessels, which in turn leads to anaemia and schistocyte formation.
  • The presence of these blood clots in the small blood vessels reduces blood flow to organs resulting in cellular injury and end organ damage.
• Many people experience an influenza-like or diarrheal illness before developing TTP
• Neurological symptoms are very common and vary greatly in severity e.g. headache, confusion, fatigue, stroke-like
• Treatment: plasmapheresis

Question 31

What are the classic 5 symptoms of TTP?

Answer 31

Classic 5 symptoms (rarely all 5):

1. Fever
2. Changes in mental status
3. Thrombocytopenia
4. Reduced kidney function
5. Haemolytic anaemia (microangiopathic hemolytic anemia).

Question 32

What is HUS?

Answer 32

Haemolytic-uremic syndrome

• A type of Thrombotic microangiopathy (TMA)
• HUS occurs after ingestion of a strain of bacteria expressing Shiga toxin such as enterohemorrhagic Escherichia coli (EHEC)
• PC: Low platelets, low red blood cells, and kidney failure following a few days of bloody diarrhea

Question 33

What is multiple myeloma?

Answer 33

• Malignancy arising from plasma cells (antibody producing cells)
• Proliferating nests of plasma cells may form deposits in bones, where they typically cause osteolytic lesions on x-ray
• In the bone marrow proliferation of plasma cells result in
  
  • reduced erythropoesis (anaemia) and
  • reduced production of platelets (thrombocytopaenia)
• Myeloma cells produce various paraproteins that may be detected in plasma (by plasma electrophoresis) or even in the urine (Bence Jones proteins)
• Additional features of myelomas:
  
  • Hypercalcaemia
  • Bone pain
  • ↑ Plasma cells on bone marrow aspirate
• Persistent back pain in an older subject - particularly when associated with anaemia and hypercalcaemia, should raise the suspicion of multiple myeloma.

Question 34

What investigations are important in myeloma?

Answer 34

1. Skeletal survey –may show characteristic lytic lesions – most commonly in the skull
2. Serum protein electrophoresis – determines the type of each protein present
3. Urine protein electrophoresis – identifies presence of Bence-Jones proteins
4. 24-hour urine immunofixation –this is useful for checking the subtype of light chains, e.g. IgA lambda, Bence-Jones proteins
5. Bone marrow aspirate –shows plasma cell infiltration of the bone marrow; used to calculate the percentage of plasma cells in the infiltrate; cytogenetic analysis of the aspirate may contribute prognostic information may also demonstrate amyloidosis

Question 35

Why is examination of the abdomen for hepato-splenomegaly an integral part of the examination when dealing with a patient presenting with lymphadenopathy?

Answer 35

Lymphomas and other forms of haematological malignancies can commonly involve other components/organs that are part of the reticulo-endothelial system such as the spleen, liver and bone marrow.