Haematology

Question 1

What are the main causes of lymphadenopathy?

Answer 1

1. Infectious
   - viruses: EBV, CMV, HIV, hepatitis, HSV, rubella
   - bacteria
   - fungi
   - parasites
2. Malignant disorders
   - primary haematological disorders: lymphoma, myeloid disorders
   - solid tumour metastases
3. Disorders with immunological mechanism
   - autoimmune disorders: SLE, RA, vasculitis
   - sarcoidosis

Question 2

What are the main causes of splenomegaly?

Answer 2

1. Haematological disorders:
   - haemolysis
   - thalassaemia major and intermedia
   - sickle cell anaemia
   - haemolytic anaemia
2. Malignancies
   - lymphomas
   - leukaemias
   - myeloma
   - metastases of solid tumours
3. Inflammation
   - sarcoid
   - serum sickness
   - SLE, RA
4. Infection
   - viral: hepatitis, EBV, CMV
   - bacterial
   - parasitic: malaria, schistosomiasis, toxoplasmosis
   - infective endocarditis
   - fungal
5. Congestive
   - cirrhosis
   - heart failure
   - thrombosis of portal, hepatic or splenic veins
6. Non-malignant, infiltrative:
   - Niemann-Pick disease
   - amyloid
   - glycogen storage disease
   - Gaucher’s disease
   - Haemophagocytic lymphohistiocytosis

Question 3

What are the three major types of anaemia and what are their causes?

Answer 3

1. Microcytic hypochromic anaemia
   - iron deficiency
   - thalassaemia
2. Normocytic normochromic anaemia
   - acute bleeding
   - haemolysis
   - marrow infiltration
   - anaemic of chronic disease (esp. CKD)
3. Megaloblastic or macrocytic
   - B12/folate deficiency
   - alcoholism
   - liver disease
   - hypothyroidism
   - myelodysplasia

Question 4

Where are the palpable lymph nodes?

Answer 4

1. cervical
2. supraclavicular
3. axillary
4. inguinal

Question 5

Where are the non-palpable lymph nodes?

Answer 5

1. hilar
2. mediastinal
3. abdominal/retroperitoneal
4. generalised lymphadenopathy

Question 6

What are the common causes of cervical lymphadenopathy?

Answer 6

• bacterial infection
• EBV, rubella, TB
• lymphoma (frequently unilateral)
• head-neck tumours (frequently unilateral)

Question 7

What are the common causes of axillary lymphadenopathy?

Answer 7

• bacterial infection
• lymphoma
• breast cancer
• melanoma

Question 8

What are the common causes of supraclavicular lymphadenopathy?

Answer 8

• lung, retroperitoneal or gastrointestinal tumours
• lymphoma
• chest or retroperitoneal bacterial or fungal infection

Question 9

What are the common causes of inguinal lymphadenopathy?

Answer 9

• bacterial infections of lower extremity, genitals or perianal regions
• pelvic tumours, lymphoma
• venereal diseases (lymphogranuloma venereum, syphilis)

Question 10

How is lymphoma broadly categorised?

Answer 10

Divided broadly into:

1. Hodgkin’s lymphoma
2. Non-Hodgkin’s lymphoma
   - indolent lymphoma (follicular lymphoma, CLL/SLL, MCL, MZL)
   - aggressive lymphoma (diffuse large B cell lymphoma)
   - very aggressive lymphoma (Burkitt’s lymphoma and Acute Lymphoblastic Lymphoma)

Question 11

What are the principles of treatment for lymphomas?

Answer 11

1. Low grade lymphoma
   - not curable
   - only treat if there is indication to treat
   - exception: need to treat MCL, follicular lymphoma may be curable with radiotherapy
2. High grade lymphoma
   - curable
   - always treat DLBCL
3. Burkitt’s or ALL:
   - very curable
   - MUST treat, otherwise fatal

Question 12

What methods are used to diagnose lymphoma?

Answer 12

1. Histology
   - look at tissue biopsy down a microscope (FNA is not diagnostic)
   - architecture
   - morphology (small cells = low grade; large cells = high grade)
2. Flow cytometry or immunohistochemistry
   - look for cell surface markers
3. Cytogenetics
   - particular genes are either diagnostic or prognostic for lymphoma
   - detects deletions, translocations, etc.
4. Molecular PCR

Question 13

What symptoms might you find on history and examination of a patient with lymphoma?

Answer 13

1. Symptoms of proliferation:
   - B symptoms: weight loss, drenching night sweats, recurrent fever
2. Symptoms related to organ damage or mechanical obstruction
   - specific organ damage
   - large lymph nodes
3. Symptoms associated with bone marrow failure
   - anaemia: tiredness, postural hypotension, SOB, pale sclera, tachycardia
   - recurrent infections
   - bleeding, bruising

Question 14

What are the two categories of multiple myeloma?

Answer 14

1. Smouldering MM
   - criteria for MM has been met (para-protein >30grams/L or bone marrow plasma cells >10%) but the disease is quiescent
   - defined by lack of end organ damage
   - no evidence that treatment will prolong survival
   - treat small group: MM with positive biomarkers
2. Active MM
   - defined by end organ damage: CRAB
   - C: hypercalcaemia due to cytokines causing bone resorption
   - R: renal damage due to hypercalcaemia and light chain toxicity
   - A: anaemia due to bone marrow invasion
   - B: bone pain due to cytokines causing bone resorption

Question 15

What proportion of smouldering MM patients are treated?

Answer 15

MM with positive biomarkers are treated.

• defined as myeloma with MRI lesions
• do not have active disease but benefit from treatment
• if patient is found to have smouldering MM, need to consider MRI scan for detection of positive biomarkers

Question 16

What are the principles of treatment for MM? (goals, who to treat, how to treat)

Answer 16

Note: MM is not curable but very treatable

Goals of treatment:

• treat disease itself
• prevent end organ damage

Two populations require treatment:

1. active MM
2. MM with positive biomarkers

If a patient requires treatment, there are two options:

1. Eligible for autologous stem cell transplants
   - patients <65 yo, no significant co-morbidities
   - induction therapy with Bortezomib + Lenalidomide
   - high dose ablative chemotherapy then ‘rescue’ with SC transplant
   - followed by maintenance therapy
2. Ineligible for SC transplant
   - people >75 yo or with significant comorbidities
   - ongoing Bortezomib + Lenalidome