24. Tumour markers of Lymph Nodes, Spleen, Thymus and Bone Marrow

Question 1

Oncogens and tumour suppresor genes by immunohistochemistry:

a) Follicular lymphoma
b) Mantle cell lymphoma, myelomas
c) Progression in lymphomas, high grade lymphomas
d) Germinal center origin (low&high grade)
e) Large B cell lymphoma
f) Burkitt’s lymphoma

Answer 1

a) Bcl-2
b) Cyclin D1
c) p53
d) Bcl-6
e) ALK (anaplastic lymphoma kinase)
f) My-c

Question 2

Difference between follicular hyperplasia and follicular lymphoma

Answer 2

Follicular hyperplasia: starry sky appearance, follicle interface with mantle zone is sharply defined
Follicular lymphoma: monomorphic appearance, follicular edge is fuzzy

Question 3

Lymphoma markers for:

a) B-cell
b) T-cell
c) Hodgkin cell
d) Mantle cell
e) Follicular
f) Small cell B cell lymphoma

Answer 3

a) CD20, CD79a
b) CD3
c) CD15, CD30
d) Cyclin D1
e) CD10, Bcl-2
f) CD5, CD23

Question 4

Structures of a spleen

Answer 4

1. white pulp
   - lymphoid follicles: Malphigian bodies
2. red pulp
   - sinuses: venous
   - cords: lymphocytes
3. weight
   - 120-150g

Question 5

Causes of splenic atrophy

Answer 5

1. Sickle cell disease
   - autosplenectomy
   - misshapen cell block blood flow to spleen. causing scarring and eventual atrophy of the organ
2. Coeliac disease
   - splenic hypofunction

Question 6

Function of spleen

Answer 6

1. haemopoiesis
2. cell sequestration
3. cell destruction
4. iron metabolism
5. antibody formation
   - IgM antibodies to opsonise encapsulated bacteria
6. Phagocytosis

Question 7

Types of splenomegaly

Answer 7

1. congestive
   - cirrhosis of liver
   - portal vein thrombus
2. disorders of blood and marrow (most common)
   - leukemia and lymphoma
   - haemolytic anaemia
   - myelofibrosis
   - myeloproliferative disease
3. collagen vascular disease
   - RA
   - SLE
   - PAN (polyarteritis nodosa)
4. storage disorders
   - hyperlipidaemias
   - lipid storage disorder
   - Gaucher’s disease
   - Neiman Pick’s disease

Question 8

Difference between splenomegaly and hypersplenism

Answer 8

splenomegaly - spleen enlargement

hypersplenism - overactive function of spleen of any size

Question 9

What is hypersplenism

Answer 9

enlarged spleen for any reason causeing destruction of blood cells and consequent reduction in these cells in the peripheral blood:

• anaemia
• thrombocytopenia
• leucopenia

Question 10

Where did the thymus arise from

Answer 10

endoderm of 3rd and 4th branchial pouch

-migrates down from neck to mediastinum

Question 11

Function of thymus

Answer 11

• responsible for differentiation and direction of T lymphocytes
• central role in cell mediated immunity

Question 12

When is enlargement of the thymus presented

Answer 12

1. myasthenia gravis
2. neoplasm
   - thymomas (thymic epithelial neoplasm)
   - lymphomas
   - germ cell tumours
   - carcinoid tumours

Question 13

What is thymoma associated with

Answer 13

1. myasthenia gravis
2. RA
3. Sjogren’s syndrome

Question 14

What is myeloproliferative cell neoplasm/disorder

Answer 14

a clonal neoplastic proliferation of stem cells, affecting all the cell lines of the bone marrow
-high peripheral cell count and hypercellular marrow

Question 15

Pathogenesis of myeloproliferative cell disorder

Answer 15

activation of mutation in gene coding for tyrosine kinase (JAK2) - causing an increased sensitivity to intercellular signalling

Question 16

How is myeloproliferative cell disorder clincally diagnosed

Answer 16

1. FBC

2. bone marrow tissue and bone marrow aspirate

Question 17

How is myeloproliferative cell disorder classified

Answer 17

1. chronic granulocytic (myeloid) leukemia
2. myelofibrosis
3. polycythaemia rubra vera
4. essential thrombocythaemia/thrombocytosis

Question 18

How is myeloproliferative cell disorder presented

Answer 18

concept:
- excess of one cell type may cause decrease of other cell types
- high content of one cell type may cause symptoms
a) anaemia and infection
b) bleeding/thrombosis
c) hyperviscosity syndrome
d) hyperuricaemia and spleen infarction

Question 19

What is myelofibrosis

Answer 19

fibrosis of marrow

• enlarged spleen
• enlarged liver
• loss of marrow cells
• life expectancy: 7 years
• terminal blast crisis

Question 20

Treatment of myelofibrosis

Answer 20

marrow stimulation with/wout splenectomy

Question 21

What is polycythaemia

Answer 21

increase red cell volume
-high Hb and haematocrit
-enlarged spleen
-marrow erythropoiesis with or without fibrosis
-thrombotic or haemorrhagic events
50% 12 year survival

Question 22

When is secondary polycythaemia presented

Answer 22

1. high altitude
2. congenital heart disease
3. tumours
   - e.g. renal cell carcinoma
4. erythropoietin production

Question 23

How to treat polycythaemia rubra vera

Answer 23

1. phlebotomy
2. radiotherapy with 32P isotope
3. hydroxyurea (myelosuppresive treatment)

Question 24

What is essential thrombocythaemia

Answer 24

clonal neoplastic proliferation of stem cells with increased platelets

• bleeding/thrombotic abnormalities
• enlarged spleen
• enlarged liver

Question 25

Treatment of essential thrombocythaemia

Answer 25

hydroxyurea

Question 26

What is chronic myeloid leukaemia

Answer 26

stem cell disorder with differentiation to leukocytes

-bone marrow overrun by white cells

Question 27

Pathogenesis of chronic myeloid leukemia

Answer 27

increased tyrosine kinase activity of Bcr-abl gene

Question 28

Presentation of chronic myeloid leukemia

Answer 28

1. anaemia
2. bruising
3. infection
4. weight loss
5. hepatosplenomegaly

Question 29

What is myelodysplastic syndrome

Answer 29

smouldering neoplastic proliferation of stem cells of bone marrow

• pre-leukaemic disorder
• low peripheral cell count with hypercellular marrow
• associated with chromosomal abnormalities
• may progress into leukaemia within 2 years
• require cytogenic studies and correlation between marrow aspirate and FBC