White Blood Cell Disorders

Question 1

Signs + symptoms of infectious mononucleosis.

Answer 1

• fever
• sore throat
• pharyngitis
• generalized lymphadenopathy
• hepatosplenomegaly
• (antibody + T cell response)

Question 2

Cause of infectious mononucleosis?

Answer 2

-Typically EBV
can also be CMV.

Serologically: EBV –> heterophile positive
CMV heterophile negative

Question 3

What does mono mainly infect in the body, and then how does our body respond?

Answer 3

• oral mucosa –> Pharyngitis
• liver –> elevating liver enzymes, causing hepatomegaly
• B cells
  Response:
• Cytotoxic T cells (increase) cause T cell hyperplasia in lymph causing general lymphadenopathy
• T cell hyperplasia in PALS causing splenomegaly
• high WBC count with atypical lymphocytes n the blood

Question 4

How can you distinguish Hodgkins and non-hodgkins histologically?

Answer 4

Hodgkins –> Reed-sternberg giant cells (neoplastic cells)

Question 5

What are the 3 main neoplastic proliferations of white blood cells?

Answer 5

1) Lymphoid neoplasms
2) Myeloid neoplasms
3) Histiocytic

Question 6

What are the 3 main groups of myeloid neoplasms?

Answer 6

1) Acute myelogenous leukaemia
2) Chronic myeloproliferative disorders
3) Myelodysplastic syndromes

Question 7

Explain pathophysiology of acute myeloid leukaemia?

Answer 7

Genetic mutation causing a “maturation block” that interferes with the differentiation of early myeloid cells, thus leads to accumulation of myeloid blast cells in the bone marrow.

Question 8

How can acute promyelocytic leukaemia be distinguished from acute monocytic and acute megakaryoblastic leukaemia?

Answer 8

Acute promyelocytic leukaemia has myeloperoxidase (MPO) in it’s cytoplasm.

Question 9

How is acute promyelocytic leukemia treated?

Answer 9

All-trans-retinoic acid (ATRA) is given. It binds to altered receptors causing myeloblasts to mature, and eventually die (lifespan 6 hrs), clearing the tumour quite quickly.

Question 10

How are lymphoblasts differentiated from myeloblasts and mature lymphocytes?

Answer 10

Lymphoblasts have a positive nuclear stain for TdT (DNA polymerase)

Question 11

What type of cells are involved in chronic lymphocytic leukemia (CLL)?

Answer 11

Neoplastic proliferation of naive B cells.

Question 12

Complications of CLL:

Answer 12

• hypogammaglobulinemia –> infections
• autoimmune hemolytic anemia
• transformation to diffuse large B-cell lymphoma (Richter transformation)

Question 13

What is the Richter transformation? Which disease states can it occur in?

Answer 13

The transformation to diffuse large B-cell lymphoma.
Can occur in:
- CLL (chronic lymphoid leukemia)
- hairy cell leukaemia

Question 14

What type of cell(s) are involved in hairy cell leukaemia?

Answer 14

Neoplastic proliferation of mature B cells

Question 15

What type of leukaemia is the most common in adults?

Answer 15

CLL (chronic lymphocytic leukemia)

Question 16

In what leukemia do you find “dry tap” from the bone marrow aspiration?

Answer 16

• Hairy cell leukemia
• myelofibrosis
  Due to marrow fibrosis.

Question 17

What do you clinically find in hairy cell leukaemia?

Answer 17

• massive splenomegaly
• pancytopenia
• dry tap in marrow aspiration
• NO lympadenopathy!! (vs CLL, where there is)
• (+) For TRAP (tartrate resistant acid phosphatase)

Question 18

What are Pautrier microbabscesses? What condition do you find them in?

Answer 18

They are little aggregations of neoplastic cells in the epidermis.
Found in mycosis fungoides (leukaemia)

Question 19

What can mycosis fungoides progress to?

Answer 19

Sezary syndrome (T cell leukaemia)

Question 20

What are cells (+) for in hairy cell leukaemia?

Answer 20

TRAP

Question 21

What does TRAP (+) indicate?

Answer 21

Hairy cell leukaemia

Question 22

What is the leukamoid reaction?

Answer 22

Increase in WBCs due to infection.

Looks like it mimics CML

Question 23

How can you distinguish CML and leukamoid reaction?

Answer 23

CML is:

• negative for LAP stain
• high basophils
• presence of t(9;22), the Philadelphia chromosome

Question 24

How do you treat CML?

Answer 24

Tyrosine kinase inhibitor

imatinab

Question 25

What does CML present with? What can it progress to?

Answer 25

- Massive splenomegaly - Increased WBCs, mainly basophils Can progress to: - AML (2/3s of cases) - ALL (1/3)

Question 26

What is polycythemia? | What is absolute and relative polycythemia?

Answer 26

Polycythemia is disease state with high hematocrit. Absolute polycythemia = increase in RBCs causing the increase in Ht Relative polycythemia = decrease in volume of plasma

Question 27

What is polycythemia vera?

Answer 27

Neoplastic proliferation of mature myeloid cells, with high RBCs mainly, but also high granulocytes and platelets.

Question 28

Signs + symptoms for polycythemia vera?

Answer 28

- headache + blurry vision - flushed skin/face (high RBC) - risk of venous THROMBOSIS!! (hepatic v., portal v., dural sinus) - itching (after bath from high mast cells)

Question 29

Treatment for polycythemia vera?

Answer 29

- phlebotomy | - hydroxyurea

Question 30

What is hydroxurea used to treat?

Answer 30

- sickle cell anemia - polycythemia vera (PV) - CML - cervical cancer

Question 31

What type of mutation is present in polycythemia vera?

Answer 31

JAK-2 kinase mutation

Question 32

Explain EPO production in reactive polycythemia

Answer 32

High EPO from ectopic production. Due to renal cell carcinoma

Question 33

What is myelofibrosis?

Answer 33

Neoplastic proliferation of mature myeloid cells, especially megakaryocytes. They overproduce PDGF (platelet derived growth factor) and cause marrow fibrosis.

Question 34

Clinical/histo signs of myelofibrosis?

Answer 34

- splenomegaly - tear drop RBCs - nucleated RBCs - immature granulocytes

Question 35

What condition do you find tear drop RBCs?

Answer 35

Myelofibrosis