Pathoma - WBC Disorders - Chronic Leukemia & Myeloproliferative Disorders

Question 1

What is the basic premise behind chronic leukemia?

Answer 1

Neoplastic proliferation of mature lymphocytes

Question 2

What is the major neoplastic cell in chronic lymphocytic leukemia (CLL) and what are their markers?

Answer 2

Naive B-cells CD5 (usually on T-cells) and CD20

Question 3

What type of cells do you see on blood smear in CLL?

Answer 3

Smudge cells

Think: CLL = crushed little lymphocytes

Question 4

What do you call CLL which has progressed to involvement of lymph nodes?

Answer 4

Small lymphocytic lymphoma

Question 5

What are some of the major complications of CLL?

Answer 5

Hypogammaglobulinemia (neoplastic B-cells do no produce immunoglobulins) Autoimmune hemolytic anemia (if the neoplastic cells do make immunoglobulin, it will be defective and attack RBCs)

Question 6

What is the Richter transformation

Answer 6

Transformation of CLL into Diffuse large B-cell lymphoma

Question 7

What is the major neoplastic cell in hairy cell leukemia?

Answer 7

Neoplastic proliferation of mature B cells characterized by hair cytoplasmic processes

Question 8

What is the positive marker in hairy cell leukemia

Answer 8

TRAP (tartrate-resistant acid phosphatase)

Question 9

Describe the “TRAP” hint and what disease it is used for

Answer 9

Hairy cell leukemia

• TRAP+
• Cells are trapped in spleen and bone marrow (splenomegaly and “dry tap” on bone marrow aspiration due to fibrosis)
• Trapped cells cannot go to usual lymph node location (no lymphadenopathy)

Question 10

What do you treat Hairy cell leukemia with?

Answer 10

2-CDA (cladribine) An adenosine deaminase inhibitor (adenosine accumulates to toxic levels in neoplastic B cells)

Question 11

What is the major neoplastic cell in Adult T-cell leukemia/lymphoma (ATLL)

Answer 11

Mature CD4+ T cells

Question 12

What disease is associated with HTLV-1

Answer 12

ATLL

Question 13

What is the common presentation of ATLL?

Answer 13

Rash, generalized LAD, hepatosplenomegaly, lytic (punched out) bone lesions with hypercalcemia

Question 14

What is the major neoplastic cell in mycosis fungoides

Answer 14

Mature CD4+ T-cells

Question 15

What is the presentation of mycosis fungoides?

Answer 15

Aggregation of neoplastic cells in the epidermis (Pautrier micoabscesses)

Question 16

What is Sezary syndrome?

Answer 16

When neoplastic cells in the epidermis in mycosis fungoides spread to the blood

Question 17

What are the characteristic cells in Sezary syndrome?

Answer 17

Sezary cells - lymphocytes with cerebriform nuclei (looks like lobes)

Question 18

What populations are most commonly affected by ATLL?

Answer 18

Japan and the Carribean

Question 19

What is the major neoplastic cell in Chronic myeloid leukemia (CML)?

Answer 19

Basophils

Question 20

What is the mutation in CML?

Answer 20

t(9;22) Philedalphia chromosomes

BCR-ABL fusion protein with increased tyrosine kinase activity

Question 21

What is the first line treatment for CML

Answer 21

Imatinib (blocks tyrosine kinase activity of the BCR-ABL mutation)

Question 22

What may CML progress to?

Answer 22

AML (2/3) or ALL (1/3)

Question 23

How do you distinguish CML from leukemoid reaction (increased granulocytes due to infection)

Answer 23

(1) CML will be negative for LAP (present in cells fighting infection)
(2) Increased basophils (leukemoid rx will not have increaed basophils)
(3) t(9;22)

Question 24

What is the major neoplastic cell in polycythemia vera?

Answer 24

RBCs (granulocytes and platelets also increased)

Question 25

What is the associated mutation in PV?

Answer 25

JAK2 kinase mutation (will lead to constitutive activation of JAK2 which is a cytoplasmic tyrosine kinase)

Question 26

Describe the symptoms of PV?

Answer 26

Symptoms mostly due to hyperviscosity of blood:

• Blurry vision and HA
• Increased risk of venous thrombosis (e.g. Budd Chiari - thrombosis of hepatic vein)
• Flushed face due to congestion (plethora)
• Itching, especially after bathing (due to histamine release from increased mast cells)

Question 27

What is the treatment of PV?

Answer 27

Phlebotomy

Question 28

How do you distinguish PV from reactive polycythemia (e.g. lung disease and ectopic EPO)

Answer 28

PV: Decreased EPO (neg. feedback) and normal SaO2

Lung disease: Decreased SaO2 and increased EPO

Ectopic EPO (e.g. renal cell carcinoma): Increased EPO and normal SaO2

Question 29

What is the major neoplastic cell in essential thrombocythemia (ET)?

Answer 29

Platelets

Question 30

What is the mutation associated with essential throombocythemia?

Answer 30

JAK2 kinase mutation

Question 31

What are the symptoms of essential thrombocytopenia

Answer 31

Can be either increased risk of bleeding or increased risk of thrombosis depending on if neoplastic platelets are working or not

Question 32

What is the major neoplastic cell in myelofibrosis

Answer 32

Megakaryocytes

Question 33

What is the mutation in myelofibrosis

Answer 33

JAK2 kinase

Question 34

What causes marrow fibrosis in myelofibrosis

Answer 34

Megakaryocytes produce excess platelet-derived growth factor (PDGF)

Question 35

Clinical/lab features of myelofibrosis

Answer 35

Splenomegaly due to extramedullary hematopoeisis

Leukoerythroblastic smear

Increased risk of infection, thrombosis, and bleeding

Question 36

Describe the blood smear of myelofibrosis

Answer 36

Leukoerythroblastic smear:

• Tear drop RBCs (from escaping from fibrotic marrow)
• Nucleated RBCs and immature granulocytes (spleen does not have reticulin, the hardware in the bone marrow that prevents immature cells from exiting)