Hem & Onc - Pathology (Myeloproliferative disorders & related topics)

Question 1

What is Langerhans cell histiocytosis?

Answer 1

Proliferative disorders of dendritic (Langerhans) cells from monocytic lineage.

Question 2

How does Langerhans cell histiocytosis present?

Answer 2

Presents in a child as lytic bone lesions and skin rash or as recurrent otitis media with a mass involving the mastoid bone.

Question 3

Describe the functioning of cells in Langerhans cell histiocytosis.

Answer 3

Cells are functionally immature and do not efficiently stimulate primary T lymphocytes via antigen presentation.

Question 4

What 2 markers are expressed by cells in Langerhans cells histiocytosis?

Answer 4

Cells express S-100 (mesodermal origin) and CD1a

Question 5

What does the S-100 marker indicate, and with what myeloproliferative disorder is it associated?

Answer 5

S-100 (mesodermal origin); Langerhans cell histiocytosis

Question 6

What EM finding is characteristic of Langerhans cell histiocytosis?

Answer 6

Birbeck granules (“tennis rackets” on EM) are characteristic

Question 7

Name 4 chronic myeloproliferative disorders.

Answer 7

(1) Polycythemia vera (2) Essential thrombocytosis (3) Myelofibrosis (4) CML

Question 8

What is important to remember about chronic myeloproliferative disorders in terms of their relation versus distinction?

Answer 8

The myeloproliferative disorders represent an often-overlapping spectrum, but the classic findings are described below.

Question 9

With what process is JAK2 involved? How does it relate to myeloproliferative disorders?

Answer 9

JAK2 is involved in hematopoietic growth factor signaling. Mutations are implicated in myeloproliferative disorders other than CML.

Question 10

What is the hematocrit in polycythemia vera?

Answer 10

Hematocrit > 55%

Question 11

What kind of mutation is associated with polycythemia vera, and in what gene is it?

Answer 11

Somatic (non-hereditary) mutation in JAK2 gene

Question 12

How does Polycythemia vera often present?

Answer 12

Often presents as intense itching after hot shower.

Question 13

What is a rare but classic symptom of Polycythemia, and what causes it?

Answer 13

Rare but classic symptom is erythromelalgia (sever, burning pain and reddish or bluish coloration) due to episodic blood clots in vessels of the extremities

Question 14

What causes secondary polycythemia?

Answer 14

Secondary polycythemia is via natural or artificial increase in EPO levels

Question 15

To which other chronic myeloproliferative disorder is Essential thrombocytosis similar? What distinguishes it?

Answer 15

Similar to polycythemia vera, but specific for overproduction of abnormal platelets –> bleeding, thrombosis

Question 16

What are the effects of Essential thrombocytosis?

Answer 16

overproduction of abnormal platelets –> bleeding, thrombosis

Question 17

What is the histological finding associated with Essential thrombocytosis?

Answer 17

Bone marrow contains enlarged megaryocytes

Question 18

What is myelofibrosis?

Answer 18

Fibrotic obliteration of bone marrow

Question 19

What are histological findings of Myelofibrosis?

Answer 19

Teardrop RBCs and immature forms of the myeloid line; Think: “Bone marrow is CRYING because it’s fibrosed”

Question 20

What change is associated with CML, and what 2 effects does it have?

Answer 20

bcr-abl transformation leads to increased cell division and inhibition of apoptosis

Question 21

What is the treatment for CML?

Answer 21

Treatment: imatinib (Gleevec)

Question 22

Give the change/presence of the following in polycythemia vera: (1) RBCs (2) WBCs (3) Platelets (4) Philadelphia chromosome (5) JAK2 mutations.

Answer 22

(1) increased (2) increased (3) increased (4) negative (5) positive

Question 23

Give the change/presence of the following in Essential thrombosis: (1) RBCs (2) WBCs (3) Platelets (4) Philadelphia chromosome (5) JAK2 mutations.

Answer 23

(1) no change (2) no change (3) increased (4) negative (5) positive (30-50%)

Question 24

Give the change/presence of the following in Myelofibrosis: (1) RBCs (2) WBCs (3) Platelets (4) Philadelphia chromosome (5) JAK2 mutations.

Answer 24

(1) decreased (2) variable (3) variable (4) negative (5) positive (30-50%)

Question 25

Give the change/presence of the following in CML: (1) RBCs (2) WBCs (3) Platelets (4) Philadelphia chromosome (5) JAK2 mutations.

Answer 25

(1) decreased (2) increased (3) increased (4) positive (5) negative

Question 26

What are the 4 types of polycythemia?

Answer 26

(1) Relative (2) Appropriate absolute (3) Inappropriate absolute (4) Polycythemia vera

Question 27

Give the change in the following with Relative polycythemia: (1) Plasma volume (2) RBC mass (3) O2 saturation (4) EPO levels.

Answer 27

(1) decreased (2) no change (3) no change (4) no change

Question 28

Give the change in the following with Appropriate absolute polycythemia: (1) Plasma volume (2) RBC mass (3) O2 saturation (4) EPO levels.

Answer 28

(1) no change (2) increased (3) decreased (4) increased

Question 29

Give the change in the following with Inappropriate absolute polycythemia: (1) Plasma volume (2) RBC mass (3) O2 saturation (4) EPO levels.

Answer 29

(1) no change (2) increased (3) no change (4) increased

Question 30

Give the change in the following with polycythemia vera: (1) Plasma volume (2) RBC mass (3) O2 saturation (4) EPO levels.

Answer 30

(1) increased (2) very increased (3) no change (4) decreased

Question 31

What causes relative polycythemia? Give 2 examples of this.

Answer 31

Decrease in plasma volume (dehydration, burns)

Question 32

What are 3 examples of conditions associated with Appropriate absolute polycythemia?

Answer 32

(1) Lung disease (2) Congenital heart disease (3) High altitude

Question 33

What are 5 examples of conditions associated with Inappropriate absolute polycythemia?

Answer 33

(1) Renal cell carcinoma (2) Wilms tumor (3) cyst (4) hepatocellular carcinoma (5) hydronephrosis

Question 34

What causes inappropriate absolute polycythemia?

Answer 34

Due to ectopic EPO

Question 35

What causes polycythemia vera?

Answer 35

Due to negative feedback