Hem & Onc - Pathology (Myeloproliferative disorders & related topics) Flashcards
Pg. 396-398 in First Aid 2014 Sections include: -Langerhans cell histiocytosis -Chronic myeloproliferative disorders -Polycythemia
What is Langerhans cell histiocytosis?
Proliferative disorders of dendritic (Langerhans) cells from monocytic lineage.
How does Langerhans cell histiocytosis present?
Presents in a child as lytic bone lesions and skin rash or as recurrent otitis media with a mass involving the mastoid bone.
Describe the functioning of cells in Langerhans cell histiocytosis.
Cells are functionally immature and do not efficiently stimulate primary T lymphocytes via antigen presentation.
What 2 markers are expressed by cells in Langerhans cells histiocytosis?
Cells express S-100 (mesodermal origin) and CD1a
What does the S-100 marker indicate, and with what myeloproliferative disorder is it associated?
S-100 (mesodermal origin); Langerhans cell histiocytosis
What EM finding is characteristic of Langerhans cell histiocytosis?
Birbeck granules (“tennis rackets” on EM) are characteristic
Name 4 chronic myeloproliferative disorders.
(1) Polycythemia vera (2) Essential thrombocytosis (3) Myelofibrosis (4) CML
What is important to remember about chronic myeloproliferative disorders in terms of their relation versus distinction?
The myeloproliferative disorders represent an often-overlapping spectrum, but the classic findings are described below.
With what process is JAK2 involved? How does it relate to myeloproliferative disorders?
JAK2 is involved in hematopoietic growth factor signaling. Mutations are implicated in myeloproliferative disorders other than CML.
What is the hematocrit in polycythemia vera?
Hematocrit > 55%
What kind of mutation is associated with polycythemia vera, and in what gene is it?
Somatic (non-hereditary) mutation in JAK2 gene
How does Polycythemia vera often present?
Often presents as intense itching after hot shower.
What is a rare but classic symptom of Polycythemia, and what causes it?
Rare but classic symptom is erythromelalgia (sever, burning pain and reddish or bluish coloration) due to episodic blood clots in vessels of the extremities
What causes secondary polycythemia?
Secondary polycythemia is via natural or artificial increase in EPO levels
To which other chronic myeloproliferative disorder is Essential thrombocytosis similar? What distinguishes it?
Similar to polycythemia vera, but specific for overproduction of abnormal platelets –> bleeding, thrombosis
What are the effects of Essential thrombocytosis?
overproduction of abnormal platelets –> bleeding, thrombosis
What is the histological finding associated with Essential thrombocytosis?
Bone marrow contains enlarged megaryocytes
What is myelofibrosis?
Fibrotic obliteration of bone marrow
What are histological findings of Myelofibrosis?
Teardrop RBCs and immature forms of the myeloid line; Think: “Bone marrow is CRYING because it’s fibrosed”
What change is associated with CML, and what 2 effects does it have?
bcr-abl transformation leads to increased cell division and inhibition of apoptosis
What is the treatment for CML?
Treatment: imatinib (Gleevec)
Give the change/presence of the following in polycythemia vera: (1) RBCs (2) WBCs (3) Platelets (4) Philadelphia chromosome (5) JAK2 mutations.
(1) increased (2) increased (3) increased (4) negative (5) positive
Give the change/presence of the following in Essential thrombosis: (1) RBCs (2) WBCs (3) Platelets (4) Philadelphia chromosome (5) JAK2 mutations.
(1) no change (2) no change (3) increased (4) negative (5) positive (30-50%)
Give the change/presence of the following in Myelofibrosis: (1) RBCs (2) WBCs (3) Platelets (4) Philadelphia chromosome (5) JAK2 mutations.
(1) decreased (2) variable (3) variable (4) negative (5) positive (30-50%)
Give the change/presence of the following in CML: (1) RBCs (2) WBCs (3) Platelets (4) Philadelphia chromosome (5) JAK2 mutations.
(1) decreased (2) increased (3) increased (4) positive (5) negative
What are the 4 types of polycythemia?
(1) Relative (2) Appropriate absolute (3) Inappropriate absolute (4) Polycythemia vera
Give the change in the following with Relative polycythemia: (1) Plasma volume (2) RBC mass (3) O2 saturation (4) EPO levels.
(1) decreased (2) no change (3) no change (4) no change
Give the change in the following with Appropriate absolute polycythemia: (1) Plasma volume (2) RBC mass (3) O2 saturation (4) EPO levels.
(1) no change (2) increased (3) decreased (4) increased
Give the change in the following with Inappropriate absolute polycythemia: (1) Plasma volume (2) RBC mass (3) O2 saturation (4) EPO levels.
(1) no change (2) increased (3) no change (4) increased
Give the change in the following with polycythemia vera: (1) Plasma volume (2) RBC mass (3) O2 saturation (4) EPO levels.
(1) increased (2) very increased (3) no change (4) decreased
What causes relative polycythemia? Give 2 examples of this.
Decrease in plasma volume (dehydration, burns)
What are 3 examples of conditions associated with Appropriate absolute polycythemia?
(1) Lung disease (2) Congenital heart disease (3) High altitude
What are 5 examples of conditions associated with Inappropriate absolute polycythemia?
(1) Renal cell carcinoma (2) Wilms tumor (3) cyst (4) hepatocellular carcinoma (5) hydronephrosis
What causes inappropriate absolute polycythemia?
Due to ectopic EPO
What causes polycythemia vera?
Due to negative feedback
