Blood and BM Path Chapter 24 - CML

Question 1

All cases of CML are ___.

Not all cases of ___ are CML.

Answer 1

All cases of CML are t(9;22) BCR-ABL1.

Not all cases of t(9;22) BCR-ABL1 are CML.

Question 2

Epidemiology of CML

Answer 2

Most frequently occurs in middle age, 40’s and 50’s. It is rarely seen in childhood.

Ionizing radiation exposure is a risk factor.

Question 3

Phases of CML

Answer 3

1. Chronic phase
2. Accelerated phase (may or may not occur) – prognosis ~2 years
3. Acute phase / Blast crisis - prognosis ~3 months

Question 4

Hiatus leucaemicus

Answer 4

Refers to the “gap” in maturation observed in the blood and bone marrow of those with acute leukemia

Notably, it is absent in chronic leukemias, since they are able to mature!

Question 5

By definition, in CML there is __% blasts in the blood and bone marrow.

Answer 5

By definition, in CML there is <20% blasts in the blood and bone marrow.

Otherwise it would be classified as an acute leukemia.

Question 6

CML often has elevated platelet counts (>600,000). So, how can we differentiate it from essential thrombasthenia?

Answer 6

• Presence of:
  
  • BCR-ABL1 translocation
  • Characteristic bone marrow changes
  • Left shift
  • Basophilia
• Absence of:
  
  • JAK2^V617F

Question 7

How can mature, neoplastic granulocytes of CML be differentiated from normal mature granulocytes?

Answer 7

They display decreased leukocyte alkaline phosphatase (LAP) activity

Despite this, their function is not impaired.

Question 8

Characteristic bone marrow features of CML

Answer 8

• Hypolobated megakaryocytes aka micromegakaryocytes
  
  • Pathognononic – lack of this feature should call the diagnosis into question
• Hypercellularity
• Increased marrow vascularity
• Pseudo-Gaucher cells (storage histiocytes mimicing those in Gaucher disease)
  
  • These cells belong to the neoplastic clone and their morphology is due to relative enzyme insufficiency resulting from phagocytosis of leukemic cells.
• Sometimes marrow fibrosis

Question 9

What is the central cell in this picture?

Answer 9

Micromegakaryocyte

Question 10

What is the central cell in this picture?

Answer 10

pseudo-Gaucher cell

Question 11

“Atypical CML”

Answer 11

Shares morphologic features with “typical” CML, but has no BCR-ABL1 fusion protein.

Important differences include:

• Lack of thrombocytosis and basophilia
• Presence of both hyperlobated and hypolobated megakaryocytes
• Dysplastic erythropoiesis with increased red cells
• Dysplastic granulopoiesis with chromatin clumping in mature granulocytes

Question 12

CML may be accompanied by ____, but should really never be accompanied by ____ on peripheral CBC.

Answer 12

CML may be accompanied by basophilia, but should really never be accompanied by eosinophilia on peripheral CBC.