Benign & Malignant Hematology

Question 1

t(15;17)

Answer 1

PML/RARA-alpha fusion protein

Diagnostic for APML

Question 2

Passenger Lymphocyte Syndrome

Answer 2

B-lymphocytes from donor (often female) form antibodies that can attack the recipient’s RBCs

• can occur several days-weeks after allo-SCT
• Ex: Donor is blood group Group O Rh+ and Recipient is Group A Rh+; B-lymphocytes from donor make anti-A Abs against recipient’s RBCs resulting in hemolytic anemia

Question 3

Hereditary Elliptocytosis

Answer 3

Hereditary defect in RBC membrane protein and RBC cytoskeleton (alpha-spectrin) that predisposes to hemolytic anemia

• Tx: Folic acid 1mg QD, transfusions PRN and splenectomy for select transfusion-dependent pta

Question 4

Most likely mutation conferring resistance to Ibrutinib in patient with Stage IV CLL with +del 17p?

Answer 4

C481S mutation

• Ibrutinib is a BTK inhibitor that irreversibly covalently binds to C481 of the kinase; C481S mutation disrupts this binding and results in resistance to Ibrutinib

Question 5

Large Granular Lymphocyte (LGL) Leukemia

Answer 5

• Clonal disorder of CD3+ cytotoxic T-cells or NK-cells (natural killer cells)
• Immunophenotype:
  T-LGL: CD3+, CD8+, CD57+
  NK-LGL: CD3(-), CD8+, CD57+
• Clinically p/w anemia, neutropenia and often asst’d with rheumatoid arthritis
• Dx: +TCR-gamma gene rearrangement detected on PCR

Question 6

Felty’s Syndrome

Answer 6

Triad:

1. Rheumatoid arthritis
2. Splenomegaly
3. Neutropenia

Question 7

CP CML Risk Stratification

Answer 7

Sokal Risk:
Age
SM present
Plts
Blast %

Hasford Risk:
Age
SM present
Plts
Blast %
Basophils
Eosinophils

Question 8

t(9;22)

Answer 8

BCR/ABL1 fusion gene = activated tyrosine kinase

• 5% of CML pts lack Philadelphia chromosome despite being positive for BCR/ABL rearrangement; most of these pts were found to have cryptic insertions between chrom 9 and 22 on FISH and were responsive to TKI therapy

Question 9

Triad of IDA, esophageal webs and glossitis/angular cheilosis.

Answer 9

Plummer-Vinson Syndrome

Pts are at increased risk for SCC of esophagus and pharynx