Approach to Acute Leukemia
Dr. Nikhil Patkar
Clinician Scientist & Asst Professor
Hematopathology Laboratory
Tata Memorial Centre
[email protected]
History
• 59 year old female, easy fatiguability
• Leucocytosis, decrease in platelets
– TLC:90,000/mm3
– Platelet counts: 54,000/mm3
• Suspected to have acute leukemia and
referred to TMH
Questions to ask when faced with
acute leukemia
• Is there an increase in blasts or blast
YES?
equivalents?
• Are there abnormal promyelocytes?
• Are there Auer rods?
• Is cytochemical MPO positive?
• Is cytochemical NSE positive?
• Must send for immunophenotyping.
NO?
NO?
NO?
NO?
Cytochemical MPO
Summary
• Morphology
– Myeloid Blasts
– Strong MPO positive
• Immunophenotype
– CD34 Negative
– HLA-DR Negative
– CD13,CD33positive, CD117 dim-negative
DIAGNOSIS?
Questions to ask when faced with
acute leukemia
• Is there an increase in blasts or blast
YES?
equivalents?
• Are there abnormal promyelocytes?
• Are there Auer rods?
• Is cytochemical MPO positive?
• Is cytochemical NSE positive?
• Must send for immunophenotyping.
NO?
NO?
NO?
NO?
Is this acute promyelocytic leukemia?
Yes / No
Is this distinction important?
How urgent is the report ?
APL with t(15;17)(q22;q12); PML-RARA
How does this determine treatment?
• AML with t(15;17)
– Treated with
• All Trans Retinoic Acid
• Or Arsenic Trioxide
– Excellent survival
– High mortality if not detected early & treated
correctly
• DIC and bleeding complications eg intracranial bleeding
– Practical working algorithm in a pathology lab
• AML M3 or non M3 AML
Overall survival (top) and disease-free survival (bottom) curves of 14 relapsed APL
patients after As2O3-induced CR.
Shen Z et al. Blood 1997;89:3354-3360
©1997 by American Society of Hematology
Cup Shaped Blasts
Cytochemical MPO Positive
Typical morphology of myeloid blasts with cup-like nuclear invagination in AML. (A) The
“cup” seems to be a part of the nucleus in Pappenheim staining, however it is positive for
myeloperoxidase (MPO) in reactive blasts.
Kroschinsky F P et al. Haematologica 2008;93:283-286
©2008 by Ferrata Storti Foundation
Cup shaped blasts are often associated with
NPM1 Mutations
NPM WT
169bp
NPM
Mutant
173 bp
FLT3-WT
330bp
Final Diagnosis
NPM1 Mutated AML, FAB AML M1