Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology...

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Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre [email protected]

Transcript of Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology...

Page 1: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

Approach to Acute Leukemia

Dr. Nikhil PatkarClinician Scientist & Asst Professor

Hematopathology LaboratoryTata Memorial [email protected]

Page 2: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

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

Page 3: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.
Page 4: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

Questions to ask when faced with acute leukemia

• Is there an increase in blasts or blast equivalents?

• Are there abnormal promyelocytes?• Are there Auer rods?• Is cytochemical MPO positive?• Is cytochemical NSE positive?• Must send for immunophenotyping.

YES?

NO?

NO?

NO?

NO?

Page 5: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

Cytochemical MPO

Page 6: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.
Page 7: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

Summary

• Morphology– Myeloid Blasts– Strong MPO positive

• Immunophenotype– CD34 Negative– HLA-DR Negative– CD13,CD33positive, CD117 dim-negative

Page 8: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

DIAGNOSIS?

Page 9: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

Questions to ask when faced with acute leukemia

• Is there an increase in blasts or blast equivalents?

• Are there abnormal promyelocytes?• Are there Auer rods?• Is cytochemical MPO positive?• Is cytochemical NSE positive?• Must send for immunophenotyping.

YES?

NO?

NO?

NO?

NO?

Page 10: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

Is this acute promyelocytic leukemia?

Yes / No

Is this distinction important?How urgent is the report ?

Page 11: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

APL with t(15;17)(q22;q12); PML-RARA

Page 12: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

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

Page 13: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

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

Page 14: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.
Page 15: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

Cup Shaped BlastsCytochemical MPO Positive

Page 16: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

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

Page 17: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

Cup shaped blasts are often associated with NPM1 Mutations

NPM WT169bp

NPM Mutant173 bp

FLT3-WT330bp

Page 18: Approach to Acute Leukemia Dr. Nikhil Patkar Clinician Scientist & Asst Professor Hematopathology Laboratory Tata Memorial Centre patkarnv@tmc.gov.in.

Final Diagnosis

NPM1 Mutated AML, FAB AML M1