This is a complilation of expected changes in the myeloid neoplasms in the upcoming 2016 update of the "WHO classification of tumours of haematopoietic and lymphoid tissues". Some of the changes may not be incorporated in the actual published book. This compilation has been prepared from presentations from persons actually concerned with revision of the book. All credits goes to them.

1. 2016 Update of
WHO Classification of Tumours
of Haematopoietic and Lymphoid
Tissues
Dr Ankit Raiyani
Dept of Hematology
SSH, Pune
What changes to expect in myeloid
neoplasm

2. Introduction
• Actual classification is yet to be published
• Some of the particulars may change in the
published copy
• Sources:
– WHO update: Myeloproliferative neoplasms, Atilio
Orazi
– WHO update: Acute Leukemia, Deniel Arber
– WHO update: MDS, Robert Hasserjian
– LEUKEMIA CLASSIFICATION 2016: WHAT, WHEN,
“WHO”, Kathryn Foucar

3. Myeloid Neoplasms- WHO 2016
• AML:
– 25 subtypes; 3 new genetic entities
– (numerous prognostic “types”)
– (new criteria for blast enumeration)
– (new familial category)
• MDS:
– 7 subtypes
– (all new names; some integration of molecular)
• MDS/MPN:
– 5 subtypes; 1 new entity (RARS-T new entity)
– (new molecular genetic criteria)
• MPN:

4. Acute Myeloid Leukemia

5. Acute Myeloid Leukemia

6. New Acute Myeloid Leukemia
subtypes 2016
• AML with RUNX1 mutation (provisional)
– Elderly male, poor prognosis
• AML with BCR-ABL 1 (provisional)
– Antigen receptor deletion (IGH)
• AML with biallelic CEBPA mutations (CEBPAdm
)
• Familial AML/MDS (multiple types)
• Promoted to full entity (No longer provisional)
– Acute Myeloid Leukemia with NPM1 mutation
– Acute Myeloid Leukemia with CEBPAdm

7. Reason to include AML RUNX1
mutation as separate entity
Jason H. Mendler et al. JCO 2012;30:3109-3118

8. Reason for including “Biallelic” to
CEBPA mutation
Kaplan-Meier curves for overall survival stratified by (A) CEBPA–wild-type (WT) or CEBPA-
mutant status, (B) CEBPA-WT, CEBPA-single, or CEBPA-double mutant status
Claire L. Green et al. JCO 2010;28:2739-2747
• 7-20% AML has CEBPA mutation
• 12-47% are monoallelic, rest biallelic

11. AML-Required studies and key
information in reports
Clinical Hx of chemo/MDS
Morphology Blast %, Dysplastic %
Flow Cytometry/
Cytochemistry
Confirm myeloid (CD 33, CD13,
MPO)
Cytogenetics AML-defining vs other (many
karyotypic subtypes)
Molecular:
(selected)*
FLT3, NPM1, CEBPA, RUNX1, BCR-
ABL1, other prognostic factors, KIT
*Only FLT3 mutation analysis required for all AML

12. New Acute Myeloid Leukemia
Criteria

13. Revised criteria for AML -MRC
• No prognostic significance of multilineage dysplasia
(MLD), IF-
– No prior h/o Myelodysplastic Syndrome
– NPM1 or CEBPAdm
positive
– Normal karyotype
• Classified under AML with NPM1m
/ CEBPAdm
• Del9q is an MDS related entity only in the absence of
NPM1 mutations
– NPM1 commonly associated with del9q and is likely not adverse
in this setting
• If prior h/o MDS, MDS/MPN, MPN or tMDS/AML or
cytogenetic abnormalities (other than del9q)-
– No survival benefit of NPM1
– Considered as AML -MRC

15. Acute Erythroleukemia
(AML M6a)
• Blast percentage to be calculated from total nucleated
cells on BMA. (not from nonerythroid cells)
• Many cases of AML M6a (by older classification) will fall
into MDS RAEB group
• Rest will be considered AML (probably AML MRC)
• Pure Erythroid leukemia will remain a separate subclass
• This is done to maintain consistency in the blast counting
in MDS/AML spectrum
– Avoid abrupt change in blasts% when erythroids reach >50%
– Erythroids may fluctuate due to therapy, metabolic changes,
EPO levels
• This will link AML M6a with MDS, with which it shares
morphologic and genetic features

19. Myelodysplastic Syndromes

22. Assessment of dysplasia

24. New handling of MDS with ring
sideroblasts
• MDS with multilineage dysplasia and ring
sideroblast will be reinstated (MLD-RS)
• MDS with SF3B1 mutation can be
classified as SLD- RS/ MLD-RS if >5%
ring sideroblasts are present
– Will not require >15% RS
• SF3B1 mutation will not affect MDS –EB
or isolated del(5q)

26. Changes in MDS del(5q)
• Allow one additional cytogenetic
abnormality
– Excluding high risk abnormalities
• TP53 mutation study or p53 immunostain
• Exclusions
– >5% blasts in PB/BM
– Significant granulocytic dysplasia

27. MDS/MPN

28. RARS-T
• Promoted to full entity under MDS/MPN
MDS like MPN like
Clinical
• Macrocytic anemia
• Transfusion requirement
• Thrombocytosis
• Need for cytoreduction
Morphological
• Erythroid dysplasia
• Ring sideroblasts
• Large megakaryocytes
with bulbous nuclei
Genetic
SF3B1 mutation (80-90%) JAK2 mutation (50-60%)
Rarely CALR/MPL

29. Updates to CMML
• Common pattern of co-mutations in
epigenetic modifier and RNA splicing gene
• TET2+SRSF4 in 30-35% CMML
• Either TET2, SRSF4, or ASXL1 in 90%
• ASXL1 a/w poor prognosis
• Presence of NPM1 or 11q23
rearrangement a/w rapid progression to
AML

30. aCML
• No changes in criteria
• Assess for CSF3R mutation (If positive
strongly consider CNL)

31. Myeloproliferative Neoplasms

35. CNL
• Integration of CSF3R mutations in
diagnosis (present in 90% CNL)

36. THANK YOU!!!