Case

5
 Case presenta+on
•  26 year old male presented with 3 weeks of
worsening flu like symptoms with a sore throat,
cervical lymphadenopathy and, more recently,
some night sweats.
•  A CBC showed leukocytosis with a WBC of 68 K
cells/microliter
•  A sample of peripheral blood was submiEed to
the laboratory for flow cytometry
 Objec&ve 1
•  For each available tube check the quality of
the data and the pre drawn gates
•  Highlight your suspected blast populaIon in
red
•  Describe the immunophenotype of the blast
populaIon using data from each tube
–  Note: A cytoplasmic tube is also available in this
case to provide addiIonal immunophenotypic
data
 List the immunophenotypic features
of the blasts
•  PosiIve for

•  NegaIve for
What is is the lineage of the blasts?

What is in your differen&al diagnosis?

What addi&onal studies would you like

to narrow your differen&al diagnosis
and render a final diagnosis?
 Flow cytometry
CD45 vs SSC defined blasts CD45 vs SSC defined blasts CD45 vs SSC defined blasts CD45 vs SSC defined blasts

CD7 APC CD2 FITC CD4 A594 CD19 PE-CF594

Case 5 TdT test .fcs Case 5 lineage.fcs CD45 vs SSC defined blasts CD45 vs SSC defined blasts

TDT FITC cMPO FITC CD117 PE-Cy5 HLA-DR PB

 Summary of flow cytometry data
•  Expanded blast populaIon comprises ~80%
of the WBC
•  Blasts express
–  CD2, CD3 (decreased on the surface), CD5, CD7
–  TdT, CD1a, parIal CD34, parIal CD117
–  CD4 and CD8 are mostly negaIve
–  No expression of B cell markers or other
myeloid markers tested
 Flow cytometric diagnosis:
T-Lymphoblas+c leukemia
Addi+onal data
•  Concurrent cytogeneIcs showed the
following:
–  Normal karyotype
–  FISH demonstrated deleIon 9p21
What is Your Final
Diagnosis?
T lymphoblas+c leukemia
 Could this be early
thymocyte precursor
T-LL?
 Early thymocyte precursor T-LL
•  Early thymocyte precursor (ETP) T-LL (10-15% of T-LL)
•  Derived from an early T cell precursor and shows T cell
differenIaIon but retains expression of some myeloid
and/or stem cell anIgens
•  DefiniIon
–  T cells: CD7, cCD3 Coustan-Smith et al. Lancet Oncology 2008;10:147-56.

*
–  Lack CD1a, CD8
–  CD5 is negaIve or decreased (<75% expression)
–  Expression of 1 or more myeloid/stem cell anIgens:
•  Expression on ≥25% of blasts
•  CD34, CD117, HLA-DR, CD13, CD33, CD11b, or CD65

* A subset of cases deemed “near ETP” meet these criteria but show increased
CD5 expression with otherwise similar features compared to typical ETP-T-LL
 Gene+cs in ETP T-LL
•  Frequent myeloid associated gene mutaIons
–  FLT3 (~35%)
•  Associated with expression of CD13 and CD117 without
CD33
–  DNMT3A (16% in adults)
•  Less frequent more typical T-LL gene
mutaIons
–  Notch 1 mutaIons (15%)
–  Clonal T cell receptor gene rearrangement (59%)
Neumann et al. Blood 2013 121(23):4749-52.
Neumann et al. PLOS ONE 2013;8(1):e53190.
Wu et al. Science TranslaIonal Medicine 2012;134(4):134ra63.
 Prognosis in ETP T-LL
•  Many studies show poorer prognosis for T-LL with an ETP
immunophenotype
–  Pediatric: Coustan-Smith et al. Lancet Oncology 2008;10:147-56.
–  Adolescents and adults: Jain et al. Blood 2016;127(15):1863-9.
•  Has not been borne out in all studies with a recent large (n=1144),
pediatric study (conducted by COG) demonstraIng no significant
differences in event free survival or overall survival for ETP T-LL
–  Wood et al. Blood, 124(21), 1 (abstract)
–  Higher rate of inducIon failure for both ETP and near ETP but 5-year
EFS and OS that were not staIsIcally different:
•  ETP (87.0%; 93.0%)
•  Near-ETP (84.4%; 91.6%)
•  Not-ETP (86.9%; 92.0%).
•  AddiIonal studies will be needed to characterize the prognosIc
impact of this subtype and to determine the opImal course of
therapy in paIents presenIng with this immunophenotype
 Could this be early
thymocyte precursor T-LL?

•  Although expression of CD34 and CD117 may
make you wonder about this possibility, the
level of CD5 and expression of CD1a take this
enIty off the list