Case 84

Submitting Author: Ok, Chi Young, MD
Institution: MD Anderson Cancer Center
Additional authors:Yang O. Huh, MD
Session: AML with recurrent genetic abnormalities Part I

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HISTORY

12-year-old female without significant prior medical history

- Chief complaint: upper respiratory infection symptom
- Splenomegaly: 1 to 2 cm below the costal margin
- Laboratory findings H/H: 11.4/32.6, WBC: 111.2, platelet 17, 96% blasts on differential

DETAILS

Site: Right posterior iliac crest. Method of fixation: formalin-fixed

Microscopic pathology:
Biopsy: Hypercellular (100%) bone marrow with intermediate sized and monotonous blasts with fine delicate nuclear chromatin and occasional starry-sky pattern
Smear: Markedly increased blasts, blasts are intermediate to large in size and show round/oval to slightly indented nuclei, fine chromatin, one or two prominent nucleoli, and small to moderate amount of basophilic agranular cytoplasm. No Auer rods are identified.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Positive stains
Lysozyme (in a subset, 10-20%), CD11c, CD117

Negative stains
MPO, TdT, CD68 (PG-M1)

CYTOGENETIC FINDINGS

48,XX,t(2;4;11)(p23;q21;q23),del(3)(q21q27),+der(4)t(2;4;11),add(6)(p11.2),del(12)(p12p13),+13,add(19)(p13.3)[20]

FISH:

-MLL gene: rearranged
-ETV gene: deleted
-PML/RARA: negative
-BCR/ABL: negative

MOLECULAR FINDINGS

- t(4;11)(q21;q23)MLL-AF4 detected by nanofluidics PCR
- FLT3: wild-type
- PML/RARA: wild-type
- RUNX1/RUNX1T1: wild-type
- CBFβ/MYH11: wild-type
- BCR/ABL: wild-type

INTERESTING FEATURES

MLL gene rearrangement with MLLT2 (AF4) as a partner is common in acute lymphoblastic leukemia, but rare (1.7%)* in acute myeloid leukemia. t(4;11) in pediatric acute myeloid leukemia is not an independent prognostic factor*. t(2;4;11) is a rare variant of MLL gene rearrangement, confirmed by PCR, in acute myeloid leukemia.

*Blood 2009;114:2489-96

PROPOSED DIAGNOSIS

Acute myeloid leukemia with MLL gene rearrangement

CONSENSUS DIAGNOSIS

Acute myeloid leukemia with (variant) t(4;11)(q21;q23); MLLT2-MLL (AF4-MLL)