Case 250

Submitting Author: Nybakken, Grant Edward, MD, PhD
Institution: Stanford University Medical Center
Additional authors:Daniel Arber, MD
Session: Acute leukemias of ambiguous lineage

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HISTORY

47 year-old woman with a history of systemic lupus erythematosus, now with acute leukemia

DETAILS

Bone marrow, iliac crest, Bouin’s fixation

Peripheral blood:

Large blasts with irregular nuclear contours, open chromatin, variably prominent nucleoli (occasionally cup-like) and scant cytoplast account for 40% of cellularity. Auer rods are not appreciated. Normochromic normocytic anemia with minimal anisopoikilocytosis and no increase in polychromasia. Platelets are decreased in number and include giant forms. No dysplasia is noted.

Aspirate smear:

Blasts (as described above) account for 95% of cellularity. Erythroid and myeloid cells are markedly decreased without evident dysplasia. Megakaryocytes are decreased in number and normal in appearance.

Cytochemistry stains for myeloperoxidase and nonspecific esterase are negative.

Bone marrow core biopsy:

The bone marrow sections are hypercellular for age (>95%). Large blasts with irregular nuclear contours, open chromatin, inconspicuous nucleoli and scant cytoplasm account for 95% of cellularity. Trilineage hematopoiesis is markedly decreased and without dysplasia.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Flow cytometry

Cells with the CD45 and side scatter characteristics of blasts (86%) with the following immunophenotype:

Positive: CD7, CD33, CD34, CD38, HLA-DR

Negative: cCD3, sCD3, CD10, CD11c, CD14, CD19, CD22, CD56, CD61, CD64, cCD79a, myeloperoxidase

CYTOGENETIC FINDINGS

92~97<4n>,XXXX,+4,+4,+6,-7,?t(10;11)(p12~13;q14~21)x2,-13,i(17)(q10),+20[cp4]/46,XX[16]

FISH for BCR/ABL1 is negative with 99% of nuclei with four signals each for BCR and ABL1

FISH for PML/RARA is negative with 96.5% of nuclei with four signals each for PML and RARA

MOLECULAR FINDINGS

Positive for EGFR L858R mutation.

Negative for BCR-ABL1 transcripts.

No mutations detected in CEBPA or exons 8 and 17 of KIT.

No insertion mutations into NPM1.

INTERESTING FEATURES

1. Acute undifferentiated leukemia expressing T (CD7) and myeloid (CD33) antigens, but lacking lineage-defining antigens.

2. There is a t(10;11) translocation, consistent with a PICALM/MLLT10 gene rearrangement, a known rearrangement found in acute leukemias of ambiguous lineage.

3. Tetraploid clone with a complex karyotype.

4. No NPM1 mutation, despite cup-like nucleoli.

5. L858R EGFR mutation identified.

PROPOSED DIAGNOSIS

Acute undifferentiated leukemia with t(10;11) translocation consistent with PICALM/MLLT10.

CONSENSUS GROUP: ADDITIONAL INFORMATION/STUDIES

Additional immunostains performed by conference consensus group:

Lysozyme: Negative
CD68: Negative
TdT: Negative

CONSENSUS DIAGNOSIS

Acute myeloid leukemia with minimal differentation, with t(10;11); PICALM/MLLT10