Case 300

Submitting Author: Hosking, Paul Robert, MD
Institution: Columbia University Medical Center, New York, NY
Additional authors:Bachir Alobeid, MD Govind Bhagat, MBBS Daniela Hoehn, MD PhD
Session: AML with myelodysplasia-related changes

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HISTORY

26-yearold male with unremarkable past medical history and a sudden onset of headache, abdominal pain and B symptoms, non-responsive to acetaminophen. He presented to his PCP, was started on broad spectrum antibiotics for a presumed infection (details unknown). After initial improvement, a subsequent CBC showed: WBC: 1.3, Hb: 6.7, Hct: 20.0, Platelets: 113, MCV: 111.1, (Differential: 4% neutrophils, 60% lymphocytes, 10% blasts, 18% atypical lymphocytes) Coags: PT: 15.1, INR: 1.17, fibrinogen: 540. LDH: 312.

DETAILS

Diagnostic Bone Marrow Examination:

Bone marrow core needle biopsy (left posterior iliac crest) was fixed in Bouin solution. Bone marrow aspiration was sent for morphological evaluation, cytogenetic analysis and flow cytometry.

• Core needle biopsy (hematoxylin and eosin) demonstrated markedly increased cellularity (~100%). The marrow space was almost entirely replaced by small-to-medium sized blasts. Normal hematopoiesis was markedly diminished.

• Wright- Giemsa stained aspirate smear demonstrated 81% blasts. Blasts were large in size, with round nuclei, smooth nuclear contour, evenly dispersed nuclear chromatin, 1 or 2 nucleoli of varying prominence with scant basophilic cytoplasm. No Auer rods.

Day 14 Bone Marrow Examination: persistent leukemia

Day 60 Bone Marrow Examination: persistent leukemia

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Diagnostic Bone Marrow Examination:

• Immunohistochemical analysis: blasts were positive for CD34, CD56 and CD123.

• Flow cytometric analysis detected an aberrant blast population positive for: CD4, CD7, CD11c, CD13 (partial), CD16/56, CD33, CD34, CD38, CD43, CD64 (subpopulation dim), CD117 (subpopulation dim), HLA-DR (bright). The blasts were negative for CD1a, cCD3, CD10, CD19, TdT and mostly MPO.

Day 14:

• Immunohistochemical analysis: blasts were positive for CD34 and CD123 with a subset expressing CD56 dim.

• Flow cytometric analysis detected an aberrant blast population that was positive for: CD4, CD7, CD11c, CD13, CD16/56 (subpopulation), CD33, CD34, CD38, CD43, CD117 and HLA-DR. A subpopulation showed expression of CD2 (dim) and CD5 (dim) and CD64. The cells were negative for CD3, CD10, CD19, cTdT, cyt. CD3, and mostly MPO.

Day 60:

• Immunohistochemical analysis: blasts were positive for CD34, further decrease in expression of CD123 and CD56

• Flow cytometric analysis showed an aberrant blast population that was positive for: CD4, CD7, CD11c, CD13, CD33, CD34, CD52 (subset dim), CD56 (dim subset), CD117 (subset), and HLA-DR.

CYTOGENETIC FINDINGS

Diagnostic Bone Marrow Examination:

G-banding karyotype analysis: 46,XY,del(5)(q22q31)[7]/46,XY[13]

Fluorescence in situ hybridization (FISH):

Deletion 5q in 91.2% cells (EGR1/5p15 probes), 47% were tetraploid.

D7S486/CEP 7, D20S108, and CEP 8 probes: no deletion or gain.

However, 4 copies of each probe were found in 58~71% cells.

Day 14 :

G-banding karyotype analysis: 46,XY,del(5)(q22q31)[7]/90~92<4N>,idemx2,-17[cp11]/46,XY[2]

Fluorescence in situ hybridization (FISH):

5q31 deletion in 87.5% cells (EGR1/5p15 probes), 64.6% tetraploid.

Loss of one copy of TP53 in 55.2% of tetraploid-range cells (TP53/ATM

probes)

Day 60:

Karyotype Failure

Fluorescence in situ hybridization (FISH):

5q31 deletion in 47.7% cells analyzed. All cells tetraploid

MOLECULAR FINDINGS

No FLT3 mutations detected.

INTERESTING FEATURES

MDS associated cytogenetic abnormality in a de novo acute leukemia with no differentiating features by cytomorphology in a young patient without any significant past medical history. Refractory to treatment.

PROPOSED DIAGNOSIS

ACUTE MYELOID LEUKEMIA WITH MONOCYTIC FEATURES

CONSENSUS DIAGNOSIS

Acute myeloid leukemia with myelodysplasia-related changes (complex karyotype including del(5)(q22q31) and tetraploidy)