Submitting Author: He, Rong, MD
Institution: Mayo Clinic
Additional authors:William G. Morice, II
Session: AML with recurrent genetic abnormalities Part I

A 37-year old man with a medical history of hypertension and hyperlipidemia presented to the emergency department with acute onset chest pain for 4 hours and nausea and fatigue for about a week. Cardiac enzymes and EKG were normal. The chest pain resolved completely with Maalox and proton pump inhibitor (PPI).

A complete blood count (CBC) showed pancytopenia (Hb 12.3g/dL, neutrophils 0.49 X 10^9/L, and platelets 129 X 10^9 /L). Peripheral blood smear revealed approximately 5% intermediate to large-sized atypical cells with reticular chromatin, round to folded nuclear contour, nucleoli and abundant pale blue-gray cytoplasm. Some contain azurophilic granules. These cells were positive for butyrate esterase and negative for chloroacetate esterase, demonstrating monocytic differentiation. Hematology consult and bone marrow biopsy were recommended.

Right posterior iliac crest bone marrow aspirate and biopsy were collected. The bone marrow aspirate was stained with Wright-Giemsa stain. The bone marrow core biosy measured 1.7 cm, and was fixed in B5 and formalin and decalcified.

The bone marrow aspirate showed approximately 80% of monoblast/promonocytes with intermediate to large size nuclei, reticular chromatin, nucleoli, and abundant blue-gray cytoplasm; many contain azurophilic granules. Maturing granulopoiesis was markedly decreased. Erythropoiesis and megakaryopoiesis were slightly decreased. No distinct dysplasia was seen.

The bone marrow biopsy demonstrated hypercellularity (90%) with extensive interstitial infiltration by leukemic blasts with intermediate to large-sized nuclei, round to folded nuclear contour, speckled chromatin, prominent nucleoli and abundant eosinophilic cytoplasm. They comprised at least 80% of the biopsy cellularity. Background trilineage hematopoiesis was decreased.

Bone marrow flow cytometry:

The monoblasts/promonocytes were positive for CD33, CD56, HLA-DR, CD15, CD45(dim) and negative for CD34, CD117, CD13, CD19 and CD10. They were strongly positive for butyrate esterase stain and negative for chloroacetate esterase stain.

46,XY,t(9;11)(p22;q23)[20]

The result is abnormal. Each metaphase has a t(9;11)(p22;q23).

nuc ish(MLLT3x3),(MLLx3),(MLLT3 con MLLx2)[401/500]

The result is abnormal and indicates MLLT3(AF9)/MLL fusion

in 80.2% of nuclei.

None

This is a classical case of acute myeloid leukemia with t(9:11)(p22;q23); MLLT3-MLL (AF9-MLL) occurring in a young adult. t(9;11) was detected by chromosome analysis and follow-up FISH studies demonstrated MLL gene separation and fusion with the MLLT3 gene. Characteristically, the blasts demonstrated monocytic differentiation by morphology, cytochemical staining, and flow cytometric immunophenotyping. Morphologically this case fulfills the diagnostic criteria for an acute monocytic leukemia.

Acute myeloid leukemia with t(9:11)(p22;q23); MLLT3-MLL

Acute myeloid leukemia with t(9;11)(p22;q23); MLLT3-MLL

Case 55