Case 345

Submitting Author: Horna, Pedro, MD
Institution: H. Lee Moffitt Cancer
Additional authors:Xiaohui Zhang, Ling Zhang
Session: AML with recurrent genetic abnormalities Part I

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HISTORY

A 51-year-old man was found to have an abnormal blood cell count (WBC 1.68 x 103/uL, ANC 0.52 x 103/uL, hemoglobin 14.8 g/dL and platelets 111 x 103/uL) during a routine medical followup for his diabetes mellitus. A laboratory investigation including Hepatitis B and C, and HIV were all negative. He was referred to H. Lee Moffitt Cancer Center for further diagnosis and treatment. Bone marrow biopsy was performed.

DETAILS

Posterior Iliac crest bone marrow aspiration and biopsies were performed. Fixation: 10% neutral buffered formalin.

Aspirate smear (Figure 1, Wright-Giemsa, 600x) showed numerous blasts with frequently bilobed nuclei and moderate amounts of cytoplasm with abundant primary granules. No Auer rods were seen. Bone marrow core biopsy (Figure 2, H&E, 100x) showed markedly hypercellular marrow completely replaced by blasts. The blasts have bilobed nuclear and markedly granular cytoplasm (Figure 3, H&E, 600x).

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Flow cytometry plots (Figure 4, ungated events) showed typical immunophenotypic features of acute promyelocytic leukemia, including high side-scatter, positive CD117 (bright) and CD33. CD34 and HLA-DR were largely negative.

CYTOGENETIC FINDINGS

FISH studies for PML-RARA (Figure 5) were consistent with 4 PML-RARA fusion genes in 94% of nuclei examined. Karyotype performed on bone marrow aspirate (Figure 6) showed tetraploidy including t(15;17)(q22;q12).

INTERESTING FEATURES

This is a case of acute promyelocytic leukemia with an unusual tetraploid karyotype including t(15;17). A bone marrow biopsy revealed a markedly hypercellular marrow. Morphologically, the leukemia cells had larger than usual nuclear configurations. The effect of the karyotyping on prognosis is unknown.

This patient was induced with ATRA and idarubicin, with significant aplasia followed by peripheral blood recovery with ANC 650 cells/uL. Subsequent bone marrow biopsy showed a normocellular marrow with no evidence of leukemia. Cytogenetic returned normal. No PML-RARA transcripts were detected. Last follow up on Jan 1, 2013 showed the patient was in complete remission after completing his consolidation therapy.

PROPOSED DIAGNOSIS

Acute promyelocytic leukemia with tetraploidy and t(15;17)(q22;q12)/PML-RARA.

CONSENSUS DIAGNOSIS

Acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARA, and tetraploidy

FIGURE 1. Bone marrow aspirate smear (Wright-Giemsa, 500x). Abundant blasts with frequently bilobed nuclei and moderate amounts of cytoplasm with abundant primary granules. No Auer rods were identified.FIGURE 1. Bone marrow aspirate smear (Wright-Giemsa, 500x). Abundant blasts with frequently bilobed nuclei and moderate amounts of cytoplasm with abundant primary granules. No Auer rods were identified.
FIGURE 2. Bone marrow core biopsy (H&E, 100x). Markedly hypercellular marrow completely replaced by blasts.FIGURE 2. Bone marrow core biopsy (H&E, 100x). Markedly hypercellular marrow completely replaced by blasts.
FIGURE 3. Bone marrow core biopsy (H&E, 500x). Abundant blasts with bilobed nuclear and markedly granular cytoplasm.FIGURE 3. Bone marrow core biopsy (H&E, 500x). Abundant blasts with bilobed nuclear and markedly granular cytoplasm.
FIGURE 4. Flow cytometry plots (ungated events, red = blasts). The blasts show typical immunophenotypic features of acute promyelocytic leukemia, including high side-scatter, CD33 and bright CD117 positivity. CD34 and HLA-DR were largely negative.FIGURE 4. Flow cytometry plots (ungated events, red = blasts). The blasts show typical immunophenotypic features of acute promyelocytic leukemia, including high side-scatter, CD33 and bright CD117 positivity. CD34 and HLA-DR were largely negative.
FIGURE 5. FISH studies showed 4 PML-RARA fusion signals.FIGURE 5. FISH studies showed 4 PML-RARA fusion signals.
FIGURE 6. Karyotyping performed on bone marrow aspirate showed tetraploidy and t(15;17)(q22;q12).FIGURE 6. Karyotyping performed on bone marrow aspirate showed tetraploidy and t(15;17)(q22;q12).