Bone marrow trephine biopsy findings in acute promyelocytic leukemia
Authors: Saeed Al‐Shieban, Christine Liu, Keith Fishlock, Philippa C. May, Jiri Pavlu, Kikkeri N. Naresh
Journal: American Journal of Hematology (2011)

A woman in her 20s presented with menorrhagia, bleeding gums, and frank hematurea. Her hemoglobulin was 9.2 g/dL and white cell count was 3.1 × 109/L, with neutrophils amounting to 0.6 × 109/L. Her platelets measured 12 × 109/L. She also had deranged clotting with prolonged prothrombin time, normal activated partial thromboplastin time, and low fibrinogen. The blood film showed abnormal promyelocytes. The bone marrow aspirate showed shift to left in granulocytic cells with maturation arrest at promyelocyte stage. There were excess blasts (18%) and abnormal hypergranular promyelocytes (67%). Faggot cells—blasts and promyelocytes with multiple Auer rods—were also seen (a–h; Giemsa 1000×). Flow cytometric analysis showed an abnormal population of cells expressing CD13, CD33, myeloperoxidase, and CD38, along with weak expression of CD11b, CD10, CD117, and CD2. These cells did not express CD34, HLA-DR, CD15, CD16, or any B lineage markers. The immunophenotypic and the morphological features on peripheral blood and bone marrow aspirate were most typical of acute promyelocytic leukemia (APL). Bone marrow trephine biopsy showed hypercellular marrow with a cellularity of nearly 100%. The myeloid:erythroid ratio was >10:1 (i; H&E 100×). Marrow showed sheets of abnormal promyelocytes with abundant granular cytoplasm (j; H&E 600×). These abnormal cells expressed myeloperoxidase (k; 600×), CD99, CD43, CD68 (l; 600×), and CD117 (weak) (m; 600×) and were negative for CD34 (n; 600×), HLA-DR (o; 600×), CD68R, and CD10. Megacaryocytes were rare. Marrow reticulin was minimally increased (Grade 1). The trephine features were characteristic of APL. Karyotypic analysis showed reciprocal translocation between the long arms of chromosomes 15 and 17 infour of ten metaphases (p). Interphase FISH analysis on cultured bone marrow cells using a probe for PML/RARA (Kreatech Diagnostics) revealed a fusion signal, consistent with a PML-RARA [t(15;17)] fusion gene, in 94 of the 100 cells analyzed (q). This finding is consistent with a diagnosis of APL. Acute promyelocytic leukemia (APL) compromises 5–8% of acute myeloid leukemias and is characterized by its distinct morphological, immunophenotypic, cytogenetic, and clinical features. The balanced chromosomal translocation t(15;17)(q22;112) (PML/RARa) is characteristic. Two morphological subtypes, the hypergranular “typical” and the hypogranular types are identified. APL is frequently associated with disseminated intravascular coagulation; and very high leukocyte count is observed in the hypogranular type. The morphologic features of APL are characterized by abnormal promyelocytes with kidney-shaped or bilobed nuclei. The cytoplasm of the hypergranular type is marked by densely packed large granules and presence of Auer rods. The bone marrow trephine biopsy is usually hypercellular and the abnormal promyelocytes have convoluted nuclei and abundant cytoplasm with numerous granules. The immunophenotyping of APL is also characteristic with expression of CD33 and CD13 and absence of CD34 and HLA-DR [1]. With appropriate therapy, complete remission rates greater than 90% can be achieved [2]. Chemotherapy that includes all-trans-retinoic acid in combination with anthracycline-containing regimens have been highly successful in achieving long-term complete remissions.