Submitting Author: Acree, Sara Cuadra, MD
Institution: LAC+USC Medical Center
Additional authors:Kiran Qidwai, MD, Russell K. Brynes, MD, Imran N. Siddiqi, MD, PhD
Session: AML with recurrent genetic abnormalities Part I

63 year old Caucasian male with no significant past medical history who developed gum bleeding following a routine dental check-up and cleaning. Due to persistent gum bleeding, the patient presented to an urgent care facility, where a peripheral smear showed blasts. A subsequent CBC at our institution showed the following: WBC 1.3 K/cumm with 62% promyelocytes/blasts, Hgb 6.8 g/dL. Hct 19.4%, and platelets 30 K/cumm.

• Bone marrow aspiration and trephine biopsy of iliac crest

• Fixation: Formalin

• Peripheral blood: The red cells are markedly decreased in number and are normochromic and normocytic. The white blood cells are decreased in number. Most of the WBC’s are abnormal promyelocytes and blasts. These cells have frequent bilobed nuclei, fine chromatin, occasional nucleoli, and abundant densely granular cytoplasm. Frequent cells with multiple Auer rods are noted. A severe neutropenia is present. Platelets are markedly decreased and are mostly unremarkable in appearance.

• Aspirate smear: The majority of cells are abnormal promyelocytes/blasts, with morphology similar to that seen on the peripheral smear. Many cells with multiple Auer rods are again noted. Residual hematopoiesis is markedly decreased, with only rare granulocytic precursors noted, and scant eosinophils and small lymphocytes. Megakaryocytes were also markedly decreased largely unremarkable.

• Clot and biopsy sections: Clot section is scant. The trephine biopsy sections are markedly hypercellular (~95%) and show marrow effacement by sheets of abnormal promyelocytes/blasts. Residual hematopoiesis is markedly decreased.

Abnormal population of early myeloid cells (~85-90% of total cells) with the phenotype CD33+, CD13+, CD117+, CD64 partial +, and negative for CD34, HLA-DR, CD11b, CD16, and B cell and T cell markers.

• Normal male karyotype: 46,XY

• Negative for RARA break-apart rearrangement by FISH

• Positive for PML/RARA

• PML/RARA fusion was detected only by RT-PCR and not by conventional karyotype or FISH using a RARA breakapart probe. This likely represents a rare, cryptic PML/RARA rearrangement.

• Acute promyelocytic leukemia with cryptic PML/RARA fusion

Acute promyelocytic leukemia with cryptic t(15;17) (q22;q12); PML-RARA

Case 435