A highly positive nonspecific esterase reaction in a t(15;17)(q22;q12) acute promyelocytic leukemia

Abstract

A 32-year-old man was admitted to the hematological department of our facility in November 2010 with fever, pharyngodynia, leucopenia, and thrombocytopenia. The patient had been in his usual state of health until approximately 2 weeks prior to admission, when he developed intermittent fevers, with temperatures of up to 39.0 C, epistaxis, and pharyngodynia. He was seen by his primary care physician 7 days prior to admission. Laboratory workup revealed leukopenia and thrombocytopenia, and he was referred to our hospital. Patient examination at the time of admission revealed no palpable swelling of the superficial lymph nodes. The liver and spleen were not palpable by abdominal exam. The complete blood count showed a reduced white blood cell (WBC) count of 2.5 9 10/L, a hemoglobin level of 13.1 g/dL and a platelet count of 92 9 10/L. The WBC differential revealed 38% neutrophils, 45% lymphocytes, and 8% blasts. Further laboratory tests revealed a coagulopathy consistent with disseminated intravascular coagulation (DIC); the D-dimer was positive (12.50 lg/mL) and the fibrin-fibrinogen deregulation products were elevated (44.7 lg/mL), while other tests of coagulation and serum and urine lysozyme levels were within normal limits. A May-Grunwald-Giemsa-stained bone marrow aspirate smear showed numerous hypergranular blasts with intense azurophilic granulation and Auer rods (faggot cells) (Fig. 1a). On cytochemical staining, the blasts were strongly positive on myeloperoxidase (MPO) staining (Fig. 1b), and strongly dual-positive on double-staining by naphthyl butyrate (nonspecific) esterase (NSE) and naphthol-ASD-chloroacetate esterase (CAE) (Fig. 1c). Sodium fluoride (NaF) inhibited NSE staining (Fig. 1d). Flow cytometry was performed on a specimen of bone marrow. The results showed predominant populations of CD33, CD13, CD34, CD14, HLA-DR, CD11b, CD117, CD64, CD15, CD65, CD71 and CD2. Cytogenetic analysis showed an abnormal karyotype, 46, XY, t(15;17)(q22;q12), in each of the 20 metaphase cells analyzed. The PML–RARA fusion transcript of the t(15;17) was confirmed by reverse-transcription polymerase chain reaction. With these findings, the patient fulfilled the diagnostic requirements for acute promyelocytic leukemia (APL) with t(15;17)(q22;q12). The patient received induction chemotherapy of alltrans-retinoic acid (ATRA), followed by anthracyclinebased chemotherapy, and achieved a hematologic remission. PML–RARA rearrangement transcript was negative by fluorescent in situ hybridization at the end of the induction treatment. The patient then began consolidation chemotherapy with idarubicin and cytarabine. APL is a subtype of acute myeloid leukemia (AML) with distinctive biologic and clinical features, characterized by a t(15;17) translocation fusing the PML and RARA genes. The introduction of ATRA therapy has dramatically improved the clinical outcome in APL over the last decade. However, prompt recognition and treatment of APL is vital for patient care, as life-threatening complications, such as bleeding, can present prior to diagnosis. Review of the peripheral blood smear with the bone marrow aspirate is necessary for the presumptive diagnosis of APL. Blasts are characterized by irregular and variable nuclear size and shape, bundles of Auer rods (faggot cells) and large, abundant, coalescent primary azurophilic granules. All the leukemic promyelocytes show a strong positive reaction to MPO. The leukemic promyelocytes are typically NSEnegative; however, approximately 25% of the cases are T. Aoki (&) T. Nishiyama N. Imahashi K. Kitamura Division of Hematology, Ichinomiya Municipal Hospital, 2-2-22 Bunkyo, Ichinomiya, Aichi 491-8558, Japan e-mail: taoki-cib@umin.net