Acute Promyelocytic Leukemia With Pseudo-Chediak-Higashi Anomaly: A Case Report and Review of the Literature

Abstract

The hypergranular type of acute promyelocytic leukemia (APL) is characterized by heavy granulation and the presence of Auer rods. These granules are usually small, azurophilic, and have the appearance of the primary granules of normal promyelocytes. There have been several reports of myeloid leukemias, 1-11 including APL, with the unusual finding of large granules (inclusions) simulating the inclusions of Chediak-Higashi, which were given the term "pseudo-Chediak-Higashi anomaly" (PSCA). 1In this report, a case of hypergranular type APL with numerous Auer rods and PSCA is described with a literature review of this unusual morphologic anomaly. Case ReportA 40-year-old woman was admitted in 1995 with headache and blurred vision. Physical examination was remarkable for ecchymoses and bilateral eye fundal hemorrhage. No organomegaly or adenopathy was present. Laboratory studies showed hemoglobin (Hb) of 98 g/L, WBC of 1.74x10 9 /L, and a platelet count of 53.0x10 9 /L. Differential count showed 12% neutrophils, 30% lymphocytes, 10% monocytes, 3% myelocytes, 22% promyelocytes and 13% blasts. Coagulation studies demonstrated a prothrombin time (PT) of >120 sec. (normal range: 9.5-14.4 sec.), partial thromboplastin time (PTT) of 38.6 sec. (normal range: 26-39 sec.), fibrinogen level of 0.6 g/L (normal range: 2-4 g/L), and a positive D-dimer test of 1000-2000 ng/mL. Bone marrow aspirate and trephine biopsy were performed. The aspirate was used for morphologic and immunophenotypic studies (see below). Acute promyelocytic leukemia (APL), hypergranular type with disseminated intravascular coagulation was diagnosed.Bone marrow aspirate, peripheral blood smears and bone marrow trephine biopsy imprints were stained with May-Grünwald-Giemsa (MGG) stain. Cytochemical stains were performed on the smear from the bone marrow aspirate, using the following stains: Sudan black B (SBB), periodic acid-Schiff (PAS), combined α-naphthol AS-D chloroacetate (CAE) and α-naphthyl acetate esterase (ANAE) stain, and acid phosphatase (AP). The marrow trephine biopsy was stained with the hematoxylin-eosin and PAS stains.Cell-suspension immunophenotypic studies were performed using the following antibodies: CD3, CD5, CD7, CD10, CD13, CD19, CD20, CD22, CD33 and HLA-DR.The marrow aspirate was markedly hypercellular, with predominance of hypergranular promyelocytes (71%). Many contained Auer rods, with some of them in bundles. Approximately 5% of these promyelocytes contained large inclusions of 1-2 μ in size. The granules were generally round and pink, and appeared to represent fusion of granules (Figure 1). The peripheral blood also showed heavily granulated promyelocytes. By cytochemical stains, both the granules and the Auer rods were positive for SBB and CAE. The cytoplasm had tinge positivity with PAS, while the large granules and Auer rods were strongly positive, and the large granules were shown more clearly by this stain. The ANAE stain was positive with fluoride inhibition.

Diagnosis of Acute Promyelocytic Leukemia After Presentation to Neuro-Ophthalmology

“…In addition to our cases, a review of the literature revealed 8 cases where a diagnosis of APML was made after ophthalmologic or neuro-ophthalmologic manifestations (8,(12)(13)(14)(15)(16)(17)(18). The cases are summarized in Table 1.…”