Acute Promyelocytic Leukemia: An Unsual Presentation

Introduction

Five to eight percent of acute promyelocytic leukemia (APL) occurs in mid-life with disseminated intravascular coagulation (DIC) being a classic presentation. Laboratory investigation usually reveals high white cell count (WBC), promyelocytes and early myeloid series with abundant auer rods, with the exception of the microgranular variant. The bone marrow in APL is usually hypercellular with positive myeloperoxidase stains and the characteristic CD33, CD13, CD15, and CD117 positivity on immunohistochemistry and flow cytometry. The presence of a reciprocal translocation t(15;17)(q22;q12) on chromosome 17 causing a fusion of the promyelocytic - and retinoic acid receptor-alpha genes (PML-RARA) is the hallmark of APL, which is found in 95% of cases. The diagnosis of APL becomes challenging when it presents with uncharacteristic features, causing a delay in early commencement of treatment. A wide index of suspicion arises from being aware of unusual presentations.

Case presentation

We therefore present a 52 year old diabetic male who while been treated for hyperosmolar non ketotic hyperglycemia (HONK) was found with persistent isolated leucopenia with severe neutropenia (WBC: 0.7, absolute neutropenia: 100) and weight loss. This was initially reckoned as an adverse reaction to medication. He was treated with granulocyte colony stimulating factor (GCSF) and he responded with an unsustained increase in WBC and declining platelet counts. His medical history was insignificant for malignancy, splenomegaly, adenopathy nor sepsis. His medications comprised of antihypertensives, antidiabetics and the statins. Bone marrow findings included patchy cellularity, marked myeloid hyperplasia, few cells with auer rods, and myeloid maturation (1% blasts, 26% promyelocytes, and 22% myelocytes). The maturation and other listed bone marrow findings were initially attributed to the effect of the GCSF, but were also highly suspicious for APL. The diagnosis of APL was not given until a molecular analysis was positive for PML-RARA fusion protein. Following a diagnosis of APL with translocation, induction chemotherapy was commenced with all-trans retinoic acid (ATRA) and arsenic trioxide, during which the patient achieved molecular remission with no evidence of residual leukemia in the bone marrow (0% blasts, 1% promyelocytes, and 6% myelocytes) and a negative flow cytometric analysis. The consolidation phase is ongoing and the patient has consistently maintained remission and normal complete blood count (WBC: 1.1, absolute neutrophil count: 300).

Discussion

This case highlights the importance of having a high index of suspicion for APL. In such clinical settings, an early bone marrow examination is imperative and can be the first pointer to the diagnosis of APL. The prior use of GCSF created a distraction by adding an increased myelocyte population to the patient's differential. Fortunately, molecular testing for PML-RARA detected the fusion protein and treatment was then initiated. Any increased promyelocyte population, regardless of the remaining differential, should always prompt a discussion regarding the high value of ruling out APL by molecular testing.