Acute leukemic transformation of myelodysplastic syndrome: Is cytochemistry still relevant?

A 59-year-old man with a history of mild cytopenias for the preceding three years presented with a 5-week history of lethargy and reduced exercise tolerance. Physical examination was normal. A complete blood count (CBC) showed pancytopenia with a hemoglobin concentration (Hb) of 114 g/L, platelets of 110 × 10⁹/L and neutrophils of 0.17 × 10⁹/L. The peripheral blood smear showed no morphologic dysplasia or circulating blasts. A bone marrow aspirate showed hypercellular fragments. There was erythroid predominance and marked trilineage dysplasia. In addition to these findings, there was a population of blastoid cells, constituting 15% of nucleated cells, with distinctive morphology (top left). These were large cells with a moderately high nuclear to cytoplasmic ratio, immature chromatin and prominent nucleoli. The deeply basophilic cytoplasm contained azurophilic granules. Cytoplasmic vacuoles and blebbing were seen in some cells. Myeloperoxidase staining was negative in the blasts. Flow cytometry surprisingly did not identify a blast population. Immunocytochemical staining using the alkaline phosphatase:anti-alkaline phosphate technique on the bone marrow aspirate was performed. The blasts were negative for CD61 and glycophorin A but weakly positive for CD13/33. Trephine biopsy sections showed an abnormal stromal background with increased edema and vascularity as well as increased T lymphocytes. The blastoid cells were not easily identifiable on a hematoxylin and eosin stain; they were negative with a large range of immunohistochemical stains including CD34, CD117, myeloperoxidase, lymphoid antigens, and plasma cell antigens. Cytogenetic analysis revealed tetrasomy 8, supporting a myeloid disorder. Although the blasts had not been identified by cytochemical, immunohistochemical or immunophenotypic techniques, a diagnosis of myelodysplastic syndrome (MDS) with excess blasts was made.1

The patient remained stable for almost three months before he developed progressive cytopenias. His CBC at this time showed the Hb had fallen to 78 g/L, platelets were 34 × 10⁹/L, and neutrophils were 0.07 × 10⁹/L. Rare circulating blasts were seen in the peripheral blood smear. A repeat bone marrow aspirate showed markedly hypercellular fragments packed with a monomorphic population of blast cells, which were cytologically identical to the those seen initially (top right). Myeloperoxidase was again negative in the blasts (bottom left). This time, α naphthyl butyrate esterase (ANBE) enzyme cytochemistry was performed which was strongly positive, confirming the monoblastic nature of the cells (bottom right). The original bone marrow aspirate was retrospectively stained with ANBE and the previously unidentified blasts were strongly positive. Flow cytometric immunophenotyping showed a large population of monoblasts with unusually high side scatter. They were positive for HLA-DR, CD15, CD11c, CD64, and CD56 but negative for CD34, CD117, and myeloperoxidase. Due to the patient's long history of cytopenias and presumed history of MDS, a final diagnosis of acute myeloid leukemia with myelodysplasia-related changes was made. As monoblasts are rarely found in MDS,2 we postulate that leukemic transformation from underlying MDS was occurring at the time of his first bone marrow biopsy.