Case Presentation: A 49-year old man with no significant medical history presented with dyspnea and presyncope. He presented similarly six weeks prior and was diagnosed with constrictive pericarditis thought to be of a viral etiology. He had reported an eighteen-kilogram weight loss, intermittent fevers, and night sweats, but, given clinical improvement, was discharged on ibuprofen and colchicine. Studies on readmission showed no further constrictive physiology but new transfusion-dependent, hypoproliferative macrocytic anemia, thrombocytopenia, and leukopenia. Peripheral blood smear showed no dysplasia. Although little aspirate was obtained from bone marrow biopsy (“dry tap”), flow cytometry showed left-shifted myeloid cells without increased blasts. Core biopsy revealed hypercellular marrow with morphology concerning for an underlying myeloid malignancy; however, FISH myelodysplastic syndrome (MDS) panel and karyotype studies showed no abnormal clonal population. Extensive testing did not reveal an infectious or autoimmune etiology. His cell counts stabilized and he was discharged with Hematology follow-up. Two weeks later, follow-up labs returned with a hemoglobin of 7 and he was sent to the ED, where a peripheral smear showed 33% blasts. Repeat bone marrow biopsy revealed acute myelogenous leukemia (AML). The patient was diagnosed with presumed MDS with progression to AML.
Discussion: MDS is a clonal disorder of hematopoiesis associated with risk of acute leukemic transformation. It often presents insidiously, with patients seeking care due to symptoms of cytopenias. This patient’s pancytopenia was likely exacerbated by the use of colchicine and may have led to an earlier presentation due to symptomatic anemia. Of note, MDS and leukemia can be associated with pericarditis; however the resolution of the patient’s pericarditis by the time of his AML diagnosis makes this etiology less likely. MDS is diagnosed by morphologic evidence of dysplasia or cytogenetic abnormalities on peripheral smear, bone marrow aspirate, or bone marrow biopsy. A blast percentage of 20% is an arbitrary threshold to distinguish MDS from AML. Diagnosis from bone marrow sampling can be challenging due to variability in the cellularity within the marrow; thus, a non-diagnostic bone marrow sample does not rule out MDS. A so-called “dry tap” is frequently attributed to faulty technique but more likely portends marrow pathology, as in the case of this patient. Transformation to AML is variable and difficult to predict. The Revised International Prognostic Scoring System predicts the risk of leukemic transformation and suggested a 25% 10-year risk of transformation in this patient. Thus, his progression to AML underscores the heterogeneity in the course of patients with MDS.
Conclusions: MDS is a clonal disorder of the bone marrow that can be challenging to diagnose, but a high index of suspicion should be maintained, particularly if another cause of pancytopenia is not identified. If initial testing is inconclusive, close interim follow-up after discharge is needed due to the risk of transformation to AML.