#00065254

A 43-year-old female with a 2-month history of very high risk (Revised International Prognostic Scoring System (IPSS-R) score of 7.5) myelodysplastic syndrome (MDS) with mutated TP53, heart failure with preserved ejection fraction and transfusion-dependent anemia was hospitalized for fever and tachycardia.  A CBC and manual differential were performed due to concern for leukemic transformation. The peripheral blood smear demonstrated pancytopenia, with normochromic normocytic anemia (hemoglobin 8.4 g/dL, MCV 90.1 fL), thrombocytopenia (PLT 28 K/μL), and left-shifted leukopenia (WBC 2.94 K/μL). Of note, the majority of neutrophils were dyspoietic; many hypogranular forms were present (100x objective, total magnification x1000). Flow cytometry detected an abnormal myelomonocytic population (58% of gated events) favored to be dysplastic neutrophils, consistent with patient’s history of MDS.

Dysplasia in >10% of the myeloid, erythroid, and/or megakaryocytic lineages is a diagnostic requirement for MDS.  Dysgranulopoiesis includes small size, nuclear (hyper- or hyposegmentation) and/or cytoplasmic (hypogranularity, Pseudo-Chédiak-Higashi granules) atypia. Hypogranularity is nonspecific; this feature has been found in SARS-CoV-2 patients and inherited conditions. Patients with TP53-mutated MDS have a higher risk for leukemic transformation, regardless of blast count. The ability to detect dysplastic neutrophils in a peripheral blood smear is a key defining feature, aiding in diagnosis and treatment.