Myelodysplastic Syndrome with Excess Blasts and Erythroid Predominance (MDS-EB-E) With NPM1 Mutation and P53 Expression

Case Report

Ann Hematol Onco. 2023; 10(6): 1440.

Myelodysplastic Syndrome with Excess Blasts and Erythroid Predominance (MDS-EB-E) With NPM1 Mutation and P53 Expression

Satarupa Mohapatra, DM; Somanath Padhi, MD*; Prabodha Kumar Das, MD, FRCPA; Gaurav Chhabra, MD

Department of Pathology and Laboratory Medicine; and Medical Oncology/Hematology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

*Corresponding author: Somanath Padhi, MD Additional Professor, Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India. Email: [email protected]

Received: August 01, 2023 Accepted: September 13, 2023 Published: September 20, 2023


Nucleophosmin 1 (NPM1) mutated Myelodysplastic Syndrome (MDS) is a distinctly rare sub-group of myeloid neoplasm with limited available data describing its biological behavior and outcome using different therapeutic strategies. We describe a case of NPM1 mutated MDS in a middle-aged male with excess blasts and excess erythroid precursors (MDS-EB-E) morphologically mimicking Acute Erythroleukemia (AEL) with an unfavorable outcome following Hypomethylating Agent (HMA) therapy. We briefly reviewed the clinicopathological and genetic landscape data of NPM1 mutated MDS along with the role of p53 immunohistochemistry in differentiating MDS-EB-E from AEL.

Keywords: Myelodysplastic syndrome; TP53; NPM1; Next generation sequencing


Myelodysplastic Syndrome (MDS) is a distinct group of clonal hematopoietic stem cell neoplasm characterised by recurrent cytogenetic abnormalities, peripheral blood cytopenia (s), normo to hypercellular marrow with dyspoietic changes, and an increased risk of transformation to acute myeloid leukemia. The 2017 modification of WHO classification of hematopoietic neoplasms describes MDS with excess blast and erythroid predominance (MDS-EB-E) as a distinct entity representing the so called erythroid-myeloid type Acute Erythroleukemia (AEL) in previous classification [1]. Although the genomic landscape data of such entity is not fully known, but presence of high-risk karyotype, and TP53, RUNX1, ASXL1 mutations are reported to be associated with adverse prognosis [2,3]. We aim to describe a case of MDS-EB-E with NPM1 mutation and highlight the biological behaviour of such rare entity published in the literature.

Case Presentation

A middle-aged male without any prior co-morbidity underwent hematological evaluation at our center for six-month history of exertional dyspnea secondary to transfusion dependent anemia (average of two packed red cell per month) associated with fatigue and weight loss. On examination, he had significant conjunctival pallor, no icterus, cyanosis, edema, lymphadenopathy and/or hepatosplenomegaly. His clinical presentation mimicked aplastic anemia, MDS, or underlying hematological malignancy such as leukemia/lymphoma. His complete blood count and peripheral blood smear examination revealed dimorphic anemia (normocytic normochromic admixed with macrocytic normochromic red cells) (secondary to transfusion) with a Hb; 65g/L (ref.; 120-140 g/L), mean cell volume; 99fL (ref.; 80-98 fL), corrected reticulocyte count; 1% (ref.; 0.5-2%), nucleated RBCs; 5/100 leukocytes]; leukopenia [leukocyte count; 2.7x109/L (ref.; 4-11x109/L) with 2% myeloid blasts, and scattered pseudo-Pelger Heut neutrophils (5% of differential); and thrombocytopenia [platelet count; 33x109/L (ref.; 150-450x109/L] with giant platelets; thus, suggestive of MDS.

Bone marrow aspirate examination revealed florid erythroid hyperplasia (70% of marrow nucleated cells) (myeloid to erythroid ratio=1:3) with dysplastic erythroid morphology in the form of megaloblastic nuclear chromatin, diffuse weak cytoplasmic positivity for Per-iodic Acid Schiff (PAS) stain, and nuclear membrane irregularity in the form of budding (noted in >30% erythroid cells); 15% non-erythroid myeloid blasts; and adequate but dysplastic (micro) megakaryocytes (Figure 1a).