The 5q-Syndrome : From Morphologic Clues to Targeted Therapy : Two Illustrative Clinical Cases

The 5q− syndrome is a distinct subtype of myelodysplastic syndromes (MDS), characterized by a specific cytogenetic abnormality and a recognizable morphologic profile. We report two illustrative clinical observations in elderly female patients highlighting the diagnostic value of peripheral blood and bone marrow morphology combined with cytogenetic analysis. Both patients presented with chronic macrocytic anemia, normal to increased platelet counts, and limited or moderate neutropenia. Bone marrow examination revealed a hypercellular marrow with prominent dysmegakaryopoiesis, characterized by small megakaryocytes with hypolobated or monolobated nuclei, a hallmark feature of the 5q− syndrome.Cytogenetic evaluation identified an isolated deletion of the long arm of chromosome 5, confirming the diagnosis. Both patients became transfusion-dependent after failure of erythropoiesis-stimulating agents. Treatment with lenalidomide resulted in rapid and sustained hematologic improvement, with achievement of transfusion independence and significant enhancement of quality of life. Treatment was generally well tolerated, although close monitoring was required due to the risk of neutropenia and infectious complications.These two cases emphasize the importance of careful morphologic assessment and cytogenetic studies in elderly patients with unexplained macrocytic anemia. They also illustrate the paradigm of precision medicine in MDS, where identification of a specific chromosomal abnormality enables targeted therapy with significant clinical benefit.Keywords 5q− syndrome; Myelodysplastic syndromes; Macrocytic anemia; Dysmegakaryopoiesis; Cytogenetics; Lenalidomide; Transfusion dependence; Precision medicine.