Abstract
<jats:p>The patient was a 57-year-old male with repeated fatigue and jaundice for more than 50 years, accompanied by tea-colored urine. He had a history of anemia for over 10 years. In February 2025, he presented with pancytopenia and massive splenomegaly, and underwent laparoscopic total splenectomy at an outside hospital. Only the platelet count returned to normal postoperatively. Routine blood tests on admission showed decreased white blood cell count and hemoglobin level, and an elevated reticulocyte percentage. Peripheral blood smear revealed approximately 10% spherocytes, nucleated red blood cells, and Pappenheimer bodies. Whole-exome sequencing identified a pathogenic mutation in the SPTB gene (encoding β-spectrin) and a myeloid neoplasm-associated mutation in DNMT3A. A diagnosis of hereditary spherocytosis (HS) complicated by clonal cytopenia of undetermined significance (CCUS) was made. During follow-up, the patient had chronic severe anemia requiring blood transfusion support. No other treatments or interventions were administered locally, and long-term monitoring of clonal mutation burden was not performed; thus the risk of disease progression could not be assessed at present. The coexistence of HS and CCUS is clinically rare and prone to misdiagnosis or missed diagnosis. Integrating clinical, morphological and genomic evidence is essential for accurate diagnosis and personalized management.</jats:p>