An 11-year-old girl was diagnosed with gray platelet syndrome (GPS) with compound heterozygous NBEAL2 mutations after presenting with recurrent epistaxis and thrombocytopenia. Bone marrow examination was performed to evaluate for myelofibrosis. Her blood film demonstrated macrothrombocytopenia (platelets 90 × 10⁹/L; mean platelet volume 12.8 fL [reference 8.6-11.1fL]) with hypogranular platelets (dashed arrows, panels A1-2, Wright-Giemsa stain; all panels, original magnification ×100). Emperipolesis in the aspirate (panels B1-2, May-Grünwald Giemsa stain) and biopsy (panels C1-2, hematoxylin and eosin stain; panels D1-2, CD61 stain) involving granulocytes (white arrows) and mononuclear cells (black arrows), including T lymphocytes, but not B lymphocytes (panel E1, CD3 stain; panel E2, CD20 stain) in hypogranular megakaryocytes was a striking feature. There was minimal reticulin fibrosis.

GPS is a rare inherited (typically autosomal recessive) platelet disorder with macrothrombocytopenia, platelet α-granule deficiency, and mild to moderate bleeding tendency. NBEAL2 encodes a protein with predicted roles in vesicular trafficking and platelet α-granule development. Homozygous or compound heterozygous NBEAL2 mutations are implicated in most families with GPS. Emperipolesis refers to passage of a cell through the cytoplasm of another. Emperipolesis is described in megakaryocytes of patients with GPS and is hypothesized to result from α-granule membrane P-selectin mislocalization. Whether emperipolesis is involved in the pathogenesis of the abnormal thrombopoiesis or myelofibrosis observed in GPS requires investigation.