Bone Marrow Morphology in Hereditary Thrombocytosis May Show Features of Myeloproliferative Neoplasms: A Case Report of a Child with Homozygous MPL Baltimore Germline Variant and Review of Literature

Abstract

Hereditary thrombocytosis (HT) is a rare cause of elevated platelet counts in children, most commonly resulting from germline variants in THPO or MPL. We report the first description of bone marrow morphology in a pediatric patient with germline homozygous MPL Baltimore (K39N) variant, a functional polymorphism resulting in HT. The patient had persistent thrombocytosis from infancy without bleeding or thrombotic complications. Bone marrow biopsy demonstrated mild hypocellularity, increased megakaryocytes forming small clusters, and megakaryocytic atypia partially overlapping with the morphologic features of myeloproliferative neoplasms (MPN). However, a somatic cytogenetic or molecular abnormality was not identified and it was determined that the thrombocytosis and bone marrow morphology were driven by the homozygous germline MPL Baltimore variant. Literature review found reports of bone marrow morphology in HT showing varying degrees of megakaryocytic proliferation and atypia with differences seen between specific germline variants. Cases with germline MPL P106L variant have similar morphology as this homozygous MPL Baltimore case. While cases of germline MPL S550N are nearly identical to MPN with more severe megakaryocytic atypia and frequent development of marrow fibrosis. This case underscores the importance of considering HT in children with unexplained thrombocytosis and highlights the diagnostic pitfall of misclassifying HT as MPN.