Bone marrow morphologic features in polycythemia vera with JAK2 exon 12 mutations

The diagnosis of polycythemia vera (PV) requires the integration of clinical and laboratory findings, bone marrow morphologic features, and JAK2 analysis. JAK2^V617F (exon 14) mutation is found in 95% of PV cases. Functionally similar mutations in JAK2 exon 12 have also been described, but a thorough bone marrow study has not been done. We identified 7 PV cases with exon 12 mutations; all had hypercellular bone marrow with erythroid hyperplasia. Small, atypical megakaryocytes predominated; atypical megakaryocyte lobation and abnormal chromatin distribution was identified in all cases. Rare clusters of megakaryocytes could be found but were typically subtle. Because JAK2 exon 12-positive PV cases lack the classic myeloproliferative morphologic features, bone marrow samples from the patients may be difficult to classify as myeloproliferative neoplasms. Clinically suspected PV with low serum erythropoietin and absent JAK2^V617F, together with the bone marrow findings of erythroid hyperplasia and subtle megakaryocytic atypia, should prompt an evaluation for an exon 12 mutation.