Persistent pancytopenia after therapy with vemurafenib plus rituximab for HCL relapsed following multiple lines of chemotherapy. Upper left panel, immunohistochemical staining of BM biopsy with an anti-CD19 monoclonal antibody before starting vemurafenib plus rituximab shows considerable infiltration by CD19⁺ leukemic hairy cells (brown). (Leica immunostaining; immunoperoxidase; hematoxylin counterstaining; ×400). Upper right panel, BM biopsy after vemurafenib plus rituximab therapy showing complete disappearance of HCL. The thin arrow indicates a single residual normal CD79a⁺ plasma cell (brown). The thick arrow points to a monolobated megakaryocyte (Leica immunostaining; immunoperoxidase; hematoxylin counterstaining; ×400). Bottom left panel, the BM biopsy after therapy with vemurafenib plus rituximab shows, on ematoxylin-eosin (EE) staining, a myelodysplastic marrow with many monolobated megakaryocytes (thick arrow). The bottom right panel shows many monolobated megakaryocytes (thick arrow) and a significant percentage of CD34⁺ blast cells (brown, thin arrow) (Leica immunostaining; immunoperoxidase; hematoxylin counterstaining; ×400). Retrospectively, monolobated megakaryocytes (thick arrow, upper left panel) and an increased number of CD34⁺ cells (inset in the upper left panel) were present also in the BM biopsy before vemurafenib plus rituximab therapy, but they had been overlooked because of the predominant HCL infiltration.