PMC5519475_01
Computed tomography (CT). CT at diagnosis (A) and at 8 months after the initiation of treatment with ruxolitinib (B).
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A 77-year-old Japanese man was referred to us because of erythrocytosis and thrombocytopenia with fatigue, weight loss (3 kg over 6 months), and splenomegaly (Fig. 1A). MF; this provided rapid histological (Fig. 2B) and hematological (Fig. 4) responses with an increase in platelets and a reduction of erythrocytosis. Moreover, the patient's splenomegaly (Fig. 1B) improved, and his body weight recovered to baseline.
The histopathological findings of the bone marrow specimen. (A) Diffuse trilineage proliferation with MF-2 fibrosis was present in whole marrow upon the diagnosis of post-PV MF. (B) Hypercellularity with fibrosis was significantly reduced and still partly present (*) at 8 months after starting the initiation of ruxolitinib treatment. Hematoxylin and Eosin staining and Gomori's silver impregnation (silver) are shown.
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A BM biopsy demonstrated hypercellularity with trilineage growth and reticulin fibrosis (Fig. 2A). MF; this provided rapid histological (Fig. 2B) and hematological (Fig. 4) responses with an increase in platelets and a reduction of erythrocytosis. Moreover, the patient's splenomegaly (Fig. 1B) improved, and his body weight recovered to baseline. Before treatment, hypercellularity and MF-2 grade reticulin fibrosis was seen throughout the BM (Fig. 2A). A BM biopsy performed at 10 months after the initiation of treatment showed a reduction in the cellularity and MF-0 to MF-1 grade fibrosis in approximately 70% of the BM, whereas 30% remained hypercellular with MF-2 grade fibrosis (Fig. 2B).
Evidence of underlying PV. (A) Burst-forming unit erythroid (BFU-E) colonies grown from 1x105 peripheral blood mononuclear cells (PBMNCs) with the indicated concentrations of erythropoietin (EPO) were counted using an inverted microscope. Some BFU-E colonies were seen in this case (dark gray) in the absence (0 U/mL) or presence of low-concentration EPO (0.3 U/mL). In contrast, in the PBMNCs of 2 healthy controls, BFU-E colonies barely grew at 0 and 0.3 U/mL EPO (light gray). The mean colony numbers of 2 plates are shown. (B) The Sanger sequence indicated substitutions of nucleotides that corresponded to JAK2H538QK539L.
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However, the patient was diagnosed with post-PV MF based on the detection of endogenous erythroid colony (EEC) formation and a known JAK2 exon 12 mutation [JAK2H538QK539L (8)] (Fig. 3), along with erythrocytosis, a decreased erythropoietin level (1.4 mIU/mL; RI, 4.2-23.7), and BM hypercellularity.
The clinical course. At 3 years before the diagnosis of post-PV MF (year X-3), the patient's peripheral blood cell count was normal. This patient had already developed erythrocytosis and thrombocytopenia at 2 years before the diagnosis (year X-2). In year X, after starting ruxolitinib treatment, his hemoglobin level (Hb) and platelet count (PLT) rapidly normalized; this effect has persisted for 16 months since the initiation of treatment. The patient's white blood cell count (WBC) has been stable.
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The previous data that were available also showed that he first developed erythrocytosis and thrombocytopenia at 2 years before his diagnosis (Fig. 4).