Clinical vignettes illustrating representative cases of ET or related myeloid neoplasms
| . | Description . | Clinical presentation . | Diagnostic approach . | Therapeutic decision-making . |
|---|---|---|---|---|
| Case 1 | Typical asymptomatic, middle-age woman with incidental thrombocytosis and the JAK2 (V617F) mutation (low-risk JAK2-mutant ET). | A 40-y-old woman was referred to us because a routine CBC showed: Hb, 13.9 g/dL; WBC count, 9.2 × 109/L; PLT count, 464 × 109/L. Physical examination was normal. | Body iron status was normal and CRP was below 1.0 mg/L. Testing for BCR-ABL1 fusion gene was negative. JAK2 (V617F) was detected on granulocyte DNA (5% mutant alleles). Bone marrow biopsy showed megakaryocyte proliferation with increased numbers of enlarged, mature megakaryocytes. Silver impregnation after Gomori showed single scattered reticulin fibers consistent with the appearance of the normal bone marrow. | Low-risk JAK2 (V617F)-mutant ET was diagnosed, and the patient was given low-dose aspirin (100 mg per day). |
| Case 2 | Young woman with incidental thrombocytosis, mild oral mucosal bleeding after tooth brushing, and type 1 CALR mutation (low-risk CALR-mutant ET with acquired von Willebrand syndrome). | A 24-y-old woman was referred to us for incidental thrombocytosis: a routine CBC showed: Hb, 13.1 g/dL; WBC count, 7.3 × 109/L; and PLT count, 1069 × 109/L. She complained of oral mucosal bleeding after tooth brushing and occasional dizziness. | As JAK2 (V617F) mutation was absent, we sequenced CALR exon 9 and detected the type 1 mutation (c.1092_1143del, L367fs*46). Bone marrow biopsy was consistent with a diagnosis of ET. | As PLT count was >1000 × 109/L and there was a history of mucosal bleeding, we assessed von Willebrand factor: ristocetin cofactor activity was low (30%) whereas the antigen level was normal, indicating an acquired von Willebrand syndrome. We therefore decided not to use low-dose aspirin: a cytoreductive treatment with interferon α will be considered if PLT count increases further (to ≥1500 × 109/L) and/or bleeding becomes more severe. |
| Case 3 | Middle-age woman with incidental thrombocytosis and the JAK2 (V617F) mutation who later also developed erythrocytosis (JAK2-mutant ET progressing to PV). | A 48-y-old woman was referred to us because a routine CBC count showed isolated thrombocytosis: Hb, 13.9 g/dL; Hct, 43.0%; MCV, 85 fL; WBC count, 9.5 × 109/L; and PLT count, 838 × 109/L. She was asymptomatic and the spleen was not palpable. | JAK2 (V617F) was detected on granulocyte DNA (38% mutant alleles). Bone marrow biopsy was consistent with a diagnosis of ET; in particular, there was no significant increase or left shift in neutrophil granulopoiesis or erythropoiesis. | The patient was given low-dose aspirin. Three years later, she developed erythrocytosis (Hb, 16.5 g/dL and Hct, 48.2%). The JAK2 (V617F) mutant allele burden was increased (65%), whereas serum erythropoietin was low 3.3 (mU/mL). Polycythemic transformation of ET was diagnosed, and a phlebotomy program aimed to maintain Hct <45% was associated to low-dose aspirin. |
| Case 4 | Asymptomatic, elderly patient with incidental thrombocytosis and the JAK2 (V617F) mutation (high-risk JAK2-mutant ET) | A 67-y-old man was found to have isolated thrombocytosis on a routine CBC count (PLT count 610 × 109/L). He previously had transurethral resection of the prostate for benign prostatic hyperplasia, and was taking a statin for hypercholesterolemia. | JAK2 (V617F) was detected on granulocyte DNA (39% mutant alleles). Bone marrow biopsy showed megakaryocyte proliferation with increased numbers of enlarged, mature megakaryocytes. Grading of fiber density showed normal findings. | The patient was given low-dose aspirin (100 mg per day). Because of age greater than 60 y, a cytoreductive treatment with hydroxyurea was also started (1 g per day). In few months, the PLT count decreased to 256 × 109/L, and the dose of hydroxyurea was reduced to 500 mg per day. |
| Case 5 | Asymptomatic, elderly patient with thrombocytosis, mild anemia and the MPL (W515L) mutation (MPL-mutant MDS/MPN-RS-T mimicking ET) | A 64-y-old woman was referred to us because a routine CBC count showed: Hb, 10.3 g/dL; MCV, 96 fL; WBC count, 6.39 × 109/L; ANC, 4.30 × 109/L; and PLT count, 730 × 109/L. | Tests for JAK2 (V617F) and CALR exon 9 mutations were negative, and the MPL (W515L) mutation was detected on granulocyte DNA. Bone marrow aspirate showed erythroid dysplasia with megaloblastoid features, 60% ring sideroblasts, and large atypical megakaryocytes; bone marrow biopsy was consistent with a MDS/MPN. Mutation analysis of SF3B1 showed a wild-type sequence. | A diagnosis of MDS/MPN-RS-T was made. The patient was given low-dose aspirin. |
| . | Description . | Clinical presentation . | Diagnostic approach . | Therapeutic decision-making . |
|---|---|---|---|---|
| Case 1 | Typical asymptomatic, middle-age woman with incidental thrombocytosis and the JAK2 (V617F) mutation (low-risk JAK2-mutant ET). | A 40-y-old woman was referred to us because a routine CBC showed: Hb, 13.9 g/dL; WBC count, 9.2 × 109/L; PLT count, 464 × 109/L. Physical examination was normal. | Body iron status was normal and CRP was below 1.0 mg/L. Testing for BCR-ABL1 fusion gene was negative. JAK2 (V617F) was detected on granulocyte DNA (5% mutant alleles). Bone marrow biopsy showed megakaryocyte proliferation with increased numbers of enlarged, mature megakaryocytes. Silver impregnation after Gomori showed single scattered reticulin fibers consistent with the appearance of the normal bone marrow. | Low-risk JAK2 (V617F)-mutant ET was diagnosed, and the patient was given low-dose aspirin (100 mg per day). |
| Case 2 | Young woman with incidental thrombocytosis, mild oral mucosal bleeding after tooth brushing, and type 1 CALR mutation (low-risk CALR-mutant ET with acquired von Willebrand syndrome). | A 24-y-old woman was referred to us for incidental thrombocytosis: a routine CBC showed: Hb, 13.1 g/dL; WBC count, 7.3 × 109/L; and PLT count, 1069 × 109/L. She complained of oral mucosal bleeding after tooth brushing and occasional dizziness. | As JAK2 (V617F) mutation was absent, we sequenced CALR exon 9 and detected the type 1 mutation (c.1092_1143del, L367fs*46). Bone marrow biopsy was consistent with a diagnosis of ET. | As PLT count was >1000 × 109/L and there was a history of mucosal bleeding, we assessed von Willebrand factor: ristocetin cofactor activity was low (30%) whereas the antigen level was normal, indicating an acquired von Willebrand syndrome. We therefore decided not to use low-dose aspirin: a cytoreductive treatment with interferon α will be considered if PLT count increases further (to ≥1500 × 109/L) and/or bleeding becomes more severe. |
| Case 3 | Middle-age woman with incidental thrombocytosis and the JAK2 (V617F) mutation who later also developed erythrocytosis (JAK2-mutant ET progressing to PV). | A 48-y-old woman was referred to us because a routine CBC count showed isolated thrombocytosis: Hb, 13.9 g/dL; Hct, 43.0%; MCV, 85 fL; WBC count, 9.5 × 109/L; and PLT count, 838 × 109/L. She was asymptomatic and the spleen was not palpable. | JAK2 (V617F) was detected on granulocyte DNA (38% mutant alleles). Bone marrow biopsy was consistent with a diagnosis of ET; in particular, there was no significant increase or left shift in neutrophil granulopoiesis or erythropoiesis. | The patient was given low-dose aspirin. Three years later, she developed erythrocytosis (Hb, 16.5 g/dL and Hct, 48.2%). The JAK2 (V617F) mutant allele burden was increased (65%), whereas serum erythropoietin was low 3.3 (mU/mL). Polycythemic transformation of ET was diagnosed, and a phlebotomy program aimed to maintain Hct <45% was associated to low-dose aspirin. |
| Case 4 | Asymptomatic, elderly patient with incidental thrombocytosis and the JAK2 (V617F) mutation (high-risk JAK2-mutant ET) | A 67-y-old man was found to have isolated thrombocytosis on a routine CBC count (PLT count 610 × 109/L). He previously had transurethral resection of the prostate for benign prostatic hyperplasia, and was taking a statin for hypercholesterolemia. | JAK2 (V617F) was detected on granulocyte DNA (39% mutant alleles). Bone marrow biopsy showed megakaryocyte proliferation with increased numbers of enlarged, mature megakaryocytes. Grading of fiber density showed normal findings. | The patient was given low-dose aspirin (100 mg per day). Because of age greater than 60 y, a cytoreductive treatment with hydroxyurea was also started (1 g per day). In few months, the PLT count decreased to 256 × 109/L, and the dose of hydroxyurea was reduced to 500 mg per day. |
| Case 5 | Asymptomatic, elderly patient with thrombocytosis, mild anemia and the MPL (W515L) mutation (MPL-mutant MDS/MPN-RS-T mimicking ET) | A 64-y-old woman was referred to us because a routine CBC count showed: Hb, 10.3 g/dL; MCV, 96 fL; WBC count, 6.39 × 109/L; ANC, 4.30 × 109/L; and PLT count, 730 × 109/L. | Tests for JAK2 (V617F) and CALR exon 9 mutations were negative, and the MPL (W515L) mutation was detected on granulocyte DNA. Bone marrow aspirate showed erythroid dysplasia with megaloblastoid features, 60% ring sideroblasts, and large atypical megakaryocytes; bone marrow biopsy was consistent with a MDS/MPN. Mutation analysis of SF3B1 showed a wild-type sequence. | A diagnosis of MDS/MPN-RS-T was made. The patient was given low-dose aspirin. |
ANC, absolute neutrophil count; Hb, hemoglobin; Hct, hematocrit.