Practice questions answers myeloid neoplasms III

Practice questions answers

Myeloid neoplasms III

© Jun Wang, MD, PhD

1. D. This patient has elevated red cell and platelet count with normal range white cells. Peripheral blood reveals immature red cells (upper right corner, adjacent to a neutrophil, and the two at lower left corner), but no blast is seen. Bone marrow has erythroid and megakaryocytic hyperplasia. This is most consistent with polycythemia vera, a type of myeloproliferative neoplasms. In order to make a diagnosis of polycythemia vera, essential thrombocythemia, or primary myelofibrosis, the presence of JAK2, CAL or MPL mutation needs to be demonstrated, and JAK2V617F is usually tested first. Splenomegaly in myeloproliferative neoplasms is caused by extramedullary hematopoiesis or functional hypersplenism, and sonographic exam and biopsy findings of spleen in myeloproliferative neoplasms are nonspecific. Cytogenetics studies can detect chromosome abnormalities, but not mutation. Myeloproliferative neoplasms commonly have normal immunohistochemistry profiles and flow cytometry studies are not useful.

2. D. The patient has elevated red cell mass and low erythropoietin, features highly suggestive of polycythemia vera. In the case of negative JAK2V617F result, JAK2exon mutation analysis is needed. Also see discussion of question 1.

3. D. Elevated red cell mass and low erythropoietin are highly suggestive of polycythemia vera. Acute myeloid leukemia is diagnosed when there are more than 20% of myoloblasts or with confirmed genetic abnormalities. Chronic myelogenous leukemia and leukemoid reaction have increased mature neutrophils, basophils and eosinophils. Essential thrombocythemia has sole thrombocytosis, but not increase red cell mass. Primary myelofibrosis has anemia. Secondary polycythemia has elevated erythropoietin, not reduced.

4. D. This patient has history of polycythemia vera. With the current presentation of anemia and presence of teardrop shaped red cells, this is most likely the spent phase with marrow fibrosis. Acute myeloid leukemia is diagnosed when there are more than 20% of myoloblasts or with confirmed genetic abnormalities. Chronic myelogenous leukemia and leukemoid reaction have increased mature neutrophils, basophils and eosinophils. Although iron deficiency may occur in polycythemia vera due to bleeding, the teardrop shaped red cells are less likely seen and the most likely cause of anemia is myelofibrosis. In order to make a diagnosis of primary myelofibrosis, other myeloproliferative neoplasms need to be ruled out.

5. C. This patient has isolated thrombocytosis and megakaryocyte hyperplasia without significant morphological abnormality. This is most consistent with essential thrombocythemia. Also see discussion of question 3.

6. D. See discussion of question 1.

7. C. Essential thrombocythemia is associated with activating mutations of JAK2, calreticulin or MPL. ABL abnormality is seen in chronic myelogenous leukemia and some acute myeloid leukemia. KIT and trisomy 22 are frequently associated with inv(16), as seen in AML with inv(16)(p13.1q22). RAR-alpha abnormality is seen in APL with PML-RARA. RUNX1 abnormality is seen in AML with t(8;21)(q22;q22.1).

8. A. Essential thrombocythemia is associated with activating mutations of JAK2, calreticulin or MPL. Elevation of erythropoietin is seen in secondary polycythemia. Elevation thrombopoietin is seen in secondary thrombocytosis. Release of TGF-beta is seen in primary myelofibrosis, and probably spent phase of other myeloproliferative neoplasms.

9. E. This patient has pancytopenia and myelofibrosis. Since she has no history of other myeloproliferative neoplasms, this is most likely primary myelofibrosis. Hairy cell leukemia usually presents with massive splenomegaly and tumor cells with thread-like extensions and is positive for CD11c. This patient does not have abnormal morphology of her white cells. Iron deficiency anemia does not have the teardrop shaped red cells nor myelofibrosis. Myelodysplastic syndrome has dysplastic changes of myeloid and/or erythroid precursors. Polycythemia vera has elevated red cell mass and low erythropoietin.

10. D. JAK2 mutation is commonly seen in myeloproliferative neoplasms, including  polycythemia vera, essential thrombocythemia, or primary myelofibrosis. ABL abnormality is seen in chronic myelogenous leukemia and some acute myeloid leukemia. Hemoglobin alpha or beta mutation is seen hemoglobinopathies, such as sickle cell anemia or thalassemia. Spectrin mutation is seen in hereditary spherocytosis.

11. A. The hepatosplenomegaly seen in myeloproliferative neoplasms is most likely associated with extramedullary hematopoiesis.

12. A. She developed acute symptoms with the presence of more than 20% myeloblasts (positive for CD33 and CD34 but negative for TdT). This is transformation into acute myeloid leukemia, that can be seen in some patients with myeloproliferative neoplasms or myelodysplastic syndrome. Aplastic anemia, reactive leukocytosis or ruxolitinib toxicity do not have blasts. Myelodysplastic syndrome may have blasts, but should be less than 20%.

13. A. This patient has pancytopenia, pseudo Pelger Huet cells (bilobed neutrophils) and bone marrow aspiration reveals dysplastic erythroid. The blast count is less than 20%. These features are consistent with myelodysplastic syndrome. Although the diagnosis of myelodysplastic syndrome is based on evaluation of bone marrow and peripheral blood smears in a proper clinical context, cytogenetics studies may help distinguish it from acute myeloid leukemia, and predict prognosis. Ferritin studies are helpful for iron deficiency anemia. Hemoglobin electrophoresis is used for hemoglobinopathies.  JAK2 V617F mutation can be seen in polycythemia vera, essential thrombocythemia, or primary myelofibrosis. Folate/vitamin B12 deficiency is seen in megaloblastic anemia. Neither myeloproliferative neoplasms nor pure anemia has leukopenia and thrombocytopenia.

14. E. See discussion of question 13.

15. D.  Myelodysplastic syndrome is associated with stem cell defects. Bone marrow suppression is associated with disrupted bone marrow microenvironment by tumor or other factors. Hemoglobinopathy, folate acid or iron deficiency are associated with anemia, without white cell or platelet abnormalities.

16. E. She developed acute symptoms with the presence of more than 20% myeloblasts. This is transformation into acute myeloid leukemia, that can be seen in some patients with myeloproliferative neoplasms or myelodysplastic syndrome. Chronic transfusion reaction, extramedullary hematopoiesis and infection do not cause elevated blasts. Myelofibrosis usually has leukopenia, not leukocytosis. In addition, the blast count is less than 20%.

17. D. EM findings of these elongated zipper like structure (Birbeck granule) in a lymph node with eosinophilic infiltrate is most consistent with Langerhans cell histiocytosis. Allergic lymphadenitis and parasite infection may have eosinophilic infiltration, but usually presents with related history and no Birbeck granules should be seen. Cat scratch disease usually presents as Acute lymphadenitis with neutrophilic infiltrate. Chronic lymphadenitis has follicular hyperplasia with normal architecture, but not eosinophilic infiltrate.  

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