| Session: Ph- chronic myeloproliferative disease |
| Case number: 079 |
Submitter(s): Jeffrey H. Malik, Dahua Zhang, Eliot C. Williams, Ken H. Young.
Clinical history
The patient was a 72-year-old male with a history of essential thrombocytosis diagnosed in 1976, who developed chronic idiopathic myelofibrosis in 2003 and treated with hydroxyurea. His past medical history was significant for venous thromboembolism, portal hypertension and interstitial lung disease. On admission(12-29-2006), he reported progressive fatigue, malaise, weight loss, severe anoxia, chills and diffuse bony achiness. His peripheral blood showed a WBC of 4.4 (2,992 neu, 704 lym, 44 mono), Hgb 8.6 g/dL, HCT 29%, PLT 295,000 and 15% blasts. He received 40,000 units of erythropoietin IV and 8,500 mg of hydroxyurea weekly.
Details of gross/microscopic pathology:
The peripheral smear revealed normocytic anemia, lymphopenia, monopenia, numerous micromegakaryocytes with hypogranular platelets, and blasts (15%).
The bone marrow aspirate smear revealed an absence of marrow particles with markedly decreased erythroid and myeloid cells. Few erythroid precursors exhibited irregular nuclear contours and nuclear blebbing. Blasts are counted at 10%.
The bone marrow biopsy (left posterior iliac crest) demonstrated marked myelofibrosis with significantly decreased hematopoietic cells. The marrow cellular components were predominantly composed of stromal cells, small lymphocytes, plasma cells and blasts. Small clusters of dysplastic megakaryocytes were also noted.
Immunophenotype (flow cytometry/immunohistochemistry):
Immunostains for CD34 and CD117 revealed increased CD34-positive blasts.
Cytogenetics:
Cytogenetics revealed 46, XY, del(13)(q12q21)[20] with a deletion in the long-arm of chromosome 13 from band 13q12 to band 13q21, resulting in the loss of an unknown tumor suppressor gene at 13q14.
Molecular analysis:
The BCR/ABL fusion associated with t(9;22)(q34q11.2) was not detected by fluorescent in situ hybridization (FISH). JAK-2 V617F mutation analysis was negative.
Interesting feature(s) of submitted case:
In comparison to the previous biopsies performed in 2003 and 2005, the current biopsy demonstrated several distinct changes including increased blasts in the peripheral blood (15%) and bone marrow (10%). Dysplastic micromegakaryocytes and hypogranular platelets were profound in the peripheral blood. These findings signify transformation of the lesion into an accelerated or blast phase. However, a diagnostic distinction from acute myeloid leukemia is difficult to clearly define.
Proposed diagnosis:
Peripheral blood with normocytic anemia, lymphopenia, monopenia, dysplastic micromegakaryocytes and 15% blasts.
- Markedly hypocellular marrow (10-20%) with panhypoplasia, marked myelofibrosis and increased blasts (10%) with features transforming into an accelerated or blast phase.
Panel diagnosis:
Review of previous biopsies (1976/2003) necessary to exclude CIMF/PMF; severe therapy related changes seen in the current case.
Comments:
Additional information from the submitter: Flow cytometry of bone marrow is not very helpful due to sampling difference in terms of blasts count. Flow cytometry analysis reveals the majority of events (about 85%) show low/absent CD45 and stain with CD61, the megakaryocytes marker. These positive events would include both nucleated megakaryocytes and platelets. Approximately 5% of the cells analyzed have the phenotype of myeloid blasts (CD34+/CD117+). The patient has had a remote splenectomy performed in the 1970 with an unknown reason.
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