| Session: Ph- chronic myeloproliferative disease |
| Case number: 219 |
Submitter(s): Claudiu V. Cotta, Carlos E. Bueso-Ramos.
Clinical history
68 y.o. female diagnosed in 1985 with polycythemia vera (P.Vera), initially treated with phlebotomy. In 1996 she developed anemia (Hb 7.3) and post-polycythemic myelofibrosis and myeloid metaplasia (PPMM) (11% blasts) with dysplastic features. Cytogenetics showed del(20q). She was transfusion dependent, had splenomegaly and received treatment with Hydrea. In 1998 she had a splenectomy at another institution, resulting in reduced frequency of blood transfusions. The bone marrow aspirate performed shortly after that at UTMDACC had 11% blasts and conventional cytogenetic analysis showed del(20q)[17]/+8, del(20q)[2]. She received erythropoietin but did not respond. The treatment was switched to interferon alpha, for 8 (1998-2007) years, the blast counts decreased (<5%) and she was diploid by conventional cytogenetics. In November 2006 her peripheral counts were WBC 9.8, Hgb 10.1, MCV 102, Plts. 285, Neutrophils 73, Lymphs 12, Monos 3, Eos 1, Basos 1, Metas 1, Blasts 9. The bone marrow biopsy showed PPMM with 10% blasts. Molecular studies showed Jak2 V617F mutation, conventional cytogenetic analysis reported 47,XY,+8,der(17)t(1;17)(q11;p13),del(20)(q13.1)[2]. Early in 2007 she became weakened, and developed fungal infections (pulmonary aspergillosis). Current CBC: WBC 9.5, Hgb 9.6, MCV 102, Plts. 202, Neutrophils 52, Lymphs 17, Monos 6, Basos 2, Blasts 23.
Details of gross/microscopic pathology:
Bone marrow biopsy shows mild bone remodeling and extensive fibrosis, with wide-open sinuses. Cellularity is variable, 70-100%. Numerous foci of immature cells are seen. Megakaryocytes are increased, of variable sizes and shapes, some clustered, some with hyperchromatic nuclei. Reticulin fibrosis is increased (3+), there is no collagen fibrosis. The aspirate smears are aparticulate, with features similar to the peripheral blood smear (25% blasts).
Immunophenotype (flow cytometry/immunohistochemistry):
Blasts are positive for CD13, CD33, CD34, CD38, CD117, HLA-DR, myeloperoxydase, and negative for lymphoid markers.
Cytogenetics:
47,XX,+8,der(17)t(1;17)(q11;p13),del(20)(q13.1)[14] and several additional abnormalities.
Molecular analysis:
Positive for Jak2 V617F mutation, PCR product with the mutation: 80.4%. One month before: no N- or K-ras mutations.
Interesting feature(s) of submitted case:
This case shows progression of P. Vera to PPMM and later to acute leukemia. Progression was accompanied by increasing blast counts (10%) and clonal genetic mutations. There was clinical, laboratory and cytogenetic response to interferon alpha. In 2006, the Jak2 mutation was identified. 21 years after the initial diagnosis, the patient had an increase in the blast counts (10%) and shortly after that progressed to blast phase, with myeloid blast phenotype. This case debates the significance of 10% blast in Ph- CMPD.
Proposed diagnosis:
Acute myeloid leukemia evolving from previously diagnosed chronic myeloproliferative disease with myelofibrosis.
Panel diagnosis:
agree with proposed diagnosis
Comments:
Panel comment: Review of original diagnostic material is advisable.
PowerPoint:
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