| Session: Ph- chronic myeloproliferative disease |
| Case number: 178 |
Submitter(s): Nicholas T. Wongchaowart, James R. Cook.
Clinical history
VZ was a 73 year-old female with a longstanding history of a chronic myeloproliferative disorder diagnosed at an outside institution who presented for a second opinion regarding marked leukocytosis and symptomatic splenomegaly. She was being treated with Hydrea (hydroxyurea), and prior therapies included splenic radiation and Agrylin (anagrelide). She had a right hemicolectomy for adenocarcinoma 1 year ago. Physical examination revealed massive splenomegaly. Bone marrow biopsy material from the time of diagnosis was not available for review. Complete blood count and differential showed WBC 89.5 x 10^3 per microliter, RBC 4.01 x 10^6 per microliter, Hgb 8.6 g per dL, MCV 82 fL, RDW-CV 22%, platelets 240 x 10^3 per microliter, neutrophils 81%, lymphocytes 3%, monocytes 3%, eosinophils 1%, basophils 5%, metamyelocytes 5%, myelocytes 2%, NRBCs 4 per 100 WBCs.
Details of gross/microscopic pathology:
Examination of the peripheral blood revealed marked leukoerythroblastosis, erythroid anisopoikilocytosis with teardrop cells, and rare circulating blasts (<1%). The bone marrow aspirate was aspicular and hypocellular, but the touch preparation from the core biopsy showed trilineage hematopoiesis with an increased myeloid to erythroid ratio, 4% blasts, and no dysplasia. The bone marrow biopsy was fixed in B5 solution and decalcified in dilute hydrochloric acid. The bone marrow was hypercellular (>90%) due to granulocytic and megakaryocytic hyperplasia. Megakaryocytes clustered focally, and occasional forms were enlarged and had hyperchromatic nuclei. Immature mononuclear cells were not increased. There was osteosclerosis, and reticulin and trichrome stains showed moderate, diffuse reticulin fibrosis without collagenous fibrosis. Storage iron was not identified.
Immunophenotype (flow cytometry/immunohistochemistry):
Immunohistochemical stains for CD34 and phosphorylated (p) -STAT5 were performed. Rare mononuclear cells were CD34 positive. Occasional megakaryocytes demonstrated nuclear staining for p-STAT5. Flow cytometry was not performed due to the aspicular and hypocellular nature of the bone marrow aspirate.
Cytogenetics:
Cytogenetic analysis revealed a normal, female karyotype.
Molecular analysis:
PCR studies for the JAK2 V617F mutation on the peripheral blood were positive, and consistent with a homozygous state. RT-PCR studies for the BCR-ABL translocation were negative.
Interesting feature(s) of submitted case:
This case was morphologically consistent with idiopathic myelofibrosis. Further investigation of the history revealed prior therapeutic phlebotomies and a diagnosis of polycythemia vera. JAK2 V617F homozygousity is reportedly preferentially seen in polycytemia vera, and may be helpful in determining if myelofibrosis represents the post-polycythemic stage of polycythemia vera versus another chronic myeloproliferative disorder. Megakaryocytic p-STAT5 staining may be a useful surrogate marker for the JAK2 mutation.
Proposed diagnosis:
Polycythemia vera, post-polycythemic (fibrotic) stage.
Panel diagnosis:
MPD unclassifiable
Comments:
Panel comment: Definitive diagnosis is not possible without review of original diagnostic material and laboratory data. Additional information from the submitter: The detailed documentation of the prior diagnosis of polycythemia vera is not available. The patient was originally biopsied in West Virginia 12 years ago, and came to Cleveland in December 2006 for a second opinion regarding her symptomatic splenomegaly. Outside, diagnostic bone marrow biopsy was not reviewed and there was no access to the original laboratory data. The diagnosis of polycythemia vera is based on clinical history alone.
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