| Session: Ph- chronic myeloproliferative disease |
| Case number: 110 |
Submitter(s): Curtis A. Hanson, William G. Morice, Animesh Pardanani.
Clinical history
A previously healthy 55 year old white male presented with an acute cerebellar infarction. The patient had no known cardiovascular risk factors. No organomegaly was identified on examination or by scans. Radiographic studies failed to find any source of the embolism and his cranial vessels appeared normal.
CBC: Hgb: 14.8 g/dL; WBC: 4.6 x10(9)/L; PLT: 390 x10(9)/L
WBC Differential (%): Neutrophils 57; lymphocytes 23; monocytes 16; eosinophils 1; basophils 1; myelocytes 2.
Details of gross/microscopic pathology:
The peripheral blood smear had no abnormalities noted. The bone marrow aspirate and biopsy (B5-fixed; acid decal) were normocellular (50%). Erythroid and granulocytic precursors were normal with no dysplasia seen. No increase in blasts was noted. In the bone marrow aspirate a small subset of the megakaryocytes appeared large with multilobated nuclei and increased N:C ratios. In the biopsy the megakaryocytes were increased in number with a subset identified that were large in size having an open chromatin pattern, visible nucleoli, and increased N:C ratios. Loose aggregates and well-formed clusters of megakaryocytes were identified.
Cytochemical stains:
An iron stain was performed on the aspirate specimen showed no ringed sideroblasts. A combined butyrate esterase /chloroacetate esterase cytochemical stain showed a normal cytochemical staining pattern. A reticulin stain showed no increase in reticulin.
Immunophenotype (flow cytometry/immunohistochemistry):
Immunohistochemical stains were performed on paraffin-embedded sections of bone marrow biopsy using antibodies against the following antigens: hemoglobin, myeloperoxidase, CD61, CD34, CD123, and CD68. The CD61 stain showed increased numbers of megakaryocytes and highlighted their cytological atypia and cluster formation. The remaining stains showed a normal distribution of hematopoietic elements.
Cytogenetics:
Cytogenetic studies were performed on the bone marrow specimen. Of 20 metaphases, 3 lacked a Y chromosome and 17 were 46,XY.
Molecular analysis:
Genomic DNA was extracted and a quantitative, allele-specific polymerase chain reaction assay used to evaluate for the point mutation causing JAK2-V617F. The assay confirmed the presence of the JAK2-V617F mutation.
Interesting feature(s) of submitted case:
Patients with BCR-ABL-negative myeloproliferative disorders may develop large-vessel arterial or venous thrombosis and frequently have been shown to have the JAK2-V617F mutation. The findings in this case of a 'latent' MPD in a patient with 'cryptogenic' stroke raise questions regarding the prevalence of MPD in cases of arterial and venous thromboses; the contribution of 'latent' MPD to thrombosis; and the frequency with which 'latent' MPD evolves to overt MPD in such patients.
Proposed diagnosis:
Chronic myeloproliferative disorder, not otherwise classified, with associated JAK2-V617F mutation.
Panel diagnosis:
agree with proposed diagnosis
Comments:
Panel comment: Gray zone presentation, probably early CIMF/PMF
PowerPoint:
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