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Chronic Myeloid Neoplasms

MDS/MPN

Myeloid neoplasm associated with PDGFRA rearrangement


Reviewer: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 11 August 2011, last major update August 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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● Also called chronic eosinophilic leukemia; chronic eosinophilic leukemia with FIP1L1-PDGFRA; myeloproliferative variant of the hypereosinophilic syndrome
● First discovered in 2003 (N Engl J Med 2003;348:1201, Proc Natl Acad Sci USA 2003;100:7830)
● More common in males; median age in late 40s
● Multisystem disorder secondary to tissue infiltration with splenomegaly, endomyocardial fibrosis causing restrictive cardiomyopathy, restrictive airway disease
● Elevated serum tryptase (not as high as in mast cell disorders) and increased vitamin B12
● Expression of FIP1L1-PDFGRA in hematopoietic progenitors may induce a myeloproliferative phenotype by activating multiple signaling molecules including STAT5 (Cancer Res 2007;67:3759)
● Fusion gene also associated with AML (Leukemia 2007;21:1183)

Diagnosis
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● Bone marrow examination with tryptase stain, T cell clonal studies
● Use of immunostains, cytogenetics and molecular studies to detect PDFGRA rearrangement and absence of BCR-ABL

Case reports
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● With Budd-Chiari syndrome (hepatic vein outflow obstruction, Intern Med 2007;46:1095)

Treatment
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● Very sensitive to imatinib (Blood 2007;109:4635)
● Cases with acute transformation also respond to imatinib
● Resistance to imatinib can develop due to T674I mutation
● Molecular monitoring appears to be useful (Blood 2007;110:3552)

Micro description
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● Peripheral blood shows eosinophilia, occasionally neutrophilia
● Monocytes and basophils are not increased
● Marked bone marrow hypercellularity due to eosinophils and myeloid precursors
● Also increased CD2 negative CD25 positive mast cells and atypical spindle shaped mast cells but no mast cell aggregates
● Reticulin fibrosis

Micro images
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Peripheral blood:

Left: anemia, leukocytosis with increased granulocytes and precursors, and eosinophilia; right: bone marrow showing hypercellularity with marked myeloid hyperplasia, mild eosinophilia, no increase in blasts

Bone marrow biopsy:

Fig A-C: marked cellularity, atypical spindle shaped mast cells and reticulin fibrosis


Fig A: ill-defined, loose aggregates of atypical mast cells highlighted with tryptase stain (fig B)


Before and after imatinib therapy

Molecular description
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● FIP1L1-PDGFRA fusion gene results from cryptic 4q12 interstitial deletion; rare FIP1L1 breakpoint (J Mol Diagn 2007;9:414)
● Other genes may partner with PDGFRA (Br J Haematol 2007;138:77)
● No KIT mutation

Differential diagnosis
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Systemic mastocytosis with eosinophilia: mast cell aggregates highlighted by tryptase stain; no elevated serum tryptase, different mutations, mast cells in mastocytosis are CD25 positive and 2/3 are CD2 positive (J Allergy Clin Immunol 2007;120:680)
Chronic eosinophilic leukemia-not otherwise categorized or Hypereosinophilic syndrome: both lack PDFGRA rearrangement

Additional references
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Orphanet J Rare Dis 2007;2:37, Atlas of Genetics and Cytogenetics

End of Chronic Myeloid Neoplasms > MDS/MPN > Myeloid neoplasm associated with PDGFRA rearrangement


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