Chronic Myeloid Neoplasms
Myeloid neoplasms associated with eosinophilia and abnormalities
Myeloid neoplasm associated with PDGFRA rearrangement

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 8 March 2017, last major update August 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Myeloid neoplasm "PDGFRA rearrangement"

Cite this page: Myeloid neoplasm associated with PDGFRA rearrangement. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/myeloproliferativePDGFRA.html. Accessed August 22nd, 2017.
Definition / general
  • 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
  • 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
Treatment
  • 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)
Microscopic (histologic) description
  • 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
Microscopic (histologic) images

Images hosted on other servers:

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:

Atypical spindle shaped mast cells

Ill defined, atypical mast cells

Before and after imatinib therapy

Molecular / cytogenetics description
Differential diagnosis