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Myeloid Neoplasm with Eosinophilia and PDGFR-alpha Rearrangement

Posted on January 12 2012

Myeloid Neoplasm with Eosinophilia and PDGFR-alpha Rearrangement
Case Study

Hypereosinophilia represents a diagnostic challenge. As in the past, one must clinically exclude benign secondary reactive causes such as infection, hypersensitivity, paraneoplastic reaction, pulmonary and autoimmune diseases. If there is persistent, unexplained eosinophilia lasting more than 6 months without attributable cause, one might consider myeloproliferative neoplasms with dominant eosinophilia, chronic eosinophillic leukemia, rare myeloid and lymphoid neoplasms with recurrent genetic abnormalities or the shrinking category of hypereosinophilia syndrome.

New molecular tests help clarify the diagnostic challenge of hypereosinophilia but paradoxically seem more complicated to those who are unfamiliar.

Entities causing hypereosinophillia that are easily evaluated in peripheral blood include atypical CML with eosinophilia, myeloid neoplasms with FIP1L1/PDGFR-alpha fusion, and JAK2 V617F-positive myeloproliferative disorders with eosinophilia, although JAK2 mutations do not completely exclude chronic eosinophilic leukemia. For these considerations, one can submit peripheral blood for FISH - BCR/ABL t(9;22), FISH -del 4q12; and PCR for JAK2 V617F mutation. Note that the FIP1L1/PDGFR-alpha fusion is typically cytogenetically cryptic and best detected by FISH for del 4q12.

By definition, chronic eosinophilic leukemia excludes neoplasms with BCR/ABL, PDGFR-alpha, PDGFR-B (5q31-33) and FGFR1 (8p11) abnormalities. In the proper morphologic and clinical setting, cytogenetic evidence for clonal genetic abnormalities supports a diagnosis of chronic eosinophilic leukemia but does not by itself exclude a myeloproliferative disorder with eosinophilia. Finally, there are rare myeloid and lymphoid neoplasms with hypereosinophilia that demonstrate abnormalities of PDGFR-B (5q31-33) and FGFR1 (8p11), requiring somewhat esoteric lab testing.

In summary, current molecular testing for neoplastic causes of hypereosinophilia often helps to clarify what used to be a diagnostic conundrum. A stepwise approach to molecular testing is recommended. Flow Cytometry Leukemia / non-Hodgkin Lymphoma FIP1L1/PDGFRA 4q12 Rearrangement BCR/ABL+9q34, t(9;22) Chromosome Analysis Bone Marrow

History

A 55 year-old male presented with unexplained eosinophilia. Bone marrow aspirate material was submitted for flow cytometry.

Special Studies

Flow Cytometry
Revealed 15% phenotypically normal eosinophils (pink) without increased or aberrant blasts, aberrant myelomonocytic antigen staining or aberrant lymphocytes.

FISH

NEGATIVE for BCR/ABL t(9;22) and POSITIVE for deletion of 4q12

Cytogenetics
Revealed an abnormal karyotype with an interstitial deletion of the long arm of chromosome 13 in 15 of 20 metaphases. 46,XY,del(13)(q12q14)[15]/46,XY[5].

References

Gotlib J. (2011). World Health Organization-defined eosinophilic disorders: 2011 update on diagnosis, risk stratification, and management. Am J Hematol. (8):677-88.

Fig 1. Flow cytometry reveals increased eosinophils (pink)

Increased EOS Pink

Fig 2. FISH reveals one normal tricolor 4q12 fusion signal and one with aberrant deletion of the orange signal
Fig. 3 FISH negative for BCR/ABL translocation
 

f-10-1787-ba
Fig 4.Karyotype 46,XY,del(13)(q12q14 karyotype_deletion_13q14

 


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