False-Negative Testing for FIP1L1::PDGFRA by Fluorescence in situ Hybridization Is a Frequent Cause of Diagnostic Delay

Acta Haematol. 2023;146(4):316-321. doi: 10.1159/000528046. Epub 2023 Jun 7.

Abstract

The imatinib-sensitive fusion gene FIP1L1::PDGFRA is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of PDGFRA-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for FIP1L1::PDGFRA. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for FIP1L1::PDGFRA. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of PDGFRA-associated disease.

Keywords: Clinical studies; Eosinophilia; Myeloproliferative disorders.

Publication types

  • Case Reports

MeSH terms

  • Benzamides
  • Delayed Diagnosis
  • Humans
  • Imatinib Mesylate / therapeutic use
  • In Situ Hybridization, Fluorescence
  • Myeloproliferative Disorders* / drug therapy
  • Neoplasms* / drug therapy
  • Oncogene Proteins, Fusion / genetics
  • Piperazines / therapeutic use
  • Pyrimidines / therapeutic use

Substances

  • Imatinib Mesylate
  • Piperazines
  • Pyrimidines
  • Benzamides
  • Oncogene Proteins, Fusion