Extramedullary Myeloid Sarcoma With Eosinophilia and FIP1L1-Pdgfra Rearrangement: Complete Cytogenetic Response To Imatinib Therapy
Authors: Matrai Zoltan , Andrikovics Hajnalka , Csomor Judit , Timár Botond , Kozma András , Tordai Attila , Masszi Tamas 
Published: October 2019

Abstract

Background
Myeloid sarcomas are rare extramedullary manifestations of acute myeloid leukemia (AML) representing less then 1% of all cases. Since they invariably progress into systemic disease, early AML-like chemotherapy is mandated. Myeloproliferations with eosinophilia and involvement of the PDGFRA, PDGFRB or FGFR1 genes are distinct entities in the 2008 WHO classification with peculiar sensitivity to tyrosine kinase inhibitors. Extramedullary myeloid sarcomas with eosinophilia and FIP1L1-PDGFRA fusion gene expression are extremely rare with only two cases described. Here we report a case of extramedullary leukemia, eosinophilia and FIP1L1-PDGFRA rearrangement responding favourably to imatinib.

Case history
A 32-year old man presented with a 3-month history of subcutaneous nodules growing gradually in the occipital, chest, abdominal and perianal regions, the largest being 50 x 60 x 18 mm in size and exulcerated. There was no weight loss or fever. Complete blood count showed WBC of 6,8 x 109/L, Hb level of 104 g/dl and platelet count of 377 x 109/L. The differential revealed 42% neutrophils, 25% lymphocytes, 5% monocytes and 28% eosinophils with an absolute eosinophil count of 1,92 x 109/L. Apart from mildly elevated LDH (539 U/L, normal range: 153 - 463 U/L), other laboratory results were unremarkable. CT scan found no lymphadenopathy or hepatosplenomegaly. Histology of the nodules showed infiltration with immature monoblasts, negative for CD34, CD117 and weakly positive for MPO and CD68. Mutations of the FLT3 and nucleophosmin genes were not present and TCR gene rearrangement analysis did not reveal clonality. Bone marrow biopsy showed an increase of eosinophilic precursors without apparent blast excess. FISH analysis of the nodules performed with the LSI FIP1L1/PDGFR alpha probe detected deletion of the CHIC2 gene in most interphase nuclei. Bone marrow karyotype was normal, and FISH probes proved negative for AML/ETO and inv(16). In 15% of interphases, the FIP1L1/PDGFR alpha fusion signal could be detected. RT PCR showed FIP1L1-PDGFR alpha gene fusion in the marrow.
A diagnosis of extramedullary myeloid sarcoma with concomittant eosinophilia and FIP1L1/PDGFRA fusion gene expression was established. To our knowledge, this is the third such case reported so far. Induction regimen consisted of 7 days of Ara-C (200 mg/m2) and 3 days of daunorubicin (60 mg/m2). This resulted in regression but not complete disappearance of the subcutaneous nodules. After the therapy-induced aplasia, restitution of platelets preceded neutrophils and mild thrombocytosis developed. The bone marrow showed increased eosinophils without blast excess. FISH analysis detected the presence of the FIP1L1-PDGFRA fusion signal in 11% of nuclei. Imatinib mesylate, 100 mg/day was started. In 14 days, the platelet count returned to normal and the residual nodules disappeared completely. After 5 weeks of imatinib therapy, the patient is doing well without any complaints and the bone marrow shows complete cytogenetic response.

Conclusion
this case of extramedullary AML, eosinophilia and FIP1L1/PDGFRA rearrangement persisting after intensive chemotherapy but responding well to low-dose imatinib emphasizes the importance to screen for mutations of the PDGFR gene in AML with major eosinophilic component due to the major therapeutic implications.

Disclosures:
No relevant conflicts of interest to declare.