Institution: Cleveland Clinic
Session: Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1
HISTORY
The patient is a 52 year old man who presented with a 3 month history of headaches, rhinorrhea, wheezing, weight loss, night sweats and pruritus. A CBC revealed normocytic anemia (Hgb = 10g/dL, MCV =90.9 fL) with marked absolute eosinophilia (8.3 k/uL). Serum tryptase levels were normal (6.2 ug/L) and total serum IgE was elevated (283 kU/L). A bone marrow aspirate and biopsy were performed. Treatment with imatinib was initiated, with subsequent normalization of eosinophil counts.
DETAILS
Examination of the peripheral blood disclosed absolute eosinophilia with normal eosinophil morphology. A bone marrow aspirate smear showed a slight myeloid predominance (M:E ratio 5:1) with 31% eosinophils. Many of the eosinophil precursors showed abnormal basophilic granules. Atypical mast cells were not identified. A bone marrow core biopsy was hypercellular (80%) with trilineage maturation, myeloid predominance, eosinophilia, and mildly increased megakaryocytes.
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Immunohistochemical stains performed on the core biopsy demonstrated scattered CD3 positive cells and few CD20 positive cells. A tryptase stain showed only rare, scattered round mast cells. Flow cytometric studies showed few, polyclonal B-cells and phenotypically unremarkable T-cells.
CYTOGENETIC FINDINGS
Metaphase cytogenetic findings demonstrated a normal male karyotype. FISH studies were negative for BCR/ABL and inv(16). FISH studies for PDGFRA rearrangements were positive in 19% of nuclei. SNP array karyotyping studies (Affymetrix CytoScan HD) confirmed a deletion on 4q12 in a small subset of cells, consistent with a PDGFRA-FIP1L1 fusion
MOLECULAR FINDINGS
PCR studies for a KIT D816V mutation were negative.
INTERESTING FEATURES
This case displays the typical clinical and pathologic features of a myeloid neoplasm with PDGFRA abnormalities, including a characteristically rapid response to imatinib therapy. In addition, the case illustrates the utility of FISH and SNP microarray studies in identifying the 4q12 deletion which leads to a PDGFRA-FIP1L1 fusion gene. Due to the small percentage of abnormal cells in the bone marrow aspirate (19% by FISH), the 4q12 deletion was initially not detected by automated microarray algorithms, but the abnormality was clearly identified on visual examination of the PDGFRA locus. This case highlights the importance of careful examination of SNP microarray data and correlation with the morphologic findings.
PROPOSED DIAGNOSIS
Myeloid neoplasm with PDGFRA rearrangement
CONSENSUS DIAGNOSIS
Myeloid neoplasm with FIP1L1-PDGFRA rearrangement, presenting as "chronic eosinophilic leukemia"