PMC4599757_01
Hematoxylin and eosin stained slide of left neck biopsy. A diffuse proliferation of intermediate to large mononuclear cells with round to irregular nuclei, dispersed chromatin, distinct nucleoli, and small amounts of cytoplasm, consistent with blast forms are seen. Admixed are plasma cells, small lymphocytes, and additional myeloid elements, including abundant eosinophilic forms
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Fig1
Additionally, admixed plasma cells, small lymphocytes and abundant eosinophilic forms were noted (Fig. 1).
Radiology showing extent of disease burden. PET-CT showing extensive intensely FDG-avid lymphadenopathy above and below the diaphragm and extensive FDG-avid skeletal/marrow disease burden
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Fig2
He then received clofarabine and cytarabine as fifth-line treatment, but his disease continued to progress (Fig. 2), and he was switched to decitabine therapy.
Molecular diagnostics of the patient's tumor. a Copy number assessment of chromosome 4 shows a one copy loss of the 5' end of PDGFRA. b Translocation analysis shows the discordant reads map to intron 10 of FIP1L1 and exon 12 of PDFGRA. c Metaphase FISH analysis shows one normal copy of chromosome 4, which retains all 3 FISH probes on 4q (green SCFD2 that is centromeric to FIP1L1, orange LNX that is located between FIPL1 and PDGFRA, and blue KIT that is telomeric to PDGFRA). The other copy of chromosome 4 shows an isolated deletion of LNX with retention of the flanking SCFD2 and KIT probes, indicative of a FIP1L1-PDGFRA rearrangement. Trisomy 8 is also present in these cells, as evidenced by 3 CEP 8 probe signals
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Fig3
Moreover, analysis of chromosome 4 showed a one copy loss of the 5' end of PDGFRA (Fig. 3a). BreaKmer, the Oncopanel algorithm that uses a 'kmer' strategy to assemble misaligned sequence reads for predicting structural rearrangements, detected discordant sequencing reads indicative of a FIP1L1-PDGFRA rearrangement (Fig. 3b). Only one LNX hybridization signal was observed in 42/100 nuclei (42 %) with retention of the flanking probes, consistent with a FIP1L1-PDGFRA rearrangement (Fig. 3c). Trisomy 8 was evidenced by the presence of three signals using he CEP 8 Spectrum Orange DNA Probe Kit (Abbott Molecular), which detects chromosome 8 alpha satellite sequences at 8p11.1-q11.1 was used to interrogate chromosome 8 copy number (Fig. 3c).
Radiology evaluation of disease burden after imatinib treatment. a PET-CT 4 weeks after initiation of imatinib treatment showing marked interval improvement in supradiaphragmatic and infradiaphragmatic lymphadenopathy as well as the skeletal/marrow disease burden. b PET-CT 6 months post imatinib treatment and 4 months reduced-intensity conditioning allogeneic stem cell transplantation shows no FDG-avid malignancy
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Fig4
PET-CT performed 4 weeks later showed marked improvement in the supradiaphragmatic and infradiaphragmatic lymphadenopathy as well as the bone marrow disease (Fig. 4a). His post-transplantation course was relatively uneventful with mild graft-versus-host disease controlled with topical therapies. He is currently 9 months post-transplant, remains on imatinib 100 mg daily, and has no evidence of disease (Fig. 4b).