Figure 1.

Myeloproliferative neoplasm with non-Langerhans cell histiocytosis and ETV6-SYK fusion responds to fostamatinib. (A, B) Clinical photographs taken approximately 6 months before treatment with fostamatinib. (C, D) Pre-treatment skin biopsy (hematoxylin and eosin staining [H&E], 200X magnification) (C) and CD163 immunohistochemistry (IHC) (200X magnification) (D) showing histiocytic infiltrate. (E) Schematic of the ETV6-SYK rearrangement identified from skin biopsy preserving exons 6-14 and the tyrosine kinase domain of SYK. (F) Interphase fluorescence in situ hybridization (FISH) analysis from bone marrow aspirate showing ETV6 rearrangement using an ETV6 break-apart probe. When ETV6 is intact, the red and green signals are adjacent and appear yellow; rearrangement splits the yellow signal into its red and green components. (G) Metaphase FISH analysis from bone marrow aspirate shows co-localization of the ETV6 (green) and SYK (red) locus-specific probes on the abnormal der(9) chromosome. (H, I) Clinical photographs taken after 5 months of fostamatinib therapy show reduction in skin lesions. (J, K) Skin biopsy (H&E, 200X magnification) (J) and CD163 IHC (200X) (K) taken after 9 months of fostamatinib treatment showing reduction in histiocytic infiltrate. (L) Pre-treatment interphase FISH analysis from bone marrow aspirate using ETV6 break-apart probe showed 78.9% of the nuclei examined were positive for ETV6 rearrangement. This improved to 58% after 7 months of therapy. At time of progression this increased to 80%.