PMC7446437_01
PMC7446437_02
(A) At diagnosis, postgadolinium axial T1-weighted magnetic resonance imaging (MRI) demonstrated a heterogeneous complex mass in the left frontal lobe. (B) After total surgical resection, postgadolinium axial T1-weighted MRI demonstrated total resection of the left frontal mass. (C) At recurrence, postgadolinium axial T1-weighted MRI demonstrated newly appearing mass within the operative bed (arrow) showing intermediate diffusion signal with corresponding contrast enhancement indicating recurrent tumor. (D) Eight weeks after larotrectinib, follow-up postgadolinium axial T1-weighted MRI demonstrated disappearing left frontal mass indicating significant treatment response
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fig1
March 2019, an 18-month-old female child was admitted with right-sided weakness and partial seizures for 4 weeks. MRI showed a large, heterogeneous, complex left frontotemporal mass with internal cystic and necrotic changes with mass effect and a rightward midline shift with enhancing focus at the left posterior thalamic region (8 x 7 x 9 cm; Fig 1A). Postoperative MRI confirmed GTR but did note a small focus of nodular enhancement in the left insular cortex suggestive of residual tumor (Fig 1B). The size of the recurrent lesion at the surgical bed was 2.3 x 2.8 x 2.7 cm and was associated with central necrosis (Fig 1C). MRI after 8 weeks of therapy showed marked tumor regression indicative of an excellent treatment response (Fig 1D).
(A) Sheet of highly cellular monomorphic round primitive cells with relative demarcation from adjacent brain tissue (hematoxylin and eosin [HE]; original magnification, x20). (B) Heterogeneous morphologic features of the neoplasm composed of focal areas of spindle cells arranged in small fascicles and primitive round cells in myxoid background with alternating hyper- and hypocellularity (HE; original magnification, x200). (C) Higher magnification of the primitive cells in the myxoid background (HE; original magnification, x200). (D) Higher magnification of the spindle cell area (HE; original magnification, x20). (E) Few neoplastic cells show cytoplasmic and nuclear immunostaining for S100 (S100; original magnification, x200). (F) Focal areas show neoplastic cells with cytoplasmic staining of synaptophysin (synaptophysin; original magnification, x400). (G) Schematic of ETV6-NTRK3 fusion detected in patient's tumor.
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fig2
The tumor was composed of hypercellular sheets of primitive round to oval cells with fine open chromatin and no visible nucleoli (Fig 2A). The growth pattern consisted of intermixed small fascicles of spindle cells and haphazardly arranged primitive round cells in a myxoid background associated with delicate vasculature (Fig 2B). The neoplastic cells were diffusely immunopositive for vimentin; were focally positive for S100 and synaptophysin; showed retained nuclear staining for INI1; and were immunonegative for SMA, EMA, CD99, CD31, CD34, and NeuN (Figs 2C to 2F). The fusion encompassed exons 1 to 5 of ETV6 and exons 14 to 20 of NTRK3, which retains the kinase domain of NTRK3 (Fig 2G).