PMC9851605_01
CT scan of the urological tract scan showing the narrowed lumen of the left pelvic ureter (A) and ipsilateral hydronephrosis (B).
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CT scans of the urological tract with contrast medium were performed with the finding of a narrowed left ureteral lumen and ipsilateral hydronephrosis ( Figure 1 ). Cytology was negative for malignancy, and subsequent diagnostic ureteroscopy revealed a polypoid fibrotic lesion, but a biopsy was not feasible.
Intraoperative frozen section showing a solid proliferation of round to ovoid epithelioid cells, with atypical nuclei and eosinophilic cytoplasm, suggesting a urothelial carcinoma (hematoxylin and eosin (H&E), x10) (A). An obstructing mass was found in the ureteral wall (H&E, x0.25) (B), which corresponded to a solid growth with spared overlining urothelium (H&E, x2) (C) and foci of necrosis (H&E, x5) (D). Notably, the tumor was composed of round to spindle, monotonous, small cells with the peculiar intracytoplasmic glycogen (H&E, x40) (E). Immunohistochemically, the tumor was negative for GATA3 (F) but showed the characteristic positivity for CD99 (G), NKX2.2 (H) and FLI1, the suspected and most common partner of translocation, confirmed at NGS analysis (I).
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Frozen sections showed a proliferation of round to ovoid epithelioid cells, arranged in solid sheets, with nuclear atypia and eosinophilic cytoplasm ( Figure 2A ). Remarkably, the overlying urothelium was spared ( Figures 2B-E ). To confirm the urothelial nature of the neoplasm, an immunohistochemical stain for GATA3 was performed, with a negative result ( Figure 2F ). Indeed, an epithelial neoplasm was excluded by immunonegativity for panCK; tumor cells were positive for CD99, FLI1, NKX2.2, synaptophysin (only focal), and negative for myogenin, ERG, and WT1 ( Figures 2G-I ).
FISH with an EWSR1 Dual Color Break Apart Rearrangement Probe detected EWSR1 translocation in 80% of tumor cells as orange and green spitting signals (white arrows) (A). Pan Solid Tumor v2 NGS analysis revealed the gene fusion involving exon 7 of EWSR1 and exon 6 of FLI, detected by a gene specific primer (GSP2) specific for EWSR1
(B).
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EWSR1 translocation was detected in 80% of cells in the tumor area ( Figure 3A ). Eventually, primary ureteral ES was diagnosed. Archer Pan Solid Tumor v2 next-generation sequence analysis (NGS) was performed. Archer Data Analysis Software 6.0 confirmed FLI-1 as the translocation partner ( Figure 3B ).
Temporal timeline.
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