The pitfalls of an invasive non-neuroendocrine GATA3- and TTF1+ urothelial carcinoma

Dear Editor,

in February 2020 a 58-year-old man was referred to the Urology Department for dysuria and hematuria. He had a history of smoking, high blood pressure and hypercholesterolemia. A urinary cytologic test showed atypical urothelial cells and he therefore underwent cystoscopy with trans-urethral resection of the bladder (TURB). Histological assessment without immunohistochemical (IHC) support revealed the presence of a high-grade papillary urothelial carcinoma (UCC) with foci of UCC in situ. He was then treated with intra-vesical Bacillus Calmette-Guérin (BCG). A follow-up TURB was performed in September 2020, without evidence of disease. The patient presented again with gross hematuria in December 2021. Cystoscopy revealed a lesion in the left vesical wall. Pathological investigation of the new TURB specimen showed highgrade infiltrative UCC with evidence of muscularis propria involvement. Imaging studies did not show any sign of other lesions in the body. In February 2022 a radical cystoprostatectomy, combined with the removal of pelvic and obturator lymph nodes, was performed. The surgical specimen featured a neoplastic mass that was also involving a vesical diverticulum, together with UCC in situ and with both gross and microscopic peri-vesical adipose tissue infiltration (Fig. 1A and 1B). Histologically, the lesion had a solid growth, with necrotic foci and focal myxoid areas. At high-power, tumoral cells had an epithelioid phenotype, with evident nucleoli and slightly granular cytoplasm. Metastatic disease was present in a regional lymph node (Fig. 1C).