PMC7541700_01
Pelvic computed tomography during treatment. (a) Pretreatment. A left ureteral tumor was observed. (b) After two courses of gemcitabine plus carboplatin chemotherapy. (c) After five courses of pembrolizumab.
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F1
TURBT revealed a left lower ureteral tumor with hydronephrosis and atrophy of renal parenchyma (Figure 1a). Tumor biopsy results led to a diagnosis of high-grade, locally advanced urothelial carcinoma with a clinical stage of T3N0M0. After two chemotherapy courses, the primary tumor and left external iliac lymph nodes became enlarged, while hematuria reappeared (Figure 1b). After five courses of pembrolizumab, CT showed 90% shrinkage of the tumor and left external iliac lymph nodes, which constituted a partial response (Figure 1c).
Surgical specimen and histopathological findings. (a) Only the scar tissue was shown at the lower ureteral site. (b) Accumulation of foamy histiocytes and infiltration of chronic inflammatory cells were observed around the necrotic tissue.
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F2
Histopathological findings showed expanded necrosis and infiltration of foamy histiocytes with no viable cells in the surgical specimens (Figure 2).
Multiplex fluorescence immunohistochemistry. Evaluation of immune cells before and after neoadjuvant therapy for upper urinary tract urothelial carcinoma. Representative multiplex fluorescence images of tumor-infiltrating T and B cells in the (A) biopsy specimen and (B) resected specimen. Nuclei, CD3, CD4, CD8, CD20, Ki67, and cytokeratin within the cells are shown in gray, blue, yellow, red, green, pink, and orange, respectively. (C) Ki67high subpopulation of CD8 T cells (yellow arrows) was determined by visualizing nuclear Ki67 (pink) expression. (D) Evaluation of each immune cell's density before and after pembrolizumab therapy in the biopsy and resected specimens.
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F3
On the other hand, despite tumor-infiltrating CD20+ B cells were not found in the biopsy specimen, they were observed surrounded by CD8+ cells in the resected specimens (Figure 3).
Immunohistochemical staining demonstrating (A) significant programmed death ligand-1 (PD-L1) expression and (B) lack of PD-L2 expession in the biopsy specimen.
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F4
The expression of PD-L1 was positive for tumor cell; meanwhile, PD-L2 was negative for the tumor cell in biopsy specimens (Figure 4).