Giant cell carcinoma of the urinary bladder : Clinicopathologic analysis and oncological outcomes

Abstract

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60-90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50-90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.

Keywords: Bladder cancer; Giant cell carcinoma; Progression; Subtype; Variant.

Fig. 1

Representative features of giant cell carcinoma of the bladder with highly pleomorphic cells and largely variable hyperchromatic nuclei at low (A), intermediate (B), and high power (C) (A, B, C hematoxylin and eosin staining). Urothelial lineage, proliferation, p53, and cytokeratin immunohistochemical markers are readily expressed by cells in giant cell carcinoma uroplakin II (D), Gata3 (E), CK20 (F), CK7 (G), Ki67 (H), p53 (I), and S100P (J). PD-L1 expression with 22C3 antibody is also shown (K)

Fig. 2

Kaplan–Meier plots showing overall and cancer-specific survival differences for giant cell carcinoma subtype vs. conventional urothelial carcinoma (A, B), stage T1 category for giant cell carcinoma subtype vs. conventional urothelial carcinoma (C, D), and AJCC stage T2-4 giant cell carcinoma subtype vs. conventional urothelial carcinoma in the current series of giant cell carcinoma subtype and conventional urothelial carcinoma (E, F)