Large nested variant of urothelial carcinoma: A clinicopathologic study of 36 cases

Abstract

Introduction

The large nested variant of urothelial carcinoma (LNUC) has been added to the WHO 2016 classification. Scant data exist, little is known about its clinical behaviour.

Material and Methods

Cases fulfilling the morphological criteria of LNUC were collected. Pure and mixed cases (i.e. with other patterns of invasive UC) were studied. Immunohistochemical staining with CK7, p63, GATA-3, CK20, p53 and Ki-67 was performed.

Results

Included were 26 cystectomies (RC) and 10 resections (TURB) belonging to 36 patients with an average age of 66.7 years. Fourteen (39%) were pure LNUCs, and 22 (61%) displayed mixed features. 70% of the TURBs had pT2 tumors while 58% of RCs had extravesical disease (≥pT3 and/or ≥pN1), with the rate of advanced disease being higher in mixed (69%) in comparison to pure cases (40%). Similarly 38% of mixed cases had nodal metastases in comparison to 20% of pure cases.

Overall, 8 patients (24%) died of disease at a mean interval time of 21.7 months, 7 patients (21%) showed recurrence or metastases. disease progression was significantly higher in mixed cases (55% and 31% in mixed and pure cases, respectively). Positive staining was: CK7=87.5%, CK20=72%, GATA-3=91%, P63=100%, p53=56%, Ki-67=mean of 16%.

Conclusion

Despite the bland cytologic appearance and deceptive pattern of invasion of the LNUC, our study validates its fully malignant potential with metastatic spread and tumor related deaths. Distinguishing mixed from pure LNUCs seems to be of value. LNUCs show comparable immunophenotype to both conventional urothelial carcinoma and the nested variant of urothelial carcinoma.

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