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Pseudopapillary Features in Prostatic Adenocarcinoma Mimicking Urothelial Carcinoma: A Diagnostic Pitfall

High-grade prostate adenocarcinoma can have overlapping morphologic features with high-grade urothelial carcinoma, a critical distinction as treatments differ substantially. Pseudopapillary features have not previously been described in high-grade acinar prostate adenocarcinoma. We reviewed our consult cases (2006 to 2013) for cases of high-grade prostate adenocarcinoma, in which the Gleason score was equal to 5+4=9 or 5+5=10, and the differential diagnosis included high-grade urothelial carcinoma. We identified 7 consult cases of high-grade prostate adenocarcinoma with pseudopapillary features, mimicking urothelial carcinoma. Three cases were originally misdiagnosed as urothelial carcinoma. In 3 cases, the outside diagnosis was urothelial carcinoma versus prostate adenocarcinoma, and 1 case had no submitting diagnosis. All cases were transurethral resections, with tumor involving the prostatic urethra in 5 cases and 6 with bladder involvement. Three patients had a known history of prostate adenocarcinoma. The tumors grew in nests and sheets, 1 with microacinar differentiation and another with focal, rare glands. In places, tumors formed papillary-appearing structures with central blood vessels. In most cases, the nuclei were uniform with prominent nucleoli. One case had pleomorphic giant cell features, and another had sarcomatoid features. Necrosis was present in 2 cases. One case had a separate focus of low-grade noninvasive urothelial carcinoma present in the bladder and a better-differentiated prostate adenocarcinoma (Gleason score 4+3=7) involving the prostate on needle biopsy. In all cases, the pseudopapillary areas showed negative immunohistochemical staining for bladder markers including GATA3 (5 cases), p63 (5 cases), CK903 (4 cases), and thrombomodulin (3 cases). All cases showed positivity for prostatic markers including PSA (5 cases), p501s (6 cases), PSMA (4 cases), and NKX3.1 (5 cases). One case showed focal, nonspecific staining for p63, and another showed focal staining for p63 and CK903 in an area with squamous differentiation, contributing to the diagnostic difficulty. In summary, high-grade prostate adenocarcinoma can present in the urinary bladder and prostatic urethra, clinically mimicking urothelial carcinoma. Although high-grade prostate adenocarcinoma typically has relatively uniform cytology, it can have pleomorphic giant cell features overlapping with urothelial carcinoma. The presence of pseudopapillary features in high-grade prostate adenocarcinoma is a newly recognized morphologic overlap that can lead to further diagnostic difficulty in distinguishing the 2 entities. For high-grade tumors involving the prostatic urethra without typical admixed lower-grade prostate adenocarcinoma, immunohistochemical studies for bladder and prostate markers should be carried out.